| 1. |
- Werkström, Viktoria, et al.
(författare)
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Inhibitory innervation of the guinea-pig urethra; roles of CO, NO and VIP
- 1998
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Ingår i: Journal of the Autonomic Nervous System. - 0165-1838. ; 74:1, s. 33-42
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Tidskriftsartikel (refereegranskat)abstract
- The inhibitory innervation of guinea-pig urethral smooth muscle was investigated histochemically and functionally. The distribution of immunoreactivities to haem oxygenases (HO), neuronal NO synthase (nNOS), and vasoactive intestinal polypeptide (VIP) was studied, and the functional effects of the corresponding putative transmitters, CO, NO, and VIP, were assessed. HO-2 immunoreactivity was found in all nerve cell bodies of intramural ganglia, localized between smooth muscle bundles in the detrusor, bladder base and proximal urethra. About 70% of the ganglionic cell bodies were also NOS-immunoreactive (IR), whereas a minor part was VIP-IR. Some ganglion cells exhibiting tyrosine hydroxylase (TH) activity were demonstrated. Rich numbers of NOS-IR varicose nerve terminals could be found innervating the smooth muscle of the urethra, whereas VIP-IR terminals were less numerous. A rich number of TH-IR terminals were observed. The bladder showed a similar distribution of nerves, although only a few number of TH-IR nerves could be found. In bladder preparations exposed to sodium nitroprusside, cGMP-IR cells could be seen, forming an interconnecting network with long spindle-shaped processes. The cGMP-IR cells were especially abundant in the outer smooth muscle layers of the bladder, but less numerous in the urethra. In urethral strip preparations, electrical field stimulation evoked long-lasting frequency-dependent relaxations. The relaxations were not inhibited by the NO-synthesis inhibitor, L-NOARG, or enhanced by the NO-precursor, L-arginine. The haem precursor, 5-aminolevulinic acid (5-ALA), or the inhibitor of guanylate cyclase, ODQ, did not affect the urethral relaxations. Exogenously applied NO, SIN-1, and VIP relaxed the preparations by approximately 50%, whereas the relaxation evoked by exogenous CO was minor. These results suggest that CO probably is not involved in non-adrenergic, non-cholinergic inhibitory control of the guinea-pig urethra, where a non-NO/cGMP mediated relaxation seems to be predominant.
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| 2. |
- Mellander, Stefan, et al.
(författare)
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Cardiovascular regulation by endogenous nitric oxide is essential for survival after acute haemorrhage
- 1997
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 160:1, s. 57-65
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Tidskriftsartikel (refereegranskat)abstract
- Our previous studies have indicated that endogenous nitric oxide serves as a physiologically important inhibitor of vascular tone during acute haemorrhage. This vasodilator action attenuates the concomitant reflex adrenergic constriction and thereby prevents critical reduction of tissue blood flow. The present study aimed to evaluate the overall importance of this nitric oxide regulation for survival after acute haemorrhage. This was done by comparative observations of survival time and circulatory, metabolic and histopathological changes after an acute standardized lethal blood loss (45%) in cats exposed to nitric oxide synthase (NOS) inhibition and in matched control animals with intact nitric oxide regulation. NOS inhibition was instituted by intravenously administered N omega-nitro-L-arginine methyl ester. The survival time averaged 2 h 49 min in the NOS-blocked animals and 10 h 14 min in the control animals (P < 0.001). NOS inhibition thus reduced the posthaemorrhagic survival time to < 30% of that in the control cats. Haemorrhage in the NOS-blocked animals led to rapidly developing arterial hypotension, increased anaerobic metabolism, metabolic lactacidosis, hyperkalaemia, and morphological tissue damage especially in heart and liver, in spite of maintained arterial normoxia, which signifies tissue hypoxia caused by seriously impaired nutritional blood supply. At the time of death of the NOS-blocked cats, the control animals still exhibited a virtually normal circulatory/metabolic state. A much later, and more slowly developing circulatory/metabolic deterioration was observed in the control animals. These differences between the two groups of animals indicate that nitric oxide release, by its vasodilator action, to a significant extent helps to maintain an adequate nutritional blood supply to the tissues in acute haemorrhage.
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| 3. |
- Gudmundsson, Thorkell E., et al.
(författare)
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Methodological aspects of flow cytometry DNA analysis in endometrial carcinoma, with special reference to sampling and reproducibility
- 1996
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 35:8, s. 999-1006
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Tidskriftsartikel (refereegranskat)abstract
- Two adjacent paraffin-embedded sections manifested concordance in ploidy status in 96% of cases (45/47), and the standard deviation (SD) for SPF was 2.7%. Analysis of 'micro-heterogeneity', within a distance of < or = 700 microm, yielded results for concordant ploidy status in 94% of cases, and the SD for SPF was 1.9% (n = 17). Frozen and paraffin-embedded material yielded concordant results for ploidy status in 87% (39/45) of cases, and SPF values were significantly lower (mean difference 1.5%) in the frozen samples. Diagnostic and repeat curettage material yielded concordant results for DNA ploidy status in 85% (40/47) of cases, and no significant difference in mean SPF (12% vs. 11%) was found. Discordant DNA ploidy results were attributable to small differences in the DNA histograms influencing the interpretation of near-diploid, near-tetraploid and small non-diploid cell populations, and the influence of debris on SPF estimation. On the basis of our findings and the practical advantage we recommend paraffin-embedded material from diagnostic curettage for FCM DNA analysis; the results are available sooner and the handling and transportation of tumor samples is more convenient.
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| 4. |
- Gudmundsson, Thorkell E, et al.
(författare)
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The prognostic information of DNA ploidy and S-phase fraction may vary with histologic grade in endometrial carcinoma
- 1995
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 34:6, s. 803-812
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Tidskriftsartikel (refereegranskat)abstract
- DNA ploidy and S-phase fraction (SPF) were determined by flow cytometry on paraffin-embedded tumor material from 243 patients treated during 1980-1985. Patients with well differentiated and moderately differentiated tumors without solid areas (n = 351) formed a low-risk group (corrected 5-year survival 90%). Twenty-four patients, dead of disease within 5 years, were compared with 52 survivors. The estimated death risk was higher for those with SPF > or = 8.0% compared with those with SPF < 8.0% (odds ratio = 18.2; p < 0.001). SPF was the only independent prognostic factor in a multivariate analysis also including age, clinical stage and grade of differentiation. Patients with moderately differentiated tumors with solid areas or poorly differentiated tumors (n = 208) were regarded as a high-risk group. There was a difference in survival according to ploidy; the corrected 5-year survival was 75% for 106 patients with diploid tumors compared with 44% for those with non-diploid tumors (p < 0.0001). In a multivariate analysis DNA ploidy, age and clinical stage were independent prognostic factors, whereas SPF was no longer significant. Thus, DNA ploidy and SPF have different prognostic values depending on histological grade of endometrial carcinoma.
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| 5. |
- Olsson, H, et al.
(författare)
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Proliferation of the breast epithelium in relation to menstrual cycle phase, hormonal use, and reproductive factors
- 1996
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Ingår i: Breast Cancer Research and Treatment. - 1573-7217. ; 40:2, s. 187-196
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Tidskriftsartikel (refereegranskat)abstract
- The proliferative rate in normal breast epithelium from 58 women undergoing reduction mammoplastics was studied using the formalin resistant antibody Ki-S5, and related to age at operation, menstrual cycle phase, family history of breast cancer, height and weight, parity, and hormonal use. The breast tissue from women operated on in the luteal menstrual cycle phase (day 15-28 among oral contraceptive (OC) users) had significantly higher proliferative rate than breast tissue removed from women in the follicular phase (day 1-14) (p = 0.01). Among women presently exposed to hormones, those with a positive family history of breast cancer among first and second degree relatives had significantly higher values than cases without such history (p = 0.02). Weight was not significantly related to proliferation rate, while a short height was associated with a significantly higher proliferation rate (p = 0.04). Women who used OCs before the first full-term pregnancy (FFTP) had a significantly higher proliferation rate compared with never users or late users (p = 0.04). No significant difference was seen between parous versus nulliparous women. The results from the univariate analysis persisted in multivariate models. An especially high proliferation rate was seen in young women with both a positive family history and present hormonal use (p = 0.001). Overall, it was found that young women had a non-significantly higher proliferation rate than older women (p = 0.10). Due to small sample size, these results must be regarded as preliminary, especially in the subgroup analyses.
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