Repeated administration of desmethylimipramine blocks the reserpine-induced increase in tyrosine hydroxylase mRNA in locus coeruleus neurons of the rat.

The levels of tyrosine hydroxylase and galanin mRNA were measured by in situ hybridization histochemistry in the rat locus coeruleus after repeated (21 days) administration of desmethylimipramine (10 mg/kg/day), of reserpine (0.25 mg/kg/day), of coadministered desmethylimipramine and reserpine, or of vehicle. Reserpine administration resulted in increased levels of both tyrosine hydroxylase and galanin mRNAs in locus coeruleus neurons as compared to vehicle-treated controls. Administration of desmethylimipramine alone failed to alter either the tyrosine hydroxylase or galanin mRNA. However, coadministration of desmethylimipramine with reserpine blocked the elevation in tyrosine hydroxylase mRNA induced by reserpine alone.     

Colour flow imaging of calf vein thrombosis.

Ultrasound and more recently colour Doppler ultrasound has been successfully used in the diagnosis of lower limb venous occlusive disease. Colour Doppler ultrasound has shown promise in the diagnosis of calf vein thrombosis but to date there has been no prospective trial to specifically evaluate its potential. In view of this, we carried out a prospective trial of 50 patients comparing the accuracy of colour Doppler ultrasound with venography in the diagnosis of deep venous thrombosis both above and below knee but in particular with respect to the detection of calf vein clot. Of the 50 patients studied, 10 had only one imaging modality performed as there were eight venographic failures and two ultrasonic failures. Comparison was only thus possible in 40 cases. As in previous studies, colour Doppler ultrasound was shown to be accurate in the diagnosis of thrombosis within the femoro-popliteal veins and had a sensitivity and specificity of 100% respectively. With respect to calf vein lesions, there was one false negative scan using the ultrasonic technique giving a sensitivity of 95%, specificity of 100% and accuracy of 97.5%. We feel colour Doppler ultrasound can and should be used as a first line alternative to venography and can be employed for the exclusion of both above and below knee deep venous thrombosis. Venography should now be reserved for those patients who are unsuitable for ultrasound examination or who have an equivocal ultrasound scan.     

Vaterian cancer in siblings

The simultaneous occurrence of Vaterian carcinoma in two siblings suggests a genetic influence in their pathogenesis. Their classic clinical presentation of obstructive jaundice and weight loss required pancreaticoduodenectomy for this neoplasm. Pedigree analysis revealed a third sibling who died from an unresectable periampullary malignancy. Neither of the probands exhibited, as late as the seventh decade, evidence compatible with a diagnosis of familial polyposis coli or Gardner's syndrome. Flow cytometry studies revealed an aneuploid distribution in one tumor and tetraploid in the other. The rarity of this neoplasm, in the absence of contributing epidemiologic factors, suggests that this is a pleotrophic manifestation of a cancer-prone genotype.     

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.     

Evaluation of cytotoxicity of some Mannich bases of various aryl and arylidene ketones and their corresponding arylhydrazones.

Mannich bases were synthesized and converted to the corresponding arylhydrazones. X-ray analysis of a ketone (1a) and a hydrazone (4d) revealed structural features of interest. All of the compounds showed cytotoxicity toward murine lymphocytic leukemia L1210 cells in the 4.9-25.0-microM range. The correlation coefficients generated by plotting the IC50 values (the concentrations of compounds that inhibit the growth of tumors by 50%) of some hydrazones against certain electronic, hydrophobic, and steric constants of the aryl substituents indicated only weak correlations. A few ketones and hydrazones displayed significant cytotoxicity to the WiDr human colon cancer cells, and these derivatives, especially the ketones, may serve as prototypes for future drug development. The KB tumor (a human epidermoid carcinoma of the nasopharynx) was somewhat refractory to selected compounds. In an in vitro assay conducted by the National Cancer Institute and involving approximately 53 tumor cell lines originating from eight neoplastic diseases, 65% of the compounds showed some selectivity toward one or more groups of cancers, principally leukemia, melanoma, and colon cancer. The bioevaluation of the ketones and hydrazones against the L1210, WiDr, and KB tumors, as well as evidence from proton nuclear magnetic resonance studies did not support the suggestion that hydrazones may be prodrugs of the corresponding ketones.     

Development of leukemia after doxorubicin and cisplatin treatment for ovarian cancer

Alkylating agents have been the major group of chemotherapeutic agents associated with an increased incidence of secondary leukemias. In ovarian cancer alkylating agents have resulted in a lesser, although still increased, risk of secondary malignancies. This paper reports two cases of ovarian cancer treated with cisplatin and doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH), and the subsequent development of an acute nonlymphocytic leukemia and a preleukemia syndrome. This regimen does not contain alkylating agents, and has not been associated with leukemia in patients with ovarian cancer. In these two cases, abnormalities of chromosomes 5, 7, 11, and 17 are reported which have been shown to occur in therapy-related leukemia.     

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.