Search PubMed⌕ Search

Biomedical subjects

K Obara

Publications and source records attributed to K Obara.

At least 73 records · Page 4Linked to original sources
PubMed1997

Specific attenuation of the pressure-induced contraction of rat cerebral artery by herbimycin A.

In order to determine whether protein tyrosine kinase mechanisms are involved in pressure-induced contraction, we compared effects of three structurally unrelated tyrosine kinase inhibitors and orthovanadate, a tyrosine phosphatase inhibitor, on the pressure-induced contraction of the posterior cerebral artery isolated from rats. The change in vessel diameter was continuously measured with a width analyzer. Herbimycin A inhibited the pressure-induced contraction, while it only slightly inhibited contractions produced by potassium chloride or 9,11-dideoxy-11alpha,9alpha-epoxymethano prostaglandin F2alpha (U46619). Genistein inhibited not only the pressure-induced contraction but also the U46619-induced one. Tyrphostin 23 significantly attenuated contractions in response to three different stimuli, i.e., pressure, potassium chloride and U46619. Orthovanadate potentiated the pressure-induced contraction. These results suggest that herbimycin A is a specific and potent inhibitor of the pressure-induced contraction and that a protein tyrosine kinase mechanism may play an important role in the genesis of the pressure-induced contraction of the rat cerebral artery.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Cerebral hemodynamics in patients with moyamoya disease and in patients with atherosclerotic occlusion of the major cerebral arterial trunks.

To determine the difference in cerebral hemodynamics between Moyamoya disease and atherosclerotic occlusion of the major cerebral arterial trunks, we measured local cerebral blood flow (CBF) and local CO2 reactivity (CO2R) by xenon-enhanced computed tomography (CT). A total of 11 adult patients with Moyamoya disease (mean age, 39.6 +/- 7.8 years) and eight patients with atherosclerotic occlusion of the major arterial trunks (mean age, 62.4 +/- 15.4 years) were studied. Regions of interest were frontal, temporal and occipital cortex, caudate, putamen and thalamus in each hemisphere. In patients with Moyamoya disease, local CBF values in the internal carotid artery territory (frontal and temporal cortex, caudate, putamen) were significantly higher than those in the occluded side of patients with atherosclerotic occlusion. Local CO2R values in the caudate and putamen were significantly higher than those in the occluded side of patients with atherosclerotic occlusion. These results suggest that the cerebral hemodynamics of Moyamoya disease differ from those of atherosclerotic occlusion of the major cerebral arterial trunks, and may be a result of the abundant collateral circulation through basal 'Moyamoya' vessels.

Adult↗
PubMed1997

Vanadate oxidation activates contraction in skinned smooth muscle without myosin light chain phosphorylation.

Phosphorylation of the myosin regulatory light chain (LC20-P1) is the major route of smooth muscle activation. However, after prior exposure to vanadate, permeabilized guinea pig taenia coli smooth muscle contracts in the absence of LC20-P1. We characterized the vanadate-induced contraction and investigated the mechanism of this novel activation pathway. Addition of vanadate to a control contracture (6.6 microM Ca2+) inhibits force (effective dose for 50% response was approximately 100 microM). In contrast, preincubation with high concentrations of vanadate (threshold at 1-2 mM) elicited a contraction on subsequent transfer of the fiber to a vanadate-free, Ca(2+)-free solution. Maximum isometric force of approximately 60% of control was obtained in fibers preincubated in 4 mM vanadate for 10 min. Addition of Ca2+ to a vanadate-induced contracture increased force, but the total force never exceeded the initial control. After maximal thiophosphorylation of LC20 with adenosine 5'-O-(3-thiotriphosphate), treatment with vanadate did not increase force. Unloaded shortening velocity (Vmax) was similar in Ca2+ and vanadate contractures and was additive. After thiophosphorylation, preincubation in vanadate had no effect on Vmax, suggesting that vanadate affected the number of activated bridges and not cycle rate. Vanadate mechanisms likely involve oxidation, since preincubation with 4 mM vanadate and 25 mM dithiothreitol (DTT) did not produce force. DTT could reverse a vanadate-induced contracture in 30-60 min. Subsequently, fibers demonstrated control contraction/relaxation cycles. Thus vanadate treatment did not cause irreversible damage, such as the extraction of proteins. Potential oxidation sites are proteins at 17 kDa and between 30 and 40 kDa, which were not alkylated by N-ethylmaleimide if they were treated in the presence of vanadate or in the rigor state. Vanadate-induced contractures are likely mediated by a reversible oxidation that activates cross bridges similarly to that of LC20-Pi and may play an important role in oxidant injury.

Animals↗
PubMed1997

Enhanced interleukin-8 production by cultured Chang liver cells subjected to ethanol exposure and subsequent stimulation with tumor necrosis factor-alpha.

We investigated the production of interleukin-8 (IL-8) and chemotactic activity released from Chang liver cells subjected to long-term treatment with ethanol (Et) and subsequent stimulation with tumor necrosis factor-alpha (TNF-alpha). Chang liver cells were cultured in the presence of 5, 50 or 100 mmol/l Et for 4 weeks and then treated with recombinant TNF-alpha (1, 10, 100 U/ml). The culture supernatants were assayed for IL-8 using a sandwich ELISA and chemotactic activity was measured using a chemotactic chamber. Total RNA was also extracted from these cells and IL-8 mRNA was assayed by RT-PCR. In addition, TNF-receptor expression on the Et-treated cells was analyzed by flow cytometry. IL-8 levels in supernatants of cells stimulated with 100 U/ml of TNF-alpha for 48 h rose significantly with increasing concentrations of Et and values obtained were as follows: 4,918 +/- 244.4 pg/ml at 0 mmol/l Et, 5,335 +/- 266.2 pg/ml at 5 mmol/l Et, 8,726 +/- 873.4 pg/ml at 50 mmol/l Et and 9,134 +/- 866.0 pg/ml at 100 mmol/l Et. The chemotactic activity also increased with increasing concentrations of Et and was almost completely suppressed by anti-IL-8 antibody. Using semiquantitative analysis of radioactivity of IL-8 mRNA using a 32P gamma ATP-labeled primer for IL-8 mRNA, Et-treated cells were shown to have markedly higher levels of radioactivity than untreated cells. In addition, TNF-receptor expression was significantly higher in cells treated with 100 mmol/l Et. These data suggest that long-term Et treatment of Chang liver cells stimulated with TNF-alpha may enhance transcription of the IL-8 gene with up-regulation of the TNF receptor.

Antibodies↗
PubMed1997

Cold snare excision is a safe method for diminutive colorectal polyps.

Cold snare excision (CSE) has proved to be an effective method for the destruction of diminutive polyps of the colon and rectum. We investigated the correlation between polyp size and bleeding time at the resected end after CSE, and also an appropriate measuring method using CSE. Eighty patients with single polyps were examined. Each polyp was identified as being 5 mm in diameter or smaller using the open-biopsy forceps technique (OBFT). The size of the polyp was calculated using our measuring system (SMS). Of the polyps identified as being 5 mm in diameter or less using OBFT, 15% were 6 mm or more using the SMS. CSE was performed for each polyp, and the time taken for the hemostasis (bleeding time of the CSE; BTCSE) was determined. In seventy-seven polyps that were 6 mm or smaller in SMS, a correlation was noted between SMS and BTCSE. In three polyps that were 7 mm or more by SMS, hemostasis took 10 min or more after CSE, and required electrocoagulation. These results suggest that CSE is a safe method for the removal of polyps determined to be 6 mm in diameter or smaller using the SMS.

Aging↗
PubMed1997

Retroperitoneal laparoscopic adrenalectomy for functioning adrenal tumors: comparison with conventional transperitoneal laparoscopic adrenalectomy.

PURPOSE: We attempted to confirm the possibility and feasibility of laparoscopic adrenalectomy via the retroperitoneal approach, and to compare results of the transperitoneal and retroperitoneal approaches. MATERIALS AND METHODS: Three men and 8 women (mean age 39.6 years) with functioning adrenocortical tumors (primary aldosteronism in 5 and Cushing's syndrome in 6) underwent laparoscopic adrenalectomy via the retroperitoneal approach using a balloon dissection technique and a newly developed ultrasonic aspirator. Results were compared to those of 27 cases of transperitoneal laparoscopic adrenalectomy. RESULTS: Although the retroperitoneal approach was successful in all 5 patients with primary aldosteronism, it succeeded in only 2 of the 6 cases of Cushing's syndrome. In 3 Cushing's syndrome cases the retroperitoneal approach was changed to the transperitoneal laparoscopic approach due to difficulty in exploration. Open laparotomy was required in 1 case of left Cushing's syndrome because of an inadvertent pancreatic injury. Subcutaneous emphysema developed in 6 patients without hypercapnia or prolonged postoperative symptoms. Mean operative time and blood loss, and time to oral intake and ambulation were 248.3 minutes, 151.4 ml., and 1.55 and 2 days, respectively. There was no difference between retroperitoneal and conventional transperitoneal laparoscopic adrenalectomy in regard to these factors or to convalescence. CONCLUSIONS: Retroperitoneal laparoscopic adrenalectomy is feasible for primary aldosteronism. However, Cushing's syndrome is presently a much more difficult indication than primary aldosteronism for this new operative technique.

Adrenal Cortex Neoplasms↗
PubMed1997

[Locations of crossover breakpoints within the CMT 1 A-REP repeat in patients with hereditary neuropathy with liability to pressure palsy--detection by recombinant chromosome-specific polymerase chain reaction].

The crossover breakpoints for hereditary neuropathy with liability to pressure palsies (HNPP) are located in the CMT 1 A-REP repeat flanking a 1.5 Mb region of chromosome 17p11.2-12. Three-unrelated HNPP patients have breakpoints in a 3.2 kb novel fragment of recombinant chromosome in the CMT 1 A-REP repeat. The fragment is detected by recombinant chromosome-specific polymerase chain reaction (PCR). Further analysis of PCR demonstrated a 1.2 kb novel junction fragment in the 3.2 kb region in all HNPP patients. The precise mapping of the breakpoints indicated that 2 patients were localized in a 700 bp interval of the 1.2 kb fragment 1.3kb telomeric to a marier transposon-like element (Kiyosawa and Chance, HMG 5: 745-753, 1996), suggesting that this region is a recombinational "hotspot" within the CMT 1 A-REP repeat for HNPP as well as CMT 1 A.

Adult↗
PubMed1996

Local cerebral blood flow in motor neuron disease: correlation with clinical findings.

Local cerebral blood flow (CBF) measured by xenon-enhanced CT was correlated with the clinical findings in 21 patients with motor neuron disease (mean +/- SD age, 60 +/- 10 years). In 11 patients, CBF was also measured after intravenous injection of 2 mg thyrotropin releasing hormone (TRH). There were no significant differences in CBF of the cerebral cortex, basal ganglia, thalamus, and subcortical white matter with respect to age, duration of illness, or presence (n = 9) or absence (n = 12) of bulbar palsy. In patients with upper motor neuron disturbance (n = 10), however, local CBF in the frontal cortex was significantly lower (p < 0.05) than in those without it (n = 11). Within the frontal cortex, CBF reduction was marked in the upper posterolateral part (p < 0.05) that included the motor and premotor areas. Intravenous administration of TRH did not significantly alter the local CBF in any of the brain regions examined. An additional patient with motor neuron disease and severe dementia showed marked CBF reduction in the frontal lobe, which was in common with but much greater than the reduction in those exhibiting subcortical dementia (e.g., progressive supranuclear palsy). We conclude that in motor neuron disease patients with upper motor neuron involvement, the selective reduction of CBF in brain regions that include primary motor and premotor areas may reflect functional disturbance or neuronal degeneration in these regions. The ameliorating effect of TRH in patients with motor neuron disease, if any, appears not to be related to increases in local CBF or activation of brain function.

Aged↗
PubMed1996

Interleukin-6 induces proliferation of rat hepatocytes in vivo.

BACKGROUND/AIMS: The aim of this study was to assess the effect of interleukin-6 (IL-6) on the proliferation of hepatocytes and to study the interaction between IL-6 and hepatocyte growth factor (HGF) in vivo. METHODS: IL-6 was injected at a dose of 200 micrograms/mg subcutaneously into rats every day for 14 days. Liver and blood samples were obtained at 1, 3, 7 and 14 days during IL-6 administration. Hepatocyte proliferative activity of sera was measured using 3H-thymidine incorporation into cultured rat hepatocytes. To evaluate the proliferative activity of the hepatocytes in tissue sections, hepatic DNA content and immunostaining of the liver tissue sections for proliferating cell nuclear antigen (PCNA) were performed. Plasma HGF levels were measured using specific EIA. In addition, total RNA was extracted from the liver and expression of HGF mRNA was detected by RT-PCR. RESULTS: The DNA contents of liver taken from IL-6-treated rats were increased during IL-6 administration compared with untreated rats. Sera taken from IL-6-treated rats at various intervals during administration also significantly increased 3H-thymidine incorporation by cultured rat hepatocytes compared with sera from untreated rats, suppressing 3H-thymidine incorporation at day 1 and 3 by anti-HGF antibody. IL-6 itself did not increase 3H-thymidine incorporation. Increased expression of PCNA in these hepatocytes was noted from 1 day after IL-6 administration, and at 14 days, the number of PCNA-positive cells was sevenfold greater than in the livers of untreated rats. However, plasma HGF levels showed a peak at day 1, decreased gradually from day 3, and became undetectable by day 14. HGF mRNA expression in livers of IL-6-treated rats was suppressed from day 3 to day 14 of IL-6 administration. CONCLUSIONS: These data show that IL-6 induces an early phase of liver cell growth in vivo and suggest that an increase level of HGF mediates this effect.

Animals↗
PubMed1996

Effects of calponin on isometric force and shortening velocity in permeabilized taenia coli smooth muscle.

Calponin, a thin filament-associated protein, inhibits actomyosin adenosinetriphosphatase in solution and has been suggested to modulate smooth muscle contractility. We used permeabilized guinea pig taenia coli smooth muscle to investigate whether calponin can modulate actin-myosin interaction in a more organized contractile system. Fibers were permeabilized with Triton X-100 and glycerol, which permit access of large macromolecules to the contractile apparatus. For contractures elicited by Ca2+ (6.6 microM + 0.1 microM calmodulin), the recombinant alpha-isoform of chicken gizzard calponin (CaP) decreased isometric force (Fo) and unloaded shortening velocity (Vus) in a dose-dependent manner; 1 microM CaP had minimal effects on force (< 10%) but reduced Vus by approximately 50% and 10 microM CaP reduced Fo to 27% of control and Vus to near zero levels. To eliminate any effects of the binding of calmodulin by CaP and consequent inhibition of myosin light chain kinase activity, we also studied fibers activated by thiophosphorylation of the myosin regulatory light chain. Fo was only moderately inhibited, remaining at approximately 75% of control in the presence of CaP (10 microM), whereas Vus was reduced to 32% of control. A similar inhibition was obtained with a mutant (CaPcys175) that retains the ability to bind to actin. CaP phosphorylated by protein kinase C and CaPcys175 mutant labeled with 1,5-IAEDANS, which bind actin poorly, were not effective inhibitors. Our results indicate that 1) CaP more strongly inhibits Vus (approximately cross-bridge cycle rate) than Fo (approximately number of activated cross bridges) and 2) the effects of CaP are related to its binding to actin. Thus the function of CaP in regulation of smooth muscle contractility may be more strongly related to its function as a modulator of velocity, as related to the "latch state," than as an "on-off" switch.

Adenosine Triphosphate↗
PubMed1996

Effect of a nonpeptide vasopressin V1 antagonist (OPC-21268) on experimental accelerated focal glomerulosclerosis.

The effects of the nonpeptide orally effective vasopressin V1 receptor antagonist OPC-21268 were studied in progressive focal glomerulosclerosis (FGS) which developed in spontaneously hypercholesterolemic (SHC) rats with manifestations of hypercholesterolemia and proteinuria. Unilateral nephrectomy was performed at 7 weeks of age to accelerate spontaneous FGS. After nephrectomy, OPC-administered rats were fed chow containing 1% OPC-21268 for 9 weeks. Treatment with vasopressin V1 antagonist significantly reduced the rate of increase in the levels of triglyceride, systolic blood pressure, serum creatinine and BUN, and prevented a significant deterioration in creatinine clearance. Rats were sacrificed at 16 weeks of age. Histologically, the index of glomerular sclerosis in the OPC group showed a significant decrease compared to that in the control group (2.2 +/- 0.1 vs. 2.6 +/- 0.1, p < 0.01). Relative interstitial volume and glomerular volume in the OPC group showed a tendency to decrease compared to those in the control group. These results indicate that vasopressin plays an important role through V1 receptors in the development of glomerulosclerosis, and vasopressin V1 antagonist may prevent the progression of renal injury in glomerulosclerosis.

Animals↗
PubMed1996

[Kinetics of peripheral blood CD34-positive cells and optimal timing of blood stem cell harvest after urological anticancer chemotherapy].

PURPOSE: We evaluated the changes in stem cells in peripheral blood and the optimal timing for harvesting peripheral blood stem cells (PBSCs) following the administration of conventional cancer chemotherapy in patients with urological malignancies. PATIENTS AND METHODS: We evaluated the changes in PBSCs after the administration of cancer chemotherapy in 12 patients with urological malignancies (6 testis cancer, 3 bladder cancer, 3 prostate cancer) using flowcytometry analysis of CD34, a marker of blood stem cell. We evaluated the optimal timing for PBSCs harvesting following the administration of conventional cancer chemotherapy in 6 patients with urological malignancies (2 patients with testis cancer, 3 patients with prostate cancer, 1 patient with bladder cancer) using flowcytometry analysis of CD34 and granulocyte-macrophage colony-forming units (CFU-GM) counts. PBSC samples from 2 patients with prostate cancer were analyzed by the reverse transcriptase-polymerase chain reaction (RT-PCR) method to detect prostate cancer cells. RESULTS: The percentages of CD34-positive cells tended to increase in the peripheral blood during the period of convalescence that followed the induction of marked myelosuppression produced by the cancer chemotherapy. The peak in CD34-positive cells occurred between days 15 and 31 after beginning of cancer chemotherapy. The percentage of CD34-positive cells was increased in the mononuclear cells in harvested PBSCs. The percentages of CD34-positive cells in peripheral blood and in mononuclear cells harvested from PBSCs was correlated with the CFU-GM counts in harvested PBSCs. The CFU-GM counts peaked between days 16 to 31 following cancer chemotherapy. RT-PCR detected prostate-specific antigen (PSA) mRNA expression in PBSCs obtained from 1 of the 2 patients with prostate cancer. An amount of contamination with PSA mRNA reduced as chemotherapy was repeated. CONCLUSION: A sufficient number of PBSCs can be harvested after conventional cancer chemotherapy without the need for special cytotoxic mobilization that may be delayed the patient's treatment. RT-PCR results suggested that the harvested PBSCs should be examined for tumor cell contamination in patients with metastasis in bone marrow. If a sufficient amount of PBSCs will be harvested, the PBSC samples from the patient with bone marrow metastasis after repeated chemotherapy should be used by priority for PBSC transplantation as of today.

Adolescent↗
PubMed1996

[Two cases of primary low spinal fluid pressure syndrome with pachymeningeal gadolinium enhancement].

We report two patients with primary low spinal fluid pressure syndrome with pachymeningeal gadolinium enhancement. Case 1 was a 36-year-old man and case 2 was a 29-year-old man. Each case developed postural headache and had no histories of head trauma, craniotomy or lumbar puncture. The spinal fluid pressures were 20 mmH2O in case 1 and 0 mmH2O in case 2 at decubitus position. Cranial MRIs revealed diffuse pachymeningeal enhancement after gadolinium infusion, flattening of the pons, and tight posterior fossa in each case. Their headache spontaneously resolved within a couple of weeks by bed rest and intravenous hydration. Follow-up MRIs which were examined 3 or 4 months later, revealed a remarkable reduction in the degree of pachymeningeal enhancement, flattening of the pons and tight posterior fossa. Primary low spinal fluid pressure syndrome should be included in the differential diagnosis of pachymeningeal enhancement on MRI.

Adult↗
PubMed1996

[Clinical evaluation of immuno-serological laboratory data].

Clinical evaluations of various laboratory data from immuno-serological tests such as rheumatoid factor, anti-nuclear antibody, and other auto antibodies were reviewed. Rheumatoid factors (RF) were discussed in relation to positivity in various diseases, immunoglobulin class of RF, and correlation between titers of RF and circulating immune complex (IC). As a result, higher frequency and higher titers of IgA-RF were found in Sjögren syndrome patients. Titers of RF did not show disease activity of RA, but those of ESR and CRP did. Anti-nuclear antibodies (ANA) were discussed in relation to positivity in healthy subjects, specific antibodies and corresponding specific disease, correlation among titers of anti-dsDNA antibody, CH50 and circulating immune complex. As a result, an ANA frequency of 40% was found in healthy young women. Values of CH50 were much better than ANA titers for evaluating clinical activity in SLE patients. Findings of anti-cardiolipin antibody in thrombosis patients with connective tissue vascular disease (CVD), anti-centromere antibody in various CVD patients as well as CREST patients and primary biliary cirrhosis patients and anti-neutrophil cytoplasmic antibodies in various vascular diseases along with inflammatory bowel disease patients were presented. Finally, useful laboratory data at different clinical steps such as diagnosis, evaluation of disease activity and estimation of prognosis were demonstrated in CVD.

Adult↗
PubMed1996

A case of idiopathic portal hypertension complicated with narrowing of intrahepatic bile ducts.

A 37-year-old woman who had portal hypertension followed by splenomegaly, developed collateral blood flow of spleno-renal shunt and paraesophageal veins, esophageal varices and further with narrowing of intrahepatic bile ducts shown by endoscopic retrograde cholangiography was described. Liver function was almost normal except the slight elevation of serum alkaline phosphatase and gamma-glutamyl transpeptidase levels. However, endoscopic retrograde cholangiography revealed the narrowing of the intrahepatic bile ducts. The histological examination of biopsied specimen showed no prominent change in portal tracts and bile ducts without cell infiltration or fibrosis in the portal area. This case will be considered as idiopathic portal hypertension complicated by narrowing of the intrahepatic bile ducts.

Adult↗