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Biomedical subjects

K Ohtsuka

Publications and source records attributed to K Ohtsuka.

At least 91 records · Page 5Linked to original sources

[Treatment of patients with recurrent esophageal carcinoma].

From 1987 to 1997, 211 patients with thoracic esophageal carcinoma underwent radical surgery. The 5 year survival rate was 87% in pTNM stage I, 64% in stage II A, 57% in stage II B, and 31% in stage III. The survival curve was improved by postoperative chemotherapy including CDDP/5-FU as compared with surgery alone. Relapse occurred in 59 of these patients (28%). Lymphatic recurrence was recognized in 32 patients, hematogenic recurrence in 19, mixed type in 4, and intramural or local recurrence in 4 patients. In spite of through lymph node dissection, postoperative lymphatic recurrence was most frequent at the upper mediastinum and neck. Among hematogenic metastases, pulmonary and hepatic metastases were observed at equal incidences. The 1 year survival rate and median survival period of the patients with recurrent carcinoma were 36% and 191 days (26-1,122), respectively. There was no significant difference in prognosis between lymphatic and hematogenic recurrence. The prognosis for patients who underwent active therapy for recurrence (42 cases) was significantly better than for those who underwent only palliative therapy (17 cases). Resection of the site of recurrence was performed in 4 cases. The combination therapy of resection or irradiation and combined chemotherapy with CDDP and 5-FU resulted in a better prognosis (median survival period was 504 days) than irradiation alone or chemotherapy alone. In conclusion, early diagnosis and active multimodality therapy were important to improve the prognosis of recurrent esophageal carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

[The immunoreactivity studies of the idiopathic inflammatory myopathy over the past three years in our laboratory].

Biopsied skeletal muscles from patients with inflammatory myopathy (6 cases of polymyositis (PM), 2 cases of dermatomyositis (DM), 5 cases of collagen disease with polymyositis and a case of allergic granulomatous angitis) were examined by comparing immunostained infiltrated cells at perivascular, perimysial and the endomysial sites as well as examining the histochemical findings on serial frozen sections from cases examined by our laboratory over the past three years. CD68 was used for macrophage, L26 for B lymphocytes, CD4 and CD8 for T lymphocytes. Expression of HLA-ABC was examined for Class I antigen and HLA-DR for Class II antigen on the muscle fibers. Many macrophages and CD8-positive T lymphocytes had infiltrated the endomysium in PM. Many CD4-positive T lymphocytes and L26-positive B lymphocytes had infiltrated perivascular sites in DM. These results were almost the same as those in many other reports. HLA-ABC was positive on the muscle sarcolemma in all cases. However, the expression of HLA-DR was not identical in all cases. It is useful to determine the diagnosis and consider a pathogenesis of inflammatory muscle diseases to analyze the infiltrated cells and the site of infiltration even in case showing few of infiltrating cells and necrotic fibers.

Adult↗

[Vascular endothelium-related factors and atherosclerosis/arteriosclerosis: serum hepatocyte growth factor as a possible indicator of vascular lesions].

To investigate the possible involvement of hepatocyte growth factor (HGF) with vascular lesions, we studied the relationship between serum HGF concentrations and the grades of retinal arteriosclerosis, coronary atherosclerosis proliferative changes in the retina of diabetic subjects, and activities of systemic vasculitis. Individuals with more advanced grades of retinal arteriosclerotic change showed higher serum HGF values (grade 0, 0.053 +/- 0.005 ng/ml ; grade 1, 0.144 +/- 0.022 ng/ml ; grade 2, 0.338 +/- 0.36 ng/ml ; grade 3, 0.526 +/- 0.051 ng/ml). The serum HGF concentration was increased in subjects with single- (0.200 +/- 0.012 ng/ml, double- (0.334 +/- 0.018 ng/ml) or triple- (0.379 +/- 0.022 ng/ml) vessel coronary heart diseases, compared with that in subjects with intact coronary arteries (0.112 +/- 0.008 ng/ml). Serum HGF in diabetes without retinopathy was lower than that in nondiabetic subjects (0.041 +/- 0.003 ng/ml vs 0.080 +/- 0.010 ng/ml, p < 0.05), but did not differ from that in other diabetic subjects with background retinopathy (0.058 +/- 0.007 ng/ml) or preproliferative retinopathy (0.048 +/- 0.010 ng/ml). Serum HGF was increased in patients with proliferative retinopathy without photocoagulation (0.213 +/- 0.025 ng/ml, p < 0.01), but not in those with photocoagulation (0.040 +/- 0.008 ng/ml). Serum HGF concentration was increased (p < 0.01) during the acute phase of Schönlein-Henoch purpura (0.31 +/- 0.15 ng/ml), a systemic vasculitis, but it returned to control levels during the remission phase (0.11 +/- 0.10 ng/ml). Increased serum HGF may be involved in the pathogenesis of arteriosclerosis/atherosclerosis, retinal neovascularization, or vasculitis, and measurement of serum HGF may be a useful test for predicting these vascular lesions.

Aged↗

Roles of brain angiotensin II and C-type natriuretic peptide in deoxycorticosterone acetate-salt hypertension in rats.

OBJECTIVE: To investigate the roles of brain angiotensin II and C-type natriuretic peptide (CNP) in the hypertensive mechanism of deoxycorticosterone acetate (DOCA)-salt hypertension. METHODS: We injected 50 microg/kg CV-11 974, an angiotensin II type-1 receptors antagonist, 30 nmol/kg CNP-22, or the vehicle (artificial cerebrospinal fluid) into the cerebral ventricle or intravenously 5 min before the intracerebroventricular infusion of 1.5 mol/I NaCl solution for 30 min into either male normotensive Wistar rats or DOCA-salt hypertensive rats anesthetized with urethane, and their arterial pressures and heart rates were continuously recorded. Blood (2 ml) was collected at the end of the infusion for the measurement of plasma concentration of arginine vasopressin. We infused 10 or 50 microg/kg per day CV-11 974, 10 or 50 nmol/kg per day CNP-22, or the vehicle (1 microl/h) into the cerebral ventricles of DOCA-salt hypertensive rats for 7 days by using osmotic minipumps, and measured their systolic arterial pressures, pulse rates, and urinary excretions of vasopressin. RESULTS: Intracerebroventricular pre-administrations of CV-11 974 and of CNP-22 inhibited increases in mean arterial pressure, heart rate, and plasma vasopressin concentration induced by intracerebroventricular infusion of 1.5 mol/l NaCl into normotensive rats; increases in hemodynamics and plasma level of vasopressin induced by intracerebroventricular infusion of 1.5 mol/l NaCl were suppressed by intracerebroventricular pre-injections of CV-11 974, but not of CNP-22, into DOCA-salt hypertensive rats. Continuous intracerebroventricular infusions of 50 microg/kg per day CV-11 974 attenuated hypertension in DOCA-salt treated rats, accompanied by a reduction in urinary excretion of vasopressin. Continuous intracerebroventricular infusions of 50 nmol/kg per day CNP-22, however, affected neither hypertension nor urinary excretion of vasopressin in DOCA-salt hypertensive rats. CONCLUSION: Brain angiotensin II could play a role in the pressor mechanism of DOCA-salt hypertension by increasing release of vasopressin via type 1 receptors. That brain CNP has an inhibitory effect on release of vasopressin in acute experiments indicates that the impairment of this inhibitory effect of brain CNP on secretion of vasopressin could be involved in the pathogenesis of DOCA-salt hypertension in rats.

Angiotensin II↗

[Usefulness of heart rate variability for evaluating cardiac autonomic nervous function].

To investigate the effect of gastric ulceration on cardiac autonomic nervous function, 24-hour ambulatory electrocardiograms were recorded in patients with artificial gastric ulcers caused by endoscopic treatment of gastric tumors. Their cardiac autonomic nervous activity was assessed by both time- and frequency-domain analyses of heart rate variability obtained from electrocardiogram recordings. The results were compared with those from patients who had undergone endoscopic treatment of esophageal varices or colorectal tumors, or gastrointestinal endoscopy alone. Parameters of time-domain analysis decreased significantly with the formation of gastric ulcers. Because parameters of frequency-domain analysis did not change in the group with gastric ulcers, this decrease in parameter of time-domain analysis suggests increased activity of cardiac sympathetic nervous system. There were no changes in the parameters of either time- or frequency-domain analysis in other groups. These results suggest that artificial gastric ulceration modifies cardiac sympathovagal balance, favoring cardiac sympathetic activity, while artificial esophageal and colon ulcers have no effect on cardiac autonomic nervous activity. Heart rate variability analysis is a useful method of evaluating possible implications between gastric ulceration and cardiac autonomic nervous function.

Aged↗

Hsp70 and Hsp40 chaperone activities in the cytoplasm and the nucleus of mammalian cells.

The existence and function of a Hsp40-Hsp70 chaperone machinery in mammalian cells in vivo was investigated. The rate of heat inactivation of firefly luciferase transiently expressed in hamster O23 fibroblasts was analyzed in cells co-transfected with the gene encoding the human Hsp40 (Ohtsuka, K. (1993) Biochem. Biophys. Res. Commun. 197, 235-240), the human inducible Hsp70 (Hunt, C., and Morimoto, R. I. (1985) Proc. Natl. Acad. Sci. U. S. A. 82, 6455-6459), or a combination of both. Whereas the expression of human Hsp70 alone in hamster cells was sufficient for the protection of firefly luciferase during heat shock, expression of the human Hsp40 alone was not. Rather, this led to a small but significant increase in the heat sensitivity of luciferase. The expression of the human Hsp40 only led to heat protection when the human Hsp70 was expressed as well. Under such conditions the rate of luciferase reactivation from the heat-inactivated state was increased, but the rate of inactivation during heat shock was not affected. Using constructs that direct firefly luciferase either to the cytoplasm or to the nucleus (Michels, A. A., Nguyen, V.-T., Konings, A. W. T., Kampinga, H. H., and Bensaude, O. (1995) Eur. J. Biochem. 234, 382-389), it was demonstrated that these chaperone functions are found in both compartments. Our data provide the first evidence on how the Hsp40/Hsp70 chaperone complex acts as heat protector in mammalian cells in vivo.

Animals↗

Expansion of intermediate T cell receptor cells expressing interleukin-2 receptor alpha- beta+, CD8alpha+ beta+, and lymphocyte function-associated antigen-1+ in the liver in association with intrahepatic islet xenograft rejection from rat to mouse: prevention of rejection with anti-interleukin-2 receptor beta monoclonal antibody treatment.

BACKGROUND: The precise mechanisms involved in islet xenograft rejection remain unknown. The purpose of the present study was to determine cellular mechanisms responsible for islet xenograft rejection in the liver to facilitate finding a procedure for prevention of immune rejection. METHODS: Hepatic mononuclear cells (MNC) as well as splenocytes, peripheral blood MNC, and thymocytes from streptozotocin-induced diabetic mice (BALB/c) rejecting the intrahepatic rat (Lewis) islet xenografts were isolated and examined by two-color FACS analysis. RESULTS: The characteristic finding of the hepatic MNC from the mice rejecting islet xenografts compared with mice receiving isografts was a significant increase in the yield as well as in the percentage of the cells expressing CD3+ interleukin-2 receptor (IL-2R) alpha- beta+, CD3+ CD8alpha+ beta+, and T cell receptor (TCR) alphabeta+ lymphocyte function-associated antigen-1+. The expression of CD3 and TCR alphabeta of these T cells was found to be of intermediate intensity (TCR(int) cells). The expansion of these TCR(int) cells occurred predominantly in the liver. There was no significant difference in the cells expressing CD3+ IL-2R alpha+, CD3+ CD4+, CD3+ TCRgammadelta+, CD3- IL-2Rbeta+ (natural killer cells), and B220+ (B cells). In vivo administration of anti-IL-2Rbeta monoclonal antibody directed to the expanded cells produced a prevention of rejection. CONCLUSIONS: These findings suggest that islet xenograft rejection in the liver from rat to mouse is an event for which the TCR(int) cells are responsible.

Animals↗

Retinal projections to the accommodation-related area in the rostral superior colliculus of the cat.

Results of previous studies have indicated that the rostral superior colliculus (SC) plays an important part in the control of accommodation. The present study was carried out to investigate retinal projections to the accommodation-related area in the rostral SC. We injected WGA-HRP into the accommodation-related area in the rostral SC of the cat, where accommodative responses were elicited by stimulation with weak currents of less than 20 microA. Following injection of WGA-HRP into the accommodation-related area in the rostral SC, retrogradely labeled ganglion cells were observed mainly in the area centralis. Projections from the contralateral eye were denser than those from the ipsilateral eye. Almost all retrogradely labeled cells were classified as gamma-cells owing to their small cell-body diameters and thin dendrites, although a few were classified as alpha-cells. These findings suggest that the accommodation-related area in the rostral SC is located in the portion corresponding to the area of representation of the central visual field and receives mainly gamma-cell projections.

Accommodation, Ocular↗

Serial dynamic magnetic resonance imaging of orbital cavernous hemangioma.

PURPOSE: To assess serial dynamic magnetic resonance imaging after rapid intravenous injection of contrast material as a tool for diagnosing orbital cavernous hemangioma. METHODS: Two patients with orbital cavernous hemangioma were studied. Gadolinium-DTPA, 0.1 mmol/kg, was injected intravenously in 10 seconds. RESULTS: On early imaging after the injection, one small point of enhancement was initially noted, and then the tumor was homogeneously enhanced. The initial enhancement point represented the connecting point of feeding vessels to the lesion. CONCLUSIONS: Dynamic magnetic resonance imaging is useful for diagnosing cavernous hemangioma and for estimating the connecting point of feeding vessels.

Adult↗

Orbital granular cell tumor developing in the inferior oblique muscle.

PURPOSE: To describe the magnetic resonance imaging and histopathologic features of an orbital granular cell tumor. METHODS: A 43-year-old man was initially examined with slowly progressive vertical diplopia. A firm mass was palpable through the left lower eyelid. Magnetic resonance imaging and histopathologic examinations were performed. RESULTS: Magnetic resonance imaging disclosed a spindle-shaped mass involving the inferior oblique muscle. Histopathologic examination disclosed that the tumor cells, diagnosed as a granular cell tumor, had infiltrated the muscle fibers. CONCLUSION: In the present case, these findings indicate that the granular cell tumor may develop in the inferior oblique muscle.

Adult↗

Enhanced magnetic resonance imaging in a patient with acute paralysis of the inferior division of the oculomotor nerve.

PURPOSE: To describe the characteristics of enhanced magnetic resonance imaging of the orbit in a patient with acute paralysis of the inferior division of the oculomotor nerve. METHOD: Using a fat-suppression technique, we performed enhanced magnetic resonance imaging of the orbit of a 36-year-old woman with acute paralysis of the inferior division of the left oculomotor nerve. RESULTS: The inferior division of the left oculomotor nerve in the orbit was markedly enhanced, suggesting inflammation of the inferior division of the oculomotor nerve. The severity of paralysis decreased immediately after intravenous corticosteroid (prednisolone acetate) administration. CONCLUSION: These findings suggest that enhanced magnetic resonance imaging with a fat-suppression technique is useful for diagnosing peripheral nerve lesions in the orbit.

Acute Disease↗

Intraocular pressure and proptosis in 95 patients with Graves ophthalmopathy.

PURPOSE: To study the cause of ocular hypertension in patients with Graves ophthalmopathy. METHODS: Intraocular pressure was measured in 190 eyes of 95 patients (mean age, 42 years; range, 11 to 86 years) with Graves ophthalmopathy. In six eyes (four patients), changes in intraocular pressure were also analyzed upon orbital decompression. RESULTS: The mean intraocular pressure +/- SD in 190 eyes was 18.36 +/- 4.02 mm Hg (range, 10 to 34 mm Hg). The intraocular pressure in 42 of the 190 eyes was 21 mm Hg or more. The intraocular pressure in 76 eyes with proptosis of 19 mm or more was 19.96 +/- 4.49 mm Hg (range, 14 to 34 mm Hg), whereas the intraocular pressure in 114 eyes with proptosis of less than 19 mm was 17.08 +/- 3.38 mm Hg (range, 10 to 28 mm Hg). The difference in the values between these two groups is statistically significant (two-tailed t test, P < .001). The mean intraocular pressure in six eyes decreased from 23.23 to 18.82 mm Hg upon orbital decompression, a difference that was statistically significant (two-tailed paired t test, P < .001). The coefficient of outflow facility was normal in these six eyes. CONCLUSION: These findings suggest that ocular hypertension in patients with Graves ophthalmopathy is caused, in part, by increased intraorbital pressure associated with proptosis.

Adolescent↗

The immunoregulatory effects of NK cells: the role of TGF-beta and implications for autoimmunity.

The cytotoxic activities of natural killer (NK) cells--important in innate immunity--have received considerable attention, but NK cells also regulate T- and B-cell functions as well as hematopoiesis. Here, David Horwitz and colleagues focus on the capacity of NK cells to regulate antibody production positively and negatively, and in particular on the role of NK-cell transforming growth factor beta (TGF-beta) in downregulation of B-cell activity.

Animals↗

Theory and computer programs for calculating solution pH, buffer formula, and buffer capacity for multiple component system at a given ionic strength and temperature.

PURPOSE: A theory and computer programs running on Microsoft Excel for Windows for calculation of solution pH, buffer formula, and buffer capacity at a given ionic strength and temperature were developed. The theory does not limit the category of buffer components, the number of buffer components, or the number of ionizations for each buffer component. The usefulness of the programs was examined. METHODS: The formulas for 7 single component buffer solutions and 2 multiple component buffer solutions composed of citrate, phosphate, Tris, borate, and glycine were calculated. The solution pH values were measured at 25, 40, 55 and 70 degrees C for comparison with the calculated pH values. RESULTS: Of the 108 predictions made, 96 were of pH values with +/- 0.1 pH unit of the measured values, at temperatures ranging from 25 degrees C to 70 degrees C and at ionic strengths ranging from 0.1 M to 0.5 M. CONCLUSIONS: These programs will be useful for identifying appropriate buffer solutions at various temperatures and/or ionic strengths.

Buffers↗

Effect of ionic strength on solution stability of PNU-67590A, a micellar prodrug of methylprednisolone.

PURPOSE: PNU-67590A is a water-soluble micellar prodrug of methylprednisolone (MP). The major products of degradation of PNU-67590A are MP by hydrolysis and methylprednisolone 17-suleptanate (17-E) by 21-->17 acyl migration. The effect of ionic strength on micelle formation and stability of PNU-67590A in aqueous solution was examined. METHODS: PNU-67590A solutions at pH 2 and 8 and ionic strength of 0.05, 0.1, 0.2, and 0.4 M were maintained at 25 degrees C in the dark to measure MP and 17-E levels over time. RESULTS: The rate of degradation of micellar PNU-67590A at pH 8 was less than that of monomeric PNU-67590A, and vice versa at pH 2. Increase in ionic strength decreased both the critical micelle concentration of PNU-67590A and the degradation of micelle PNU-67590A at both pHs, resulting in improved overall stability of PNU-67590A. CONCLUSIONS: Formulation of PNU-67590A in a concentrated solution with high ionic strength will maximize stability and shelf-life.

Drug Stability↗

Gambling activities of young Australians: developing a model of behaviour.

As more gambling venues open in Australia, youth gambling as problem behaviour has been identified. The aim of this study was to assess youth gambling in a population with easy access to gambling, and to evaluate the adequacy of a model for predicting adolescent gambling frequency and problem gambling. The model comprised a combination of the Theory of Reasoned Action (TRA) (Ajzen & Fishbein, 1980), personality variables (venturesomeness, impulsiveness), and cognitive bias variables derived from Weinstein's (1980) propositions concerning unrealistic optimism about future life events. A sample of 1017 school- and university-based adolescents indicated relatively low frequencies of gambling and low scores on the problem gambling scale, with males scoring higher than females on both measures. The TRA was supported with about 30% of the variance of each of gambling behaviour and problem gambling accounted for by intentions, attitudes, and subjective norms. Personality factors added significantly to the prediction of gambling. The cognitive bias variables, although independently not statistically significant, further contributed to prediction.

Journal Article↗

The in-vivo activity of an antifungal antibiotic, benanomicin A, in comparison with amphotericin B and fluconazole.

The in-vivo antifungal activity of benanomicin A administered intravenously or subcutaneously was compared with that of amphotericin B and fluconazole using animal models of systemic infections with Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans. The efficacy of benanomicin A in C. albicans infection was more pronounced when administered in multiple doses than in a single dose. This was also true of fluconazole, but not of amphotericin B, which showed no difference between single and multiple dosings. Benanomcin A eradicated C. albicans cells from the kidneys of infected mice in a manner comparable to that of amphotericin B, but more effectively than fluconazole. The histopathological findings obtained from the kidneys of the C. albicans-infected mice confirmed the therapeutic efficacy of benanomicin A. The subcutaneous ED50 values of benanomicin A were 1.30 mg/kg/day (C. albicans) and 19.0 mg/kg/day (A. fumigatus) which were intermediate between those of amphotericin B and fluconazole in the two models. The subcutaneous ED50 value of benanomicin A for C. neoformans was 21.5 mg/kg/day, which was higher than that of amphotericin B.

Amphotericin B↗

Sodium intake regulates renin gene expression differently in the hypothalamus and kidney of rats.

OBJECTIVE: To elucidate the different effects of sodium intake on renin messenger RNA (mRNA) in the hypothalamus and the kidney and to investigate the role of hypothalamic renin in sodium-induced hypertension. DESIGN AND METHODS: We investigated the expression of the renin gene in the hypothalamus and the kidney of rats with altered sodium intake and those administered either deoxycorticosterone acetate (DOCA) or sodium. Diets containing a high (8% NaCl), normal (2% NaCl), or low (0.2% NaCl) amount of sodium were administered to 12-week-old male Wistar rats for 10 days or 8 weeks before the rats were killed. Male Wistar rats administered either DOCA or 1% NaCl were killed 2 weeks (during the prehypertensive stage) or 6 weeks (during the hypertensive stage) after the start of treatment. The hypothalamus and kidneys were excised for extraction of total RNA. Competitive polymerase chain reaction of renin mRNA and deletion-mutated renin RNA was performed, and the renin mRNA concentration was calculated. RESULTS: A high sodium intake for 10 days increased the renin mRNA in the hypothalamus; the hypothalamic renin mRNA had not been suppressed after 8 weeks of a high sodium intake despite the lowering in renal renin mRNA. Renin mRNA levels in the hypothalamus were not suppressed either in the prehypertensive or in the hypertensive stage in rats treated with DOCA or sodium, or both, although the renal renin mRNA was reduced in rats administered DOCA or sodium, or both, compared with that in sham-treated control rats, during both stages. CONCLUSIONS: The expression of the renin gene is regulated differently in the rat hypothalamus from that in the kidney. The constant expression of the renin gene in the hypothalamus during a chronic high sodium load might be related at least in part to the mechanism of the activated brain renin-angiotensin system in sodium-induced hypertension.

Animals↗