Metastatic mammary carcinoma of the middle ear

Malignancies of the middle ear and mastoid are rare and secondaries in the ear are extremely rare. A rare case of metastic adenocarcinoma from the breast is presented herewith.     

Effect of melanotropin release inhibiting factor on changes by haloperidol and centbutindole in cerebral cortical 5-hydroxytryptamine receptors

The effect of melanotropin release inhibiting factor (Pro-Leu-Gly-NH2, MIF) was determined on changes induced by two neuroleptics, haloperidol and centbutindole, in cerebral cortical 5-hydroxytryptamine (5-HT) receptors. Male Sprague-Dawley rats were injected daily i.p. with vehicle, haloperidol (1.0 mg/kg) or centbutindole (0.5 mg/kg), respectively, for 21 days. On day 22, these 3 groups were further divided into 2 subgroups and injected with either vehicle or MIF (2.0 mg/kg, i.p.) daily for 3 days. 3H-5-HT was used to study 5-HT1 receptors, and 3H-spiroperidol to label 5-HT2 receptors in the cerebral cortex. Chronic administration of haloperidol significantly increased (39.7%) the maximal binding capacity (Bmax) of 3H-5-HT binding to 5-HT1 receptors. Dissociation constant (Kd) values did not change. Centbutindole had no effect on 5-HT1 receptors. MIF had no effect on 5-HT1 receptors, nor did it alter haloperidol-induced increases in the Bmax of 3H-5-HT binding to 5-HT1 receptors. Chronic administration of centbutindole significantly increased (61.1%) the Bmax of 3H-spiroperidol binding to 5-HT2 receptors. No change occurred in the Kd values. Chronic treatment with haloperidol had no effect on 5-HT2 receptor characteristics. MIF had no effect on 5-HT2 receptors or on the increase in 5-HT2 receptor density induced by centbutindole. The behavioral syndrome induced by 5-hydroxytryptophan (5-HTP) (50, 100 and 200 mg/kg, i.p.) was also measured in rats treated chronically with haloperidol or centbutindole. Haloperidol had no effect on the 5-HTP syndrome, whereas centbutindole stimulated by 24-45% the intensity of the syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)     

Autosomal dominant inheritance of spondyloenchondrodysplasia

Spondyloenchondrodysplasia comprises generalized enchondromatosis with platyspondyly and is thought to be inherited as an autosomal recessive condition. A mother and son are reported with typical features of spondyloenchondrodysplasia. Their similar radiographic and MRI findings are presented. The radiologic appearance of the spine changed over time, illustrating the evolving phenotype of this condition. Transmission from mother to son suggests that dominant pattern of inheritance is possible. A classification of the enchondromatoses is discussed.     

High throughput parallel analysis of hundreds of patient samples for more than 100 mutations in multiple disease genes

As more mutations are identified in genes of known sequence, there is a crucial need in the areas of medical genetics and genome analysis for rapid, accurate and cost-effective methods of mutation detection. We have developed a multiplex allele-specific diagnostic assay (MASDA) for analysis of large numbers of samples (> 500) simultaneously for a large number of known mutations (> 100) in a single assay. MASDA utilizes oligonucleotide hybridization to interrogate DNA sequences. Multiplex DNA samples are immobilized on a solid support and a single hybridization is performed with a pool of allele-specific oligonucleotide (ASO) probes. Any probes complementary to specific mutations present in a given sample are in effect affinity purified from the pool by the target DNA. Sequence-specific band patterns (fingerprints), generated by chemical or enzymatic sequencing of the bound ASO(s), easily identify the specific mutation(s). Using this design, in a single diagnostic assay, we tested samples for 66 cystic fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell anemia (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations, four mutations in Canavan disease, four mutations in Fanconi anemia, and five mutations in BRCA1. Each mutation was correctly identified. Finally, in a blinded study of 106 of these mutations in > 500 patients, all mutations were properly identified. There were no false positives or false negatives. The MASDA assay is capable of detecting point mutations as well as small insertion or deletion mutations. This technology is amenable to automation and is suitable for immediate utilization for high-throughput genetic diagnostics in clinical and research laboratories.      

Integration and proliferation of transplanted cells in hepatic parenchyma following D-galactosamine-induced acute injury in F344 rats

To determine whether liver repopulation with cell transplantation could be of therapeutic value in acute hepatic failure, it is necessary to establish the fate of transplanted hepatocytes. This study used dipeptidyl peptidase IV-deficient F344 rats as recipients to analyse the engraftment and proliferation of transplanted hepatocytes. Syngeneic hepatocytes were transplanted intrasplenically 24-30 h after induction of liver injury by D-galactosamine (GalN). Portosystemic shunting was analysed with 99m-Tc-labelled albumin microspheres. GalN-treated rats showed characteristic hepatic necrosis, inflammation, gamma-glutamyl transpeptidase activation, and regenerative activity, without increased portosystemic shunting (>99% 99m-Tc activity was in the liver in normal and GalN-treated rats). Transplanted cells entered hepatic sinusoids promptly and were observed in liver plates at 48 h. The number of transplanted cells increased in GalN-treated rats by approximately seven-fold (range two- to 12-fold), along with evidence for DNA synthesis between 3 and 14 days after cell transplantation and greater prevalence of larger transplanted cell clusters. These findings indicate that the liver can be safely repopulated in animals with acute liver failure, although the time required for regenesis of plasma membrane structures and proliferation in transplanted hepatocytes will need to be considered in developing therapeutic strategies.     

Mouse homologues of the human AZF candidate gene RBM are expressed in spermatogonia and spermatids, and map to a Y chromosome deletion interval associated with a high incidence of sperm abnormalities

An RNA-binding motif (RBM) gene family has been identified on the human Y chromosome that maps to the same deletion interval as the 'azoospermia factor' (AZF). We have identified the homologous gene family (Rbm) on the mouse Y with a view to investigating the proposal that this gene family plays a role in spermatogenesis. At least 25 and probably >50 copies of Rbm are present on the mouse Y chromosome short arm located between Sry and the centromere. As in the human, a role in spermatogenesis is indicated by a germ cell-specific pattern of expression in the testis, but there are distinct differences in the pattern of expression between the two species. Mice carrying the deletion Yd1, that maps to the proximal Y short arm, are female due to a position effect resulting in non-expression of Sry ; sex-reversing such mice with an Sry transgene produces males with a high incidence of abnormal sperm, making this the third deletion interval on the mouse Y that affects some aspect of spermatogenesis. Most of the copies of Rbm map to this deletion interval, and the Yd1males have markedly reduced Rbm expression, suggesting that RBM deficiency may be responsible for, or contribute to, the abnormal sperm development. In man, deletion of the functional copies of RBM is associated with meiotic arrest rather than sperm anomalies; however, the different effects of deletion are consistent with the differences in expression between the two species.      

Aeromonas hydrophila and aspiration pneumonia: a diverse presentation

Although there are ever increasing reports of extraintestinal human infections caused by Aeromonads, in both immunocompromised and immunocompetent patients, respiratory tract infections remain uncommon. We describe a case of aspiration pneumonia in an immunocompetent patient with multiple sclerosis, caused by a community acquired, multidrug resistant strain of Aeromonas hydrophila sensitive only to meropenem. The case highlights the clinical significance of Aeromonas hydrophila as a respiratory pathogen, as well as the community origin of multidrug resistance and the utility of newer carbapenems in such cases.