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Biomedical subjects

H Takimoto

Publications and source records attributed to H Takimoto.

At least 91 records · Page 5Linked to original sources
PubMed1988

Effect of chemical modification at C1 of the glucosamine backbone of lipid A-subunit analog GLA-27 on manifestation of immunopharmacological activity.

The effect of chemical modification at the C1 position of GLA-27, 4-O-phosphono-D-glucosamine carrying N-3-tetradecanoyloxytetradecanoyl [C14-O-(C14)] and 3-O-tetradecanoyl (C14) groups, was investigated. Replacement by SH or S-acetyl groups of the OH group resulted in the enhancement of mitogenicity but gave rise to a reduction, in macrophage-stimulating ability such as induction of tumor necrosis factor and enhancement of phagocytic and cellular acid phosphatase activities. Bisphosphorylation at C1 and C4 resulted in a slight decrease in mitogenicity or almost complete loss of the macrophage-stimulating ability.

Animals↗
PubMed1988

An adoptive immunotherapy of patients with medulloblastoma by lymphokine-activated killer cells (LAK).

An adoptive immunotherapy of 6 patients with medulloblastoma by lymphokine-activated killer (LAK) cells is described. They were from 2 to 9 years in age and had cerebrospinal fluid (CSF) dissemination of the tumours. All patients underwent the whole-neuraxis irradiation and chemotherapy. After the usual treatments, they were submitted to an adoptive transfer of one-haplotype identical LAK cells. The LAK cells were induced from peripheral blood lymphocytes (PBL) of their relatives with human recombinant interleukin-2 (rIL-2). 3 - 15 x 10(9) LAK cells were transferred intrathecally in 2-3 months. In 3 of 6 patients, neurological signs were improved and malignant cells had never been detected on CSF cytology after the adoptive immunotherapy. One among these 3 patients showed complete response in 20 months. Thus, this is an attractive approach for the treatment of medulloblastoma with CSF dissemination of the tumour which current therapeutic intervention can not cure.

Cerebellar Neoplasms↗
PubMed1988

Activation of murine peritoneal macrophages by intraperitoneal administration of a traditional Chinese herbal medicine, xiao-chai-hu-tang (Japanese name: shosaiko-to).

Macrophage activation by a traditional Chinese herbal medicine, xiao-chai-hu-tang (Japanese name: shosaiko-to), was investigated. Intraperitoneal (i.p.) administration of shosaiko-to into (BALB/c x DBA/2)F1 mice resulted in marked activation of macrophages with respect to phagocytic and lysosomal enzyme activities (acid phosphatase and N-acetyl-beta-D-glucosaminidase) compared with the control. The maximal responses were induced by an i.p. injection of 3 mg shosaiko-to 4 days previously. Enhanced activities induced by shosaiko-to were also seen in C3H/HeJ mice, which is a non-responder strain to bacterial lipopolysaccharide (LPS). Significant macrophage accumulation in the peritoneal cavity and increased lysosomal enzyme activities were observed in mice injected with shosaiko-to. Shosaiko-to exhibited significant cytostasis-inducing activity. In addition, the administration of shosaiko-to led to a moderate expression of Ia antigen on the surface of peritoneal macrophages. These results suggest that shosaiko-to is a potent macrophage activator.

Animals↗
PubMed1988

Importance of fatty acid substituents of chemically synthesized lipid A-subunit analogs in the expression of immunopharmacological activity.

The immunopharmacological activities of chemically synthesized lipid A-subunit analogs, 4-O-phosphono-D-glucosamine derivatives carrying different N- and 3-O-linked acyl groups, were investigated. None of the synthetic compounds tested exhibited any detectable pyrogenicity at a dose of 10 micrograms/kg. Weaker lethal toxicity in galactosamine-sensitized mice was detected at 1 microgram per mouse for all the synthetic compounds except GLA-58. Among (RS) stereoisomers of 4-O-phosphono-D-glucosamine derivatives carrying a 3-O-tetradecanoyl (C14) group with different N-linked acyloxyacyl groups, i.e., 3-dodecanoyloxytetradecanoyl [C14-O-(C12)], 3-tetradecanoyloxytetradecanoyl [C14-O-(C14)], and 3-hexadecanoyloxytetradecanoyl [C14-O-(C16)] groups (termed GLA-57, GLA-27, and GLA-58, respectively), GLA-27 exhibited significant colony-stimulating factor-inducing and tumor necrosis factor-inducing activities, mitogenicity, polyclonal B-cell activation activity, macrophage activation, and adjuvanticity. The activities of GLA-57, which had an N-linked C14-O-(C12) group, were equivalent to or somewhat weaker than those of GLA-27 with a C14-O-(C14) group. Significant immunopharmacological activities were not observed for GLA-58, carrying a C14-O-(C16) group bound to the amino group. GLA-59, carrying 3-O-linked 3-hydroxytetradecanoyl (C14OH) and N-linked C14-O-(C14) groups, showed much higher activities than GLA-27, GLA-60, a compound which possesses the same fatty acid substituents as GLA-59 but with reversed binding sites, showed the strongest B-cell activation and adjuvant activities among the synthetic compounds. Among stereoisomers of GLA-59 and GLA-60 composed of fatty acid substituents with the (RR) and (SS) configuration, compounds with the (RR) configuration elicited stronger activities than the (SS) stereoisomers. The importance of fatty acid substituents, including stereospecificity for the expression of immunopharmacological activities of 4-O-phosphono-D-glucosamine derivatives, was demonstrated.

Adjuvants, Immunologic↗
PubMed1987

Effect of stereospecificity of chemically synthesized lipid A-subunit analogues GLA-27 and GLA-40 on the expression of immunopharmacological activities.

Tumor necrosis factor (TNF)-inducing, mitogenic, polyclonal B cell activation (PBA), macrophage activation and antiviral activities of chemically synthesized lipid A-subunit analogues, GLA-27 and GLA-40, were investigated. The structure of GLA-27 comprises 4-O-phosphono-D-glucosamine carrying tetradecanoyl and 3-tetradecanoyloxytetradecanoyl [C14-O-(C14)] groups as the 3-O- and 2-N-acyl substituents, respectively. GLA-40 is a 1-deoxy compound of GLA-27. The activities of stereoisomers, (R) and (S) forms at the C3 position of the C14-O-(C14) group, of both compounds were also investigated. TNF-inducing activity of the (S) isomers of GLA-27 and GLA-40 was stronger than that of the (R) isomers while the (R) isomers exhibited stronger mitogenic and PBA activities than the (S) isomers. With respect to macrophage activation such as phagocytosis, acid phosphatase and N-acetyl-beta-D-glucosaminidase activity as cellular lysosomal enzymes and cytostasis, peritoneal macrophages obtained from mice administered i.p. with test samples showed significant activities. Among stereoisomers of GLA-27, the (R) isomer exhibited somewhat stronger phagocytic and lysosomal enzyme activities than those of the (S) isomer while there was no appreciable difference in the activities between the isomers of GLA-40. Significant cytostasis-inducing activity was observed in stereoisomers tested. All of the isomers showed remarkable antiviral activity against vaccinia virus.

Animals↗
PubMed1986

Role of bradykinin for orthostatic hypotension in diabetes mellitus.

A possible contribution of circulating kinin for orthostatic hypotension (OH) in diabetic patients was investigated using a sensitive RIA of plasma bradykinin (BK). Thirty six diabetics underwent 10 min of orthostasis, in which 20 patients developed OH. The baseline plasma BK was 15.8 +/- 1.8 pg/ml in diabetics with OH, which increased to 31.0 +/- 5.6 pg/ml (p less than 0.05). The basal plasma BK was 19.4 +/- 4.1 and 17.8 +/- 2.3 pg/ml in normal subjects (n = 10) and in diabetics without OH (n = 16), respectively. These values were not significantly different from the diabetics with OH. In response to standing there were no significant changes in plasma BK in both groups. There was a significant correlation between the absolute increment of plasma BK and the decrement of systolic blood pressure (BP) when all diabetic patients were compared (r = -0.364, p less than 0.05). The baseline PRA and plasma norepinephrine (NE) were similar in normal subjects and diabetics with or without OH. In response to standing there were approximately two-fold increases in PRA and plasma NE. There was no significant correlation between plasma NE increment and the fall in systolic BP. These results suggest that kinins may participate in OH in diabetic patients.

Bradykinin↗
PubMed1985

[Do giant negative T waves represent apical hypertrophic cardiomyopathy? Left ventriculographic and cardiac biopsy studies].

Whether giant negative T waves (GNT) of 1 mV or greater represent the electrocardiographic characteristics of idiopathic cardiomyopathy, particularly apical hypertrophic cardiomyopathy, is controversial. To clarify this point, a comparative study was conducted for 57 persons with GNT (GNT+ group) and 57 persons of hypertrophic cardiomyopathy with either asymmetric septal hypertrophy or diffuse hypertrophy of the ventricular wall in the absence of GNT (GNT- group). Patients with cerebral vascular accidents, myocardial infarctions, valvular heart disease, myopericarditis, and implanted pacemakers were excluded from the study because these patients' ECGs may show GNT. Left ventriculograms were investigated at end-diastole in the right anterior oblique projection. The GNT+ group showed a spade-like configuration indicating a marked reduction in the lumen of the apical cavity in 25 cases (43.9%); a kidney or banana-like configuration indicating the inferior wall bulging into the left ventricular cavity in its mid-zone in eight cases (14.0%), and an oval configuration which indicated no deformity of the left ventricular cavity in 24 (42.1%). The spade-like configuration was also seen in four cases (7.0%) of the GNT- group. A study of ventricular wall thicknesses based on left ventriculography showed that 25.5% of cases with GNT did not have concomitant apical hypertrophy. Generally, the GNT+ group cases had a significantly thicker anterior left ventricular wall and apical hypertrophy compared to the GNT- group. The hypertrophic states of the apical wall and anterior wall of the left ventricle correlated well. The GNT+ group included a significantly larger percentage of patients who were middle aged and older than did the GNT- group, and the frequency of accompanying hypertension was significantly higher in the former. The confirmed or suspected familial occurrence of cardiomyopathy (CM) was observed in 32 cases (56.1%) of the GNT- group, and in 18 cases (31.6%) of the GNT+ group, i.e., the incidence was significantly lower in the GNT+ group. In an endomyocardial biopsy study, 40 cases (70.1%) of HCM without GNT had bizarre myocardial hypertrophy with disorganization (BMHD). The incidence of BMHD in the GNT+ group was 21/57 (36.8%)-significantly lower than in the GNT- group. In the GNT- group, there was no significant difference in the incidence of BMHD between relatively young and old patients or between patients with and without accompanying hypertension; whereas, in the GNT+ group, it was significantly lower among those with accompanying hypertension and in older patients than in those without accompanying hypertension and in younger patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1984

[The role of prostaglandins for norepinephrine clearance in borderline hypertension].

Studies were done to determine the role of endogenous prostaglandins (PGs) for norepinephrine (NE) clearance in 10 male borderline hypertensives (BHT) (age: 20-28) and six age-matched male normotensives (NT). Two experimental protocols were followed in these subjects: 10 min orthostasis with blood sampling (protocol I), and 100 ng/kg/min of L-NE infusion for 60 min at supine position. Blood was collected from indwelling catheter at every min for 10 min after stopping the NE infusion (protocol II). Plasma NE was measured by THI method using HPLC. Disappearance curve of plasma NE was analyzed following the two compartment open model. The orthostasis and the steady state NE infusion were repeated after 150 mg/day of indomethacin (Ind) for three days. There were significant increases in plasma NE after orthostasis in both groups: from 180.8 +/- 28.0 pg/ml to 346.2 +/- 78.0 pg/ml (p less than 0.05) in NT and from 120.1 +/- 12.8 pg/ml to 289.6 +/- 20.3 pg/ml (p less than 0.001) in BHT, but there were no significant differences between the two groups. Ind pretreatment did not alter these responses. The calculated half-time of the first exponential phase (T 1/2) was 1.50 +/- 0.07 min in NT which decreased to 0.98 +/- 0.10 min (p less than 0.05) after Ind pretreatment. In BHT, T 1/2 was 1.03 +/- 0.08 min (p less than 0.01 vs NT), which was not significantly changed after Ind. These results may suggest that endogenous PGs have some role(s) in NT for NE clearance, probably exerting inhibitory action on neuronal uptake. In BHT, neuronal uptake of NE is increased, probably due to an adaptation mechanism to elevated blood pressure.

Adult↗
PubMed1984

Circadian rhythm of plasma aldosterone and time dependent alterations of aldosterone regulators.

In order to investigate the relative contribution of ACTH, the renin angiotensin and dopaminergic system to the circadian rhythm of plasma aldosterone, hormone levels were determined at hourly intervals over a 24 h span in four supine healthy men. Blood was withdrawn under basal conditions (control), after either dexamethasone, captopril or bromocriptine++ (CB-154) administration. Plasma aldosterone rhythmicity was abolished in dexamethasone treated groups but not in captopril or CB treated groups. Time dependent alterations of aldosterone regulators were analyzed by multiple regression methods at 3 hourly intervals. These results indicate that plasma aldosterone rhythmicity is predominantly under the control of ACTH whereas the renin angiotensin or dopaminergic system plays a little role. In supine, sodium repleted states, ACTH is a potent stimulus of aldosterone at 000-0600 h and 1700-1900 h clocktime, whereas during daytime renin-angiotensin is an additional regulator.

Adrenocorticotropic Hormone↗
PubMed1984

Role of prostacyclin in blood pressure regulation and aldosterone production in conscious rabbits.

The effects of subdepressor infusion of prostacyclin (PGI2, 5.3 pmol min-1 kg-1) on arterial pressure and aldosterone production induced by angiotensin II (ANG II) were studied in conscious rabbits. Indomethacin pretreatment caused an augmented blood pressure response after ANG II infusion, which returned to near control level after concomitant infusion of a subdepressor dose of PGI2. Aldosterone production after ANG II was significantly attenuated after pretreatment with indomethacin. PGI2 infusion restored this reduced response to near control level. These results may suggest that PGI2 in the circulation could also serve to modulate the pressor and hormonal action(s) of ANG II.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Effects of infection of Eimeria tenella, E. acervulina, and E. maxima upon Salmonella typhimurium infection in chickens.

Three experiments were conducted to examine whether Salmonella typhimurium infection is enhanced by concurrent infection with Eimeria tenella, E. acervulina, or E. maxima. There were two groups in each experiment: birds infected with a daily oral dose of approximately 1 X 10(4) cfu of S. typhimurium for 5 days after coccidial infection and birds infected with S. typhimurium alone with the similar exposure schedule. Chickens were necropsied 7, 10, and 14 days after coccidial infection. The numbers of S. typhimurium in the contents of ceca and small intestine were counted, and numbers of chickens positive for S. typhimurium in the liver and bile were examined. In E. tenella infection, the S. typhimurium counts in the ceca and small intestine of concurrently infected chickens were significantly greater than those of birds infected with S. typhimurium alone. In E. acervulina infection, the S. typhimurium counts in the ceca of chickens killed 14 days after E. acervulina infection and the numbers of birds positive for S. typhimurium in the ceca of chickens killed 10 and 14 days after E. acervulina infection were significantly greater than those of chickens infected with S. typhimurium alone. In E. maxima infection, the numbers of birds positive for S. typhimurium in the ceca and liver of chickens killed 7 days after E. maxima infection were significantly greater than those of birds infected with S. typhimurium alone. Results of this study indicate that infection with E. acervulina or E. maxima is able to enhance S. typhimurium infection in chickens.

Animals↗