Characterization of susceptible chiasma configurations that increase the risk for maternal nondisjunction of chromosome 21

Recent studies of trisomy 21 have shown that altered levels of recombination are associated with maternal non-disjunction occurring at both meiosis I (MI) and meiosis II (MII). To comprehend better the association of recombination with nondisjunction, an understanding of the pattern of meiotic exchange, i.e. the exchange of genetic material at the four-strand stage during prophase, is required. We examined this underlying exchange pattern to determine if specific meiotic configurations are associated with a higher risk of non-disjunction than others. We examined the crossover frequencies of chromosome 21 for three populations: (i) normal female meiotic events; (ii) meiotic events leading to MI non-disjunction; and (iii) those leading to MII non-disjunction. From these crossover frequencies, we estimated the array of meiotic tetrads that produced the observed crossovers. Using this approach, we found that nearly one-half of MI errors were estimated to be achiasmate. The majority of the remaining MI bivalents had exchanges that clustered at the telomere. In contrast, exchanges occurring among MII cases clustered at the pericentromeric region of the chromosome. Unlike the single exchange distributions, double exchanges from the non-disjoined populations seemed to approximate the distribution in the normal population. These data suggest that the location of certain exchanges makes a tetrad susceptible to non- disjunction. Specifically, this susceptibility is associated with the distance between the centromere and closest exchange. This result challenges the widely held concept that events occurring at MII are largely independent of events occurring at MI, and suggests that all non-disjunction events may be initiated during MI and simply resolved at either of the two meiotic stages.      

Increased chondroitin sulphate proteoglycan expression (B5 immunoreactivity) in metastases of uveal melanoma

Background: Metastatic uveal melanoma has a poor prognosis andlimited therapeutic options. Proteoglycans are involved in tumorcell invasion and metastatic behavior. The mAbB5 stains a chondroitinsulphate proteoglycan (CSPG) on cutaneous melanoma cells. Here,we compare the B5-staining of CSPG in primaries and metastasesof uveal melanoma. Material and methods: Immunohistopathological staining was performedin 15 cutaneous and 39 uveal melanoma samples. A score for intracellularand surface staining was established. B5 staining was comparedin primaries and metastases of uveal melanoma using Student'st-test. Results: Eight of 11 (73%) uveal melanoma metastases were positivefor B5-staining whereas only 5 of 28 (18%) primary uveal melanomasamples were B5-positive (P < 0.001). Nine of 15 cutaneousmelanoma samples (60%) were B5-positive without significantdifference between primary and metastatic lesions. Surface stainingwas found both on uveal melanoma metastases and cutaneous melanomas. Conclusions: CSPG was expressed significantly more often inmetastases than in primaries of uveal melanoma. It potentiallymay be one factor associated with metastatic spread. Furtherstudies are needed to determine its use as prognostic factor.The mAbB5 may also be a promising tool for immunotherapy dueto its strong staining of CSPG on the surface of cutaneous andmetastatic uveal melanoma cells. Key words: uveal melanoma, ocular melanoma, chondroitin sulphate proteoglycan, immunotherapy, immunohistochemistry     

A COMPARISON OF NSP-RETICULONS WITH CONVENTIONAL NEUROENDOCRINE MARKERS IN IMMUNOPHENOTYPING OF LUNG CANCERS

Neuroendocrine-specific protein (NSP)-reticulons are endoplasmic reticulum-associated protein complexes, which have been identified as markers for neuroendocrine differentiation. In this study, the expression of two members of the family of NSP-reticulons, NSP-A and NSP-C, have been investigated in different types of lung cancer and compared with the expression patterns of five conventional neuroendocrine markers, the neural cell adhesion molecule (NCAM), synaptophysin, chromogranin A, Leu-7, and neurofilament proteins. NSP-A and NSP-C antibodies were reactive with most carcinoid tumour and small cell lung carcinoma (SCLC) cases, while atypical carcinoid tumours showed a variable expression. In the total group of neuroendocrine tumours, a high concordance of expression was found between NSP-A and NSP-C, while their expression correlated well with NCAM and synaptophysin positivity. Chromogranin A, Leu-7, and neurofilament proteins were shown to be expressed to a limited extent in these neuroendocrine tumours. In a selected group of non-SCLCs known to exhibit neuroendocrine features, NSP-A expression was detected at much higher frequency than NSP-C. In virtually all NSP-A positive cases, this expression was associated with one or more of the other neuroendocine markers. NSP-A expression showed a stronger correlation with conventional neuroendocrine markers than NCAM. In detecting neuroendocrine differentiation in non-SCLC, NSP-A is more sensitive than synaptophysin, chromogranin A, Leu-7, and neurofilament proteins. It is concluded that NSP-reticulons are valuable markers in the diagnosis of neuroendocrine differentiation in non-SCLC and should be used in conjunction with NCAM. © 1997 John Wiley & Sons, Ltd.     

TESTS OF GEOGRAPHICAL CORRELATION WITH ADJUSTMENT FOR EXPLANATORY VARIABLES: AN APPLICATION TO DYSPNOEA IN THE ELDERLY

We propose a test of correlation of the residuals in generalized linear models which is a generalization of the spatial autocorrelation test based on Moran's I. It allows adjustment for sizes of geographical areas and for explanatory variables. A formula is given to compute the weights according to the alternative hypothesis. We compare inference using the distribution in the model and using the permutation distribution. A simulation study showed that the model-based test may be very conservative and this leads to a loss of power compared to the permutation test or to the model-based test with correction for estimated parameters. As this latter is intractable for very large samples when the model includes explanatory variables, we recommend the use of the permutation test. The permutation test is used to study geographical correlation of dyspnoea in the elderly. © 1997 by John Wiley & Sons, Ltd.     

Effectiveness of health services for young children in an outpatient department]

The main indices are provided of the effectiveness of a new organisational form of health care delivery for children of the first three years of life--the department for young children. As a result of restructuring the services of the base polyclinics and establishing additional services, the volume and quality of followup care for young children have increased, the activities carried out within a family and populations at risk have improved. Morbidity according to the number of visits by children to the polyclinics was reduced by 17.3%.     

Role of nitric oxide and lipid peroxidation in pathogenesis of acute experimental pancreatitis

In experiment, conducted on 130 Wistar line rats, there was studied up the influence of nitric oxide on the peroxidal oxidation of lipids intensity, activity of enzymes of the antioxidant defense system and morphological changes in acute pancreatitis. Modern suggestions about the influence of the nitric oxide system on pathogenetic mechanisms of an acute pancreatitis and possibilities of correcting therapy were scrutinized. It was established, that the nitrates and the nitrites content in the blood serum of experimental animals correlates positively with the pancreatic oedema index and severity of its morphological changes as well. Intraperitoneal injection of 20% water solution of L-arginine in dosage 200 mg per 100 g of an animal body mass have had aggravated an acute pancreatitis course; intravenous injection of 1% water solution of methylene blue in dosage 1 mg per 100 g of an animal body mass caused pancreatoprotective effect.