Reduction of intrinsic sinoatrial frequency and norepinephrine response of the exercised rat

Physical training is associated with a reduction of intrinsic sinoatrial activity; the present study examined the role of the parasympathetic nervous system in this reduction. Six groups of rats were studied for 10 weeks: inactive control; treadmill exercised; parasympathetic receptor blockade with atropine; exercise plus atropine; parasympathetic receptor stimulation with carbachol; and exercise plus carbachol. In vivo ISF (cardiac frequency 20 min after injection of propranolol and atropine) was measured at 3-week intervals. At the end of 10 weeks the right atrium was excised, in vitro measurements were made of ISF, and chronotropic dose-response curves to acetylcholine and norepinephrine were established. In vivo, ISF was reduced with time, the greatest reduction being found in the exercise plus atropine group; the treadmill-exercised and the atropine-treated groups also had a greater reduction than the control group. In vitro, no differences were observed in acetylcholine responses. The maximum norepinephrine chronotropic response was reduced in the treadmill-exercised and the exercise plus atropine groups. The maximum norepinephrine-induced frequency correlated with the in vitro ISF (r = 0.75). Thus, ISF was reduced with training, but this effect was independent of parasympathetic activity. The properties of the sinoatrial node which set ISF also influenced the maximum norepinephrine response.     

Randomized trial of etoposide and cisplatin versus etoposide and carboplatin in patients with good-risk germ cell tumors: a multiinstitutional study

PURPOSE: This multicenter, randomized phase III clinical trial evaluated the efficacy of etoposide plus carboplatin (EC) versus etoposide plus cisplatin (EP) in good-risk germ cell tumor (GCT) patients. PATIENTS AND METHODS: Between October 1986 and December 1990, 270 patients with good-risk GCTs were randomized to receive four cycles of either EP or EC. The etoposide dose in all patients was 100 mg/m2 on days 1 through 5. EP patients received cisplatin at 20 mg/m2 on days 1 through 5 and therapy was recycled at 21-day intervals. For EC patients, the carboplatin dose was 500 mg/m2 on day 1 of each cycle and the EC recycling interval was 28 days. RESULTS: Two hundred sixty-five patients were assessable: 131 patients treated with EC and 134 treated with EP. One hundred fifteen of 131 assessable patients (88%) treated with EC achieved a complete response (CR) versus 121 of 134 patients (90%) treated with EP (P = .32). Sixteen patients (12%) treated with EC relapsed from CR versus four patients (3%) treated with EP. Therefore, 32 patients (24%) who received carboplatin experienced an event (incomplete response [IR] or relapse) compared with 17 of 134 patients (13%) who received cisplatin (P = .02). At a median follow-up of 22.4 months, event-free and relapse-free survival were inferior for patients treated with EC (P = .02 and P = .005, respectively). No difference in overall survival was evident (P = .52). CONCLUSION: Two-drug therapy with EC using this dose and schedule was inferior to therapy with EP. Cisplatin remains as the standard platinum analog in the treatment of patients with good-risk GCTs. Carboplatin should be restricted to investigational trials in GCT.     

Characterization of mat A-2, mat A-3 and deltamatA mating-type mutants of Neurospora crassa

The mating-type locus of Neurospora crassa regulates mating identity and entry into the sexual cycle. The mat A idiomorph encodes three genes, mat A-1, mat A-2, and mat A-3. Mutations in mat A-1 result in strains that have lost mating identity and vegetative incompatibility with mat a strains. A strain containing mutations in both mat A-2 and mat A-3 is able to mate, but forms few ascospores. In this study, we describe the isolation and characterization of a mutant deleted for mat (deltamatA), as well as mutants in either mat A-2 or mat A-3. The deltamatA strain is morphologically wild type during vegetative growth, but it is sterile and heterokaryon compatible with both mat A and mat a strains. The mat A-2 and mat A-3 mutants are also normal during vegetative growth, mate as a mat A strain, and produce abundant biparental asci in crosses with mat a, and are thus indistinguishable from a wild-type mat A strain. These data and the fact that the mat A-2 mat A-3 double mutant makes few asci with ascospores indicate that MAT A-2 and MAT A-3 are redundant and may function in the same pathway. Analysis of the expression of two genes (sdv-1 and sdv-4) in the various mat mutants suggests that the mat A polypeptides function in concert to regulate the expression of some sexual development genes.     

Effect of contrast agents on the activity of acid phosphatase in mouse neutrophils]

We report a case of Pasteurella multocida pneumonia and empyema in an otherwise healthy patient. The most frequently observed human complication with this microorganism is a local wound infection. Only a few cases of pneumonia have been described, and most of the patients were immunodeficient.     

Computed tomographic angiography of the thoracic vessels: the method, initial experience and outlook for its use

The paper presents the data available in the literature on computed tomographic angiography and the first experience with it to study thoracic vessels. It details the principles of spiral computed tomography and CT angiography. Practical aspects of their implementation, as well as basic concepts are outlined. It is concluded that CT angiography is promising in studying thoracic vessels in various abnormalities.     

Iterative selection from a Salmonella typhimurium cosmid library can lead to the isolation of an atypically small plasmid

OBJECTIVE: To determine whether ocular cicatricial pemphigoid (OCP) may represent a distinct immunopathologic disease when it is pure ocular cicatricial pemphigoid (POCP) (e.g., only confined to the conjunctiva) or when it is associated with skin or extraocular mucous membrane lesions or both (OCP+). DESIGN: Prospective, immunologic, and immunopathologic study with special emphasis on direct immunoelectron microscopy. PARTICIPANTS: Six patients with POCP and seven patients with OCP+. INTERVENTION: After informed consent was obtained, a conjunctival biopsy was performed in all patients. Skin and extraocular mucosa biopsy specimens were harvested in selected cases only. MAIN OUTCOME MEASURES: Results of direct immunofluorescence and direct immunoelectron microscopy without freezing on conjunctival and skin biopsy specimens, indirect immunofluorescence, and Western immunoblotting analysis were analyzed. RESULTS: Results of direct immunoelectron microscopic examination of the conjunctiva showed the presence of immune deposits in the upper lamina lucida of the basement membrane zone in the six patients with POCP, whereas the immune reactants were located in the lower part of the lamina lucida and in the lamina densa of the basement membrane zone (conjunctiva, buccal mucosa, and skin) in the seven patients with OCP+. Direct immunofluorescence was positive in the biopsy specimens of three patients with POCP (50%) and the seven patients with OCP+ (100%). Results of indirect immunofluorescence study showed circulating autoantibody levels only in two patients with OCP+, and results of Western immunoblot analysis were negative. CONCLUSIONS: Results of direct immunoelectron microscopic examination of the conjunctiva support the hypothesis that POCP may be a disease entity distinct from mucocutaneous cicatricial pemphigoid.     

Changes in human immunodeficiency virus type 1 envelope glycoproteins responsible for the pathogenicity of a multiply passaged simian-human immunodeficiency virus (SHIV-HXBc2)

In vivo passage of a poorly replicating, nonpathogenic simian-human immunodeficiency virus (SHIV-HXBc2) generated an efficiently replicating virus, KU-1, that caused rapid CD4(+) T-lymphocyte depletion and AIDS-like illness in monkeys (S. V. Joag, Z. Li, L. Foresman, E. B. Stephens, L.-J. Zhao, I. Adany, D. M. Pinson, H. M. McClure, and O. Narayan, J. Virol. 70:3189-3197, 1996). The env gene of the KU-1 virus was used to create a molecularly cloned virus, SHIV-HXBc2P 3.2, that differed from a nonpathogenic SHIV-HXBc2 virus in only 12 envelope glycoprotein residues. SHIV-HXBc2P 3.2 replicated efficiently and caused rapid and persistent CD4(+) T-lymphocyte depletion in inoculated rhesus macaques. Compared with the envelope glycoproteins of the parental SHIV-HXBc2, the SHIV-HXBc2P 3.2 envelope glycoproteins supported more efficient infection of rhesus monkey peripheral blood mononuclear cells. Both the parental SHIV-HXBc2 and the pathogenic SHIV-HXBc2P 3.2 used CXCR4 but none of the other seven transmembrane segment receptors tested as a second receptor. Compared with the parental virus, viruses with the SHIV-HXBc2P 3.2 envelope glycoproteins were more resistant to neutralization by soluble CD4 and antibodies. Thus, changes in the envelope glycoproteins account for the ability of the passaged virus to deplete CD4(+) T lymphocytes rapidly and specify increased replicative capacity and resistance to neutralization.