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Biomedical subjects

K Miki

Publications and source records attributed to K Miki.

At least 217 records · Page 12Linked to original sources

Mechanism of thirst attenuation during head-out water immersion in men.

The purpose was to determine whether extracellular volume or osmolality was the major contributing factor for reduction of thirst in air and head-out water immersion in hypohydrated subjects. Eight males (19-25 yr) were subjected to thermoneutral immersion and thermoneutral air under two hydration conditions without further drinking: euhydration in water (Eu-H2O) and euhydration in air, and hypohydration in water (Hypo-H2O) and hypohydration in air (3.7% wt loss after exercise in heat). The increased thirst sensation with Hypo-H2O decreased (P < 0.05) within 10 min of immersion and continued thereafter. Mean plasma osmolality (288 +/- 1 mosmol/kgH2O) and sodium (140 +/- 1 meq/l) remained elevated, and plasma volume increased by 4.2 +/- 1.0% (P < 0.05) throughout Hypo-H2O. A sustained increase (P < 0.05) in stroke volume accompanied the prompt and sustained decrease in plasma renin activity and sustained increase (P < 0.05) in plasma atrial natriuretic peptide during Eu-H2O and Hypo-H2O. Plasma vasopressin decreased from 5.3 +/- 0.7 to 2.9 +/- 0.5 pg/ml (P < 0.05) during Hypo-H2O but was unchanged in Eu-H2O. These findings suggest a sustained stimulation of the atrial baroreceptors and reduction of a dipsogenic stimulus without major alterations of extracellular osmolality in Hypo-H2O. Thus it appears that vascular volume-induced stimuli of cardiopulmonary baroreceptors play a more important role than extracellular osmolality in reducing thirst sensations during immersion in hypohydrated subjects.

Adult↗

Purification and characterization of intracellular proteinases in Pleurotus ostreatus fruiting bodies.

A serine proteinase (ProA, EC 3.4.22.9) and two metalloendopeptidases (ProB, EC 3.4.99.32 and ProC, 3.4.24.4), have been purified to homogeneity from the fruiting bodies of Pleurotus ostreatus. ProA is a serine proteinase with a mass of 30 kDa, which has amidolytic and esterolytic activities besides proteolysis and catalyzes preferential cleavage of the peptide bonds involving the carboxyl groups of hydrophobic amino acid residues in oxidized bovine insulin B chain. The N-terminal amino acid sequence was VTQTNAPWGLSRL. ProB is a zinc-enzyme with a mass of 18 kDa, which is devoid of lysine, and its N-terminal sequence was ATFVGCSATRQ. The enzyme is inactivated completely by EDTA and 1,10-phenanthroline, and Zn(2+)-depleted ProB can regain the activity with Zn2+, Co2+, or Mn2+. Specific cleavage of Pro29-Lys30 in oxidized bovine insulin B chain, preferential generation of lysylpeptides from proteins, and a high susceptibility of polylysine suggest that ProB splits specifically the peptide bonds involving the alpha-amino group of lysyl residues. ProC is a metalloendopeptidase of a mass of 42.5 kDa, and Zn2+ was the most effective divalent metal ion to activate the EDTA-inactivated enzyme.

Amino Acid Sequence↗

[Workload of women workers rearing their children, evaluated by catecholamine excretion, salivary cortisol and self-rated scores of fatigue].

The study was designed to examine the extent of the workload in female workers with children, in the office and at home, as compared with that of male workers with children and single women workers. Urine and saliva were collected during the daytime and evening on workdays and days off, and catecholamines in urine and cortisol in saliva were analyzed. Heart rate, blood pressure and frequencies of subjective fatigue symptoms were also measured. In the three groups, urinary excretion of adrenaline during daytime work was found to be significantly higher than on days off. The difference between workdays and days off in evening adrenaline excretion tended to be greater in the 'women with children' group than in their male counterparts. Urinary noradrenaline and salivary cortisol in women with children showed a tendency to be higher in the afternoon and evening on workdays than that on days off, while no difference between workdays and days off was observed in the other two groups. The heart rate in women with children was greater during the evening on workdays than that on days off. The frequency of subjective fatigue symptoms in women with children increased with the time of day on workdays, but remained unchanged on days off. The findings suggest that the workload of female workers rearing their children is greater than that of male counterparts, both in the office and at home, on workdays.

Adult↗

Circadian rhythm of catecholamine excretion in rats after phase shift of light-dark cycle.

To clarify the time course of circadian rhythm adaptation to a phase shift of the light-dark (LD) cycle, urinary excretion of catecholamines was measured in rats before and after a 12-hour or 6-hour phase delay of a 12-hour light and 12-hour dark schedule. In rats under a basal condition, distinct circadian rhythms in catecholamine excretion were observed, especially in adrenaline excretion. During the 1st and 2nd days after a 12-hour phase delay, the acrophase and amplitude of adrenaline rhythm remained almost unchanged, but thereafter the acrophase was retarded and the amplitude was reduced. The acrophase once again became constant after 5 or 6 days, but the ratio of amplitude to mesor in the circadian rhythm of adrenaline excretion and the ratio of light-period to 24-hour noradrenaline excretion were readjusted to the new LD schedule on 11th or 12th day. IN the 6-hour phase delay of the LD cycle, similar findings were observed, and the results suggested adaptation on the 5-6th day. It is considered that the circadian rhythms of the sympathetic adrenomedullary function are restored, at the latest, 12 days after a 12-hour delay of the LD cycle, and 6 days after a 6-hour delay, suggesting that rats need approximately 1 day to adapt to a 1-hour phase shift.

Animals↗

Substance P induced by peripheral nerve injury in primary afferent sensory neurons and its effect on dorsal column nucleus neurons.

Using in situ hybridization and the retrograde tracer, Fluorogold, we examined the expression of preprotachykinin (PPT) mRNA in the rat dorsal root ganglion neurons projecting to the gracile nucleus. Seven days after unilateral sciatic nerve transection, some medium- to large-sized neurons in the rat dorsal root ganglia projecting to the gracile nucleus express PPT mRNA, whereas very few gracile nucleus-projecting neurons on the contralateral side express PPT mRNA. Immunohistochemistry revealed an increase in substance P (SP) immunoreactivity in the gracile nucleus and large myelinated fibers in the dorsal root 2 weeks after unilateral sciatic nerve transection. The results suggest that medium to large DRG cells that project to the gracile nucleus express PPT mRNA de novo in response to peripheral nerve injury, and increased SP is transported to the gracile nucleus through large myelinated fibers. To determine whether the increased SP might affect the excitability of the gracile nucleus neurons postsynaptically, Fos expression after electrical stimulation of the injured sciatic nerve was examined. Multiple injections of the NK-1 receptor antagonist, CP-96,345, suppressed stimulus-induced Fos expression in gracile nucleus neurons including thalamic relay neurons. The inactive enantiomer, CP-96,344, had no effect on stimulus-induced Fos expression. These data indicate that the de novo synthesized SP in the lesioned primary afferent neurons may be involved in an augmentation of excitability in the dorsal column-medial lemniscus sensory pathway. This hyperexcitability may play a role in the pathogenesis of abnormal neuropathic sensations following peripheral nerve injury.

Animals↗

[Prevalence of urinary incontinence among institutionalized persons aged 60 and over in Japan].

In order to estimate the prevalence of persons experiencing urinary incontinence among the institutionalized aged 60 and over in Japan, a questionnaire survey was conducted in 16 prefectures in February 1991. The questionnaires were distributed and collected by the nurses in hospitals and in other facilities. A total of 10,022 residents were asked to answer a questionnaire on their urinary incontinence condition and 9,798 responses were analysed. The main results were as follows; 1) The prevalence rate of urinary incontinence occurring almost daily in hospitalized persons aged 60 and over was 23.3% for men, 23.8% for women. 2) The prevalence rate of urinary incontinence occurring almost daily in institutionalized persons aged 60 and over in special nursing homes was 64.2% of the aged 60 and over for men, 67.9% for women. 3) The prevalence of urinary incontinence increased with age for both sexes especially in hospitalized persons. 4) The 95% confidence interval estimate for the number of the hospitalized over 60 years old suffering from almost daily urinary incontinent incidents was estimated to be from 31,000 to 113,000 in men and from 60,000 to 182,000 in women. 5) The 95% confidence interval estimate for the number of the institutionalized in special nursing home over 60 years old suffering from almost daily urinary incontinent incidents was estimated to be from 34,000 to 50,000 in men and from 97,000 to 119,000 in women. 6) The 95% confidence interval estimate for the number of the institutionalized over 60 years old suffering from almost daily urinary incontinent incidents was estimated to be from 318,800 to 570,600 in both sexes. 7) A random sampling survey is required to elucidate the actual state of prevalence in all generations. 8) Future research should emphasize the assessment of preventive and medical interventions, as incontinence is preventable and medical and surgical treatment options are available.

Age Factors↗

[Pepsinogen].

It is generally accepted that extensive chronic atrophic gastritis is a precursor to gastric cancer in populations at high risk for this tumor. To improve the effectiveness of gastric cancer screening, we have devised a new screening method that investigates the serum pepsinogen levels and applied a serum pepsinogen test to mass screening for gastric cancer at a certain workplace for the first time. This screening system (named "stomach dry dock") is based on the findings that many gastric cancer develop in the stomach mucosa affected by severe and extensive chronic atrophic gastritis. Using the serum tests (Pepsinogen I/II RIA BEAD Kit: Dainabot Co., LTD. Japan) we have screened 14,862 employees of a certain company in 1991-93 and 25 cases (0.17%) of gastric cancer including 21 cases (84%) of early gastric cancer and 10 cases (0.07%) with gastric adenoma; precancerous lesion. The results are better than that of the traditional barium X-ray screening (incidence of gastric cancer is 0.07%) in the same company. In conclusion the best sensitivity for detecting gastric cancer is achieved by the mass screening with serum pepsinogen tests in combination with X-ray or endoscopy.

Chronic Disease↗

Congenital hypothyroidism: assessment with ultrasound.

PURPOSE: To determine the clinical utility of cervical ultrasound in patients suspected of having congenital hypothyroidism. METHODS: Thirty-seven patients with suspected congenital hypothyroidism underwent ultrasound and scintigraphic evaluation of the thyroid anatomy, morphology, and function. The ultrasound findings and laboratory data were compared with the standard-of-reference scintigraphic findings and laboratory data for diagnosing specific causes in those patients, and prognosis was correlated with the ultrasound findings. RESULTS: Ultrasound was not reliable for detecting ectopia (n = 8) or differentiating ectopia from aplasia (n = 1). Ultrasound showed ectopia in six (four in the mouth floor and two in the tongue base) of eight cases (75% sensitivity). Ultrasound did not show one ectopia in the floor of mouth because its echogenicity was similar to that of surrounding tissues. A second ectopia, in the hypopharynx, was missed because of hindrance of the laryngeal air. Radioactive iodine uptake and scintigraphy was required for the patients with enlarged glands in the normal place to differentiate dyshormonogenesis from other categories. Specific causes were diagnosed correctly with ultrasound findings and laboratory data alone in all of the 20 patients who had hemiaplasia or small or normal-size glands in the normal location. Incidences of heterogeneity and hypoechogenicity of the thyroid gland in patients with prolonged clinical course (whose replacement therapy or follow-up extended for more than 1 year) were significantly higher than those in patients with short clinical course. CONCLUSION: Ultra-sound can obviate the need for scintigraphy in more than half (54%) of patients with possible congenital hypothyroidism. Ultrasound has a potential to predict prognosis of these patients.

Congenital Hypothyroidism↗

The Comprehensive Assessment List for Affective Disorders (COALA): a polydiagnostic, comprehensive, and serial semistructured interview system for affective and related disorders.

This supplement describes the development and structure of the Comprehensive Assessment List of Affective Disorders (COALA) system, which was recently developed for a collaborative follow-up study of a broad spectrum of affective disorders in Japan and which consists of a series of semistructured interviews for affective and related disorders. The COALA distinguishes itself from the extant semistructured interviews by being able to provide polydiagnostic, comprehensive and serial assessments. It is polydiagnostic because it derives diagnoses according to 29 historical and modern diagnostic systems through computer algorithms. It is comprehensive because it not only depicts the symptoms profile and rates their severity according to various endogenicity indices and severity rating scales but also measures, in the psychosocial domain, the life events and their characteristics. In addition, it has sections for past illnesses and family history. It is serial because the system includes follow-up semistructured interviews that can be administered monthly and that monitor changes in the psychopathological and psychosocial features. The theoretical underpinnings of the COALA system, especially its polydiagnostic approach to a broad spectrum of affective disorders and its treatment of psychosocial factors, are discussed in view of recent proposals for the future nosological research. The findings of the interrater reliability study (n = 107) are also presented, with satisfactory to excellent results for almost all of the psychopathological and psychosocial variables, all of the composite severity ratings and most of the polydiagnostic evaluations.

Female↗

Relationship between Helicobacter pylori infection, atrophic gastritis and gastric carcinoma in a Japanese population.

AIM: To evaluate the possible relationship between Helicobacter pylori infection and gastric carcinoma, and its precursor lesion, intestinal metaplasia, in a Japanese population. SUBJECTS AND METHODS: H. pylori infection was identified by the presence of anti-H. pylori immunoglobulin (Ig)G. The frequency of H. pylori infection was compared in 109 patients with gastric carcinoma, the same number of patients with atrophic gastritis and asymptomatic controls matched for age, sex and place of birth. To study the relation between H. pylori and intestinal metaplasia, sera and gastric antral and corpus mucosal biopsies were obtained from 58 asymptomatic controls, 92 patients with chronic gastritis and 80 patients with peptic ulcer. RESULTS: The presence of IgG antibody to H. pylori was significantly more frequent in those with gastric carcinoma than in asymptomatic controls (87.2 versus 74.3%; odds ratio 2.4; 95% confidence interval 1.2-4.8). The positive rates of H. pylori IgG antibody were 80.7% in patients with atrophic gastritis. Mean serum gastrin and pepsinogen II levels in H. pylori-positive patients were higher than those in H. pylori-negative patients. Serum gastrin and pepsinogen I levels were significantly higher in controls than gastric carcinoma patients (P < 0.01 and P < 0.05, respectively). Serum pepsinogen I:II ratios were significantly lower in controls than in gastric carcinoma patients (P < 0.01). Intestinal metaplasia was strongly associated with H. pylori infection, and was only found in patients with IgG antibodies to H. pylori. CONCLUSIONS: These results suggest that H. pylori infection is associated with the development of gastric cancer by providing a suitable environment for carcinogenesis of the gastric mucosa, such as gastric atrophy and intestinal metaplasia.

Enzyme-Linked Immunosorbent Assay↗

Phase I clinical study with 8-chloro-cAMP and evaluation of immunological effects in cancer patients

The site-selective cyclic AMP analogue 8-chloro-cAMP (8-Cl-cAMP) is able to inhibit the growth of a wide variety of cancer cell lines in vitro and in vivo. 8-Cl-cAMP has been extensively investigated as a new potential anticancer agent and, more recently, preclinical Phase I studies have been conducted in animal models to study its toxicity. We have conducted the first Phase I trial with 8-Cl-cAMP to define the maximum tolerated dose, toxicity, plasma drug levels, and immunological effects in patients with cancers refractory to standard treatments. We have administered 36 courses of 8-Cl-cAMP to 17 patients by continous i.v. infusion of the drug for 5 days/week for 2 weeks followed by a 1-week rest period. Six increasing dose levels, from 0.01 to 0.25 mg/kg/h, were explored. Drug plasma levels were determined and the expression of interleukin 2 receptor alpha amount of natural killer cells, and cytolytic activity against K562 cells were measured in peripheral blood lymphocytes. A grade 4 and a grade 3 increase in serum creatinine and a grade 2 increase in blood urea nitrogen observed in two patients were the dose-limiting toxicity. The maximum tolerated dose (0.2 mg/kg/h) determined a grade 1 increase in serum creatinine. An increase in calcium levels was observed in several patients. The 8-Cl-cAMP plasma concentrations obtained at the steady state were in the range previously shown to be effective for cancer cell growth inhibition in vitro. Interleukin 2 receptor alpha expression, natural killer cell number, and cytolytic activity from peripheral blood lymphocytes were markedly increased after 8-Cl-cAMP administration at all dose levels. In conclusion, at doses below the maximum tolerated dose, 8-Cl-cAMP was not toxic but reached plasma concentrations in the potential therapeutic range for growth inhibition. Moreover, 8-Cl-cAMP determined a marked biomodulatory effect and showed antitumor activity.

Journal Article↗

Molecular cloning of a novel thyroid/steroid receptor superfamily gene from cultured rat neuronal cells.

Brain neuronal cells in primary culture provide one system for the analysis of neuronal development, including apoptosis. By PCR amplification, with primers designed from conserved sequences among nuclear receptors, a novel member of the thyroid/steroid receptor superfamily was identified from forebrain neuronal cells undergoing apoptosis and designated as NOR-1 (neuron derived orphan receptor). A cDNA clone of NOR-1 encodes a 68kDa, 628 amino acid residue-containing protein, with an amino acid sequence highly homologous to the Nur77 family in its DNA-binding domain and moderately so in its putative ligand-binding domain. Using mobility shift assay, we showed that the NOR-1 protein binds to the B1a response-element which has been identified as the target sequence of the Nur77 family, suggesting that three members of the Nur77 family may transactivate common target gene(s) at different situations.

Amino Acid Sequence↗

Hepatocyte growth factor region specifically stimulates gastro-intestinal epithelial growth in primary culture.

Hepatocyte growth factor (HGF) stimulated the growth of fetal rat gastrointestinal epithelial cells in primary culture with a clear dose-response relationship. The epithelial response to the mitogenic activity of HGF was different among the region of the gastro-intestinal tract; glandular stomach most responsive, followed by intestine and forestomach. The interaction of HGF with other growth factors in inducing the epithelial growth was also different depending on the type of the epithelial cells, indicating a region-specific growth regulation in the gastro-intestinal tract. Analyses using Northern blot and RT-PCR revealed that HGF mRNA was expressed only in mesenchymes but not in epithelia of the gastro-intestinal tract while expression of c-met (HGF receptor) gene was observed in both tissues. These results suggest that gastro-intestinal mesenchymes secrete HGF which stimulates the growth of attaching epithelial cells by a paracrine mechanism, and that the epithelial response to HGF is controlled by a region-specific growth regulatory mechanism.

Animals↗

Crystallization of mutant beta subunit of F1-ATPase from thermophilic Bacillus PS3.

The mutant beta subunit of F1-ATPase from a thermophilic Bacillus strain, PS3, in which tyrosine at position 341 is replaced by leucine (beta Y341L) was expressed in Escherichia coli and crystallized by the vapor-diffusion procedure. Small needle-like crystals were obtained using ammonium sulfate as a precipitant and grown by the stepwise seeding method. The crystals obtained by this procedure diffracted X-rays to about 3 A resolution. The diffraction patterns indicated that the crystals belong to the orthorhombic system and the space group I222 or I2(1)2(1)2(1) with unit-cell dimensions of a = 232 A, b = 66 A, and c = 80 A. It is thought that the asymmetric unit comprises one beta Y341L molecule.

Bacillus↗

Structural characterization of porcine enteropeptidase.

Enteropeptidase (EC 3.4.21.9) is a key enzyme in the intestinal digestion cascade responsible for the conversion of trypsinogen to trypsin, which then activates various pancreatic zymogens. In order to structurally characterize the enzyme, we purified the enzyme from porcine duodenal mucosa and showed that it consists of three polypeptide chains, which we named "mini" chain (M chain), light chain (L chain), and heavy chain (H chain) in order of increasing molecular size. Based on their NH2-terminal sequences, a cDNA clone for porcine enteropeptidase was isolated and analyzed. The clone was 3597 base pairs long, which encoded 1034 amino acid residues of a single-chain precursor form of enteropeptidase. The precursor contained an additional NH2-terminal 51-residue sequence including a putative internal signal sequence, followed by the M chain (66 residues), the H chain (682 residues), and the L chain (235 residues) in that order. The H chain had regions partially homologous in sequence with low density lipoprotein receptor and complement components. On the other hand, the L chain was highly homologous with the catalytic domains of trypsin-like serine proteinases. The structural model of the L chain suggests that the sequence, Arg885-Arg-Arg-Lys888, is probably involved in the unique substrate specificity of the enzyme, preferring acidic amino acid residues at the P2-P5 sites.

Amino Acid Sequence↗

Glucocorticoids inhibit the proliferation of mucosal cells and enhance the expression of a gene for pepsinogen and other markers of differentiation in the stomach mucosa of the adult rat.

Adrenalectomy caused a significant decrease in the mucosal level of pepsinogen in the adult rat stomach. This decrease was mainly due to a reduction in the level of the main component of rat pepsinogen isozymogens, namely, Pg1 and in the level of expression of Pg1 mRNA, with a maximal effect being evident 48 hours after operation. Immunohistochemical analysis revealed that the level of expression of Pg1 in the pepsinogen-producing cells was decreased throughout the stomach mucosa and this decrease was especially marked in the immature chief cells located in the glandular neck of the fundic mucosa. Adrenalectomy also increased the proliferation of mucosal cells and suppressed the expression of cathepsin E and class III mucin, markers of differentiated stomach mucosa. All these changes were reversed by hydrocortisone replacement and the extent of the recovery of the level of Pg1 mRNA was dependent on the dose of hydrocortisone, indicating the transcriptional control of the Pg1 gene by hydrocortisone. The observed results suggest that the continuous presence of glucocorticoids is necessary for active transcription of Pg1 gene in fully differentiated stomach mucosa and that glucocorticoids are important regulators of both the function and the morphology of stomach mucosal cells.

Adrenalectomy↗