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Biomedical subjects

H Ishihara

Publications and source records attributed to H Ishihara.

At least 307 records · Page 17Linked to original sources

Effects of axial traction stress on solute transport and proteoglycan synthesis in the porcine intervertebral disc in vitro.

The effects of axial traction stress on intradiscal hydration, solute transport and proteoglycan synthesis were examined in 658 porcine coccygeal intervertebral discs in vitro. Measurements were performed in three tissue fractions: nucleus pulposus, inner and outer annulus fibrosus. At 0.80 MPa traction stress, the equilibrium hydration did not change in the nucleus pulposus. However, in the inner and outer annulus, the equilibrium hydration was reduced, and the change led to an increase of the effective fixed charge density. Diffusion of solute to the nucleus pulposus was significantly suppressed at 0.80 MPa traction stress. The fluid flow of the intervertebral disc tended to be suppressed during the creep recovery process after compression. The proteoglycan synthesis rate in the outer annulus was markedly suppressed by traction stress of 0.80 MPa for 4 h, but not that in the nucleus pulposus. These results suggest that a prolonged excessive axial traction stress induces a decrease in tissue hydration in the annulus fibrosus, and this may lead to an increase in the fractional volume of solid in the matrix and tissue osmotic pressure, resulting in diffusion inhibition of solute and suppression of proteoglycan synthesis. Thus, prolonged and excessive spinal traction may accelerate disc degeneration.

Animals↗

The initial distribution volume of glucose and cardiac output after haemorrhage in dogs.

The purpose of the study was to evaluate the role of insulin in glucose kinetics after glucose administration using an insulinogenic index to indicate the magnitude of insulin response. The initial distribution volume of glucose (IDV-G) was calculated with a one-compartment model from repeated measurements of plasma glucose concentration three to seven minutes after administration of 100 mg.kg-1 glucose. The IDV-G was compared with the insulin response and the thermodilution assessments of cardiac output, measured simultaneously both before and after induced haemorrhage (30 ml.kg-1 over 30 min) in 12 adult mongrel dogs. The plasma insulin concentration was measured during the procedure and insulinogenic indices were calculated. There was no correlation between the IDV-G and insulinogenic indices, but there was a correlation between the IDV-G and thermodilution cardiac output before and after induced haemorrhage (r = 0.85, n = 24, P < 0.001). We conclude that the initial distribution volume of glucose is an indication of cardiac output in normo- and hypovolaemic dogs. Modification of glucose kinetics by the insulin response to glycaemic stimuli was negligible in that short period of time.

Animals↗

Mitochondrial diabetes mellitus: prevalence and clinical characterization of diabetes due to mitochondrial tRNA(Leu(UUR)) gene mutation in Japanese patients.

Mutations in the mitochondrial gene were recently identified in a large pedigree of diabetes mellitus and deafness. As the mitochondrial gene is materially inherited, Japanese diabetic patients whose mothers were also diabetic were screened, using peripheral leucocytes, for an A to G transition at nucleotide pair 3243 of the mitochondrial gene, a tRNA(Leu(UUR)) mutation. This mutation was identified in four pedigrees from among 300 unrelated patients who were screened. Diabetes co-segregated with the mutation, except in one young subject, and was maternally inherited. The apparent onset of disease occurred between 11 and 68 years of age. Some of the affected members developed hearing impairment and congestive heart failure due to cardiomyopathy, though generally long after the onset of diabetes, and these patients had therefore not been diagnosed as having a specific form of diabetes. The duration of sulphonyl-urea treatment was not more than 8 years in these pedigrees and affected members were prone to progression to insulin-requiring diabetes. Thus, these patients were secondary sulphonylurea failures. Long-term follow-up revealed that the underlying disorder in affected members is a progressive impairment of insulin secretion. Some were initially diagnosed as having IDDM based on an apparent acute onset in youth and the clinical severity of their diabetes. Others were regarded as having MODY with an aggressive course. The mitochondrial gene mutation or diabetes is not transmitted to all offspring of the affected mothers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Tachykinins induce a [Ca2+]i rise in the acinar cells of feline tracheal submucosal gland.

The intracellular Ca2+ concentration ([Ca2+]i) of acinar cells of isolated submucosal glands from trachea was measured using a fluorescent dye, Fura-2. Neurokinin A (NK-A) produced a sustained rise in [Ca2+]i in a dose-dependent manner, reaching a response of 500 to 600% of the prior baseline value at 10(-6) or 10(-5) M, and the NK-A evoked [Ca2+]i was significantly higher than that by substance P (SP) at similar concentrations. NK-B did not induce significant increases in [Ca2+]i. In a Ca(2+)-free solution, NK-A produced a transient rise in [Ca2+]i, which returned to the baseline within 3 min. Mucus glycoprotein (MGP) secretion, estimated by measuring trichloroacetic-acid (TCA) precipitable glycoconjugates, was stimulated by NK-A or SP. These findings indicate that tachykinins produce a rise in [Ca2+]i by both entry from the extracellular solution and release from intracellular storage, probably by NK-2 receptor stimulation, and stimulate MGP secretion from airway submucosal glands.

Animals↗

Relation between ventriculoarterial coupling and myocardial energetics in patients with idiopathic dilated cardiomyopathy.

OBJECTIVES: The purpose of this study was to evaluate left ventricular contractility, arterial loading conditions and the way their interaction affects myocardial energetics. BACKGROUND: Ventriculoarterial coupling, defined as the ratio of effective arterial elastance to left ventricular end-systolic elastance, is known to reflect the mechanoenergetic performance of the heart. However, relations between the coupling and efficiencies of energy transfer from oxygen consumption to hydraulic energy have not been fully investigated in failing hearts. METHODS: Pressure-volume data were measured in 23 patients with idiopathic dilated cardiomyopathy by using a conductance catheter, and myocardial oxygen consumption was obtained simultaneously in 16 patients by a double-thermistor coronary sinus catheter. End-systolic elastance was determined by transient inferior cava occlusion. RESULTS: Data are reported as mean value +/- SE. Ventriculoarterial coupling at baseline was 3.24 +/- 0.28. It decreased from 3.12 +/- 0.43 to 1.86 +/- 0.15 (p < 0.05) for the group receiving dobutamine infusion and from 3.16 +/- 0.45 to 1.78 +/- 0.22 (p < 0.01) for the group receiving the oral phosphodiesterase inhibitor MS-857. The ratio of pressure-volume area to myocardial oxygen consumption had a positive correlation with ventriculoarterial coupling. The ratio of external work to pressure-volume area had a hyperbolic correlation with the coupling. The mechanical efficiency defined as the ratio of external work to myocardial oxygen consumption remained within a narrow range (16.4 +/- 1.2%). CONCLUSIONS: The degree of ventriculoarterial coupling is far from optimal and the cardiovascular performance is severely depressed mechanically and energetically in patients with idiopathic dilated cardiomyopathy. Although inotropic agents improve the coupling, they have a minimal effect on mechanical efficiency.

Cardiac Catheterization↗

Retroperitoneal lymphadenectomy, including the para-aortic nodes in patients with stage III ovarian cancer.

The role of lymphadenectomy in patients with advanced ovarian cancer is controversial. To evaluate the effect of lymphadenectomy, we retrospectively assessed the outcome of 53 patients with stage III epithelial ovarian cancer who were divided into two groups, which were matched for age distribution and postoperative chemotherapy, but received different surgical procedures. A total of 29 patients (group A) underwent hysterectomy, bilateral salpingoophorectomy, omentectomy, and retroperitoneal lymphadenectomy, including resection of the para-aortic nodes. The remaining 24 patients (group B) received hysterectomy, bilateral salpingoophorectomy, and omentectomy without retroperitoneal lymphadenectomy. Postoperative chemotherapy consisted of a combination of cisplatin, Adriamycin, and cyclophosphamide in both groups. The 2-year survival rate for group A was significantly greater than that for group B, but there was no significant difference between the groups with regard to the estimated 5-year survival rate. The 2-year survival rate of patients with positive nodes who underwent lymphadenectomy was similar to that of patients with negative nodes. Multivariate analysis indicated that lymph node involvement did not relate to prognosis of the patients undergoing lymphadenectomy. While a defined randomized trial is required to reach substantive conclusion, it is suggested that lymphadenectomy may be useful for improvement of the prognosis of patients with advanced ovarian cancer.

Adult↗

Synergistic enhancement of cisplatin cytotoxicity by SN-38, an active metabolite of CPT-11, for cisplatin-resistant HeLa cells.

A cisplatin (cis-diamminedichloroplatinum(II); CDDP)-resistant HeLa cell line (HeLa/CDDP cells), which showed more than 8-fold resistance to CDDP compared to the parent cells, was newly established for this study. HeLa/CDDP cells accumulated 50% less platinum than the parent cells. There was no difference in intracellular glutathione (GSH) content between the parent and HeLa/CDDP cells. The dose modification factor by DL-buthionine-S,R-sulfoximine (BSO) pretreatment was similar in both cell lines. HeLa/CDDP cells had cross-resistance to diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA), (cis-diammine(glycolato)platinum (254-S), but not to (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)platinum(II) (DWA2114R), adriamycin, or VP-16. HeLa/CDDP cells showed a collateral sensitivity to 7-ethyl-10-hydroxycamptothecin (SN-38), an active metabolite of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11). Furthermore, isobologram analysis indicated synergistic interaction of CDDP and SN-38 only for HeLa/CDDP cells. The present study suggests that combination therapy with CDDP and CPT-11 may be potentially useful in the treatment of some patients with CDDP-resistant cancer.

Camptothecin↗

Relationship between diabetic autonomic neuropathy and gastric contents.

Delayed gastric emptying secondary to diabetic autonomic neuropathy (DAN) is a recognized risk factor for aspiration pneumonitis. The purpose of this study is to determine whether bedside autonomic function tests (AFTs) would predict gastric contents. Gastric volume and its pH were measured in 36 patients with diabetes mellitus (DM) and 15 nondiabetic patients at induction of general anesthesia for elective ambulatory surgery. Manifestations of autonomic dysfunction were assessed preoperatively in all 51 patients with five commonly used cardiovascular AFTs. According to the results of these five tests, 16 patients with DM met the criteria for the diagnosis and are called "DAN positive." The remaining 20 diabetics did not meet the criteria and are called "DAN negative." Fifteen patients without DM did not meet the criteria and are called "nondiabetics." Diabetic patients were significantly older and more obese than nondiabetics and those with DM more than 10 yr were more often DAN positive. Solid, undigested food particles were found more often in the gastric contents of DAN-positive patients compared to nondiabetics. Gastric liquid volume and pH were similar in diabetic patients (DAN positive and DAN negative) and nondiabetic controls. These results demonstrate that diagnosis of DAN by commonly used cardiovascular AFTs does not predict larger gastric liquid volume or lower pH, but does predict the presence of solid food particles.

Adult↗

Timing in administration of a heat-killed Lactobacillus casei preparation for radioprotection in mice.

A single subcutaneous injection of a preparation of heat-killed Lactobacillus casei (LC 9018), given before or after irradiation, significantly increased the survival rate of mice that had received 8.5-Gy 137Cs whole-body gamma-irradiation. A similar radioprotective effect was observed when LC 9018 was administered within the period from 2 days before irradiation to 9 h after irradiation, the pre-irradiation treatment being slightly better than the post-irradiation treatment. Increases in the weight of the spleen and in the number of endogenous spleen colonies on days 8 and 12 after irradiation suggested that the radioprotective effect was based on enhanced recovery of hematopoietic tissues. The activity of macrophage colony-stimulating factor (M-CSF) in serum was rapidly increased by the treatment and was maintained at the elevated level for 13 days. At the same time, an increased level of M-CSF mRNA was detected in the livers of the treated mice. However, LC 9018 failed to save the lives of mice when administered 3 days after irradiation, although it increased serum M-CSF as effectively as noted above. The small advantage of the pre-irradiation over the post-irradiation treatment was not explained by the increases of metallothionein in the hematopoietic tissues of the treated mice.

Adjuvants, Immunologic↗

[Prognosis of idiopathic interstitial pneumonia].

Idiopathic interstitial pneumonia (IIP) is characterized by chronic inflammation and fibrosis of the lung. It carries a poor prognosis and the treatment for IIP has not yet been established. We evaluated 116 cases of IIP retrospectively, and analyzed possible prognostic factors, such as the mode of detection, clinical symptoms, chest X-ray findings, pulmonary function tests, blood chemistry, bronchoalveolar lavage (BAL), and treatments. The 5-year survival rate from the onset was 39.5% and the 10-year survival rate was only 12.7%. The 5-year survival rate from the appearance of dyspnea on exertion was 23.2% and 10-year survival rate was 9.0%. According to the results of the Kaplan-Meier analysis, patients with low% FVC (< 70%), those with high values of ESR, those with high values of CRP, and those with advanced chest X-ray shadows did not survive as long as other patients. Multivariate analysis with a proportional hazards model revealed that a high percentage of eosinophils in BALF was associated with a poor prognosis. Analysis with a logistic model revealed that being male having a low %DLCO were associated with a poor prognosis.

Female↗

Anterior interbody fusion with and without interspinous block implementation for lumbar isthmic spondylolisthesis.

The clinical and radiographic results of lumbar isthmic spondylolisthesis were compared between interspinous block-assisted anterior interbody fusion (block-assist group, n = 16) and anterior interbody fusion with no use of the block (nonassist group, n = 17) with an average follow-up of 7 years (range 1 1/3-13 years). Satisfactory relief of low-back pain, significantly early interbody union (union rate 88%, p < 0.05), and spontaneous fusion of pars defect (fusion rate 44%, p < 0.05) were obtained in the block-assist group. In the nonassist group, interbody union was markedly delayed (p < 0.05), the union rate was 53%, and spontaneous fusion of the pars was found in 12% of patients. The overall clinical results at final follow-up in both groups did not show a statistically significant difference, but the results tended to be superior in the block-assist group.

Adolescent↗

[Emergency caesarean section for a patient with chronic schizophrenia].

A 39-year-old female with chronic schizophrenia underwent an emergency caesarean section under general anesthesia at her 39th week of gestation. A diagnosis of schizophrenia was made at 28 years of age and since then oral antipsychotic drugs, haloperidol and levomepromazine had been given orally. She had only taken haloperidol 4 mg per day between the 12th week of gestation and the day of surgery. At the 39th week of gestation, she developed a marked excitement which would have caused fetal distress. We decided to terminate her gestation. As the excitement was diagnosed as psychokinesis, we avoided using phenothiazine which might affect fetus and administered haloperidol 5 mg intramuscularly 210 and 30 minutes before emergency caesarean section. Anesthesia was induced with intravenous thiopental 300 mg and suxamethonium 60 mg. Pentazocine 30 mg in combination with nitrous oxide 70% in oxygen was given for the maintenance of anesthesia. During operation blood pressure was 160-180/80-90 mmHg, the heart rate was 90-100 beats.min-1. Hypertension and tachycardia might have been partially due to preoperative haloperidol. The induction-delivery time was 4 minutes 30 seconds. Plasma haloperidol levels were 23.8 ng.ml-1 in maternal venous blood and 8.8 ng.ml-1 in umbilical vein just after the delivery. The Apgar score was 7 at one minute and 8 at five minutes after delivery. The baby developed slight muscle weakness and poor sucking for two days after delivery and this was supposedly due to effect of preoperative haloperidol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Development of glycosylated human interleukin-1 alpha, neoglyco IL-1 alpha, coupled with D-mannose dimer: synthesis and biological activities in vitro.

Interleukin 1 (IL-1) is a nonglycosylated cytokine with pleiotropic effects on various cell types. In order to investigate the effect of carbohydrate introduction on IL-1 activity and to develop IL-1 with less deleterious effects recombinant human IL-1 alpha was chemically coupled with mannose dimers, alpha-D-Man1-6-D-Man[Man2(alpha 1,6)] and alpha-D-Man1-4-D-Man[Man2(alpha 1,4)]. About 5 molecules of mannose dimers were introduced per molecule of IL-1. Anti-IL-1 alpha antibody reacted only weakly with the glycosylated IL-1s. Conversely, antibody against the mannose dimer reacted with only glycosylated IL-1. The effect of glycosylation on IL-1 activity was evaluated by measuring a variety of IL-1 activities in vitro, including proliferative effect on T cells, antiproliferative effect on melanoma cells, stimulatory effect on IL-6 synthesis by melanoma cells, and stimulatory effect on prostaglandin E2 synthesis by fibroblast cells. Glycosylated IL-1s exhibited reduced activities, which were 10-fold to more than several hundred-fold lower than those of the original IL-1 alpha depending upon different aspects of activities addressed. Man2(alpha 1,6)-introduced IL-1 exhibited lower activity than Man2(alpha 1,4)-introduced IL-1. The competitive binding of 125I-IL-1 alpha to mouse T cells with unlabeled IL-1s suggests that the reduced activity of glycosylated IL-1s is due, at least partially, to the decrease of their receptor binding abilities.

Animals↗

DX-9065a, a new synthetic, potent anticoagulant and selective inhibitor for factor Xa.

DX-9065a is an orally active newly synthesized and specific inhibitor for factor Xa. We have examined the property of DX-9065a in vitro and ex vivo. DX-9065a prolonged human plasma recalcification time, APTT and PT. Its doubling concentrations for clotting times of each coagulation assay were 0.49, 0.97 and 0.52 microM, respectively. Kinetic study revealed that DX-9065a inhibited competitively human factor Xa (Ki value: 41 nM). Ki values (microM) for other human serine proteases were as follows; thrombin > 2000, trypsin 0.62, chymotrypsin > 2000, plasmin 23, t-PA 21, plasma kallikrein 2.3 and tissue kallikrein 1000. DX-9065a up to 100 microM had no effects on human platelet aggregation. After intravenous or oral administration, DX-9065a significantly prolonged APTT and PT with a dose dependent manner. These effects were well correlated with anti-Xa activity in plasma. These results suggest that DX-9065a may become an anticoagulant by means of the specific inhibition of factor Xa.

Adenosine Diphosphate↗