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Biomedical subjects

M Yamamura

Publications and source records attributed to M Yamamura.

At least 289 records · Page 16Linked to original sources

Native and induced rat kidney metallothioneins and their relation to cadmium toxicity.

The concentrations of zinc, copper, iron, manganese, magnesium, and phosphorus in the kidneys were determined for control female rats of five different ages (4, 8, 12, 16, and 20 weeks old). The concentration of copper increased with age and it was attributed to three metallothionein peaks on a SW 3000 column. Parenteral administration of Cd-thionein caused swelling of kidneys to different degrees, depending on the age of the rats; the youngest rats were affected most. The concentrations of cadmium and the six metals in the kidneys at 12 hr and 7 days after injection were determined and compared with controls. The distribution among protein fractions of cadmium, zinc, and copper, which are related to metallothionein, were examined by gel permeation chromatography. The elution profiles of the three metals changed not only with the ages of the rats but also with time after injection. The changes were correlated with the copper content in the metallothioneins and with swelling of the kidneys. The changes also correlated with native metallothionein levels.

Aging↗

Distribution of cadmium in heavily cadmium-accumulated rat liver cytosols: metallothionein and related cadmium-binding proteins.

Distribution profiles of cadmium (Cd) in the cytosols of livers prepared from repeatedly Cd-injected rats (3.0 mg Cd/kg body weight, 4 times a week for 1, 2, 3, or 4 weeks) were characterized by high-performance liquid chromatography with a flame atomic absorption spectrophotometer (HPLC-AAS). The accumulation of Cd and decrease of relative zinc (Zn) to Cd ratio in metallothionein were accompanied by the change of distribution profile of Cd in the cytosol fraction. Cd distributed to the heat-unstable high molecular weight proteins was assumed to be non-selectively bound free Cd and a toxic chemical form. Two kinds of heat-stable Cd-binding proteins other than metallothionein increased with the accumulation of Cd; one was metallothionein dimers, and the other was thought to be Cd-binding proteins of shorter amino acid chain than metallothionein and related to metallothionein.

Animals↗

[Effects of afloqualone, a new centrally acting muscle relaxant, on DRL response and CER in rats (author's transl)].

In gross-behavioral observations, chlordiazepoxide, diazepam, meprobamate, and pentobarbital-Na produced excitatory behavior at 5 and 10, 1 and 2, 100 and 200, and 10 and 20 mg/kg p.o., respectively whereas afloqualone produced no excitatory behavior at doses up to 20 mg/kg p.o., these doses induce muscle relaxation and motor depression. Afloqualone depressed DRL response at 10 and 20 mg/kg p.o. Similar effects were seen with chlorpromazine (5, 10, 20 mg/kg p.o.). Chlordiazepoxide, meprobamate, and pentobarbital-Na facilitated DRL response at doses producing excitatory behavior. Methamphetamine (0.5, 1, 2 mg/kg p.o.) facilitated the response, dose-dependently. In CER, chlordiazepoxide (5, 10, 20 mg/kg p.o.), diazepam (1, 2, 5 mg/kg p.o.), and meprobamate (50, 100, 200 mg/kg p.o.) dose-dependently increased the response during the alarm period, regardless of the response during the safe period. Pentobarbital-Na (5, 10, 20 mg/kg p.o.) had much the same effect. Afloqualone slightly increased the response during the alarm period in one out of 3 rats at 5, 10, and 20 mg/kg p.o., respectively. Chlorpromazine and methamphetamine had no influence on the response during the alarm period at doses up to 20 and 2 mg/kg p.o., respectively. These results suggest that the pharmacological properties of afloqualone, as related to behavior differ from those of anti-anxiety drugs, hypnotics, and stimulants.

Animals↗

HLA-D/DR linked immune response to Candida allergen: an in vivo and in vitro study in Japanese.

Immune response to Candida allergen in man was studied using the lymphocyte reaction in vitro and the skin test in vivo. One hundred and ten normal healthy Japanese were typed for HLA-A, B, D and DR. It was found that HLA-B7, Dw1 and DR1 were strongly associated with high responsiveness and Den and Mt2 with low responsiveness. In a family study, the inheritance of high responsiveness was observed. In the reaction patterns of HLA-D homozygote and heterozygote cells, it was found that Dw1/DR1 and Dw12/DR2 were associated with a high responders and that DYT/DR4 and DEn (6.1)/DR- were associated with low responders. It is considered that the Dw1/DRl gene might be more dominant as an immune response; the Ir gene when compared to a gene such as the DYT, and the EDn (6.1) as an immune suppressive; Is gene. A genetic factor can be implicated in the secondary response (but not the primary response) to Candida allergen. Therefore, the existence of HLA-linked Ir and/or Is gene to Candida allergen is discussed.

Adult↗

Role of macrophages in T lymphocyte response to Candida allergen in man with special reference to HLA-D and DR.

Activation of naturally sensitized human T lymphocytes to Candida allergen was studied using three HLA-D and DR heterozygote Japanese cells (Dw1.DR1/DYT.DR4, Dw12.DR2/DYT.DR4, DYT.DR4/DEn.DR blank) and four HLA-D and DR homozygote cells (Dw1.DR1, Dw12.DR2, DYT.DR4, DEn.DR blank). In vitro activation of T lymphocytes to Candida allergen was found to require the presence of autologous or allogeneic compatible HLA-Dw1.DR1 and Dw12.DR2 macrophages.

Antigens, Fungal↗

[General pharmacology of 6-amino-2-fluoromethyl-3-(o-tolyl)-4(3H)-quinazolinone (afloqualone), a new centrally acting muscle relaxant. I. Effects on the central nervous system (author's transl)].

The general pharmacology of afloqualone, a new centrally acting muscle relaxant, in the CNS was examined in mice and rats and findings compared with those of other central muscle relaxants. Afloqualone showed relatively strong hexobarbital and barbital anesthesia potentiating action. Taking into account the dose ratio of anesthesia potentiating action to the muscle relaxing action, however, the potency of anesthesia potentiating action of afloqualone is lower than that of chlormezanone. At doses producing muscle relaxing action, afloqualone inhibited spontaneous motor activity, methamphetamine-induced hypermotility, pentylenetetrazol-, nicotine-, and maximum electroshock-convulsions, fighting episodes in foot-shocked mice, conditioned avoidance response in rat pole-climbing test, and acetic acid-induced writhing syndrome and lowered normal body temperature. The dose ratios of these pharmacological actions to muscle relaxing action of afloqualone, however, were larger than those of chlormezanone and mephenesin. This suggests that the central depressant activity of afloqualone is less potent and the specificity of muscle relaxing action of afloqualone is higher than those of climbing behaviour, physostigmine-induced death, serotonin-induced heat twitch, and reserpine-induced hypothermia, even at 50 mg/kg. Tolperisone showed neither muscle relaxing action nor other central actions when administered orally.

Agonistic Behavior↗

[General pharmacology of 6-amino-2-fluoromethyl-3-(o-tolyl)-4(3H)-quinazolinone (afloqualone), a new centrally acting muscle relaxant. II. Effects on the peripheral system (author's transl)].

The general pharmacology of afloqualone, a new centrally acting muscle relaxant, in the peripheral system, was examined in laboratory animals and findings compared with those of some other central muscle relaxants. Afloqualone dose dependently inhibited respiration, lowered arterial blood pressure, decreased heart rate, and slightly increased femoral and renal arterial blood flow in parallel with hypotension, at doses of 1 or 2 to 20 mg/kg iv. in anesthetized cats. Afloqualone also inhibited cardiac movement in situ in anesthetized rabbits and decreased internal pressure in the urinary bladder in anesthetized cats. In in vitro experiments, afloqualone inhibited spontaneous movements of isolated rabbit atrium and ileum and isolated rat uterus at considerably high concentrations of 10(-6) g/ml or more. Oral administration of afloqualone, however, had no significant influence on respiration, the cardiovascular, digestive, and autonomic nervous systems, and urogenital organs, at doses up to 50 mg/kg except for a comparatively potent inhibitory effect on carrageenin-induced paw edema in rats. Afloqualone induced neither surface nor infiltration anesthesia.

Animals↗

Cadmium-binding proteins induced in the earthworm.

Earthworms, Eisenia foetida, grown in composts of different cadmium concentrations accumulated cadmium in a dose-dependent manner and the cadmium was bound to three different molecular weight cadmium-binding proteins induced in the earthworm. The three proteins were stable to heat treatment and accompanied by a concomitant increase of absorbance at 254 nm and not at 280 nm. Each of the three proteins is a mixture of isoproteins; the molecular weight of one of the three proteins was estimated to be about 7,000 daltons, on the assumption that the cadmium-binding protein is similar in chromatographic properties to metallothionein.

Animals↗

Metabolic fate of earthworm cadmium-binding proteins in rats.

Three different molecular weight cadmium-binding proteins isolated from the earthworm, Eisenia foetida, were injected intraperitoneally into young female rats. Cadmium bound to earthworm protein-I (estimated molecular weight, 63,000-70,000 daltons) and -II (estimated molecular weight about 7,000 daltons) was recovered from the kidney supernatants as metallothionein, which indicated that the proteins were degraded and that the cadmium liberated from the degraded proteins induced metallothionein biosynthesis in the kidneys. However, cadmium bound to earth-worm protein-III (estimated apparent molecular weight about 2,000 daltons) was recovered primarily from urine as a form bound to the protein. Compared with cadmium bound to albumin, metallothionein, and the low molecular weight cadmium-binding protein in Chlorella, the metabolic fates of cadmium bound to the three earthworm proteins were explained by the differences of molecular sizes and stability constants. Induced metallothioneins showed different chromatographic properties with time after injections on a Sephadex G-75 column and on a gel permeation column (TSK GEL SW 3,000).

Animals↗

Decreased copper content in rat kidney metallothionein and its relation to acute cadmium nephropathy.

Repeated s.c. injections of cadmium chloride into rats (3 mg Cd/kg body weight, 4 times a week) caused acute and transitory tubular necrosis after 2 to 3 weeks; recovery was observed after 4 weeks despite continued loading. Kidney copper decreased for the first 3 weeks and was slightly increased after 4 weeks. Distribution profiles of cadmium (Cd), zinc (Zn), copper (Cu) on an SW column revealed that elution profiles of kidney metallothionein changed from typical kidney with high copper content to typical liver metallothioneins with tubular necrosis and restoration.

Animals↗

Induction of zinc-thionein in rat liver and kidneys by zinc loading as studied at isometallothionein levels.

Zinc acetate was injected i.p. into female rats to try to clarify the detailed induction and degradation pathways of zinc-thionein (Zn-th) at isometallothionein levels in liver and kidneys. Injected zinc in serum decreased with the induction of Zn-th in the liver and kidneys, and the amounts of Zn-th in both tissues attained maxima 24 h after injection. The relative ratios of isometallothioneins changed with time in both tissues. The changes are compared with those of cadmium (Cd) loading.

Animals↗