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Biomedical subjects

S Kitahara

Publications and source records attributed to S Kitahara.

At least 73 records · Page 4Linked to original sources
PubMed1995

Ex vivo anti-platelet effects of isocarbacyclin methyl ester incorporated in lipid microspheres in rabbits.

Effect of TTC-909, a chemically stable isocarbacyclin methyl ester (CAS 88931-51-5, TEI-9090) incorporated in lipid microspheres, on platelet aggregation was tested in conscious rabbits. TTC-909 significantly inhibited platelet aggregation induced by ADP at early times after bolus i.v. injection from the dose of 0.3 micrograms/kg in a dose-dependent manner. Similarly, TTC-909 significantly inhibited platelet aggregation induced by ADP during the venous infusion from the dose of 100 ng/kg/min, also in a dose-dependent manner. The anti-platelet effect of TTC-909 was observed at a dose lower than that inducing hypotensive effect when given as both bolus i.v. and venous infusion. On the other hand, prostaglandin (PG) E1 (LM)--PGE1 incorporated in lipid microspheres--reduced blood pressure without having an anti-platelet effect. These results indicate that TTC-909 may be a potent anti-thrombotic drug.

Alprostadil↗
PubMed1995

[Sphingolipid changes in rat cerebral cortex during focal ischemia--how does ceramide accumulate in an ischemic condition?].

Levels of ceramide, sphingomyelin, cerebroside and gangliosides were determined in rat cerebral cortex during focal ischemia produced by middle cerebral artery occlusion. Ceramide began to increase at 6 hours of ischemia and increased to 4.5 folds at 96 hours. Amino-linked fatty acids in increased ceramide were composed solely of non-hydroxy fatty acids, and stearic acid was the most prominent. Sphingomyelin, whose amino-linked fatty acids were mostly stearic acid, decreased in a time-dependent manner and became about a half of controls at 96 hours. Hydroxy fatty acid linked cerebroside decreased at and after 6 hours of ischemia, whereas significant decrease of non-hydroxy fatty acid linked cerebroside occurred only at 96 hours of ischemia. There were no measurable changes in the levels of gangliosides. The results suggested that ceramide was produced in the cerebral cortex by the breakdown of sphingomyelin during ischemia.

Animals↗
PubMed1994

gamma-Glutamylcysteine ethyl ester for myocardial protection in dogs during ischemia and reperfusion.

OBJECTIVES: The aim of this study was to examine the infarct-limiting effects of gamma-glutamylcysteine ethyl ester, a newly discovered synthetic precursor of glutathione biosynthesis, in a canine model of myocardial infarction. BACKGROUND: Reduced glutathione plays an important role in protecting cells against damage induced by reactive oxygen species during myocardial ischemia and reperfusion. Gamma-glutamylcysteine ethyl ester is capable of penetrating into cells in its intact form and increasing intracellular glutathione levels. METHODS: Dogs were subjected to a 90-min coronary occlusion followed by 5 h of reperfusion. An intravenous bolus injection of gamma-glutamylcysteine ethyl ester (3 or 10 mg/kg body weight) was administered immediately before reperfusion. Regional myocardial blood flow was measured with the use of colored microspheres. RESULTS: Gamma-glutamylcysteine ethyl ester effectively reduced infarct size in a dose-dependent manner (mean +/- SEM 26.4 +/- 3.5% in the low dose group [3 mg/kg, n = 10] and 19.0 +/- 3.4% in the high dose group [10 mg/kg, n = 10]; each p < 0.05 vs. the value in the control group [40.6 +/- 4.8%, n = 10]). There were no differences between the control and treated groups in hemodynamic variables or regional myocardial blood flow either during the ischemic period or after reperfusion. The reduced glutathione content of ischemic myocardium in the control group (0.62 +/- 0.11 mumol/g, p < 0.01) was significantly lower than that in nonischemic myocardium (1.46 +/- 0.07 mumol/g), and it was preserved by treatment in a dose-dependent manner (3 mg/kg, 0.83 +/- 0.06 mumol/g; 10 mg/kg, 0.92 +/- 0.14 mumol/g; each p < 0.05 vs. control level). There were no differences in oxidized glutathione content between nonischemic and ischemic myocardium or among the three groups. CONCLUSIONS: Gamma-glutamylcysteine ethyl ester, a precursor of glutathione, significantly attenuates myocardial ischemia and reperfusion injury when administered immediately before reperfusion.

Animals↗
PubMed1994

Effect of granulocyte colony-stimulating factor on neutropenia in liver transplant recipients with hypersplenism.

The authors present details of their initial experience with use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) for preventing neutropenia caused by hypersplenism, and, possibly, for reducing the risk of postoperative infections in pediatric liver transplant recipients. Seven patients with end-stage liver disease, three of whom had severe hypersplenism, underwent living related liver transplantation (LRLT). The rhG-CSF was administered to the latter three patients. Peripheral neutrophil counts decreased immediately after reperfusion (to 1500 +/- 300/microL) in the three patients, and returned to normal with use of rhG-CSF 3 to 10 days after transplantation. The dosage was adjusted to maintain peripheral leukocyte and granulocyte counts above 5,000/microL and 2,000/microL, respectively. This initial clinical trial showed that rhG-CSF administration restores the leukocyte counts of patients who have hypersplenism, without any significant adverse effects, and that rhG-CSF holds promise for reducing the risk of infections after liver transplantation.

Child↗
PubMed1994

Effects of prostaglandins E1, E2 and F2 alpha on contractility and cAMP and cGMP contents in lower urinary tract smooth muscle.

Prostaglandin (PG) E1, E2 and F2 alpha contracted smooth muscle strips from male adult rabbit urinary bladder. Contractile responses to each PG were significantly greater in urinary bladder body than in urinary bladder base. The magnitude of contractile response to each PG was F2 alpha > E2 > E1 in both of the bladder body and the bladder base. These contractions were almost completely eliminated by a calcium entry blocker, verapamil but not by atropine, phentolamine, propranolol or tetrodotoxin. PG E1 and E2 significantly relaxed the male rabbit urethral smooth muscle strips, whereas PG F2 alpha contracted the urethral smooth muscle strips. Cyclic adenosine monophosphate (cAMP) but not cyclic guanosine monophosphate (cGMP) increased significantly after administration of PG E1 or E2 in the urethral muscle strip. These results suggest that the regional differences in the magnitude of contractile responses to PG E1, E2 and F2 alpha between the bladder dome and the base and also suggest the contractile differences of PG E1 and E2 for the urinary bladder and the urethra; contractions for bladder and relaxations for urethra. These results also demonstrate that contractions induced by PG E1, E2 and F2 alpha in urinary bladder smooth muscles and by PG F2 alpha in urethral smooth muscles are mainly mediated by calcium influx and that relaxations induced by PG E1 and E2 in urethral smooth muscles are mediated by cAMP but not by cGMP.

Alprostadil↗
PubMed1994

[Treatment results of radical nephrectomy for relatively confined small renal cell carcinoma--translumbar versus transabdominal approach].

We performed radical nephrectomy for 166 patients with renal cell carcinoma over 25 years period between 1967 and 1991. Among them, 49 patients had stage T1-3 NOMOVO tumors less than 6 cm in maximum diameter. Twenty-seven of them received radical nephrectomy by a modified translumbar approach whereas the conventional transabdominal approach was applied to the remaining 22 patients. We retrospectively studied treatment results of the 49 patients to evaluate the current translumbar approach. There was no significant difference in the age and sex distribution of the patients, and the size, stage, grade and histological subtype of the tumor between translumbar and transabdominal groups, although the incidence of venous invasion (pVla) was significantly greater in translumbar group. Statistical analysis revealed shortened operating time, decreased blood loss and quickened postoperative recovery (resuming oral intake or walking) in translumbar group as compared to those in transabdominal group. No major complication was observed in both groups. There was no significant difference in actuarial survival rate or disease-free survival period between the two groups. Actuarial three-year survival rate was 96% for translumbar and 89% for transabdominal group, respectively. Sites of metastasis were lung (2 patients) or bone (1 patient) in translumbar group and bone (1 patient) or unknown (1 patient) in transabdominal group. With the favorable prognosis comparable to that of transabdominal radical nephrectomy and the relatively small invasiveness, the current translumbar radical nephrectomy appears to be the choice for the patients with relatively confined small renal cell carcinoma.

Adult↗
PubMed1993

CO-N reaction--a new serological activity index--on Wegener's granulomatosis.

Cordyceps ophioglossoides is one of the Japanese old 'Kanpoh' drugs used for metrorrhagia as a decoction. We found that CO-N, a galactosaminoglycan from Cordyceps ophioglossoides, reacted with sera from patients with some collagen diseases. By using CO-N, we made a new serological activity index (CO-N reaction). In the present study, we investigated CO-N reaction on patients with Wegener's granulomatosis (WG). The aggregation titres of CO-N (CO-N numbers) displayed a possible correlation with their clinical activity. CO-N reaction might also serve an important role in supporting the diagnosis of active WG and in helping to assess the degree of disease activity. The purpose of this report is to introduce this new serological activity index for Wegener's granulomatosis.

Adolescent↗
PubMed1993

Laryngeal closure at the level of the false cord for the treatment of aspiration.

A new procedure for aspiration which closes the larynx at the level of the false cords is reported. This method is not harmful to the vocal folds and maintains arytenoid movement, thus preserving phonatory function. With the advance of the operative technique for aspiration and swallowing rehabilitation, patients who have recovered from aspiration can be helped. Our procedure can be recommended for such cases.

Aged↗
PubMed1993

Distinctive increases in HLA-DR+ and CD8+57+ lymphocyte subsets in Wegener's granulomatosis.

Lymphocyte subset abnormalities have been observed in a series of patients diagnosed with Wegener's granulomatosis (WG). Fifteen patients with WG were evaluated for lymphocyte subset abnormalities by two-color immunofluorescence flow cytometry. The WG group showed a decrease in CD4+ cells and an extraordinary increase in HLA-DR+ cells. The average percentages of HLA-DR+ cells of the normal group and WG group were 11.0 +/- 4.0 and 40.5 +/- 13.9% (CD3+HLA-DR+ = 20.3 + 9.4%). Within the CD8 family, CD8+57+, CD8+38+ and CD8+HLA-DR+ cells were markedly elevated. Our findings differ from other series which reported that the lymphocyte subsets in the peripheral blood of patients with WG were normal.

Adult↗
PubMed1993

[Cyclosporine disposition in living related donor partial liver transplant recipients].

We studied the disposition of cyclosporine (CyA) in 8 living related donor partial liver transplant recipients (patient A-H). CyA blood levels were determined by fluorescence polarization immunoassay with specific monoclonal antibody (m-FPIA) and fluorescence polarization immunoassay with non-specific polyclonal antibody (p-FPIA). The ratio of the blood levels of CyA determined by p-FPIA to those by m-FPIA varied significantly, because the levels determined by p-FPIA were influenced by the function of graft liver. Thus, the levels of CyA determined by p-FPIA could not be used for the adjustment of CyA dose. The CyA dose ratios [DR; CyA blood level (mg/l)/dose (mg/kg)] of 3 in 8 patients were relatively large in 1-4 d after the transplant operation, however, it decreased within 2-5 d after the operation. CyA DR gradually increased from 5-8 d after the transplantation, and it reached to a maximum in 10-13 d in 5 patients to whom CyA was administered intravenously over 12 d after transplantation. The average ratio of DR in oral administration to that in intravenous one was about 43%. CyA bioavailability in the patient of living related partial liver transplantation was as usual as that in other organ transplant patient except for cadaveric liver transplant patients. The average DR of intravenous CyA administration in liver transplant recipients was 1.5 times larger than that in bone marrow transplant patients. CyA disposition had large inter-individual and intra-individual variation, and CyA blood level and DR varied in clinical time course at least within 1.5 month after operation. Therefore, it is necessary to measure CyA blood level frequently and to adjust CyA dose.

Administration, Oral↗
PubMed1993

[Relationship between cervical osteophytes and globus sensation--a study based on altered swallowing function].

The swallowing function of ten patients showing marked cervical osteophytes were studied by double contrast pharyngogram and manometric examinations. In five cases in which the pharyngeal clearance was B type according to Shuzaki's classification, a significant increase in the maximal swallowing pressure value on the oral side ipsilateral to the osteophytes was often observed. In five cases in which the pharyngeal clearance showed A + A' type (marked impairment), the frequency of significantly decreased maximal swallowing pressure on the oral side ipsilateral to the osteophytes and abnormal waveforms of the swallowing pressure were high. However, no definite correlation was noted between these changes in swallowing function and osteophyte site. Therefore, there are two possible outcomes of the changes in swallowing function caused by cervical osteophytes: one is a compensatory increase in pharyngeal constriction aimed at maintaining relatively good pharyngeal clearance, the other is impaired pharyngeal constriction and the pharyngeal clearance. These changes in swallowing function would impact on globus sensation.

Aged↗
PubMed1993

[Intra-arterial CDDP and CDDP plus THP-ADM therapy for bladder cancer].

From 1983 to 1988, 20 patients (group A: 3 stage T1, 4 stage T2 and 13 stage T3-4 tumors) with bladder cancer were treated with single injection of CDDP (150-200 mg/body), and 28 patients (group B: 4 stage T1, 9 stage T2 and 15 stage T3-4 tumors) were treated twice with injection of CDDP (100 mg/m2) and THP-ADM (40 mg/m2) mixture from the internal iliac artery. As a rule, one half of the agents was equally given for the both sides, while 75% dose was given to the tumor side to the case with unilateral localized tumors. Then total or partial cystectomy was followed. When residual invasive cancer was pathologically present in operative specimens, patients underwent three to six courses of adjuvant chemotherapy including CDDP. Clinical response rate (CR+PR) to the intra-arterial chemotherapy in group A and B were 39% and 62%, respectively. Pathological response rate (grade 3 and grade 4 by Oboshi and Shimozato classification) were 17% in both group. After total cystectomy, the 2-year cancer specific survival rates of 17 patients in group A and 22 patients in group B were 75% and 59%, respectively. The 2-year cancer specific survival rates of 8 patients in group A and 10 patients in group B with pT3b were 63% and 54%, respectively. No cancer death occurred thereafter in the patients of group A during another three years. The 3-year cancer specific survival rate of 9 patients after partial cystectomy (3 in group A, 6 in group B) was 86%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Is injectable collagen truly safe?

Most patients have no response to injectable collagen or silicone, but some cases may have positive or 'undersea' (= clinically negative but immunologically positive) response to collagen. From the results of the Macrophage migration inhibition test, the relative immunogenicity was augmented most when we used implants with the following combination. The first immunization was collagen and the second one was collagen with silicone. The augmented antigenicity might be enough to cause an allergic reaction to the patients who had no response to each implant alone.

Adjuvants, Immunologic↗
PubMed1992

The effects of gamma-glutamylcysteine ethyl ester, a prodrug of glutathione, on ischemia-reperfusion-induced liver injury in rats.

This study was designed to clarify the effects of changes in liver tissue glutathione (GSH) concentration on postischemic liver injury together with the effects of gamma-glutamylcysteine ethyl ester (GCE), a prodrug of GSH, and GSH. Rats were pretreated with GSH (50 mg/kg, i.v.), or GCE (50 mg/kg, i.v.), or untreated. In each rat, liver was isolated, and liver mitochondria were prepared after 2 h of ischemia or 1 h of reperfusion following 2 h of ischemia. Mitochondrial function was measured polarographically. Liver adenine nucleotide concentrations were also determined using high-performance liquid chromatography. Liver tissue GSH, an oxidized form of glutathione (GSSG) concentrations, and activities of GSH peroxidase and GSSG reductase were determined enzymatically. Liver hypoxanthine and xanthine concentrations were determined by HPLC. Liver tissue concentration of lipid peroxide was measured. Leakages of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and adenine nucleotides into the hepatic vein after reperfusion were also measured. Administration of GCE improved the recovery of mitochondrial function and maintained tissue GSH concentration concomitantly. Increases in liver lipid peroxide concentration after reperfusion, and leakage of liver cell enzymes and adenine nucleotides were mitigated by administration of GCE. Administration of GSH itself failed to maintain tissue GSH concentration and had no protective effects. From these results, it is concluded that in the postischemic process, free radical formation might be enhanced, and the radical scavenging system deteriorated. To enhance the radical scavenging system is a possible maneuver to prevent radical-related cell damage associated with reperfusion, because pharmacological reduction of breakdown of ATP to hypoxanthine and xanthine seems to be difficult. GCE maintained liver GSH concentrations and mitigated postischemic liver injury, concomitantly. Clinical use of GCE might be recommended.

Adenine Nucleotides↗