Role of monogenic diabetes genes on beta cell function in Italian patients with newly diagnosed type 2 diabetes. The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 13.

We tested the hypothesis that common genetic variability of beta-cell genes responsible for monogenic diabetes may affect beta cell function in type 2 diabetes mellitus (T2DM). We studied 794 drug- naïve GAD-negative patients with newly diagnosed T2DM (age: median=59 years; I.Q. range: 52-66; body mass index: 29.3 kg/m2; 26.6-32.9). Beta-cell function was assessed by state-of-art mathematical modeling of glucose/C-peptide curves during a 240'-300' frequently sampled oral glucose tolerance test, to provide the beta-cell responses to the rate of increase in glucose concentration (derivative control: DC) and to glucose concentration (proportional control: PC). Forty-two single nucleotide polymorphism (SNPs), selected to cover over 90% of common genetic variability, were genotyped in nine monogenic diabetes genes: HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, KCNJ11 and ABCC8. Allelic variants of four SNPs (rs1303722 and rs882019 of GCK, rs7310409 of HNF1A and rs5219 of KCNJ11) were significantly associated with DC of beta-cell secretion (all P < 0.036). Allelic variants of four other SNPs (rs2868094 and rs6031544 of HNF4A, and rs1801262 and rs12053195 of NEUROD1) were associated with PC of beta-cell secretion (P < 0.02). In multivariate models, GCK, HNF1A and KCNJ11 SNPs explained 2.5% of the DC variability of beta-cell secretion, whereas HNF4A and NEUROD1 SNPs explained 3.6% of the PC variability of beta-cell secretion. We conclude that common variability of monogenic diabetes genes is significantly associated with an impaired beta-cell function in patients with newly diagnosed T2DM; thereby, these genes might be targeted by specific treatments in T2DM.

Primary tumours of the liver: a review of 249 cases.

A total of 249 primary liver tumours was found in a 12-year necropsy and biopsy material. The majority of cases were liver carcinomas underlying liver cirrhosis, but several rare types were also observed. Histological classification, liver tissue changes around the tumours as well as the electron microscopic features of the tumours are discussed. Around the tumours three different types of dysplasia were noted and it is considered important to carry out further investigations to establish whether or not they are genuine precancerous conditions.

[Electron microscopy of colonic polyps. I. Comparative study of epithelial cells from adenomatous and adenopapillary polyps]. / Vastagbélpolypusok elektronmikroszkópiája. I. Adenomatosus és adenopapillaris polypusok hámsejtjeinek összehasonlító vizsgálata.

Ultrastructural characteristics of premalignant epithelial dysplasia were studied electronmicroscopically by comparing epithelial cells of adenomatous- and adenopapillary polyps. In adenomatous polyps the rate of absorptive and goblet cells, their electron microscopic appearance did not differ from those of the normal colonic mucosa. In dysplastic areas of adenopapillary polyps severe proliferation of undifferentiated epithelial cells and disturbance of the maturation of absorptive and goblet cells was found. Severe damage to the cell membrane, atypical vacuola and dense bodies in the apical areas of absorptive cells were also seen. An abundance of Leuchtenberger's inclusion bodies as an important sign of the malignant transformation have occurred.

[Electron microscopy of colonic polyps. II. Leuchtenberg's inclusion bodies]. / Vastagbélpolypusok elektronmikroszkópiája. II. Leuchtenberger-féle zárványtestekröl.

Characteristic features of Leuchtenberger's inclusion bodies of adenomatous, adenopapillary and papillary polyps of the colon were studied by electron microscope. Authors believe that in the development of intracellular inclusion bodies focal degradation of the cytoplasma, of intercellular inclusion bodies, strangulation of certain areas of it may play a role. It is assumed that the development of inclusion bodies is a result of impairment of the cell membrane of proliferating, undifferentiated epithelial cells of the colonic mucosa. Increasing frequency of inclusion bodies in polyps undergoing malignant transformation seems to be an important morphologic feature.

[Light and electron microscopic study of melanosis coli]. / Melanosis coli fény- és elektronmikroszkópos vizsgálata

The authors describe the results of light- and electronmicroscopic investigation of the colonic mucosa in melanosis, occurring at a 35 years old male patient. In the tunica propria mucosae pigment storage macrophages described histologically can be recognized as well by the aid of electron microscope. In contrast to the light-microscopic picture, electronmicroscopically separation of the epithelial cells of the mucosa, accumulation of foreign material in the enlarged intercellular spaces, accumulation of granular-fibrillar matrix in the tunica propria and presence of plasma cells with increased secretory activity can be revealed. It is assumed, that separation of epithelial cells of the mucosa goes with the disturbance of the absorptive function. It can not be excluded, that electronmicroscopically revealed lesions of the coolnic musoca aggravate the severe obstipation. For this reason early diagnosis of the melanosis coli and ceasing the medication with athranol-glycosida-containing laxatives are very important.