[Chronic non-suppurative destructive cholangitis (CNSDC)].
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Autoimmune Diseases↗
Biomedical subjects
K Shiraki
Publications and source records attributed to K Shiraki.
The involvement of polyamines in the proliferation of cultured retinal pigment epithelial cells.
PURPOSE: To investigate the involvement of polyamines (putrescine, spermidine, and spermine) in the proliferation of retinal pigment epithelium (RPE) using cultured bovine RPE cells. METHODS: The polyamine content and the activities of rate-limiting enzymes in polyamine biosynthesis (ornithine decarboxylase [ODC] and S-adenosylmethionine decarboxylase [SAMDC]) and in polyamine biodegradation (spermidine spermine N1-acetyltransferase [SAT]) were measured after proliferative stimulation by 10% fetal calf serum (FCS). DNA synthesis was determined by [3H]thymidine incorporation into the acid-insoluble fraction after the addition of an inhibitor of ODC (alpha-difluoromethylornithine [DFMO]) or SAMDC (methylglyoxal bis[guanylhydrazone] [MGBG]). The effects of exogenous polyamines on DNA synthesis after the additions of inhibitors also were determined. RESULTS: ODC and SAMDC activities were elevated after stimulation by FCS and reached their peaks 16 hours and 4 hours, respectively, after the addition of FCS. SAT activity was not increased. Polyamine content was increased significantly after stimulation by FCS. DFMO did not inhibit DNA synthesis induced by FCS, and only putrescine content was decreased significantly among polyamines. However, MGBG inhibited DNA synthesis in a dose-dependent manner, and the amounts of spermidine and spermine were decreased significantly. Exogenous polyamines, especially spermine, restored MGBG-induced inhibition of DNA synthesis. CONCLUSIONS: Polyamines are essential for the proliferation of cultured bovine RPE cells. These data suggest that, of the polyamines, spermine has the greatest effect on DNA synthesis although other polyamines can substitute for spermine at higher concentrations with similar results. As for polyamine metabolism in RPE proliferation, it is possible that SAMDC is the key enzyme rather than ODC.
Acetyltransferases↗
Neutralization of human immunodeficiency virus type 1 (HIV-1) with antibody from carriers' plasma against HIV-1 protein p17.
It was investigated whether human antibody against HIV-1 protein p17 (anti-p17) in HIV carriers' plasma has the ability to neutralize the infectivity of HIV. By the pretreatment of HIV-1 with anti-p17 from HIV carriers, progeny HIV-1 production from cells infected with virus pretreated with anti-p17 was suppressed and/or delayed. The neutralizing activity of anti-p17 was decreased in the presence of recombinant p17. The latter obviously masked the neutralizing activity of anti-p17. The relevant epitope(s) on p17 is located apparently on the surface of HIV virions and the binding of anti-p17 to p17 impairs the infectivity of HIV. This implies that anti-p17, if stably present in HIV carriers' plasma, may also play an important role in reducing the infectivity of HIV-1 in vivo.
Antibody Specificity↗
Paresthesia induced by cutaneous infection with herpes simplex virus in rats.
To assess the effects of herpetic infection on somatic sensations, herpes simplex virus type-1 was inoculated into the unilateral hind paw of the rat and its behavioral responses to noxious pressure and tactile stimulation were examined. Herpetic infection significantly increased the nociceptive threshold of the treated hind paw with a delay around 4 days. The increase in the nociceptive threshold continued at least until post-inoculation day 21 and was larger at night than in the morning. Any alterations in tactile responses were not observed during this period. Herpetic DNA was detected by polymerase chain reaction in the inoculated skin, but not in the dorsal root ganglia on the inoculated side, on the next day after inoculation. But on the following days it was detected in the dorsal root ganglia, but not in the skin. These results suggest that herpetic infection of the dorsal root ganglion produces paresthesia as a functional abnormality of the sensory neurons in rats.
Animals↗
Trifluoroethanol-induced stabilization of the alpha-helical structure of beta-lactoglobulin: implication for non-hierarchical protein folding.
Trifluoroethanol (TFE) is known to stabilize the alpha-helical structure in proteins and their fragments. However, the relationship between the TFE-induced structures and the native structure is not clear. Here we show that beta-lactoglobulin, which consists predominantly of beta-sheets, exhibited a markedly high propensity to form an alpha-helical structure in the presence of TFE, as measured by far-UV circular dichroism. A cooperative transformation from the beta-sheet structure to an alpha-helical structure occurred at a TFE concentration between 10% and 20%. These results were in contrast to a gradual beta-sheet to alpha-helix transition of the constant fragment of the immunoglobulin light chain, which is also a beta-sheet protein. To understand the significance of the high helical propensity of beta-lactoglobulin, we measured the TFE-induced conformational transition of more than 20 proteins of various secondary structural types. Whereas the alpha-helical proteins showed a propensity to form an extensive helical structure in TFE, the helical propensity of proteins with a low helical content in the native state varied. The helical content in TFE was correlated more with the helical content predicted by a secondary structure prediction than with the helical content of the native structure, suggesting that the stability of the helical structure in TFE is determined by local interactions between nearby amino acid residues. Our results suggest that an alpha-helical intermediate can accumulate during the refolding process of beta-lactoglobulin and that a hierarchical model of protein folding is not necessarily true for some beta-sheet proteins including beta-lactoglobulin.
Animals↗
Efficacy of kakkon-to, a traditional herb medicine, in herpes simplex virus type 1 infection in mice.
Kakkon-to is one of the representative traditional herb medicines (Kampo formulae) and has been used historically for the treatment of infectious diseases in China and Japan. The efficacy of this preparation was characterised using a cutaneous herpes simplex virus type 1 (HSV-1) infection in mice as a model for human viral infection. Kakkon-to at a dose corresponding to human use reduced significantly the mortality of HSV-1-infected mice and localised skin lesions. Delayed type hypersensitivity (DTH) response to HSV-1 antigen was significantly stronger in treated mice than in untreated mice. However, no histopathological difference was noted in the skin lesions between treated and untreated mice except for the size of the lesions. Kakkon-to did not inhibit the growth of HSV-1 in vitro. Natural killer cell activity, natural cytotoxic killer cell activity, and the population of T-cell subsets in spleen cells of infected mice were not affected by the drug. Kakkon-to did not augment interferon induction and anti-HSV-1 antibody production, nor increased cytokine levels such as interleukin-1 alpha, interleukin-2, interferon-gamma, and tumour necrosis factor-alpha in sera of infected mice. Thus, Kakkon-to induced strong DTH to HSV-1 in infected mice, which may have caused localisation of skin lesions and reduction in the mortality of treated mice.
Animals↗
Indocyanine green angiography in choriocapillary atrophy induced by sodium iodate.
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Animals↗
Two independent outbreaks of measles in partially vaccinated junior high schools in Tottori, Japan.
We analyzed retrospectively a relative risk of measles attacks in vaccinated vs. unvaccinated students using two independent outbreaks in Japan. The first involved 33/328 (10%) students where 64% students and 30% measles cases had been vaccinated. The second involved 27/241 (11%) students where 81% students and 48% measles cases had been vaccinated. The attack rates of vaccinated vs. unvaccinated students were significantly low (p < 0.001), but they accounted 25% in both episodes. The statistically significant clinical features among vaccinated and unvaccinated cases included the average duration of fever, 5.16 +/- 1.71 vs. 6.67 +/- 2.19 days (p = 0.01) and the incidence of complications, 0 vs. 25%, respectively. These results suggested that the measles in vaccinated cases were mostly due to secondary failures.
Adolescent↗
Hemolytic anemia provoked by recombinant alpha-interferon.
A 30-year-old female with chronic hepatitis C treated with recombinant alpha-interferon developed serious hemolytic anemia after receiving 10 million units a day for 4 weeks. The results of Coombs' tests were negative before and after interferon therapy. The hemolytic anemia gradually improved after the withdrawal of recombinant alpha-interferon and the administration of methyl-prednisolone. The clinical course suggested that the recombinant alpha-interferon had provoked the hemolytic anemia.
Adult↗
Colony-stimulating factors and coxackievirus B3 myocarditis in mice: macrophage colony-stimulating factor suppresses acute myocarditis with increasing interferon-alpha.
The effects of macrophage colony-stimulating factor (M-CSF) and granulocyte colony-stimulating factor (G-CSF) on murine coxsackievirus B3 myocarditis were investigated. A total of 4 x 10(6) U/kg/day M-CSF and 20 micrograms/kg/day G-CSF were injected subcutaneously every day on day 0 to day 14 starting simultaneously with virus inoculation. Serum interferon-alpha was measured periodically. The survival rate of the M-CSF group was higher than that of the untreated control group (p < 0.05). On days 7 and 14 cardiac disease was significantly lower in the M-CSF group than in the untreated control group. Myocardial virus titers on day 7 in the M-CSF group were lower compared with those of the untreated control group. No significant difference was seen in the survival, cardiac disease, or myocardial virus titers between the G-CSF and the control groups. Monocyte counts on days 7 and 14 in the M-CSF group were increased compared with those in the control group. Serum interferon-alpha titers in the M-CSF and G-CSF groups on day 4 and those in the M-CSF group on day 7 were significantly increased in comparison with those of the untreated control group. We conclude that M-CSF but not G-CSF has the potency to limit myocardial virus titers and to reduce cardiac disease in the acute coxsackievirus B3 myocarditis. This ability is associated with an elevated interferon-alpha. Thus macrophages may play a defensive role in this model.
Acute Disease↗
Inhibitory action of acyclovir (ACV) and penciclovir (PCV) on plaque formation and partial cross-resistance of ACV-resistant varicella-zoster virus to PCV.
Penciclovir has potent antiviral activity against varicella-zoster virus (VZV). We have characterized the inhibitory effects of penciclovir and acyclovir on the plaque formation of cell-free VZV and cross-resistance of acyclovir-resistant VZV to penciclovir. The apparent effective concentration for 50% plaque reduction (EC50) of penciclovir determined on the third day was significantly lower than that determined on the fourth or fifth day. The size of plaques was smaller in the presence of penciclovir than in the presence of acyclovir. The effective concentrations for 50% reduction of the number of infected cells per plaque were 1.40 and 5.00 micrograms/ml for penciclovir and acyclovir, respectively. Thus penciclovir suppressed spread of infection within developing plaques more efficiently than acyclovir. Five acyclovir-resistant VZV strains with altered DNA polymerase selected by acyclovir were examined for cross-resistance to penciclovir. They were 11- to 18-fold more resistant to ACV than the parent strain, but only 4- to 5-fold more resistant to PCV. Penciclovir-triphosphate carrying the 3'-hydroxyl group of 2'-deoxyribose might have better affinity to the altered viral DNA polymerase than acyclovir-triphosphate without the 3'-hydroxyl group.
Acyclovir↗
Effects of granulocyte colony-stimulating factor upon coxsackievirus B3 myocarditis in mice.
Granulocyte colony-stimulating factor is a potent activator of mature granulocytes, and subsequently enhances superoxide release. The purpose of this study was to investigate the effects of granulocyte colony-stimulating factor upon murine coxsackievirus B3 myocarditis in relation to free radical-mediated cardiac damage. Two-week-old, male, C3H/He mice were inoculated intraperitoneally with coxsackievirus B3. Granulocyte colony-stimulating factor 20 micrograms.kg-1.day-1, polyethylene glycol-conjugated superoxide dismutase (an enzyme catalyzing the conversion of O2- to H2(O2)) 1 x 10(3) U.kg-1.day-1 and granulocyte colony-stimulating factor 20 micrograms.kg-1.day-1, plus polyethylene glycol-conjugated superoxide dismutase 1 x 10(3) U. kg-1. day-1, were injected subcutaneously daily on days 0 to 14. Treated groups were compared to the infected, untreated group. The survival rate in the polyethylene glycol-conjugated superoxide dismutase group was higher than that of the untreated group on day 14, but on day 7, cardiac pathology was not significantly different among the four groups. On day 14, the scores of cellular infiltration, myocardial necrosis and calcification were lower in the polyethylene glycol-conjugated superoxide dismutase group and in the granulocyte colony-stimulating factor plus polyethylene glycol-conjugated superoxide dismutase group than in the untreated group. The myocardial virus titres on days 7 and 14 did not differ significantly among the four groups. The number of total white blood cell and neutrophil counts were significantly greater in the granulocyte colony-stimulating factor group than in the untreated group on day 7. Taken altogether with the previous reports and present evidence that the administration of granulocyte colony-stimulating factor did not exacerbate coxsackievirus B3 myocarditis, it may be that oxygen-free radicals appeared to be derived not from leukocytes but from other components in this experimental model of myocarditis, whereas the myocardium was inflamed with leukocytes.
Animals↗
Mechanism of thirst attenuation during head-out water immersion in men.
The purpose was to determine whether extracellular volume or osmolality was the major contributing factor for reduction of thirst in air and head-out water immersion in hypohydrated subjects. Eight males (19-25 yr) were subjected to thermoneutral immersion and thermoneutral air under two hydration conditions without further drinking: euhydration in water (Eu-H2O) and euhydration in air, and hypohydration in water (Hypo-H2O) and hypohydration in air (3.7% wt loss after exercise in heat). The increased thirst sensation with Hypo-H2O decreased (P < 0.05) within 10 min of immersion and continued thereafter. Mean plasma osmolality (288 +/- 1 mosmol/kgH2O) and sodium (140 +/- 1 meq/l) remained elevated, and plasma volume increased by 4.2 +/- 1.0% (P < 0.05) throughout Hypo-H2O. A sustained increase (P < 0.05) in stroke volume accompanied the prompt and sustained decrease in plasma renin activity and sustained increase (P < 0.05) in plasma atrial natriuretic peptide during Eu-H2O and Hypo-H2O. Plasma vasopressin decreased from 5.3 +/- 0.7 to 2.9 +/- 0.5 pg/ml (P < 0.05) during Hypo-H2O but was unchanged in Eu-H2O. These findings suggest a sustained stimulation of the atrial baroreceptors and reduction of a dipsogenic stimulus without major alterations of extracellular osmolality in Hypo-H2O. Thus it appears that vascular volume-induced stimuli of cardiopulmonary baroreceptors play a more important role than extracellular osmolality in reducing thirst sensations during immersion in hypohydrated subjects.
Adult↗
Responses of the circulatory system and muscle sympathetic nerve activity to head-down tilt in humans.
These experiments were conducted to examine whether changes in central and peripheral hemodynamics were proportional to muscle sympathetic nerve activity (MSNA) during graded head-down tilt (HDT). Twelve healthy males (19-42 yr old) underwent HDT at 15 degrees and 30 degrees for 10 min each with a 10-min rest period between the trials. MSNA at 15 degrees HDT declined by 31 +/- 5% (P < 0.05) for burst rate and by 37 +/- 3% (P < 0.05) for total activity. At 30 degrees HDT, the reduction in MSNA was 51 +/- 5% for burst rate (P < 0.05 vs. 15 degrees HDT) and 46 +/- 5% for total activity (P < 0.05 vs. 15 degrees HDT). Stroke volume increased (P < 0.05) during both 15 degrees and 30 degrees HDT, but heart rate and blood pressure remained unchanged. A concurrent increase in central venous pressure (P < 0.05) and stroke volume with a reduction of thoracic impedance (P < 0.05) suggests that both pressure and volume in the atrium were elevated during HDT, and the magnitude of these changes was greater (P < 0.05) at 30 degrees HDT than at 15 degrees HDT. Forearm blood flow increased during HDT at both 15 degrees and 30 degrees, and the magnitude of the increase was greater (P < 0.05) at 30 degrees HDT. It is concluded that the magnitude of the loading of the cardiopulmonary mechanoreceptors during HDT was higher at 30 degrees in comparison to 15 degrees. This increased the afferent firing rate by the cardiopulmonary receptors and probably inhibited sympathetic outflow in the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Mechanisms and factors for development of HBV asymptomatic carrier].
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Carrier State↗
[Clinical study of fulminant hepatitis type B of infant caused by vertical transmission].
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Female↗
A clinical study of lectin-reactive alpha-fetoprotein as an early indicator of hepatocellular carcinoma in the follow-up of cirrhotic patients.
Levels of two types of lectin-reactive alpha-fetoprotein (AFP), designated AFP-L3 and AFP-P4+P5, were analyzed with Lens culinaris agglutinin A and AFP-P4+P5 with erythroagglutinating phytohemagglutinin, respectively, in an attempt to determine the utility and significance of these macromolecules as early indicators of hepatocellular carcinoma during the periodic follow-up of cirrhotic patients. The subjects were 51 of 190 consecutive cirrhotic patients in whom hepatocellular carcinoma developed during a 6-year follow-up period and 21 cirrhotic patients without hepatocellular carcinoma. Serum AFP levels were of limited value to diagnose and predict hepatocellular carcinoma. The relative levels of AFP-L3 and AFP-P4+P5 in patients with hepatocellular carcinoma at the time of tumor detection were significantly higher than those in patients with cirrhosis. The sensitivity was 61%, and the specificity was 90%. Fourteen patients (48%) of 29 patients with small hepatocellular carcinomas less than 2 cm in diameter showed elevated percentage of lectin-reactive AFP. Retrospective examination of 21 patients who were positive for lectin-reactive AFP at diagnosis of hepatocellular carcinoma showed that 41% of them had already expressed lectin-reactive AFP 12 months before the direct detection of hepatocellular carcinoma by diagnostic imaging. These results lead us to conclude that the level of lectin-reactive AFP is a suitable predictive marker for the early recognition of hepatocellular carcinoma in the follow-up of patients with cirrhosis, and that measurements of the level of lectin-reactive AFP should be added to the screening methods that are now in use.
Biomarkers, Tumor↗
Effects of diving and hyperbaria on responses to exercise.
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Atmospheric Pressure↗