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Biomedical subjects

Y Ohtsubo

Publications and source records attributed to Y Ohtsubo.

31 records · Page 2Linked to original sources

Lithium addition to neuroleptic treatment in chronic schizophrenia: a randomized, double-blind, placebo-controlled, cross-over study.

We studied the effect of lithium addition to neuroleptic treatment in chronic schizophrenia, for which contradictory results have been produced in previous studies. Twenty-one chronic schizophrenic inpatients received lithium in a study with randomized, double-blind, placebo-controlled, cross-over design consisting of 8 weeks each of treatment with lithium capsules and identical placebo capsules. The total Brief Psychiatric Rating Scale (BPRS) scores at week 8 of the lithium treatment were improved significantly compared with those at week 8 of the placebo treatment. Of the BPRS subscales, however, only anxiety-depression improved, whereas none of the subscales for anergia, thought disturbance, activation and hostile-suspiciousness improved. There was no significant difference between the total Scale for the Assessment of Negative Symptoms (SANS) scores at any time during lithium and placebo treatment. These results suggest that the addition of lithium to neuroleptic treatment improves anxiety-depression in chronic schizophrenia.

Adult↗

Pseudomonas fluorescens KKL101, a benzoic acid degrader in a mixed culture that degrades biphenyl and polychlorinated biphenyls.

A mixed culture we had isolated, which degrades biphenyl/polychlorinated biphenyls, is composed of two strains, Pseudomonas fluorescens KKL101 and Pseudomonas sp. strain KKS102. KKS102 produces benzoic acid as a dead-end metabolite in the degradation of biphenyl. In this study we showed that KKL101 grew on benzoic acid as a sole source of carbon. This indicated a role of KKS102 in the growth of KKL101 and KKL101 for the growth of KKS102 in the mixed culture.

Bacteriological Techniques↗

Control of in vivo fate of albumin derivatives utilizing combined chemical modification.

Three types of bovine serum albumin (BSA) derivatives such as lactosylated BSA (LBSA), mannosylated BSA (Man-BSA), and cationized BSA (cBSA) were synthesized and their hepatic disposition characteristics in mice were evaluated by pharmacokinetic analysis. At lower doses (< or = 1 mg/kg), LBSA and Man-BSA were very rapidly eliminated from the blood circulation due to uptake by parenchymal and nonparenchymal cells of the liver, respectively, via receptor-mediated endocytosis (Nishikawa et al., 1992; Nishida et al., 1991a, b). These uptake processes were nonlinear and the apparent hepatic uptake clearances (CLliver) were decreased at administered doses higher than 1 mg/kg, e.g. 10, 20, and 100 mg/kg. The liver accumulation of cBSA was also nonlinear, but its binding and/or uptake capacity in the liver was larger than those of LBSA and Man-BSA; i.e., CLliver decreased at doses higher than 20 mg/kg. In the next step, we modified these BSA derivatives by attaching polyethylene glycol (PEG), a modifier known to reduce the hepatic uptake and increase plasma retention, to achieve precise control of the in vivo disposition characteristics of BSA derivatives. By conjugation with PEG having a molecular weight of 10 kDa, the CLliver values of LBSA, Man-BSA, and cBSA were decreasing to one-seventh, one-fortyfifth, and one-onehundredthirtieth, respectively. However, liver accumulation of PEG modified LBSA and Man-BSA at 24 h after i.v. injection was not significantly different from unmodified BSA derivatives. These results suggest that it is possible to control the hepatic uptake of protein drugs by a combination of introduction of charge or sugar moieties and PEG conjugation.

Animals↗

[Avascular necrosis in the femoral heads of spontaneously hypertensive rats--a study on differing incidence between the sexes].

The author investigated the influence of sexual glands and testosterone on the incidence of femoral head lesions, those are osteonecrosis or ossification disturbance in the femoral heads, of spontaneously hypertensive rats (SHR). The rats were divided into the following six experimental groups: 1) untreated males (I M group); 2) castrated males (II M group); 3) castrated males treated with testosterone (III M group); 4) untreated females (I F group); 5) ovariectomized females (II F group); and 6) ovariectomized females treated with testosterone (III F group). We then compared the incidence of lesions in the 20 femoral heads in each group. There were 18, 5, 16, 6, 9, and 10 lesions in the I M, II M, III M, I F, II F and III F groups, respectively. The incidence was remarkably high in the I M group and III M group. Moreover, the incidence of abnormal findings in the growth plate of the femoral heads showed a pattern similar to that of the femoral head lesions. The above findings suggest a difference in the incidence of femoral head lesions between the sexes results from the effect of testosterone on the growth plate.

Animals↗

Growth inhibition of tumour cells by a liposome-encapsulated, mycolic acid-containing glycolipid, trehalose 2,3,6'-trimycolate.

In vivo growth of syngeneic tumour cells in the peritoneal cavity was strongly inhibited by intraperitoneal injection of a liposome-encapsulated, mycolic acid-containing glycolipid, trehalose 2,3,6'-trimycolate (TTM), derived from a non-pathogenic, acid-fast bacterium. Gordona aurantiaca. Peritoneal macrophages from mice after this treatment lysed tumour cells in vitro at a low effector/target ratio, and their culture supernatant inhibited tumour cell growth. The supernatant inhibited growth of not only tumour necrosis factor (TNF)-sensitive tumour cells, but also TNF-insensitive tumour cells. This inhibitory activity was enhanced by addition of lipopolysaccharide (LPS) to the culture medium of the macrophages. The macrophages released more superoxide (O2-), TNF and interleukin-1 (IL-1) on LPS triggering, and the releases of these compounds were further increased by addition of recombinant interferon-gamma (IFN-gamma) to the medium. Moreover, splenic T cells of TTM liposome-primed mice were found to produce eight times more IFN-gamma upon stimulation with LPS. These results indicated that priming with TTM liposomes resulted in strong activation of macrophages, which lysed tumour cells directly and also inhibited tumour cell growth by released factors.

Animals↗

Induction of interferons (IFNs) and tumor necrosis factor (TNF) in mice by a novel glycolipid trehalose 2,3,6'-trimycolate from Rhodococcus aurantiacus (Gordona aurantiaca).

The immunomodifying activity of a novel mycoloyl glycolipid, trehalose 2,3,6'-trimycolate (GaGM), from a unique psychrophilic acid-fast bacterium, Rhodococcus aurantiacus, was examined. ICR mice were primed intravenously (i.v.) or intraperitoneally (i.p.) with liposomes containing GaGM (300 micrograms/mouse), and were administered LPS dissolved in saline (25 micrograms/mouse, i.v.) 2 weeks later. Two hours after injection of LPS, interferons (IFNs) and tumor necrosis factor (TNF) were induced significantly in mice sera. The increase in activities of IFNs and TNF was approximately paralleled with granuloma formation in spleen of mice primed with GaGM. However, IFNs and TNF were not induced either in mice primed with GaGM but not elicited with LPS, or in those primed with GaGM and elicited by GaGM. Both activities induced were lower in mice primed with trehalose mono- or dimycolate from R. aurantiacus (GaTMM, GaTDM) or TDM from Nocardia rubra than in GaGM-primed mice. Time course study showed that the maximum activity of each interferon (alpha, beta, or gamma) was observed at different stages after LPS administration; IFN-alpha, IFN-beta, and IFN-gamma appeared 3, 2, and 6 hours most abundantly after LPS administration, respectively.

Animals↗

Induction of tumoricidal activated macrophages by a liposome-encapsulated glycolipid, trehalose 2,3,6'-trimycolate from Gordona aurantiaca.

A mycolic acid-containing glycolipid, trehalose 2,3,6'-trimycolate, prepared from a non-pathogenic acid-fast bacterium Gordona aurantiaca, was shown to induce strong tumoricidal activity in peritoneal exudate cells by intravenous or intraperitoneal injection of liposome-encapsulated preparations. The mycolic acid derivative containing a high proportion of unsaturated fatty acids rendered macrophages cytotoxic against syngeneic mastocytoma cells in the absence of endotoxin, for over 14 days after the injection. The macrophages were ascertained to be at low intracellular levels of a lysosomal enzyme beta-galactosidase and an ectoenzyme alkaline phosphodiesterase, a specific pattern as previously described for "primed macrophages". However the culture supernatants of the peritoneal exudate cells were not cytotoxic.

Adjuvants, Immunologic↗

[Disturbance of the autonomic nerve system in patients with chronic renal failure--represented by variation coefficient of R-R intervals in the ECG as a parameter].

Autonomic nerve dysfunction in patients with chronic renal failure has of late become an issue to be investigated. R-R intervals in resting electrocardiograms were measured to evaluate activities of the cardiac parasympathetic nerve system. A total of 140 patients with chronic renal failure were studied to be compared with 20 normal controls (cont.) and 39 with diabetes mellitus (DM). Of these patients 15 were subjected to conservative treatment (CRF), while 125 patients were undergoing hemodialysis due to chronic renal failure-100 of them derived from chronic glomerulonephritis (HD) and 25 from diabetes mellitus (DM.HD). The variation coefficient of the R-R interval (CVRR) was measured after the subject patients had rested for over 15 minutes before a dialysis session. The mean CVRR were 2.15 +/- 1.25% in CRF group, 2.36 +/- 1.37% in HD and 1.37 +/- 0.99% in DM.HD. These values were significantly lower than in control group (4.70 +/- 2.64%). On the other hand, the value in DM.HD group, as shown above, was significantly lower than in HD. In CRF group the CVRR values lowered as residual renal functions decreased. No significant correlations between CVRR S and the duration of hemodialysis treatment were noted among the groups. In HD group the CVRR S were significantly lower in patients with hypotensive tendency during hemodialysis than in those who enjoyed good control of blood pressure. These results suggest that the measurement of CVRR S can be of help in evaluating autonomic nerve dysfunction in patients with chronic renal failure.

Adult↗

[An immune adjuvant activity of mycolic acid-containing glycolipid, trehalose-2,3,6'-trimycolate, derived from Gordona aurantiaca].

A mycolic acid-containing glycolipid, trehalose-2,3,6'-trimycolate (GaGM), derived from Gordona aurantiaca, an acid-fast bacterium closely related taxonomically to Mycobacterium, was investigated for its immune adjuvant activity on cell-mediated responses in the mouse. I.V. injection of liposomes containing GaGM enhanced the generation of cytotoxic T-lymphocyte (CTL) against syngeneic and allogeneic tumor cells. In addition, the injection of GaGM augmented the natural killer (NK) activity and the antibody-dependent cellular cytotoxicity (ADCC). These results suggest that the injection of GaGM induces the production of interleukin-2 (IL-2), since such effector cells as CTL, NK and K cells have been shown to require IL-2 for their development.

Adjuvants, Immunologic↗

[In vitro activation of immune cells by a mycolic acid-containing glycolipid, trehalose-2,3,6'-trimycolate, derived from Gordona aurantiaca].

A mycolic acid-containing glycolipid, trehalose-2,3,6'-trimycolate (GaGM), derived from Gordona aurantiaca, an acid-fast bacteria closely related taxonomically to Mycobacterium, was investigated for its immune adjuvant activity in vitro. The liposomes containing GaGM showed strong mitogenic effects on murine spleen cells at the doses used (25-100 micrograms/ml), but not on T-cell-depleted spleen cells or macrophage-depleted spleen cells. These results suggest that the mitogenic property of liposomes containing GaGM differs from that of such as lipopolysaccharide, a B-cell mitogen and that its mitogenic effects depend on the presence of macrophages. In addition, liposomes containing GaGM augmented the mixed lymphocyte reaction (MLR) and in vitro induction of cytotoxic T-lymphocytes (CTLs) against allogeneic tumor cells. These results suggest that liposomes containing GaGM have immune adjuvant properties in vitro and the adjuvant activity may be related to such cytokines as interleukin-1 and -2.

Adjuvants, Immunologic↗

Short- and long-term effects of nisoldipine on cardiac function and exercise tolerance in patients with hypertrophic cardiomyopathy.

UNLABELLED: Nisoldipine is a second generation dihydropyridine calcium antagonist having characteristics of strong coronary artery dilating effect and less negative inotropic action. The purpose of this study was to evaluate the effect of nisoldipine on the cardiac function (systolic and diastolic) and the exercise tolerance, in patients with hypertrophic cardiomyopathy (HCM). SUBJECTS: Twenty-three patients with HCM were studied. METHODS: We measured the following indices using M-mode and pulsed wave Doppler echocardiography before and after nisoldipine therapy; left ventricular fractional shortening (LVFS), isometric relaxation time (IRT), deceleration half-time (DHT) of early diastolic mitral (E) flow, late diastolic mitral (A) flow and A/E ratio. Symptom-limited treadmill exercise test was performed. Exercise tolerance (EX) time was measured. Nisoldipine of 10 mg/day was orally administered. Same tests were repeated on day 14 and after 6 months. RESULTS: 1) Short-term effects; LVFS did not change (55.9 +/- 5.9%-->57.0 +/- 7.4%, NS) after 2 weeks. However, LV diastolic function significantly improved (IRT; 92.1 +/- 7.7 ms-->85.2 +/- 11.6 ms, p < 0.05, DHT; 70.7 +/- 16.2 ms-->63.3 +/- 3.7 ms, p < 0.05). EX time increased (8.9 +/- 2.6 min-->10.0 +/- 3.3 min, p < 0.05), 2) Long-term effects; LV diastolic function had a tendency toward improvement, but is statistically not significant (IRT; 91.1 +/- 7.6-->83.8 +/- 11.6 ms, DHT; 73.1 +/- 23.4-->61.0 +/- 11.4 ms, A/E; 1.26 +/- 0.29-->1.11 +/- 0.36) after 6 months. EX time was significantly increased (9.4 +/- 1.7--> 10.1 +/- 1.7 min, p < 0.05). CONCLUSIONS: Nisoldipine improved LV diastolic dysfunction and exercise tolerance in patients with HCM. These effects were similar to the first generation calcium antagonists. LV diastolic dysfunction may be improved due to the reduction of intracellular calcium concentration and the relief of myocardial ischemia by strong coronary artery dilating effect. However, nisoldipine did not affect the LV systolic function because of its less negative inotropic effect.

Adult↗