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Biomedical subjects

Y Murakami

Publications and source records attributed to Y Murakami.

At least 397 records · Page 22Linked to original sources
PubMed1997

Central serotonin level-dependent changes in body temperature following administration of tryptophan to pargyline- and harmaline-pretreated rats.

1. The effect of tryptophan on body temperature was studied in rats pretreated with pargyline, an irreversible monoamine oxidase inhibitor (MAOI), and harmaline, a reversible MAOI. 2. Tryptophan (100 mg/kg IP) produced hypothermia followed by hyperthermia in pargyline-pretreated rats, and hypothermia in harmaline-pretreated rats, but tryptophan did not cause body temperature changes by itself. 3. The tryptophan-induced hypo- and hyperthermic effects, which peaked at about 1 and 6 hr after tryptophan administration, respectively, were accompanied by a significant increase in serotonin (5-HT) levels in the pargyline-pretreated rat brain (75%-138.7% and 207%-240.9% increase, respectively), and the 5-HT levels in the hyperthermic state were significantly higher than those in the hypothermic state. 4. In harmaline-pretreated rats, tryptophan also increased the central 5-HT levels (80.5%-95.5% increase) in the hypothermic state, and the effect peaked at about 1 hr after tryptophan administration. The central 5-HT levels in harmaline-pretreated rats slightly decreased at 6 hr after tryptophan administration and were significantly lower than those in the hyperthermic state in the pargyline-pretreated rats. 5. Tryptophan (100 mg/kg IP) administration decreased 5-hydroxy indole acetic acid (5-HIAA) levels, 5-HT turnover, and dopamine (DA) turnover in the brain of pargyline-pretreated rats, but these parameters were not significantly different between the hypothermic and hyperthermic states (i.e., at 1 and 6 hr after tryptophan administration, respectively). 6. These results suggest that the tryptophan-induced body temperature change depends on the different 5-HT levels in the brain and that the 5-HT level needed to induce hyperthermia is higher than that needed to induce hypothermia.

Animals↗
PubMed1997

The relationship between orthostatic dizziness and hypotension in male medical students.

We carried out a questionnaire survey regarding symptoms of orthostatic dysregulation (OD) and administered the Schellong test (orthostatic test) to 123 normal male medical students aged 21-29 years to investigate the relationship between orthostatic dizziness and hypotension. OD was identified in 15 (12.2%) of the subjects based on the questionnaire results. Orthostatic dizziness was noted in 40.7% of the subjects (50/123). The occurrence of orthostatic dizziness was most significantly related to systolic pressure decrease during the procedure for the Schellong test. These results suggest that the testing procedure introduced by Schellong can be useful, and clinically applicable to the assessment of orthostatic dizziness, since it presents the advantage of being simple enough to carry out in clinical practice.

Adult↗
PubMed1997

Synthesis and pharmacological properties of ureidomethylcarbamoylphenylketone derivatives. A new potent and subtype-selective nonpeptide CCK-B/gastrin receptor antagonist, S-0509.

A novel series of CCK-B/gastrin receptor antagonists-ureidomethylcarbamoylphenylketone derivatives-were designed, synthesized, and evaluated for activity. Structure-activity relationship studies revealed the importance of a carboxylic acid at substituent R2 and tert-butoxycarbonyl group at R1 in structure A. Compound 7a (S-0509) showed remarkable affinity for the CCK-B/gastrin receptor and a subtype selectivity profile in vitro. Administration (id) of 7a led to excellent inhibition of gastric acid secretion induced by pentagastrin in anesthetized rats with an ED50 value of 0.014 mg/kg. Furthermore, 7a proved to have poor blood-brain permeability by its small effect on enhancement of morphine analgesia. Thus, S-0509 has an increase in selectivity for the peripheral effects of gastrin antagonism from the central effects of CCK-B antagonism.

Animals↗
PubMed1997

Pyrrolidine dithiocarbamate inhibits cytokine-induced VCAM-1 gene expression in rat cardiac myocytes.

We investigated whether interleukin-1alpha (IL-1) would induce gene expression of vascular cell adhesion molecule-1 (VCAM-1) in cardiac myocytes and, if so, whether nuclear factor kappaB (NF-kappaB) was involved. We evaluated the VCAM-1 gene expression in cultured neonatal rat cardiac myocytes by the reverse transcription-polymerase chain reaction. IL-1 alone or together with interferon-gamma (IFN) induced VCAM-1 gene expression in the cells. Induction of VCAM-1 gene expression in response to IL-1 and IFN was antagonized in a concentration-dependent manner by pyrrolidine dithiocarbamate, an inhibitor of NF-kappa b activation (25-100 microM). Tosyl-lysine-chloromethyl ketone, another inhibitor of NF-kappa b activation, also inhibited the expression of the VCAM-1 gene in response to IL-1 and IFN. Thus, VCAM-1 gene expression appeared to be mediated by NF-kappa b in cardiac myocytes, and this cardiac myocyte VCAM-1 may be involved in cardiac inflammatory disorders. Disruption of expression of VCAM-1 by inhibition of NF-kappa b activation may indicate a target for pharmacologic intervention intended to limit cardiac inflammation.

Animals↗
PubMed1997

The relationship between psychosomatic factors and orthostatic dysregulation in young men.

We carried out a questionnaire survey regarding symptoms of orthostatic dysregulation and administered the Japanese Edition of the Cornell Medical Index-Health Questionnaire (JCMI) and the Yatabe-Guilford Personality Test (Y-G test) to 151 male medical students (mean age, 24.6 yr). Orthostatic dysregulation was identified in 19 (12.5%) of the subjects based on the questionnaire results. The percentage classed as types III (possible neurotic) and IV (probable neurotic) according to the health questionnaire was 47.3% in the 19 with orthostatic dysregulation and 8.9% in the controls (n = 78). The percentage classed as types B and E, suggestive of emotional or psychological disturbance according to the personality test, was 42.1% in those with orthostatic dysregulation and 8.9% in the controls. These differences were significant (P < 0.01). These results suggest that psychosomatic factors influence the occurrence of orthostatic dysregulation in young men.

Abdominal Pain↗
PubMed1997

Prognostic value of Ki-67 antigen and p53 protein in urinary bladder cancer: immunohistochemical analysis of radical cystectomy specimens.

OBJECTIVE: To investigate the role of tumour proliferation and p53 expression as a marker of survival in patients with urinary bladder cancer who undergo radical cystectomy. PATIENTS AND METHODS: Samples were obtained from 31 patients (29 men and two women, mean age 66.0 years, range 46-80) with transitional cell carcinoma of the bladder who underwent radical cystectomy. The 31 formalin-fixed radical cystectomy specimens were stained immunohistochemically for Ki-67 antigen and p53 protein using MIB1 and p53 antibodies, respectively, and the results correlated with tumour grade, stages and prognosis. RESULTS: The Ki-67 index was significantly greater in high-grade tumours and in those overexpressing p53 (> 20% positive nuclei). Patients whose tumour samples had a high Ki-67 index (> 32%) had a significantly worse prognosis than those with a lower index (P < 0.01). There was a similar correlation between Ki-67 index and prognosis in high-risk patients (grade 3 and pT3-4; P < 0.05). Although the associations between tumour grade, stage and p53 expression were not statistically significant, patients whose tumour samples overexpressed p53 had a lower survival rate (P < 0.05). No patients with tumours having a low Ki-67 and low p53 index (n = 14) died of urinary bladder cancer during the follow-up. CONCLUSION: These results suggest that immunohistochemical analyses for Ki-67 and p53 are useful prognostic indicators in patients with urinary bladder cancer who undergo radical cystectomy; the prognostic role of these markers was particularly important in high-risk (grade 3 and pT3-4) patients.

Aged↗
PubMed1997

Gene identification in 1.6-Mb region of the Down syndrome region on chromosome 21.

The Down syndrome (DS) region has been defined by analyses of partial trisomy 21. The 2.5-Mb region between D21S17 and ERG is reportedly responsible for the main features of DS. Within this 2.5-Mb region, we focused previously on a distal 1.6-Mb region from an analysis of Japanese DS patients with partial trisomy 21. Previously we also performed exon-trapping and direct cDNA library screening of a fetal brain cDNA library and identified a novel gene TPRD. Further screening of a fetal heart cDNA library was performed and a total of 44 possible exons and 97 cDNA clones were obtained and mapped on a BamH1 map. By rescreening other cDNA libraries and a RACE reaction, we isolated nearly full-length cDNAs of three additional genes [holocarboxylase synthetase (HCS), G protein-coupled inward rectifier potassium channel 2 (GIRK2), and a human homolog of Drosophila minibrain gene (MNB)] and a coding sequence of a novel inward rectifier potassium channel-like gene (IRKK). The gene distribution and direction of transcription were determined by mapping both ends of the cDNA sequences. We found that these genes, except IRKK, are expressed ubiquitously and are relatively large, extending from 100 kb to 300 kb on the genome. These nearly full-length cDNA sequences should facilitate understanding of the detailed genome structure of the DS region and help to elucidate their role in the etiology of DS.

Amino Acid Sequence↗
PubMed1997

Photodynamic effect of polyethylene glycol-modified fullerene on tumor.

Fullerence (C60) efficiently generates singlet oxygen when irradiated with light, and thus should have a photodynamic effect on tumors, if it is accumulated in the tumor tissue. To explore tumor targeting of C60, we chemically modified the water-insoluble C60 with polyethylene glycol (PEG), not only to make it soluble in water, but also to enlarge its molecular size. When injected intravenously into mice carrying a tumor mass in the back subcutis, the C60-PEG conjugate exhibited higher accumulation and more prolonged retention in the tumor tissue than in normal tissue. The conjugate was excreted without being accumulated in any specific organ. Following intravenous injection of C60-PEG conjugate or Photofrin to tumor-bearing mice, coupled with exposure of the tumor site to visible light, the volume increase of the tumor mass was suppressed and the C60 conjugate exhibited a stronger suppressive effect than Photofrin. Histological examination revealed that conjugate injection plus light irradiation strongly induced tumor necrosis without any damage to the overlying normal skin. The antitumor effect of the conjugate increased with increasing irradiation power and C60 dose, and cures were achieved by treatment with a dose of 424 micrograms/kg at an irradiation power of 107 J/cm2. These findings indicate that PEG-modified C60 is a candidate agent for photodynamic tumor therapy.

Animals↗
PubMed1997

Identification of a frameshift mutation resulting in premature termination and loss of cell wall anchoring of the PAc antigen of Streptococcus mutans GS-5.

Most strains of Streptococcus mutans possess a 190-kDa protein antigen (PAc) on their cell surfaces, while strain GS-5 produces extracellularly a 155-kDa PAc protein. The pac gene of strain GS-5 consists of 3,477 bp and codes for a protein of 1,158 amino acids. One insertion of an adenine into the 3,469th, 3,470th, or 3,471st position from the start codon results in a frameshift mutation at codon 1157 with subsequent termination after 3 additional codons.

Amino Acid Sequence↗
PubMed1997

Role of the charged tail in localization of a surface protein antigen of Streptococcus mutans.

To make clear the role of the C terminus of a surface protein antigen (PAc) of Streptococcus mutans, stepwise truncations beginning at the C terminus of PAc were performed by utilizing site-directed mutagenesis. A remarkable increase in the amount of cell-free PAc was observed upon deletion of four or more amino acid residues at the C terminus. On the other hand, the amount of cell surface PAc gradually decreased when increasing numbers (four or more) of amino acid residues were deleted at the C terminus, and deletion of six amino acids involving both the total charged tail and Leu, an amino acid residue immediately upstream of the charged tail, resulted in a drastic reduction in the amount of cell surface PAc. These results indicate that the cytoplasmic charged tail and Leu residue are required for cell surface localization of PAc in S. mutans.

Antigens, Bacterial↗
PubMed1997

Function of a cell adhesion molecule, plexin, in neuron network formation.

Plexin is a type I membrane protein which was identified in Xenopus nervous system by hybridoma technique. Molecular cloning studies demonstrated that the extracellular segment of the plexin protein possesses three internal repeats of cysteine cluster which are homologous to the cysteine-rich domain of the c-met proto-oncogene protein product. A cell aggregation test revealed that the plexin protein mediated cell adhesion via a homophilic binding mechanism, in the presence of calcium ions. Plexin was expressed in the neuronal elements composing particular neuron circuits in Xenopus CNS and PNS. These findings indicate that plexin is a new member of the Ca(2+)-dependent cell adhesion molecules, and suggest that the molecule plays an important role in neuronal cell contact and neuron network formation.

Amino Acid Sequence↗
PubMed1997

Interaction between oral alpha-streptococci and group A streptococci in patients with tonsillitis.

The incidence of oral alpha-streptococci with inhibitory activity against group A streptococci, as a defense mechanism against bacterial infection in the oral cavity, was investigated in 141 patients with streptococcal tonsillitis. The study population included both children (n = 79) and adults (n = 62). Infection by group A streptococci appeared to be more common in children than in adults, as the detection rates of inhibitory alpha-streptococci in healthy children (29.7%), as well as pediatric patients with tonsillitis (14.9%), were lower than those in adults (63.0%; p < .01). It is possible to consider oral alpha-streptococci with inhibitory activity to be among the indications for tonsillectomy in patients with streptococcal tonsillitis, since the detection rate of inhibitory alpha-streptococci in surgical cases (10.9%) was significantly lower than that in nonsurgical cases (31.1%; p < .01). The high detection rate of these strains during the postoperative state supported the observation that the incidence of group A streptococcal infection was decreased postoperatively. Accordingly, it is useful to investigate bacterial interference between oral alpha-streptococci and group A streptococci in patients scheduled for tonsillectomy.

Adolescent↗
PubMed1997

Clinicopathologic study of leptomeningeal carcinomatosis involving the temporal bone.

The temporal bone pathology of a 71-year-old man with bilateral sensorineural hearing loss and facial paralysis caused by diffuse metastatic leptomeningeal carcinomatosis is described. The origin of this malignant disease was an extremely rare entity, a transitional cell carcinoma of the renal pelvis. Histopathologic study of the temporal bone demonstrated that tumor cells filled the internal auditory meatus, infiltrated into the Rosenthal's canals, and reached the scala tympani of the basal turn of the bilateral cochleas. The vestibulocochlear nerve and facial nerve trunks in the internal auditory meatus had been destroyed by the bilateral tumor invasion. Case reports of temporal bone metastases of leptomeningeal carcinomatosis published since 1965 were reviewed. In leptomeningeal carcinomatosis, it is suggested that tumor cells infiltrate the internal auditory meatus of both ears simultaneously from the cerebrospinal fluid, involving the seventh and eighth nerve trunks, and then cause bilateral sensorineural hearing loss and facial paralysis.

Aged↗
PubMed1997

Clinical observations on acute low-tone sensorineural hearing loss. Survey and analysis of 137 patients.

We retrospectively analyzed the clinical records of 137 patients who were treated at our clinic for acute low-tone sensorineural hearing loss of unknown cause over a period of 8 years. The analyses of the clinical records indicated the following clinical characteristics: female preponderance; peak incidence during the fourth decade of life; frequent accompanying tinnitus, sensation of ear fullness, and/ or autophony; suspicion of bilateral involvement; and association with autonomic imbalance. The hearing in most of the patients completely recovered, but some selected patients experienced fluctuating hearing loss or progression to Meniere's disease. Our results suggest that a subgroup of patients with severe initial hearing loss should be carefully followed up, although it is difficult to predict the outcome of this disorder.

Acute Disease↗
PubMed1997

Incomplete thyrotroph suppression determined by third generation thyrotropin assay in subacute thyroiditis compared to silent thyroiditis or hyperthyroid Graves' disease.

Serum TSH concentrations were determined by both second and third generation assays in three types of thyrotoxicosis associated with subacute thyroiditis, silent thyroiditis, and hyperthyroid Graves' disease at the time of each patient's initial visit to the clinic. Serum TSH concentrations as measured by the second generation assay with an analytical sensitivity of 0.04 mU/L were below the detection limit in every patient. In contrast, serum TSH concentrations as measured by the third generation assay with an analytical sensitivity of 0.009 mU/L were below the detection limit in 18 of 21 (86%) patients with Graves' disease, 18 of 20 (90%) with silent thyroiditis, but only 4 of 18 (22%) with subacute thyroiditis. Changes in serum TSH concentrations were studied in healthy volunteers given daily 75 micrograms of T3; their serum TSH concentrations on the second generation assay fell below the detection limit within 3 days in every subject. However, the TSH concentration measured by the third generation assay remained above the detection limit in 6 of 8 normal subjects even on the 14th day of therapy. The reason for incomplete TSH suppression in most subacute thyroiditis patients may be that these patients had notable neck pain, and their initial visit to the clinic may have occurred earlier after the onset of disease than with patients who have had silent thyroiditis or Graves' disease. Thus, the serum TSH concentration had not decreased sufficiently below the detection limit at the time blood was drawn. The data suggest also that the highly sensitive TSH assay, if the level is above the detection limit, can be used to suppose that the short duration of the initiation of thyrotoxicosis indicates a case of subacute thyroiditis.

Acute Disease↗
PubMed1997

Stress dose-dependent suppression of heat shock protein gene expression by inhibiting protein synthesis during heat shock treatment.

When a clone of Chinese hamster ovary (CHO) cells transfected with a plasmid containing a luciferase reporter gene under the control of the human heat shock protein (hsp) 70 gene promoter was treated with cycloheximide during heat exposure at 42 and 43 degrees C for 15 to 100 minutes and then incubated at 37 degrees C after removal of cycloheximide, reporter gene expression was suppressed by the protein synthesis inhibitor only at small heat shock doses (i.e., heat shock of less than 40 minutes at 42 degrees C and 15 minutes at 43 degrees C). A similar stress dose-dependent suppression of reporter gene expression by cycloheximide was also demonstrated by treatment with sodium arsenite at 37 degrees C. However, dexamethasone-dependent reporter gene expression in a different CHO clone was not inhibited after the inducer treatment for different times in the presence of cycloheximide. In addition, synthesis of most cellular proteins (except for hsp) was not affected after heat shock treatment with cycloheximide. The results suggested that the cycloheximide inhibition of gene expression is specific to hsp gene expression induced by limited stress doses. Furthermore, a prior 42 degrees C heat shock treatment for 30 minutes induced a decreased responsiveness (tolerance) to a second 42 degrees C heat treatment for hsp gene expression, but tolerance did not develop in cells exposed to the first heat shock in the presence of cycloheximide. These results confirm previous findings that induction of hsp gene expression by stress is balanced by the severity of stress and rate of protein synthesis. They also support the proposed model of autoregulation of hsp gene expression by levels of free hsp70.

Animals↗
PubMed1997

Effects of mitragynine on cAMP formation mediated by delta-opiate receptors in NG108-15 cells.

Mitragynine, a major constituent of the young leaves of Mitragyna speciosa KORTH., has been reported to exert antinociceptive activity in mice. To determine the mechanism the influence of mitragynine on cAMP content was measured in NG108-15 cells which possess delta opioid receptors and alpha 2B-adrenoceptors. Mitragynine inhibited the forskolin-stimulated cAMP content in a concentration dependent manner as well as morphine and noradrenaline. Mitragynine- and morphine-induced inhibition of cAMP content were blocked by naloxone. Although idazoxane inhibited noradrenaline-induced inhibition of the cAMP content, idazoxane had no effect on mitragynine-induced inhibition. These results suggest that mitragynine acts directly on opioid receptors, but not on alpha 2-adrenoceptors, to show antinociceptive activity.

Analgesics↗