Differential expression of oestrogen receptor isoforms and androgen receptor in the normal vulva and vagina compared with vulval lichen sclerosus and chronic vaginitis.

BACKGROUND: Although the expression of the oestrogen receptor (ER) alpha isoform and androgen receptor (AR) has been examined in vulval lichen sclerosus (VLS), the distribution pattern of ERalpha, ERbeta and AR has not been described in chronic atrophic vaginitis nor correlated with markers of proliferation (Ki-67) in either of these diseased tissues. OBJECTIVES: To measure the levels and distribution of ERalpha, ERbeta and AR immunoreactivity in relation to Ki-67 in normal and diseased vulva and vagina. METHODS: The expression of ERalpha, ERbeta and AR in relation to the proliferation marker Ki-67 in VLS, squamous hyperplasia of the vulva and chronic atrophic vaginitis was determined by immunohistomorphometric analysis and compared with that in normal vulva and vagina. RESULTS: VLS showed similar ERalpha and ERbeta expression in the 'epidermal' and 'dermal' tissue layers to that of normal vulvae, whereas AR expression appeared to be absent in most cases. ERbeta and Ki-67 expression was correlated with ERalpha expression but only in the 'fibrovascular' layer of the vulva. ERalpha expression was absent from the 'fibromuscular' layer of diseased vulvae, while ERbeta expression was absent in normal tissues but was highly expressed in diseased vulvae. ERalpha expression was significantly correlated with AR expression in the fibrovascular layer of the vagina and inversely correlated with Ki-67 staining in the parabasal cells of the epidermis in patients with chronic atrophic vaginitis. CONCLUSIONS: These data suggest that ER expression and levels may be implicated in the aetiopathology of VLS and chronic atrophic vaginitis.

Variability of vascularity in nasal mucosa as demonstrated by CD34 immunohistochemistry.

Regional anatomical variations in the nasal vasculature have not been studied histologically. Immunohistochemistry performed using marker for CD34 antigen on vascular endothelium biopsied from 5 sites on the lateral nasal wall and compared with one septal biopsy. No significant regional variations in microvascular architecture over the lateral wall of the nose were found. * Lateral wall measurements were significantly different to the septal measurements (P = 0.0003, 0.01). Suggests biopsies can be taken from any site on the lateral wall and give a representative sampling of the vascularity for research purposes.

Heterozygosity for hereditary hemochromatosis is associated with more fibrosis in chronic hepatitis C.

Hepatic iron has been associated with more aggressive liver disease in chronic viral hepatitis. We evaluated whether the recently described C282Y mutation of the hemochromatosis gene, designated HFE (responsible for at least 83% of hereditary hemochromatosis), was associated with more advanced liver disease in chronic hepatitis C. One hundred thirty-seven patients with biopsy-proven chronic hepatitis C were studied and liver biopsies scored for necroinflammation (grade 0-18) and fibrosis (stage 0-6). Genomic DNA was amplified by polymerase chain reaction and the C282Y mutation identified by restriction with RsaI and electrophoretic separation of restriction fragments. Ten (7.3%) patients had the C282Y mutation. No C282Y homozygous patients were identified. Age, sex distribution, and estimated weekly alcohol consumption were not significantly different between those with and without the mutation. Serum ferritin was higher in the heterozygotes (mean, 339 microg/L) compared with homozygous wild types (153 microg/L; P = .0005). In the majority of patients, liver iron was graded 0 out of 4, but hepatocyte iron staining was more commonly present in heterozygotes compared with homozygous normals (30% compared with 4% [P = .02]). Liver disease was more advanced in those with the mutant allele (mean fibrosis stage: 3.6, compared with wild type: 1.5 [P = .01]). Cirrhosis was found more often in those with the mutation (40%) compared with those without (8.7%) (P = .01; odds ratio: 7.6 [1.9-31.2]). There was no significant difference in inflammation scores between heterozygotes and wild type (mean, 5.4 compared with 4.1). Hepatitis C virus (HCV)-RNA titers were measured by branched DNA assay (HCV RNA 2.0-Chiron), and there was no difference between heterozygous and homozygous normal patients. Thus, despite relatively minor increases in iron stores, individuals who are heterozygous for hemochromatosis appear to develop more fibrosis in chronic hepatitis C. Venesection may be useful therapy in this subgroup.

Heterozygotes for HFE mutations have no increased risk of advanced alcoholic liver disease.

BACKGROUND: Iron overload is common in the livers of alcoholics and may play a role in disease pathogenesis. An MHC like gene, HFE, has recently been identified that is mutated in most patients with hereditary haemochromatosis (C282Y in 90% and H63D in 45% of the remainder). AIM: To examine the hypothesis that these mutations determine hepatic iron status in alcoholics and play a role in pre-disposition to advanced alcoholic liver disease. METHODS: The HFE gene was genotyped in 257 patients with alcoholic liver disease and 117 locally matched healthy volunteers. In addition, iron staining was scored (0-4) on biopsy specimens from fibrotic/cirrhotic patients with and without HFE mutations matched for age and sex. RESULTS: Some 15.7% of fibrotic/cirrhotic patients were C282Y heterozygotes compared with 13.7% of controls (p = 0.77). One control and three patients were C282Y homozygotes. Of chromosomes without the C282Y mutation, 68/442 (15.4%) of patients' chromosomes carried the H63D mutation compared with 36/216 (16.6%) of control chromosomes (p = 0.91). Significant (> grade 1) hepatocyte iron staining was seen in 6/23 C282Y heterozygotes and 4/26 H63D heterozygotes compared with 4/23 controls. CONCLUSIONS: Possession of a single copy of either of the two HFE mutations influences neither liver iron content nor the risk of fibrotic disease in alcoholics.

Morphological changes during hepatocellular maturity in neonatal rats.

BACKGROUND: Hepatocellular maturation is characterised by the progressive transition from an architecture in which hepatocyte plates are at least two cells thick to the familiar adult pattern in which liver cell plates are predominantly single-cell in thickness. A similar process also has been noted during compensatory hyperplasia following damage, or destruction to the hepatic parenchyma. The pathological events that underlie these processes remain inadequately explained. A new morphological approach has been developed to study the maturity of rat neonatal livers in order to identify the factors which govern the structured morphogenesis of the liver in greater detail. METHODS: Sections of hepatic tissue obtained from the left lateral and right posterior lobes from neonatal rats were studied at 8, 10, 11, 13, 14, 18, 23, and 28 days postpartum. These were mounted, fixed, and stained with haematoxylin and eosin and analysed using a modified point-counting technique. Following validation of the technique, the proportion of single-cell plates to double-cell plates was then calculated at each time point. RESULTS: Liver sections from 8-day neonatal rats had the lowest percentage of single-cell thick plates of 16.9 +/- 4.6% and the lowest standard deviation (mean +/- SD). The hepatic architecture had fully matured by 28 days and was characterised by predominantly single-cell plates (84.6 +/- 4.6%) lining the hepatic sinusoids. During the intervening time, the standard deviations increased significantly, peaking between 18-23 days, and reflected the rapidly changing morphology of the liver during this maturation process of the conversion of double-cell plates to single-cell plates. CONCLUSIONS: It is concluded that the process of hepatocellular maturity in the neonatal Sprague-Dawley rat is reproducibly complete by 28 days and that further studies may now be conducted to determine the anatomical and pathophysiological changes that govern this important transition.

Pathologic and hemodynamic sequelae of unilobar biliary obstruction and associated liver atrophy.

A patient is presented with unilobar biliary obstruction associated with marked liver atrophy and compensatory hypertrophy. Characteristically she was not jaundiced and had no portal hypertension. Quantitative measurements of the degree of hepatocyte hyperplasia showed that over 50% of cells in the hypertrophied lobe were hyperplastic. Surprisingly, a similar percentage of cells in the atrophied lobe were also hyperplastic. No difference was found in the size of hepatocytes between the two lobes or among the hepatocyte subpopulations in the atrophied lobe. The findings in this case suggest (1) lobar atrophy induces a hyperplastic response in more than one half of the cells of the contralateral lobe; (2) the development of atrophy consequent on biliary obstruction is likely the result of destruction of whole cells rather than cytoplasmic loss; (3) the development of a hyperplastic response within the atrophied lobe is a new finding and is consistent with the hormonal theory of hepatic regeneration; and (4) striking compensatory hypertrophy of the liver is associated with normal portal venous pressure.