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Biomedical subjects

K Obara

Publications and source records attributed to K Obara.

At least 91 records · Page 5Linked to original sources
PubMed1995

Fibroblast contractility without an increase in basal myosin light chain phosphorylation in wild type cells and cells expressing the catalytic domain of myosin light chain kinase.

We investigated the role of myosin light chain (MLC20) phosphorylation (MLC-P) in non-muscle contractility by comparing MLC-P and the contractile properties of wild type 3T3 fibroblasts and 3T3 fibroblasts expressing the catalytic domain of myosin light chain kinase (tMK). MLC-P is 0.96 MOL of PO4/mol of MOL20 in cell expressing tMK compared to 0.20 mol of PO4/mol of MLC20 in control cells. Expressing tMK also results in a 2-fold increase in cortical stiffness compared to control cells. Contractile properties were quantified by growing wild type and transfected fibroblasts in collagen and attaching the ensuing fibers to an apparatus for performing mechanical measurements. Serum stimulation resulted in a dose-dependent increase in force with maximal force generated in the presence of 30% (v/v) serum. Surprisingly, MLC-P did not increase in wild type cells following stimulation with 30% serum, and tMK expression did not affect the contractile properties of fibers made from these cells. Moreover, the dose responses to serum, maximal force, force-velocity relationships, and dynamic stiffness were similar in the wild type cells and fibroblasts expressing tMK. These data demonstrate that non-muscle cells can generate force without an increase in MLC-P, and that an increase in MLC-P does not affect the contractile properties of fibroblast fibers.

3T3 Cells↗
PubMed1995

Levodopa-induced local cerebral blood flow changes in Parkinson's disease and related disorders.

Local cerebral blood flow (CBF) in the steady state and after intravenous administration of levodopa (1 mg/kg) was measured by xenon-enhanced computed tomography in patients with Parkinson's disease (PD, n = 16), progressive supranuclear palsy (PSP, n = 6), olivopontocerebellar atrophy (OPCA, n = 5), and arteriosclerotic parkinsonism (AP, n = 7). Three patterns of local CBF changes following levodopa were observed: (1) diffuse CBF increases, especially in striatum and thalamus, as found in patients with PD; (2) no significant changes in CBF, as in patients with OPCA and AP; and (3) CBF reductions in basal ganglia and thalamus, as seen in patients with PSP. The CBF increases after levodopa in PD may be secondary to metabolic activation of the nigrostriatal dopaminergic system. The poor CBF responses in patients with OPCA, AP, and PSP appeared to reflect degeneration of the dopaminergic neurons and dopamine receptors to various degrees. The CBF increases, especially in striatum and thalamus, tended to be greater (not significant) among responders to oral levodopa therapy. Levodopa-induced CBF measurements may be useful for the differential diagnosis of parkinsonian syndromes of various etiologies, but are not necessarily sufficient for predicting outcomes of long-term levodopa therapy.

Adult↗
PubMed1995

Cardiovascular and renal protective effects of losartan in spontaneously hypertensive rats with diabetes mellitus.

1. Cardiovascular and renal benefits of a specific angiotensin II (AII) receptor antagonist, losartan (LOS), were assessed in diabetic rats with renal impairment. 2. Uninephrectomized SHR made diabetic by streptozotocin administration were given LOS (5 mg/kg per day, i.p.) alone, captopril (CAP) (50 mg/kg per day, i.p.) alone, or a combination of CAP and LOS via osmotic minipumps for 8 weeks. 3. Both CAP alone and LOS alone completely blocked the development of hypertension in diabetic SHR in the same manner. CAP + LOS did not enhance the antihypertensive effects of LOS alone or CAP alone. 4. CAP + LOS, LOS alone and CAP alone significantly decreased urinary protein excretion and serum creatinine to the same extent. 5. These results indicate that both LOS and CAP exert antihypertensive and renoprotective effects in this model: these actions are mainly through inhibition of AII production.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Association of primary sclerosing cholangitis, thymoma and hypogammaglobulinemia.

A 64-year-old Japanese woman with thymoma has been suffering from diarrhea and increased alkaline phosphatase levels without jaundice. Her serum immunoglobulin levels of IgM and IgG were less than half of the normal levels, with an increase in CD8 (suppressor/cytotoxic) T cell percentage and a decrease in CD4 (helper) T cell percentage, resulting in a lower CD4/CD8 ratio of 0.31. These immunological features are in accordance with those of hypogammaglobulinemia complicating thymoma. Cholangiography and a liver biopsy specimen disclosed the presence of primary sclerosing cholangitis (PSC). PSC has been recognized in various immunodeficiency syndromes and this case shows that thymoma complicated by hypogammaglobulinemia is associated with PSC.

Agammaglobulinemia↗
PubMed1995

Prospective CT confirms differences between vascular and Alzheimer's dementia.

BACKGROUND AND PURPOSE: Cognitive test performances were correlated prospectively with changes in cerebral CT measurements of atrophy, infarct volume, ventricular enlargement, local tissue density, and local perfusion to contrast annual rates of changes among patients with ischemic vascular dementia (IVD) or dementia of the Alzheimer type (DAT). METHODS: The cerebral atrophic index (ATI; ratio of cerebrospinal fluid or infarcted brain to intracranial volume), infarct volume ratio, ventricular volume ratio (VVR; ventricular volume/intracranial volume), cortical and subcortical gray and white matter local perfusion (local cerebral blood flow [LCBF]), and local Hounsfield unit (HU) density were measured concurrently and compared longitudinally with Cognitive Capacity Screening Examinations (CCSE) scores among 24 treated IVD (age, 68.2 +/- 9.7 years; follow-up, 42 +/- 27 months) and 24 DAT patients (age, 74.2 +/- 6.2 years; follow-up, 30 +/- 19 months). RESULTS: IVD annual changes were as follows: CCSE, +1.2 +/- 5.9; ATI, +2.1%/y; VVR, +3.2%/y; and LCBF in the subcortical basal ganglia, -0.74 mL.100 g-1.min-1.y-1 (-1.8%/y). DAT annual changes were as follows: CCSE, -1.8/y; ATI, +8.1%/y; VVR, +9.6%/y; cortical LCBF, -2.0 mL.100 g-1.min-1.y-1 (-5.2%/y); LCBF in the basal ganglia, -3.0 mL.100 g-1.min-1.y-1 (-6.7%/y); white matter LCBF, -0.75 mL.100 g-1.min-1.y-1 (-4.1%/y); and all cortical tissue densities, -0.83 HU/y (-2.1%/y). In IVD, multiple regression analyses correlated cognitive changes directly with (1) recurrent silent infarctions and (2) bidirectional changes of perfusions within frontal white matter, thalamus, and internal capsules. In DAT, cognitive declines correlated with cerebral atrophy and cortical hypoperfusion related to frontotemporal and parietal cortical polioaraiosis (decreased gray matter tissue densities). CONCLUSIONS: In IVD, recurrent strokes were not observed clinically during risk factor control, and antiplatelet therapy and cognitive impairments improved or stabilized. In DAT, cognitive performance relentlessly declined. Ischemic pathogenesis for vascular dementia is supported by the following: (1) cognitive declines correlate directly with recurrent "silent" strokes, and (2) bidirectional cognitive changes correlate directly with frontal white matter, thalamic, and internal capsular perfusional changes.

Aged↗
PubMed1995

Clinical effectiveness of lansoprazole in patients with gastric ulcers: evaluation of quality of ulcer healing based on endoscopic ultrasonographic findings.

The effects of lansoprazole (30 mg/day) in 18 patients with gastric ulcers and the quality of ulcer healing were studied using endoscopy (including dye endoscopy) and endoscopic ultrasonography (EUS). The results showed an 8-week endoscopic healing rate of 94.4% and an S2-stage shift rate of 11.1%. In dye endoscopic findings of 11 S1-stage patients, S1b healing with regenerated mucosa close to S2 was seen in 63.6%. In a study of EUS findings, E0 with few relapses and high quality of healing accounted for 44.4%. When E0 rates were compared with the scarring images seen in endoscopic findings, the rates were 100% for S2, 66.7% for S1b, and 33.3% for S1a. These results indicate that a high degree of ulcer healing was achieved with lansoprazole, as good contraction of the ulcer tissue and early maturation of regenerated epithelium were observed.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

[A successful 5'-DFUR and CDDP combination therapy for an advanced gastric cancer complicated with multiple liver metastases].

A 71-year-old man with Borrmann type 3 gastric cancer with multiple liver metastases had been treated with 5'-DFUR 1400 mg/m2/day, p.o. day 1-day 4/2w and CDDP 80 mg/m2 i.v. day 5/4w, which was repeated for 4 cycles. After 2 cycle treatment, all metastatic lesions in the liver disappeared on the computed tomography scan, indicating a complete response. The primary gastric lesion was reduced, indicating a partial response. There was no significant side effect during the 4 cycles of this therapy. He is alive 6 months after the therapy with a partial response. This 5'-DFUR and CDDP combination therapy seemed to be effective for advanced gastric cancer.

Adenocarcinoma↗
PubMed1995

Antihypertensive and renal-protective effects of losartan in streptozotocin diabetic rats.

OBJECTIVE: To assess the renal benefits of a specific angiotensin II receptor antagonist, losartan, in diabetic rats with renal impairment. DESIGN AND METHODS: Uninephrectomized streptozotocin diabetic spontaneously hypertensive rats (SHR) were randomly assigned to receive vehicle, or to receive losartan or captopril, or both, intraperitoneally via osmotic minipumps for 8 weeks. RESULTS: Blood pressure and urinary protein excretion in the diabetic SHR increased progressively during the experimental period. Both captopril treatment and losartan treatment completely blocked the development of hypertension in diabetic SHR. Simultaneous administration of captopril and losartan did not enhance the antihypertensive effects of losartan treatment or captopril treatment. Furthermore, losartan treatment, captopril treatment and losartan + captopril treatment all significantly decreased urinary protein excretion, urinary albumin excretion and serum creatinine to the same extent. These effects were sustained for the entire experimental period and were not associated with any significant changes in body weight, urine volume, urine sugar and urinary electrolytes excretion. These results were confirmed by morphological analysis of kidneys in each group of rats. Losartan treatment, captopril treatment and losartan+captopril treatment all significantly and effectively protected against an increase in the percentage of focal glomerular sclerosis. Losartan treatment and captopril treatment both significantly attenuated the increase in heart weight: body weight ratio. The heart weight: body weight ratio in the losartan-treated group was significantly lower than in the captopril-treated group. CONCLUSIONS: These results indicate that hypertension could accelerate diabetic renal impairment and that losartan has antihypertensive and renoprotective effects in this rat model. They also suggest that the antihypertensive and renoprotective effects of captopril treatment in this rat model are caused mainly by inhibition of angiotensin II production rather than stimulation of the kallikrein-kinin system or of vasodilator prostaglandins. The difference in potency between losartan treatment and captopril treatment to attenuate the increase in heart weight: body weight ratio might partly explain the existence in the heart of angiotensin-forming pathways, which are not dependent on angiotensin converting enzyme.

Angiotensin II↗
PubMed1995

Cerebral density and perfusion measured among heart disease patients with and without stroke.

This investigation was designed to clarify the chronic effects of cardiogenic emboli on cerebral perfusion and tissue densities within remaining noninfarcted brain. Local cerebral perfusion and tissue densities were measured by xenon-contrasted CT scanning and compared by cross-sectional designs among normal volunteers without heart disease (Group C, n = 44), normal volunteers with heart disease (Group N, n = 20), patients with heart disease and lacunar infarctions (Group L, n = 31) and patients with heart disease associated with cardiogenic cerebral embolism (Group E, n = 12). In Group E, remaining cortical and subcortical gray and white matter perfusion were reduced compared to Groups C and N (p = 0.01), but did not differ from Group L, who had similar profiles of risk factor for stroke. In Group E, perfusion was reduced within the thalamus ipsilateral to cortical infarctions (p < 0.05). There were no differences in remaining tissue densities between Groups E and L. It is concluded that reduced cerebral perfusion in noninfarcted regions among patients with cardiogenic emboli appears to be related to atherosclerosis of small cerebral vessels in a similar manner to patients with lacunes, but thalamo-cortical disconnections also contribute to cerebral hypoperfusion.

Adult↗
PubMed1995

Effect of ethanol on DNA synthesis and c-met induction in Chang liver cells with long-term culture.

This investigation was performed to determine whether ethanol affects induction on Chang liver cells of the c-met protooncogene product (c-met), a cell-surface receptor for hepatocyte growth factor (HGF). These cells were cultured for 4 weeks with 5, 50, or 100 mmol/L ethanol, or 10, 100, or 200 mumol/L acetaldehyde. Ethanol was found to inhibit [3H]thymidine incorporation by cells in a dose-dependent manner. In addition, acetaldehyde at 100 mumol/L also inhibited [3H]thymidine uptake. Treatment with recombinant HGF led to enhanced [3H]thymidine incorporation by cells treated with ethanol or acetaldehyde as well as by those left untreated, with no significant differences in the rates of increase among these three cell groups. The amount of c-met messenger RNA, however, was unaffected by treatment with ethanol or acetaldehyde. Expression of c-met as measured by cell ELISA was also unchanged by both treatments. These results suggest that ethanol has no effect on c-met induction on Chang liver cells and that HGF may not be involved in the ethanol induced inhibition of DNA synthesis.

Cells, Cultured↗
PubMed1994

Cognitive declines correlate with decreased cortical volume and perfusion in dementia of Alzheimer type.

Cerebral CT changes are correlated with cognitive declines among 18 patients with probable dementia of Alzheimer type (DAT) (7 men, 11 women, mean age 75.4 years) and are compared for control purposes with similar measures among 18 age-matched normal volunteers (8 men, 10 women, mean age 73.7 years). Mean follow-up intervals are 28.6 months for DAT and 27.0 months for controls. For DAT, annual rates for ventricular volume enlargement are +9.2% and for cortical atrophy are -2.1%. Annual reductions in regional cerebral perfusions per 100 g brain/min, are: total cortex -1.1 ml, frontal -1.2 ml, temporal and parietal -0.9 ml, basal ganglia -1.6 ml, thalamus -2.5 ml, total white matter -0.6 ml, frontal white matter -0.7 ml. At entry evaluation, compared to normals, DAT patients had reduced CT densities in white matter, but not in cortex. Nevertheless, cortical CT densities declined progressively at annual rates of -0.72 Hounsfield units (HU), but remained constant in white matter. Annual point score declines for Cognitive Capacity Screening Examinations were -2.0 and for Mini Mental State: -2.8. Controls showed no cognitive change. Multiple regression analyses correlate cognitive declines with: (1) reductions in perfusion within parietal cortex (p = 0.015), (2) decreases in cortical volume (p = 0.019), and (3) decreases in HU within subcortical gray matter (p = 0.007).

Aged↗
PubMed1994

Effect of cytochalasin B on intestinal smooth muscle cells.

The inhibitory effect of cytochalasin B on contraction of smooth muscle cells isolated from guinea-pig taenia coli was investigated. Cytochalasin B (10-70 microM) inhibited the high K+ (70 mM)-induced contraction in a dose-dependent manner, and the maximum and the half-maximum effects were obtained at 50 and 15 microM, respectively. Cytochalasin B (70 microM) decreased ATPase activity in skinned guinea-pig taenia coli. However, cytochalasin B (50 microM) had no significant effect on the voltage-dependent Ca2+ currents, the passive membrane properties or the membrane potential. Cytochalasin B also had no effect on the phosphorylation of 20 kDa myosin light chain induced by high K+ and cytosolic Ca2+ levels. These results suggest that the inhibition of contraction by cytochalasin B may be due to its effects on actin of microfilaments and contractile filaments of guinea-pig taenia coli smooth muscle cells.

Actins↗
PubMed1994

A case of Behçet's disease with occlusion of both caval veins and "downhill" esophageal varices.

A case of Behçet's disease (BD) with occlusion of both caval veins and "downhill" esophageal varices is reported. A 59-year-old male patient had esophageal varices, established as the "downhill" type by endoscopy, venography, and contrast-enhanced computed tomography (CE-CT) scan. Venography via both jugular veins did not lead to the visualization of the superior vena cava (SVC), but revealed numerous collateral veins, which formed esophageal varices en route. Venography via both femoral veins did not lead to the visualization of the inferior vena cava (IVC), but revealed numerous collateral veins, which flowed into the portal vein together with the jugular flow. CE-CT scan revealed the disappearance of the SVC and the lower part of the IVC, below the hepatic vein. The patient was diagnosed as having BD, based on his history of recurrent oral and skin lesions over the past 26 years.

Behcet Syndrome↗
PubMed1994

CT changes associated with normal aging of the human brain.

CT was used to measure changes in cerebral gray and white matter tissue densities associated with normal aging, using a cross-sectional design, in order to provide normative data for comparisons with abnormal aging such as dementias of Alzheimer's and vascular types. Cerebral compartmental densities were measured using plain CT, and their perfusion values were recorded during stable xenon inhalation (CT-CBF), among 81 neurologically and cognitively normal volunteers of different ages. Results led to the conclusion that cortical gray matter tissue densities progressively decline (polio-araiosis) after age 60. Cortical polio-araiosis is coupled with regional hypoperfusion but not with cortical atrophy. It is speculated that the cortical hypodensity identified by CT imaging parallels declines in cortical synaptic density, as reported from autopsy studies using anti-synaptophysin staining of cerebral cortex obtained from normal people above and below age 60. The coupling of cortical hypoperfusion with polio-araiosis is believed to reflect age-related reductions of cortical metabolic demands as reported by PET. During normal aging leuko-araiosis correlates directly with cortical atrophy, suggesting that anterograde axonal degeneration resulting from cortical neuronal dearborization play a role in its causation.

Adult↗
PubMed1994

Problems encountered with longitudinal neurological, psychometric and cerebral CT imaging among stroke data bank patients with dementia.

41 patients (30 men, 11 women, mean age 65.3 +/- 9.7 years) with probable ischemic vascular dementia diagnosed according to stated clinical criteria at least 3 months after hospital discharge and among a few nonhospitalized subjects with thorough clinical, neurovascular and neuroimaging workup have been followed for the past 7 years with serial measures of neurological and cognitive status and cerebral blood flow using stable xenon-enhanced CT. Cognitive impairments correlated with cerebral ischemia rather than CT measurements of infarcted brain volume. A minimum of one follow-up was required and follow-up intervals ranged from 4 months to 6.6 years (mean 3.4 +/- 1.6 years). 9 patients (22.0%) were lost to follow-up, 4.9% died, 9.8% became incapacitated by additional strokes, 2.4% by cancer and 4.9% moved away. Cross-sequential designs adjust for problems of attrition. Mortality rates of 1.4%/year during 1986-1993 are significantly lower than 2.0%/year between 1983 and 1986. Declines in mortality are attributed to control of risk factors and antiplatelet treatment of atherosclerotic cerebral vascular disease and anticoagulant treatment of patients with cardiogenic embolism.

Aged↗
PubMed1994

Measurement of urinary endothelin-1-like immunoreactivity and comparison with other urinary parameters in patients with primary vesicoureteral reflux. A preliminary report.

By using a radioimmunoassay specific for endothelin-1 (ET-1), we measured urinary excretion of ET-1-like immunoreactivity in 63 spot urine samples of 48 patients with primary vesicoureteral reflux (VUR). Urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), beta 2-microglobulin (beta 2-MG), microalbumin (Alb), and creatinine (Cr) were also measured. There was no significant correlation in any pairs of ET-1 and NAG, ET-1 and beta 2-MG or ET-1 and Alb. In patients with grade 2, grade 3, and grade 4 VUR, urinary ET-1/Cr was significantly higher than normal (p < 0.05). Comparing the grade of reflux according to the International Classification with urinary ET-1/Cr, the ratio of more than normal urinary ET-1/Cr increased in proportion to the grade of reflux, but it conversely decreased in grade 5. In conclusion, urinary ET-1 may be an indicator of distal renal tubular or collecting duct injury in patients with primary VUR.

Acetylglucosaminidase↗