Genotype-phenotype correlation in von Hippel-Lindau families with renal lesions

von Hippel-Lindau (VHL) disease arises from mutations in the VHL gene and predisposes patients to develop a variety of tumors in different organs. In the kidney, single or multiple cysts and renal cell carcinomas (RCC) may occur. Both inter- and intrafamilial heterogeneity in clinical expression are well recognized. To identify VHL-dependent genetic factors, we investigated the renal phenotype in 274 individuals from 126 unrelated VHL families in whom 92 different VHL mutations were characterized. The incidence of renal involvement was increased in families with mutations leading to truncated protein (MLTP) or large rearrangement, as compared to families with missense changes (81 vs. 63%, respectively; P=0.03). In the latter group, we identified two mutation cluster regions (MCRs) associated with a high risk of harboring renal lesions: MCR-1 (codons 74-90) and MCR-2 (codons 130-136). In addition, the incidence of RCC was higher in families with MLTP than in families with missense changes (75 vs. 57%; P=0.04). Furthermore, mutations within MCR-1 but not MCR-2 conferred genetic susceptibility to develop RCC. Overall, our data argued for a substantial contribution of the genetic change in the VHL gene to susceptibility to renal phenotype in VHL patients.     

A-raf oncogene localizes on mouse X chromosome to region some 10–17 centimorgans proximal to hypoxanthine phosphoribosyltransferase gene

The localization of the A-rafcellular oncogene on the mouse X chromosome has been determined using Xbal-restricted DNAs prepared from progeny of an interspecies backcross between the B6.CBA.R1 and the Spe/Pas mouse strains. This localization to the proximal part of the mouse X chromosome has been confirmed by the use of somatic cell hybrids, carrying partially deleted X chromosomes and suggests that the A-raf oncogene localizes to a region lying some 10–17 centimorgans proximal to the hypoxanthine phosphoribosyltransferase (Hprt) gene between the locus DXPas4and the locus DXPas7defined by the cross-reacting human X chromosome-specific probe DXS32 (M2C). This localization on the mouse X chromosome is compatible with the presence of the A-rafoncogene on the short arm of the human X chromosome between the centromere and Xp21.     

Neural changes in cat auditory cortex after a transient pure-tone trauma

Here we present the changes in cortical activity occurring within a few hours after a 1-h exposure to a 120-dB SPL pure tone (5 or 6 kHz). The changes in primary auditory cortex of 16 ketamine-anesthetized cats were assessed by recording, with two 8-microelectrode arrays, from the same multiunit clusters before and after the trauma. The exposure resulted in a peripheral threshold increase that stabilized after a few hours to on average 40 dB in the frequency range of 6-32 kHz, as measured by the auditory brain stem response. The trauma induced a shift in characteristic frequency toward lower frequencies, an emergence of new responses, a broadening of the tuning curve, and an increase in the maximum of driven discharges. In addition, the onset response after the trauma was of shorter duration than before the trauma. The results suggest the involvement of both a decrease and an increase in inhibition. They are discussed in terms of changes in central inhibition and its implications for tonotopic map plasticity.     

Postpartum depression and mother-infant relationship at 3 months old

Background: This paper is part of a prospective, epidemiologic study concerning postpartum depression (PPD). The women were first examined during pregnancy; after delivery they were seen with their infants at 3 and 18 months. The present study focuses on the 3-months-postpartum results. Methods: A sample of 570 women and their infants were examined 3 months after delivery. Using the EPDS (Edinburgh Postnatal Depression Scale; Cox et al., 1987. Br. J. Psychiatry 150:782–786), 10.2% of these new mothers presented PPD. The focus of the study concerned the effects of this neurotic disorder on the mother, the infant and on the mother–infant relationship. Results: The deleterious effects concerning the infant were functional disorders such as eating or sleeping difficulties. The ‘depressed’ dyads presented less vocal and visual communications, less corporal interactions and less smiling. Conditions surrounding delivery and tiredness at 3 months are linked to difficulties in mother–infant relationship for the non-depressed mothers. Logistic models showed that primiparous PPD mothers have difficulties bathing their infants, whereas multiparous PPD mothers are more tired. Limitation: This study did not take into account either protective factors or the effects of the infant himself. Clinical relevance: Knowledge of the mothers’ and infants’ difficulties may help caregivers to detect these at-risk dyads and initiate therapeutic measures.     

RECOMBINATION FRACTIONS IN THE HLA SYSTEM BASED ON THE DATA SET ‘PROVINCES FRANÇAISES’: INDICATIONS OF HAPLOTYPE-SPECIFIC RECOMBINATION RATES

In the large genetic survey ‘Provinces Françaises’ the recombination fractions in the HLA system have been estimated by a family analysis programme (FAP). A total of 1332 families were analysed and in general the findings were in agreement with recombination fractions reported previously. The maternal recombination rates were on average 1.8 times higher than the corresponding ones for males. The comparison of the recombination fractions with the corresponding physical distances suggests the existence of hot spots of recombination. The analysis did not show deviations from expected values for HLA-A and B alleles on HLA-A/B recombinant haplotypes. However, analysis of HLA-B/DR recombinant haplotypes showed a skewed distribution of B and DR alleles. The significance of the findings is difficult to evaluate as all results are estimated numbers and frequencies but a manual analysis of the recombinant families confirmed the observations. HLA-B/DR recombinant haplotypes carried often HLA-DR3 and DR11 whereas DR2 and DR7 were more rarely present on recombinant haplotypes. DR4 had an increased incidence on BF/DR recombinant haplotypes but not on A/B or B/BF recombinant haplotypes. Some of the haplotypes with the strongest linkage disequilibria as A1, B8, DR3 and A3, B7, DR2 seem to be less frequently involved in recombinations than other haplotypes. Variations of recombination rates depending on certain alleles or haplotypes might partially explain the conservation of some haplotypes or part of haplotypes in Caucasoids.     

Concentration of zinc, copper, selenium and aluminium in nutritive solutions for parenteral administration]

Total parenteral nutrition (TNP) therapy is widely used. However the quantitative requirements or the toxicity of trace elements in parenteral solutions are difficult to assess. This paper deals with a study performed by the Trace Element Commission of the Société Fran?aise de Biologie Clinique. Trace metals (zinc, copper, selenium and aluminium) which are mainly involved in TPN solutions are analyzed in 12 different parenteral nutrition solutions commercially available. This multicentric assay (5 different sites of analysis) shows that a slight pollution can be noted for nearly all the solutions examined. But at this level (10 mumol/l for the most concentrated solution), the zinc intake cannot induce any toxicity. For copper and selenium the results indicated a negligible pollution. Small-volume solutions added with zinc, copper and selenium are correctly supplemented. As regard aluminium pollution, 4 solutions among 12 contain non negligible amounts of aluminium. The consequences of this TPN overload especially for young infants, indicate that the struggle against this pollution has to be strengthened.     

Partial purification and characterization of B cell growth factor constitutively secreted by human T-cell hybridoma

Human T cell hybridomas were established by fusion of PHA-activated PBL with the 8-azaguanine resistant human T-leukemic cell line CEM-CM3. High levels of B cell growth factor (BCGF) activity were detected in the supernatants of hybridoma C8-2B2 and its subclones. Hybridoma C8-2B2, in addition to the Leu 3a, also expressed the OKT11 surface marker which was not detectable on the parent CEM-CM3 cells. BCGF from the culture supernatant was purified by combined use of salt fractionation and gel filtration to 36.6 fold with 23.9% recovery of activity. The BCGF produced by hybridoma C8-2B2 has a molecular weight range of 16,000–20,000 in two major electrophoretically different forms with pI values of 6.4 and 7.4.     

Serum trace elements and myocardial infarction

The authors report trace elements concentrations (zinc, nickel, selenium, copper, manganese and chromium) during myocardial infarction described in some publication. Serum zinc decreases during the first two days after acute myocardial infarction and returns to normal level in two weeks. Serum nickel increases during the first 36 hours and copper during the first four days. The different explanations of these disturbances are also exposed.     

5-Azacytidine produces differential undercondensation of alpha,beta and classical human satellite DNAs

Fluorescencein situ hybridization employing human alphoid, beta and classical satellite DNA probes was performed on 5-azacytidine treated and untreated chromosomes obtained from human lymphocytes. The individual used in this study presented a polymorphism of constitutive heterochromatin of chromosomes 1 and 9 as revealed byin situ digestion with the restriction endonucleaseAlul. Neither the alphoid nor the beta satellite DNA domains were susceptible to condensation-inhibition by 5-azacytidine. Only the classical satellite localized on chromosome 9 was affected. The constitutive heterochromatin size polymorphism was shown to depend mainly on variations of the classical satellite DNA domain. Therefore, condensation-inhibition, as a phenomenon which may modify the natural folding of the chromatin fibre, regionally affects human constitutive heterochromatin and seems to be dependent on the heterochromatic family.