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Biomedical subjects

M Perera

Publications and source records attributed to M Perera.

At least 19 recordsLinked to original sources
PubMed2005

Disruption of the murine PIASx gene results in reduced testis weight.

PIASx belongs to the PIAS protein family, the members of which modulate activities of several transcription factors and act as E3 ligases in the sumoylation pathway. The PIASx gene is highly expressed in testis, suggesting a role in spermatogenesis. To investigate the function of PIASx in vivo, we have disrupted the PIASx gene in mice. Interestingly, the knockout mice were viable and fertile. Despite the normal fertility, the testis weight of the mutant animals was reduced and their number of apoptotic testicular cells was increased. Also, the sperm count of mutant mice tended to be reduced, but the quality of their sperm cells was normal. No significant changes were observed in the serum levels of LH and FSH or in the intratesticular testosterone concentration between the knockout animals and their wild-type littermates. Compensatory increases in other PIAS protein mRNAs were not observed in the knockout mice. These results imply that PIASx is required quantitatively rather than qualitatively for normal spermatogenesis.

Animals↗
PubMed2002

Hormone replacement therapy can augment vascular relaxation in post-menopausal women with type 2 diabetes.

BACKGROUND: Diabetes is a major risk factor for coronary heart disease in women and event rates increase substantially after the menopause. Observational studies have suggested that estrogens may provide cardioprotection by regulating endothelial nitric oxide synthase. METHODS: In order to examine the effect of hormone replacement therapy (HRT) on endothelium-dependent and -independent vascular relaxation in post-menopausal women with type 2 diabetes, an open study was conducted in which gluteal biopsies were collected from 17 women before and after 6 months of transdermal 17 beta-estradiol (80 microg twice weekly) in combination with oral norethisterone (1 mg daily). Small arteries (<550 microm) were dissected from fat and mounted on a wire myograph for assessment of relaxation in response to acetylcholine (ACh), bradykinin (BK) and sodium nitroprusside (SNP). RESULTS: Maximal relaxation responses to ACh, BK and SNP in women with diabetes and non-diabetic control subjects were 52 +/- 8 versus 96 +/- 2% (P < 0.05), 76 +/- 7 versus 97 +/- 1%, (P < 0.05) and 91 +/- 2 versus 98 +/- 1% (P < 0.05) respectively. After 6 months of HRT, maximal relaxation responses to ACh, BK and SNP in women with diabetes (compared with pre-HRT) were: 88 +/- 4 (P < 0.05), 93 +/- 3 (P < 0.05) and 98 +/- 1% (P < 0.05) respectively. At baseline and after HRT, EC50 (concentration required to obtain 50% of maximum response) data exhibited similar changes. CONCLUSIONS: HRT had potentially beneficial effects on vascular relaxation. Data were consistent with improvements in endothelial function, vascular smooth muscle function, or both. Controlled studies are required to confirm and extend these findings.

Acetylcholine↗
PubMed2001

The effects of transdermal estradiol in combination with oral norethisterone on lipoproteins, coagulation, and endothelial markers in postmenopausal women with type 2 diabetes: a randomized, placebo-controlled study.

People with type 2 diabetes have a substantially increased risk of coronary heart disease (CHD). Short-term studies with unopposed oral estradiol in women with diabetes have suggested potentially beneficial effects on lipids, thrombotic factors, and insulin sensitivity. However, most (nonhysterectomized) postmenopausal women require combined estrogen-progesterone preparations. We randomized 43 women with type 2 diabetes either to continuous transdermal estradiol (80-microg patches) in combination with oral norethisterone (1 mg daily) or to identical placebos. Blood samples were taken before and after 6 months for measurement of lipoproteins, coagulation factors, and endothelial markers. Total cholesterol and triglyceride concentrations decreased by 8% and 22%, respectively, in those receiving hormone replacement therapy (P < 0.05 relative to change in placebo group after adjustment for baseline concentrations). There was a trend toward a reduction in high density lipoprotein cholesterol concentration (P = 0.06). Factor VII activity decreased by 16% (P < 0.001), and von Willebrand factor antigen decreased by 7% (P = 0.014) with active treatment. Levels of fibrinogen, tissue plasminogen activator, fibrin D dimer, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, lipoprotein(a), and leptin were not significantly altered. No change in glycemic control was detected. Overall, lipid changes may be considered slightly beneficial with respect to CHD risk. The significant decrease in factor VII activity in this study is notable, because elevated factor VII activity has been associated with an increased risk of coronary thrombosis and normally increases with administration of oral estrogen-containing preparations. In addition, a reduction in von Willebrand factor antigen is consistent with an improvement in endothelial function. We suggest that the regimen used in this study may have the potential to reduce CHD risk in women with type 2 diabetes.

Administration, Cutaneous↗
PubMed1999

Differential transcriptional control as the major molecular event in generating Otx1-/- and Otx2-/- divergent phenotypes.

Otx1 and Otx2, two murine homologs of the Drosophila orthodenticle (otd) gene, show a limited amino acid sequence divergence. Their embryonic expression patterns overlap in spatial and temporal profiles with two major exceptions: until 8 days post coitum (d.p.c. ) only Otx2 is expressed in gastrulating embryos, and from 11 d.p.c. onwards only Otx1 is transcribed within the dorsal telencephalon. Otx1 null mice exhibit spontaneous epileptic seizures and multiple abnormalities affecting primarily the dorsal telencephalic cortex and components of the acoustic and visual sense organs. Otx2 null mice show heavy gastrulation abnormalities and lack the rostral neuroectoderm corresponding to the forebrain, midbrain and rostral hindbrain. In order to define whether these contrasting phenotypes reflect differences in expression pattern or coding sequence of Otx1 and Otx2 genes, we replaced Otx1 with a human Otx2 (hOtx2) full-coding cDNA. Interestingly, homozygous mutant mice (hOtx2(1)/hOtx2(1)) fully rescued epilepsy and corticogenesis abnormalities and showed a significant improvement of mesencephalon, cerebellum, eye and lachrymal gland defects. In contrast, the lateral semicircular canal of the inner ear was never recovered, strongly supporting an Otx1-specific requirement for the specification of this structure. These data indicate an extended functional homology between OTX1 and OTX2 proteins and provide evidence that, with the exception of the inner ear, in Otx1 and Otx2 null mice contrasting phenotypes stem from differences in expression patterns rather than in amino acid sequences.

Animals↗
PubMed1998

Evoked potential abnormality scores are a useful measure of disease burden in relapsing-remitting multiple sclerosis.

Fifty patients with relapsing-remitting multiple sclerosis were examined and studied with serial evoked potential and magnetic resonance imaging (MRI) measurements as part of a clinical trial. An evoked potential abnormality score (EPAS) for each testing session was calculated consisting of the total number of abnormal tests. The EPAS correlated well with Expanded Disability Status Scale (EDSS) at years 0, 1, and 2, with Spearman correlation coefficient scores of 0.68, 0.66, and 0.72, respectively. MRI lesion volume correlations ranged from 0.27 to 0.34 for the EDSS. EPAS are a potentially useful surrogate measure of clinical disability in relapsing-remitting multiple sclerosis.

Disability Evaluation↗
PubMed1998

Immunohistochemical localization of DARPP32 in striatal projection neurons and striatal interneurons in pigeons.

DARPP32 is a D1-receptor associated signaling protein found in striatal projection neurons in mammals, including both substance P-containing (SP+) neurons and enkephalinergic (ENK+) projection neurons. The present study used immunohistochemical single- and double-labeling to examine the cellular localization of DARPP32 in pigeon striatum. Single-label studies revealed that DARPP32 is present in numerous medium-sized striatal perikarya and DARPP32+ axons and terminals were seen to profusely innervate the two major striatal projection targets, the pallidum and the substantia nigra. The single-labeling studies indicated that about 60% of all striatal perikarya labeled for DARPP32+ in striatum, which exceeds the abundance of either SP+ or ENK+ perikarya. Single-labeling studies also showed that the abundance of DARPP32+ fibers and terminals in pallidum exceeds that of either SP+ or ENK+ fibers and terminals in pallidum. Double-labeling found that 30-50% of striatal SP+ perikarya and 7-24% of ENK+ striatal perikarya labeled for DARPP32 in pigeon, and confirmed that DARPP32 was found in both SP+ and ENK+ fibers and terminals in pallidum. In contrast to its prevalence in striatal projection neurons, DARPP32 was virtually absent from cholinergic and NPY+ striatal interneurons, as also true in mammals. Our data are consistent with the interpretation that many SP+ neurons and many ENK+ neurons in avian striatum possess D1-type dopamine receptors and use a DARPP32 signalling pathway, although this may be more common for SP+ than for ENK+ neurons.

Animals↗
PubMed1989

Are large-scale volunteer community health worker programmes feasible? The case of Sri Lanka.

National community health worker (CHW) programmes supported by Ministries of Health have been introduced in a number of countries as part of their primary health care policy. Although in many of these programmes the CHWs are salaried or receive an honorarium, there are a number of large-scale programmes in which CHWs work as unpaid volunteers. This paper looks at one such programme in Sri Lanka, in order to understand the motivation of such volunteers and to consider the feasibility of relying on volunteers to support primary health care policies. The lessons from the Sri Lanka case are generalized to other studies. The conclusion is that large-scale community level volunteer programmes will be characterized by high attrition and low activity rates and will only be sustainable under particular enabling conditions.

Community Health Workers↗
PubMed1989

National community health worker programs: how can they be strengthened?

This article is based on a collaborative research study of policy and practice in national community health worker (CHW) programs in developing countries. The study involved a review of the relevant literature, case studies in Botswana, Colombia and Sri Lanka, and an international workshop where the future of such programs was discussed. The findings of this research are discussed under four headings: unrealistic expectations, poor initial planning, problems of sustainability, and the difficulties of maintaining quality. It is clear that existing national community health worker programs have suffered from conceptual and implementation problems. However, given the interest and political will, governments can address these problems by adopting more flexible approaches within their CHW programs, by planning for them within the context of all health sector activities rather than as a separate activity, and by immediately addressing weaknesses in task allocation, training and supervision. CHWs represent an important health resource, whose potential in extending coverage and providing a reasonable level of care to otherwise underserved populations must be fully tapped.

Botswana↗
PubMed1988

Structure and nerve cell organisation in the cerebral cortex of the dolphin Stenella coeruleoalba a Golgi study. With special attention to the primary auditory area.

Cytoarchitectonic studies of the primary acoustic area, primary visual area and associative cortex of the convexity of the dolphin Stenella coeruleoalba using the Golgi method revealed a thick molecular layer, an accentuated Layer II, poor stratification of the underlying laminae and the absence of an identifiable Layer IV, as well as little areal variability. The morphology and distribution of nerve cells in the three regions, resembled those already known in other mammals. Distinctive cellular types were, however, present, such as extraverted pyramidal neurons in Layer II and giant multipolar and bi-tufted cells with smooth, beaded dendrites and extended, generalized axonal arborizations in Layers III and V. Spiny stellate cells were located in the inner region of Layer III and in Layer V; these cells exhibited a long descending axon and many recurrent and oblique collaterals. Although the basic structure of the cerebral cortex is thus similar to that observed in insectivores and chiropterids, dolphins have dramatically increased numbers of cerebral convolutions exceeding those found in most advanced terrestrial mammals.

Animals↗
PubMed1987

IgA related disorders in rheumatoid arthritis.

Serum monomeric and polymeric IgA, IgA rheumatoid factor (IgA-RF) and IgA containing circulating immune complexes (IgA-CIC) were studied in 192 patients with rheumatoid arthritis (RA) to explore the relationships among IgA related abnormalities and to investigate their potential associations with disease activity, immunoregulatory disorders and effect of treatments. Total serum IgA and polymeric IgA (p-IgA) levels were elevated in 23 and 11% of patients with RA, respectively. Their respective mean concentrations in serum were significantly elevated compared to normal values (p less than 0.001 and p less than 0.004). A preferential increase in polymeric rather than monomeric IgA was observed. IgA-RF, detected by a solid phase ELISA, was found in 71% and was associated with decreased grip strength (p less than 0.005), active disease (p less than 0.05), increased p-IgA level (p less than 0.001), elevated p-IgA:total IgA ratio (p less than 0.05), the presence of IgA-CIC (p less than 0.005) and IgM-RF (p less than 0.005). Complement fixing IgA-CIC were detected in 40% of patients by IgA specific conglutinin and anti-C3 binding solid phase ELISA. High molecular weight IgA species precipitated by 2.5% polyethylene glycol from RA sera positive for IgA-CIC were shown to be IgA-RF complexed to IgG. Taken together, our results suggest that IgA-RF are essentially polymeric in nature and circulate as IgA-RF-IgG immune complexes. Although the presence of IgA-CIC was not associated with disease activity, IgA-CIC activated C3 and thus are potentially pathogenic.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1987

Comparison of auditory-evoked potential detection methods using signal detection theory.

The performance of statistical evoked-potential detection methods was compared with that of human observers and among themselves by means of receiver operating characteristics (ROC) curves. The test material was a collection of brain stem auditory-evoked responses obtained from 98 infants with 60 and 30 dB nHL clicks. The observers and the statistical methods had to discriminate these responses from control recordings obtained without acoustic stimulation. Although the observers' criteria on different days varied considerably, the discrimination capacity was more stable. The discrimination capacity depended on the observers' experience. The statistical methods tested were the correlation coefficient (CCR), the standard deviation ratio (SDR) and a new method named T2R. The most efficient detection method was T2R. For false-alarm rates of 0.01 the statistical methods were more efficient than the human observers. Signal detection theory is useful for the evaluation of evoked-potential analysis methods.

Brain Stem↗
PubMed1985

Evaluation of clinical and prognostic significance of T cell regulatory subsets in rheumatoid arthritis.

Phenotypic analysis of circulating lymphocytes and T cell subsets using monoclonal antibodies was performed on 60 patients with rheumatoid arthritis (RA). A significant lymphopenia was observed in RA patients and correlated with the use of disease suppressant drugs (p less than 0.0001). A significant decrease in the number of suppressor/cytotoxic T cells resulted in an increase in the TH/TS ratio in 40% of RA patients. This elevated ratio did not correlate with disease activity, the presence of extraarticular features, autoantibody production or immune complex formation. We conclude that the evaluation of the TH/TS ratio has no diagnostic or prognostic value.

Arthritis, Rheumatoid↗
PubMed1982

The effect of veiled cells on lymphocyte function.

The response of lymphocytes to stimulation with Con A has been studied in the presence of veiled cells collected from the afferent lymph. In these enriched cultures the response occurred earlier with smaller numbers of lymphocytes and at lower concentrations of Con A. Veiled cells also caused clumping of lymphocytes in unstimulated cultures. In stimulated cultures small cells with veil-like projections appeared after 48 hr, but were not seen in unstimulated cultures.

Animals↗
PubMed1976

In vitro cross-allergenicity of major aeroallergenic pollens by the radioallergosorbent technique.

Cross-reactivity between major classes of aeroallergenic pollens has been estimated by comparing the inhibitory effects of selected allergens upon the reaginic activity of other native and non-native varieties, as measured by the radioallergosorbent technique (RAST). Common allergenic determinants were demonstrated in indigenous and nonindigenous ragween species. Although patterns of inhibitory capacity were less uniform among grass pollens, endemic species tended to have more common allergenic properties than nonendemic species. Tree pollens exhibited the greatest degree of heterogeneity, confirming the previous view that these pollens tend to be less cross-reactive. Concomitant skin test threshold studies utilizing the same groups of pollens were in general agreement with in vitro results. Because, threshold skin testing was affected by a number of uncontrollable variables, however, the current modification of RAST in estimating cross-allergenicity was more accurate and reliable than data based upon cutaneous tests. It was concluded that reagin neutralization by the RAST method is the best currently available method of assessing cross-allergenic properties of pollens.

Absorption↗