Bloom''s syndrome with porokeratosis of Mibeili and multiple cancers of the skin, lung and colon

A 38-year-old Japanese male with Bloom's syndrome (BS) and porokeratosis of Mibelli (PM) developed multiple carcinomas of the skin and lung. There were multiple, spontaneous chromosomal aberrations and frequent sister chromatid exchanges (SCE). Cutaneous delayed-type hypersensitivity reactions were defective and serum IgM was decreased. The lung cancer was treated with radiation, which was effective but caused a severe pulmonary atelectasis and esophageal stricture. The patient expired one-and-a-half years later because of pneumonia. Autopsy disclosed an adenocarcinoma of the colon. The concurrent PM was considered responsible for the occurrence of multiple skin cancers.     

The polypeptides of adenovirus. V. Young virions, structural intermediate between top components and aged virions

The turnip yellow mosaic virus (TYMV) RNA-replicase bound to the chloroplast fraction of a participate cell-free preparation isolated from TYMV-infected Chinese cabbage leaves catalyzes the synthesis of RNA of the viral type, “plus” RNA, in the absence of added “minus” RNA template. Addition of TYMV-RNA does not stimulate RNA synthesis. The complex formed by the replicase bound to “minus” RNA template can be removed from the chloroplast fraction by solubilization with a non-ionic detergent, Lubrol W, and separated from insoluble material by centrifugation. The resulting supernatant contains the template-bound replicase as well as a small proportion of template-free replicase molecules. Treatment of this preparation with a polyethylene glycol-dextran two-phase aqueous system at high salt concentration removes the replicase from the template and yields, after centrifugation, a polyethylene glycol upper phase containing the template-free replicase molecules (PEG-enzyme) and a lower dextran phase containing a small proportion of replicase molecules still bound to their template. The soluble PEG-enzyme is markedly stimulated by added RNA. With TYMV-RNA as the added RNA, the product synthesized by the enzyme is RNA complementary to TYMV-RNA, i.e., “minus” RNA, indicating the enzyme uses the viral RNA as template. The “minus”-RNA synthesized remains hydrogen bonded to the viral RNA template and forms a RNase resistant, double-stranded structure. Chromatography on cellulose CF 11 column reveals two different double-stranded structures, one, fully double-stranded, in which the synthesized “minus” RNA strand is hydrogen bonded to template RNA of equal length, and one partly double-stranded and partly single-stranded in which probably the template RNA is very much longer than the synthesized “minus” RNA. The PEG-enzyme seems to be sensitive to high ionic strength since its activity can be completely suppressed by various salts; removal of the salts restores the activity.     

Congenital spongiform change in the brain stem nuclei of a domestic kitten

This report describes a novel spongiform change in the brain stem nuclei of a 9-month-old mixed breed kitten with neurological signs. Histologically, vacuoles were found in perineuronal spaces and neuropil, with mild to moderate astrocytosis in the brain stem nuclei. Vacuoles were not observed in the cytoplasm of neurons and no evidence of neuronal loss was found. Ultrastructurally, there were intramyelinic vacuoles with separation of lamellae at intraperiod lines and larger spaces formed by coalescence of ruptured vacuoles. Immunohistochemically, abnormal accumulation of prion protein (PrP) was not detected in the brain stem lesions. This is, to our knowledge, the first report of a feline spongiform change localized in the brain stem nuclei.     

The action of BDNF on GABAA currents changes from potentiating to suppressing during maturation of rat hippocampal CA1 pyramidal neurons

During the development of the hippocampus, the action of GABA shifts from depolarizing to hyperpolarizing, and brain-derived neurotrophic factor (BDNF) has important roles in GABAergic transmission. We demonstrate that BDNF (20 ng ml⁻¹) rapidly and reversibly potentiates postsynaptic GABA_A receptor-mediated currents (by 80.5 ± 14.3 %, n = 10) in hippocampal CA1 pyramidal neurons isolated from postnatal day (P)6 rats, using nystatin-perforated patch-clamp recordings. This potentiation is caused by an elevation of intracellular Ca²⁺ that occurs in response to the activation of Trk B receptor tyrosine kinase and phospholipase C-γ. The modulation of the GABA_A responses by BDNF in hippocampal CA1 pyramidal neurons isolated from P10 rats was more diverse (from potentiating to inhibitory), and at P14, BDNF induced a long-lasting inhibition. In addition, Ca²⁺/calmodulin-dependent protein kinase 2 plays important roles in the potentiating, but not in the inhibitory effect, of BDNF on the GABA_A responses. These results suggest that changes in the intracellular signalling pathway could contribute to the developmental shift of the actions of BDNF on inhibitory systems.     

Abnormalities of fecal flora in patients with acrodermatitis enteropathica

Fecal flora in two female patients with acrodermatitis enteropathica (AE) were investigated in connection with the efficacies of zinc sulfate and Entero-Vioform (EV). The following results were obtained.

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Suppression of neointimal thickening by a newly developed HMG-CoA reductase inhibitor,BAYw6228, and its inhibitory effect on vascular smooth muscle cell growth

1. The aim of this study was to determine whether BAYw6228 (BAYw), a newly developed 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, could suppress an atherogenic process such as intimal thickening by a mechanism other than lowering the level of serum cholesterol.
2. First, we evaluated the in vitro effect of BAYw on the proliferation of vascular smooth muscle cells (SMC) from various species: Sprague-Dawley (SD) rats, New Zealand (NZ) white rabbits, intimal cells from Watanabe hereditary hyperlipidemic (WHHL) rabbit and SMC from the new-born human aorta. The increasing rate of total protein content of these cells was inhibited by the addition of BAYw in a dose-dependent fashion. In the presence of 2% foetal calf serum (FCS), the value of IC₅₀ was 1.0 μM in SD rats. 2.1 μM in NZ white rabbits, and 0.3 μM in WHHL rabbits. With human SMC, the value was 0.02 μM in the presence of 10% FCS and 0.2 μM with a mixture of growth factors.
3. Based on these above in vitro findings, we next examined the in vivo effect of the agent to determine whether it could suppress rabbit intimal thickening induced by balloon catheterization. A balloon catheter was inserted from a peripheral branch of the left external carotid artery to the aorta to denude the endothelium of the left common carotid artery in Japanese white rabbits. After 12 days they were divided into control and BAYw groups. The former were subcutaneously injected with saline and the latter with BAYw 1 mg kg⁻¹ day⁻¹. Two days after the beginning of treatment, a second balloon injury was performed to the previously injured left common carotid artery in both groups. After another two weeks, the left common carotid artery was removed and variously stained. Although the total serum cholesterol in the BAYw group was significantly lower than in the control (P<0.05), the difference was not enough to affect intimal thickening. In addition, the BAYw group had a smaller intima/media ratio than the control group, decreasing to 45% of control (P<0.05). By anti-α smooth muscle actin antibody staining, these intimal thickening areas were entirely occupied by SMCs, and their amount was attenuated by BAYw. By anti-rabbit macrophage antibody (RAM 11) staining, the number of positive cells in the intimal thickening was markedly decreased in the BAYw group compared to control (P<0.01).
4. These results indicate that BAYw has an inhibitory effect on intimal thickening by attenuating intimal SMC proliferation and infiltration of macrophages, suggesting that BAYw could be effective in the prevention of the progression of atherosclerotic plaque-like restenosis after angioplasty.

     

The superiority of UW solution for maintaining ATP concentrations during pulmonary preservation

We evaluated three solutions used for preserving lungs, namely, University of Wisconsin (UW), Euro-Collins (E-C), and low potassium dextran (LPD), by measuring the high energy phosphates in the preserved lung tissue. The left lungs of Sprague-Dawley rats were excised and flushed with 5 ml of one of the solutions at 10°C through the pulmonary artery, after which they were deflated and immersed in the solution at 10°C for 24 h. The tissue adenosine triphosphate (ATP) concentration in mol/g tissue wet weight after 24 h of storage was 2.55 ± 0.48 (n = 7) in the UW lungs, 1.98 ± 0.25 (n = 6) in the E-C lungs, and 1.53 ± 0.32 (n = 4) in the LPD lungs, being significantly higher in the UW lungs than in either the E-C or LPD lungs (P < 0.05). The histopathological findings of the E-C lungs were more deteriorated, with marked interstitial edema, septal hypertrophy, and perivascular hyaline degeneration, than either the UW or LPD lungs. Thus, the findings of this study indicate the superiority of UW solution for lung preservation.     

Overtime, psychosocial working conditions, and occurrence of non- insulin dependent diabetes mellitus in Japanese men

OBJECTIVES: To ascertain the effects of overtime and psychosocial job conditions on the occurrence of non-insulin dependent diabetes mellitus (NIDDM) in Japan. DESIGN: An eight year prospective cohort study. SETTING: An electrical company in Japan. PARTICIPANTS: In 1984, a mailed questionnaire was sent to industrial workers of an electrical company in Japan. After excluding those who had a history of diabetes mellitus or other chronic diseases, 2597 male respondents were prospectively followed up for the succeeding eight years. Data from 2194 (84%) who were completely followed up were analysed. The occurrence of NIDDM during the follow up period was assessed according to the WHO criteria on the basis of an annual screening programme. MAIN RESULTS: The age adjusted incidence of NIDDM was significantly higher in those who worked overtime more than 50 hours per month than in those who worked 25 hours or less per month (p < 0.05). It was significantly higher in those who worked with new technology at baseline than in those who did not (p < 0.05). Cox's proportional hazard model indicated that those who worked overtime more than 50 hours per month had 3.7 times higher risk of NIDDM after controlling for known risk factors (p < 0.01) and those who worked with new technology had 2.4 times higher risk of NIDDM (p < 0.05). CONCLUSIONS: It is suggested that longer overtime and use of new technology are risk factors of NIDDM in Japanese men.     

Tumor scintigraphy by the method for subtracting the initial image with technetium-99m labeled antibody

The method for subtracting the initial image from the localization image was evaluated for radioimmunoscintigraphy of tumors with technetium-99m (Tc-99m) labeled antibodies. Monoclonal antibodies were parental mouse and mouse-human chimeric antibodies to carcinoembryonic antigen (CEA), designated F11-39 and ChF11-39, respectively, both of which have been found to discriminate CEA in tumor tissues from the CEA-related antigens. After reduction of the intrinsic disulfide bonds, these antibodies were labeled with Tc-99m. In vivo studies were performed on athymic nude mice bearing the human CEA-producing gastric carcinoma xenografts. Though biodistribution results showed selective and progressive accumulation of Tc-99m labeled antibodies at the tumor site, high radioactivity in blood was inappropriate for scintigraphic visualization of the tumors within a few hours. We examined the subtraction of the initial Tc-99m image from the Tc-99m localization image after a few hours. Subtracted images of the same count reflected the in vivo behavior of the Tc-99m radioactivity. The subtracted scintigrams revealed excellent tumor images with no significant extrarenal background. Visualization of the tumor site was dependent on antigen-specific binding and nonspecific exudation. These results demonstrate that a method of subtraction of the initial image may serve as a potentially useful diagnostic method for an abnormal site for agents with a low pharmacokinetic value.