Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone mouse lung tumorigenesis by arylalkynes, mechanism-based inactivators of cytochrome P450

Arylalkynes such as 4-phenyl-1-butyne (PBY), 5-phenyl-1-pentyne (PPY) and 2-ethynylnaphthalene (2-EN) are suicide inhibitors of cytochrome P450 enzymes. Arylalkyl isothiocyanates such as 6-phenylhexyl isothiocyanate (PHITC) are structurally related to arylalkynes and are known to inhibit the cytochrome P450 mediated metabolic activation and tumorigenicity of a tobacco-specific lung carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In this study, we compared the ability of PBY, PPY, 2-EN and PHITC to inhibit A/J mouse lung tumorigenesis by NNK. Groups of 20 female mice were gavaged with 5 mumol of arylalkyne or PHITC in corn oil. Two hours later they were given a single i.p. injection of 10 mumol NNK. The mice were killed 16 weeks later. PPY and PHITC were both potent inhibitors of tumorigenesis by NNK, reducing lung tumor multiplicity from 8.35 tumors per mouse to 0.40 and 0.35 respectively. PBY and 2-EN also significantly inhibited tumor multiplicity. The results of this study demonstrate that arylalkynes and PHITC are potent inhibitors of NNK induced lung tumorigenesis in A/J mice, consistent with the hypothesis that inhibition of specific cytochrome P450 enzymes is involved in inhibition of tumorigenesis.     

Intussusception caused by a carcinoma of the cecum during pregnancy: report of a case and review of the literature

Respiratory infections are the most common infection in children. They differ remarkably according to age, bacteria and viruses. Therefore a careful history of outbreak, age, former infections, involvement of surroundings, symptoms, etc are essential. The present study included 50 children, aged between 0.3 and 12 yrs, all treated ambulatorily. 21 received brodimoprim (B) and 29 erythromycin (E). Indications were: tonsillitis, bronchitis, otitis media, sinusitis and scarlet fever. Dosages were: B was given 10 mg/kg body weight (b.w.) initially followed by 5 mg/kg b.w., once-a-day. The duration of treatment varied between 4 and 14 days (mean 8.3 days). E was given 30.50 mg/kg b.w. 3 times per day; duration 4 to 14 days (mean 8.6 days). Overall results were: in group B:12 cures, 5 improvements, 3 failures; 1 not assessable. In group E: 20 cures, 8 improvements, 1 failure. Side effects: in group B: vomiting (1), skin reaction (2), discontinuation (2); in group E: skin reaction (1), diarrhea (5), diarrhea+vomiting (1); discontinuation (2). The differences in efficacy and tolerability in the two groups are not statistically significant. The improved compliance with a single versus t.i.d. dosages has to be taken into account.     

Surgical treatment of metastatic lung tumors

To evaluate an association between Helicobacter pylori (H. pylori) infection and chronic atrophic gastritis (CAG), an established precursor of gastric cancer, we performed a cross-sectional study using IgG antibody against H. pylori and pepsinogens of blood donors in four prefectures in Japan. Although a geographic correlation between the age-adjusted prevalence rates for H. pylori infection and those for CAG was not seen, the age-adjusted odds ratios (OR) of H. pylori infection for CAG were high in each area (around five for men and from four to 12.6 for women). The association between them weakened with advancing age; the ORs in the youngest age group (16-29 yrs) and in the oldest age group (50-64 yrs) were 12.5 and 2.8 for men, and 11.5 and 5.2 for women, respectively. These findings suggest that H. pylori infection is strongly associated with CAG, while there are some other factors interacting in the development of CAG. A prospective cohort study in which CAG and H. pylori infection are taken into account will be necessary to assess the risks of gastric cancer.     

The percutaneous endoscopic treatment of staghorn nephrolithiasis

Hyperferremia is shown to affect antioxidant system of the body, oxidation-reduction reactions in the cells seen as shifts in lymphocyte chemiluminescence. Dynamic changes in lymphocyte chemiluminescence reflect the level of hyperferremia.     

Treatment of hemifacial spasm with botulinum toxin

We injected botulinum toxin to treat hemifacial spasm, and investigated the effects and the patient's impression of this treatment. Average duration of improvement lasted about 3.5 months in both the initial treatment group and the recurrent group. However the patients in the recurrent group received fewer units of botulinum toxin than those in the initial treatment group. Except for local paralysis that disappeared within a month, there were very few complications. Most patient were satisfied with this treatment. We conclude that the treatment of hemifacial spasm with botulinum toxin is both simple and useful.     

The significance of spinal cord compression as the initial manifestation of lymphoma

Sex hormones have profound effects on immune responses and may influence the outcome of autoimmune diseases such as rheumatoid arthritis (RA). We investigated the effect of gonadal steroids on the production of interleukin-1 (IL-1) and IL-6, cytokines believed to be important in the pathogenesis of RA. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy male donors and male patients with RA, and were stimulated with lipopolysaccharide (LPS) in the presence of different concentrations of 17-beta-estradiol, progesterone or testosterone. In studies of cells from normal male donors, 17-beta-estradiol at pharmacological concentrations (> or = 10(-6) M) enhanced IL-1 and IL-6 secretion as well as the production of cell-associated IL-1. Progesterone and testosterone at similar concentrations inhibited IL-1 secretion but had no significant effect on IL-6 secretion or on the production of cell-associated IL-1. In studies of male RA donors, 17-beta-estradiol failed to enhance IL-1 or IL-6 secretion and progesterone failed to inhibit IL-1 secretion. The inhibitory effects of testosterone, however, appeared to be similar to that in normal donors. It is suggested that 17-beta-estradiol may promote IL-1 and IL-6 production and release, while gestation hormone, progesterone, and testosterone may inhibit IL-1 release in vivo. These data may partly explain the gender and age differences in the incidence of RA and the development of the disease in men with low and androgen levels.     

Effects of glucose load on brain extracellular lactate concentration in conscious rats using a microdialysis technique

Changes in the brain lactate concentration in cerebral extracellular fluid (ECF) during intravenous infusion of glucose and local administration of glucose were investigated in adult, conscious, unrestrained rats, with a microdialysis probe in the posterior hippocampus. The rats were infused intravenously with either 25% sucrose solution or 25% glucose solution at a rate of 16.6 microliters.min-1.100 g-1 for three hours. The blood glucose concentration reached 17.0 +/- 2.6 mM at the end of the glucose infusion, and brain ECF glucose showed a parallel change with the blood glucose concentration and increased to 2.37 +/- 0.30 mM. However, blood and brain ECF glucose concentrations did not change in animals infused with the sucrose solution. On the other hand, the blood lactate concentration in the glucose-infused group also increased from 0.93 +/- 0.18 mM to 2.85 +/- 0.39 mM at the end of the glucose infusion, which was significantly higher than that measured in the sucrose-infused group. The blood lactate level in the glucose-infused group returned to the basal level by the end of the experiment. Brain ECF lactate concentrations increased from 1.21 +/- 0.06 mM to 1.69 +/- 0.11 mM in glucose-infused animals, but did not change in the sucrose-infused animals. The brain ECF lactate concentration showed a positive correlation with the brain ECF glucose concentration in glucose-infused animals. Another group of rats was administered glucose locally for 90 min after substitution of artificial cerebrospinal fluid.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cloning of a novel signal-transducing adaptor molecule containing an SH3 domain and ITAM

We molecularly cloned a cDNA coding for a novel phosphotyrosine molecule with a 70 kDa molecular mass, named STAM (signal transducing adaptor molecule), which is tyrosine-phosphorylated rapidly after stimulation with various cytokines such as IL-2, IL-3, IL-4, IL-7, GM-CSF, EGF and PDGF. STAM contains an SH3 (Src-homology 3) domain and the ITAM (immunoreceptor tyrosine-based activation motif), suggesting that STAM acts as an adaptor molecule involved in signal transducing pathways from the cytokine receptors.     

Expression of V642 APP mutant causes cellular apoptosis as Alzheimer trait-linked phenotype

APP is a transmembrane precursor of beta-amyloid. In dominantly inherited familial Alzheimer's disease (FAD), point mutations V6421, V642F and V642G have been discovered in APP695. Here we show that expression of these mutants (FAD-APPs) causes a clone of COS cells to undergo apoptosis associated with DNA fragmentation. Apoptosis by the three FAD-APPs was the highest among all possible V642 mutants; normal APP695 had no effect on apoptosis, suggesting that apoptosis by APP mutants in this system is phenotypically linked to the FAD trait. FAD-APP-induced apoptosis was sensitive to bcl-2 and most probably mediated by heteromeric G proteins. This study presents a model system allowing analysis of the mechanism for FAD-APP-induced cytotoxicity.