Prognostic factors determining response to antidepressant drugs in psychiatric out-patients and general practice

The outcome of antidepressant drug treatment was measured in 200 patients, 145 seen in psychiatric out-patient clinics and 55 in general practice, after 4 weeks of therapy. The results of the 200 patients taken together suggested that prognosis was largely determined by factors dependent on the natural history of the disorder and that clinical symptoms were unimportant, but when the results for patients in each drug group were analysed separately symptoms were more important than natural history factors. We conclude that clinical symptoms are only important predictors of response to antidepressant drugs when the patients studied are homogeneous with regard to natural history factors, particularly duration of illness.     

Activation of extracellular signal-regulated kinases in the sciatic nerves of rats with experimental autoimmune neuritis

To investigate whether the phosphorylation of extracellular signal-regulated kinase (ERK) is involved in autoimmune injury of the peripheral nervous system (PNS), the expression of phosphorylated ERK (p-ERK) was analyzed in experimental autoimmune neuritis (EAN) in rats. Western blot analysis showed that the level of p-ERK was increased significantly in the sciatic nerves of rats on days 14 (p<0.05) and 24 (p<0.01) post-immunization, compared with controls, and its reaction declined at day 30 post-immunization. Immunohistochemistry showed that p-ERK protein was weakly expressed in Schwann cells and vascular endothelial cells in the sciatic nerves of CFA-immunized control rats. In EAN-affected sciatic nerves, p-ERK immunoreactivity was found mainly in ED1-positive macrophages on days 14 and 24 post-immunization. Moreover, on days 24 and 30 post-immunization, p-ERK immunoreactivity increased gradually in the Schwann cells of rat sciatic nerves with EAN. Based on these results, we postulated that the phosphorylation of ERK has an important role in the differentiation and survival of cells, including inflammatory cells and Schwann cells, in the rat sciatic nerve in EAN. Specifically, the activation of ERK in the recovery phase of EAN paralysis seems to be related in the survival of Schwann cells.     

Typing of Hantaviruses from five continents by polymerase chain reaction.

Hantavirus, a genus in the family Bunyaviridae, is comprised of at least four serologically distinct types: Hantaan, Seoul, Puumala and Prospect Hill. The present communication reports the use of polymerase chain reaction (PCR) for typing 27 independently isolated Hantaviruses from 5 different continents. Total cellular RNA was extracted from virus-infected Vero E6 cell monolayers by the acid guanidium thiocyanate-phenol-chloroform method. We have utilized 5 different sets of oligonucleotide primers ranging from 18 to 22 nucleotides in length; one set was specific for a conserved region of the S genomic segment and used as genus-specific primers, the other 4 sets of primers were designed from unique sequences of the M genomic segment such that each primer set was specific to only one serological type of Hantavirus. The PCR products were analyzed by restriction endonuclease digestion for further confirmation. We typed 10, 12, 3 and 1 isolates into Hantaan, Seoul, Puumala and Prospect Hill respectively. The results of PCR were 100% agreeable with that of serological typing, and thus, PCR can be used as an adjunct test with serological method(s) or an independent test for diagnosis and for typing of new isolates of Hantaviruses.     

Histopathologic changes of the spleen in suckling rats inoculated with Hantaan virus.

The purpose of this study is to delineate the histopathologic findings of the spleen after Hantaan viral inoculation, which is the largest lymphoid organ in rats, and to identify the viral location by anti-Hantaan virus (HTNV) monoclonal antibody. All the sixty one suckling rats of less than twenty four hours of age were used. Except twenty one rats of control group, twenty-five rats inoculated intracerebrally for the early change and fifteen suckling rats inoculated intramuscularly for the late change were uniformly susceptible to lethal infection with the ROK 84-105-1 strain of seed HTNV. The characteristic histopathologic findings were; appearance of macrophages below the splenic capsule on the 3rd day, small lymphocytes around the periarteriolar sheath on the 5th day increasing in numbers on the 7th day, and a markedly expanded marginal zone with some immunoblasts and plasma cells as well as decreased extramedullary hematopoiesis on the 9th and 14th days. Time of onset of histopathologic changes in spleen thickness, appearance of medium and large lymphocytes and degree of extramedullary hematopoiesis were influenced by inoculation route, whereas expansion of the marginal zone was affected by postnatal age.     

Ataxia-telangiectasia: phenotype/genotype studies of ATM protein expression, mutations, and radiosensitivity

Previous studies on a limited number of ataxia-telangiectasia (A-T) patients with detectable levels of intracellular ATM protein have suggested a genotype/phenotype correlation. We sought to elucidate this possible correlation by comparing ATM protein levels with mutation types, radiosensitivity, and clinical phenotype. In this study, Western blot analysis was used to measure ATM protein in lysates of lymphoblastoid cell lines (LCLs) from 123 unrelated A-T patients, 10 A-T heterozygotes, and 10 patients with phenotypes similar to A-T. Our Western blot protocol can detect the presence of ATM protein in as little as 1 microg of total protein; at least 25 microg of protein was tested for each individual. ATM protein was absent in 105 of the 123 patients (85%); most of these patients had truncating mutations. The remaining subset of 18 patients (15%) had reduced levels of normal-sized ATM protein; missense mutations were more common in this subset. We used a colony survival assay to characterize the phenotypic response of the LCLs to radiation exposure; patients with or without detectable ATM protein were typically radiosensitive. Nine of 10 A-T heterozygotes also had reduced expression of ATM, indicating that both alleles contribute to ATM protein production. These data suggest that although ATM-specific mRNA is abundant in A-T cells, the abnormal ATM protein is unstable and is quickly targeted for degradation. We found little correlation between level of ATM protein and the type of underlying mutation, the clinical phenotype, or the radiophenotype.     

Antifungal susceptibility testing of yeast isolates from blood cultures by microbroth dilution and the E test

The results of microbroth dilution were compared with those of the E test for 169 yeast isolates tested for their susceptibility to antifungal agents. All isolates were tested by both methods against amphotericin B, ketoconazole, fluconazole, and itraconazole. The E test results generally correlated well with those obtained by the reference method. There was at least 80% agreement of minimum inhibitory concentration results within two dilutions for all yeast species and agents tested, except forCryptococcus neoformans tested with fluconazole (8% agreement). The E test appears to be a suitable alternative antifungal susceptibility test method for yeasts, although improvements are required for testingCryptococcus neoformans against fluconazole.     

Yeast-specific DNA probes and their application for the detection of Candida albicans.

Two DNA fragments cloned from the genome of Candida albicans ATCC 10261 may be useful in the rapid diagnosis of disseminated candidosis. One sequence (probe EOB1) was specific for C. albicans (positive hybridisation with 45 strains tested). The second sequence (probe EOB2) detected C. albicans, as well as five other pathogenic Candida spp. and Saccharomyces cerevisiae, but did not react with human or bacterial DNA. Both probes were repetitive sequences in the genome of C. albicans. Probe EOB1 was used to detect, without DNA amplification, 500 C. albicans yeast cells in 1 ml of human blood.