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Biomedical subjects

T Shibata

Publications and source records attributed to T Shibata.

At least 523 records · Page 29Linked to original sources

Consecutive cerebral MRI findings of acute relapsing disseminated encephalomyelitis.

A seven year old girl with acute relapsing disseminated encephalomyelitis (ARDEM) was observed with serial magnetic resonance imaging (MRI) examination. She had the first encephalomyelitis episode at the age of 2 years 9 months. She entered remission with steroid therapy. She suffered a recurrence at the age of 7. Steroid therapy was instituted and consecutive magnetic resonance imaging (MRI) was performed. In spite of rapid improvement of neurological abnormality with steroid and steroid pulse therapy, disseminated high intensity lesions in T2-weighted imaging which were considered as demyelination remained for a long time. Magnetic resonance imaging seems to be most suitable for evaluating the clinical condition and long-term follow-up of ARDEM.

Adrenal Cortex Hormones↗

Monitoring serum tryptic activity and effect of trypsin inhibitor on rat acute pancreatitis.

The effect of a novel synthetic trypsin inhibitor, 4-(2-succinimidoethylthio)-phenyl 4-guanidinobenzoate methanesulfonate (E3123), on severe acute pancreatitis was studied in trypsin-taurocholate-induced acute experimental pancreatitis in rats. Rats were divided into four groups according to difference of subdivided doses of E3123 with fixing the total dose at 3 mg/kg body weight. Group A: 1.5 mg/kg of E3123 subcutaneously (SC) each at 1 h before and after induction of pancreatitis. Group B: 1 mg/kg SC each at 1 h before, 1 and 3 h after induction. Group C: 1.5 mg/kg SC each at 1 and 3 h after induction. Group D: 1.5 mg/kg SC each at 3 and 5 h after induction of pancreatitis. The survival rate at 24 h was significantly improved in group B (77% in group B, vs. 36% in paired control; p < 0.01) and in group C (70 vs. 38%; p < 0.05), but not in group A or D. Residual tryptic activity of serum alpha 2-macroglobulin trypsin complex (alpha 2M-TRY) was reduced after the injection of E3123 though immunoreactive trypsin remained unchanged in the early phase of pancreatitis. The reduction of alpha 2M-TRY reflected the inhibitory capacity of E3123 in plasma. E3123 showed favorable effects on the initial stage of severe acute pancreatitis and the effects were probably based on the inhibition of alpha 2M-TRY activity in serum.

Acute Disease↗

Regulation of pancreatic polypeptide release is mediated through M3 muscarinic receptors.

The purpose of this study was to determine the regulation of pancreatic polypeptide (PP) release by using pirenzepine (a specific M1 muscarinic receptor antagonist), 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP, a specific M3 muscarinic receptor antagonist), atropine (a nonspecific muscarinic receptor antagonist), and loxiglumide (cholecystokinin, CCK, receptor antagonist) in dogs. In conscious dogs with chronic gastric and duodenal fistulas, release of PP and exocrine pancreatic secretion were stimulated by constant intravenous infusion of CCK-8 (200 ng/kg/h). Graded doses of pirenzepine (0.18-4.7 mmol/kg/h), 4-DAMP (6.7-180 nmol/kg/h), or atropine (0.89-24 nmol/kg/h) dose-dependently reduced plasma PP responses to CCK-8 without influence on exocrine pancreatic secretion. ID50 calculated from these results were 492 +/- 150 nmol/kg/h for pirenzepine, 10.7 +/- 1.8 nmol/kg/h for 4-DAMP and 19.4 +/- 5.2 nmol/kg/h for atropine. A similar sequence in the inhibitory potency was observed in 2-deoxy-D-glucose (2-DG, 100 mg/kg)-stimulated PP release, exocrine pancreatic, and gastric secretions. On the other hand, loxiglumide, a CCK receptor antagonist, did not influence PP release stimulated by 2-DG. These findings suggest that both CCK- and 2-DG-stimulated PP releases are mainly under cholinergic nerve control mediated by M3 muscarinic receptor in dogs.

Animals↗

Molecular and cellular basis for pathogenicity of autoantibodies.

Using two different kinds of monoclonal autoantibodies, anti-mouse RBC (MRBC) autoantibodies and IgG3 rheumatoid factor (RF) cryoglobulins, we have attempted to better define the molecular and cellular basis of the pathogenicity of autoantibodies. Among eight anti-MRBC monoclonal antibodies (mAbs) obtained from NZB mice, only five of them are able to cause anemia. The distinct differences in specificity between pathogenic and non-pathogenic anti-MRBC mAbs emphasize the importance of autoantibody specificity for the pathogenesis of autoimmune hemolytic anemia. Histological examination has revealed that Fc gamma receptor-mediated erythrophagocytosis and sequestration of agglutinated RBC in spleens and livers are the major pathogenic mechanisms of hemolytic anemia. This indicates that the affinity of autoantibodies for the Fc gamma receptors of phagocytes and/or the ability to cause hemagglutination, both of which vary among immunoglobulin isotypes, are additional factors determining the pathogenic activity of anti-MRBC autoantibodies. Studies on a panel of anti-IgG2a RF mAbs derived from MRL-lpr/lpr mice have demonstrated that only the IgG3 isotypes of RF mAb are able to generate cryoglobulins and to induce skin leukocytoclastic vasculitis and glomerulonephritis in normal mice. Although the cryoglobulin activity of RF mAb associated with the IgG3 isotype has been shown to be solely responsible for the generation of glomerular lesions (both RF and cryoglobulin activities are necessary for cutaneous vascular lesions), the absence of nephritogenic activity by some IgG3 monoclonal cryoglobulins supports the idea that qualitative features of cryoglobulins are critical to determine their pathogenic activities. Of interest, IgG3 autoantibodies lacking the cryoglobulin activity may not be harmful, but even protective against the development of IgG3 cryoglobulin-mediated tissue lesions, because they inhibit the cryoglobulin formation of pathogenic IgG3 autoantibodies as a result of their nonspecific IgG3 Fc-Fc interaction. Our results on monoclonal autoantibodies clearly indicate the importance of certain subpopulations of autoantibodies in the pathogenesis of autoantibody-mediated cellular and tissue injuries.

Anemia, Hemolytic, Autoimmune↗

[Single-dose toxicity study and twenty-eight-days intravenously repeated dose toxicity study of desethyl-piperacillin in rats].

Desethyl-piperacillin (desethyl-PIPC) is an active metabolite of PIPC which was newly found in clinical field. We carried out a single intravenous toxicity study at the dosage of 2000 mg/kg, and 28-days intravenous toxi-city study at the daily dosage of 400 mg/kg followed by 28-days recovery study using both sexes of rats. The following results were obtained. In the single dose toxicity study, no deaths occurred in rats injected 2000 mg/kg of desethyl-PIPC, therefore it is presumed that minimal lethal dose of desethyl-PIPC is over 2000 mg/kg in both sexes. As clinical signs, decrease in locomotor activity, deep breath and loose stool were observed. In the patho-logical study, dilatation of cecal lumen was observed macroscopically, but no significant changes were observed histologically. In the repeated dose toxicity study, loose stool, increase in water consumption, dilatation of cecal lumen and increase in its weight were noted. These abnormal findings were considered to be due to antimicrobial activity of desethyl-PIPC. In addition, decrease in the ratio of serum gamma-globulin and increase in the ratio of alpha 1-globulin were observed, but A/G ratio was not affected. After withdrawal of desethyl-PIPC administration, these abnormal findings tended to disappear. As mentioned above, the minimal lethal dose of desethyl-PIPC is over 2000 mg/kg in the single dose toxicity study and abnormal signs were slight in the repeated dose toxicity study at the dosage of 400 mg/kg of desethyl-PIPC for 28 days in rats. It is, therefore, concluded that desethyl-PIPC is a low toxic metabolite of PIPC.

Alpha-Globulins↗

Clonal analysis of Hodgkin's disease shows absence of TCR/Ig gene rearrangement, compared with T-cell-rich B-cell lymphoma and incipient adult T-cell leukemia/lymphoma.

To better characterize the clonality and pathogenesis of Hodgkin's disease (HD), we used polymerase chain reaction (PCR) and Southern blot to analyze the rearrangement of immunoglobulin (Ig) and T-cell receptor (TCR) genes, the bcl-2 oncogene, and the Epstein-Barr virus (EBV) genotype. In situ hybridization studies of EBV were also done. Twenty-six cases of HD were compared with 15 cases of non-specific lymphadenitis, 7 with incipient adult T-cell leukemia/lymphoma (ATLL), and 4 T-cell rich B-cell lymphomas (TRBL), all of which histologically resembled HD. EBV genes were detected in 20 of 26 HD patients (77%) and in 7 of 15 patients with non-specific lymphadenitis (47%), 5 of 7 with incipient ATLL (71%), and 1 of 4 with TRBL (25%). In contrast to specimens of non-specific lymphadenitis, TRBL, and incipient ATLL, only one EBV genotype was evident in the specimens of HD. EBV latent membrane protein (LMP) was detected immunologically in 16 of 26 HD patients (62%), one of four TRBL (25%) and one of seven incipient ATLL (14%), but it was not evident in non-specific lymphadenitis. The LMP positive cases showed amplified EBV genomes. Only one of the 26 cases of HD had a bcl-2 gene rearrangement by PCR, but this was not seen in any other disease. The bcl-2 protein was detected immunologically in seven of the 26 HD patients (27%) and in one of the seven incipient ATLL cases (14%). EBV has been reported to upregulate bcl-2 expression, but in this study the presence of bcl-2 protein did not correlate with the presence of the t(14;18) translocation or EBV-LMP. All TRBLs showed rearrangement of the immunoglobulin genes by PCR and/or Southern blot, and the giant cells were of B-cell type. All incipient ATLLs displayed rearrangement of the TCR genes, and the giant cells were of T-cell origin. In seven of 26 HD cases, the giant cells were weakly stained with T-cell antibodies, in another seven positive with B-cell antibodies and in 18 instances polyclonally positive for both kappa and lambda. However, PCR and Southern blot displayed only two cases of TCR gene rearrangement, while two others had very weak rearrangements of immunoglobulin gene positive only by PCR. Thus the T and B-cell genotype did not correlate with the T and B-cell phenotype recorded in these cases. The absence of Ig and TCR gene rearrangements seems to be common in HD, compared with in TRBL and incipient ATLL.

Base Sequence↗

[Early detection of pancreatic cancer by serum markers].

Serum markers such as pancreatic enzymes and tumor markers are useful for the diagnosis of pancreatic cancer. Among 40 cases of pancreatic cancer, elevated values were observed for immunoreactive elastase (IRE) in 70% and for CA19-9 in 73%. Elevated serum IRE was observed more frequently in head cancer and resectable cancer, whereas elevation in CA19-9 occurred more often in body-tail cancer and unresectable cancer. Elevation of serum IRE and CA19-9 are useful for diagnosis of pancreatic cancer but it is not specific for pancreatic cancer. Therefore, we studied the clinical usefulness of a combination assay of various serum markers such as CA19-9, lipase, serum iron, amylase, albumin globulin ratio, tissue polypeptide antigen, immunoreactive trypsin, and CA125 using the logistic regression analysis. This assay showed higher sensitivity and high specificity for pancreatic cancer than CA19-9. This combination assay may be very useful for the diagnosis of pancreatic cancer.

Amylases↗

[Region-specified PCR-mutagenesis: its application to locate epitopes for anti-RecA protein-monoclonal IgGs ].

Even though various techniques for site-directed mutagenesis have been developed, random mutagenesis is an important and complementary approach to locate functional domains on polypeptides and RNA, and to modify their biochemical and biological properties. Region-specified PCR-mutagenesis is a powerful and simple technique for this purpose. A couple of primers specifies a DNA region to be mutagenized. By use of Taq DNA polymerase and the addition of deoxyinosine-triphosphate (dITP), PCR causes various base-substitutions in the region. By screening of a change in a phenotype of the protein, one can obtain mutants with significant phenotype at 10(-2) from an expressed library of mutagenized DNA.

Antibodies, Monoclonal↗

[Effect of celiac plexus block and thoracic epidural block on arterial ketone body ratio].

We evaluated the effect of intraoperative celiac plexus block (CPB) and thoracic epidural block (TEB) on arterial ketone body ratio (AKBR) in the patients undergoing total or partial gastrectomy. Mean arterial pressure (MAP), heart rate, AKBR, and arterial blood gas were measured at the end of esophago-jejunostomy, gastro-duodenostomy, or gastro-jejunostomy (pre-block) and at the end of operation (post-block), respectively. After pre-block measurement, CPB with 99.5% ethanol 15-20 ml was carried out in 8 patients with advanced gastric cancer (CPB group); TEB with 2% lidocaine was performed on 8 patients (TEB group); and neither CPB nor TEB was done on 8 patients (control group). A significant reduction in MAP was observed after CPB and TEB. There was no difference in the degree of MAP decrease between CPB group and TEB group. No change in MAP was observed in control group. In CPB group significant decreases in AKBR, pH, and BE were induced by CPB. However, there were no difference in AKBR, pH, and BE between pre-block values and post-block values in TEB group as in the control group. These findings suggest that ethanol used in CPB reduces the redox state of hepatic mitochondria and increases lactate. Therefore we should pay attention to the changes in AKBR, pH, and BE after celiac plexus block with ethanol.

Aged↗

A case of nephrotic syndrome associated with traumatic chronic osteomyelitis.

A 19-year-old male developed nephrotic syndrome during the course of chronic osteomyelitis complicating a traumatic suppurative arthritis of the knee. Renal biopsy revealed severe mesangial proliferative glomerulonephritis, and immunofluorescent microscopy demonstrated the presence of IgA. Nephrotic syndrome remitted during the treatment for chronic osteomyelitis, suggesting a close association of the two conditions.

Adult↗

[Microwave tumor coagulation (MTC) in liver tumor: indication and percutaneous approach].

Indications for microwave tumor coagulation (MTC) and percutaneous approach in liver tumor were investigated. The study population comprised 26 patients with unresectable liver tumor (4 with hepatocellular carcinoma, 22 with metastatic liver tumor) who underwent MTC at our department after April 1990. Concomitant therapies were alcohol injection in 2 patients, hepatectomy in 12 and selective arterial chemotherapy in 20. Percutaneous MTC was performed on 2 patients with a single lesion under general anesthesia. Following tip coagulation electrode penetration under echo guidance, the lesion was thermally coagulated at 60W. To establish indications for MTC by the effect of thermal coagulation, survival periods were compared by underlying disease, number of masses coagulated, and maximum tumor size, in 23 patients who had undergone MTC at least 1 year previously. Thirteen of these 23 survived for 1 year or longer, including all 3 with hepatocellular carcinoma, 3 with breast cancer, 2 with leiomyosarcoma (gastric, small intestine), 4 of the 10 with colon cancer and 1 of the 2 with pancreatic cancer. According to evaluation of the degree of coagulation, complete coagulation was obtained in 11 of 23, all of whom had at most 6 tumor masses (of up to 3 cm in diameter) coagulated, and 9 of whom survived for 1 year or longer. Percutaneous MTC, of low invasiveness, proved useful as a tool of regional cancer therapy.

Breast Neoplasms↗

[A successful repair of acquired left ventricular-right atrial communication due to infective endocarditis].

A 17-year-old boy, who had suffered from streptococcal infective endocarditis, was referred to our hospital because of the uncontrolled infection and severe right ventricular failure despite 2 months of vigorous antimicrobial therapy. Preoperative two-dimensional and Doppler echocardiography revealed a shunt from the left ventricule or aorta to the right atrium. Both aortic and tricuspid valves had vegetations and severe regurgitations. He underwent an operation because of the persistent infection and worsening heart failure. Intraoperatively, the aortic valve was found to be severely damaged and to have numerous vegetations on both surfaces. The tricuspid valve had multiple vegetations on the atrial surface only, and its annulus was markedly dilated. There was a perforation in the septal leaflet of the tricuspid valve, and an exploration of the focal site disclosed a perimembranous ventricular septal defect (VSD) communicating directly between the left ventricle and right atrium. Aortic and tricuspid valve replacements and patch closure of the VSD were done successfully and his postoperative course was uneventful except for the episode of ventricular tachycardia, torsade de pointes, on the fifth postoperative day.

Adolescent↗

[The two cases of examination of chemotherapy in advanced gallbladder carcinoma].

Two cases of advanced carcinoma of gallbladder were treated by combination chemotherapy consisting of 5-FU, leucovorin and continuous administration of etoposide. One of the cases was a male 61 years old and another was a female 64 years old, both of whom were diagnosed as inoperable cases by imaging studies. When combination chemotherapy consisting of 5-FU (750mg/day or 1,000mg/day infusion) was given, leucovorin (30mg/day) and etoposide (25mg/day oral or 33mg/day continuous infusion), angiography or other imaging studies pointed out a reduction in their lesions of over 50%, and their QOL was markedly improved.

Administration, Oral↗

[Effect of dopamine and prostaglandin E1 on portal venous oxygenation].

We evaluated the effects of dopamine (DA) and PGE1 on portal venous oxygenation in patients undergoing gastrectomy. Thirty-two patients studied were anesthetized with isoflurane and nitrous oxide in oxygen. They were divided into three groups: DA was infused at a rate of 3 micrograms.kg-1.min-1 in 10 patients (DA group), PGE1 was infused at a rate of 0.02 microgram.kg-1.min-1 in 10 patients (PGE1 group), and the remainders did not receive DA nor PGE1 (control group). There were no significant differences in PaO2 and SaO2 among three groups. However, portal venous PO2 and SaO2 in DA and PGE1 group were significantly higher than those in the control group. These results suggest that DA and PGE1 elevate the portal venous PO2 and SO2 by increasing splanchnic blood flow more than its oxygen uptake or without increasing splanchnic oxygen uptake, and increase the oxygen supply to the liver.

Aged↗

[Significance of urinary fibrin/fibrinogen degradation product (FDP) D-dimer measured by highly sensitive ELISA method with a new monoclonal antibody (D-D E72) in various renal diseases].

In order to clarify the abnormalities of the coagulation and fibrinolysis system in patients with various renal diseases, we produced a new monoclonal antibody for FDP (fibrin/fibrinogen degradation product) D-dimer (D-D E72). We also established a new highly sensitive method of enzyme-linked immunosorbent assay (ELISA) for urinary FDP D-dimer using this monoclonal antibody. The urine from 110, patients with various renal diseases was investigated for the FDP D-dimer. The results are summarized as follows: 1) Urinary FDP D-dimer in normal subjects was 0.69 +/- 0.60 ng/ml. 2) The level of urinary FDP D-dimer in patients with primary nephrotic syndrome and in patients with chronic renal failure was significantly higher than that of normal subjects, whereas the urinary FDP D-dimer levels in patients with diabetes mellitus were higher than those of normal subjects. 3) In the CGN and NS groups there was a tendency for an increase in the level of urinary FDP D-dimer in more active forms of the disease. 4) A significant correlation between urinary FDP D-dimer and urinary protein in the CGN and NS groups was demonstrated. 5) In all of the renal diseases investigated in this study, the ratio of urinary FDP D-dimer to total FDP was less than 4%.

Adolescent↗