Inheritance of human breast cancer: evidence for autosomal dominant transmission in high-risk families.

Segregation analysis of breast cancer in families can provide the logical basis and the specific genetic models for mapping and identifying genes responsible for human breast cancer. Patterns of breast cancer occurrence in families were investigated by complex segregation analysis. In a sample of 1579 nuclear families ascertained through a population-based series of probands, an autosomal dominant model with a highly penetrant susceptibility allele fully explained disease clustering. From the maximum-likelihood Mendelian model, the frequency of the susceptibility allele was 0.0006 in the general population, and lifetime risk of breast cancer was 0.82 among susceptible women and 0.08 among women without the susceptibility allele. Inherited susceptibility affected only 4% of families in the sample: multiple cases of this relatively common disease occurred in other families by chance. The same genetic models, with higher gene frequency, explained disease clustering in an extended kindred at high risk of breast cancer. Evidence for a highly penetrant, autosomal dominant susceptibility allele for breast cancer in a high-risk family and the general population suggests that high-risk families can serve as models for understanding breast cancer in the population as a whole.     

Molecular phylogeny of the insect order Hymenoptera: apocritan relationships.

Phylogenetic relationships among the major groups of hymenopteran insects were investigated by using comparative sequence information from the mitochondrial 16S rRNA gene. The placement of the ectoparasitic Stephanidae as the sister group to the remaining Apocrita confirmed ectoparasitism as the ground plan biology for the Apocrita. Endoparasitism evolved at least eight times within the Apocrita, and the consequent association with polydnaviruses and virus-like particles evolved at least three times. The Evaniomorpha were consistently placed as basal to the remaining Apocrita but were not resolved as monophyletic. The Gasteruptiidae were resolved as the sister group to the Evaniidae, but the relationship between the Trigonalyoidea and the Evanioidea was unclear. The Proctotrupomorpha (sensu Rasnitsyn) was resolved by topology-dependent permutation tail probability (T-PTP) testing as monophyletic, with strong evidence for a sister group relationship between the Platygastroidea and the Chalcidoidea. Strong evidence was found for the monophyly of the Ichneumonomorpha (Ichneumonidae + Braconidae) and the sister-group relationship between the Aculeata (Vespomorpha) and the Ichneumonomorpha.     

Effects of prolactin on secretion and synthesis of human chorionic gonadotropin in human term placentas in vitro: short-term increase in secretion, followed by medium-term suppression of synthesis and secretion.

We studied the influence of human prolactin on the secretion and de novo synthesis of human chorionic gonadotropin (hCG) in the human term placenta in culture. Placental tissue from 14 patients with uncomplicated pregnancies and deliveries was prepared mechanically, with addition of a Percoll gradient step. hCG levels were determined in the culture media and in the cytosolic fraction of cells by means of an enzyme immunoassay with coated beads. The amount of newly synthesized hCG was measured by the extent of incorporation of 35S-methionine into the hCG molecule. Our results showed that human prolactin had two different effects in vitro: between 1/2 and 1 h, prolactin slightly increased secretion of hCG into the culture medium without affecting de novo synthesis; after 2 h, prolactin began to cause a significant decrease in both secretion and de novo synthesis of hCG over several hours. It appears that both effects are receptor mediated, for ovine prolactin failed to produce any response. We conclude that prolactin is one of the main factors regulating the synthesis and secretion of hCG in the human trophoblast at term.     

The Role of Instructional Set on Alcoholic Performance

This study was conducted to determine whether alcoholic and control subjects respond differently to manipulations that either enhance personal involvement (PI) or reduce negative affect (R, relaxation) on tests of neuropsychological function. In Phase 1, 48 male alcoholics and 36 male control subjects completed neuropsychological tasks under standard instructional sets. In Phase 2, subjects completed equivalent forms of these tests under one of three randomly assigned conditions; the PI condition in which subjects were encouraged to identify specific ways of improving their performance, the R condition in which subjects participated in a short relaxation exercise designed to reduce anxiety, or a No Treatment (NT) condition in which no attempt to manipulate the subjects' involvement or affect was made. Alcoholics were inferior to controls in both Phase 1 and Phase 2 [Fs (1,82) > 5.03, ps < 0.03]. The experimental manipulation differentially affected measures of negative affect and effort in the predicted direction. There were no group x condition interactions. Alcoholic and control subjects responded comparably to the experimental manipulations. This investigation, in combination with others using related manipulations, reinforces the hypothesis that alcohol-related cognitives dysfunction reflects an underlying deficit in brain states.     

NIH conference. Membranous nephropathy.

Membranous nephropathy is a worldwide problem that accounts for about 20% of the cases of the adult-onset nephrotic syndrome. This disease places many patients at risk for both end-stage renal failure and the complications of hyperlipidemia. Immune-mediated injury to the glomerular capillary wall in patients with membranous nephropathy is characterized by subepithelial immune complex formation and generation of the membrane attack complex of complement. Glomerular capillary hypertension, hyperlipidemia, and possibly cytokines could contribute to the glomerular sclerosis seen in the advanced stages of the disorder. In some cases, production of pathogenic antibody can be suppressed by treating the underlying condition. The mechanisms of action of immunosuppressive agents are being investigated and treatments are being tested in clinical trials to optimize the balance of efficacy and toxicity. Alternate-day treatment with corticosteroids is often recommended for nephrotic patients with idiopathic membranous nephropathy, but this approach has not been proved beneficial. Ongoing studies are evaluating whether cytotoxic drugs or cyclosporin A combined with prednisone is more effective than treatment with corticosteroids alone. Lipid-lowering drug therapy is warranted in cases of the persistent nephrotic syndrome to avert the cardiovascular sequelae of hyperlipidemia.     

Fine-needle aspiration cytology of an endometrioid-like variant of yolk sac tumor.

A 36-year-old male with a history of immature teratoma and embryonal carcinoma of the testis was admitted to the hospital for abdominal pain and fever. A CT scan revealed a large right abdominal mass. The patient's serum alpha-fetoprotein (AFP) was 46.8 ng/ml (reference < 25 ng/ml). Fine-needle aspiration (FNA) of the mass revealed malignant glandular cells. Chemotherapy was instituted, followed by resection of the large abdominal mass. The tumor was grossly encapsulated, consisting of large areas of necrotic, hemorrhagic tissue surrounded by smaller, multiloculated cysts. Microscopically, the tumor had a villoglandular pattern and variably stratified tall columnar cells. A prominent feature of the columnar cells was supranuclear and subnuclear vacuolization. Intracytoplasmic PAS-positive, diastase-resistant hyaline globules were occasionally present. AFP by immunoperoxidase was prominent within the tumor. This recurrence of the previously diagnosed testicular teratoma with embryonal carcinoma represents a yolk sac tumor with components strongly resembling endometrioid carcinoma, a variant only recently described in eight cases of ovarian origin (Clement et al.: Am J Surg Pathol 1987; 11(10):767-778). We believe this is the first reported case of an endometrioid-like variant of testicular yolk sac tumor and also the first report of the FNA cytology findings in this variant.