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Biomedical subjects

J Minami

Publications and source records attributed to J Minami.

At least 55 records · Page 3Linked to original sources

Responses of natriuretic peptides to acute and chronic salt loading in normotensive and hypertensive subjects.

Responses of endocrine systems to acute and chronic salt loading were examined in normotensive and hypertensive subjects. In the acute salt load study, isotonic saline (20 ml/kg for 1 h) was intravenously infused in 10 normotensive subjects and 12 patients with essential hypertension. Plasma noradrenaline was suppressed by saline infusion in the normotensive subjects (-19%, p < 0.05), but was not suppressed in the hypertensive patients (-5%, NS). Plasma brain natriuretic peptide concentration was significantly increased in the hypertensive patients (+15%, p<0.05), while it was unchanged in the normotensive subjects. In the chronic salt load study, 9 normotensive subjects and 30 patients with essential hypertension underwent two 7-d periods of 30 and 260 mmol/d sodium intake. On the basis of the blood pressure change, 17 hypertensive patients were classified as salt-resistant and 13 as salt-sensitive. The salt-sensitive hypertensive patients had suppressed plasma renin activity even during low-salt intake. During high salt intake, the plasma noradrenaline concentration failed to decrease in the salt-sensitive hypertensive patients (-6%, NS), whereas it fell significantly in the normotensive subjects (-27%, p < 0.05) and the salt-resistant hypertensive patients (-33%, p < 0.01). The high-salt intake also increased plasma concentrations of brain natriuretic peptide as well as atrial natriuretic peptide in all groups. In the salt-sensitive hypertensive patients, there was a positive correlation between the increase in blood pressure and that in atrial natriuretic peptide (r= 0.84, p< 0.01). These data indicate that brain natriuretic peptide is involved in chronic changes in body fluid volume. In patients with essential hypertension, acute volume expansion also evokes the response of brain natriuretic peptide. Salt-sensitive hypertension seems to be characterized by blunted response of the sympathetic nervous system. In addition, an increase in atrial natriuretic peptide is likely to play an important role in mechanisms counteracting salt-induced elevation of blood pressure.

Adult↗

Comparison between cilnidipine and nisoldipine with respect to effects on blood pressure and heart rate in hypertensive patients.

Cilnidipine is a new and unique 1,4-dihydropyridine calcium antagonist that has both L-type and N-type voltage-dependent calcium channel blocking actions. We compared the effects of cilnidipine and another once-daily dihydropyridine calcium antagonist, nisoldipine, on 24-h blood pressure and heart rate in patients with essential hypertension. We enrolled 10 hypertensive outpatients [9 men and 1 woman; age, 55+/-3 yr (means+/-SEM)] in this study. Their ambulatory blood pressure and heart rate were monitored for 24 h at intervals of 30 min with a portable recorder (TM-2425) after 8 wk of treatment with cilnidipine (5 to 20 mg once daily) and after 8 wk of treatment with nisoldipine (5 to 20 mg once daily). The order of the two treatments was randomized. Blood pressure and heart rate measurements for a 24-h period were analyzed for four segments of the day: morning (06:00 to 11:30), afternoon (12:00 to 17:30), nighttime (18:00 to 23:30), and sleeping time (0:00 to 5:30). Blood pressure levels were similar during the two treatment periods for each 6-h segment of the day. Heart rate was significantly higher during treatment with nisoldipine than during treatment with cilnidipine in the morning segment [by 4.1+/-1.3 beats/min (p < 0.05)] and the afternoon segment [by 6.4+/-3.6 beats/min (p< 0.05)]. These results suggest that cilnidipine is effective as a once-daily antihypertensive agent and causes reflex tachycardia less than does nisoldipine.

Antihypertensive Agents↗

Seasonal variations in office and home blood pressures in hypertensive patients treated with antihypertensive drugs.

OBJECTIVE: To analyze various factors influencing season variations in blood pressure under ordinary circumstances. METHODS: We examined home and office blood pressures in 315 outpatients with essential hypertension. The majority (88%) were being administered antihypertensived drugs. Their office and home blood pressures were recorded in 1993. The patients were 156 men and 159 women, aged 60.8 +/- 0.6 years (mean +/- SEM). The office blood pressure was measured monthly by the same physicians. The home blood pressure was measured every day by the patients, in the morning and evening. RESULTS: The home blood pressures both in men and in women exhibited significant seasonal variations, to a similar extent. The winter-summer difference in home blood pressure was 3.9 +/- 0.5 mmHg systolic and 1.7 +/- 0.3 mmHg diastolic for the men and 4.6 +/-0.5 mmHg systolic and 2.4 +/- 0.3 mmHg diastolic for the women. The office blood pressure of the men also exhibited significant seasonal variation. There was no seasonal variation in office systolic blood pressure in the women. The levels of home blood pressure in the men and women were similar during each season, whereas the office systolic blood pressure of the women was significantly higher than that of men throughout the year. For the total group of patients, the winter-summer differences in home systolic blood pressure was positively correlated to age. The seasonal variations in blood pressure were not affected by body mass index, smoking status, and administration of antihypertensive medication.CONCLUSIONS: Seasonal variations in blood pressure existed both for male and for female hypertensive patients and occurred even for subjects being treated with antihypertensive drugs. However, there was no seasonal variation in the office systolic blood pressure of women, suggesting that the differences between the office and home blood pressures and between thermoregulatory mechanisms for the sexes may have obscured it.

Journal Article↗

Immunotactoid glomerulopathy: report of a case.

We report a 51-year-old man diagnosed as having immunotactoid glomerulopathy (IT) who achieved partial remission after approximately 1 year of a low-dose prednisolone regimen. On admission, he was noted to show proteinuria, hypoproteinemia, and hypocomplementemia. On electron microscopy of the renal biopsy specimen, the mesangial and subendothelial areas were expanded because of the electron-dense deposits, which were represented by mostly straight and nonbranching hollow microtubule structures. The microtubular width was on average 22.0 nm. Clinical and histological findings did not support the diagnosis of amyloidosis, cryoglobulinemic glomerulonephritis, systemic lupus erythematosus, or paraproteinemias. Under treatment with oral prednisolone, 4 months later, the patient's serum albumin level increased from its lowest level of 2.3 to 3.6 g/dL, and CH50 from the lowest level of less than 6.3 to 32.4 U/mL. A 24-hour collection of urine showed that the protein had decreased from its highest level of 3.9 g to 2.0 g. This case suggests the effectiveness of long-term, low-dose prednisolone therapy for IT.

Biopsy, Needle↗

Effect of the Hanshin-Awaji earthquake on home blood pressure in patients with essential hypertension.

At 5:46 AM on January 17, 1995, the Hanshin-Awaji district of Japan was struck by a major earthquake. We investigated changes in home blood pressure (BP) of 36 hypertensive patients before and after the earthquake. In the 16 patients who lived within 50 km from the epicenter, the home Bp on the day of the earthquake was significantly higher than that just before the earthquake (+11/+6 mm Hg; P < .01 for systolic BP and P < .05 for diastolic BP). It remained higher throughout the first week after the earthquake, then gradually returned to the baseline level within 4 weeks. The home BP did not change significantly in the 20 patients who lived farther than 50 km from the epicenter. The earthquake-induced stress increased the BP in these hypertensive patients; however, its pressor effect was not persistent.

Aged↗

Blunted parasympathetic modulation in salt-sensitive patients with essential hypertension: evaluation by power-spectral analysis of heart-rate variability.

OBJECTIVE: To evaluate autonomic nervous function by power-spectral analysis of heart-rate variability in salt-sensitive and non-salt-sensitive patients with essential hypertension under the conditions of low and high salt intakes. DESIGN AND METHODS: The blood pressures, heart rates, and electrocardiogram R-R intervals of 20 hypertensive patients were measured at intervals of 30 min during a 24 h period using a portable recorder (TM-2425) on the last day of the high- (250 mmol NaCl/day) and low-salt (25 mmol NaCl/day) diet periods. The patients whose 24 h average mean blood pressures were increased by more than 10% by the high salt intake were defined as salt-sensitive (n = 10); the other patients were considered non-salt-sensitive (n = 10). Power-spectral analysis of R-R intervals was performed to obtain the low-frequency component (0.05-0.15 Hz) and the high-frequency component (0.15-0.40 Hz). RESULTS: The average 24 h blood pressure in the salt-sensitive patients was increased by the high salt intake [by 19.1 +/- 2.0/9.1 +/- 0.8 mmHg (mean +/- SEM)], whereas the heart rate did not change. In contrast, the increase in 24 h blood pressure in the non-salt-sensitive patients caused by the high salt intake was not significant and the heart rate was decreased significantly by the high salt intake (by 5.9 +/- 1.4 beats/min). The high-salt diet increased significantly the high-frequency component and decreased the low-frequency:high-frequency component ratio both during the daytime and during the night-time for the non-salt-sensitive patients. In contrast, the high-frequency component and the night-time low-frequency: high-frequency component ratio of the salt-sensitive patients did not respond to dietary salt manoeuvres. CONCLUSIONS: Responses of the parasympathetic and sympathetic nervous systems to dietary salt manoeuvres were blunted in salt-sensitive patients. These altered modulations of the autonomic nervous system may contribute to the salt sensitivity of the blood pressure in patients with essential hypertension.

Blood Pressure↗

Lambda-toxin of Clostridium perfringens activates the precursor of epsilon-toxin by releasing its N- and C-terminal peptides.

The effect of lambda-toxin, a thermolysin-like metalloprotease of Clostridium perfringens, on the inactive epsilon-prototoxin produced by the same organism was examined. When the purified epsilon-prototoxin was incubated with the purified lambda-toxin at 37 C for 2 hr, the 32.5-kDa epsilon-prototoxin was processed into a 30.5-kDa polypeptide, as determined by SDS-polyacrylamide gel electrophoresis. A mouse lethality test showed that the treatment activated the prototoxin: the 50% lethal doses (LD50) of the prototoxin with and without lambda-toxin treatment were 110 and 70,000 ng/kg of body weight, respectively. The lethal activity of the prototoxin activated by lambda-toxin was comparable to that with trypsin plus chymotrypsin and higher than that with trypsin alone: LD50 of the prototoxin treated with trypsin and trypsin plus chymotrypsin were 320 and 65 ng/kg of body weight, respectively. The epsilon-toxin gene was cloned and sequenced. Determination of the N-terminal amino acid sequence of each activated epsilon-prototoxin revealed that lambda-toxin cleaved between the 10th and 11th amino acid residues from the N-terminus of the prototoxin, while trypsin and trypsin plus chymotrypsin cleaved between the 13th and 14th amino acid residues. The molecular weight of each activated epsilon-prototoxin was also determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The C-terminus deduced from the molecular weight is located at the 23rd or 30th amino acid residue from the C-terminus of the prototoxin, suggesting that removal of not only N-terminal but also C-terminal peptide is responsible for activation of the prototoxin.

Amino Acid Sequence↗

Crescentic glomerulonephritis and elevated antimyeloperoxidase antibody in a patient with Churg-Strauss syndrome.

A 45-year-old man with a long history of bronchial asthma was admitted to the National Cardiovascular Center with complaints of severe pain, swelling, and ecchymoses of the lower extremities. A diagnosis of Churg-Strauss syndrome was made because of marked eosinophilia, vasculitis, and a history of asthma. Urinalysis revealed severe proteinuria and microscopic hematuria. A renal biopsy demonstrated extensively crescentic glomerulonephritis. The antineutrophil cytoplasmic antibody against myeloperoxidase (MPO-ANCA) level, determined by enzyme-linked immunosorbent assay (ELISA), was 494 ELISA units. Under treatment with prednisolone, the symptoms and eosinophilia improved within 3 days. The MPO-ANCA level decreased to its lowest value, and renal function was ameliorated within 3 months. The patient has been followed regularly on an ambulatory basis with a regimen of prednisolone.

Anti-Inflammatory Agents↗

Behaviour of adrenomedullin during acute and chronic salt loading in normotensive and hypertensive subjects.

1. Responses of adrenomedullin to acute and chronic salt loading were examined in normotensive and hypertensive subjects. 2. In the acute salt load study, isotonic saline (50 ml/kg for 1 h) was intravenously infused into nine normotensive subjects and 11 patients with essential hypertension. Plasma adrenomedullin was higher in hypertensive than in normotensive subjects but was unchanged by saline infusion in either the normotensive (before infusion, 2.4 +/- 0.2 fmol/ml; after infusion, 2.4 +/- 0.1 fmol/ml) or hypertensive (before infusion, 3.0 +/- 0.1 fmol/ml; after infusion, 2.9 +/- 0.2 fmol/ml) group, while renin was suppressed and atrial natriuretic peptide was markedly increased. Plasma endothelin was not affected either. 3. In the chronic salt load study, seven normotensive subjects and 23 patients with essential hypertension underwent two 7-day periods of 30 and 260 mmol/day sodium intake. Depending on the blood pressure change, 13 hypertensive subjects were classified as salt-resistant and 10 as salt-sensitive. Salt-sensitive hypertensive subjects had suppressed plasma renin activity even during low salt intake. Plasma adrenomedullin or endothelin were not affected by the salt intake changes in any group; however, the high salt intake increased atrial natriuretic peptide in all groups. 4. These data indicate that the circulating level of adrenomedullin is not changed by either acute or chronic salt loading in normotensive subjects and patients with essential hypertension.

Adrenomedullin↗

Seasonal variations in office, home and 24 h ambulatory blood pressure in patients with essential hypertension.

OBJECTIVE: To study the influence of seasons on blood pressure in ordinary circumstances. DESIGN AND METHODS: We examined seasonal variations of home and 24 h ambulatory and office blood pressures in outpatients with essential hypertension. Office, home and ambulatory blood pressures of 50 outpatients with essential hypertension were recorded in 1993. The subjects were 26 women and 24 men, aged 59.3 +/- 1.1 years (mean +/- SEM). Office blood pressure was measured monthly by physicians. Home blood pressure was measured every day by the patients in the morning and evening. Ambulatory blood pressure was recorded every 30 min in summer and in winter. The order of ambulatory blood pressure monitoring was randomized. The daytime and night-time blood pressures were calculated according to the true waking and sleeping times of the individual patients. RESULTS: Both office and home blood pressures showed significant seasonal variations. The winter-summer differences in office and home blood pressures were 4.7 +/- 1.3/ 3.3 +/- 0.9 and 5.9 +/- 1.1/2.7 +/- 0.6 mmHg, respectively. They were not influenced by the presence of antihypertensive agents. The winter-summer difference was also significant for daytime ambulatory blood pressure (3.5 +/- 1.4/ 2.5 +/- 0.8 mmHg), but not for night-time ambulatory blood pressure (-2.9 +/- 1.7/-1.2 +/- 1.0 mmHg) or average 24 h blood pressure (1.5 +/- 1.3/1.2 +/- 0.7 mmHg). There were no significant differences in the waking and sleeping times between the two seasons. CONCLUSIONS: Office, home and daytime ambulatory blood pressure levels were higher in winter than they were in summer in patients with essential hypertension. However, the seasonal variations in average 24 h blood pressure may be small because of the lack of changes in night-time blood pressure.

Adult↗

An upstream activating sequence containing curved DNA involved in activation of the Clostridium perfringens plc promoter.

The plc gene, which encodes phospholipase C (alpha-toxin) of Clostridium perfringens, possesses three poly(A) tracts forming an intrinsically curved DNA region immediately upstream of the promoter. The in vivo transcriptional activity of the plasmid-borne plc gene was stimulated by this curved-DNA-containing sequence, depending on its proper linear and rotational orientation. The in vitro transcriptional activity of the plc gene was also stimulated by the upstream sequence. In addition, the stimulatory effect of the sequence and the degree of DNA bending were greater at lower temperature, as was demonstrated by both in vitro and in vivo transcription assays, and a gel-mobility assay, respectively. A similar temperature effect was also observed with the chromosomal plc gene. These observations suggest that the upstream DNA curvature per se stimulates the initiation of transcription of the plc gene, possibly through direct contact with RNA polymerase.

Base Sequence↗

Expression of the colH gene encoding Clostridium histolyticum collagenase in Bacillus subtilis and its application to enzyme purification.

The colH gene encoding 116-kDa collagenase of Clostridium histolyticum (cColH) was cloned into an Escherichia coli-Bacillus subtilis shuttle vector to develop a method for purification of recombinant collagenase (rColH). When plasmid pJCM310 containing the colH gene was introduced into B. subtilis DB104 and the transformant was grown in LB broth at 37 C, stability of the plasmid was not maintained. However, stability was partly improved by growing the transformant in a modified LB broth containing 0.5 M sodium succinate with gentle shaking at 35 C. When the transformant was grown to an optical density of 0.4 at 600 nm in this medium, pJCM310 was stable and rColH was produced in sufficient amounts. rColH was purified to homogeneity by ammonium sulfate precipitation, gel filtration and ion-exchange chromatography. The yield of rColH from an 800-ml culture was 0.53 mg and its specific activity was estimated to be 1,210 U per mg of protein. The purified rColH was capable of degrading native type-I collagen fibril from bovine achilles tendon, as was demonstrated by zymography. A comparison of the N-terminal amino acid sequence between cColH and rColH revealed that rColH has 10 extra N-terminal amino acid residues. However, the peptide mapping of rColH with V8 protease was virtually identical to that of cColH. Furthermore, the molecular mass of rColH was estimated to be 112,999 Da by mass spectrometry, coinciding with the value of 112,977 Da, which was predicted from the nucleotide sequence of the colH gene. Therefore, the recombinant B. subtilis culture is capable of serving as a useful source for enzyme purification.

Amino Acid Sequence↗

Analysis of the phospholipase C gene of Clostridium perfringens KZ1340 isolated from Antarctic soil.

Clostridium perfringens KZ1340 isolated from Antarctic soil was first classified as Clostridium plagarum and later as a lecithinase-negative variant of C. perfringens. Although the strain produced no detectable lecithinase (phospholipase C, PLC) activity in the culture supernatant, it was shown by Southern blot hybridization to possess a PLC-encoding gene (plc). To determine the cause of the PLC deficiency, we cloned and sequenced the plc gene from KZ1340. The deduced amino acid sequence consists of 398 amino acid residues, coinciding with those of the plc genes previously determined. Tyrosine was substituted for histidine at amino acid position 148, which is thought to bind a zinc ion essential for PLC activity. Northern blot analysis revealed that KZ1340 expressed the plc gene at an extremely low level. Furthermore, the plc gene cloned from C. perfringens strain 13 into a plasmid was expressed weakly in KZ1340, compared to that in strain 13. This indicates that the former strain represses plc gene expression in trans. When a phylogenetic tree of plc genes was constructed, the KZ1340 plc gene formed a monophyletic branch along with those of various other C. perfringens strains, supporting the classification of the strain as a variant of C. perfringens.

Amino Acid Sequence↗

Purification, characterization, and primary structure of Clostridium perfringens lambda-toxin, a thermolysin-like metalloprotease.

The lambda-toxin of Clostridium perfringens type B NCIB10691 was purified by ammonium sulfate precipitation, followed by size exclusion, anion-exchange, and hydrophobic interaction chromatography. The purified toxin had an apparent molecular mass of 36 kDa, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The toxin possessed casein-hydrolyzing activity, which was inhibited specifically by metal chelators, indicating that the toxin is a metalloprotease. The gene encoding the lambda-toxin (lam), which was shown by Southern analysis to be located on a 70-kb plasmid, was cloned into Escherichia coli cells. Nucleotide and N-terminal amino acid sequencing revealed that the lam gene encodes a 553-amino-acid protein, which is processed into a mature form, the molecular mass of which was calculated to be 35,722 Da. The deduced amino acid sequence of the mature enzyme contains an HEXXH motif characteristic of zinc metalloproteases and is homologous to other known enzymes belonging to the thermolysin family. The purified toxin degraded various biologically important substances, such as collagen, fibronectin, fibrinogen, immunoglobulin A, and the complement C3 component. It caused an increase in vascular permeability and hemorrhagic edema on injection into the dorsal skin of mice. These results suggest that the toxin contributes to the pathogenesis of histolytic infection by lambda-toxin-producing C. perfringens.

Amino Acid Sequence↗

Cloning and sequencing of a unique antigen MPT70 from Mycobacterium tuberculosis H37Rv and expression in BCG using E. coli-mycobacteria shuttle vector.

MPB70 is known to be an immunogenic mycobacterial protein secreted in large amounts from Mycobacterium bovis BCG (BCG) Tokyo. The analogous gene for MPT70 was cloned from Mycobacterium tuberculosis H37Rv which produces this protein in only a small amount. The gene encoding 193 amino acid residues including 30 amino acids for the signal peptide, the promoter-like sequence, and the ribosome-binding site, was completely identical to that of BCG Tokyo. Computer analysis revealed that the carboxy-terminal half of MPT70 was homologous to amino acid sequences of fasciclin I, osteoblast-specific factor 2 (OSF-2), and human transforming growth factor-beta induced gene product (beta IG-H3). Escherichia coli (E. coli) -mycobacteria shuttle vectors containing mpt70 or mpb70 genes 0.7kbp upstream of the 5' end of them were able to be expressed in BCG Pasteur which is a MPB70 low-producer, but the extent of the expression was not that of a high-producer.

Amino Acid Sequence↗

Phylogenetic analysis of phospholipase C genes from Clostridium perfringens types A to E and Clostridium novyi.

The phylogenetic interrelationships between strains of 5 toxin types (A to E) of Clostridium perfringens were examined by analysis of differences in the nucleotide sequences of phospholipase C genes (plc genes) among 10 strains, including 3 strains for which the plc gene sequences have been previously reported. A plc gene was also cloned from a Clostridium novyi type A strain and sequenced to analyze the interspecies diversity of plc genes. Phylogenetic trees constructed by the neighbor-joining method revealed that the phylogeny of C. perfringens strains is not related to toxin typing, in agreement with the results of a comparative genome mapping study by Canard et al. (B. Canard, B. Saint-Joanis, and S. T. Cole, Mol. Microbiol. 6:1421-1429, 1992). Various C. perfringens phospholipase C enzymes were purified from cultures of Escherichia coli cells into which the encoding plc genes had been cloned. All of the enzymes showed the same specific activity. On the other hand, the level of plc transcripts differed greatly (up to 40-fold) from one C. perfringens strain to another. No significant difference in the nucleotide sequence of the plc promoter region was observed for any of the plc genes. These results suggest that the variation in phospholipase C activity among different strains is not due to mutation in the plc coding region but to that in an extragenic region. The evolution of C. perfringens phospholipase C is discussed on the basis of similarities and differences between clostridial plc genes.

Amino Acid Sequence↗