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Biomedical subjects

F Yamaguchi

Publications and source records attributed to F Yamaguchi.

At least 73 records · Page 4Linked to original sources
PubMed1991

Transgenic mice for the amyloid precursor protein 695 isoform have impaired spatial memory.

Transgenic mice for the human amyloid precursor protein 695 (APP695) isoform may provide an animal model of Alzheimer's disease (AD). To evaluate this, the spatial learning abilities of transgenic and wild strain mice were compared in the Morris water maze task. The transgenic mice were significantly retarded in initial learning and in learning a new escape location, although in each case they eventually reached control levels. The transgenic mice also showed slower swimming speed and reduced nocturnal activity, which may contribute to their deficit in spatial learning. Preliminary neuropathological investigations failed to reveal amyloid depositions. Thus, a gene dosage effect of APP695 may account for the memory impairment but not the plaque formation associated with AD.

Amyloid beta-Peptides↗
PubMed1991

Anti-thyroid peroxidase antibodies in sera from healthy subjects and from patients with chronic thyroiditis: differences in the ability to inhibit thyroid peroxidase activities.

A significant percentage (6.4%) of healthy subjects was found to contain anti-thyroid peroxidase (TPO) antibodies in their sera. However, in contrast with IgG from sera of patients with chronic thyroiditis, IgG from sera of healthy subjects did not inhibit TPO activities both in guaiacol and iodide assays. In addition, anti-TPO antibodies from healthy subjects did not block the inhibition of enzyme activities by anti-TPO antibodies from patients. These findings suggest that anti-TPO antibodies from healthy subjects do not bind to the epitopes relating to substrate-combining sites of TPO. Thus, the specificities of anti-TPO antibodies in healthy subjects may differ from those in cases of chronic thyroiditis.

Adult↗
PubMed1990

Insulin-like growth factor I (IGF-I) distribution in the tissue and extracellular compartment in different regions of rat brain.

The regional distribution of insulin-like growth factor I (IGF-I) was examined in the tissue and extracellular compartment of rat brain. The tissue content of IGF-I was the highest in the pituitary gland, followed by the olfactory bulb, upper brainstem, cerebellum, striatum, hippocampus, lower brainstem, and cerebral cortex. The extracellular concentration was studied by intracerebral microdialysis technique, and the highest content was found in the hippocampus, followed by the olfactory bulb, hypothalamus, cerebellum, striatum, and cerebral cortex. The tissue and extracellular contents were significantly correlated in the olfactory bulb, hypothalamus, cerebellum, striatum, and cerebral cortex. IGF-I might act by paracrine and/or autocrine regulatory mechanisms in these regions.

Animals↗
PubMed1990

Phototoxic potential of quinolone antibacterial agents in Balb/c mice.

The phototoxic potentials of quinolone antibacterial agents were investigated in Balb/c strain mice. The mice were orally administered nalidixic acid (NA), enoxacin (ENX), ofloxacin (OFLX), ciprofloxacin (CPFX), lomefloxacin (LMFX) and DR-3355 (s-isomer of OFLX), and immediately exposed to ultraviolet-A (UVA) for 4 h (21.6 joules/cm2). The ears were examined for overt damage, as a major phototoxic parameter, 0, 24 and 48 h after irradiation ended. At doses of 200 mg/kg, LMFX, NA and ENX caused marked cutaneous phototoxic reactions on the ears, whereas CPFX, OFLX and DR-3355 caused none. At 800 mg/kg, however, CPFX, OFLX and DR-3355 also caused phototoxic reactions on the ears. These phototoxic changes were characterized grossly by erythema, and histopathologically by edema and infiltration of inflammatory cells, especially neutrophils, into the connective tissue surrounding the cartilage. The 50% erythema-inducing doses of LMFX, ENX, NA, OFLX, DR-3355 and CPFX were calculated at 19, 102, 143, 553, 619 and 741 mg/kg, respectively. Thus, the phototoxic potencies of the quinolones tested were: LMFX greater than ENX, NA greater than OFLX, DR-3355, CPFX.

4-Quinolones↗
PubMed1990

In vivo analysis of extracellular proteins in rat brains with a newly developed intracerebral microdialysis probe.

Peptides and proteins in the extracellular space in the central nervous system were investigated in vivo using an intracerebral microdialysis probe. The molecular cut-off of the hollow fiber which was used for the probe was approximately 100 kDa. We examined recovery rates of several compounds in vitro. The recovery rates of proteins and peptides were between 7-28%, with the exceptions of substance P and insulin-like growth factor I. The recovery rates of monoamines and their metabolites were 22-40%. In in vivo studies, two major proteins with apparent molecular weights of 62 kDa and 12 kDa, and several minor proteins (28 kDa, 43 kDa, 52 kDa and 70 kDa) were detected by SDS-polyacrylamide gel electrophoresis in the dialysate from a probe implanted in the striatum of anesthetized rats. These results suggest that the newly developed, intracerebral microdialysis probe might be useful for investigating the dynamic changes of peptides and proteins in the central nervous system.

Animals↗
PubMed1990

Stimulation of macrophages by muroctasin to produce colony-stimulating factors.

Murocatasin (N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine, MDP-Lys(L18], a muramyl dipeptide derivative, has been reported to increase the number of peripheral granulocytes and monocytes after subcutaneous administration to animals and humans. When macrophage cell lines such as P388D1 and J774.1 cells were incubated with muroctasin in vitro, the production of colony-stimulating factor (CSF) from these cells was increased significantly. By Northern blot analysis, expression of the M-CSF gene, but not the G-CSF gene, in these macrophage cell lines was found to be enhanced by treatment with muroctasin. However, expression of the G-CSF gene in NFSA cells, a fibrosarcoma cell line established as a G-CSF producer, was actually enhanced by incubation with the conditioned medium from P388D1 cells stimulated with muroctasin. Thus, the hematopoietic activity of muroctasin was suggested to be attributable primarily to the enhanced production of M-CSF from macrophages. The enhanced G-CSF production from NFSA cells may be due at least to interleukin-1 released from muroctasin-stimulated macrophages.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

[A case of intracranial hypoglossal neurinoma with no preoperative hypoglossal nerve palsy].

A case of intracranial hypoglossal neurinoma without hypoglossal nerve palsy is reported. A 43-year-old housewife was admitted to our hospital with vertigo and left occipital headache. Neurologically, no cranial nerve deficits were present. CT scan and cerebral angiography showed a mass in the lower left posterior fossa. MRI also revealed a well circumscribed extra-axial mass compressing brain stem and cerebellum to the right. Left suboccipital craniotomy was performed and the tumor was removed subtotally. From the operative findings, the 8th to 11th cranial nerves were not related to the tumor, however, the origin of the tumor was not confirmed. The histology showed Antoni A type neurinoma mixed partially with Antoni B type. After the operation, the tongue deviation appeared to the left, but no other cranial nerve deficit was noticed. Post-operative neuroradiological reexaminations defined slight enlargement of the hypoglossal canal. Then, we concluded that the origin of the tumor must have been the hypoglossal nerve. Most intracranial hypoglossal neurinoma grow in the hypoglossal canal followed by enlargement or erosion of the hypoglossal canal. The author thought that this case suggests that this hypoglossal neurinoma originated from a few rootlets of hypoglossal nerve and grew mainly between the medulla and the hypoglossal canal.

Adult↗
PubMed1989

Studies on experimental conditions for detecting phototoxic potentials of drugs in Balb/c mice.

This study was designed to establish a procedure for detecting the phototoxicity of drugs in an animal model. Experimental conditions in relation to intensity distribution of ultraviolet-A (UVA), duration of irradiation, and suitable region for irradiation were investigated. One black light gave a wide constant-energy region when the distance from the light source to the irradiation area was 15 cm. The intensity distribution of a bank of 10 black lights formed a pattern like the contour map of a truncated cone in the irradiation area. In phototoxic studies, Balb/c strain mice were orally administered chlorpromazine and nalidixic acid, clinically known as photosensitizers, and were immediately exposed to UVA irradiation. The optimal irradiation time was 4 hours at an energy of 20 Joules/cm2, which with a high frequency caused erythema on the surface of the ears in the central area, which received about 1.5 mW/sec.cm2, but no reaction occurred in the surrounding area (0.5-0.8 mW/sec.cm2). These results indicate that it is important to select a suitable irradiation area and sufficient intensity of irradiation in order to determine whether a drug has phototoxic potential.

Animals↗
PubMed1989

[Convulsions observed during administration of antidepressants].

We investigated the incidence of convulsions observed during treatment with antidepressants. Among the patients observed in this department, 582 cases received the antidepressants for more than 2 months were selected. 8 cases (1. 4%) of these patients showed convulsions. Detailed evaluation revealed a high incidence of convulsions occurred in patients who were administered more than two kinds of antidepressants. Among tetracyclic antidepressants, viz. maprotiline and clomipamine, and tricyclic antidepressants, viz. amitriptyline indicated a high incidence rate of convulsions. On the contrary, mianserin and imipramine tended to show a lower incidence. In 4 cases, acute toxic symptoms were seen before the convulsion, and the serum concentration of antidepressants in these patients was high. If toxic symptoms and elevated level of serum concentration are useful indicator for prediction of convulsion by treatment with antidepressants, these might be a noteworthy clinical findings. At present, if doctors are required to administer more than moderate amounts of more than two antidepressants, careful administration is desirable. With the accumulation of such cases, it is necessary to obtain further evaluation of the relationship between toxic symptoms and serum concentration of antidepressants.

Adult↗
PubMed1988

Antigenicity study of muroctasin.

Antigenicity study of N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysi++ + ne (MDP-Lys(L18), muroctasin) was carried out in mice, guinea pigs and rabbits with passive cutaneous anaphylaxis (PCA), systemic anaphylaxis (SA), Arthus and delayed skin reaction and enzyme-linked immunosorbent assay (ELISA). Mice were sensitized intraperitoneally, twice at 3-week intervals, with MDP-Lys(L18) (40, 400 or 4000 micrograms/kg) or MDP-Lys(L18)-ovalbumin (OA) conjugate (500 micrograms/kg) in alumina gel. No IgE antibodies to MDP-Lys(L18) were detected in the sera obtained from the sensitized mice by 24-h PCA in rat. Guinea pigs were sensitized subcutaneously with MDP-Lys(L18) (4, 40 or 400 micrograms/kg) or MDP-Lys(L18)-OA (2 mg/kg) emulsified in Freund's complete and incomplete adjuvant, 3 times at 2-week intervals. No SA was observed in the sensitized animals after the intravenous injection of MDP-Lys(L18) (1 mg/kg). Rabbits were sensitized subcutaneously with MDP-Lys(L18) (2 or 20 micrograms/kg) or MDP-Lys(L18)-OA (2 mg/kg) emulsified in Freund's incomplete adjuvant, 3 times at 2-week intervals. Neither Arthus nor delayed skin reaction was observed in the sensitized animals after the intradermal injection of MDP-Lys(L18) (2 micrograms/site). Although antibodies to MDP-Lys(L18) were not detected in MDP-Lys(L18) sensitized animals, the antibodies were detected in two out of 9 guinea pigs and all of the rabbits in the MDP-Lys(L18)-OA sensitized groups by 4-h PCA after the intravenous injection of MDP-Lys(L18) (1 mg/kg). These results suggest that MDP-Lys(L18) may possess antigenic potential by PCA reaction in guinea pigs.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Phase I study and clinical pharmacological study of muroctasin.

In a first part a phase I clinical study on the immunomodulator N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin) in male healthy volunteers was performed to assess safety, immunological activities, and preliminary pharmacokinetics of the drug by subcutaneous administration. 1. Safety Slight increase (38 degrees C) in body temperature was observed in a high-dose group by subcutaneous administration. Redness was noted as a change in the injection site, but no dose-dependency was seen in this respect. No other noticeable subjective nor objective symptoms were detected. On the other hand, positive C-reactive protein (CRP) (1 case out of 35) and slight increase in gamma-glutamyl transpeptidase (gamma-GTP, 1 case out of 35) associated with the use of this drug were observed. But the causal relationship of gamma-GTP with this drug was not clear because the finding returned to normal value during the treatment. 2. Immunological activities and leucocyte count Mitogenic responses of lymphocytes were augmented after subcutaneous administration of this drug. Increase in peripheral leukocyte count was also observed. This was due to the increase in neutrophil count. 3. Pharmacokinetics Pharmacokinetic parameters (maximum serum levels, area under serum concentration-time curve, time to reach maximum blood level, biological half-life) were obtained after a single administration of 400 micrograms: Cmax: 6.93 +/- 1.32 ng/ml (mean +/- SE), AUC: 37.22 +/- 6.51 ng/ml/h, tmax: 1.32 +/- 0.26 h and t1/2: 2.7 +/- 0.8 h. The safety of subcutaneous administration of MDP-Lys (L18) injection has been confirmed in 35 male healthy volunteers. It was suggested that adequate doses for phase II studies in patients were 200 micrograms to 400 micrograms. In a second part a clinical pharmacological study (single subcutaneous administrations of 100 micrograms and 200 micrograms and multiple 5 day subcutaneous administration of 200 micrograms of MDP-Lys (L18) was performed on male healthy volunteers to assess pharmacokinetics, effect on leukocyte function and on immune system, and safety: 1. Pharmacokinetics a) serum concentration after single administration Cmax in 100 micrograms and 200 micrograms were 1.48 and 2.78 ng/ml, respectively. The AUC values were 6.71 and 15.62 ng/ml/h, respectively, with dose dependency.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Induction of colony-stimulating factor and stimulation of stem cell proliferation by injection of muroctasin.

Modulation of myelopoiesis by anomeric mixture of N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutamyl]-N6-stearoyl-L-lysin e (MDP-Lys(L18), muroctasin), a muramyl dipeptide analog, was investigated in mice. When BDF1 mice were subcutaneously treated with a single dose of 100 micrograms of MDP-Lys(L18), an increase in the number of peripheral blood leukocytes, a rise in the serum levels of colony-stimulating factor (CSF), proliferation of multipotential stem cells in the bone marrow and the spleen, and an expansion of granulocyte-macrophage progenitors in the bone marrow were observed. These findings suggest that the increase in the number of peripheral blood leukocytes in BDF1 mice by MDP-Lys(L18) is due to CSF production and stimulation of stem cell proliferation.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Production of colony-stimulating factor from macrophages by muroctasin.

The effect of a muramyl dipeptide analog, N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutamyl]-N6-stearoyl-L-lysin e (MDP-Lys(L18), muroctasin), on the colony-stimulating factor (CSF) production was investigated in vitro. MDP-Lys(L18) stimulated murine peritoneal macrophages to induce CSF. However, the compound produced more CSF in the presence of both macrophages and T cell enriched fraction than in the absence of T cells. This phenomenon was found to be attributed to the fact that MDP-Lys(L18) also stimulated macrophages to induce interleukin 1 (IL-1) and the IL-1 induced CSF production by T cells. These findings suggest that macrophages may be the first target cells of MDP-Lys(L18) to produce CSF.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Beneficial effect of muroctasin on experimental leukopenia induced by cyclophosphamide or irradiation in mice.

Subcutaneous injection of N2-[N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin), a synthetic muramyl dipeptide derivative, favoured recovery of mice from experimental leukopenia induced by cyclophosphamide or by irradiation with X-rays. These effects were observed only when MDP-Lys(L18) treatment occurred after cyclophosphamide injection or X-ray irradiation. Prophylactic treatment resulted in neither preventive nor restorative efficacy on leukopenia. In contrast, glutathione was hardly effective on leukopenia in both models, irrespective of treatment timing. The restorative efficacy of muroctasin was found to be dose-dependent and to be attributable at least to its augmenting effect on colony-stimulating factor production, followed by the marked proliferation and differentiation of myeloblasts towards mature granulocytes in the bone marrow. These beneficial effects of MDP-Lys(L18) warrant further evaluation of its clinical usefulness.

Acetylmuramyl-Alanyl-Isoglutamine↗