| 1. |
- Akagi, Nana, et al.
(author)
-
Effect of acute endolymphatic hydrops overload on the endolymphatic sac
- 2008
-
In: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 128:3, s. 239-44
-
Journal article (peer-reviewed)abstract
- CONCLUSIONS: Homeostasis of endolymph volume is a complex mechanism, in which the endolymphatic sac (ES) may play an important role. OBJECTIVES: To elucidate the effect of acute endolymphatic hydrops (EH) on the ES and to gain further information about the volume and pressure regulative function of the ES. MATERIALS AND METHODS: Distilled water was injected into the middle ear cavity of adult CBA/J mice. The ESs were studied morphologically by light and transmission electron microscopy. RESULTS: Mild EH was found, particularly in the upper turn of the cochlea. Acute EH led to an increase in the size of the ES lumen, accompanied by collapse of the lateral intercellular spaces and dense perisaccular tissue, changes which had reversed 2 h after the injection.
|
|
| 2. |
- Akagi, Nana, et al.
(author)
-
Effect of inner ear blood flow changes on the endolymphatic sac
- 2008
-
In: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 128:11, s. 1187-95
-
Journal article (peer-reviewed)abstract
- CONCLUSIONS: That the endolymphatic sac (ES) reacts to changes in inner ear blood flow may be important for homeostasis of the inner ear fluid volume and pressure. OBJECTIVES: To elucidate the effect of changes in inner ear blood flow on the ES and to learn more about the volume and pressure regulatory function of the ES. MATERIALS AND METHODS: Epinephrine or sodium nitroprusside (SNP) was injected into the middle ear cavity of adult CBA/J mice. The ES were analyzed morphologically by light microscopy. RESULTS: Epinephrine reduced the luminal size of the ES leading to an accumulation of intraluminal homogeneous substance. Injection of SNP increased the size of the ES lumen, accompanied by a collapse of the lateral intercellular space (LIS) and dense perisaccular tissue. These changes were almost reversed 4 h after injection.
|
|
| 3. |
- Anniko, Matti
(author)
-
Acta Oto-Laryngologica
- 2018
-
In: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 138:3, s. 192-193
-
Journal article (other academic/artistic)
|
|
| 4. |
- Anniko, Matti, et al.
(author)
-
Alpha-Bungarotoxin Inhibits Outer Hair Cell Motility in situ
- 1995
-
In: Journal for Oto-Rhino-Laryngology. - : S. Karger AG. - 0301-1569 .- 1423-0275. ; 57:2, s. 105-109
-
Journal article (peer-reviewed)abstract
- The effect of two substances (alpha-bungarotoxin, alpha-BGTX, a small protein, and the local anesthetic bupivacaine hydrochloride) with an assumed effect on outer hair cell (OHC) motility were analyzed after exposing the cochlea via the round window membrane. Electrophysiological measurements were performed with a very narrow frequency-specific gating (+/- 100 Hz) technique to determine auditory brainstem response (ABR) thresholds, including ABR-based frequency tuning curves. Exposure to alpha-BGTX gave a minor improvement in thresholds, interpreted as a facilitation of OHCs, i.e. releasing their efferent inhibitory control, whereas exposure to bupivacaine hydrochloride impaired ABR thresholds, possibly due to immobilization of OHC motility via the lateral cell membrane. Our results are consistent with the hypothesis that efferent influence on the cochlea may be linked with a modulation of the mechanical function of OHCs. We can now postulate that there is in vivo evidence that acetylcholine exerts its effect at the OHCs via an alpha-BGTX alpha-BGTX binding acetylcholine receptor.
|
|
| 5. |
- Anniko, Matti, et al.
(author)
-
Cytoskeletal basis for contractility of outer hair cells in the normal adult human organ of Corti : Comparisons with vestibular hair cells
- 1995
-
In: Journal for Oto-Rhino-Laryngology. - 0301-1569 .- 1423-0275. ; 57:2, s. 61-7
-
Journal article (peer-reviewed)abstract
- The present study is the first consecutive analysis of the adult normal human organ of Corti and vestibular hair cells with regard to the expression of F-actin, actin-associated proteins (alpha-actinin, alpha- and beta-spectrins, vinculin and tropomyosin), beta-tubulin and the calcium-binding protein synaptophysin. The expression of these cytoskeletal and their associated proteins in man is largely similar to, although not identical with, that previously described for several other mammalian species. However, a few very unusual staining patterns were found. In several long outer hair cells a rod of F-actin extended from the infracuticular area to the cell nucleus. Fluorescence for tropomyosin occurred both in the cuticular plates of the outer and inner hair cells, and in the area of close apposition between the base of the outer hair cell and the apical part of Deiter's cell. In contrast, the vestibular hair cells showed immunoreactivity for tropomyosin only in the cuticular plates.
|
|
| 6. |
- Anniko, Matti, et al.
(author)
-
Cytoskeletal proteins in human hair cells
- 1995
-
In: Acta oto-laryngologica. Supplementum. - 0365-5237 .- 1651-2464. ; 519, s. 8-12
-
Journal article (peer-reviewed)abstract
- Human cochlear and vestibular hair cells (HCs) were analysed for the three major cytoskeletal types of structures: microfilaments, microtubules, and intermediate filaments and several of their associated proteins. Specific immunomorphological features were identified: the apical surface, the infracuticular rod of F-actin, the cytoplasm and the HC bases and their interactions with adjacent supporting cells. There is morphological evidence for at least three functionally interacting units: the OHC as a cytoskeletal string interacting with the Deiter's cell, being a part of the rigid pancellular protein shell of the organ of Corti; compartmentalization of HCs (surrounded by rigid intermediate filament proteins in the supporting cells); and a calcium-guided short-loop feed-back control of type I HCs. The cytoskeletal composition of all four types of human HCs and their adjacent structures is similar to, although not identical with, corresponding compositions in other mammalian species.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Anniko, Matti, et al.
(author)
-
Hyaluronic acid as a molecular filter and friction reducing lubricant in the human inner ear
- 1995
-
In: Journal for Oto-Rhino-Laryngology. - 0301-1569 .- 1423-0275. ; 57:2, s. 82-6
-
Journal article (peer-reviewed)abstract
- Immunofluorescence for hyaluronic acid occurred intracellularly in morphologically highly specialized areas in the adult human inner ear, for instance in the cuticular plates of all types of hair cells, at the apposition between outer hair cells and Deiter's cell bodies and in the near-surface area of Hensen's cells. The cytoskeletal organization in these regions is characterized by tightly packed filamentous proteins. Under physiological stimulus these regions undergo micromechanical change, either actively moving (force generation) or passively vibrating with changes in elasticity. Hyaluronic acid might therefore act as a friction-reducing molecular lubricant. In the lateral wall of the cochlea an accumulation of hyaluronic acid occurred in the loose connective tissue of the spiral ligament, in particular close to the stria vascularis. Due to its complex molecular network, hyaluronic acid offers considerable resistance to bulk flow of water and may exclude molecules. The basal cell region of the stria vascularis is thus given additional support to minimize (seal?) the stria vascularis towards all other areas except the endolymphatic space. Here, hyaluronic acid could act as a molecular filter.
|
|
| 10. |
- Anniko, Matti, et al.
(author)
-
Microtubule-associated proteins in adult human sensory organs
- 1995
-
In: Journal for Oto-Rhino-Laryngology. - 0301-1569 .- 1423-0275. ; 57:2, s. 78-81
-
Journal article (peer-reviewed)abstract
- The distribution of microtubule-associated proteins MAP-1 and MAP-2 was analysed with immunomorphological techniques in the serially sectioned adult human membranous labyrinth. In the organ of Corti, monoclonal antibodies to MAP-1 did not stain. Positivity for MAP-2 occurred in the entire outer hair cell cytoplasm, in the inner hair cells (?), in the nerve fibres and in the cytoplasm of epithelial cells of the spiral prominence. In addition, staining for MAP-2 was identified in many (but not all) cells or Reissner's membrane. Immunofluorescence for MAP-1 occurred in the supporting cells of the cristae and maculae interpreted to be localized in the apical region adjacent to the sensory cells. Thus, the distribution of MAP-1 and MAP-2 in the adult human membranous labyrinth was the same as described for several animal species with regard to the cochlea. In contrast to such a pattern, both MAP-1 and MAP-2 were identified in the human vestibular organs, thus identifying a subpopulation of centrally located nerve calyces and possibly also the apical portion of vestibular hair cells.
|
|
| 11. |
|
|
| 12. |
- Anniko, Matti, et al.
(author)
-
Nitric oxide in guinea pig vestibular sensory cells following gentamicin exposure in vitro
- 2001
-
In: Acta Oto-Laryngologica. - 0001-6489 .- 1651-2251. ; 121:3, s. 346-50
-
Journal article (peer-reviewed)abstract
- Gentamicin-induced production of nitric oxide (NO) in the vestibular end organs of the guinea pig was investigated using the new fluorescence indicator 4,5-diaminofluorescein diacetate for direct detection of NO. Utricular maculae and isolated vestibular sensory cells were examined to locate NO production sites. The fluorescence intensity of the sensory cells was augmented by stimulation with gentamicin. This increase in fluorescence was inhibited by the presence of the non-specific inhibitor for nitric oxide synthase, L-N(G)-nitroarginine methylester, and by the non-specific N-methyl-D-aspartic acid antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate. These findings indicate that NO may play an important role in the ototoxicity of aminoglycoside.
|
|
| 13. |
- Anniko, Matti, et al.
(author)
-
Protein patterns in human vestibular ganglion cells and hair cells, with functional interpretations
- 1993
-
In: Acta oto-laryngologica. Supplementum. - 0365-5237. ; 503, s. 136-142
-
Journal article (peer-reviewed)abstract
- Cytoskeletal organization was analysed in the vestibular ganglion cells and in the sensory epithelia of all five vestibular organs of the adult human temporal bone. A pancellular rigidity of the upper surfaces of the vestibular organs, evidenced by large quantities of intermediate filaments and actin, seems of importance for the mechanoelectrical transduction by opposing the motion of the cupulae and statoconial layers. Immunostaining for the calcium-binding protein synaptophysin in the sensory hair bundles and in the area close to the cuticular plates--the first of its kind to be demonstrated in human vestibular organs--indicates the presence of calcium-dependent ionic channels. The hypothesis is presented that the calyx might be involved in a short-loop feed back control of type I hair cells, i.e. of the mechanoelectrical transduction itself. Subpopulations of vestibular ganglion cells were identified by the staining pattern of cytoskeletal proteins, but not by ordinary ultrastructural analysis.
|
|
| 14. |
- Anniko, Matti, et al.
(author)
-
The human spiral ganglion
- 1995
-
In: Journal for Oto-Rhino-Laryngology. - 0301-1569 .- 1423-0275. ; 57:2, s. 68-77
-
Journal article (peer-reviewed)abstract
- The adult normal human spiral ganglion (SG) was analyzed with regard to ultrastructure and immunohistochemistry. The cytoskeleton of the SG cells was found to comprise F-actin, intermediate filaments (IFs) and microtubules (MTs). The IF subgroups (cytokeratins, Cks; neurofilaments, NFs, vimentin, glial fibrillary acidic proteins, GFAP; desmin) displayed characteristic staining patterns. Ck No. 8 was found in all SG cells, whereas vimentin was lacking. GFAP stained only a small subpopulation of SG cells (type 2?). The light (68 kD) and medium-sized chains of NFs occurred in all SG cells and axons, whereas the 200-kD NF subunit was only found in the axonal hillock of (type 2?) SG cells, but in no other part of the cytoplasm, and regionally in nerve fibres. MAP-1 and MAP-2 occurred in all SG cells but only MAP-1 was found in the nerve fibres. The calcium-binding protein synaptophysin (SY) was expressed only in SG cells, in contrast to the S-100 which occurred more generally in the labyrinth. The neuropeptides VIP and substance P were identified in all SG cells, in contrast to NPY which was expressed in a small subpopulation of SG cell (type 2?). Staining for neuron-specific enolase (NSE) identified most (type 1?) but not all SG cells. The cell surface glycoprotein Thy-1 was expressed in SG cells in a way similar to that described for neurons in the CNS. The SG cells express a high degree of cytoskeletal complexity, allowing one to distinguish between type 1 and type 2 cells. The cell bodies and their adjacent nerve fibres show characteristic features of calcium-binding proteins, surface membrane glycoproteins, NSE and neuropeptides but the basic pattern is still similar to neurons in the CNS.
|
|
| 15. |
- Anniko, Matti, et al.
(author)
-
Örat
- 2001. - 2
-
In: Öron, näs- och halssjukdomar, huvud- och halskirurgi. - Stockholm : Liber. - 9147048956 ; , s. 9-103
-
Book chapter (other academic/artistic)
|
|
| 16. |
|
|
| 17. |
- Cheng, Junping, 1965-
(author)
-
Radioimmunotherapy in Experimental Head and Neck Squamous Cell Carcinoma : Tumour-targeting in vitro and in vivo
- 2005
-
Doctoral thesis (other academic/artistic)abstract
- Radioimmunotherapy (RIT) has been shown to be a practicable way to treat head and neck squamous cell carcinoma. A specific antibody recognizes the charasteristic structure of tumour cells when loaded with cytotoxic agents (toxins, drugs, radionuclides, etc). But RIT kills not only tumour cells with attached radionuclides but also adjacent tumour cells due to the “cross fire effect”. To be efficacious, RIT depends closely on suitable monoclonal antibody, on the properties of the chosen radionuclides, and on a suitable labelling method for attaching radionuclide to antibody. In this study we initially used radionuclide-labelled cMAB U36, via linker DABI in order to improve the retention of radio-conjugates in the tumour cells. Improved retention is important because the longer the radionuclide remains in tumour cells, the more effective will the tumour cells be eradicated. In the investigation, both normal mice and HNSCC-bearing nude mice were used to compare our form of treatment against other radio-iodination methods. In the biodistribution study, normal mice showed that radioactive uptake in organs diminished with time, irrespectively of whether the conjugate was directly or indirectly labelled. But in thyroid, there was a tenfold greater accumulation of direct-labelled than of indirectly labelled conjugate.In tumour-bearing nude mice, by contrast, the results showed promising uptake of radioactivity, but little uptake in direct-labelled conjugate in thyroid. Significant differences were observed on comparing tumour: organ ratios between 131I-cMAb U36 vs. 125I-DABI-cMAb U36.In the present study, cMAb U36 labelled with 211Astatine was initially used to treat HNSCC in nude mice. The biodistribution of 211At-cMAb U36 did not reveal any significant difference between an antibody-blocked group and a non-blocked group. But it did highlight the characteristics of a successful targeting conjugate in HNSCC-bearing nude mice.In the subcutaneous therapy experiment, most of the treated tumours (n=18) had disappeared by the 26th day, in both U36-blocked and non-blocked groups. Treatment in the intravenous therapy experiment had also proved effective. In the antibody non-blocked group, the smallest tumour volume was 25 mm3 (average 111 mm3) vis-á-vis 65 mm3 (average 145 mm3) in the blocked group. None of tumours grew again following treatment.
|
|
| 18. |
|
|
| 19. |
- Cheng, Junping, et al.
(author)
-
Radioimmunotherapy with astatine-211 using chimeric monoclonal antibody U36 in head and neck squamous cell carcinoma
- 2007
-
In: The Laryngoscope. - 0023-852X .- 1531-4995. ; 117:6, s. 1013-1018
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: In advanced head and neck squamous cell carcinoma (HNSCC), there is a need for an adjuvant treatment. We aim to evaluate the biodistribution and therapeutic effect of radioimmunotherapy using the alpha emitting, astatine-211-labeled, chimeric monoclonal antibody U36 (U36) on the HNSCC cell line UT-SCC7 in vivo. STUDY DESIGN: Xenograft tumors were inoculated subcutaneously in nude mice. Astatine-211-labeled U36 was injected intravenously with or without blocking of target with nonlabeled U36. METHODS: In the biodistribution experiments, radioactivity was measured in tumors and various organs at set time points. In the therapeutic experiments, two groups (with or without blocking) received therapy, and the tumor growth was compared with that of controls. In addition, one group received nonlabeled U36 only. RESULTS: The biodistribution experiments demonstrated that astatine-211-labeled U36 could target UT-SCC7 xenografts in nude mice. With time, uptake increased in tumors and decreased in normal organs. Nonlabeled U36 did not influence tumor growth. In the two therapy groups, 18 of 20 tumors responded to therapy by decreasing or stabilizing their volumes. Significant difference was seen between the treated groups and the controls (P < .05). CONCLUSION: The study illustrates the specific binding of astatine-211-labeled U36 to HNSCC and suggests radioimmunotherapy with the alpha emitting radionuclide to be a useful treatment modality.
|
|
| 20. |
- Cheng, Junping, et al.
(author)
-
Targeting of a head and neck squamous cell carcinoma xenograft model using the chimeric monoclonal antibody U36 radioiodinated with a closo-dodecaborate-containing linker
- 2004
-
In: Acta Oto-Laryngologica. - 0001-6489 .- 1651-2251. ; 124:9, s. 1078-85
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: High rates of local recurrence and distant metastases following surgery of high-grade head and neck squamous cell carcinoma (HNSCC) necessitate the use of adjuvant systemic treatment. Radioimmunotargeting might be a possible treatment modality in this case. The nuclear properties of 131I make it a suitable isotope for treatment of minimal residual disease and small metastases, but the conventional radioiodine label has poor cellular retention and its radiocatabolites accumulate in the thyroid. We attempted to overcome these problems by using closo-dodecaborate derivatives for attachment of radioiodine. MATERIAL AND METHODS: We investigated the feasibility of targeting an SCC25 HNSCC xenograft in vivo using a benzylisothiocyanate derivative of closo-dodecaborate (DABI) as radioiodine linker and the chimeric anti-CD44v6 antibody U36. 125I was used in biodistribution studies. RESULTS: The use of DABI enabled tumor targeting and decreased the radioactivity uptake of the thyroid. CONCLUSION: Tumor localization of DABI-labeled U36 was similar to its para-iodobenzoate-labeled counterpart, presumably due to the strong dependence of targeting efficiency on tumor size.
|
|
| 21. |
- Cheng, Junping, et al.
(author)
-
The use of closo-dodecaborate-containing linker improves targeting of HNSCC xenografts with radioiodinated chimeric monoclonal antibody U36
- 2010
-
In: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997. ; 3:1, s. 155-160
-
Journal article (peer-reviewed)abstract
- Radionuclide imaging of head and neck squamous cell carcinoma (HNSCC) using monoclonal antibodies (MAbs) has the potential to contribute to improved diagnosis and staging, thereby making more effective treatment possible. Chimeric monoclonal antibody U36 (cMAb U36), specific to CD44v6 antigen. is a candidate for the targeting of HNSCC. The aim of this study was to compare the influence of indirect iodination via closo-dodecaborate-based linker (DABI) with the influence of direct radioiodination on the biodistribution of the chimeric anti-CD44v6 antibody U36. The study was performed using nude mice bearing UT-SCC7 HNSCC xenografts using the paired-label method. The biodistribution of cMAb U36 labelled directly with I-131 and using DABI with I-125 was compared in the same animals. The influence of DABI on the tumour-to-organ ratio was evaluated. For both conjugates, radioactivity uptake in blood and organs decreased with time, except in tumours and the thyroid. DABI-labelled cMAb U36 was characterised by fast blood clearance and an elevated uptake in the liver and spleen. The use of DABI enabled a 1.5 to 2-fold improvement in the tumour-to-blood and tumour-to-organ ratios in comparison with direct radioiodination, with the exception of the liver and spleen. These results indicate that DABI is a promising linker for the coupling of radioiodine to HNSCC-targeting antibodies.
|
|
| 22. |
- Ekberg, Tomas, et al.
(author)
-
Clinical impact of positron emission tomography (PET) with (18F)fluorodeoxyglucose (FDG) in head and neck tumours
- 2007
-
In: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 127:2, s. 186-193
-
Journal article (peer-reviewed)abstract
- Conclusion. PET plays an important role in staging, on suspicion of recurrence and for detection of occult primary tumours in the head and neck. Objective: Since 1998 we have used positron emission tomography (PET) with (F-18)fluorodeoxyglucose (FDG) to assess selected patients. This procedure has often helped in making decisions on staging and treatment. Patients and methods. The case records of the first 80 patients (104 PET examinations) were studied retrospectively. Results. A total of 39 examinations were performed for staging. PET detected all primary tumours except two (stage T1), and staging was adjusted after 13%. In all, 33 PET examinations were performed on suspicion of recurrent tumour. In 52% of these PET determined further treatments; in 21% PET had a direct impact on the surgical planning. In 18 patients with metastases from an occult primary tumour, PET detected 39% of those tumours; in 22% it was the sole modality to do so. No recurrences or second primary tumours were detected when PET was used for follow-up of clinically cured patients. Results were similar when squamous cell carcinomas (SCCs) were considered alone as compared to the complete material. The mean standardized uptake value (SUV) was higher for cases deemed tumour-positive than in negative cases.
|
|
| 23. |
- Ekberg, Tomas, 1966-
(author)
-
Diagnosis and Radioimmunotherapy of Head and Neck Squamous Cell Carcinomas
- 2008
-
Doctoral thesis (other academic/artistic)abstract
- The diagnosis and treatment of patients with advanced tumors in the head and neck is an interesting challenge where there is a need for new approaches in diagnostics and adjuvant treatment. Differences in antigen expression between tumors and normal tissues provide a means for application of antibody-based targeting techniques. By targeting a structure that is abundant on tumor cells and limited on normal cells, radioactivity can be delivered.The use of positron emission tomography (PET) in patients with head and neck tumors is evaluated in this thesis. PET using the tracer fluorodeoxyglucose (FDG) is found to play an important diagnostic role and often has a direct clinical impact on planned surgery or other treatment. Possible targeting structures are also investigated in this thesis, and it is concluded that the EGFR and CD44v6 stand out as possible antigens for targeting approaches of squamous cell carcinomas in the head and neck (HNSCC). A radioimmunoassay for quantification of EGFR and CD44v6 is validated and concluded to be a valuable complement to immunohistochemistry for the analysis of tumors and for the planning of radioimmunotherapy. Finally, promising results of radioimmunotherapy in tumor bearing mice with the monoclonal antibody U36 labeled with the alpha emitter astatine-211 are presented.These results demonstrate how differences between tumors and normal tissues can be used to improve diagnostic outcomes and indicate that radioimmunotherapy can be a future adjuvant therapy or treatment of residual disease in HNSCC.
|
|
| 24. |
- Ekberg, Thomas, et al.
(author)
-
Expression of EGFR, HER2, HER3, and HER4 in metastatic squamous cell carcinomas of the oral cavity and base of tongue
- 2005
-
In: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 26:5, s. 1177-85
-
Journal article (peer-reviewed)abstract
- The expressions of all four receptors in the epidermal growth factor receptor family, EGFR. HER2, HER3, and HER4 were evaluated by immunohistochemistry in 19 cases of metastatic squamous cell carcinoma of the oral cavity and base of tongue. EGFR had a similar and high expression in both primary tumours and the corresponding metastases, while the expression in normal epithelium was lower in most cases. HER2 was not expressed to the same extent as EGFR. However, when HER2 was well expressed, it was in most cases expressed to the same extent and intensity in the primary tumours, metastases, and normal epithelium. The expression of HER3 and HER4 varied and was mainly cytoplasmic in all cases studied. No overexpression of HER3 and HER4 in tumours was seen as compared to normal epithelium. In order to further investigate the distribution of HER3, two HER3 expressing cell lines originating from tongue cancer were analysed in vitro, using radiolabelled anti-HER3 antibodies directed to the extracellular domains of the receptor. The results indicated that HER3 was not present in measurable amounts in the cellular membrane. There is a need for improved diagnostics and therapy for the studied type of tumours, e.g. using radiolabelled antibodies or ligands, and EGFR seemed suitable as target since the expression was high, membrane associated and similar in the primary tumours and the corresponding metastases.
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
- Gao, Chaobing, et al.
(author)
-
Up-regulated expression of Dicer reveals poor prognosis in laryngeal squamous cell carcinoma
- 2014
-
In: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 134:9, s. 959-963
-
Journal article (peer-reviewed)abstract
- Conclusions: Increased expression of Dicer may be a prognostic biomarker for patients with laryngeal squamous cell carcinoma (LSCC). Objectives: Recent studies have shown that many microRNAs (miRNAs) play an important role in the development and progression of human cancers. Dicer, one of the most important enzymes of the miRNA machinery, performs the final step of biogenesis of miRNAs. This study aimed to investigate the impact of Dicer expression on patient survival in human LSCC. Methods: We detected the expression of Dicer in larynx tissue specimens from 76 LSCC samples and 26 polyps by immunohistochemistry. The clinicopathological and prognostic significance of Dicer expression was investigated in LSCC. Results: Our data showed that the expression of Dicer was significantly higher in the LSCC than in the polyp tissue specimens. Moreover, the expression level of Dicer was significantly associated with the pTNM stage and tumor lymph node metastasis. Kaplan-Meier survival analyses revealed a strong association between tumor Dicer expression and the survival of the patients with LSCC.
|
|
| 30. |
- Haylock, Anna-Karin, 1972-
(author)
-
Targeting molecules for diagnostics of Head and Neck squamous cell carcinoma
- 2017
-
Doctoral thesis (other academic/artistic)abstract
- To personalize treatment for cancer, correct staging of the primary tumor, nodal disease and metastatic disease is of essence. By targeting tumor specific receptors with radiolabeled antibodies, specificity and accuracy of imaging may be improved. Radio-immunodiagnostics can potentially detect small volume disease, occult metastasis and recurrent cancer in treated tissue. This thesis focuses on evaluation of radio-immunoconjugates directed towards CD44v6, which is a surface receptor overexpressed in many head and neck squamous cell carcinomas. At the outset, the monoclonal chimeric antibody cMab U36 and its cleavage products Fab’ and F(ab’)2 were labeled with 125I and assessed in vitro and in vivo (paper I). The best distribution pattern and tumor to organ ratio was achieved with F(ab’)2. Due to the immunological responses humans can develop towards chimeric antibodies, they are not optimal for clinical use, and subsequently fully human antibody fragments were developed. AbD15179, which is a monovalent fragment, was labeled with 111In and 125I and evaluated in vitro and in mice bearing CD44v6-expressing tumors. Tumor to organ ratios were improved compared to cMab U36 derived fragments, and 111In-AbD15179 displayed a more favorable distribution compared to 125I-AbD15179 (Paper II). A bivalent Fab-dHXL, AbD19384 derived from AbD15179, was then constructed and labeled with 125I and evaluated in cell- and biodistribution studies. Furthermore, an imaging study in a small animal PET was performed with 124I-AbD19384 (Paper III). Uptake in kidneys was reduced and liver uptake increased compared to AbD15179 reflecting the larger molecule. The high CD44v6 expressing tumor was clearly visualized with maximum uptake at 48 hours post injection.In paper IV human single chain fragments towards CD44v6v were selected, and the top candidates A11 and H12 were further evaluated in vitro and in vivo. Single chain fragments are small molecules exhibiting fast clearance and high affinity to the target. The study proved this by demonstrating superior tumor to blood ratios of radiolabeled A11 and H12 compared to previously studied molecules.
|
|
| 31. |
- Hsu, Wey-Jim, et al.
(author)
-
Image analysis of neurofilament immunoreactivity in human spiral ganglion
- 1997
-
In: Journal for Oto-Rhino-Laryngology. - 0301-1569 .- 1423-0275. ; 59:2, s. 258-62
-
Journal article (peer-reviewed)abstract
- Computer-assisted image analysis was used to study the immunoreactivity to NF-L, NF-M and NF-H in human spiral ganglion cells. The concentrations, represented by the relative mean grey of NF-L, NF-M and NF-H, were calculated and compared. The cell-area mean-grey correlations for NF-L, NF-M and NF-H were analysed and calculated, showing that NF-M is more specific to the larger cells (type 1?) and NF-H is more specific for the smaller cells (type 2?), while NF-L is non-specific for cell size. These findings confirm several previous assumptions by providing a quantitative basis. We conclude that image analysis is a useful-even essential-tool for the analysis of immunostained temporal bone sections.
|
|
| 32. |
- Hsu, Wey-Jim, et al.
(author)
-
Staphylococcus aureus exotoxin has limited and transient effects on cochlear electrophysiology
- 1998
-
In: Journal for Oto-Rhino-Laryngology. - : S. Karger AG. - 0301-1569 .- 1423-0275. ; 60:1, s. 12-17
-
Journal article (peer-reviewed)abstract
- Seven ears of Sprague-Dawley rats were exposed to 20 microliters Staphylococcus aureus exotoxin suspension by injection via the tympanic membrane into the round window niche. Another 6 ears were exposed to 20 microliters broth as controls. ABR was performed in the interval 2-31.5 kHz immediately before and 1, 2, 5, 7 and 10 days after the exposure. Although threshold changes could be found in the toxin-exposed group but not the control group in the frequency range 10-20 kHz, there were only statistically significant threshold changes--at 31.5 kHz--on the 1st, 2nd, 5th, and 7th days after the exotoxin injection. S. aureus exotoxin has minor transient but reversible effects on the inner ear, causing chiefly high-frequency threshold and latency changes.
|
|
| 33. |
- Hägg, Mary, et al.
(author)
-
Influence of lip force on swallowing capacity in stroke patients and in healthy subjects
- 2010
-
In: Acta oto-laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 130:11, s. 1204-1208
-
Research review (peer-reviewed)abstract
- Conclusion: In spite of no clinical signs of facial paresis, a pathological lip force (LF) will strongly influence swallowing capacity (SC). Stroke patients with impaired SC suffer a subclinical facial paresis. The results support earlier findings that LF training can be used to treat dysphagia. Objectives: Lip muscle training with an oral screen can improve both LF and SC in stroke patients, irrespective of the presence or absence of facial palsy. The aim was therefore to study the influence of LF on SC. Methods: This prospective study included 22 stroke patients, aged 38-90 years, with dysphagia, 12 with initial unilateral facial paresis and 45 healthy subjects, aged 25-87 years. All were investigated with a Lip Force Meter (LF100), and with an SC test. Results: A significant correlation was found between LF/SC (p = 0.012) in stroke patients but not in healthy subjects. LF/SC was not age-related in stroke patients. LF was not age-dependent in healthy subjects, but SC decreased with increasing age (p < 0.0001). However, SC did not reach a pathological value and a regression analysis showed that 73% of the variation in SC is attributable to LF and age.
|
|
| 34. |
- Hägg, Mary, et al.
(author)
-
Lip muscle training in stroke patients with dysphagia
- 2008
-
In: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 128:9, s. 1027-1033
-
Journal article (peer-reviewed)abstract
- Conclusion. Training with an oral screen can improve lip force (LF) and swallowing capacity (SC) in stroke patients with oropharyngeal dysphagia, irrespective of the duration of pretreatment of dysphagia, and irrespective of the presence or absence of central facial paresis. It is more plausible that treatment results are attributable to sensory motor stimulation and the plasticity of the central nervous system than to the training of the lip muscles per se. Objectives. A close relationship has been demonstrated between LF and SC in stroke patients whether or not they are affected by facial paresis. It is not known how training of lip function can improve swallowing capacity. The present study was therefore designed to ascertain: (i) if training with an oral screen can improve the LF and SC of stroke patients with oropharyngeal dysphagia, to establish (ii) if improvement in LF and SC is connected with the presence or absence of central facial palsy, (iii) on the interval between stroke onset and initiation of treatment, (iv) on age, or (v) on sex. Subjects and methods. This was a retrospective study of 30 stroke patients, 49-88 years old, who were investigated with a Lip Force Meter, LF100 (LF100) and a swallowing capacity test (SCT) before and after a period of self-training lasting at least 5-8 weeks, using an oral screen. Initial central facial paresis was present in 24 patients. Results. The median LF was 7 Newtons (N) (range 0-27) before treatment and 18.5 N (range 7-44) after treatment (p < , 0.001). The median SC was 0 ml/s (range 0-9.1) before treatment and 12.1 ml/s (range 0-36.7) at follow-up (p < , 0.001). There was no significant difference in swallowing improvement between patients with versus those without facial paresis. The interval between stroke attack and start of treatment, ranging from a few days up to 10 years, had no significant influence on the treatment results, nor did age or sex. The facial paresis was improved or at least ameliorated in all patients after the lip training period.
|
|
| 35. |
- Hägg, Mary, et al.
(author)
-
Reliable Lip force measurement in healthy controls and in patients with stroke : methodological study
- 2008
-
In: Dysphagia (New York. Print). - : Springer Science and Business Media LLC. - 0179-051X .- 1432-0460. ; 23:3, s. 291-296
-
Journal article (peer-reviewed)abstract
- A prefabricated oral screen has shown promising results as a muscle self-training device to improve the lip function of stroke patients affected by oropharyngeal dysphagia. However, a technique for the measurement of lip muscle force, whether in healthy individuals or in stroke patients, is lacking. The present study was designed to (1) test the intra- and interreliability of lip force measurements by means of a newly devised Lip Force Meter, LF100, (2) determine a normal lower limit for lip force in newtons (N), and (3) ascertain the instrument's sensitivity and specificity. LF100 is a modified strain gauge for recording the ability of lips to withstand pressure from a predentally placed oral screen. Forty-two healthy controls and 22 stroke patients agreed to participate in the trial. The controls and patients were examined three times with the LF100, with 2-min rest intervals, twice by investigator MH and once by investigator MO. Intrainvestigator reliability with the LF100 proved excellent in both controls and patients: ICC was 0.83 and 0.90, respectively. Interinvestigator reliability was good or excellent in both groups: ICC was 0.71 and 0.91. There was a significant difference in lip force between controls and stroke patients (mean = 24.7 +/- 6.3 N and 9.5 +/- 5.5 N, p < ; 0.001). The sensitivity of LF100 was 91% and the specificity 95%. The cutoff level for normal lip force was 15 N. The LF100 showed itself to be a suitable and reliable instrument for measuring lip force.
|
|
| 36. |
- Hägg, Mary, 1954-
(author)
-
Sensorimotor Brain Plasticity in Stroke Patients with Dysphagia : A Methodological Study on Investigation and Treatment
- 2007
-
Doctoral thesis (other academic/artistic)abstract
- AimsThe aims of the thesis were to validate investigation instruments for stroke patients with dysphagia, and to improve oropharyngeal dysphagia therapies.Methods/ResultsA Lip Force Meter, LF 100, affirmed excellent intra- and inter-reliability, sensitivity and specificity. Controls had significantly stronger lip force (LF) and swallowing capacity (SC) than stroke patients. A normal lower limit of LF was set to 15 Newton. Dysphagia symptoms improved in 7 stroke patients after a 5-week sensorimotor stimulation therapy comprising manual body and facial regulation in combination with palatal plate application. Impaired LF and impaired SC were parallel phenomena in 22 acute stroke patients and did not differ regardless of presence or absence of facial palsy. LF and SC improved and were parallel phenomena in 30 stroke patients and did not differ regardless of presence or absence of facial palsy, time lag between stroke attack and start of treatment, or age. SC was normalized in 19 of 30 dysphagia patients after a 5-8-week daily lip muscle self-training with an oral screen. ConclusionsLF100 is an appropriate and reliable instrument for measuring lip force. Dysphagia improvement, by body and facial sensorimotor stimulation in combination with palatal plate application, or by training with an oral screen is excellent examples of brain plasticity and cortical reorganisation. . Swallowing capacity and lip force in stroke patients are parallel phenomena. A sub clinical facial paresis seems to be present in most stroke patients. Training with an oral screen can improve LF and SC in stroke patients with oropharyngeal dysphagia.
|
|
| 37. |
- Iguchi, Hiroyoshi, et al.
(author)
-
Acute effects of semicircular canal destruction on the cochlea, with and without preceding Pseudomonas aeruginosa exotoxin A treatment
- 1998
-
In: Acta Oto-Laryngologica. - 0001-6489 .- 1651-2251. ; 118:4, s. 511-8
-
Journal article (peer-reviewed)abstract
- Acute electrophysiological and morphological changes in the cochlea following destruction of the semicircular canals (SCCs) were investigated to elucidate differences in cochlear vulnerability to surgical procedure under two conditions: normal healthy condition and a pathological condition induced by Pseudomonas aeruginosa exotoxin A (PaExoA). Frequency-specific auditory brainstem response recording and examination by light microscopy (LM) and scanning electron microscopy (SEM) were performed in the acute stage, immediately following, and 2, 5, and 10 days after the intervention. All normal healthy rats showed noticeable hearing loss immediately after the operation, predominantly in lower frequency areas, followed by complete recovery within 5 days. LM revealed rupture and slight distension of Reissner's membrane. SEM revealed considerable disarray of the stereocilia, especially on the outer hair cells (OHCs) of the third row in the upper half-turns of the cochlea. By contrast, all rats under pathological conditions showed delayed and incomplete hearing recovery from postoperative hearing loss. LM revealed various kinds of cochlear reaction, such as distension of Reissner's membrane, infiltration of inflammatory cells into the cochlea, and severe inflammatory change. Damage both of inner hair cells in the basal turn and of OHCs in the upper half-turns was more noticeable, compared with that under normal conditions. These findings indicate that SCC destruction under pathological conditions induced by PaExoA is detrimental to postoperative hearing recovery, even if the preoperative hearing level had appeared electrophysiologically normal.
|
|
| 38. |
- Iguchi, Hiroyoshi, et al.
(author)
-
Interleukin 8 can affect inner ear function
- 1998
-
In: Journal for Oto-Rhino-Laryngology. - : S. Karger AG. - 0301-1569 .- 1423-0275. ; 60:4, s. 181-9
-
Journal article (peer-reviewed)abstract
- The chemokine interleukin 8 (IL-8) was instilled into the round window niche of rats through a small perforation in the tympanic membrane in order to study its effect on inner ear function by electrophysiological and morphological techniques. The frequency-specific auditory brainstem response (ABR) was recorded at the frequencies 4, 8, 10, 12, 16 and 20 kHz just before and 1, 2, 5 and 14 days after instilling IL-8 to ascertain the hearing level during each interval. Morphological examination by light microscopy was performed during the same interval following the instillation of IL-8. On day 1, the rise in ABR threshold was within 5 dB SPL (non-significant elevation). However, a significant threshold elevation (above 5 dB SPL) occurred in high-frequency areas (16 and 20 kHz) on day 2, and in middle frequency areas (10 and 12 kHz) on day 5 with sensorineural hearing loss type intensity-latency curves. By day 14, the elevated thresholds had returned to pre-instillation levels. In the lowest areas (4 and 8 kHz), no significant threshold elevation was detected at any time during the observation period. By light microscopy, on day 1, clusters of inflammatory cells (predominantly neutrophils) were observed just outside the round window membrane (RWM), while only a few neutrophils were detected in the cochlea. These cells were still present outside the RWM on day 2. The neutrophils had disappeared by day 5 and only macrophages were present on the middle ear side of the RWM. However, throughout the observation period, the organ of Corti and stria vascularis appeared to be intact. These results suggest that IL-8 in the middle ear cavity is able to influence inner ear function.
|
|
| 39. |
- Ishibashi, Takuya, et al.
(author)
-
Changes in transient receptor potential vanilloid (TRPV) 1, 2, 3 and 4 expression in mouse inner ear following gentamicin challenge
- 2009
-
In: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 129:2, s. 116-26
-
Journal article (peer-reviewed)abstract
- CONCLUSION: It is suggested that transient receptor potential vanilloid (TRPV)-1 and -2 may be of pathological significance for sensory cells and ganglions, while TRPV-3 and -4 may play an important part in neuroprotection of the inner ear. OBJECTIVE: Changes in the expression of TRPV-1, -2, -3, and -4 in gentamicin (GM)-treated mouse inner ear were studied. MATERIALS AND METHODS: CBA/J mice were used in this study. The localization of TRPV-1, -2, -3, and -4 in the inner ear of both untreated and GM-treated CBA/J animals (intratympanic injection of 5 mg GM) was investigated by immunohistochemistry. RESULTS: TRPV-1, -2, and -3 were co-expressed in the inner ear sensory and ganglion cells, while TRPV-4 was also expressed in the stria vascularis and vestibular dark cells. Following GM treatment, the intensity of immunofluorescent reaction to TRPV-1 and TRPV-2 increased, while that to TRPV-3 and TRPV-4 decreased.
|
|
| 40. |
- Ishibashi, Takuya, et al.
(author)
-
Expression of transient receptor potential vanilloid (TRPV) 1, 2, 3, and 4 in mouse inner ear
- 2008
-
In: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 128:12, s. 1286-93
-
Journal article (peer-reviewed)abstract
- CONCLUSION: It is suggested that transient receptor potential vanilloids (TRPVs) may play a functional role in cell physiology and TRPV-4 and -2 may play an important part in fluid homeostasis in the inner ear. OBJECTIVE: Expression of TRPV-1, -2, -3, and -4 in the normal mouse inner ear was studied. MATERIALS AND METHODS: CBA/J mice were used in this study. The localization of TRPV-1, -2, -3, and -4 in the inner ear, i.e. cochlea, vestibular end organs, and endolymphatic sac, was investigated by immunohistochemistry. RESULTS: TRPV-1, -2, and -3 were co-expressed in hair cells and supporting cells of the organ of Corti, in spiral ganglion cells, sensory cells in vestibular end organs, vestibular ganglion cells, and sensory nerve fibers. TRPV-2 was also detected in the stria vascularis, dark cells, and endolymphatic sac. TRPV-4 was expressed in hair cells and supporting cells of the organ of Corti, in marginal cells of the stria vascularis, spiral ganglion cells, vestibular sensory cells, vestibular dark cells, vestibular ganglion cells, and epithelial cells of the endolymphatic sac.
|
|
| 41. |
- Kakoi, Hiroyuki, et al.
(author)
-
Auditory epidermal cell migration : V. Transmission electron microscopic study of tympanic membrane and external auditory canal in mouse
- 1996
-
In: Journal for Oto-Rhino-Laryngology. - 0301-1569 .- 1423-0275. ; 58:5, s. 280-7
-
Journal article (peer-reviewed)abstract
- The morphology of the tympanic membrane (TM) and external auditory canal (EAC) in mice was examined by transmission electron microscopy, in seven different regions: the handle of the malleus (HM) region, the intermediate and annular regions of the pars tensa (PT), the region of the pars flaccida (PF), the annular and osseous regions of the EAC and the cartilaginous region of the EAC. Each region displayed its own unique findings. In most regions of the TM and EAC-except the intermediate region of the PT-basal layer cells formed cytoplasmic processes (CPs) on their basal surface and adhered to the basement membrane (BM) by means of hemidesmosomes (HDs). This observation may suggest the presence of stem cells. In contrast, basal cells in the intermediate region of the PT did not extend any CPs from the basal surface but attached to the BM by a few characteristic spots of HD-like density but lacking the characteristics of HDs. It is concluded that stem cels are not present there and that basal cells connect loosely with the BM, thus providing the necessary morphological conditions to migrate laterally toward the annular region. The outermost layer of the epidermis in the annular region of the EAC showed numerous cytoplasmic projections (so-called 'finger-like projections'), representing keratinization and desquamation of epidermal cells (keratinocytes). These projections are believed to be the terminal differentiation of epidermal cells originating from the general centre in the HM region of the PT. The epidermis of the PF is an extension of the upper wall of the EAC, but the two regions differ morphologically.
|
|
| 42. |
- Kakoi, Hiroyuki, et al.
(author)
-
Auditory epidermal cell migration : VII. Antigen expression of proliferating cell nuclear antigens, PCNA and Ki-67 in human tympanic membrane and external auditory canal
- 1997
-
In: Acta Oto-Laryngologica. - 0001-6489 .- 1651-2251. ; 117:1, s. 100-8
-
Journal article (peer-reviewed)abstract
- A location of proliferating cells was investigated in eight human normal tympanic membranes (TMs) and external auditory canals (EACs) by an immunohistochemical method using two different types of antibodies for nuclear antigens in proliferating cells: anti-PCNA monoclonal antibody, and anti-Ki-67 polyclonal antibody. Four specimens prepared for cryostat sections were immunostained by both antibodies. Another four were fixed in 4% formaldehyde solution, embedded in paraffin wax and were reacted only with anti-PCNA antibodies. The expression pattern of Ki-67 was basically the same as of PCNA. In the pars tensa (PT), immunoreactivities were expressed in the nuclei of basal layer cells and cells just overlying the basal layer of epidermis both in the handle of the malleus (HM) and annular regions. In the intermediate region of the PT, no immunoreactivity was found basically, apart from a few labelled cells observed in the upper-third of the superior quadrant. In the pars flaccida (PF) and in both the osseous and cartilaginous regions of the EAC, positive cells were also situated in the basal layer and the deeper aspect of the suprabasal layers without any specific distributing pattern. It was certified that the generation centre of epidermal cells (keratinocytes) in the PT was located in both the HM and annular regions, and that stem cells in the PF and the EAC were uniformly scattered in the basal layer and the deeper aspect of the spinous layer. According to these findings, the migratory patterns of auditory epidermal cells in the human TM and EAC were discussed.
|
|
| 43. |
- Kakoi, Hiroyuki, et al.
(author)
-
Auditory epithelial migration : I. Macroscopic evidence of migration and pathways in the rat
- 1996
-
In: Acta Oto-Laryngologica. - 0001-6489 .- 1651-2251. ; 116:3, s. 435-8
-
Journal article (peer-reviewed)abstract
- Auditory epithelial migration (AEM) was studied in the rat for up to 42 days following the application of dye on the tympanic membrane (TM) and external auditory canal (EAC). Migratory pathways were similar to those in the human. In the pars tensa (PT), pathways were radially and centrifugally oriented from the handle of the malleus (HM) toward the annulus. However, the pathway along the HM from the umbo to the pars flaccida (PF), as reported in the human, was not observed in the rat; instead, a shallow downward pathway along the HM. In the PF, the radial spread of dye-markings from the proximal part of the HM to the upper wall of the EAC, as found in the human, was also observed in the rat. We conclude that the TM and EAC of the rat constitute an appropriate experimental model with which to study the human type of AEM.
|
|
| 44. |
- Kakoi, Hiroyuki, et al.
(author)
-
Auditory epithelial migration : II: Morphological evidence for auditory epidermal cell migration in rat
- 1996
-
In: Acta Oto-Laryngologica. - 0001-6489 .- 1651-2251. ; 116:6, s. 850-3
-
Journal article (peer-reviewed)abstract
- Morphology of the tympanic membrane (TM) and external auditory canal (EAC) was studied in healthy, intact rat ears. TM-perforated ears (3 days after making the perforation) and TM-perforation-healed ears (14, 28 and 42 days after making the perforation). In intact ears, the epidermis in the annular region of the EAC displayed a characteristic appearance with cytoplasmic protrusions. We termed these protrusions as "finger-like projections". In contrast to the rat, the annular region of the EAC in the guinea-pig did not show "finger-like projections". Following a perforation in the centre of the anterior or the posterior quadrant of the pars tensa in rats the "finger-like projections" disappeared from the annular region on the perforated side of the EAC, while the projections remained on the malleus side of the perforation edge. In perforation-healed ears analysed 42 days after the perforation, the "finger-like projections" had recurred in the annular region on the perforated side of the EAC. The "finger-like projections" are likely to express maturation (keratinization) and desquamation of epidermal cells in the pars tensa and also could constitute morphological evidence of their migration on the TM.
|
|
| 45. |
- Kakoi, Hiroyuki, et al.
(author)
-
Auditory epithelial migration : III. An immunohistologic study using anti-BrdU antibody on tympanic membrane in mouse
- 1997
-
In: Annals of Otology, Rhinology and Laryngology. - 0003-4894 .- 1943-572X. ; 106:5, s. 414-21
-
Journal article (peer-reviewed)abstract
- A localization pattern of epidermal cells on the tympanic membrane (TM) and their migratory patterns were studied in mice, by means of immunohistologic technique using an anti-bromodeoxyuridine (BrdU) antibody. The BrdU was instilled intraperitoneally and the animals were painlessly sacrificed between 1 hour and 10 days after the injection. An immunostaining technique using anti-BrdU antibodies was applied on whole mount TM tissues. One hour after injection, BrdU-labeled cells were found in the handle of the malleus (HM) region and in the annular region of the pars tensa of the TM. Some labeled cells were observed in the intermediate region of the upper half of the superior quadrant, but no labeled cells were found in the remaining part of the intermediate region. Labeled cells were also evident in the pars flaccida without any particular pattern of distribution. As time elapsed after the injection, the labeled cells first appearing in the HM region had migrated laterally and inferiorly from the HM toward the annulus, while those in the annular region had considerably decreased in number. Results of the present study are the following: 1) the proliferation center of epidermal cells in the pars tensa is located in two different areas, i.e., the HM region and annular region, 2) newly generated cells in the HM region migrated from the HM region toward the annular region, whereas those in the annular region migrate from the the annular region to the external auditory canal, and 3) no specific generation center is located in the pars flaccida. On the basis of these results, we discuss the relationship between the site of the proliferation center of epidermal cells and their migratory patterns.
|
|
| 46. |
- Kakoi, Hiroyuki, et al.
(author)
-
Auditory epithelial migration : IV. Light and scanning electron microscopic studies of the tympanic membrane and external auditory canal in the mouse
- 1996
-
In: Journal for Oto-Rhino-Laryngology. - 0301-1569 .- 1423-0275. ; 58:3, s. 136-42
-
Journal article (peer-reviewed)abstract
- The fine structures of the tympanic membrane and external auditory canal (EAC) were observed in the mouse under both the light microscope and scanning electron microscope. According to the differences in morphological features of the epidermis and epidermal cells, they were grossly classified into 8 types of region: (1) the region of the handle of the malleus, (2) the intermediate region of the pars tensa (PT), (3) the annular region of the PT, (4) the region of the pars flaccida, (5) the annular region of the anterior, inferior and posterior walls of the EAC, (6) the osseous region of the anterior, inferior and posterior walls of the EAC, (7) the region of the upper wall of the EAC and (8) the cartilaginous region of the anterior, inferior and posterior walls of the EAC. The specific structure "finger-like projections' was visualized throughout in the annular region of the EAC. The morphology of the region of the upper wall of the EAC was almost identical with that of the cartilaginous region of the anterior, inferior and posterior walls of the EAC.
|
|
| 47. |
- Kakoi, Hiroyuki, et al.
(author)
-
Cytokeratin expression patterns by one- and two-dimensional electrophoresis in pars flaccida cholesteatoma and pars tensa cholesteatoma
- 1995
-
In: Acta Oto-Laryngologica. - 0001-6489 .- 1651-2251. ; 115:6, s. 804-10
-
Journal article (peer-reviewed)abstract
- Expression patterns of cytokeratins (CKs) in normal skin, in pars flaccida type cholesteatoma (PFTC), and in pars tensa type cholesteatoma (PTTC) were examined by means of one- and two-dimensional electrophoretic techniques. Both CKs 14 and 5 pair (CKs 14/5) and CKs 10/1 were found in all materials. Neither CKs 16/6 nor 19 was found in the skin. CKs 16/6 and 19 were both found in 3 out of 5 PFTCs, only CKs 16/6 in 1 out of 5 and neither CKs 16/6 nor 19 in 1 out of 5. CKs 16/6 and 19 were both found in 1 out of 3 PTTCs, only CKs 16/6 in 1 out of 3 and neither CKs 16/6 nor 19 in 1 out of 3. There was no significant difference in the CKs expression patterns between PFTC and PTTC. The expression of CKs 16/6 and 19 suggested that their matrix epithelia were hyperproliferative. However, not all of the cholesteatomas were always hyperproliferative. Patterns of the terminal differentiation of CKs 1, 5, 10 and 14 in the PFTC or the PTTC were basically the same as those in the skin. In the cholesteatoma, eack CK gradually diminished in molecular weight in the cornified layer and debris. Desmosomal proteins were abundant in skin but not in cholesteatomas.
|
|
| 48. |
- Kakoi, Hiroyuki, et al.
(author)
-
Morphological changes in rat submandibular gland mucous cells during fixation with 10% formalin
- 1996
-
In: European Archives of Oto-Rhino-Laryngology. - 0937-4477 .- 1434-4726. ; 253:4-5, s. 214-21
-
Journal article (peer-reviewed)abstract
- The features of mucous cells in 10% formalin (FA)-fixed submandibular glands differ markedly from those fixed in glutaraldehyde (GA). We therefore studied morphological changes in mucous cells during 10% FA fixation. Mucous cells were fixed in either 10% FA, neutral sodium-phosphate-buffered (Na-PBed) 10% FA, ice-cold 10% FA or an ice-cold fixative mixture of 2.0% paraformaldehyde (PA) and 0.5% GA. Two different methods were used: immersion fixation and venous perfusion fixation. The 10% FA-fixed tissues had elliptical or flattened nuclei, a clear cytoplasm and no secretory granules. Tissues fixed with the fixative mixture displayed almost round nuclei, a broad endoplasmic reticulum and abundant secretory granules in the cytoplasm. Tissues immersion-fixed with neutral Na-PBed 10% FA or perfusion-fixed with ice-cold 10% FA had almost the same light microscopic appearance as that of the mixture-fixed tissues. To elucidate the process of morphological changes during 10% FA fixation at room temperature, samples immersed in 10% FA for varying periods of time were postfixed immediately in the fixative mixture and exposed to microwave irradiation. This method produced a variety of findings, even within the same section. There was a significant difference in the findings seen in the center of the section and at the periphery. The initial changes caused by 10% FA were rupture of the secretory granules located in the perinuclear region and destruction of the perinuclear organelles such as Golgi apparatus, mitochondria and endoplasmic reticulum. Absorption of the endoplasmic reticulum progressed so that the perinuclear region became translucent. To obtain a better structure in mucous cells from the fixed submandibular gland tissues, an appropriate fixative such as GA should be used and the fixative should infiltrate into the tissues as quickly as possible.
|
|
| 49. |
- Kareem, Heewa, et al.
(author)
-
Blocking EGFR in the liver improves the tumor-to-liver uptake ratio of radiolabeled EGF
- 2010
-
In: Tumor Biology. - : Springer. - 1010-4283 .- 1423-0380. ; 31:2, s. 79-87
-
Journal article (peer-reviewed)abstract
- Overexpression of epidermal growth factor receptor (EGFR) in several types of malignant tumors correlates with disease progression. EGFR could, therefore, be an excellent candidate for targeted radionuclide diagnostics. However, the high natural expression of EGFR in the liver may be problematic. The aim of this study was to improve the tumor-to-liver ratio of radiolabeled epidermal growth factor (EGF) by blocking its uptake by the liver with a nonradiolabeled EGFR-targeting molecule in tumorbearing mice. Intraperitoneally injected nonradiolabeled EGF was first evaluated as a blocking agent, preadministered at various time intervals before intravenous injection of 125I-labeled EGF. The anti-EGFR Affibody molecule (ZEGFR:955)2 was then assessed as a blocking agent of 111In-labeled EGF in a dual isotope study (50, 100, and 200μg, preadministered 30 or 60 min before 111In-EGF). The 30-min preadministration of nonradiolabeled EGF significantly decreased 125I-EGF uptake in the liver, whereas uptake in the tumor remained unchanged. Furthermore, preadministration of only 50μg (ZEGFR:955)2 as a blocking agent 30 min before the 111In-EGF decreased the uptake of 111In-EGF by the liver and increased its uptake by the tumor, thereby increasing the tumor-to-liver ratio sixfold. We conclude that the Affibody molecule (ZEGFR:955)2 shows promise as a blocking agent that could enhance the outcome of radionuclide-based EGFRexpressing tumor diagnostics and imaging.
|
|
| 50. |
- Katagiri, Yoshiaki, et al.
(author)
-
Long-term administration of vasopressin can cause Meniere's disease in mice
- 2014
-
In: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 134:10, s. 990-1004
-
Journal article (peer-reviewed)abstract
- Conclusion: A new murine model of Meniere's disease has been developed, based on long-term administration of vasopressin. Induction of vestibular dysfunction in the present animal model can cause additional stress, by reducing inner ear blood flow. Latanoprost, a selective agonist for the FP prostanoid receptor, may become a new remedy for Meniere's disease. Objective: The purpose of this study was to develop a more suitable animal model, with a closer resemblance to the pathophysiological process in Meniere's disease. Methods: Adult CBA/J or ICR mice were treated by subcutaneous injection of vasopressin for 5 days up to 8 weeks. Morphological analyses were performed of the cochlea, vestibular end organs and endolymphatic sac. The effect of latanoprost on the development of endolymphatic hydrops was also examined. Results: All experimental animals showed mild to moderate endolymphatic hydrops, increasing in severity as the vasopressin treatment was prolonged. Animals treated with vasopressin for 8 weeks showed severe endolymphatic hydrops with partial loss of outer hair cells and spiral ganglion cells. These animals also had a reversible vestibular dysfunction following intratympanic injection of epinephrine. Latanoprost inhibited the development of endolymphatic hydrops caused by vasopressin.
|
|
