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Biomedical subjects

J Nakanishi

Publications and source records attributed to J Nakanishi.

At least 19 recordsLinked to original sources

The present mercury contents of scalp hair and clinical symptoms in inhabitants of the Minamata area.

A total of 191 fishermen and their family (32-82 years) living in some mercury-polluted areas along the Shiranui Sea volunteered for the present study. They made a living by fishery and had formerly eaten the methyl mercury-contaminated fish and shellfish caught there. The questionnaire on subjective symptoms, fish eating habits, and past living history was conducted on the subjects. In addition, they were clinically examined in detail by several neurologists and scalp hair was collected. With six exceptions, all the 185 subjects showed a normal total mercury level in hair (<10 ppm). The ratio of methyl mercury to total mercury was 79-94% on the average for each group examined, suggesting indirect contamination (perhaps through the food chain). Despite their low mercury level in scalp hair, however, the subjects showed various neurological symptoms, particularly, sensory disturbance (such as the glove and stocking type), at a very high rate. Thus, it seems fair to state that, in addition to officially recognized Minamata disease patients, there still exist many people with atypical, slight Minamata disease on the coast of the Shiranui Sea. The current hair mercury level is not necessarily useful as a criterion for diagnosing chronic Minamata disease because of the long lapse of time.

Adult

Dry condition affects desquamation of stratum corneum in vivo.

We examined whether a dry condition actually induces scaly skin in vivo. Hairless mice were kept in a high humidity condition or a low humidity condition and skin changes were examined. Scales appeared on the backs of mice kept for 3 days under the dry condition. The weight of stratum corneum (SC) was increased at this point, and these alterations were not accompanied with hyperproliferation of the nucleated cell layer of the epidermis. A decrease of desmosomal degradation was observed, though, desquamation-related enzyme activity was not altered. The regulation mechanism of desquamation is not yet clear, however, in vitro experiments suggest that the water content in SC is an important factor. The water content of SC was decreased in the dry condition. These results indicate that a dry environment perturbs desmosome degradation in intact SC by decreasing the water content of SC, and the consequent impairment of desquamation in normal skin in vivo may lead to the induction of a scaly skin surface.

Animals

Cholesterol sulfate inhibits proteases that are involved in desquamation of stratum corneum.

We previously reported that desmosomes play a key role in the adhesion of corneocytes, and their digestion by two types of serine proteases leads to desquamation. Patients with recessive X-linked ichthyosis show hyperkeratosis attributable to desmosomes, associated with an increased content of cholesterol sulfate (CS) and an increased thickness of stratum corneum. In this study, therefore, we examined the possibility that CS provokes the abnormal desquamation, acting as a protease inhibitor. Scaling was induced on mice after topical application of chymostatin and leupeptin. Visible scale was also observed on mice after topical application of CS. We found that the stratum corneum thickness of CS-treated mice was increased in comparison with that of vehicle-treated mice. The thickness of the epidermis and the labeling index with proliferating cell nuclear antigen from CS-treated mice was almost the same as that from vehicle-treated mice. Moreover, in the stratum corneum of CS-treated mice, the content of desmosomes was higher than that in vehicle-treated mice. CS also inhibited the protease-induced cell dissociation of human stratum corneum sheets. In vitro, CS competitively inhibited both types of serine protease: the Ki for trypsin was 5.5 x 10(-6) M and that for chymotrypsin was 2.1 x 10(-6) M. These results indicate that CS retards desquamation by acting as a protease inhibitor. Thus, accumulation of stratum corneum in recessive X-linked ichthyosis may be a result of the inhibition by excessive CS of proteases involved in the dissolution of desmosomes, required for desquamation of the stratum corneum.

Animals

Electrochemical evaluation of chemical selectivity of glutamate receptor ion channel proteins with a multi-channel sensor.

A new method for evaluating chemical selectivity of agonists towards receptor ion channel proteins is proposed by using glutamate receptor (GluR) ion channel proteins and their agonists N-methyl-D-aspartic acid (NMDA), L-glutamate, and (2S, 3R, 4S) isomer of 2-(carboxycyclopropyl)glycine (L-CCG-IV). Integrated multi-channel currents, corresponding to the sum of total amount of ions passed through the multiple open channels, were used as a measure of agonists' selectivity to recognize ion channel proteins and induce channel currents. GluRs isolated from rat synaptic plasma membranes were incorporated into planar bilayer lipid membranes (BLMs) formed by the folding method. The empirical factors that affect the selectivity were demonstrated: (i) the number of GluRs incorporated into BLMs varied from one membrane to another; (ii) each BLM contained different subtypes of GluRs (NMDA and/or non-NMDA subtypes); and (iii) the magnitude of multi-channel responses induced by L-glutamate at negative applied potentials was larger than at positive potentials, while those by NMDA and L-CCG-IV were linearly related to applied potentials. The chemical selectivity among NMDA, L-glutamate and L-CCG-IV for NMDA subtype of GluRs was determined with each single BLM in which only NMDA subtype of GluRs was designed to be active by inhibiting the non-NMDA subtypes using a specific antagonist DNQX. The order of selectivity among the relevant agonists for the NMDA receptor subtype was found to be L-CCG-IV > L-glutamate > NMDA, which is consistent with the order of binding affinity of these agonists towards the same NMDA subtypes. The potential use of this approach for evaluating chemical selectivity towards non-NMDA receptor subtypes of GluRs and other receptor ion channel proteins is discussed.

Animals

Progressive decrease in hair diameter in Japanese with male pattern baldness.

Fifty-six Japanese with male pattern baldness were evaluated for changes in their hair diameters over three years. The mean hair diameter significantly decreased each year. The average decrease was 1.1 microns per year. Although the percentage of vellus hair increased by 3.6% over three years, this increase rate was lower than that found in Caucasians. To precisely examine the change in hair diameter, the mean distribution of this diameter was investigated. At the beginning of the study, clear peaks were observed at 95 microns in the twenties and 45 microns in the fifties. The number of thicker hairs decreased and the high frequency peak shifted to a thinner hair diameter over 3 years. To quantify the change in the distribution of hair diameter, the percentage of hairs of more than 60 microns was examined. There was a statistically significant 5.61% decrease in the percentage of hairs with a diameter of more than 60 microns over three years. Our findings suggest that the progression of male pattern baldness in Japanese is slower than that of Caucasians and that the percentage of hairs of more than 60 microns is a sensitive index to evaluate the progression of male pattern baldness and the effects of hair growth or hair loss preventive agents.

Adult

[Characteristics of psychosocial nursing care--the dimensions of psychosocial nursing care to promote empowerment among patients].

UNLABELLED: Nurses provide the psychosocial nursing care to promote the patients' empowerment. In spite of recognizing the importance of psychosocial nursing. The research reported here is part of a large study designed to explore the psychosocial nursing intervention strategies. This part of the study is focused on characteristics of psychosocial nursing care as identified by nurses. Research design was descriptive and qualitative. Subjects were a convenient sample of nurses who have more than 5 years experience and agreed to participate in this research. Data was collected through semistructured interviews. Data was recorded on a tape and transcribed, then analyzed based on Grounded Theory Approach. SUBJECTS: The number of subjects consisted of 39 nurses. The average age and duration of clinical experience was 36.6 years old and 12.6 years. RESULT: Sixteen of the characteristics of psychosocial nursing to promote the empowerment among the patients were identified; 1) respect the patients' decision making, 2) clinical judgment from multiple perspectives, 3) predictability, 4) flexibility, 5) classification of the patients by comparison, 6) monitoring, 7) relief from reality, 8) relief from pain and suffering, 9) enhancement of the patients' ego strength, 10) nurture of hope, 11) support individualized daily living styles, 12) encouragement of the patients'own problem solving abilities, 13) respect of individuality, 14) self-utilization, 15) self-control based on professional identity, 16) utilization of team power. DISCUSSION: Nurses choose from the sixteen dimensions of psychosocial nursing and organizing them in order to stabilizing the patients' conditions.

Decision Making

A method evaluating population risks from chemical exposure: a case study concerning prohibition of chlordane use in Japan.

The proposed method evaluating population risks from chemical exposure is based on estimation of the individual variabilities in the internal concentration of the chemical of concern and estimation of the magnitude of toxic effect caused at a given internal concentration. We assume a log-normal distribution for individual variability and propose loss of life expectancy (LLE) as a measure of the magnitude of toxic effects. We applied it to the evaluation of the governmental action of prohibiting the use of chlordane as a termiticide in Japan. Because the method is applicable to both carcinogenic and noncarcinogenic chemicals, the cancer risk due to chlordane and the noncancer risk due to chlorpyrifos, a major substitute, were evaluated and compared. The estimated values of risk represented in terms of LLE are 0.10 days for residents of untreated houses, 1.9 days for residents of treated houses, and 4.4 days for termite control workers when chlordane is used, and 0, 2.8, and 31 days when chlorpyrifos is used, respectively. From the result of the case study, we can see that the prohibition of chlordane is not necessarily effective in reducing risk.

Adult

Chondroblastoma of bone. A clinical, radiological, light and immunohistochemical study.

The clinical and morphological findings of 53 chondroblastomas in the files of the Bone Tumour Registry of Westphalia are presented. The mean age of all patients was 19.2 years. The male-to-female ratio was 1.5:1. Forty-two of the tumours (79.8%) were located in the long tubular bones and short tubular bones of the hands and were closely related to the growth plate. Six cases (11.3%) were found in the flat bones, 4 cases (7.5%) in the tarsal bones and 1 case (1.9%) in the craniofacial bones. The characteristic radiological feature of 44 investigated lesions was a mostly eccentric radiolucency with a geographic pattern of bone destruction and matrix calcifications. Periosteal reaction was evident in 9% of the cases. Most tumours demonstrate the typical morphological features of chondroblastoma, but 3 cases resembled a giant cell tumour. In 2 cases a haemangiopericytoma-like growth pattern was observed. Nine of the tumours had an aneurysmal bone cyst-like component. Vascular invasion was seen in 1 case. Immunohistochemically most cells in 30 of the cases and fetal chondroblasts in 3 cases were strongly positive with vimentin and S-100 protein. Collagen type II was positive in the chondroid matrix of the tumours and in fetal cartilage tissue; collagen type VI was present focally around individual tumour cells and was always seen in the chondroid matrix of the lesions and in fetal cartilage. These findings support the cartilaginous nature of these tumours. In paraffin sections, 46.6% of the cases revealed a distinct positive reaction of some tumour cells with the monoclonal cytokeratin antibody KL1 (molecular weight 55-57 kDa). Only 4 of them demonstrated a coexpression with the other monoclonal cytokeratin antibody CK (clone MNF 116, molecular weight 45-56.5 kDa). In paraffin sections all fetal chondroblasts were negative with both cytokeratin antibodies. Frozen sections of 3 tumours showed a strong positive reaction with both cytokeratin antibodies in many chondroblasts, indicating an "aberrant" cytokeratin expression. Osteoclast-like giant cells stained positive with leucocyte-common antigen (LCA) and with the macrophage-associated antibody KP1, but were negative with the other macrophage-associated antibody MAC 387. Recurrence rate was 10.7%. The clinical course of all tumours was benign.

Adolescent

[Peripheral blood stem cell autografts (PBSCT) in the treatment of 30 children with acute leukemias and lymphoma].

Thirty children (1-16 y.o.; median, 10 y.o.) with acute leukemia or non-Hodgkin's lymphoma (NHL) associated with high-risk features underwent high-dose chemotherapy without total body irradiation and peripheral blood stem cell autografts (PBSCT). Eighteen patients had acute lymphoblastic leukemia (ALL), 6 had acute non-lymphoblastic leukemia (ANLL), 2 had mixed-lineage leukemia and 4 had NHL. Twelve patients with two or more high-risk features (WBC greater than 10 x 10(4)/microliter, T- or B-phenotypes, infancy, massive organ infiltration, or induction failure) underwent PBSCT in 1st CR. Twelve patients underwent PBSCT in 2nd CR, and 4 in the subsequent remission greater than or equal to 3rd CR). Two patients were treated at refractory relapse. After PBSCT the number of days required to achieve a granulocyte count of 0.5 x 10(9)/l and a platelet count of 50 x 10(9)/l was 6.39 (median, 13) and 9-427 (median, 16), respectively. The disease-free survival rate was 6/12 in 1st CR group (6-41 mo) and 6/16 in the patients who underwent PBSCT in 2nd or subsequent remission (2-35 mo). The data justify the incorporation of PBSCT in the design of salvage protocol for children with leukemias or NHL. However, the application of the procedure as part of initial therapy in patients still remaining in 1st CR should be regarded as highly experimental and deserve further clarification.

Acute Disease

[Optimal methods for peripheral blood progenitor assay and its relevance in the blood cell autotransplantation].

Methylcellulose culture study revealed that the potency of recombinant granulocyte-colony stimulating factor (G-CSF) or granulocyte/macrophage (GM)-CSF to support the growth of purified target cell populations from peripheral blood of patients undergoing peripheral blood stem cell (PBSC) autotransplantation was inferior to that of PHA-stimulated lymphocyte conditioned medium (PHA-LCM) or interleukin-3 (IL-3). In liquid-suspension limiting dilution assay the cells responded directly to IL-3 by proliferation with single-hit kinetics. Hence, optimal culture for PBSC should include the use of PHA-LCM or IL-3. Further study disclosed a linear relationship between the number of CFU-GM infused into the patients and days required to achieve a granulocyte count above 0.5 x 10(9)/l.

Adolescent

Involvement of protein kinase in the regulation of beta-adrenergic receptors by antidepressants.

The role of serotonin (5-HT) and protein kinases in the regulation of the beta-receptor induced by typical and atypical antidepressants was investigated. Treatment with either mianserin or maprotiline for seven days produced a significant decrease in the beta-receptor density measured 6h after the last dose. The reduction in beta-receptors disappeared within 24h. However, combined treatment of mianserin or maprotiline with either fluoxetine or 5-hydroxytryptophan significantly decreased beta-receptors even 24h after the last dose. Following treatment with p-chlorophenylalanine the reduction in beta-receptors induced by desipramine was reversible within 24h. These results demonstrate that an increase in the synaptic 5-HT availability may contribute to the prolongation of the beta-receptor down-regulation by antidepressants. The intraventricular infusion of 12-0-tetradecanoyl-phorbol-13-acetate (TPA), a potent protein kinase C (PK-C) activator for seven days caused a significant decrease in beta-receptors, while forskolin or dibutyryl cyclic adenosine monophosphate had no influence on the receptor. The TPA-induced and desipramine-induced decreases in beta-receptors were not additive, suggesting that a similar mechanism is involved. The infusion of the PK-C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) caused an inhibition of the desipramine-induced decrease in beta-receptors. It is suggested that the beta-receptor down-regulation by antidepressants might be also regulated by PK-C through 5-HT-Ca2+-inositol-phospholipid systems.

5,7-Dihydroxytryptamine

[Effects of cadralazine on the respiration, circulation, kidney, autonomic nervous system, digestive system, blood and so on].

The general pharmacological effects of cadralazine and its major metabolite ISF 2405 were studied by comparing them with those of hydralazine. Cadralazine at 3.0 mg/kg, i.v., increased respiratory movement and heart rate and decreased blood pressure in cats. Cadralazine at 3.0 mg/kg, i.v., inhibited the hypertensive response induced by adrenaline, but showed little effect on the hypotensive response induced by acetylcholine in cats. Cadralazine and ISF 2405 at 10(-4) g/ml had negative chronotropic effects on isolated guinea-pig atria. The drug at 2.5 mg/kg, p.o., inhibited the passage of BaSO4 in the gastrointestinal tract in mice. The drug at 5.0 mg/kg, i.d. or more inhibited gastric secretion in rats. Cadralazine, except at higher doses, had little effect on spontaneous gastric motility and uterine spontaneous movement in rats. Cadralazine at 2.5 mg/kg, p.o., or more reduced or tended to reduce urine volume and urinary excretion of electrolytes. The drug showed little effect on coagulation and osmotic fragility in blood cell in rats nor on hemolysis and platelet aggregation in rabbits. ISF 2405, however, showed slight or moderate influence on hemolysis at concentrations as high as 0.01-1.0%. Cadralazine at 5.0 mg/kg, p.o. or more antagonized carrageenin-induced hind paw edema in rats. In conclusion, these effects of cadralazine were found to be qualitatively identical with those of hydralazine.

Animals

Immunohistochemical studies on the roles of substance P in the rat hypothalamus: possible implication in the hypothalamic-hypophysial-gonadal axis.

The hypothalamic neurons containing substance P (SP) were examined immunohistochemically in rats with a normal estrous cycle or persistent estrus (PE), in pregnancy and in lactating state. In PE animals, the neurons increased in number 1 week after ovariectomy, but then decreased and disappeared. During pregnancy, there were many SP neurons at an early stage but later they gradually decreased in number and disappeared. Consequently, during lactation no SP neurons were evident. The external layer of the median eminence (ME) contained many immunolabeled nerve terminals. In the ME prepared by a freeze-drying technique and immunostained with gold-labeled IgG by the postembedding procedure, the immunolabeled terminals were seen to contain large cored vesicles (50-100 nm) labeled with gold and unlabeled small clear vesicles (30-50 nm). In normal cycling rats, the terminals contained large cored vesicles in diestrus, small clear vesicles in estrus, and both in proestrus. In PE rats, the terminals contained only small clear vesicles, but the cored vesicles appeared after ovariectomy. In the early stage of pregnancy, the terminals contained only small clear vesicles, but the large cored vesicles appeared in late pregnancy and during lactation. These findings present further evidence that the hypothalamic SP neurons are involved in the hypothalamic-hypophysial-gonadal axis in rats.

Animals

Differential immunolabeling for electron microscopy of diverse peptidergic neurons.

We describe a simple and reliable method for differential immunolabeling of pre- and post-synaptic signal peptides at the ultrastructural level. Hypothalamic tissues of rats, including the suprachiasmatic nucleus, were cut on a Vibratome. Visualization of the immunolabeling of somatostatin (SRIH) and vasoactive intestinal polypeptide (VIP) was performed with avidin-biotin-peroxidase-diaminobenzidine (DAB). The end product of the DAB to VIP was further silver-intensified in a physical processing using silver nitrate, and the silver grains were finally substituted for gold. DAB-labeled SRIH fibers synapse on gold-labeled VIP perikarya and dendrites in the suprachiasmatic nucleus.

Animals

Production of metalloproteinase in gastric tissue with acetic acid-induced ulcer or taurocholic acid-induced gastritis.

A metalloproteinase was extracted from a medium of cultured gastric tissues following acetic acid-induced ulcer or taurocholic acid-induced gastritis, and the enzyme was partially purified by Sephadex G-200 column chromatography. This proteinase was released in active and latent forms with apparent molecular weights of 170,000 and 210,000, respectively. Its activity was abolished by treatment with ethylenediaminetetraacetic acid or 1,10-phenanthroline, but not with phenylmethylsulfonyl fluoride or soybean trypsin inhibitor. This enzyme degraded type I gelatin and type IV collagen but did not attack type I collagen. In contrast, very little of this enzyme was released from gastric tissue following erosion caused by water-immersion stress or from normal gastric tissue. These results suggest that this metalloproteinase plays an important role in gastric lesions by breaking down the basement membrane.

Acetates

GRF neurons in the rat hypothalamus.

The growth hormone-releasing factor (GRF)-containing neuronal system was immunohistochemically studied in the rat hypothalamus. The immunolabeled cell bodies were determined by intraventricular administration of colchicine 24 h before killing. In intact animals, the neurons appeared in the ventral portion of the arcuate nucleus (group 1) and in the area surrounding the ventromedial nucleus (group 2). Most of the cell bodies also indicated immunoreactivity for tyrosine hydroxylase (TH). The immunoreactive fibers accumulated showing a palisade arrangement in the external layer of the median eminence. The rats treated neonatally with monosodium glutamate revealed group 2 neurons and a few immunoreactive fibers in the median eminence. Half-anterolateral deafferentation of the medial basal hypothalamus, which was performed to isolate group 1 neurons or both group 1 and 2 neurons from the other brain parts, did not remarkably affect the appearance of the fibers in the median eminence. However, the perikarya were hypertrophic and strongly immunolabeled for GRF and TH. It is concluded that the fibers containing GRF in the median eminence derive mostly from group 1 neurons, and that the neurons may be regulated by an inhibitory mechanism by other neurons on the outside of the deafferented hypothalamic islands. GRF synthesized in group 2 neurons may act on other neurons as a neurotransmitter-like substance.

Animals