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Biomedical subjects

M Higuchi

Publications and source records attributed to M Higuchi.

At least 361 records · Page 20Linked to original sources

Effects of hydrocortisone on the vertebral cartilage plate in mice. A light and electron microscopic study.

Together with other side effects, the clinical use of steroid appears to produce disorders in the spinal column, especially in young patients. However, morphologic details of steroid induced changes in the spinal column are little known. In this study, mice were treated with daily intramuscular injections of hydrocortisone at doses of 1, 5, and 10 mg/kg body weight for 1, 2, or 4 weeks after 2 weeks of age, and the cartilage plates of the lumbar vertebrae were examined, compared with controls, by light and electron microscopy. Cartilage plates consist of an outer zone, abutting the nucleus pulposus and an inner zone oriented toward the vertebral body. The outer zone is divided into a superficial layer and a deep calcified layer. With steroid therapy, chondrocytes in the inner zone and the superficial layer of the outer zone became degenerative or necrotic. In mice treated with 5 and 10 mg hydrocortisone/kg body weight, ossification appeared earlier in the deep calcified layer than in control animals. After 2 weeks of treatment, the cartilage tissue of the inner zone in mice treated with 10 mg hydrocortisone contained ossification gaps, columnar bone tissue, connecting the bony vertebral body, and the deep calcified layer of the outer zone. The thickness of each layer was measured by light microscopy. By hydrocortisone treatment, the whole of the cartilage plate decreased in thickness, the two cartilage layers of the inner zone and the superficial layer of the outer zone became thinner, and the calcified or ossified layer of the outer zone became widened.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ultrastructure of the nucleus pulposus in the intervertebral disc after systemic administration of hydrocortisone in mice.

The nucleus pulposus of the lumbar intervertebral disc of mice given daily intramuscular injection of hydrocortisone at a dose of 1, 5, 10 mg/kg body weight for 1-4 weeks from 2 weeks of age was studied by electron microscopy. The hydrocortisone administration induced degeneration of the notochordal cells in the nucleus pulposus. The degenerative changes occurred earlier in the periphery of the nucleus pulposus than in the central region and developed earlier in mice treated with higher doses of hydrocortisone than in mice treated with lower doses. From the results, it is likely that steroid treatment accelerates the aging process of the nucleus pulposus and causes dysfunction of the intervertebral disc.

Animals↗

Effect of captopril on transplanted schistosome egg granulomas in skin.

Groups of athymic nude (nu/nu) and littermate (nu/+) mice received transplants into skin of hepatic egg granulomas isolated from Schistosoma mansoni-infected nu/+ mice. Some were fed captopril, an angiotensin-converting enzyme inhibitor, and other animals served as controls. Lesions were removed at 2, 4, and 6 weeks after implantation and prepared for light and electron microscopy. The number of new egg granulomas repopulated by recipient cells was compared by counting more than 100 eggs per specimen, randomly, double blind, and the effects of captopril on developing granulomas were determined. Results in nude mice indicated a trend for increasing granuloma takes with time in captopril-treated animals compared to controls, especially in mice who started therapy 2 weeks after transplantation. In nu/+ recipients the differences were more striking and statistically significant at 2 and 6 weeks after grafting. The granulomas in treated mice in both groups were larger than those in controls, but the cellular composition in the granulomas that developed were similar. New granulomas consisted mainly of eosinophils and mixed-function macrophages, although some purely secretory macrophages also were seen. The findings demonstrate that captopril ingestion enhanced granulomatous inflammation induced by skin transplantation of schistosome egg granulomas and significantly increased isograft takes. The results may have relevance for treating cutaneous diseases like sarcoidosis with captopril.

Animals↗

Cyclic Cushing's syndrome combined with cortisol suppressible, dexamethasone non-suppressible ACTH secretion: a new variant of Cushing's syndrome.

A 55 year old woman with an unusual form of Cushing's disease was studied. During several periods (periods lasting up to 84 days) evidence of cortisol hypersecretion with cycles occurring every 6 days was found. Suppression of plasma cortisol through orally administered dexamethasone (up to 32 mg per day) could not be achieved either during periods of cyclic cortisol hypersecretion or during apparent remission with normal cortisol secretion. Marked suppression of plasma ACTH was measured in response to an iv infusion of 50 mg cortisol over a period of 55 min whereas a similar test with 2 mg dexamethasone (iv bolus) did not suppress ACTH secretion. Transsphenoidal exploration of the sella revealed a tumour surrounding the anterior pituitary. Examination of the pituitary showed a few tiny tumour structures embedded in normal tissue which could not be removed, when the tumour was resected selectively under preservation of normal appearing tissue. Post-operatively, clinical and chemical remission (normal response to 1 mg dexamethasone) was observed for about 4 months. Thereafter, cortisol hypersecretion occurred again necessitating bilateral adrenalectomy. Our results are compatible with the assumption that normal hypothalamic-pituitary-adrenal suppressibility with cortisol, but not with dexamethasone, was caused by the loss of feedback receptors for dexamethasone in the presence of cortisol receptors in the cells which secrete ACTH or CRF. The combination of cyclic hypercortisolism with dexamethasone non-suppressible Cushing's syndrome has not been reported before and thus represents a new variant of Cushing's syndrome.

Adrenocorticotropic Hormone↗

Dissociation between kallikrein and aldosterone in Cushing's disease with periodic hormonogenesis.

It has been suggested that the renal kallikrein-kinin system is dependent on mineralocorticoid activity. This hypothesis was studied in a patient with cyclic Cushing's syndrome combined with cortisol suppressible, dexamethasone non-suppressible ACTH secretion. The 24-h urinary excretions of sodium, potassium, cortisol, active and inactive kallikrein, aldosterone, and prostaglandin E2 (PGE2) were studied during normal and excessive cortisol secretion and after bilateral adrenalectomy. Kallikrein, PGE2 and potassium rose during cortisol overproduction while aldosterone and sodium decreased. Kallikrein, PGE2 and potassium were positively related to cortisol excretion, whereas urinary aldosterone and sodium showed a negative relationship to cortisol. Kallikrein was inversely related to aldosterone. Excretion of inactive kallikrein followed closely the changes of active kallikrein. During cortisol excess, as in our patient, the mineralocorticoid activity of cortisol will exceed that of aldosterone. This suggests that the alterations in kallikrein, aldosterone and PGE2 during cortisol excess in the present study were due to the mineralocorticoid potency of the steroid.

Adrenalectomy↗

[Chronic toxicity study on difluprednate in dogs].

The chronic toxicity of a new topical glucocorticoid, difluprednate (DFBA) was studied in Beagle dogs. DFBA ointment (0.05%) was percutaneously treated to the back of dogs at daily doses of 125, 12.5 and 1.25 micrograms/kg for 6 months. The local effects of DFBA In the treated area, thinning of the skin and inhibition of the fur-growth were observed with scale and erythema. The skin showed histological atrophy of the epidermis, a decrease of the adipose tissue and atrophy of the adnexa. These changes returned to normal after the 2-month withdrawal period. The systemic effects of DFBA In the 125 micrograms/kg group, the following changes were observed, although neither death nor severe symptoms occurred: General observations were seen an increase of water intake and urinary volume. A decrease of lymphocytes and eosinophils, and an increase of neutrophils were observed in the hematological examination. There were high sodium and low potassium levels, and an increase of alkaline phosphatase and gamma-glutamyltranspeptidase activities in the biochemical examination. The organ weights showed a decrease of the thymus, adrenals, prostate and ovaries, and an increase of the liver and kidney. An atrophy of the lymphatic tissues and adrenal cortex, retardation of the sexual maturation, glycogen deposit in the hepatic cells, slight degeneration of the renal tubuli, and slight thinning of the sternum and non-treated skin were noted in the pathological examination. These changes returned to normal after the 2-month withdrawal period. In the 12.5 micrograms/kg group, the atrophic changes in the thymus, adrenal and non-treated skin appeared slight. In the 1.25 micrograms/kg group, no changes were found. Conclusively, all the local and systemic changes observed by DFBA in this study were due to the already known pharmacological effects of glucocorticoids. It is considered that a 12.5 micrograms/kg dosage is similar to a non-effect dose.

Animals↗

[Prevalence of antibody to adult T-cell leukemia virus in Hokkaido District].

In order to investigate the spread of adult T-cell leukemia (ATL) virus in the inhabitants of ATL-non-endemic Hokkaido, we surveyed the antibodies to ATL-associated antigen (ATLA) in 29516 healthy individuals by indirect immunofluorescence test using MT-1 for target cell. Of the healthy inhabitants, only 219 individuals (0.74%) were anti-ATLA positive as carriers. Prevalence of anti-ATLA was 0.63% (111 of 17590) in males and 0.91% (108 of 11926) in females. This difference by sex is significant. In several regions, the inhabitants were found to show relatively high incidence (greater than 2%) of the antibodies, and these regions have a tendency to cluster around the western side of Hidaka mountains or Akan area. The highest rate (5.2%) of anti-ATLA positive carriers was shown in a certain town of Hidaka area.

Adolescent↗

Effect of nifedipine treatment on cardiac myosin ATPase activity and responsiveness of cardiovascular system in the dog.

Effects of nifedipine treatment on cardiac myosin ATPase activity and responsiveness of cardiovascular system to catecholamine have been studied. Eight mongrel dogs weighing 7.5 to 13.5 kg were given nifedipine orally twice daily (60 mg/day) for 2 weeks. Ten minutes after the first administration of nifedipine (30 mg p.o.) the heart rate increased significantly and it lasted for, at least, 4 hours. Two-week treatment of nifedipine caused a decrease of the resting heart rate, but the maximal heart rate increase by nifedipine administration was almost the same as the one on the first day. The effects of norepinephrine on heart rate and blood pressure, responsiveness of isolated coronary arteries to some agents inducing a contraction and, Ca2+-activated and K+-activated cardiac myosin ATPase activities were not significantly different between control and nifedipine treatment groups.

Adenosine Triphosphatases↗

[Prenatal assessment of fetal lung maturity by the stable microbubble method--fundamental and clinical study].

Diagnostic value of RDS was investigated by the Stable Microbubble Method. When this method was applied to the tracheal fluid of fetuses in rabbit (28 days of gestation), the PV curve and lung-thoracic compliance showed mature patterns in the test results for weak, medium, and strong as compared with those for zero and very weak in which they showed an immature pattern. Results by this method correlated with the DSPC level in human amniotic fluid, and were little affected by the contamination of meconium or fresh plasma. Amounts of DSPC were 0.69 +/- 0.05 (mg/dl, Mean +/- SE) in zero, 1.19 +/- 0.15 in very weak, 3.99 +/- 5.06 in weak, 6.58 +/- 2.01 in medium, and 7.70 +/- 1.15 in strong test results. The coefficient of correlation was 0.56 (p less than 0.01). In the clinical study, when the mature level was arbitrarily defined as weak, the diagnostic accuracy was 76.8%, false negative rate was 0%, and false positive rate was 27.5%. If the mature level was defined as very weak, the diagnostic accuracy was 94.2% and the false positive rate was 3.4%. But the false negative rate increased to 18.8%. The diagnostic accuracy of this method was higher than the double shake test (72.2%), and was as high as the measurement of the DSPC level (92.0%).

Amniotic Fluid↗

Clinical observations on Behçet's disease in Tianjin, China.

Frequency and clinical manifestations of Behcet's disease were investigated in the Teaching Hospital of Tianjin Medical College, China. Diagnosis of Behcet's disease was made according to the diagnostic criteria proposed by the Japanese Research Committee on Behcet's disease. Forty-two patients, 14 men and 28 women, were found to have Behcet's disease. Fourteen patients belonged to the complete type and 28 to the incomplete type. Frequency of ocular lesions, especially in women patients, was lower and that of genital ulcers higher in China than those in Japan. Epidemiological and anthropological significance for the development of this disease was discussed.

Adolescent↗

The surgical reconstruction of fractures and fracture dislocations of the thoraco-lumbar spine.

Sixty patients have undergone surgical reconstruction of the injured thoraco-lumbar spine during the period 1968 to 1978 at the Spinal Unit of the National Murayama Hospital. The aim of treatment of any fracture, dislocation, or fracture-dislocation of the spine is to render it stable and painfree. This is best achieved by reduction and stabilisation of the involved segment of the spinal column. Where the posterior ligaments and intervertebral disc are ruptured healing of these structures with return to normal stability cannot be anticipated. In order to obtain permanent stability at the affected vertebral level we elect to perform anterior intervertebral fusion.

Adult↗