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Biomedical subjects

K Yoshimura

Publications and source records attributed to K Yoshimura.

At least 109 records · Page 6Linked to original sources

Structure of the human neutrophil elastase gene.

The gene for human neutrophil elastase (NE), a powerful serine protease carried by blood neutrophils and capable of destroying most connective tissue proteins, was cloned from a genomic DNA library of a normal individual. The NE gene consists of 5 exons and 4 introns included in a single copy 4-kilobase segment of chromosome 11 at q14. The coding exons of the NE gene predict a primary translation product of 267 residues including a 29-residue N-terminal precursor peptide and a 20-residue C-terminal precursor peptide. Analysis of the N-terminal peptide sequence suggests it contains a 27-residue "pre" signal peptide followed by a "proN" dipeptide, similar to that of other blood cell lysosomal proteases. The sequences for the mature 218-residue NE protein are included in exons II-V. The 5'-flanking region of the gene includes typical TATA, CAAT, and GC sequences within 61 base pairs (bp) of the cap site. The sequence 1.5 kilobases 5' to exon I contains several interesting repetitive sequences including six tandem repeats of unique 52- or 53-bp sequences. The 5'-flanking region also contains a 19-bp segment with 90% homology to a segment of the 5'-flanking region of the human myeloperoxidase (MPO) gene, a gene also expressed in bone marrow precursor cells and a protein stored in the same neutrophil granules as NE. In addition, like the MPO gene, the NE 5'-flanking region has several regions with greater than or equal to 75% homology to sequences 5' to c-myc, but there is no overlap between the NE-c-myc and MPO-c-myc homologous sequences.

Amino Acid Sequence

Human lysozyme: sequencing of a cDNA, and expression and secretion by Saccharomyces cerevisiae.

A cDNA encoding human lysozyme was isolated from a human placenta cDNA library. The cDNA was 1.5 kb in size and coded for a signal peptide consisting of 18 amino acids and mature lysozyme. The amino acid sequence of the mature lysozyme, deduced from the nucleotide sequence, was identical with the published sequence. In the 3'-noncoding region of the cDNA, an Alu sequence was found in the reverse orientation. In a protein coding region, the human lysozyme cDNA shows 60.1% and 51.3% similarity with chicken lysozyme and human alpha-lactalbumin cDNAs, respectively. When the cDNA was expressed in Saccharomyces cerevisiae, an active and correctly processed human lysozyme was secreted efficiently into the culture medium.

Amino Acid Sequence

Distribution of Clostridium botulinum in Japan and in Shinkiang district of China.

Soil specimens obtained from several areas of Japan, which are closely located to or facing the Continental land of China, were examined for the distribution of Clostridium botulinum, especially pertaining to types A and B. A total of 266 specimens of Japan, when cultured, showed no type A or B toxicity, although 30 (11.3%), 4 (1.5%), and 10 (3.8%) of the specimens showed C1, C2, and type E toxicities, respectively. On the contrary, types A and/or B toxicities were shown, by the same method, in 14 of 20 specimens of Shinkiang district, China. The highest number of C. botulinum cells found in one gram of soil specimen was 25 for type A and 10 for type B.

China

T-cell-dependent eosinophilia in the cerebrospinal fluid of the mouse infected with Angiostrongylus cantonensis.

Eosinophilia of the cerebrospinal fluid (CSF) in permissive (rats) and non-permissive (mice) hosts infected with Angiostrongylus cantonensis, and the possible mechanism of the eosinophilia were studied. In three strains of thymic mice (ICR, ddY and BALB/c), the infection provoked a marked CSF eosinophilia starting at around day 12, reaching a peak level at day 20 and maintaining significantly high levels until day 35. In contrast, in athymic nude mice of BALB/c strain the infection failed to evoke this eosinophilia, suggesting T-cell dependence of murine CSF eosinophilia. Humoral antibodies did not correlate with the induction of eosinophilia. A time-course study of worm recovery in the mouse brains indicated a gradual but consistent reduction in worm burden in accordance with the rapid rise in CSF eosinophil levels. Bone marrow eosinophilia occurred in mice at day 5, which preceded CSF eosinophilia. Jirds, a permissive but less susceptible host, developed a CSF eosinophilia with a peak level at day 17, but which declined rapidly following the peak. Permissive rat hosts developed significant peripheral and bone marrow eosinophilia at day 35 but their CSF eosinophilia was markedly less prominent than that of mice and jirds. These data clearly indicate that there are distinct differences in the mechanism of eosinophilia and eosinophilia-inducing factors between permissive and non-permissive hosts.

Angiostrongylus

Ultrastructural and morphometric analyses of eosinophils from the cerebrospinal fluid of the mouse and guinea-pig infected with Angiostrongylus cantonensis.

Guinea-pigs infected with Angiostrongylus cantonensis developed pleocytosis and eosinophilia in the cerebrospinal fluid (CSF) at day 12 post-infection (p.i.), showing a peak response at day 20 p.i., followed by a gradual reduction. Ultrastructural observations on CSF eosinophils from infected mice and guinea-pigs revealed various signs of eosinophil degranulation after day 14 p.i., suggesting the exocytosis of lysosomal material. Morphometric analysis indicated that CSF eosinophils after day 22 p.i. contained fewer granules as well as smaller granules than those at days 14-20 p.i. These data suggest that CSF eosinophils release granule constituents into the outside of the cells and these secretion products could interact with the intracranial worms and are probably related to worm death. As degenerative atrophy or partial loss of Purkinje cells and the spongy vacuolation of the white matter were noted in the cerebellum of infected mice, it was suggested that CSF eosinophils could be a possible cause of neurological disorders in angiostrongyliasis cantonensis.

Angiostrongylus

Cardiac pacemaker regulated by respiratory rate and blood temperature.

A new method using respiratory rate and temperature as the guides for optimal pacing is proposed. A pacemaker was fabricated which senses these two parameters simultaneously. The pacemaker functions by calculating the cardiac rate, which would be derived from the respiratory rate and the blood temperature. The higher of the two rates is adopted as the cardiac pacing rate, i.e., at which stimuli will be delivered. The operation was tested in a mongrel dog with complete atrioventricular block. After the induction of anesthesia, a thermistor temperature probe was inserted into right atrium and a respiratory rate sensor was attached around the chest. After administration of a pyrogenic drug, both respiratory rate and blood temperature increased. The pacing rate was increased from 178 beats/minute(bpm) at 36.4 degrees C, blood temperature, and 26.5 acts/minute(apm), respiratory rate, to 233 bpm at 40.1 degrees C and 40.0 apm. Cardiac output was increased from 2.15 liters/minute(l/pm) at the beginning to 2.50 l/pm at maximum. The transition of the guide from respiratory rate to temperature was observed at about 38 degrees C.

Animals

Dibutyryl cyclic AMP inhibits acute hypoxic pulmonary vasoconstriction in conscious sheep.

We examined the effects of cell-permeable dibutyryl cyclic AMP (DBcAMP) on acute hypoxic pulmonary vasoconstriction (HPV) in conscious sheep. Mean left and right atrial, pulmonary, and systemic pressures (Pla, Pra, Ppa, and Psa, mm Hg), cardiac output (CO, L/min), and heart rate were measured continuously. Systemic (SVR) and pulmonary vascular resistances (PVR) were calculated by (Psa-Pra)/CO and (Ppa-Pla)/CO, respectively. Five groups of experiments were performed using the same sheep (n = 6). After a 30-min baseline period, sheep inhaled a hypoxic gas mixture (O2:N2 = 1:9) for 40 min. Pretreatment with DBcAMP (200 micrograms/kg/min) inhibited HPV (Ppa, 12.0 +/- 2.3 to 20.0 +/- 2.3 versus 13.2 +/- 2.5 to 14.3 +/- 1.4 mm Hg, p less than 0.01; PVR, 2.61 +/- 0.81 to 4.15 +/- 1.14 versus 2.30 +/- 0.87 to 2.52 +/- 0.59 mm Hg/L/min, p less than 0.01). DBcAMP treatment (200 micrograms/kg/min) after induction of HPV also significantly attenuated hypoxic pulmonary response (Ppa, 19.0 +/- 1.7 to 14.2 +/- 2.3 mm Hg, p less than 0.01; PVR, 3.92 +/- 0.39 to 2.34 +/- 0.34 mm Hg/L/min, p less than 0.01) without significant decreases in Psa and SVR. Pretreatment with DBcAMP (200 micrograms/kg/min) did not significantly alter pulmonary pressor responses to bolus injections of prostaglandin F2 alpha (PGF2 alpha) (10 micrograms/kg) and norepinephrine (4 micrograms/kg). These results may suggest that intracellular augmentation of cyclic AMP plays a crucial role in modulating HPV.

Acute Disease

Thromboxane synthetase inhibition and pulmonary response to hypoxia in conscious adult sheep.

This study investigated the effects of a thromboxane synthetase inhibitor (OKY-046) and a cyclooxygenase inhibitor (ketoprofen) on hypoxic pulmonary vasoconstriction in conscious adult sheep in order to evaluate the physiological role of thromboxane and other cyclooxygenase products. In addition, we studied the effects of histamine H1 (chlorpheniramine) and H2 antagonists (cimetidine) on hypoxic pulmonary vascular tone. Hypoxia caused a 37% rise in pulmonary arterial pressure (p less than 0.05) and a 36% increase in pulmonary vascular resistance (p less than 0.05). Pretreatment with intravenous OKY-046 10 mg/kg or ketoprofen 2 mg/kg had no effect on normoxic pulmonary vascular tone and inhibited the increase in plasma TXB2 concentration during hypoxia without affecting the pulmonary pressor response to hypoxia. Cimetidine produced an increase in hypoxic pulmonary vascular tone when individual members of the group were compared, but there was no statistically significant difference when the group was compared to the control study. Chlorpheniramine had no effect on hypoxic pulmonary tone. These data suggest that hypoxic pulmonary vasoconstriction is not mediated by release of TXA2, that hypoxic vascular tone is not modulated by cyclooxygenase products, and that the histamine H2 receptor may play a modulating role in hypoxic pulmonary vasoconstriction in conscious adult sheep.

Acrylates

[Effects of flutropium bromide, a new antiasthma drug, on mediator release from mast cells and actions of mediators].

The effects of flutropium bromide (Ba598Br), a new antiasthma drug possessing the quarternary ammonium structure of atropine derivatives, on mediator release from mast cells and on actions of leukotriene (LT) D4 and serotonin were investigated. Flutropium bromide (3 and 10 mg/kg, i.v.) showed an inhibitory action on the 48 hr homologous PCA in guinea pigs. Atropine showed no inhibitory effect. Flutropium bromide also inhibited the release of histamine from isolated rat mast cells stimulated by antigen, although the inhibitory action was weaker than that of disodium cromoglycate. Atropine also had no inhibitory action in this case. Flutropium bromide and atropine showed no antagonistic action against LTD4-induced contraction of isolated tracheal smooth muscle of guinea pigs. Inhalation of flutropium bromide (0.3%) also showed no antagonistic action against serotonin-induced bronchoconstriction in dogs. From the above results, it is indicated that flutropium bromide has a weak mast cell stabilizing action, but no antagonistic action against LTD4 and serotonin.

Animals

Suppression of hepatic HMG-CoA reductase activity by beta-muricholic acid in mice fed a diet containing cholesterol and cholic acid.

A diet containing cholesterol and cholic acid (SID) is known to induce the formation of cholesterol fatty liver as well as cholesterol gallstones. The activity of HMG-CoA reductase, one of the key enzymes for cholesterol synthesis in the liver, is significantly lowered by addition of beta-muricholic acid to SID. The prevention of fatty liver formation by beta-muricholic acid was accompanied by the suppression of HMG-CoA reductase activity.

Animals

The increased sympathoadrenal activity in patients with high altitude pulmonary edema is centrally mediated.

To assess the role of catecholamines in the pathogenesis of high altitude pulmonary edema (HAPE), 24-hour urinary catecholamine excretions and plasma catecholamine concentrations were measured. We also performed brain computed tomography (CT) in the same 8 serial patients with HAPE. 24-hour urinary norepinephrine excretion showed a statistically high value on admission compared with that after recovery (396.9 +/- 92.9 micrograms/24 hr, decreasing to 93.0 +/- 31.1 micrograms/24 hr, mean +/- S.E., p less than 0.01). 24-hour urinary epinephrine excretion on admission was also remarkably high, and returned later normal (62.9 +/- 25.8 micrograms/24 hr, decreasing to 12.7 +/- 4.2 micrograms/24 hr, p less than 0.05). Plasma norepinephrine concentration was also high, but returned to normal (0.260 +/- 0.073 ng/ml, to 0.11 +/- 0.043 ng/ml) by the time of discharge. Brain CT scans revealed diffuse low density of the entire cerebrum, small ventricles, disappearance of sulci, and small cistern, suggesting cerebral edema. These findings may suggest that the heightened sympathoadrenal activity that occurred in the patients concomitant with cerebral edema was related to the high altitude illness rather than to simple exposure to high altitude.

Adrenal Glands

[A case of adenomatous polyps with prostatic type epithelium].

A 41-year-old male presented with gross hematuria and was found to have a polypoid lesion of the prostatic urethra. This proved to be an adenomatous polyp with prostatic type epithelium. Transurethral resection was performed on August 3, 1985. He had no evidence of recurrence following the operation. Previously reported cases of relevance are briefly discussed.

Adult