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Biomedical subjects

K Kawamura

Publications and source records attributed to K Kawamura.

At least 361 records · Page 20Linked to original sources

Nifedipine in divided doses does not reverse left ventricular hypertrophy in spontaneously hypertensive rats.

This study investigated whether nifedipine administered in divided daily doses would diminish left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHR). We administered nifedipine (12 mg/kg/day) in 3 divided doses by gastric gavage to 15-week-old male SHR (n = 10) for 4 weeks. Age- and sex-matched SHR served as controls (n = 10). Left ventricular (LV) function was evaluated by LV catheterization and cardiac output was determined by the thermodilution method. Plasma renin activity (PRA) and plasma norepinephrine levels were measured. Nifedipine significantly decreased blood pressure (p less than 0.01), shortened time constant T (p less than 0.05), and increased cardiac output (p less than 0.05). Nifedipine did not impair the LV systolic and diastolic indices during acute afterload elevation with angiotensin II. LV weight was similar in the 2 groups of rats. While PRA was unaltered, plasma norepinephrine levels were higher in the nifedipine-treated rats (p less than 0.05). These data indicate that nifedipine in 3 divided doses reduced blood pressure in SHR without compromising cardiac function but did not reverse LVH. The short hypotensive duration of nifedipine and its enhancement of sympathetic nervous activity may be responsible for the failure to reverse LVH, despite adequate blood pressure control.

Adrenergic Fibers↗

Clinical significance of normal cardiac silhouette in dilated cardiomyopathy--evaluation based upon echocardiography and magnetic resonance imaging.

It is generally believed that patients with dilated cardiomyopathy have a large cardiac silhouette on chest roentgenography. Contrary to this general belief, we have recently examined several patients with a dilated left ventricle (LV) on echocardiography but in whom the cardiothoracic ratio (CTR) was within normal limits. To investigate this apparent discrepancy, we evaluated the relationship between LV dimensions, measured on M-mode echocardiography, and CTR in 49 patients with dilated cardiomyopathy. Among these patients, 11 (22%) had a CTR less than 50% and 38 (78%) had a CTR greater than 50%. The spatial orientation (cardiac rotation) of the LV within the thorax was evaluated by magnetic resonance imaging (MRI) in 5 patients with a CTR less than 50% and in 7 patients with a CTR greater than 50%, in comparison with 7 normal controls. In each of these patients, cardiac rotation was assessed from both a transverse and a frontal MRI section. In both groups, LV end-diastolic dimension was greater than 5 cm. Transverse cardiac rotation was 32 +/- 8 degrees in patients with a CTR less than 50%. This was significantly lower than in the 7 normal controls (43 +/- 7 degrees) (p less than 0.05). In patients with a CTR greater than 50%, however, transverse cardiac rotation (55 +/- 5 degrees) was significantly greater than in normal controls (p less than 0.01). No differences in frontal cardiac rotation was observed between the 2 groups. These data indicate that a normal cardiac silhouette in patients with dilated cardiomyopathy can be explained on the basis of a counterclockwise transverse rotation of the heart within the thorax, and it cannot always rule out the dilatation of the LV.

Adolescent↗

Cerebellar form of progressive multifocal leukoencephalopathy in a patient with chronic renal failure.

Progressive multifocal leukoencephalopathy (PML) developed in a 64-year-old woman who had undergone hemodialysis treatment due to chronic renal failure (CRF) for 6 yr. Her initial symptom was ataxia, and computed tomographic (CT) scan and magnetic resonance imaging (MRI) suggested a demyelinating disease of the cerebellum. Her cell-mediated immunity was impaired. At autopsy, the cerebellar disease was confirmed as PML by ultrastructural and immunohistochemical studies. Moreover, the JC type of papova virus infection was verified by Southern blot analysis.

Cerebellar Diseases↗

Prominent negative T waves with QT prolongation indicate reperfusion injury and myocardial stunning.

To observe the clinical course after reperfusion and recovery from myocardial stunning of the left ventricular anterior wall, we prospectively reviewed and analyzed cardiac enzymes, ECG changes, echocardiograms, and cineangiograms in 8 patients with the acute ischemic syndrome who fulfilled the following criteria: 1) no history of previous myocardial infarction, 2) repeated and/or prolonged episodes of chest pain, 3) critical stenosis of the left anterior descending artery with wall motion abnormalities, 4) successful emergency percutaneous transluminal coronary angioplasty, and 5) normal wall motion on repeat cineangiography 4 to 8 weeks later. Creatine kinase (CK) and/or its cardiac isoenzyme (CK-MB) were minimally elevated in all cases. Wall motion was normalized with the reduction of end-systolic volume (end-diastolic volume: from 139 +/- 25 to 140 +/- 37 ml, ns, end-systolic volume: from 68 +/- 16 to 39 +/- 13 ml, p < 0.001, ejection fraction: from 51 +/- 6 to 71 +/- 6%, p < 0.001). Serial echocardiograms showed normalization of wall motion within 4 to 28 days. T wave inversion in the left precordial leads developed 30 min to 5 hours after the cessation of chest pain or successful reperfusion, and prominent negative T waves (1.6 +/- 0.6 mV) with QT prolongation (0.56 +/- 0.08 sec) in V3 or V4 reached their peak values within one to 5 days. ECG abnormalities resolved after 21 to 95 days. These ECG findings may indicate reperfusion injury and the presence of myocardial stunning in the anterior wall of the left ventricle.

Aged↗

Effect of magnesium deficiency on 15-hydroxyeicosatetraenoic acid in cultured human umbilical arterial endothelial cells.

Effects of magnesium deficiency on the production of 15-hydroxyeicosatetraenoic acid (15-HETE) and cytosolic free calcium concentration in human umbilical arterial endothelial cells were studied by radioimmunoassay. 15-HETE release by endothelial cells incubated with normal magnesium media (900 microM Mg2+) for 24 h was 2.2 +/- 0.3 ng/mg protein. 15-HETE release gradually increased in proportion to decrease of magnesium. Low magnesium media (180 microM Mg2+) caused an increase in 15-HETE release in a time-dependent manner. Cytosolic free calcium concentration of endothelial cells in normal magnesium media fluctuated between 129.4 nM and 134.2 nM during a 24 h period. Low magnesium media (180 microM Mg2+) caused a time-dependent rise in cytosolic free calcium concentration which is consistent with a time-dependent increase in H-HETE release. High magnesium medium (1800 microM Mg2+) did not have any effect on cytosolic free calcium concentration or 15-HETE production. In conclusion, 15-HETE release by endothelial cells was stimulated by increase in cytosolic free calcium concentration induced by magnesium deficient media. It is suggested that magnesium deficiency induces atherosclerosis via increase in 15-HETE production.

Calcium↗

Effect of 25-hydroxycholesterol on cytotoxicity and prostacyclin production in cultured human umbilical arterial endothelial cells.

The effect of cholesterol or 25-hydroxycholesterol on DNA synthesis and prostacyclin synthesis by cultured human umbilical arterial endothelial cells was investigated. Cells incubated with 25-hydroxycholesterol showed an increased rate of cell death, decreased [3H]-thymidine incorporation and increased prostacyclin production as compared to either the control or the pure cholesterol group. 25-hydroxycholesterol caused a concentration- and time-dependent increase in prostacyclin synthesis. The intracellular free calcium concentration of endothelial cells incubated with 25-hydroxycholesterol was markedly increased in a time-dependent manner. Calcium uptake by endothelial cells incubated with 25-hydroxycholesterol for 24 h was markedly increased. It is suggested that 25-hydroxycholesterol may depress DNA synthesis and increase prostacyclin synthesis via an elevation in the intracellular free calcium concentration of endothelial cells.

Calcium↗

[Immunophenotypic and immunogenotypic analyses of acute leukemia and lymphoblastic lymphoma expressing myeloid and lymphoid antigens].

By using monoclonal antibodies against lymphoid and myeloid differentiation antigens, surface marker analysis was performed on the tumor cells from 42 patients with acute leukemia and lymphoblastic lymphoma. Nine (21%) of 42 cases were diagnosed biphenotypic leukemia. Two (17%) of the 12 patients with acute myeloid leukemia, four (18%) of 22 with acute lymphocytic leukemia and three (38%) of 8 with lymphoblastic lymphoma expressed both lymphoid and myeloid antigens. Tumor cells from six patients expressed both T-cell and myeloid antigens, and those from three other expressed both B-cell and myeloid antigens. Southern blot analysis was performed on the DNA from four patients with biphenotypic leukemia cells expressing T-cell and myeloid antigens. DNA from one patient showed clonal rearrangement of the immunoglobulin heavy chain (IgH) gene, and that from one other showed clonal rearrangement of both IgH gene and T-cell receptor beta-chain gene. DNA from two other patients showed a germline configuration of both genes. These results indicate that biphenotypic leukemia, especially T-cell and myeloid phenotype, is not so rare in acute leukemia and lymphoblastic lymphoma. The results of immunogenotypic analysis were not consistent with those of immunophenotypic analysis in biphenotypic leukemia.

Acute Disease↗

[Pharmacokinetic and clinical studies on panipenem/betamipron in the pediatric field].

UNLABELLED: Panipenem/betamipron (PAPM/BP), one of the carbapenems, was studied for its absorption and excretion, and clinical efficacy. The following is a summary of the results: 1. Absorption and excretion: Fourteen patients with their ages between 2 years and 14 years were administered with PAPM/BP 10 mg/kg, 20 mg/kg or 30 mg/kg, in 30-minute intravenous drip infusion. Maximum serum levels of PAPM, at dose levels of 10 mg/10 mg/kg, 20 mg/20 mg/kg and 30 mg/30 mg/kg of PAPM/BP, were 27.37 micrograms/ml, 59.3 micrograms/ml, 91.7 micrograms/ml, respectively, at the end of infusion. The half-lives of the 3 dose levels were all within 0.90-0.96 hour. Mean peak serum levels of BP, at dose levels of 10 mg/10 mg/kg, 20 mg/20 mg/kg and 30 mg/30 mg/kg, were 21.77 micrograms/ml, 35.29 micrograms/ml, 50.08 micrograms/ml, respectively, with half-lives of 0.55-0.63 hour. Urinary recovery rates of PAPM in the first 8 hours after administration at dose levels of 10 mg/10 mg/kg, 20 mg/20 mg/kg and 30 mg/30 mg/kg, were 15.9-31.1%, 15.3-36.9%, 11.0-40.5%, respectively, and those of BP during the same time were 33.1-79.1%, 41.3-93.4%, 12.9-94.4%, respectively. 2. CLINICAL RESULTS: Thirty-nine patients, including 2 with purulent meningitis, 1 with septicemia (suspect), 18 with acute pneumonia, 5 with bronchiolitis, 2 with tonsillitis (unable to receive oral antibiotics), 3 with cervical purulent lymphadenitis, 2 with bacterial enteritis, 6 with urinary tract infections were treated with PAPM/BP at dose levels of 30-100 mg/kg/day. Clinical responses in the patients were excellent or good. Even 2 patients with purulent meningitis were treated with PAPM/BP at dose levels of no less than 20 mg/kg x 3 and 33 mg/kg x 3. Most of respiratory and urinary tract infection cases of moderate severities were treated at dose levels of 30-60 mg/kg/day, i.e., 10 mg/kg x 3 or 20 mg/kg x 3. No adverse reaction was observed. One patient suffered from frequent watery diarrhea but the drug was continued to be administered and the patient recovered quickly. Abnormal laboratory findings were noted, in 2 cases with elevation of platelet, in 1 case with elevation of GOT, in 1 case with elevation of monocyte, in 1 with eosinophilia, in 1 with eosinophilia and decrease in platelet count, in 1 with eosinophilia and elevation of GOT and in 2 with elevation of GOT and GPT, but these abnormalities in the 9 cases were slight and transient.

Adolescent↗

[Pharmacokinetic and clinical studies on meropenem].

Pharmacokinetic and clinical studies on meropenem (MEPM, SM-7338), a new developed carbapenem, were performed and the following results were obtained. 1. Absorption/excretion: Pharmacokinetics of MEPM was studied in 9 children using doses of 10 mg/kg and 20 mg/kg by a 30 minute-drip infusion. Peak plasma levels and plasma half-lives of the 2 doses were 28.4 and 43.0 micrograms/ml, and 0.70 and 0.80 hours, respectively. Their urinary recovery rates were 42.5 to 67.6% and 29.9 to 62.6%, respectively. Cerebrospinal fluid levels and penetration rates of MEPM in a patient with purulent meningitis were 0.66 to 4.01 micrograms/ml and 1.6 to 12.2%, respectively. 2. Clinical study: Forty-nine patients were treated with MEPM at doses exceeding 100 mg/kg/day with purulent meningitis and 30 to 60 mg/kg/day with other infections. MEPM gave "excellent" or "good" responses in 48 cases, an efficacy rate of 98.0%. Only one patient with subdural abscess showed fair response. Diarrhea and rash were observed in 1 case each. Abnormal laboratory test results were noted in 5 patients including elevation of GOT, GPT and eosinophils. In no cases the treatment had to be discontinued.

Absorption↗

Occurrence in vivo of 5-hydroxytryptophol in the brain of rats treated with ethanol.

The effect of ethanol (EtOH) on the release of dopamine (DA) and 5-hydroxytryptamine (5-HT) and the efflux of their metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindol-3-ylacetic acid (5-HIAA) and 5-hydroxytryptophol (5-HTOL) from the striatum of the freely moving rat were studied in vivo using brain microdialysis. Striatal DA and 5-HT release was maximally enhanced at first fraction after the administration of EtOH (2 g/kg, i.p.). The level of the DA-oxidized metabolite, DOPAC, decreased significantly. In the 5-HT metabolic pathway, the oxidized metabolite, 5-HIAA, did not show significant changes, whereas levels of the biogenic alcohol 5-HTOL were increased to 180% at 90 min following EtOH administration. It is suggested that EtOH, most probably via acetaldehyde, could shift 5-HT metabolism from the oxidative to the reductive pathway in the rat brain.

3,4-Dihydroxyphenylacetic Acid↗

Human T-cell leukemia virus type I as agent inducing genetic changes in infected human lymphocytes.

Sera and DNA samples, including cord blood, were examined from six members of a three-generation family suspected of being carriers of HTLV-I. Serum antibodies to HTLV-I were detected by Western blot analysis more clearly in adults than in children. DNA sequences related to HTLV-I-gag and -tax, but not -pol genes were detected more clearly in specific PCR products of DNA of adults than those of children, and of the cord blood by Southern hybridization analysis. HTLV-I-related DNA sequences were also detected in some HTLV-I-seropositive as well as seronegative patients with T-cell dyscrasia and with other diseases, including carcinoma. Frequencies of chromosome abnormalities were found to be significantly higher in lymphocytes of HTLV-I-seropositive persons than in those of HTLV-I-seronegative persons. Immortalization of cultured lymphocytes following infection with HTLV-I was found to be accompanied by chromosome and gene rearrangements. Transformation of these cells following treatment with carcinogens was found to be accompanied by additional chromosome rearrangements. These results suggest that some persons may be born with HTLV-I-related sequences that are repressed in childhood. Repeated expression of their products may result not only in the host antibody response but also in increased chromosomal instability and in increased risk for further genetic changes of carrier cells when exposed to environmental carcinogens.

Adolescent↗

Comparative ultrastructure of the tip of ventricular papillary muscle.

Electron microscopic studies of the tips of left ventricular papillary muscles from seven human, two monkey, three sheep, and two chicken hearts were done to elucidate the fine structure of myotendinous junctions. The human specimens were from normal hearts obtained 3 to 9 hours postmortem from persons aged 7 months to 30 years (mean, 13.3 years). We found no significant ultrastructural differences between the human hearts and those of monkey, sheep, and chicken. Myocardial fibers were elongated and thinner (tapered) in the tips of papillary muscles. In addition to usual working myocardial cells, the distal end of narrowing muscle fibers also contained small pale cardiocytes containing fewer myofibrils and smaller mitochondria. These cells were similar to P cells or transitional cells in the conduction system. Nerve axons and Schwann cells were commonly seen in the interstitium, usually in association with capillaries. Fibroblasts and axon varicosities were occasionally seen extremely close to the cardiocytes. These specialized myocardial cells associated with rich neural tissue in the papillary muscle tip possibly function as foci of local automaticity. This histologic organization may also represent neurosensory function responding to and monitoring local pressure changes, efferent adrenergic or cholinergic neural activity, or both.

Adolescent↗

[A series of anesthesia for a child with Lowe's syndrome].

A series of anesthesia for a child with Lowe's syndrome was reported. The boy underwent general anesthesia for 6 times for ophthalmic and dermatologic surgeries in approximately eight years since the age of only four months when the first anesthesia had been given. From the third to the fifth episodes of anesthesia, marked metabolic acidosis was noted, but at the first and second anesthesia, metabolic acidosis had not been recognized. Such acidosis was corrected each time by 7% NaHCO3 infusion at the early stage of anesthesia, and afterwards uneventful courses were seen. In the last anesthesia, acidosis was not found, though disturbance of renal functions were suspected because of abnormal urinary NAG and beta 2-microglobulin value in blood. Attention should be paid to possible anesthetic hazards in Lowe's syndrome patients such as metabolic acidosis due to the renal-tubular dysfunction, the risk of convulsion, glaucoma, the fragility of the bone structures, and so forth.

Acidosis↗

Neuropeptide Y stimulates prostacyclin production in porcine vascular endothelial cells.

We investigated the effects of neuropeptide Y on the prostacyclin production of cultured porcine aortic endothelial cells by measuring the stable metabolite of prostacyclin, 6-keto-prostaglandin F1 alpha, by radioimmunoassay. Neuropeptide Y induced dose- and time-dependent stimulation of prostacyclin production by cultured porcine aortic endothelial cells. The lowest stimulatory concentration of neuropeptide Y was 10(-8) M and maximal response, a 2.8 fold rise, was obtained with 10(-6) M. The stimulation lasted at least 24 h. The effect was associated with the stimulation of arachidonic acid release. Our data suggest that neuropeptide Y may inhibit the development of atherosclerosis by stimulating prostacyclin synthesis.

6-Ketoprostaglandin F1 alpha↗

Patients with idiopathic cardiomyopathy belong to the same mitochondrial DNA gene family of Parkinson's disease and mitochondrial encephalomyopathy.

Comparison of total mitochondrial DNA sequences of patients with idiopathic (deleted or hypertrophic) cardiomyopathy with those of patients with Parkinson's disease and mitochondrial encephalomyopathies revealed distinct clustering of point mutations among patients. Furthermore, an inverse relation was found between the total number of base-substitution and life span of the patients. Among point mutations found in each patient, sequentially diverged six clusters consisting of 14, 10, 7, 1, 2, and 3 mutations, respectively, were detected. Five sub-clusters consisting of 2, 2, 11, 1, and 1 mutations, respectively, were detected. From each cluster, the patient's unique mutations were diverged with three types of the mutations specific for the disease. The divergence allowed construction of a phylogenetic tree which clearly indicated that patients with idiopathic cardiomyopathy belong to the same mitochondrial DNA gene family of Parkinson's disease and mitochondrial encephalomyopathies.

Adult↗

Autonomous growth of human T-lymphotropic virus type I infected human lymphocytes treated with N-methyl-N'-nitro-N-nitrosoguanidine and ultraviolet rays.

Human T-cell cultures infected with human T-lymphotropic virus type I (HTLV-I) and interleukin-2 (IL-2)-dependent for their continuous growth were treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and then maintained in the medium containing phorbol 12-myristate 13-acetate (TPA). Cells achieved independence from IL-2 but became TPA-dependent for continuous growth. Multiple ultraviolet (UV) irradiations of TPA-dependent cells resulted in their autonomous growth. G-band karyotype analysis revealed multiple chromosomal abnormalities that were seen in cells before and after MNNG treatment and UV irradiations, and those that were only seen in autonomously growing cells. Viral expression was found to be transiently enhanced in association with emergence of certain chromosomal changes. Exposure of HTLV-I infected cells to certain mutagens may promote the occurrence of the specific rearrangement of cellular genes responsible for regulation of cellular and viral replication and may lead these cells to neoplastic transformation.

Cell Division↗