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Biomedical subjects

M Shibata

Publications and source records attributed to M Shibata.

At least 505 records · Page 28Linked to original sources

Transplantation of syngeneic transfected cells to probe the in vivo immune response to viral proteins.

BALB/3T3 cells were transfected with the glycoprotein D (gD) gene of herpes simplex virus (HSV) and a cell line expressing gD on the cell surface was isolated. In vitro, 51Cr release tests showed that the transfected cells were destroyed by anti-HSV antibody in the presence of complement. To investigate in vivo immune response, the gD-transfected cells were transplanted into the footpads of syngeneic HSV-immunized or unimmunized BALB/c mice. In unimmunized mice, transfected cells remained intact for 7 days or longer, and the site of injection showed only slight lymphocyte infiltration. In contrast, in immunized mice, transfected cells elicited massive lymphocyte infiltration and were mostly destroyed by day 4. Analysis of infiltrating cells revealed that they were mainly Thy1+ and CD8+ lymphocytes along with small numbers of CD5+, CD4+, and B lymphocytes. These studies show that transfected murine cells expressing gD can be used to study the in vivo immune response to single viral proteins and they argue that the immune response contributes to the pathogenesis of HSV infection.

Animals↗

Steroid therapy for bronchopneumonia in chronic granulomatous disease.

In general, immunosuppressive agents such as corticosteroids are considered to be a contraindication for immunocompromised hosts with an active infection. Recently, however, a few cases have been reported where the obstructive lesions caused by the excessive inflammation in chronic granulomatous disease were successfully resolved with corticosteroids, resulting in a remission of the infection. As we have also experienced a case in which oral corticosteroid used in combination with antibiotics had a beneficial effect on an intractable respiratory tract infection which occurred in a patient with chronic granulomatous disease, we present the case report. Although it may be very difficult to determine the candidates, we consider that in selected cases a corticosteroid therapy with concomitant use of antibiotics will be a choice for the treatment of intractable infections in chronic granulomatous disease.

Adolescent↗

Activated oxygen species do not mediate hypercapnia-induced cerebral vasodilation in newborn pigs.

In newborn pigs, vasodilation in response to hypercapnia is dependent on prostaglandin (PG) H synthase. We investigated the contribution of activated oxygen by-products to hypercapnia-induced PGH synthase-dependent dilation of pial arteries and arterioles in anesthetized newborn pigs. Activated oxygen species were generated on the cerebral surface using xanthine oxidase and hypoxanthine. Catalase, H2O2, and iron or N-(2-mercaptopropionyl)-glycine (MPG) were used to separate effects of superoxide anion and hydroxyl radical. All the activated oxygen species tested caused vasodilation of both arteries and arterioles. Vasodilation to all activated oxygen species was largely reversible with only the hydroxyl radical encouraging combination of xanthine oxidase, hypoxanthine, H2O2, and FeCl3, causing significant dilation 20 min after removal of treatment. Cotreatment with MPG blocked this residual dilation. Neither pretreatment with the extracellular superoxide anion radical scavenger, superoxide dismutase (SOD), the intracellular superoxide anion radical scavenger, Tiron, the H2O2 scavenger, catalase, nor hydroxyl radical scavengers, dimethyl sulfoxide (DMSO) and MPG, altered vasodilation of pial arteries or arterioles in response to hypercapnia. Furthermore, the increase in cerebral prostanoid synthesis in response to hypercapnia was not affected by pretreatment with SOD, Tiron, catalase, DMSO, or MPG. We conclude that the progressively reduced forms of oxygen that would be produced during PGH synthase metabolism of arachidonic acid can dilate pial arteries and arterioles of newborn pigs. However, these activated oxygen species are not responsible for the vasodilation to hypercapnia in the newborn pig, suggesting that eicosanoids cause the dilation.

Animals↗

Prostanoids attenuate pial arteriolar dilation induced by cortical spreading depression in rabbits.

The role of prostanoids in mediating cerebrovascular responses to cortical spreading depression (CSD) was examined in anesthetized rabbits. CSD was elicited by KCl microinjection, and its propagation was monitored electrophysiologically. Pial arterial diameter was determined using a closed cranial window and intravital microscopy, and regional cerebral blood flow (rCBF) was determined using laser flowmetry. Levels of peri-arachnoid cerebrospinal fluid prostanoids were determined by radioimmunoassay. CSF increased pial arteriolar diameter 62% and rCBF 354% over the baseline levels. Locations of propagating CSD, dilating pial arteriole, and increased rCBF were always closely associated spatiotemporally. Cerebrospinal fluid prostanoid levels increased during single CSD-induced arteriolar dilation, and they were further augmented during multiple CSDs. Indomethacin enhanced both CSD-induced vasodilation (88%) and rCBF increase (580%), but it decreased the cerebrospinal fluid levels of prostanoids below the baseline levels and prevented their increase during CSD-induced vasodilation. These results indicate that prostanoids are synthesized from neurons or glial cells and/or the brain vessels and, as the net result, counteract pial arteriolar dilation and rCBF increase during CSD. In addition, they support the hypothesis that the vasodilation is caused primarily by neurogenic factors associated with CSD.

Animals↗

Differential effects of cytokines on thermosensitive neurons in guinea pig preoptic area slices.

This study was undertaken to determine whether the reported different courses of the febrile responses to the cytokines interleukin-1 beta (IL-1), interferon-alpha 2 (IFN), and tumor necrosis factor-alpha (TNF) might have neuroelectrophysiological correlates. The reactions of individual thermosensitive neurons in the preoptic area (POA) were evaluated by recording their extracellular single-unit firing rates (FR) in slices of guinea pig POA perfused with artificial cerebrospinal fluid (aCSF), human recombinant IL-1 (50-500 ng), IFN (1,000-8,000 U), and TNF (400-5,000 ng) (all doses per min/ml aCSF); thermosensitivity was assessed by FR responses to changes of perfusate temperature (32-42 degrees C). Overall, these cytokines depressed the FR of warm-sensitive units and excited those of cold-sensitive units, in agreement with expectations. However, the responses of individual neurons treated with two or all three cytokines were dissimilar: 61% of the units tested reacted differentially to two or three cytokines, 32% exhibited identical responses, and 7% had no response to any cytokine. These results support the possibility that IL-1, IFN, and TNF may affect not the same but rather distinct neurons functionally connected to common pyrogenic effectors. Thus they suggest that differential neuronal substrates may be utilized by each cytokine to exert its pyrogenic effect.

Animals↗

Detection of pre-C and core region mutants of hepatitis B virus in chronic hepatitis B virus carriers.

We analyzed the pre-C and core region of hepatitis B virus (HBV) DNA by a polymerase chain reaction in 22 chronic carriers. In 9 hepatitis B e antigen-positive asymptomatic carriers, a single DNA band was detected at the expected size, whereas additional shorter DNA bands were observed in 7 out of 11 patients with chronic hepatitis. The smaller-sized DNAs from one chronic hepatitis patient had various lengths of deletions spanning from 105 to 183 bp in the middle of the core gene, and all deletions included common nucleotide sequences. All of the smaller-sized DNAs from the other patients proved to be variant core genes. They were deleted in similar regions by Southern analysis using oligonucleotide probes. A follow-up study revealed that four out of seven chronic hepatitis patients with a short core gene seroconverted to antibody to hepatitis B e antigen, but those with only a "wild type" did not. In another set of sequence studies, clones isolated from two chronic carriers displayed heterogeneity of the pre-C and core gene which was more often present in sera with normal alanine aminotransferase levels than with abnormal levels. These results suggest that mutant HBV alters the host immune response, and may modulate the clinical course of HBV infection. An alternative possibility is that chronic hepatitis selects for mutant forms.

Adolescent↗

Pressure-volume relationships of finger arteries in healthy subjects and patients with coronary atherosclerosis measured non-invasively by photoelectric plethysmography.

Knowledge of the mechanical properties of the small arteries is important for understanding physiological and pathophysiological conditions in the human peripheral circulation. We have recently developed a new method for the noninvasive measurement of arterial elastic properties in human fingers using photoelectric plethysmography. In this study, the pressure-volume relationship, an index for expressing arterial elasticity, was measured by this method in the finger arteries of 91 healthy subjects and 102 patients with coronary artery disease. Aging effects on the elastic properties of finger arteries were examined in healthy subjects classified into three groups: under 30, 31-49, and over 50 years of age. The pressure-volume curve shifted downward with increase in age, indicating that the elasticity of finger arteries decreased with age. Patients with 75% or greater coronary stenosis, as compared with age-matched healthy subjects, showed distinctly lower elasticity of finger arteries. As the number of diseased coronary arteries increased, the elasticity of finger arteries tended to decrease steadily. The elasticity of finger arteries decreased in coronary disease patients with hypertension much more than in those without hypertension. These results suggest that age-related changes in arterial elasticity can occur in peripheral small arteries, and that peripheral arteries in patients with coronary atherosclerosis are less elastic than those in healthy subjects.

Adult↗

[The mechanism of electromyographic silent periods preceding a ballistic voluntary plantar flexion].

The present study was designed to investigate the neurophysiological mechanism of electromyographic silent periods(SP) preceding a ballistic voluntary movement. Ten male subjects were asked to respond to the flashing light by performing a plantar flexion as strongly and quickly as possible. The myoelectric signals from agonist (m. gastrocnemius, caput laterale: LG, m. soleus: SOL) and antagonist (m. tibialis anterior: TA) were simultaneously recorded together with the isometric contraction force signal. The excitability of the alpha motoneuron pools by means of the H reflex analysis was also determined at various phases of the movement. The results obtained are as follows: 1) In five out of 10 subjects, the electromyographic silent period was consistently observed (SP Group), while the rest of the subjects did not show such changes (NSP Group). 2) The maximum rate of tension raise (dF/dt) in SP Group (32.3 +/- 24.9 N/ms) was significantly (p less than .05) greater than NSP Group (15.1 +/- 12.0 N/ms). 3) In SP Group, the averaged H-wave mean amplitude decreased about 40ms prior to the appearance of SP. From these results, it can be concluded that SP in this study was attributable to the supraspinal influences so as to allow a specific motor program to be executed for selective recruitment of phasic (high threshold) motor units.

Adult↗

Measurement of local capillary permeability in skeletal muscle by microscopic clearance method.

To measure local capillary permeability to lipid-insoluble substances, we developed a microscopic tissue clearance method. It has been theoretically predicted that, when a tissue is stained with a dye by suffusing its solution around the tissue, subsequent concentration changes of the dye in the tissue due to adequate capillary flow washout takes a monoexponential time course of which decay constant is equal to the local capillary permeability surface area product (PS) per unit tissue volume. Therefore, when the capillary surface area (S) is calculated from the open capillary density in the adjacent tissue, it is possible to estimate the local permeability (P). This method was applied to the rabbit tenuissimus muscle under maximum vasodilatation, using Cr-EDTA (M.W. = 341) as a tracer. The correlation coefficient of the obtained clearance curves to the monoexponential decay was averaged to be 0.958 +/- 0.029 in 12 curves. The calculated values of Cr-EDTA permeability, 6.0 +/- 0.7 x 10(-6) cm/s, fairly well agreed with those reported for sucrose (M.W. = 342). It was concluded that this method is useful to measure local capillary permeability of small lipid-insoluble tracers.

Animals↗

The in vitro and in vivo inhibition of protein glycosylation and diabetic vascular basement membrane thickening by pyridoxal-5'-phosphate.

We studied the effect of pyridoxal-5'-phosphate (PAL-P) on protein glycosylation and diabetic nephropathy in NSY mice. In experiment 1, an in vitro model of the browning phenomenon involving the incubation of lysine and glucose was inhibited by PAL-P. In experiment 2, administration of PAL-P to congenitally diabetic NSY mice markedly reduced the thickening of the glomerular basement membrane. These results suggest that PAL-P has the potential to be used for reducing the nephrotic complications of diabetes mellitus.

Animals↗

Purification and characterization of aseanostatins: actinomycete-derived fatty acid inhibitors to myeloperoxidase release from human polymorphonuclear leukocytes.

We found inhibitors, designated aseanostatins P1 and P5, against myeloperoxidase (MPO) release from human polymorphonuclear leukocytes (PMN). Aseanostatins were extracted from an actinomycete isolated in Thailand and purified by a series of column chromatography of charcoal and silica gel, and HPLC. Physico-chemical characterization by gas liquid chromatography and GC-MS indicated that aseanostatins were fatty acids. The active forms of aseanostatins were recovered by hydrolyzing their methyl esters after HPLC. Two components P1 and P5 with the IC50 of 0.96 and 0.54 microgram/ml to the MPO release were obtained as pure forms, indicating aseanostatin P5 was higher activity than aseanostatin P1. The component P1 was identical with 12-methyltridecanoic acid and P5 was indistinguishable to 12-methyltetradecanoic acid (ante-i-15:0). Aseanostatin P5 (1 microgram/ml) did not inhibit beta-glucuronidase release, but O2- production a little. It has no effect on chemotaxis of PMN to fMet-Leu-Phe (10(-8)M), PMN adhesion or phosphorylation of a 64-kD protein in the PMN cell-lysate system.

Actinomycetales↗

[Influence of hepatitis C virus on the alcoholic liver diseases].

In order to know the influence of hepatitis C virus (HCV) on the alcoholic liver diseases (ALD), 124 patients with ALD were divided into two groups by positive or negative anti-HCV, and differences of histological findings, laboratory data, evolution of histopathology and liver disease of those who developed hepatocellular carcinoma (HCC) between both groups were investigated. There were 31 patients (25%) in the anti-HCV positive group and 93 patients (75%) in the negative group. Histologically, viral changes were seen in most patients (55%) of the positive group, whereas those were seen in a few patients (15%) of the negative group. The patients of the positive group showed higher serum adenosine deaminase levels compared with those of the negative group. However, as regards the evolution of histopathology, amount of alcohol consumed seemed to be more responsible than positive anti-HCV. Three out of 6 patients with HCC were anti-HCV positive cirrhotics, although there were three anti-HCV negative HCC patients: one with cirrhosis and two with hepatic fibrosis.

Adenosine Deaminase↗

[Studies on the mode of progression of alcoholic liver disease].

In order to elucidate the mode of progression of alcoholic liver disease, relationships among the drinking style, laboratory data, anti-HCV antibody and histological changes were investigated on 36 patients in whom the liver biopsy was repeatedly done. Following results were obtained (1) In the group of continuous drinking over 100g ethanol per day, histological progression was found in 11 of 13 patients (85%) regardless of positive anti-HCV. On the other hand, in the group of abstinence or temperance less than 60g daily alcohol intake, histological improvement was found in 6 of 11 patients (55%). (2) Histological improvement was predominantly seen by abstinence or temperance in the cases with lower levels of serum IgA and adenosine deaminase (ADA) on hospitalization and those with rapid decrease in serum gamma-GTP after hospitalization. In conclusion, the amount of ethanol was considered to be the most important factor to affect on a progression of alcoholic liver diseases. Assessment of laboratory data such as IgA and ADA on hospitalization and change in gamma-GTP after hospitalization were also thought to be useful in foreseeing the prognosis of alcoholic liver disease.

Alcohol Drinking↗

Clinical manifestations of primary herpes simplex virus type 1 infection in a closed community.

The clinical features and the molecular epidemiology of primary herpes simplex virus type 1 (HSV-1) infection among children younger than 3 years of age were investigated in day-care nursery. Serial sera were assayed for anti-HSV-1 glycoprotein B antibody by enzyme-linked immunosorbent assay. Serologic examinations revealed 55 cases of primary HSV infection during the observation period. Fifty-one of them (93%) had typical herpetic gingivostomatitis, showing a high rate of clinically overt infection. Four outbreaks of herpetic gingivostomatitis were observed during the observation period. Forty-one children were infected with HSV-1 in the outbreaks. The rates of infection in the susceptible children were 81%, 73%, 78%, and 100%, respectively, in the four outbreaks. Restriction endonuclease analysis of DNA of isolated HSV revealed that only one strain of HSV-1 had been transmitted among children for a long period.

Age Factors↗

Effect of an oral adsorbent (AST-120) in rats with daunomycin-induced chronic renal failure.

The effect of an oral adsorbent (AST-120) was examined in rats with daunomycin-induced chronic renal failure. Sixteen pairs of daunomycin rats which had similar levels of proteinuria at 4 weeks after being injected with daunomycin were selected. One rat of each pair served as a control and was fed on a standard diet, while the other rats were fed on a diet containing AST-120. The blood creatinine and blood urea nitrogen (BUN) were significantly lower in the rats fed with AST-120 than in the controls. Moreover, the life span of the rats fed with AST-120 was significantly prolonged as compared to that of the control rats. These findings suggest that oral administration of AST-120 may help to prevent rapid deterioration of renal function in experimental chronic renal failure induced by daunomycin in rats.

Administration, Oral↗

[Optimal hypervolemic therapy for symptomatic vasospasm].

Thirty-five patients with symptomatic vasospasm (SV) following aneurysmal subarachnoid hemorrhage (SAH) were managed according to a method based on hemodynamic manipulation, monitored by Swan-Ganz catheter. Nine out of these had delayed surgery. For those who developed SV, the pulmonary wedge pressure (Pcwp) and/or central venous pressure (CVP) were immediately increased up to the point at which neurological deficit was reversed by rapid injection of fresh frozen plasma, albuminates, low molecular dextrose, and glycerol. On this regimen, patients were closely observed for any neurological change. Then the hemodynamic parameters were maintained as optimal values until they could be reduced below optimal values without reappearance of neurological deficit. In inoperable patients, special attention was given in making a decision about discontinuing the regimen. The results were compared with thirty-seven patients with SV who were treated with conventional hypervolemic therapy (CHT) by continuous administration of albuminates. In the treatment of CHT, optimal values could hardly be established, so the same hemodynamic parameters were applied in all the cases. From this study, in the majority of the cases optimal values were found as follows: Pcwp up to 10-15 mmHg, and CVP below 11 cmH2O. On the contrary, in 20% of patients, neurological deficit was reversed by increasing CVP to a point not above 7 cmH2O. Correlation between neurological reversal and systemic blood pressure was not statistically significant. After this regimen (OHT), 74% of patients showed immediate improvement after volume expansion, and, in 80%, outcome was good, while 20% died. The motor function at the time of discharge was more than 3 on the manual test in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Central Venous Pressure↗