| 1. |
- Abbasi, Sakineh, et al.
(författare)
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Association of estrogen receptor-alpha A908G (K303R) mutation with breast cancer risk
- 2013
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Ingår i: International Journal of Clinical and Experimental Medicine. - 1940-5901. ; 6:1, s. 39-49
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Tidskriftsartikel (refereegranskat)abstract
- Genetic mutations in premalignant breast lesions may have a role in malignancy progression or influence the behavior of subsequent disease. A point mutation in estrogen receptor-alpha (ER-&ALPHA) as A908G (Lys303 -> Arg) was originally involved to hypersensitive to estrogen breast hyperplasia. We detected this mutation among Iranian women with invasive breast cancer. A population-based case-control study was conducted in 150 newly diagnosed invasive breast cancer and 147 healthy control individuals controls to screen for presence of the ER-alpha A908G mutation by using single-strand conformation polymorphism (SSCP) analysis and 33Pcycle DNA sequencing. We detected the 10.7% ER-alpha A908G mutation in the form of heterozygote genotype only among cancer patients (chi(2)=22.752, P=0.00). The allelic frequency of mutant allele AGG in codon 303 was significantly (chi(2)=29.709, P=0.001) higher in patients with the family history of breast cancer (28.9%) than those without the family history of breast cancer (1.9%). Our data suggest that ER-alpha codon 303 mutation is correlated with various aspects of breast cancer in Iran. ER-alpha genotype might represent a surrogate marker for predicting breast cancer developing later in life.
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| 2. |
- Abbasi, Sakineh, et al.
(författare)
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Estrogen receptor genes variations and breast cancer risk in Iran
- 2012
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Ingår i: International Journal of Clinical and Experimental Medicine. - 1940-5901. ; 5:4, s. 332-341
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Tidskriftsartikel (refereegranskat)abstract
- Evidence suggests that alterations in estrogen signaling pathways, including estrogen receptor alpha (ER-alpha) and estrogen receptor beta (ER-beta) occur during breast cancer development. ER-alpha and ER-beta genes polymorphisms have been found to be associated with breast cancer and clinical features of the disease in the western countries. In the current study, we evaluated the hypothesis that certain sequence variants of the ER-alpha and ER-beta genes are associated with an additively increased risk for breast cancer in Iranian women breast cancer patients. The genes were scanned in 150 Iranian patients with newly diagnosed invasive breast tumors and in healthy control individuals by PCR single-strand conformation polymorphism (SSCP) method. Three single nucleotide polymorphisms (SNPs) in codon10 (TCT -> TCC), codon 352 (CCG -> CCC) and codon 594 (ACG -> ACA) in ER-alpha gene and one SNP codon 392 (CTC -> CTG) in ER-beta were revealed have additive effects in developing breast cancer and LN metastases. Also, SNP in codon 392 of estrogen receptor-beta gene is more effective (threefold) than those SNPs in codons 10, 325, 594 of estrogen receptor-alpha gene in developing LN metastases in breast cancer patients. SNPs in estrogen receptor alpha and beta have additive effects in increasing risk for developing breast cancer with LN metastases among Iranian women breast cancer patients.
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| 3. |
- Basu, Samar, et al.
(författare)
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Cytokine-mediated inflammation is independently associated with insulin sensitivity measured by the euglycemic insulin clamp in a community-based cohort of elderly men
- 2011
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Ingår i: International Journal of Clinical and Experimental Medicine. - : E-Century Publishing. - 1940-5901. ; 4:2, s. 164-168
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Tidskriftsartikel (refereegranskat)abstract
- Both clinical and experimental studies suggest a close relation between an inflammatory state and insulin resistance. We investigated the association between cytokine-mediated inflammation (high sensitivity C reactive protein [hsCRP] and interleukin [IL] 6) and insulin sensitivity (insulin-mediated glucose disposal rate, assessed by the euglycemic insulin clamp) in a community-based cohort, with subgroup analyses of normal weight individuals without diabetes mellitus and metabolic syndrome (NCEP). hsCRP and IL- 6 were inversely associated with insulin sensitivity (multivariable-adjusted regression coefficient for 1-SD increase of hsCRP -0.12 (-0.21-(-0.03), p=0.01) and of IL-6 - 0.11 (-0.21-(-0.02), p=0.01) in models adjusting for age and components of the metabolic syndrome (systolic and diastolic blood pressure, antihypertensive drugs, HDL-cholesterol, triglycerides, fasting plasma glucose, waist circumference). The multivariable-adjusted association between hsCRP, IL-6 and insulin sensitivity were of a similar magnitude in normal weight individuals without diabetes and without the metabolic syndrome. Our data show that cytokine -mediated subclinical inflammation is independently associated with decreased insulin sensitivity also in apparently metabolically healthy normal weight individuals, indicating that the interplay between inflammatory processes and insulin resistance is present already in the early stages of the development of glucometabolic disease. (IJCEM1012002).
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| 4. |
- Blom, Elisabeth, et al.
(författare)
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68Ga-Labeling of RGD peptides and biodistribution
- 2012
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Ingår i: International Journal of Clinical and Experimental Medicine. - 1940-5901. ; 5:2, s. 165-172
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Tidskriftsartikel (refereegranskat)abstract
- Several peptides comprising Arg-Gly-Asp (RGD) domain and macrocyclic chelator were labeled with 68Ga for the imaging of angiogenesis. The analogues varied in peptide constitution, linker and chelator type. The labeling efficiency did not vary with the peptide constitution and linker type, but depended on the chelator type. Four of the compounds containing 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) chelator were labeled at 90 ± 5°C using conventional or microwave heating reaching 90% of 68Ga incorporation after 5 and 2 min respectively, when the concentration of the precursor was 2.5 μM. The compound having 2,2',2''-(1,4,7-triazonane-1,4,7-triyl)triacetic acid (NOTA) as the chelator could be labeled at room temperature within 5 min using 2.5 μM peptide precursor. Two of the compounds contained a poly (ethylene glycol) (PEG) linker to the chelator. The biodistribution of the analogues was studied in male rats.
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| 5. |
- Blom, Elisabeth, et al.
(författare)
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Ga-68-Labeling of RGD peptides and biodistribution
- 2012
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Ingår i: International Journal of Clinical and Experimental Medicine. - 1940-5901. ; 5:2, s. 165-172
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Tidskriftsartikel (refereegranskat)abstract
- Several peptides comprising Arg-Gly-Asp (RGD) domain and macrocyclic chelator were labeled with Ga-68 for the imaging of angiogenesis. The analogues varied in peptide constitution, linker and chelator type. The labeling efficiency did not vary with the peptide constitution and linker type, but depended on the chelator type. Four of the compounds containing 2,2', 2 '', 2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl) tetraacetic acid (DOTA) chelator were labeled at 90 +/- 5 degrees C using conventional or microwave heating reaching 90% of Ga-68 incorporation after 5 and 2 min respectively, when the concentration of the precursor was 2.5 mu M. The compound having 2,2', 2 ''-(1,4,7-triazonane1,4,7-triyl)triacetic acid (NOTA) as the chelator could be labeled at room temperature within 5 min using 2.5 mu M peptide precursor. Two of the compounds contained a poly (ethylene glycol) (PEG) linker to the chelator. The biodistribution of the analogues was studied in male rats.
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| 6. |
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| 7. |
- Engler, Henry, et al.
(författare)
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Imaging astrocytosis with PET in Creutzfeldt-Jakob disease : case report with histopathological findings
- 2012
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Ingår i: International Journal of Clinical and Experimental Medicine. - 1940-5901. ; 5:2, s. 201-207
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Tidskriftsartikel (refereegranskat)abstract
- In a previous study, patients with suspect Creutzfeldt-Jakob's disease (CJD) have been examined with Positron Emission Tomography (PET) combining N-[11C-methyl]-L-deuterodeprenyl (DED) and [(18)F] 2- fluorodeoxyglucose (FDG) in an attempt to detect astrocytosis and neuronal dysfunction, two of the hallmarks in CJD. Increased DED uptake with pronounced hypometabolism matching the areas with high DED retention was found in the fronto-parieto-occipital areas and cerebellum of patients with confirmed CJD. However, the temporal lobes did not present such a pattern. In 6 of the 15 examined patients the autopsy was performed, but a strict comparison between the PET results and the histopathology could not be done. Recently, one patient with suspect CJD was examined with PET using DED and FDG. The results of the examinations in this patient showed a pattern similar to that found in the brain of the CJD patients from the first study. The patient died shortly after the examination and an autopsy could be performed. The autopsy showed neuronal death, astrocytosis and spongiform changes in the brain. The diagnosis of definite sporadic CJD was established by the Western blot analysis, confirming the presence of the prion resistant protein (PrPres). The PET data demonstrated high DED uptake and extreme low glucose uptake in the left brain hemisphere whereas the right side was less affected. The autopsy was performed allowing the comparison between high DED uptake and the histopathological findings of reactive astrocytosis revealed by immunostaining with antibodies against glial fibrillary acid protein (GFAP). The results confirmed the presence of a pattern with high ratio DED/FDG, similar to that found in the previous study and revealing for the first time, a good correlation between high DED uptake and high density of reactive astrocytes as demonstrated by immunostaining.
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| 8. |
- Eriksson, Staffan
(författare)
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Thymidine kinase 1 is a better prognostic marker than Ki-67 for pT1 adenocarcinoma of the lung
- 2014
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Ingår i: International Journal of Clinical and Experimental Medicine. - 1940-5901. ; 7, s. 2120-2128
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The sensitivity and reliability of the biomarkers thymidine kinase 1 (TK1) and Ki-67 were studied in relation to clinical features and prognosis of survival for pathological-T1 (pT1) lung adenocarcinoma patients. Methods: TK1 and Ki-67 expression was determined in 80 patients with pT1 adenocarcinoma of the lung and in 20 specimens from normal lung tissues, using immunohistochemistry. Results: TK1 was found in most lung tumor cells both in the cytoplasm and the nuclei. The positive labelling index (LI) for total TK1 was significantly higher than that for Ki-67. There was a significant correlation between the LI of total TK1 and lymph node metastasis, degree of tumor invasion and pathologic stages, which was not found for Ki-67. In addition, the overall 5-year survival of patients was statistically significant different between low and high levels of TK1 expression, but not in cases of Ki-67. A multivariate analysis revealed that expression of TK1, lymph node involvement and TNM pathology staging could serve as independent prognostic factors for the disease progression of pT1 lung adenocarcinoma patients. Conclusions: Compared with Ki-67, TK1 is a more reliable proliferation index in pT1 adenocarcinoma of lung, which can evaluate the invasion and the prognosis of tumor.
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| 9. |
- Farnebo, Simon, et al.
(författare)
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Continuous assessment of concentrations of cytokines in experimental injuries of the extremity
- 2009
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Ingår i: International Journal of Clinical and Experimental Medicine. - : e-Century Publishing Corporation. - 1940-5901. ; 2:4, s. 354-362
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Tidskriftsartikel (refereegranskat)abstract
- Background. Inflammation plays an important part in the healing process. Little is known about the extent local inflammatory trauma response interacts with the central circulation and inflammation produced by central organs. The aim of the present study was to examine whether high cut-off microdialysis catheters offer potential to in real time assess interstitial cytokines variations in conjunction to markers of metabolism distal to a blunt vascular contusion. Methods. In a standardised contusion trauma model, microdialysis catheters (high MW (100kDa)) were inserted in the gracilis muscle distal to the trauma for the local assessment of IL-6, IL-8, TNF-a, total protein and the metabolic mediators (glycerol, puruvate and lactate). The contra lateral uninjured leg served as control of the centrally mediated inflammation propagated to the extremities. Results. The trauma led to a significant and quantitatively large (8-10 fold) increase in inflammatory cytokines (IL6 and 8) as measured both in the injured and control legs. There was only a minor, and not significant increase in concentrations of cytokines in the injured leg compared to the control leg.. There were no signs of ischemia in either leg. Conclusion. The new finding in this study is that both central, and local, inflammatory responses as well as metabolic mediators may be assessed continuously in skeletal muscle tissue distal to a major injury in an animal model. The findings suggest that the large trauma elicits a generalised inflammatory response to trauma rather than propagating a local one distal to the trauma.
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| 10. |
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| 11. |
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| 12. |
- Helmersson-Karlqvist, Johanna, et al.
(författare)
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24-Hour ambulatory blood pressure associates inversely with prostaglandin F-2 alpha, interleukin-6 and F-2-isoprostane formation in a Swedish population of older men
- 2012
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Ingår i: International Journal of Clinical and Experimental Medicine. - 1940-5901. ; 5:2, s. 145-153
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Tidskriftsartikel (refereegranskat)abstract
- Vasoconstrictive prostaglandins (PGs), such as PGF(2 alpha), F-2-isoprostanes, and systemic inflammation may be involved in the physiological regulation of blood pressure (BP) and the pathophysiology leading to hypertension. However, studies evaluating these parameters and BP in human populations are sparse. We analysed the cross-sectional associations between 24-hour ambulatory BP and urinary 15-keto-dihydro-PGF(2 alpha) (indicator of PG-mediated vasoconstriction and inflammation), plasma interleukin-6 (IL-6), C-reactive protein (CRP), serum amyloid A (SAA) and urinary F-2-isoprostanes (indicator of vasoconstriction and oxidative stress) in 619 men in a Swedish older population (Uppsala Longitudinal Study of Adult Men, age 78 years). Both systolic and diastolic 24-hour BP correlated inversely with concentrations of 15-keto-dihydro-PGF(2 alpha) (P < 0.01) and F-2-isoprostanes (P< 0.01) independent on other cardiovascular risk factors. Additionally, diastolic 24-hour BP inversely correlated with plasma IL-6 (P< 0.05) and 24-hour pulse pressure showed a positive linear correlation with IL-6, CRP and SAA. In conclusion, high BP is associated with decreased formation of vasoconstrictive PGF(2 alpha) and F-2-isoprostanes in this population of older men. These findings, although unlike our original hypothesis, might have an important physiological function which needs to be further evaluated.
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| 13. |
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| 14. |
- Koulouras, Vasilios P., et al.
(författare)
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Effects of inhaled carbon monoxide and glucocorticoids in porcine endotoxin sepsis
- 2011
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Ingår i: International Journal of Clinical and Experimental Medicine. - 1940-5901. ; 4:1, s. 53-66
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Recent animal studies have demonstrated that pre-treatment with inhaled carbon monoxide (iCO) exert anti-inflammatory effects in various septic models. In all these models, there is no information whether iCO might act therapeutically after the onset of septic damage. The objective of this study was to investigate the potential anti-inflammatory effects of iCO to treat established injury in a model of porcine endotoxin sepsis.METHODS:Five groups of pigs (n=6 in each group), were studied under anesthesia and mechanical ventilation: healthy control group (HC); lipopolysaccharide (LPS) groups, animals received continuous IV infusion of LPS for 6 hours; 2.5 hours after of LPS infusion treated groups received either: 250 ppm of iCO for 3.5 h, (LPS+CO group); 3 mg/Kg hydrocorti-sone bolus [Steroid (ST)], (LPS+ST group); or both steroid and iCO, (LPS+CO+ST group). Measurements of haemodynamics, blood gases, respiratory mechanics and biochemistry of organ function, were made. At the end of the experiment lung tissue was taken for analysis of histology and inflammatory markers: tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), activator protein-1 (AP-1) and glucocorticoid receptor (GR).RESULTS:LPS administration induced a dramatic inflammatory injury in lungs, increased expression of TNF-α, NF-κB, AP-1, down regulation of GR, pulmonary hypertension and severe deterioration of respiratory mechanics, oxygenation and organ function. Treatment with steroids and to greater extent with iCO significantly improved the microscopic appearance of the lung but had no effect on inflammatory markers. iCO significantly decreased pulmonary hypertension induced by LPS, without an obvious protective effect on organ function.CONCLUSION:Using this porcine sepsis model we find that treatment with iCO after the septic damage decreases pulmonary hypertension and partially protects the lung tissue from the inflammatory destruction induced by LPS but has no beneficial effects on organ function.
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| 15. |
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| 16. |
- Lindqvist, Markus, et al.
(författare)
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Plasma glycosylphosphatidylinositol phospholipase D (GPI-PLD) and abdominal aortic aneurysm.
- 2012
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Ingår i: International Journal of Clinical and Experimental Medicine. - 1940-5901. ; 5:4, s. 306-9
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Tidskriftsartikel (refereegranskat)abstract
- Recent reviews state that a circulating biomarker predicting aortic rupture risk would be a powerful tool to stratify patients with small screen-detected abdominal aortic aneurysm (AAA). In a current proteomic pilot-study elevated levels of the enzyme Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) was shown in patients with small AAA compared with controls without aneurysm. In the present study we investigated the impact of plasma GPI-PLD as a biomarker in patients with AAA in relation to aneurysm size, and rupture. Plasma GPI-PLD was measured in patients with AAA (nonruptured, n=78 and ruptured, n=55) and controls without aneurysm (n=41) matched by age, sex and smoking habit. The plasma GPI-PLD levels were significantly lower in patients with ruptured compared nonruptured AAA which we interpreted as a result of hemodilution due to hemorrhage in patients with ruptured AAA. The plasma GPI-PLD levels were similar in patients with nonruptured AAA compared to the controls without aneurysm. Furthermore, there was no correlation between plasma GPI-PLD and aneurysm size in the group of patients with nonruptured AAA. In conclusion, the present study fails to show a connection between GPI-PLD and AAA. However, the definite role of GPI-PLD as a predictive marker needs to be further clarified in a follow-up cohort study.
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| 17. |
- Mutalifu, Yalikun, et al.
(författare)
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Multiple different laminar velocity profiles in separate veins in the microvascular network of brain cortex in rats
- 2011
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Ingår i: International Journal of Clinical and Experimental Medicine. - Madison, WI, United States : e-Century Publishing. - 1940-5901. ; 4:1, s. 10-16
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Tidskriftsartikel (refereegranskat)abstract
- The orthogonal polarisation spectral (OPS) imaging technique is a method that enables intravital microscopy of the tissue microvasculature particularly including the erythrocytes and leucocytes. As a new finding we here report multi flow, i.e, several different laminar velocity profiles in each and separate veins (diameters < 200 μm) of the microcirculation of the rat brain cortex. The phenomenon was present in all 20 preparations studied and these different laminar velocity profiles were regularly maintained in length beyond 20 times the diameter of parent vessel. In single veins up to 9 different laminar velocity profiles were discernible, each with a different red blood cell velocity. These multi flow profiles may theoretically be anticipated based on what is known in rheological physiology as the Fahreus - Lindqvist effect. It may also be predicted in tissues that have both high and heterogeneous blood flows in conjunction with large local variations in metabolic activity as are present in the cortex of the brain. The new information is that the extent and magnitude of this multi laminar flow phenomenon especially in the venular network of the brain exceeds what has previously been known. The physiological importance of these finding warrants further studies.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Zhang, Hong, 1957-, et al.
(författare)
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Upregulation of nucleoporin 88 is associated with nodal metastasis and poor differentiation in oral squamous cell carcinoma
- 2016
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Ingår i: International Journal of Clinical and Experimental Medicine. - : e-Century Publishing. - 1940-5901. ; 9:5, s. 8399-8404
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Tidskriftsartikel (refereegranskat)abstract
- Nucleoporin 88 (Nup 88) is a component of the nuclear pore complexes (NPCs) that mediates nucleocytoplasmic trafficking of macromolecules, Nup 88 has been reported to be up-regulated in a wide variety of malignancies. Studies show that overexpression of this antigen is associated with the development, agressiveness, differentiation and prognosis in some tumours. Since no study has been carried out in the relationship between the Nup 88 expression and clinicopathological features in the patients with oral squamous cell carcinoma (OSCC), this study aimed to determine Nup 88 expression in OSCC and its clinicopathological significance. Nup 88 expression was examined by immunohistochemistry in 20 normal oral mucosa specimens and 83 OSCC tissues. The frequency of positive Nup 88 expression was gradually increased from normal oral mucosa (10%) to primary OSCC (40%, P=0.012). The Nup 88 positive rate in OSCC patient with nodal metastasis was significantly higher than those without nodal metastasis (64% vs. 21%, P=0.000085). The frequency of positive Nup 88 expression was significantly different between worse and better differentiation (80 vs. 27%, P=0.000024). Nup 88 expression was not related to the patients' gender, age, location and tumour size (P>0.05). In conclusion, Nup 88 may play an important role in tumorigenesis in oral squamous cell carcinoma. Upregulation of Nup 88 is associated with nodal metastasis and poor differentiation in oral squamous cell carcinoma.
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