Biochemical genetic studies on wild populations of the Vicia amoena complex (tribe Vicieae: Fabaceae)

A 45-year-old human immunodeficiency virus (HIV)-infected patient has suffered for a period of 4 years from recurrent and, later on, persistent oral pseudomembranous candidosis. The Candida isolates proved to be resistant to azole derivates in vitro and in vivo. Treatment with amphotericin B parenterally was successful in February 1996, but had to be stopped when chemotherapy for lymphoma was started. In August 1996, the patient showed a shift from the pseudomembranous to the erythematous type of oral candidosis; antiretroviral combination therapy including the HIV protease inhibitor saquinavir had been started 4 months previously. In July 1997, the patient was still suffering from a persistent oral candidosis of the erythematous type.     

Tyrosine phosphorylation as a convergent pathway of heterotrimeric G protein- and rho protein-mediated Ca2+ sensitization of smooth muscle of rabbit mesenteric artery

1. The aim of this study was to determine whether different signal transduction mechanisms underlie the Ca2+ sensitizing effects of guanosine 5'-O-(3-thiotriphosphate) (GTP(gamma)S) and receptor agonists on beta-escin-skinned smooth muscle of rabbit mesenteric artery. 2. In the homogenate of the beta-escin-skinned arterial strip, C3 exoenzyme of Clostridium botulinum catalyzed the [32P]-ADP-ribosylation of only one protein that had the same molecular mass as the protein detected in Western blots with anti-rho p21 antibody. Pretreatment of preparations with C3 resulted in great inhibition of GTP(gamma)S-induced Ca2+ sensitization, although the effect of GTP(gamma)S at higher concentrations (> or = 30 microM) was not completely blocked by this treatment. In contrast, the enhancement by phenylephrine and histamine, in the presence of guanosine 5'-triphosphate, of the Ca2+-induced contraction was not affected by C3 pretreatment. 3. The protein kinase C (PKC) inhibitors calphostin C and staurosporine completely eliminated the enhancement by phorbol ester 12,13-dibutyrate of the Ca2+-induced contraction. However, these PKC inhibitors had no effect on GTP(gamma)S- and receptor agonist-induced Ca2+ sensitization. 4. The tyrosine kinase inhibitors genistein and tyrphostin 25 caused an irreversible and complete block of the enhancement by GTP(gamma)S of the Ca2+-induced contraction without affecting this Ca2+ contraction. The inactive genistein analogue daidzein did not modify the effect of GTP(gamma)S. The Ca2+ sensitizing effects of phenylephrine and histamine were also blocked by these tyrosine kinase inhibitors. 5. These results suggest that rho p21 predominantly mediates GTP(gamma)S-induced Ca2+ sensitization of beta-escin-skinned smooth muscle of rabbit mesenteric artery, while the Ca2+ sensitizing actions of heterotrimeric G protein-coupled receptor agonists do not involve this small G protein. However, it seems that tyrosine phosphorylation, but not PKC activation, plays an important role in both of the rho p21 protein- and heterotrimeric G protein-mediated Ca2+ sensitization mechanisms.     

Care of esophageal cancer patients with diabetes mellitus--preoperative management and treatment

The care of esophageal cancer patients with diabetes mellitus is described. The main points are as follows. 1. Prevention and control of infection. 2. Sufficient nutritional support (2000 Kcal/day) and hydration. 3. Control of plasma glucose level (150 mg/dl-250 mg/dl) by means of insulin. 4. An absence of ketone bodies and minimum glucose level (< 10 g/day) in the urine. 5. Prevention and control of hypoglycemia. Good control of diabetes mellitus in esophageal cancer patients may contribute to reduced surgical rislcs.     

Dental survey at school with the purpose to select children with no actual need of dental treatment

The purpose of this study was to develop an examination method to select children without from children with need of dental treatment. Furthermore the objective was that these examinations could be performed as a survey at school, without utilizing an expensive and fully equipped dental clinic but still maintain the certainty for the individual not to be at increased risk to be declared false caries-free, in comparison with ordinary examination at a dental clinic. The material comprised 88 children 10-13 years old. The children were subject to a survey-examination at school and a few weeks later at a dental clinic by the same examiner. Initially the children were examined at school by two examiners in order to measure the inter-examiner variability. The results showed that 2 of the 88 examined children (2.3%) were judged false healthy at school examination with respect to caries. The inter-examiner variability in diagnosing caries was greater than the intra-examiner variability between survey at school and examination at the dental clinic.     

Prevalence and role of anticardiolipin antibodies in Crohn disease

OBJECTIVES: Anticardiolipin antibodies belong to the group of antiphospholid antibodies, and may be seen in association with endothelial damage and recurrent vascular thrombosis. The aim of our study was to determine in patients with Crohn's disease the frequency of anticardiolipin antibodies, and to correlate their presence with clinical activity and treatment of the disease. METHODS: One hundred and thirty-eight sera from patients with Crohn's disease and 118 from age-matched controls were tested for IgG anticardiolipin antibodies. In the Crohn's disease group, we determined whether the patients had a past history of vascular thrombosis, a clinically active intestinal disease, or a current immunosuppressive therapy (steroids or azathioprine). RESULTS: Anticardiolipin antibodies were found significantly more often in patients with Crohn's disease than in controls: 11.0% versus 2.5%, P < 0.02. Three patients with Crohn's disease had a past history of vascular thrombosis, but none of them had anticardiolipin antibodies. The presence of anticardiolipin antibodies was not correlated with the fact that patients had a clinically active disease (P = 0.77), or a current immunosuppressive therapy at the time of the serological test (P = 0.95). CONCLUSIONS: There is a significantly high prevalence of patients with anticardiolipin antibodies during Crohn's disease. The positivity of the test does not seem to be correlated to the existence of a past history of vascular thrombosis, nor to the clinical activity of the disease.     

Induction of necrosis by zinc in prostate carcinoma cells and identification of proteins increased in association with this induction

Endothelin-1 (ET-1) is a cardiovascular peptide that binds to two distinct receptors, ET(A) and ET(B), resulting in systemic and regional vasoconstriction, alteration in sodium excretion, mitogenesis, and release of other vasoactive peptides such as atrial natriuretic peptide (ANP). A role for ET-1 has been proposed in congestive heart failure (CHF) based on the increase in circulating ET-1 in this cardiovascular disease state. The present study determined the cardiorenal and endocrine responses to chronic selective oral ETA antagonism in experimental CHF. Two groups of conscious dogs underwent 21 days of pacing-induced CHF. These groups included a control untreated group (n = 6) and a group that received an orally active ET(A) receptor antagonist (A-127722, Abbott Pharmaceuticals, 5 mg/kg PO bid, n = 6). Each group was studied at baseline before the onset of CHF and after 14 and 21 days of CHF. Compared with the CHF control group, the ET(A) receptor antagonism group at 14 days of CHF showed lower mean arterial pressure and systemic vascular resistance. Similarly, ET(A) receptor antagonism markedly attenuated the increase in circulating ANP despite similar atrial pressures. At 21 days of CHF, ET(A) receptor antagonism lowered pulmonary artery pressure, pulmonary vascular resistance, and systemic vascular resistance in association with a higher cardiac output. Plasma ANP remained suppressed. Despite the lower mean arterial pressure and circulating ANP in the ET(A) receptor antagonist group, the absolute decrease in sodium excretion from baseline was less compared with the untreated CHF control group. The present investigation supports the conclusion that endogenous ET-1 participates in the systemic and pulmonary vasoconstriction, the elevation of ANP, and the sodium retention that characterize this model of experimental CHF, suggesting a potential therapeutic role for ET(A) receptor antagonism in CHF.     

Gene engineering studies on sleep

Recent advancements in molecular engineering techniques have enabled us to study sleep of animals lacking or overproducing any protein molecule we are interested in. Abnormalities in sleep have already been observe in knockout mice lacking the gene for prion protein, 55 kD-receptor of tumor necrosis factor, etc. We also started a project to examine the effect of the loss or the overproduction of prostaglandin D synthase in sleep. The enzyme is responsible for biosynthesis of prostaglandin D2, the most potent endogenous substance to promote sleep reported so far. We generated both knockout and transgenic mice of prostaglandin D synthase. We are currently analysing the sleep of these mutant mice.     

Tobramycin-EDTA conjugate: a noninnocent affinity-cleaving reagent

The design, synthesis, and ribozyme inhibitory activity of a novel EDTA-aminoglycoside conjugate are reported. This affinity cleaving reagent is a noninnocent RNA binder: its RNA affinity, judged by its ability to inhibit the hammerhead ribozyme HH16, is different than the parent natural product and is markedly dependent on the oxidation state of the chelated metal ion.