Biomedical subjects

K Harada

Publications and source records attributed to K Harada.

At least 505 records · Page 28Linked to original sources

PubMed1996

Bacterial changes in neonatal intensive care unit.

Organisms routinely cultured from throat swabs and infectious agents of sepsis and/or meningitis were reviewed. During the last 12 years, Klebsiella pneumoniae and Escherichia coli have been replaced by Staphylococcus aureus and Pseudomonas aeruginosa as the predominant isolates from throat swabs after admission. These change in the etiologic pattern of infectious agents of sepsis and/or meningitis, i.e., K. pneumoniae, E. coli, S. aureus, P. aeruginosa and staphylococcus epidermidis, were in agreement with the organisms isolated from the throat swabs after admission. The S. aureus isolated from throat swabs after admission showed a decrease in the bacterial activity of cloxacillin, cephazolin and cefotaxime since 1978.

Bacteria↗

PubMed1996

A mother and daughter with agenesis of the corpus callosum.

A mother and daughter with agenesis of the corpus callosum are reported. There have only been 11 prior case reports of the familial occurrence of agenesis of the corpus callosum in the absence of extracranial malformations. Most of these reports have described familial occurrence among siblings. The present communication is only the second description of a parent and child with agenesis of the corpus callosum. A review of the published cases of familial syndrome unrelated agenesis of the corpus callosum indicates that both mental, developmental and neurologic disorders in cases involving parent and child are milder than those in cases involving siblings. Of additional interest, electroencephalography performed in this patient during sleep, frequently revealed bilateral asynchronous sleep spindles, supporting the hypothesis of previous investigators that the synchronicity of sleep spindles requires intact intercerebral commissures.

Agenesis of Corpus Callosum↗

PubMed1996

Treatment of aplastic anemia with antithymocyte globulin, cyclosporin A, methylprednisolone, danazol and recombinant human granulocyte-colony stimulating factor.

The main purpose of the present study was to determine the response rate to immunosuppressive therapy combined with recombinant human granulocyte-colony stimulating factor (rhG-CSF) and its efficacy for preventing infections in patients with severe aplastic anemia. The treatments included one course of antithymocyte globulin, cyclosporin A, methylprednisolone, danazole and rhG-CSF. Three patients had very severe aplastic anemia and two had moderate aplastic anemia. One patient relapsed 13 months following the first course of therapy and received a second course. Five patients received six courses of treatment and the response rate at 6 months was 83.3%. All patients achieved an absolute neutrophil count of greater than 1.0 x 10(9)/L within 40 days. All patients with a complete response are transfusion-free and doing well. All five patients are currently alive and have not had any episode of infection for 17-53 months. The results of the study indicate that this therapy may improve the poor prognosis of young patients with severe aplastic anemia. It has a good response rate and induces a rather rapid increase in the neutrophil count, which protects against life-threatening bacterial and fungal infections.

Adolescent↗

PubMed1996

Dissociation of P2 purinoceptor-mediated increase in intracellular Ca2+ level from myosin light chain phosphorylation and contraction in rat aorta.

1. The effects of P2 agonists, adenosine-5'-triphosphate (ATP), alpha, beta-methylene-adenosine-5'-triphosphate (alpha, beta-me-ATP) and adenosine 5-O-(3-thiotriphosphate) (ATP gamma S), on the intracellular free Ca2+ level ([Ca2+]i), myosin light chain (MLC) phosphorylation and force of contraction were examined in vascular smooth muscle of rat aorta. 2. ATP (0.1 microM-1 mM), alpha, beta-me-ATP (0.1-100 microM) and ATP gamma S (1-100 microM) induced transient increases followed by sustained increase in [Ca2+]i. The effects of these agonists were concentration-dependent. Compared with the effects of a high concentration of KCl (17.5-72.4 mM), the contractions induced by these P2 purinoceptor agonists were smaller at a given [Ca2+]i. 3. In the absence of extracellular Ca2+ (with 0.5 mM EGTA), ATP gamma S (10 microM) induced large transient increase in [Ca2+]i with only small contraction in Ca(2+)-free solution. In contrast, alpha, beta-me-ATP (10 microM) induced only a very small increase in [Ca2+]i and contraction. 4. ATP (1 mM), alpha, beta-me-ATP (10 microM) and ATP gamma S (10 microM), added during stimulation with 0.1 microM noradrenaline, induced additional and transient increases in [Ca2+]i which were also not associated with contraction. 5. High K+ (72.4 mM) increased MLC phosphorylation with a similar time course to that of the increase in [Ca2+]i (peak phosphorylation was 56% when [Ca2+]i increased to 100%). In contrast, the time course of the increase in MLC phosphorylation due to ATP (1 mM) did not coincide with that of the large increases in [Ca2+]i; MLC phosphorylation increased to only 31% when [Ca2+]i increased to 163%. The MLC phosphorylation due to alpha, beta-me-ATP (10 microM) and ATP gamma S (10 microM), measured at peak [Ca2+]i, were only 19% and 14%, respectively, irrespective of a large increase in [Ca2+]i (138% and 188%, respectively). 6. The absence of a clear relationship between P2-purinoceptor-mediated increase in [Ca2+]i (either by Ca2+ influx or Ca2+ release) and MLC phosphorylation or force generation appears to imply that elevation in [Ca2+]i does not contribute to these responses.

Adenosine Triphosphate↗

PubMed1996

Plasma concentration of granulocyte-colony-stimulating factor in neonates.

We determined the plasma concentration of granulocyte-colony-stimulating factor (GCSF) and the neutrophil count in 108 infants (gestational age 23-41 weeks; birthweight 478-4935g). The GCSF levels in the very low birthweight infants without infection were comparable to those in the full-term infants. Infants as premature as 23 weeks of gestation showed similar GCSF levels to mature neonates. GCSF levels decreased significantly by day 7 after birth. The levels were not significantly correlated with the neutrophil count. The mean plasma level of GCSF increased significantly when infection developed and was significantly higher in the infants with sepsis than in those with non-septic infections (p < 0.01). The results suggest that GCSF may be the major determinant of neutrophil kinetics both during fetal life and after birth.

Birth Weight↗

PubMed1996

A case of Guillain-Barré syndrome accompanied by sympathetic overactivity and hypertensive encephalopathy.

Hypertension has often been observed in patients with Guillain-Barré syndrome, and various underlying mechanisms have been implicated. We report the case of a child with the Guillain-Barré syndrome whose hypertension was associated with increases in both renin activity and circulating catecholamines. This case also appeared to be complicated by hypertensive encephalopathy. Following administration of intravenous regitine, a blood pressure change was observed and cardiac performance was assessed by two-dimensional echocardiography. Results indicated that increased total peripheral resistance may have been responsible for the symptoms and the hypertension. The hypertension was effectively managed by nifedipine, captopril and prazosin without the need for beta-blockade.

Child, Preschool↗

PubMed1996

Analysis of suppressor mutations of spoIVCA mutations: occurrence of DNA rearrangement in the absence of site-specific DNA recombinase SpoIVCA in Bacillus subtilis.

The spoIVCA gene of Bacillus subtilis encodes a site-specific recombinase, which excises a 48-kb skin element from the chromosomal DNA by DNA rearrangement and creates a new composite gene, sigK, on the chromosome. From spoIVCA mutants, we have isolated Spo+ revertants which have no skin element but have an intact sigK gene. This result suggests that the DNA rearrangement can occur in the absence of spoIVCA.

Bacillus subtilis↗

PubMed1996

Transcription factor PU.1 mediates induction of c-fms in vascular smooth muscle cells: a mechanism for phenotypic change to phagocytic cells.

The macrophage colony-stimulating factor receptor encoded by the c-fms gene is expressed in vascular intimal smooth muscle cells isolated from atherosclerotic lesions. A combination of platelet-derived growth factor-BB and epidermal growth factor induces stable expression of c-fms in normal vascular medial smooth muscle cells. The mechanism by which these growth factors induce c-fms expression has now been investigated in an attempt to gain insight into the events that underlie the phenotypic conversion of vascular smooth muscle cells in atherosclerosis. Deletion analysis of the c-fms promoter revealed that the region including a binding site for transcription factor PU.1 was required for transcriptional activity in human aortic medial smooth muscle cells. Mutation in the PU.1 binding site markedly reduced promoter activity. Northern (RNA) blot analysis demonstrated that growth factors induced the expression of PU.1 mRNA in vascular medial smooth muscle cells and that PU.1 mRNA was expressed in vascular intimal smooth muscle cells. PU.1 antisense oligonucleotides inhibited growth factor-induced c-fms expression and foam cell formation. These results suggest that transcription factor PU.1 plays an essential role in the phenotypic conversion of vascular smooth muscle cells to macrophagelike cells by mediating the induction of c-fms.

Aorta↗

PubMed1996

Vascular endothelial growth factor administration in chronic myocardial ischemia.

Vascular endothelial growth factor (VEGF) is a potent mitogen capable of stimulating angiogenesis. We examined the effect of VEGF administration in a model of chronic porcine myocardial ischemia. Nineteen pigs were instrumented with proximal left circumflex coronary artery (LCX) Ameroid constrictors. In eight animals VEGF (2 microgram) with heparin (50 U) was administered extraluminally to the LCX myocardium with an osmotic pump for 4 wk and 11 other animals served as controls. VEGF-treated animals demonstrated higher flow in the LCX territory during both rest and pacing compared with untreated controls (rest: 1.35 +/- 0.1 vs. 0.80 +/- 0.09 ml.min-1.g-1; pacing; 2.01 +/- 0.37 vs. 1.01 +/- 0.07 ml.min-1.g-1, P < 0.05, VEGF vs. controls). The observed improvement in regional coronary flow in VEGF-treated animals resulted in better preservation of endothelium-dependent microvessel relaxation as well as fractional LV shortening in the LCX territory during pacing in the VEGF-treated than in control animals (controls: 7.1 +/ 2.6 vs. 3.6 +/- 2.0%, rest vs. pacing; VEGF: 6.9 +/- 2.9 vs. 6.3 +/- 2.9%, rest vs. pacing). We conclude that VEGF administration in a gradual coronary occlusion model in pigs results in improvement of coronary flow and preservation of regional hemodynamics in the compromised myocardium.

Animals↗

PubMed1996

Nitric oxide and endothelin 1 during postnatal life.

Nitric oxide (NO) is a potent vasodilator produced by endothelial cells. Endothelin 1 (ET-1), another agent made by endothelial cells, is the most potent vasoconstrictor known to date. Endogenous NO and ET-1 may play a part in the normal physiological pulmonary vascular changes during the postnatal period. However, the changes of NO and ET-1 in healthy neonates have not been defined. We determined serum NO metabolites, i.e., nitrites and nitrates, and plasma ET-1 in 19 healthy neonates at birth (cord blood) and at ages 5 and 30 days. The sums of serum nitrite and nitrate (NOx) levels were 27.5 +/- 12.8, 53.8 +/- 14.2, and 38.3 +/- 13.2 mumol/l at birth, age 5 days, and age 30 days, respectively. The plasma ET-1 concentrations were 3.9 +/- 1.6, 1.1 +/- 0.2, and 1.1 +/- 0.2 x 10(6) mumol/l at birth, age 5 days, and age 30 days, respectively. These changes in healthy neonates suggest the presence of active physiological roles for NO and ET-1 in circulatory adaptation to extra-uterine life.

Aging↗

PubMed1996

Normal nonuniformity of left ventricular contraction. Assessment by cine MR imaging with presaturation myocardial tagging.

PURPOSE: To identify the normal performance of left ventricular (LV) regional contraction using cine MR imaging with presaturation myocardial tagging. MATERIAL AND METHODS: Sixteen normal volunteers were examined on a 1.5 T MR system with tagging cine sequences. Tags were applied at end-diastole as 2 parallel black lines on short-axis and 4-chamber sections, and the fractional shortenings were calculated at 7 LV locations. RESULTS: The following results were obtained with significance: a transmural gradient of contractility in the short-axis section; prolonged late-systolic endocardial shortening and epicardial early termination in the free wall; initial delay of shortening in the anterior wall; apical predominance of contractility; predominance of circumferential shortening in the free wall and of meridional shortening in the septum. These findings could be associated with myocardial fiber architecture, presumed wall stress and temporal asynergy of excitation. CONCLUSION: Cine MR imaging with myocardial tagging proved to be useful in assessing the nonuniformity of LV contraction.

Adult↗

PubMed1996

Serum immunoreactive activin A levels in normal subjects and patients with various diseases.

We developed and validated a RIA for measuring serum activin A. The least detectable value of this assay was 0.1 micrograms/L, and the antibody used cross-reacted slightly with bovine inhibin (3.2%) and porcine activin AB (10.0%) but not with porcine activin B (< 0.5%). Serum activin A was extracted with acetonitrile and trifluoroacetic acid to get rid of the interaction with possible binding proteins in serum. As a result of this extraction procedure, the dose-response curve of serum extract was parallel to the standard curve and a single immunoreactive (ir-) peak was demonstrated on gel chromatographic analysis with constant recovery rates over 80%. Serum ir-activin A level in healthy adults was 1.27 +/- 0.03 micrograms/L (mean +/- SEM, n = 180); being 1.38 +/- 0.05 micrograms/L (n = 90) in male, and 1.16 +/- 0.05 micrograms/L (n = 90) in female subjects, with a tendency to increase with age. Serum ir-activin A level during pregnancy showed a marked increase with the advance of gestation; 1.65 +/- 0.41 micrograms/L (n = 7) in the early, 4.50 +/- 1.13 micrograms/L (n = 21) in the middle, and 16.32 +/- 2.25 micrograms/L (n = 26) in the late trimester, with a rapid decline after delivery. On the other hand, serum ir-activin A level was elevated in patients with hyperthyroidism (1.91 +/- 0.37 micrograms/L, n = 31), liver cirrhosis (2.03 +/- 0.71 micrograms/L, n = 10), chronic renal failure (3.41 +/- 0.34 micrograms/L, n = 41), and advanced solid cancer (2.24 +/- 0.52 micrograms/L, n = 67). These findings indicate that serum ir-activin A level varies with physiological conditions such as aging and pregnancy, and that it may reflect the altered production and metabolism of activin A in certain diseased conditions.

Activins↗

PubMed1996

Mechanisms of satigrel (E5510), a new anti-platelet drug, in inhibiting human platelet aggregation. Selectivity and potency against prostaglandin H synthases isozyme activities and phosphodiesterase isoform activities.

Satigrel (E5510, 4-cyano-5,5-bis(4-methoxyphenyl)-4-pentenoic acid) is a potent inhibitor of platelet aggregation. Like cyclooxygenase/prostaglandin H synthase (PGHS) inhibitors such as aspirin, which suppress platelet aggregation by inhibiting thromboxane A2 production, satigrel inhibits collagen- and arachidonic acid-induced aggregation of human platelets. In contrast to other PGHS inhibitors, satigrel, like cyclic nucleotide phosphodiesterase (PDE) inhibitors such as cilostazol, shows inhibitory activity against thrombin-induced platelet aggregation. To investigate the mechanism of the anti-platelet activity of satigrel, we examined the selectivity and potency of satigrel against PGHS isozyme activities and PDE isoform activities. Two isozymes of PGHS are known; constitutive enzyme (PGHS1) and inducible enzyme (PGHS2). Satigrel showed inhibitory activity against PGHS1 (IC50: 0.081 microM) and PGHS2 (IC50: 5.9 microM), suggesting the selective inhibition of PGHS1. Indomethacin, which is a selective inhibitor of PGHS1, showed similar selectivity against PGHS isozymes (IC50: 0.12 microM and 1.4 microM, respectively). These results support that satigrel suppresses thromboxane A2 production by inhibiting PGHS1. It is known that three isozymes of PDE exist in human platelets: Type V, which specifically hydrolyzes guanosine 3',5'-cyclic monophosphate (cGMP), Type III, which mainly hydrolyzes cAMP, and Type II, which hydrolyzes both cGMP and cAMP. We separated these three isozymes from human platelets and examined the inhibitory activity of satigrel against each enzyme. Of the three isozymes, the inhibitory activity of satigrel was the most potent against Type III PDE (IC50: 15.7 microM). The IC50 value for Type III corresponded with that for thrombin-induced platelet aggregation. Type V and Type II were also inhibited by satigrel (IC50: 39.8 and 62.4 microM, respectively). In human platelets, satigrel increased both cAMP and cGMP levels in a dose-dependent manner (100, 300 microM). In conclusion, satigrel inhibits collagen- and arachidonic acid-induced platelet aggregation through preventing thromboxane A2 synthesis by selective inhibition of the target enzyme, PGHS1, which exists in platelets. The anti-aggregating activity of satigrel against thrombin-induced aggregation may be due to elevation of the cyclic nucleotide levels through the inhibition of PDE isozymes.

Blood Platelets↗

PubMed1996

Effects of LHRH, FSH and activin A on follistatin secretion from cultured rat anterior pituitary cells.

We demonstrated the release of follistatin, an activin-binding protein, from cultured rat anterior pituitary cells by measuring immunoreactive (ir-) follistatin in a specific immunoradiometric assay. Ir-follistatin release gradually increased in cultures over 1-18 days and reached its maximal level at 12-15 days of incubation. The basal ir-follistatin levels in the culture media increased about 3- (P < 0.01) and 5-fold (P < 0.001) in 2 and 10% fetal calf serum for 6 days, respectively. LHRH and activin A caused an approximately 2.0- (P < 0.05) and 1.8-fold (P < 0.05) rise in ir-follistatin release, respectively, in contrast to the lack of significant FSH effects. The culture medium condensed on sulfate-cellulofine gel was resolved by polyacrylamide gel electrophoresis and blotted with anti-follistatin polyclonal antibody, resulting in at least three protein bands ranging from 35 to 50 kDa under non-reducing conditions. These results indicated that follistatin is produced in anterior pituitary cells and that its secretion is regulated at least in part by LHRH and activin, implying an autocrine/paracrine role of activin and follistatin in the pituitary.

Activins↗

PubMed1996

Regulation of immunoreactive activin A secretion from cultured rat anterior pituitary cells.

Immunoreactive activin A (ir-activin A) release from cultured rat anterior pituitary cells was examined by measuring ir-activin A in culture medium by a specific radioimmunoassay. Ir-activin A release into the medium increased over 1-18 days, and reached a maximal level at 12-15 days. The basal levels of ir-activin A in the culture media were 0.70 +/- 0.10 (mean +/- SD), 1.30 +/- 0.36 and 1.83 +/- 0.44 ng/10(6) cells, when cultured for 6 days with 0, 2 and 10% fetal calf serum, respectively. LHRH induced an approximate 1.4-fold increase in ir-activin A release in contrast to a 40-60% inhibition with FSH, but LH did not affect the activin A release. In the presence of 12-o-tetradecanoylphorbol acetate (TPA), iractivin A release was enhanced, but no significant effect was induced by forskolin. Activin A was distinctly immunostained in cultured rat anterior pituitary cells. These results suggested that activin A release from the pituitary is modified by FSH and LHRH, and that the activation of protein kinase C may be involved in the action of LHRH.

Activins↗

PubMed1996

Determination of free follistatin levels in sera of normal subjects and patients with various diseases.

We developed an assay system for measuring free follistatin by using an anti-follistatin mouse monoclonal antibody and [125I]activin A. The sensitivity of this assay was 0.5 microgram/l and cross-reactivities with inhibin, luteinizing hormone, follicle-stimulating hormone and growth hormone were all less than 0.5%. The dose-response curves of human sera and follicular fluid were parallel to the standard curve, and the follicular fluid contained a large amount of follistatin (6.4 +/- 0.5 mg/l, mean +/- SEM; N = 13). The within- and between-assay coefficients of variation calculated from the analysis of serum samples of four different concentrations were 3.3-7.8% and 3.9-11.0%, respectively. The recovery rates of free follistatin at five different doses were 86.4 - 102.4%. When activin A was added to the same sample, free follistatin recovery rate declined dose-dependently. Gel filtration analyses of human serum and follicular fluid resulted in a single peak corresponding to authentic follistatin. Using this assay, free follistatin concentrations in sera were measured in normal, pregnant and diseased subjects. The free follistatin level in serum of normal adults was 3.5 +/- 0.2 micrograms/l (N = 60), which was significantly elevated in pregnant women (16.7 +/- 1.3 micrograms/l, N = 56), and in patients with chronic liver disease (8.1 +/- 1.1 micrograms/l, N = 20), chronic renal failure (6.7 +/- 0.9 micrograms/l, N = 42), advanced solid cancer (8.5 +/- 1.0 micrograms/l, N = 39) and hematological malignancies (6.8 +/- 1.0 micrograms/l, N = 18). These data indicated that the free follistatin concentration in serum is detectable and varies during pregnancy and in various diseased states.

Adult↗

PubMed1996

An infant case of Ebstein's anomaly of the tricuspid valve with abnormal diastolic filling pattern of the left ventricle.

We report herein an infant case of Ebstein's anomaly with abnormal diastolic filling pattern of the left ventricle. We also compare the case with a comparable case without such abnormal filling pattern. The patient, who had pulmonary valve stenosis, patent ductus arteriosus and mild mitral regurgitation, underwent transventricular valvotomy at 30 days of age. Postoperative course was uneventful. Serial Doppler echocardiographic studies were performed at 2 hr, 40 days, and 52 days of age. Peak velocity and flow velocity-time integral of early diastole, and ratios of the peak velocities and velocity time integrals of the early diastole and atrial contraction were below the 95% confidence limits of the normal controls. Our case suggests that left ventricular diastolic dysfunction may exist in the Ebstein's anomaly when it is associated with mitral valve abnormality such as mitral regurgitation.

Diastole↗

PubMed1996

Transgenic mouse and gene therapy.

In the transgenic mouse, a specific gene can be transduced or deleted to study its function and relation to human diseases. Recently, various lines of transgenic mice that overexpress or lack a specific gene have been established and are available to study the pathophysiology of human diseases, including atherosclerosis, diabetes, and hyperlipidemia. We have established transgenic mouse lines with an integrated rat apolipoprotein (apo) E gene under control of the metallothionein promoter. Overexpression of apoE in the liver reduced plasma cholesterol and triglyceride levels and prevented diet-induced hypercholesterolemia. Another transgenic model with overexpression of apoE under control of the H2 Ld promoter in the arterial wall was established. In this model, the formation of fatty streak lesions was markedly inhibited, suggesting that apoE has antiatherogenic actions. Finally, we discuss gene therapy, which will be an important therapeutic approach to correct genetic abnormalities found in metabolic diseases.

Animals↗