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Biomedical subjects

S Sakaguchi

Publications and source records attributed to S Sakaguchi.

At least 109 records · Page 6Linked to original sources
PubMed1997

Duration of chronic HCV infection and efficacy of interferon in chronic hepatitis C patients with a history of blood transfusion. The Study Group for Treatment of Hepatitis in the Kyushu Area.

To investigate correlations between the interval between blood transfusion and the start of IFN therapy, and IFN efficacy, we studied chronic hepatitis C patients with a history of blood transfusion. The subjects were 122 patients with chronic hepatitis C and a history of blood transfusion at 64 institutions. The patients were treated with high or low-dose IFN. High-dose therapy consisted of intramuscular injection of human lymphoblastoid interferon (HLBI), 6 x 10(6) IU daily for 2 weeks, then 3 times a week for 22 weeks, and low-dose interferon therapy of intramuscular injection of HLBI, 6 x 10(6) IU daily for 2 weeks, then 3 x 10(6) IU 3 times a week for 22 weeks. Normal serum ALT levels for 6 months or more after completing IFN (complete response) were found in 44/122 (36.2%) patients and HCV RNA was no longer detectable after completing IFN therapy in 19/68 (27.9%). Patients in whom the interval between blood transfusion and the start of IFN therapy was less than 20 years had significantly higher rates of HCV RNA-negative complete response than those in whom the interval was 20 years or more (p < 0.039). When chronic HCV infection is caused by blood transfusion, the efficacy of IFN depends on the duration of chronic HCV infection. Since the duration of HCV infection is a factor in predicting efficacy, early IFN therapy may be more effective.

Adult↗
PubMed1997

Specific changes in human brain after hypoglycemic injury.

BACKGROUND AND PURPOSE: Very few reports are available on serial changes in the human brain after severe hypoglycemic injury. The aim of this study was to investigate sequential neuroradiological changes in brains of patients after hypoglycemic coma compared with those after cardiac arrest previously studied with the same methods. METHODS: We repeatedly studied CT scans and MR images obtained at 1.5 T in four vegetative patients after profound hypoglycemia associated with diabetes mellitus. RESULTS: In all patients, consecutive CT scans showed symmetrical, persistent low-density lesions with transient enhancement in the caudate and lenticular nuclei and transient enhancement in the cerebral cortex 7 to 14 days after onset. Serial MR images consistently revealed symmetrical lesions of persistent hyperintensity and hypointensity on T1- and T2-weighted images, respectively, in the caudate and lenticular nuclei, cerebral cortex, substantia nigra, and/or hippocampus from 8 days to 12 months after onset. CONCLUSIONS: Repeated MR images revealed specific lesions in the bilateral basal ganglia, cerebral cortex, substantia nigra, and hippocampus, which suggests the particular vulnerability of these areas to hypoglycemia in the human brain. We speculate that the localized lesions represent tissue degeneration, including some combination of selective neuronal death, proliferation of astrocytic glial cells, paramagnetic substance deposition, and/or lipid accumulation. The absence of localized hemorrhages on MR images in hypoglycemic encephalopathy is in marked contrast to the presence of regional minor hemorrhages in postischemic-anoxic encephalopathy.

Aged↗
PubMed1997

Nonpharmacologic treatment of atrial fibrillation: current and evolving strategies.

Atrial fibrillation is the most common cardiac arrhythmia requiring treatment. Limitations of medical treatment have prompted development of nonpharmacologic therapies for this arrhythmia. These are aimed at ventricular rate control during atrial fibrillation, termination of the arrhythmia, and/or prevention of recurrences. Ventricular rate control can be achieved with transcatheter ablation or modification of the atrioventricular node. The MAZE operation is effective in preventing arrhythmia recurrence, but because it requires cardiac surgery, its appeal is limited. Development of the technique for direct transcatheter ablation of atrial fibrillation is eagerly anticipated and may represent the standard curative treatment of the future. In appropriately selected patients, implantable device therapy may play an important role in the treatment of paroxysmal atrial fibrillation.

Anti-Arrhythmia Agents↗
PubMed1997

[Postoperative complications of anterior and middle skull base surgery].

The authors present the postoperative complications of skull base surgery based on a 10-year experience with 26 patients operated on via the supraorbital trans-basal or orbitozygomatic approach. The lesions included 19 malignant tumors and seven benign tumors. Postoperative cerebrospinal (CSF) leak occurred in one of the two patients in whom the dural defects were repaired with a fascia lata graft. None of the remaining 24 patients who were repaired with a musculopericranial flap suffered postoperative CSF leak. Three patients developed epidural abscess, but no infection was seen in the patients who had been reconstructed with a vascularized musculo-cutaneous flap to occlude the dead space. Preoperative radiation therapy correlated with a high incidence of postoperative infection. Cranial nerve deterioration or palsy occurred in four patients. Intraoperative injury of the internal carotid artery occurred in one patient who developed severe neurological deterioration. After an average follow-up period of 40 months (range 12 to 109 months), 68% of patients with malignant tumors and 100% of patients with benign tumors were alive with no evidence of recurrence.

Abscess↗
PubMed1997

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents. Special references to bacteria isolated between July 1995 and June 1996].

Isolated bacteria from infections in general surgery during the period from July 1994 to June 1995 were investigated in a multicenter study in Japan, and the following results were obtained. One hundred and sixty-four strains were isolated from primary infections, and 202 strains were isolated from postoperative infections. From primary infections, anaerobic Gram-positive bacteria were predominant, while from post operative infections, aerobic Gram-positive bacteria were predominant. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus faecalis was the highest, followed by that of Staphylococcus aureus from postoperative infections. Among anaerobic Gram-positive bacteria, the isolation rate of Peptostreptococcus spp. was the highest from both types of infections. Among anaerobic Gram-negative, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa in this order, and from postoperative infections, P. aeruginosa was the most predominantly isolated, followed by Enterobacter spp. and Klebsiella spp. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis group was the highest from both types of infections. We noticed that MICs of cefazolin against three out of 23 strains of E. coli were higher than 100 micrograms/ml. Among anaerobic bacteria, there were many resistant strains against penicillins and cephems with MICs higher than 100 micrograms/ml, and the same trend was observed among other Bacteroides spp. and Prevotella spp.

Bacterial Infections↗
PubMed1997

[Recent advances in animal models of autoimmune disease].

Various autoimmune diseases can be induced in normal animals by simply manipulating the thymus/T cells. For example, elimination of CD25+CD4+ T cells, which constitute about 10% of peripheral CD4+ T cells of normal mice, leads to the development of various organ-specific autoimmune diseases, such as thyroiditis, gastritis, adrenalitis, insulitis, sialoadenitis, oophoritis, or orchitis. Reconstitution of CD25+CD4+ T cells prevents the autoimmune development. Elimination/reduction of CD25+CD4+ T cells induced by genetical manipulation of T-cell ontogeny or caused by environmental agents, such as virus infection, also causes similar autoimmune diseases in normal mice. These newly developed animal models of autoimmune disease will be useful for elucidating the mechanism of immunologic self-tolerance and pathogenetic mechanism of autoimmune disease.

Animals↗
PubMed1997

[Changes in porphyrin metabolism of mice given beryllium and/or zinc].

Beryllium chloride and/or zinc chloride were intraperitoneally injected into mice. The amount of beryllium (Be) injected corresponded to 1/10th of the LD50 dose intravenously administered. The amount of zinc (Zn) injected was the same as Be. The changes in porphyrin metabolism of the mice were studied. Delta-aminolevulinic acid dehydratase (ALA-D) activities in the blood were found to increase significantly in Zn and BeZn groups when compared to the control level. The blood porphobilinogen deaminase (PBG-D) activity in the Zn group was slightly less than that in the controls. The ALA-D and PBG-D activities in liver were higher in the Be and BeZn groups than in the controls. The splenic ALA-D activities were significantly higher in the Zn and BeZn groups than in the control and Be groups. The splenic PBG-D activities were markedly higher in the Be and/or Zn groups than in the controls. An increase in ALA-D activities in the blood and spleen was observed in the BeZn group, together with an increase in ALA-D activities caused by Zn administration. Furthermore, the increase in PBG-D activities in liver and spleen was observed in the Be and/or Zn groups. The results suggested that chemical similarity between Be and Zn brought about these phenomena.

Animals↗
PubMed1997

[Isolation rate of Enterococcus spp. from surgical infections and their susceptibilities].

Enterococcus spp. isolated from surgical infections during the period from July 1982 to June 1995 were investigated in a multicenter study involving 19 hospitals in Japan, and the following results were obtained. 1. Though the isolation rate of Enterococcus faecalis and other Enterococcus spp. were not high from primary infections, and from postoperative infections the isolation rate of other Enterococcus spp. was also low, the isolation rate of E. faecalis was highest from postoperative infections after 1993. 2. Vancomycin (VCM) showed strongest activity against E. faecalis, and followed by those of ampicillin (ABPC), imipenem. levofloxacin (LVFX) and meropenem in this order. Against other Enterococcus spp., VCM showed strongest activity, and followed by those of ABPC and LVFX. There were no resistant strains against VCM.

Ampicillin↗
PubMed1997

[Characteristics of home parenteral nutrition and effectiveness of 3 way valved PICC in regional medical care].

Home medical care is becoming a greater matter of concern along with the increasing population of elderly persons. The various difficulties in home care are also found in regional care, and it could be said that in Japan regional care serves as an "advanced model" for home medical care. Ohya Town is located in the mountains of northern Hyogo Prefecture. It has a population of about 5,000 of which 32% is elderly people. There is no railroad, and it takes around 30 minutes to travel to the central hospital from the area. The three town clinics are in contact with each other and with the central hospital concerning medical information. The characteristics of Home Parenteral Nutrition in this underpopulated district are discussed and reported in reference mainly to cases in which the 3 way valved peripherally inserted central venous catheter (Groshong Catheter) is used, in comparison with HPN cases in the city university hospital.

Catheterization, Central Venous↗
PubMed1996

Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation.

Neonatal thymectomy (NTx), especially around day 3 after birth, causes various organ-specific autoimmune diseases in mice. This report shows that: (a) T cells expressing the interleukin 2 receptor alpha chains (CD25) ontogenically begin to appear in the normal periphery immediately after day 3, rapidly increasing within 2 wk to nearly adult levels (approximately 10% of CD3+ cells, especially of CD4+ cells); (b) NTx on day 3 eliminates CD25+ T cells from the periphery for several days; inoculation immediately after NTx of CD25+ splenic T cells from syngeneic non-Tx adult mice prevents autoimmune development, whereas inoculation of CD25- T cells even at a larger dose does not; and furthermore, (c) similar autoimmune diseases can be produced in adult athymic nu/nu mice by inoculating either spleen cell suspensions from 3-d-old euthymic nu/+ mice or CD25+ cell-depleted spleen cell suspensions from older, even 1-yr-old, nu/+ mice. The CD25- populations from neonates or adults are also similar in the profile of cytokine formation. These results, taken together, indicate that one aspect of peripheral self-tolerance is maintained by CD25+ T cells that sustain potentially pathogenic self-reactive T cells in a CD25- dormant state; the thymic production of the former is developmentally programmed to begin on day 3 after birth in mice. Thus, NTx on day 3 can, at least transiently, eliminate/reduce the autoimmune-preventive CD25+ T cells, thereby leading to activation of the self-reactive T cells that have been produced before NTx.

Age Factors↗
PubMed1996

Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene.

Prion protein (PrP) is a glycoprotein constitutively expressed on the neuronal cell surface. A protease-resistant isoform of prion protein is implicated in the pathogenesis of a series of transmissible spongiform encephalopathies. We have developed a line of mice homozygous for a disrupted PrP gene in which the whole PrP-coding sequence is replaced by a drug-resistant gene. In keeping with previous results, we find that homozygous loss of the PrP gene has no deleterious effect on the development of these mice and renders them resistant to prion. The PrP-null mice grew normally after birth, but at about 70 weeks of age all began to show progressive symptoms of ataxia. Impaired motor coordination in these ataxic mice was evident in a rotorod test. Pathological examination revealed an extensive loss of Purkinje cells in the vast majority of cerebellar folia, suggesting that PrP plays a role in the long-term survival of Purkinje neurons.

Animals↗
PubMed1996

T cell-mediated maintenance of natural self-tolerance: its breakdown as a possible cause of various autoimmune diseases.

This paper shows that elimination of a small subpopulation of peripheral T cells can elicit activation/expansion of self-reactive T cells from the remaining T cells and produce a wide spectrum of organ-specific and systemic autoimmune diseases in normal mice; reconstitution of the eliminated T-cell population prevents autoimmune development. This regulatory T-cell population expresses the CD25 molecule, apparently includes 'activated' T cells, and suppresses immune responses to non-self as well as self antigens in an antigen-nonspecific manner. Although the degree of abnormality in the T-cell regulation significantly influences the spectrum, incidence, and severity of autoimmune disease, the T-cell abnormality itself cannot determine the specificities of the elicited autoimmune responses since a comparable degree of abnormality causes different autoimmune diseases depending on the mouse strains used. Host genetic elements thus significantly contribute to determining the specificities. These findings taken together indicate that one aspect of natural self-tolerance is maintained by a T cell-mediated or -dependent control of potentially pathogenic self-reactive T cells in the periphery, and that defective control, caused by environmental insults or genetic abnormalities, suffices to activate self-reactive T cells, eliciting various autoimmune diseases depending on the genetic makeup of the host.

Animals↗
PubMed1996

The enhancing effect of tumour necrosis factor-alpha on oxidative stress in endotoxemia.

The enhancing effect of tumour necrosis factor-alpha (TNF-alpha) on oxidative stress with or without a sublethal dose of endotoxin was examined. The mortality of mice treated with recombinant human TNF-alpha (1 x 10(4) units/mouse, intravenously) and endotoxin (0.01-1 mg/kg, intraperitoneally) was dependent on the dose of endotoxin. The liver lipid peroxide level, superoxide anion generation and serum lactate dehydrogenase activity, especially serum lactate dehydrogenase-5 isozyme leakage, in mice 2-4 hr after administration of recombinant human TNF to endotoxin-pretreated mice (0.5 mg/kg, intraperitoneally) were markedly higher than in those without endotoxin, whereas the administration of recombinant human TNF significantly decreased the non-protein sulfhydryl level, superoxide dismutase and glutathione peroxide activities in the liver of endotoxin-injected mice compared with those in mice treated with recombinant human TNF or endotoxin alone. Furthermore, findings clearly demonstrated that J774A.1 cells stimulated with recombinant human TNF (1 x 10(4) units/ml) can effectively produce nitric oxide in the presence of endotoxin, and the production was dependent on the dose of endotoxin (0.01-10 micrograms/ml). The level of lipid peroxide in mice 4 hr after administration of recombinant human TNF and lead acetate (50 mg/kg, intravenously) was markedly higher than that in the mice treated with recombinant human TNF alone. By contrast, injection of polymyxin-B (20 mg/kg, intraperitoneally, an anti-endotoxin drug) markedly decreased the lipid peroxide level in the liver of the mice treated with recombinant human TNF and lead acetate. These findings suggest that the oxidative stress caused by TNF occurs as a enhancing effect of endotoxin or by bacterial translocation from the intestinal gut under reduction of reticuloendothelial system function in various disease states, and that the effect of TNF may cause a marked increase of toxicity of oxidative stress by endotoxin.

Animals↗
PubMed1996

Effects of antitumor activity and protection of shock symptoms by a traditional Chinese medicine (sho-saiko-to) in recombinant human tumor necrosis factor administered mice.

The effects of a traditional Chinese medicine Sho-saiko-to (Kampo prescription) were investigated on the various metabolic disorders and antitumor activity of recombinant human tumor necrosis factor (rhTNF) administered to mice. The glycogen level in liver of rhTNF (5 x 10(4) units/mouse, i.v.)-injected mice was markedly lower at 4 h post-intoxication than that in the control, whereas the administration of rhTNF to Sho-saiko-to (500 mg/kg/d, p.o.)-pretreated mice resulted in a greater level of glycogen than that in rhTNF alone-treated mice. In mice pretreated with Sho-saiko-to, the level of fibrinogen 4 h after rhTNF injection markedly increased as compared to that in mice treated with rhTNF alone. We also estimated the NO2 in murine macrophage cell line J774A.1 using mice serum after administration of Sho-saiko-to. Our results clearly demonstrated that J774A.1 cells stimulated with endotoxin (1 micrograms/ml) and rhTNF (1 x 10(4) units/ml) can effectively produce nitric oxide (NO), and ascertained the suppressive effect of Sho-saiko-to (500 mg/kg/d, p.o)-pretreated serum on NO generation by endotoxin/TNF-activated J774A.1 cells. When the cells were incubated with endotoxin/TNF and Sho-saiko-to pretreated serum (10-100 microliters), the NO level was significantly lower than that in control serum incubated with endotoxin/TNF alone. The effect of Sho-saiko-to (1 and 10 micrograms/ml) on in vitro cytotoxicity by rhTNF in Meth-A Sarcoma cells was observed to be in a dose dependent fashion. In addition, there was a remarkable enhancement of antitumor activity of rhTNF by Sho-saiko-to pretreatment in mice. These findings suggest that the Kampo prescription Sho-saiko-to may protect mice from severe shock syndrome by rhTNF, and that it may enhance rhTNF-induced activity.

Animals↗
PubMed1996

[The changes of complement activities in sera of mice after subcutaneous administration of beryllium chloride].

We studied changes of the complement pathway activities and the content of C3 in sera of mice, administered BeCl2 (containing 5 micrograms of Be per mouse) or CuCl2 (containing 5 micrograms of Cu per mouse) by a single subcutaneous injection. The value of the classical complement pathway activity (CH50) of the Be group 3 days after administration was significantly higher than that of the control group (P < 0.001). It was significantly lower than in the control group after 7 days (P < 0.001). On the other hand, the CH50 value of the Cu group 3 hr after administration tended to increase, however, it was significantly lower than in the control group after 7 days (P < 0.01). The change of the alternative complement pathway activity (ACH50) value of the Be group was similar to the change of the CH50 value of the group. The ACH50 value of the Cu group 3 days after administration tended to increase but it was the same as the ACH50 value of the control group after 7 days. The C3 contents of both the Be and Cu groups 3 days after administration were significantly higher than in the control group (P < 0.001). The aspartate aminotransferase (AST) activity of the Be group 7 days after administration was significantly higher than that of the control group (P < 0.01). By contrast, AST activity of the Cu group 3 hr after administration was significantly higher than in the control group (P < 0.05). The value of the alanine aminotransferase (ALT) activity of the Be group was low (P < 0.01), but that of the Cu group was high (P < 0.05), 3 hr after administration. These values of both groups after 7 days, however, were significantly higher than in the control group (P < 0.05). The AST/ALT ratio in mice was very high at 3 hr, and it remained high by 7 days after Be injection. On the other hand, the ratio of the Cu group was almost constant for 7 days after Cu injection. Thus, these values changed with relative expedition after Be injection. Therefore, we confirmed that measurements of complement activities and the content of C3 were valuable indices for assaying acute effects of Be on mice.

Alanine Transaminase↗
PubMed1996

[Isolation rate of Pseudomonas aeruginosa from surgical infections and their susceptibilities].

Pseudomonas aeruginosa isolated from surgical infections during the period from July 1982 to June 1995 were investigated in a multicenter study involving 19 hospitals in Japan, and the following results were obtained. 1. Though the isolation rate of P. aeruginosa was not high from primary infections, it was more frequently isolated from postoperative infections throughout the study period. Enterococcus spp., P. aeruginosa and Staphylococcus aureus including MRSA were predominant among postoperative infections. From the postoperative cases that had previous antibiotic treatment, Enterococcus spp., MRSA and P. aeruginosa were more predominantly isolated than from those without previous treatments with antibiotics. 2. Cefozopran, ceftazidime, cefsulodin, aztreonam, carumonam, gentamicin, amikacin and ofloxacin had strong activities against P. aeruginosa. We recognize recently that antibiotic-resistant strains of P. aeruginosa against imipenem and ofloxacin have been increasing year by year.

Anti-Bacterial Agents↗