Oral mucous membrane pemphigoid and pemphigus vulgaris-a retrospective two-center cohort study.

OBJECTIVES: Few studies have compared oral mucous membrane pemphigoid (MMP) and pemphigus vulgaris (PV). Descriptive analysis of oral features, extent of extra-oral involvement, and management outcomes were performed. SUBJECTS AND METHODS: Patients with PV and MMP, the latter with exclusive oral involvement at first presentation, were included. RESULTS: There were 26 MMP (46%) and 31 PV (54%) patients. Desquamative gingivitis was evident in 84% of MMP cases compared to 28% of PV cases (P < 0.05). Non-gingival lesions were noted in 6% of MMP cases compared to 55% of PV cases (P < 0.01). Management of MMP consisted of only topical corticosteroids in 88% of cases while 12% of cases required concomitant systemic therapy. All PV cases (100%) required systemic therapy. No patients with MMP developed scarring or ocular lesions, and one patient (4%) developed cutaneous lesions. Five PV cases (16%) had oral cavity involvement only with three (60%) developing pharyngeal involvement and two (40%) developing cutaneous lesions on follow-up. CONCLUSION: Oral MMP presents primarily as desquamative gingivitis, infrequently involving extragingival sites, and is highly amenable to topical therapy, while PV is a systemic mucocutaneous disease with extensive non-gingival oral lesions that almost always requires systemic therapy.

Differential effects of acute and chronic exposure to interferon-gamma on cyclic adenosine 3',5'-monophosphate response element-regulated gene expression.

TSH stimulates proliferation and maintains differentiated function in thyroid follicular cells. The mitogenic activity and the stimulatory effects of TSH on thyroid-specific gene expression are impaired by interferon-gamma (IFNgamma); however, the mechanisms for these effects have not been elucidated in detail. We examined the effects of IFNgamma on acute responses to TSH in rat thyroid cells. IFNgamma did not impair TSH-stimulated p70/p85 ribosomal protein S6 kinase (p70/p85s6k) activity or cAMP response element (CRE)-regulated gene expression, although it inhibited DNA synthesis and thyroglobulin expression, effects measured over a more prolonged time course than those on kinase activity and reporter gene expression. Unexpectedly, when cells were chronically exposed to IFNgamma, CRE-lacZ promoter activity was decreased, whereas other cAMP-mediated signals, such as p70/p85s6k activity and CRE-binding protein phosphorylation, were unaffected. Activating protein-1-regulated promoters were also impaired by IFNgamma treatment, but with kinetics that differed from those of CRE-regulated promoters. Neither acute nor chronic treatment with interleukin-1beta impaired cAMP signaling, indicating that the effects of IFNgamma are specific. These studies identify CRE- and activating protein-1-regulated promoters as targets of IFNgamma in thyroid cells and fibroblasts. IFNgamma-mediated inhibition of these promoters, in addition to those containing thyroid-specific transcription factor-1-binding sites, may contribute to the profound effects of IFNgamma on thyroid cells.

The deletion/insertion polymorphism of the angiotensin converting enzyme gene and cardiovascular-renal risk.

OBJECTIVE: This meta-analysis attempted to derive pooled estimates for the associations between various cardiovascular-renal disorders and the deletion/insertion (D/I) polymorphism of the angiotensin converting enzyme (ACE) gene. METHODS: Case-control studies were combined, using the Mantel-Haenszel approach. Joint P values for continuous variables were calculated by Stouffer's method. Continuous measurements reported in different units were expressed on a percentage scale using the within-study mean of the II genotype as the denominator. RESULTS: The computerized database used for this analysis included 145 reports with an overall sample size of 49 959 subjects. Overall, possession of the D allele was associated with an increased risk of atherosclerotic and renal microvascular complications. In comparison with the II reference group, the excess risk in DD homozygotes (P < 0.001) was 32% for coronary heart disease (CHD; 30 studies), 45% for myocardial infarction (20 studies), 94% for stroke (five studies) and 56% for diabetic nephropathy (11 studies). The corresponding risk in DI heterozygotes amounted to 11% (P= 0.02), 13% (P= 0.02), 22% (P= 0.10) and 40% (P < 0.001), respectively. Hypertension (23 studies), left ventricular hypertrophy (five studies), hypertrophic or dilated cardiomyopathy (eight studies) and diabetic retinopathy (two studies) were not related to the DI polymorphism. Publication bias was observed for CHD, myocardial infarction and microvascular nephropathy, but not hypertension. In studies with DNA amplification in the presence of insertion-specific primers, the risk associated with the DD genotype increased to 150% [95% confidence interval (CI) 76-256; four studies] for diabetic nephropathy, but decreased to 12% (95% CI -3 to 28; seven studies) for CHD and 14% (95% CI -6 to 37; four studies) for myocardial infarction. On the other hand, the pooled odds ratios did not materially change if the meta-analysis was limited to articles published in journals with an impact factor of at least 4. Furthermore, compared with the II control group, the circulating ACE levels (29 studies) were raised 58 and 31% (P < 0.001) in DD and DI subjects, respectively. In contrast, plasma renin (10 studies), systolic and diastolic blood pressure (46 studies) and body mass index (30 studies) were not associated with the D allele. CONCLUSION: The D allele is not associated with hypertension, but behaves as a marker of atherosclerotic cardiovascular complications and diabetic nephropathy. These associations do not necessarily imply a causal relationship and may have been inflated by publication bias. Nevertheless, their possible therapeutic implications may be subject to further investigation in prospective (intervention) studies.

Genetic variability in the renin-angiotensin system: prevalence of alleles and genotypes.

BACKGROUND: Variants of the human genes coding for renin, angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and the angiotensin II type-I receptor (AT1R) are inconsistently associated with cardiovascular-renal disease, possibly because of genetic differences in the background populations. METHODS: This systematic review of the literature investigated genetic variation in the renin system according to race, sex and age. Across studies with relevant information, multivariate analyses also accounted for the methods of genotyping and the enrollment of subjects as controls, cases or groups studied cross-sectionally. RESULTS: The 185 reviewed reports included 64978 subjects. In five studies (n=989) on the renin gene, the Hind III and Taq I polymorphisms varied with the groups' average age, whereas the Bg I, Bg II and Hind III but not Taq I sites differed according to race. Among 135 studies (n=44697) on the deletion/insertion (D/I) polymorphism of the ACE gene, the frequency of the D allele was 54.0%. Its prevalence was not related to sex and black race, was 49.9% lower in Asians, 10.0% lower in studies relying on I-specific primers, 4.9% higher for each 25-year increment in the average age of the groups studied, and 16.7% higher in cases than controls. Among 12 studies (n=4952) on the T174-->M variant of the AGT gene, the M174 frequency was 11.0%, did not vary according to sex and enrollment group, was 56.7% lower in blacks and 39.5% lower for each 25-year increase in the groups' mean age. Across 44 studies (n=16713) on the M235-->T substitution in the AGT gene, the T235 prevalence was 51.6%. Its frequency was not related to sex and the method of genotyping, tended to be 7.5% lower for each 25-year increase in average age, was from 4.6 to 6.6 times higher in nonwhites than whites and 13.2% higher in cases than controls. Among 13 studies (n=4332) on the A1166-->C variant of the AT1R gene, the C1166 allelic frequency was 25.7%. Its prevalence was independent of the enrollment group, 77.4% lower in Asians, and nearly doubled for each 25-year increment in age. CONCLUSION: With adjustments applied for the subjects' enrollment group and the methods of genotyping, genetic polymorphism in the renin system varies according to race and age, but not sex. One possible application of the present results is to provide allelic and genotypic frequencies, which could be used to assess power, to perform sample size calculations, or to predict selection bias in future studies.