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Biomedical subjects

N Yamaguchi

Publications and source records attributed to N Yamaguchi.

At least 451 records · Page 25Linked to original sources

The NMDA receptor antagonist MK-801 has a dissociative effect on seizure activity of hippocampal-kindled cats.

This study assessed the behavioral and electrographic effects of (+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine maleate (MK-801) (0.1 and 0.5 mg/kg, IP), a noncompetitive antagonist of the NMDA receptors, in hippocampal (HIP)-kindled cats. MK-801 at a higher dose significantly reduced the afterdischarge duration, but not the behavioral seizure stage, of HIP-kindled seizures. This anticonvulsant effect occurred in association with the appearance of severe behavioral toxicity and paradoxical worsening of background electroencephalogram characterized by profound spike and wave discharges. The present data suggest the dissociative effect of MK-801 on seizure activity and limitations of its clinical utility as an antiepileptic agent.

Animals↗

Ordering of human chromosome 3p markers by radiation hybrid mapping.

To construct a panel of radiation hybrids (RHs) for human chromosome 3p mapping, mouse microcell hybrid cells, A9(neo3/t)-5, containing a single copy of human chromosome 3p with pSV2neo plasmid DNA integrated at 3p21-p22 were irradiated and fused to mouse A9 cells. A panel of 96 RHs that retain several sizes and portions of human chromosome 3p segments was used to map 25 DNA markers for chromosome 3p. Eight of them, H28, H29, H32, H33, H35, H38, H48, and H64, were cloned from Alu-primed PCR products using A9(neo3/t)-5 cell DNA as a template. The most likely order of the 24 markers, except for H28, based on the statistical ordering method proposed by Falk, was cen-D3S4-D3S3-D3S30-H29-D3S13-D3S2-+ ++H48-D3F15S2-D3S32-D3S23-CCK-H35-H33- D3S11-D3S12-RARB-THRB(ERBA2-pBH302)- H64-H38-RAF1-D3S18-H32-D3S22-pter. The order and location of these markers were in good agreement with those previously determined by other mapping methods, suggesting that a panel of these 96 RHs is a valuable source for a rapid mapping of human chromosome 3p markers.

Chromosome Mapping↗

Intracoronary administration of saralasin: effects on cardiac arrhythmias induced by ischaemia and reperfusion in the anaesthetised dog.

OBJECTIVE: The aim was to study (1) the effects of intracoronary saralasin, an angiotensin II receptor antagonist, on ischaemia induced and reperfusion induced regional cardiac noradrenaline release and ventricular arrhythmias; and (2) the implication of angiotensin II in coronary constriction during myocardial ischaemia. METHODS: Eighteen adult mongrel dogs, weight 22.6(SD 1.1) kg, anaesthetised with sodium pentobarbitone, were used for the study. The left anterior descending coronary artery was ligated for 60 min and then reperfused for 30 min. Saralasin (60 micrograms.kg-1, n = 9) or its vehicle (Ringer lactate, n = 9) was injected into the artery at the beginning of the occlusion period. Two epicardial veins, one running parallel to the left anterior descending coronary artery and the other parallel to the circumflex coronary artery, were cannulated for the measurement of their respective blood flows and of noradrenaline, lactate, and creatine kinase release. RESULTS: Saralasin decreased the incidence of ventricular fibrillation during coronary occlusion (from 44% in the vehicle treated group to 0% in the saralasin treated group, p = 0.0412). This effect was accompanied by significant vasodilatation in both epicardial veins during myocardial ischaemia. Neither the increases in noradrenaline, lactate, and creatine kinase release nor the incidence and duration of the ventricular arrhythmias following reperfusion were modified by the administration of saralasin. CONCLUSIONS: Intracoronary saralasin in the early phase of myocardial ischaemia increases the epicardial venous blood flow significantly, suggesting that angiotensin II is implicated in coronary constriction during ischaemia. This haemodynamic effect is accompanied by a significant decrease in the incidence of ventricular fibrillation. However, the renin-angiotensin system does not appear to be implicated in the reperfusion induced noradrenaline release nor in the incidence of the ventricular arrhythmias.

Animals↗

Molecular cloning and partial characterization of a novel collagen chain, alpha 1(XVI), consisting of repetitive collagenous domains and cysteine-containing non-collagenous segments.

In an effort to identify new members of the collagen family, we screened a human placenta cDNA library with a collagenous probe. A novel 3.7 kb cDNA was identified encoding an open reading frame of 1,186 amino acids and containing a termination codon. The predicted polypeptide consists of 9 repetitive collagenous (stretches of Gly-X-Y) and several non-collagenous segments. Two cysteinyl residues separated by two amino acid residues (Cys-X-X-Cys) are regularly located in the N-terminal region of each non-collagenous segment. The deduced amino acid sequence described above is distinct from those of known types of collagen. Therefore, this novel collagen chain is designated alpha 1(XVI). Northern blot analysis revealed an alpha 1(XVI) mRNA of 5.2 kb, indicating that the overlapping cDNA clones isolated in this study covered nearly three-fourths of the mRNA. As a tool for further study on the expression of type XVI collagen, we prepared an antibody against the nonadecapeptide CFLSLERPRAEEARGDNSE, derived from the putative translation product of the cDNA. In immunoblot analysis, the antibody recognized a 160 kDa protein, which was bacterial collagenase-sensitive. Immunohistochemical stainings of human placental tissues with anti-peptide antibody revealed a positive reaction with amnion, the membranous tissue lining the amniotic cavity. The gene of alpha 1(XVI) chain, COL16A1, is mapped on the short arm of human chromosome 1 (1p13-p34).

Amino Acid Sequence↗

Induction of cytokines in human peripheral blood mononuclear cells by mycoplasmas.

Various species of mycoplasmas were tested for their ability to induce cytokine production in human peripheral blood mononuclear cells (PBMC). Human PBMC were incubated with Mycoplasma pneumoniae, M. hyorhinis, M. arginini, M. salivarium, M. orale, M. gallisepticum or A. laidlawii for 48 hr, and the activities of interleukin-1 beta (IL-1 beta), IL-2, IL-4, IL-6, tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN) in the supernatants were determined by ELISA or bioassay. All mycoplasma species induced IL-1 beta, IL-6 and TNF-alpha, although IL-2 was induced only by M. pneumoniae. IFN was induced by 5 of the 7 species, and the IFN produced was antigenically confirmed to be mainly IFN-alpha. On the other hand, mycoplasma-stimulated cultures did not contain detectable amounts of IFN-beta and IL-4 activities. Furthermore, the cytokines were induced by mycoplasmal contaminating cells in human PBMC as well as by mycoplasma alone. These results suggest that many kinds of cytokines induced by mycoplasma contamination in cell culture affect immunological experiments in vitro.

Biological Assay↗

A case-control study on occupational lung cancer risks in an industrialized city of Japan.

A hospital-based case-control study was conducted to evaluate occupational risks of lung cancer in an industrialized city of Japan. The lung cancer cases were obtained from 3 major hospitals in the city. The control group consisted of patients with a variety of diseases hospitalized in the same wards of the same hospitals as the cases. After matching on sex, 5-year age category and hospital, 144 cases and 676 controls comprised the study group. A self-administered questionnaire was used to obtain lifetime job histories and smoking status. The conditional logistic regression model was used to estimate relative risks after controlling for smoking and employment in other jobs. The workers in shipbuilding, ironworks and other plants (mostly chemical plants) showed statistically significant increases in lung cancer risk with relative risks of 6.18, 2.02, and 2.66, respectively. An increase in risk with the duration of employment was also observed in the "other plants" category. Building and road construction workers also showed increased relative risks, 1.95 and 1.79, but they were not significant. When the risk was evaluated on the exposure chemicals, the workers exposed to inorganic acids and bases had significantly increased risk. The workers exposed to asbestos, dust or organic chemicals also showed increased risk but the effects were not significant. The combined effect of smoking and employment in ironworks showed a good fit to an additive model, while that in the "other plants" category was closer to a multiplicative model.

Adenocarcinoma↗

A 50-year projection of lung cancer deaths among Japanese males and potential impact evaluation of anti-smoking measures and screening using a computerized simulation model.

The lung cancer death rate among Japanese males was projected for 50 years to the year 2041 by a computerized simulation model. Long-term effects of anti-smoking measures and mass screening on lung cancer deaths were also evaluated. The simulation showed that the age-adjusted lung cancer death rate would increase and reach a peak of 166 per 100,000 in 1989 and then decrease to 148 per 100,000 in 2003. It then shows an increasing tendency again, up to 255 per 100,000 in 2028. The smoking initiation rates estimated from the observed lung cancer death rates showed that the changes in death rates may be attributed to a lower smoking initiation rate among those born in the 1930's. Promotion of mass screening programs is effective more quickly than anti-smoking measures but the reduction in annual cancer deaths is expected to be only 11%, even if 100% participation is achieved by the year 2000. A reduction in smoking initiation rate, on the other hand, affects lung cancer deaths very slowly. It was predicted that a 1% annual reduction in smoking initiation rate would result in a 20% decrease in the number of lung cancer deaths in 2041. A smoking cessation program is intermediate with regard to promptness. The predicted reductions in lung cancer deaths in 2041 were 13%, 47%, and 66%, respectively, when the annual smoking cessation rate was increased from 0.46% (present status) to 1%, 3%, and 5%. In conclusion, the combined application of all three preventive measures seems essential to realize the most effective reduction in lung cancer deaths.

Age Factors↗

Cytoskeletal protein abnormalities in patients with olivopontocerebellar atrophy--an immunocytochemical and Gallyas silver impregnation study.

A highly sensitive silver technique for glial cytoplasmic inclusions (GCI) in olivopontocerebellar atrophy (OPCA) was applied to tissues from 15 patients with neurodegenerative disorders including OPCA, Joseph disease, Alzheimer's disease (AD), Huntington's chorea, Pick disease and three control non-neurological subjects. Brain tissue from both OPCA and AD impregnated positively. Neurons, astroglia and oligodendroglia in the putamen, pontine nucleus and inferior olivary nucleus all impregnated in addition to white matter oligodendroglia. Neuronal inclusions in the pontine nucleus appeared as compact or fibrillary masses, and GCI-bearing oligodendroglia and astrocytes showed homogeneously impregnated somata. The myelinated pontocerebellar tract and the white matter surrounding the inferior olivary nucleus contained a small number of impregnated nerve fibres with a hollow structure, which resembled the myelin sheath. Immunocytochemical studies to clarify these argyrophilic structures in the OPCA subjects employed paired helical filament (PHF), microtubule associated proteins (MAPs), MAP1, MAP2, MAP5, tau, ubiquitin, neurofilament (200 or 70 kilodaltons) and myelin basic protein (MBP) antisera. GCI-bearing white matter oligodendroglia expressed PHF, tau, MAP5 and ubiquitin immunoreactives and non-argyrophilic astroglia were positive for MAP5 antiserum alone. In the putamen, pontine nuclei and inferior olivary nuclei, impregnated neurons as well as the GCI-bearing oligodendroglia immunostained with PHF, tau, MAP5 and ubiquitin antisera and impregnated astroglia were also immunoreactive to these antisera except for being tau negative in the putamen. Silver impregnated nerve fibres showed only MBP immunoreactivity. These findings indicate that the argyrophilia in the OPCA subjects closely correlates with PHF and tau immunoreactivities.

Aged↗

Left hypofrontality correlates with blunted affect in schizophrenia.

Regional cerebral blood flow (rCBF) during the resting state was measured using the 133Xe inhalation technique in 39 patients diagnosed as having schizophrenic disorder according to the DSM-III criteria and 30 age- and sex-matched healthy volunteers. All the patients were receiving neuroleptic medication. The bilateral hemispheric mean flow values in the schizophrenic patients decreased significantly and the relative flow distribution reduced significantly only in the left frontal region compared to the controls. The lower the left frontal blood flow in schizophrenics, the more pronounced were the negative symptoms including blunted affect, avolition-apathy and inattention. These results suggest that the negative symptoms in schizophrenics are related to left frontal lobe dysfunction.

Adult↗

A computerized tomographic study in patients with delusional and non-delusional depression.

This is a description of a computerized tomographic study of 45 non-delusional depressed, 29 delusional depressed patients and 77 neurotic control subjects. The cerebral atrophy ratio (CAR) on the three different slices and the ventricular ratio (VBR) of the anterior horn and the body of the lateral ventricles were calculated, analyzed and compared using Student's t test. Compared to the control subjects, the non-delusional depressive patients had greater CAR values than the controls but there were no significant differences of VBR values between the two groups. The patients with delusional depression had significantly larger CAR and VBR values than the non-delusional depressives and control subjects. The delusional depressives had greater brain atrophy than the non-delusionals and it was suggested that organic cerebral factors may have etiological significance in the depressions, especially the delusional depressives.

Adult↗

Eating disorder and schizophrenia.

Five cases with eating disorders (one case with anorexia nervosa alone, 4 cases with anorexia nervosa and bulimia nervosa) complicated with schizophrenia and 3 cases of bulimia nervosa complicated with schizophrenia were reported. The eating disorders and schizophrenia were diagnosed according to the diagnostic criteria of DSM-III-R. As to the type of schizophrenia, 4 patients were of an undifferentiated type and 4 cases were of a disorganized type. Regarding the prepsychotic personality, 6 of the 8 cases showed schizothyme personality traits. All the patients showed depressive symptoms which are relatively common in eating disorders. In all the patients, significant social or school life difficulties persisted and a resumption of premorbid functioning was not seen. The possibility of an affinity between anorexia nervosa and schizophrenia was discussed.

Adult↗

A retrospective study on delirium type.

The clinical features of delirium type were retrospectively studied to characterize a delirium type in consecutive 106 patients. The subjects suffered from 15 medical diseases and were grouped into hyperactive, hypoactive and mixed types according to their cardinal features. The incidence of delirium was the highest in 70-year-old subjects and there was a gender effect in all the subjects. A decade effect was present in the outcome, delirium type and delirium duration. The delirium type was associated with age at the delirium onset, outcome and underlying disease. The incidence of hypoactive type correlated with that of mixed and hyperactive types, and a high rate of full recovery in the hyperactive type and a high rate of death in the mixed type were noted. The increase in incidence of the mixed type and the decrease in incidence of the hyperactive type contributed to a poor outcome. Malignancy, hepatic, cerebrovascular and bone and joint diseases highly correlated with the occurrence of delirium.

Adult↗

Sympathoadrenal system in neuroendocrine control of glucose: mechanisms involved in the liver, pancreas, and adrenal gland under hemorrhagic and hypoglycemic stress.

Glucose homeostasis is maintained by complex neuroendocrine control mechanisms, involving three peripheral organs: the liver, pancreas, and adrenal gland, all of which are under control of the autonomic nervous system. During the past decade, abundant results from various studies on neuroendocrine control of glucose have been accumulated. The principal objective of this review is to provide overviews of basic adrenergic mechanisms closely related to glucose control in the three peripheral organs, and then to discuss the integrated glucoregulatory mechanisms in hemorrhage-induced hypotension and insulin-induced hypoglycemia with special reference to sympathoadrenal control mechanisms. The liver is richly innervated by sympathetic and parasympathetic nerves. The functional implication in glucoregulation of sympathetic nerves has been well-documented, while that of parasympathetic nerves remains less understood. More recently, hepatic glucoreceptors have been postulated to be coupled with capsaicin-sensitive afferent nerves, conveying sensory signals of blood glucose concentration to the central nervous system. The pancreas is also richly supplied by the autonomic nervous system. Besides the well documented adrenergic and cholinergic mechanisms, the potential implication of peptidergic neurotransmission by neuropeptide Y and neuromodulation by galanin has recently been postulated in the endocrine secretory function. Presynaptic interactions of these putative peptidergic neurotransmitters with the classic transmitters, noradrenaline and acetylcholine, in the pancreas remain to be clarified. It may be of particular interest that it was vagus nerve stimulation that caused a dominant release of neuropeptide Y over that caused by sympathetic nerve stimulation in the pig pancreas. The adrenal medulla receives its main nerve supply from the greater and lesser splanchnic nerves. Adrenal medullary catecholamine secretion appears to be regulated by three distinct local mechanisms: adrenoceptor-mediated, dihydropyridine-sensitive Ca2+ channel-mediated, and capsaicin-sensitive sensory nerve-mediated mechanisms. In response to hemorrhagic hypotension and insulin-induced hypoglycemia, the sympathoadrenal system is activated resulting in increases of adrenal catecholamine and pancreatic glucagon secretions, both of which are significantly implicated in glucoregulatory mechanisms. An increase in sympathetic nerve activity occurs in the liver during hemorrhagic hypotension and is also likely to occur in the pancreas in response to insulin-induced hypoglycemia. The functional implication of hepatic and central glucoreceptors has been suggested in the increased secretion of glucose counterregulatory hormones, particularly catecholamines and glucagon.

Adrenal Glands↗

Effects of clentiazem (TA-3090) and nifedipine on basal circulating catecholamine levels and on stimulation-evoked adrenal catecholamine secretion in anesthetized dogs.

The effects of TA-3090 (clentiazem) and nifedipine on basal sympathoadrenal activity and on the adrenal medullary response during splanchnic nerve stimulation were studied in dogs anesthetized with sodium pentobarbital. Plasma concentrations of epinephrine and norepinephrine were measured in aortic and adrenal venous blood before and after acute administration of the drugs, as well as during left splanchnic nerve stimulation before and after administration of drugs. Following intravenous injections, TA-3090 (30, 100, and 300 micrograms/kg) did not affect basal circulating catecholamine levels, whereas nifedipine (10, 30, and 100 micrograms/kg) markedly increased aortic epinephrine and norepinephrine concentrations in a dose-dependent manner in correlation with progressive decreases in mean arterial pressure. The changes in aortic epinephrine and norepinephrine concentrations were inversely related to those in mean arterial pressure (r = 0.603, p < 0.01; r = 0.536, p < 0.01; respectively). In response to direct splanchnic nerve stimulation (2 Hz, 2 ms, 1 min, 12 V), adrenal venous epinephrine and norepinephrine concentrations significantly increased, with a high degree of reproducibility. The catecholamine responses to splanchnic nerve stimulation were not affected by either TA-3090 or nifedipine at any dose tested. The present results suggest that the increases in circulating catecholamine levels following nifedipine administration are due to baroreflex activation secondary to the drug-induced hypotension. The study indicates that both TA-3090 and nifedipine did not significantly affect L-type Ca2+ channels related to catecholamine release in the adrenal medulla under the present experimental conditions.

Adrenal Glands↗

Evidence against a humoral control mechanism in adrenal catecholamine secretion during insulin-induced hypoglycemia.

The present study tested the hypothesis that a humoral control mechanism is involved in the enhanced adrenal catecholamine secretion during insulin-induced hypoglycemia. The experiments were carried out in anesthetized dogs in which neuronal and humoral components were simultaneously determined by measuring catecholamine output from the right innervated and the left acutely denervated adrenal gland, respectively. Different levels of hypoglycemia were induced by intravenous injection of insulin with doses of 0.075 (n = 6), 0.150 (n = 6), and 0.300 IU/kg (n = 6) in three separate groups of dogs. Catecholamine output in the right innervated gland increased dose dependently (P less than 0.05), reaching a maximum level 45 min after insulin administration. By contrast, catecholamine output from the left denervated adrenal gland remained unchanged at all doses tested. In sham-denervated animals (n = 7), catecholamine output from the left adrenal gland increased to a magnitude similar to that observed in the right innervated gland after insulin administration. Plasma glucose concentration significantly decreased in a dose-dependent manner, reaching a nadir 30 min after insulin administration. Maximum decreases in plasma glucose concentration could be strongly correlated with maximum increases in catecholamine output from the right innervated adrenal gland (r = -0.66, n = 18, P = 0.011), but not with those from the left denervated gland (r = -0.32, n = 18, P = 0.455). The present results do not support the functional existence of a humoral mechanism permitting the release of adrenal catecholamines during insulin-induced hypoglycemia.

Adrenal Glands↗

Are there sequential morphometrical changes in the nucleus basalis in Alzheimer's disease?

Degenerated neurons of the nucleus basalis of Meynert (nbM) were quantitatively analyzed in 3 normal and 3 Alzheimer's disease (AD) subjects. In this study, the Ch4 of the nbM was examined using the indirect immunoperoxidase method with a monoclonal antibody to acetylcholinesterase (AChE) counterstained with cresyl violet. AChE-rich neurons were designated as the cholinergic neurons. The cross-sectional area of all the Ch4 neurons with clearly visible nucleoli in one preparation was measured using a computer image analyzing system. Furthermore, we compared these data with the numbers of neurofibrillary tangles (NFTs) and neuritic plaques (NPs) in the temporal cortex by Gallyas silver stain. The cholinergic neurons decreased in number and size according to the length of the disease duration but the surviving cholinergic neurons in the size range from 800 to 1,000 micron 2 in a case with short clinical duration were increased in number. The non-cholinergic neurons showed only atrophy without definite neuronal cell depletion. The 400- to 1,000-microns 2-sized non-cholinergic neurons were markedly decreased in number, and the number of 300-microns 2-sized non-cholinergic neurons remained unchanged. Although there was an inverse correlation between the degree of atrophy and depletion of the cholinergic neurons with the number of NFTs and NPs in 2 AD cases with 3 and 6 years of disease duration, this correlation was not found in an AD case with 12 years of disease duration, probably due to extensive and profound grey matter degeneration.

Acetylcholinesterase↗