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Biomedical subjects

J Adachi

Publications and source records attributed to J Adachi.

At least 145 records · Page 8Linked to original sources

A clinician's guide for conducting randomized trials in individual patients.

In determining optimal treatment for a patient conventional trials of therapy are susceptible to bias. Large-scale randomized trials can provide only a partial guide and have not been or cannot be carried out for most clinical disorders. However, randomized controlled trials (RCTs) in individual patients (N of 1 RCTs) may in some circumstances provide a solution to this dilemma. In an N of 1 RCT a patient undergoes pairs of treatment periods (one period of each pair with the active drug and one with matched placebo, assigned at random); both the patient and the clinician are blind to allocation, and treatment targets are monitored. N of 1 RCTs are useful for chronic, stable conditions for which the proposed treatment, which has a rapid onset of action and ceases to act soon after it is discontinued, has shown promise in an open trial of therapy. The monitoring of treatment targets usually includes quantitative measurement of the patient's symptoms with the use of simple patient diaries or questionnaires. Pairs of treatment periods are continued until effectiveness is proved or refuted. The cooperation of a pharmacy is required for the preparation of matching placebos and conduct of the trial. Formal statistical analysis may be helpful for interpreting the results. The practical approach presented in this paper allows clinicians to conduct their own N of 1 RCTs.

Clinical Trials as Topic↗

[rdw rats, a new hereditary dwarf model in the rat].

A new hereditary dwarf mutation was found in Csk: Wistar-Imamichi rat breeding colony. The mutant rats and control normal rats were studied with clinical, genetical and histological examination. The result showed that the present mutation was inherited in autosomal recessive trait (gene symbol; rdw) and was provoked with the hypoplasia of pars distalis (anterior pituitary), in particular the secretory cells of GH, PRL and TSH. The characteristics of the present mutant (rdw) was very similar to dw mouse, and was usefull for endocrinological research as an animal model of human pituitary dwarfism.

Animals↗

[Change in the electrical impedance caused by cornification of the epithelial cell layer of the vaginal mucosa in the rat].

The electrical impedance in the vagina (EIV) is significantly high in the proestrus stage compared with other stages of the estrous cycle in rats. Therefore, the EIV can be used to detect the optimum day for mating. The relation between the EIV and the conditions of the epithelial cell layer of vaginal mucosa were investigated. The EIV was at a high level (over 3,000 omega) in vaginas in the proestrus stage in either intact or excised vaginal mucus. But it decreased (under 3,000 omega) after the epithelium of the vaginal mucosa was removed. The EIV of ovariectomized rats was low, but increased after Estradiol administration. The cornification of the epithelial cell layer of the vaginal mucosa occurred concurrently with the high EIV in the proestrus stage and after Estradiol administration. This indicates that the cornification of the epithelial cell layer of the vaginal mucosa may cause the elevation of EIV in the proestrus stage, the optimum day for mating in the rats.

Animals↗

Inherited hydrocephalus in Csk: Wistar-Imamichi rats; Hyd strain: a new disease model for hydrocephalus.

Hydrocephalic rats were found in a breeding colony of Csk: Wistar-Imamichi strain rats. In males, the hydrocephalus were serious and could be detected from 7 days after birth. Survival was 3-4 weeks. In females, the hydrocephalus was moderate, there was no abnormal external appearance, and the rats were able to mature. Ventricular dilatation was excessive in males but moderate in females. The total frequency of hydrocephalus was 34.3% in both males and females. Breeding data indicated that this disease is heritable and is single dominant and X-linked (symbol, Hyd). The female moderate hydrocephalics could be detected by progeny tests without examining brain sections. No evidence of developmental anomaly was observed in the ventricles. This hydrocephalus was classified as being of the communicating type, and this strain was named the Hyd strain as an animal model for human hydrocephalus.

Animals↗

[A method for detecting the optimum day for mating during the 4-day estrous cycle in the rat; measuring the value of electrical impedance of the vagina].

A method for detecting the optimum day for mating in the rat was investigated. Cyclic changes of electrical impedance of vagina (EIV) were studied in the rats. EIV indicated high value (over 3,000 omega) only at proestrus, and it was lower (under 3,000 omega) at other stage of estrous cycle. These results apparently indicate that measuring the EIV made to distinguish proestrus from other phases of estrous cycle. The female caged with male showed high copulation rate (88 approximately 96%) when her EIV had been over 3,000 omega.

Animals↗

Individual and ethnic differences in ethanol elimination.

The effects of polymorphism of aldehyde dehydrogenase (ALDH) and obesity (body weight/lean body mass) on the rate of ethanol elimination were studied. One hundred and forty subjects of healthy Japanese male volunteers who ingested 0.4 g/kg of ethanol were divided into two groups, i.e., a normal ALDH group with a low Km isozyme of ALDH and a deficient group. They were further divided into three groups in which the obesity increased in the order group A, B, C. Ethanol elimination (ER) and beta were significantly higher in the normal ALDH group than in the deficient group. In the normal ALDH subjects, beta of group C(0.187 mg/ml/hr) was higher than that of group B(0.155 mg/ml/hr). No difference in ER was observed among the three groups of the obesity in each ALDH group. Distribution volume of ethanol, r, estimated by Watson's method (0.65 to 0.89) was more accurate than Widmark's r(0.5 to 1.00). Ethanol elimination rate in the normal ALDH subjects was greater than that in Caucasian reported by other authors. Body weight was correlated well with liver weight in 135 autopsy materials.

Adult↗

TPA-induced alteration of actin organization in cultured human keratinocytes.

Distribution of actin filaments of human epidermal keratinocyte in the primary culture was observed by immunofluorescence staining. In the cytoplasm, actin was distributed diffusely, and strong antiactin immunofluorescence was observed along the leading edge, showing ruffling and the contact zone to the neighboring cell. 12-O-Tetradecanoylphorbol-13-acetate (TPA) induced organization of actin filaments. Many short bundles of actin filaments appeared shortly after the addition of 16 nM TPA, and large actin-containing ribbons of crescent-shape, circular or gyrus-like form were sometimes observed. Phorbol-12-13-diacetate, a non-promoter phorbol ester, induced a similar change, but to a much lesser extent. Addition of 1 mM cycloheximide did not interfere with the organization of actin filaments by TPA. La3+ aborted it completely possibly by replacing Ca2+ at the binding site of the cell surface, and the cultivation in low Ca2+ environment suppressed the effect of TPA. These findings make a contrast to those reported in fibroblasts, and may be linked to the characteristic response of cultured human keratinocytes to TPA in the proliferation of cells and induction of ornithine decarboxylase.

Actins↗

[Histological study on the arterial wall of Göttingen miniature swine].

In order to clarify the histological aspects of arterial walls of miniature swine, 41 arterial segments removed from each of 17 Göttingen miniature swines/csk at 6-12 months after birth were examined by light microscopy. Every segment was classified into three types--elastic, transitional, and muscular--according to its histological architecture. Each type was identified on the basis of relative volume and disposition of elastic tissues, collagenous fibers, and smooth muscles in three coats, Tunica intima, Tunica media, Tunica externa. The distribution of each type was demonstrated in a transition from the elastic to the muscular type. The transitional type was designated as a representative type of artery in transitional regions between elastic and muscular types and had some characteristic structures like a mixture of both of them. This type also had longer regions in the back district with the heart as the starting point, such as the Aorta abdominalis, than that of the front. Every artery belonging to the three types had some different structures at different levels, respectively. It was supposed that the histological arrangement of tissues in the walls of a vessel from various parts of the arterial tree would respond properly to the functional demand.

Animals↗

[Göttingen miniature swine as a model for diet-induced atherosclerosis].

Twenty-four Göttingen Miniature Swine/csk, in order to evaluate their potential usefulness as a model for experimental atherosclerosis studies, were fed diets of three types, a high-fat plus high cholesterol diet, a high-fat diet, and a commercial diet. Each group consisted of 4 males and 4 females. Swine fed the experimental diet were investigated by gross, microscopic and serum biochemical examination on the 1st, 3rd, 6th and 9th month after start of experimentation. Lesions of atherosclerosis were observed in the high-fat plus high-cholesterol diet group. After a month on the experimental diet, intimal thickening was detected in the abdominal aorta just above the origin of internal iliac artery, left coronary artery and ascending aorta by microscopic examination. Thereafter, on the 9th month after the start, there was more extensive and severe atherosclerosis. These lesions were classified into two types by the difference in the histologic architecture of arterial wall. One was fatty streaks that were in thoracic aorta belonging to the elastic type and the other was fibrous plaques that were in abdominal aorta and iliac artery and so on, belong to the transitional or muscular type. High-fat plus high-cholesterol diet feeding led to elevated serum cholesterol and beta-lipoprotein levels, and had an effect on several kinds of metabolism. All of the swine fed high-fat or commercial diet had little gross, microscopic lesions and had no change in serum cholesterol and beta-lipoprotein levels. Hypercholesterolemia and hyper-beta-lipoproteinemia had a close relation to the development and acceleration of atherosclerosis. It was possible to show that the diet induced atherosclerosis was similar in quality to that observed in humans, and that the Göttingen miniature swine was a suitable animal for the study of atherosclerosis.

Animals↗

Bio-inorganic effects of D-penicillamine in children and in the elderly.

The principle mechanisms of action of dimethylcysteine (D-penicillamine) are thiazolidine formation, sulphhydryl -disulphide exchange, chelation and superoxide dismutase-like activity; as a consequence, it can enter into many varied biological interactions. Thiazolidine formation with maturing collagen makes D-penicillamine potentially teratogenic; sulphhydryl -disulphide exchange allows the formation of a mixed disulphide with L-cysteine from the L-cystine dimer; chelation permits it to bind metals such as copper; and superoxide scavenging makes it theoretically capable of influencing the inflammatory response of specific cell systems. Not surprising, D-penicillamine is of value in the treatment of cystinuria, Wilson's disease, juvenile rheumatism, rheumatoid arthritis and various other conditions.

Abnormalities, Drug-Induced↗

Alcohol sensitivity related to polymorphism of alcohol-metabolizing enzymes in Japanese.

Normal Japanese subjects were divided into two groups, i.e., one with both low and high Km isozymes of aldehyde dehydrogenase for acetaldehyde, and the other deficient in the low Km isozyme. After intake of 0.4 g/kg alcohol, the deficient subjects showed high level of blood acetaldehyde, facial flushing and the other dysphoric symptoms, including increase of pulse rate, decrease of diastolic blood pressure, changes of pulse wave in the fingertip, and elevation of the arterial pressure and blood flow rate in common carotid arteries as well as increase of plasma catecholamines level. In contrast, subjects with normal ALDH did not show these changes. From the observation of liver specimens obtained at autopsy, the frequency of deficient phenotype of ALDH in Japanese was presumed to be about 36%.

Acetaldehyde↗