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Biomedical subjects

M Yamakado

Publications and source records attributed to M Yamakado.

At least 19 recordsLinked to original sources

Reassemblage of primary cell aggregates and modulation of subcortical connections in the thalamic relay nucleus: effects of vibrissal damage in the developing whisker-to-barrel pathway in the mouse.

To investigate the mechanisms underlying the reorganization of barrels in the whisker-tobarrel pathway, the facial vibrissae of mice were damaged by electrocauterization at alternate positions on either postnatal day 0 (P0) or P3, before or after the onset of cell aggregation in the thalamus and cortex. Animals were subsequently killed on P8, topographical changes were examined by cytochrome C oxidase histochemistry, and afferent connections were identified using DiI tracer. The cytoarchitecture was characterized with bisbenzimide counterstain. Regardless of when damage was done, the reorganized barreloids and barrels in the thalamus and cortex, respectively, were integrated in an array that represented the topography of undamaged vibrissae. In the brainstem, although the original framework of the array was preserved, defective cell aggregates remained, possibly still in contact with damaged vibrissae. During normal development, on P0 cell aggregates are formed only in the brainstem, and begin to be organized at the other levels of the pathway on P3. Therefore, when damage is induced on P3, the primary cell aggregates are replaced by new, possibly recombined, cell aggregates in the thalamus and cortex to represent the new peripheral topography. The presumably recombined aggregates indicate that cell reassemblage occurred between neighboring cell aggregates. Concomitant with these changes, afferent fibers originating in the brainstem and thalamus extended their terminal arborizations to delineate the new cell aggregates in the thalamus and cortex, respectively. These findings indicate that activity-dependent competitive interactions of afferents may play a crucial role in organizing the topography of cell aggregation and reassemblage in response to vibrissal damage at each level of the pathway.

Afferent Pathways

Mechanism of oral absorbent AST-120 in lipid abnormalities in experimental uremic rats.

BACKGROUND: We have reported that oral sorbent AST-120 (AST) is effective in delaying the induction of dialysis in patients with chronic renal failure (CRF) because of its effect on lipid metabolism. To clarify the precise mechanism of AST in lipid abnormalities in CRF, we examined the effect of AST on plasma lipid profile, total bile acids (TBA), and lipoprotein lipase (LPL) activity in experimental uremic rats. METHODS: Uremic rats were prepared using male Wistar rats by ligating 5/6 of the renal artery. Uremic rats were randomly divided into two groups as follows: a control group in which rats were maintained on the standard diet and an AST group in which rats were maintained on a diet containing 5 g of AST per 100 g of standard diet for 10 weeks. Plasma LPL activity was measured as free fatty acid (FFA) generation after intravenous administration of heparin. RESULTS: Plasma creatinine at 1.5 +/- 0.1 mg/dl was lower in the AST group than the 1.9 +/- 0.5 mg/ml level in the control group. AST significantly decreased plasma total cholesterol from 192 +/- 29 to 142 +/- 25 mg/dl, triglycerides from 198 +/- 71 to 99 +/- 38 mg/dl, and TBA from 19.6 +/- 2.6 mumol/liter to 8.8 +/- 3.5 mumol/ml. Plasma LPL activity at 0.22 +/- 0.01 mumol FFA/min/hr was significantly higher in the AST group than 0.15 +/- 0.03 mumol FFA/min/hr in the control group. CONCLUSIONS: These results suggest that AST may improve plasma lipid abnormalities by binding to bile acids in the intestinal lumen and preventing their reabsorption and inhibiting the reduction of LPL activity in experimental uremic rats.

Administration, Oral

Influence of smoking on serum carcinoembryonic antigen levels in subjects who underwent multiphasic health testing and services.

We quantified the effect of smoking on serum carcinoembryonic antigen (CEA) levels in 1341 subjects who underwent the multiphasic health testing and services in our center. Four hundred and sixty seven of them were smokers and the rest were nonsmokers. In males subjects, serum CEA levels were significantly higher in smokers (3.11 +/- 1.8 ng/ml) than in nonsmokers (2.14 +/- 1.8 ng/ml) (mean +/- SD; p < 0.01). For females, however, the levels had no significant differences between smokers (2.11 +/- 0.91 ng/ml) and nonsmokers (1.87 +2- 1.3 ng/ml). The CEA-positive subjects were 44, of whom 32 were male custom heavy smokers, and only 2 of them had gastrointestinal cancer. We concluded that the serum CEA level was influenced by smoking especially in males and its clinical significance for detection of carcinoma was doubtful.

Carcinoembryonic Antigen

Ultrasonographically assessed carotid intima-media thickness and risk for asymptomatic cerebral infarction.

Cerebral infarction (CI) is still a leading cause of death in Japan. Thus, the management of risk factors for CI as primary prevention is one of the most important tasks in multiphasic health testing and services. To determine whether carotid intima-media thickness (IMT) is a risk for CI, ultrasonographically assessed carotid IMT was compared between normal subjects (N) and subjects with asymptomatic CI (ACI) in 243 subjects who underwent human brain dry dock. ACI was found in 68 people (28.0%). Age, body mass index, and mean blood pressure were higher in ACI than in N. Also, atherogenic index was higher in ACI than in N. Carotid IMT was significantly thicker in ACI than in N. Furthermore, incidence of atherogenic plaque in ACI was significantly higher than that in N. In conclusion, not only aging, obesity, blood pressure, and plasma lipids, but also carotid IMT may be a risk for ACI.

Adult

Differential fasciculation of follicular nerves for transferring specifically localized cues of the vibrissa rudiments to the central trigeminal sensory system in mice, as exploited with DiI and DiA labeling.

Vibrissa connections play a decisive role in setting the somatotopic coordinates in the trigeminal sensory system. Although previous studies have examined the development of peripheral patterning, certain questions are still in dispute, for example, the way vibrissa connections are structured, and the relationship between periphery and central organization, and ganglion cell organization. In order to fill the blanks left by previous studies, the extension of ganglionic branches and the formation of vibrissa connections were reexamined by using fluorescent carbocyanin dyes, DiI and DiA, during embryonic days 10 to 14 in mouse. Whole-mount preparations satisfactorily demonstrated the ganglionic fiber system, which allowed detailed analysis at both macroscopic and microscopic levels. We show here that the differential fasciculation of follicular nerves is the critical process for organizing vibrissa connections which modulate the initially extending fiber pattern. Follicular nerves developed by fine fibers arising from initially ordered root fascicles, so as to connect with vibrissa rudiments that developed on the facial prominences. During differential fasciculation, ganglion cells were segregated into distinct groups by the vibrissa connections, whereas central fiber terminals did not yet develop specific structures in the nuclear region. In the primary order of the trigeminal sensory system, vibrissa connections in the periphery were organized before those of the central structure. These results indicate that trigeminal ganglion cells have a critical binomial function in order to transfer the somatotopic relations among vibrissa rudiments into the topographic coordinates of the central system.

Animals

[Endocarditis].

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Acute Disease

[Heart failure].

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Cardiac Output, Low

The effect of age on glucose tolerance and plasma insulin level in hypertensive and normotensive subjects.

To elucidate the effect of aging and blood pressure on glucose tolerance, we examined the subjects who received 75g OGTT annually for 10 years. They were classified into 2 groups by blood pressure, and into 4 groups by age. The study group consisted of 34 cases (mean 62 years old), including 11 hypertensive (HT) and 23 normotensive (NT) control. All cases had their body weight fluctuate in less than 4 kgs. After blood pressure was measured, blood was drawn for determination of plasma glucose and insulin concentrations in each subject before 75g OGTT and 30, 60, 90, 120 minutes afterward. sigma BS and sigma IRI were defined as the sum of 5 points in BS and IRI, respectively. Insulinogenic index (I.I) was defined as deltaIRI/deltaBS in 30 min. sigma IRI/sigma BS and I.I of each year were calculated serially. They were compared between HT and NT group, and among 4 groups of age; 40s, 50s, 60s and 70s. sigma IRI/sigma BS was significantly decreased in both HT and NT groups (0.52 +/- 0.05 (mean +/- SE) to 0.29 +/- 0.04; p <0.0001 vs. 0.42 +/- 0.05 to 0.23 +/- 0.02; p < 0.0001, respectively). But significant difference between the 2 groups was not observed. No significant difference of sigma IRI/sigma BS among 4 groups of age was found. There were significant differences between I.I of the first year and that of several years, but they did not correlate linearly. These data indicate that the effect of age on the diminution of sigma IRI/sigma BS was significant for 10 years follow-up of the same subjects in both HT and NT groups. But there were no significant differences in classified groups by blood pressure and age.

Aged

Remodelling in the array of cell aggregates in somatotopic representation of the facial vibrissae through the trigeminal sensory system of the mouse.

The disposition of the facial vibrissae of the mouse is represented as a matrix-like array of cell aggregates in rows and columns at every station of the whisker-to-barrel pathway. In order to evaluate the role of each station in this pathway, lesions were made in the facial vibrissae of the mystacial group on P0-P3, and the animals were sacrificed on P8. The effects of the lesions on the cell aggregates in the array were analyzed by using cytochrome oxidase and gallocyanin cell-staining methods. Division of cell aggregates in the array was controlled by row basis interactions through the pathway up to the cerebral cortex. In this organization, affected cell aggregates which corresponded to the damaged vibrissae were eliminated and/or fused together in the array of the thalamic relay nucleus. On the basis of thalamic modification, the final array of cell aggregates was remodelled in the cerebral cortex. In contrast, affected cell aggregates remained degenerative spaces at the original sites in the array in relation to the damaged vibrissae in the brain stem trigeminal nuclear complex. These results indicate that a protoframework with row basis orientation for the division of cell aggregates is prepared in every station of the pathway at the time of lesioning, and adjustment of subcortical alterations in the thalamic relay nucleus is a decisive process to let the cerebral cortex remodel the topographic array of cell aggregates.

Animals

Changes of the expression and distribution of retinoic acid receptors during neurogenesis in mouse embryos.

The expression and distribution of three retinoic acid receptors, alpha, beta, and gamma, were investigated in the CNS of mouse embryos during development. mRNAs and protein of RAR-beta that were expressed in the spinal cord of the 12.5-day mouse embryo decreased during development but they were not decreased in the brain. The RAR-beta-positive cells were already present in the ventral region of the spinal cord of 10.5-day mouse embryos, gradually appeared in the dorsal region during development and then disappeared from the spinal cord after birth. In the brain, RAR-beta-positive cells were detected in the mesencephalon and rhombencephalon but not in the telencephalon of the 12.5-day mouse embryos. RAR-beta-positive cells were present in the hippocampus and cingulum but not in the neocortex of 14.5-day mouse embryos. Most neurons in the hippocampus of 16.5-day mouse embryos and the cortex of newborn mice were RAR-beta-positive. In the spinal cord, RAR-alpha mRNAs and proteins also decreased during development but more gradually than RAR-beta mRNAs and proteins. During development, the distributions of RAR-alpha and -beta in the spinal cord and brain did not differ substantially. The main difference was the appearance of a subtypes of RAR-alpha, a 52-kDa protein, in the brain of newborn mice. On the other hand, RAR-gamma proteins were only faintly detected in the spinal cord and the brain of the mice during the embryonal stages but these increased after birth. The distribution of RAR-alpha- or -beta-positive cells were consistent with the neurogenesis during development in the spinal cord and brain.

Amino Acid Sequence

[A case of Crow-Fukase syndrome associated with membranoproliferative glomerulonephritis].

Crow-Fukase syndrome is a rare multiorgan disorder. Although renal disorders, such as proteinuria, and renal impairment, have been observed in half the cases of this syndrome, there have been few reports describing the renal lesions. We report here a case of this syndrome associated with membranoproliferative glomerulonephritis. A 43-year-old woman was referred to our hospital because of hyperglycemia. She had also been suffering from hyperpigmentation, hepatosplenomegaly, lymphadenopathy, polyneuropathy and endocrine dysfunction, including diabetes mellitus and amenorrhea. Serum electrophoresis showed M protein and immunoelectrophoresis revealed IgA (lambda). Bone marrow aspiration showed a slight increase in the number of plasma cells. Urine protein was 30 mg/dl, BUN was 17 mg/dl and creatinine 0.8 mg/dl. Light microscopic examinations showed enlargement of glomeruli with proliferation of mesangial cells and matrix, a lobular pattern of the glomeruli and thickening of the glomerular basement membrane and associated double contour. Electron microscopic examinations showed thickened capillary walls, associated mesangial interposition and subendothelial dense deposits. Moreover, fine granular deposits of IgM, C3, and fibrinogen along the basement membrane were observed on immunofluorescent studies.

Adult

[A case of sporadic acute type A hepatitis associated with acute renal failure].

We report a case of sporadic acute type A hepatitis associated with acute renal failure, due to mesangioproliferative glomerulonephritis and interstitial nephritis. A 42 year-old-man was admitted to Mitsui Memorial Hospital because of jaundice and oliguria with fever in February, 1989. His serum creatinine was 12.2 mg/dl, BUN 87 mg/dl, GOT 57 U/l and GPT 358 U/l. The serum IgM antibody to hepatitis A virus was positive, which indicated recent infection with hepatitis A virus. Hemodialysis and steroidal therapy were started, and the patient's acute renal failure and liver dysfunction ameliorated within one month. Light microscopic examinations showed an increased number of mesangial cells and an increased amount of mesangial matrix, and also showed inflammatory cell invasion in the interstitium. Electron microscopic examinations showed proliferation of mesangial cells and matrix, and a dense deposit along the basement membrane. On immunofluoresent studies, fine granular deposits of IgA and Clq were observed in the mesangium.

Acute Disease

Corticotropin-releasing hormone, proopiomelanocortin, and glucocorticoid receptor gene expression in adrenocorticotropin-producing tumors in vitro.

To differentiate between ectopic ACTH syndrome and Cushing's disease, gene expression of corticotropin-releasing hormone (CRH), proopiomelanocortin (POMC), and glucocorticoid receptor was examined in 10 pituitary adenomas (Cushing's disease) and in 10 ectopic ACTH-producing tumors. CRH increased plasma ACTH levels in all patients with Cushing's disease and in five patients with ectopic ACTH syndrome whose tumors contained CRH and CRH mRNA. In five CRH nonresponders, CRH was not detected in tumors that contained no CRH mRNA or that contained only long-size CRH mRNA. Dexamethasone (Dex) decreased plasma ACTH levels in all patients with Cushing's disease and in three patients with ectopic ACTH-producing bronchial carcinoid. These tumors contained glucocorticoid receptor mRNA. CRH increased and Dex decreased ACTH release and POMC mRNA levels in pituitary adenoma and bronchial carcinoid cells. PMA increased POMC mRNA levels only in carcinoid cells. These results reveal characteristics of ectopic ACTH-producing tumors: long-size CRH mRNA and PMA-induced POMC gene expression. In addition, there are two ectopic ACTH syndrome subtypes: tumors containing ACTH with CRH (CRH responder) and tumors without CRH. Dex decreases ACTH release and POMC mRNA levels in some bronchial carcinoids. Therefore, CRH and Dex tests have limited usefulness in differentiating between Cushing's disease and ectopic ACTH syndrome.

8-Bromo Cyclic Adenosine Monophosphate

Comparing postgraduate medical education at university and non-university hospitals in Japan.

In 1988 the authors surveyed all the teaching hospitals in Japan to evaluate the present status of postgraduate medical education (PGME); they received responses from 67 (84%) of the university and 172 (89%) of the non-university teaching hospitals. It was found that a large proportion of residents had spent two years in a residency without having had a single experience of some of the basic clinical skills. Consequently the residents' confidence in their abilities to perform these skills was low. The residents at the university hospitals, in particular, had had fewer experiences and were less confident about their clinical skills than were the residents at the non-university hospitals. The lack of standard and minimum requirements for PGME in Japan may be the cause of the poor level of acquisition of clinical skills of residents during PGME. Other possible causes are the tendency in Japanese medical society to attach greater importance to academic attainment than to clinical competence and the excessive gravitation of residents toward university hospitals. The authors suggest their results show the necessity to improve the training in basic clinical skills in PGME in Japan, especially in university hospitals.

Clinical Competence