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Biomedical subjects

K Kawamura

Publications and source records attributed to K Kawamura.

At least 235 records · Page 13Linked to original sources
PubMed1996

Vasospastic angina in patients with systemic triglyceride storage disease with Jordans' anomaly and cardiomyopathy.

Vasospastic angina was demonstrated clinically and angiographically in a 54-year-old patient with systemic triglyceride storage disease and cardiomyopathy. He and his younger sister had been diagnosed in 1985 as having systemic triglyceride storage with Jordans' anomaly. In 1993, he began complaining of rest and effort chest pain in the morning, which was accompanied by ST depression by ECG. Sublingual nitroglycerine was effective for treating this pain. Intracoronary injection of acetylcholine induced severe coronary vasoconstriction in the left anterior descending artery. Left ventricular contraction was diffusely impaired. Deposits of numerous triglyceride droplets and a decrease in the density of myofibrils in cardiocytes were found in the specimens obtained by endomyocardial biopsy. The impaired left ventricular contraction may have been due to the changes in myocardial cells. His sister complained of a similar chest pain that was completely controlled by calcium channel antagonis. Thus, our cases demonstrated vasospastic angina associated with cardiomyopathy secondary to systemic triglyceride storage disease with Jordans' anomaly, though the causal relationship between these conditions remains unclear.

Adult↗
PubMed1996

Comparison of the therapeutic effects of the beta-blocking agent bisoprolol and the calcium-blocking agent diltiazem in patients with heart failure due to dilated cardiomyopathy.

Beta-blocking agents reduce mortality and improve symptoms in patients with dilated cardiomyopathy (DCM). There have been reports that diltiazem, a calcium-blocking agent, is also effective in such patients. We prospectively compared the effects of the beta-blocking agent bisoprolol with those of the calcium-blocking agent diltiazem in 18 patients (11 males and 7 females, age 14 to 68) with DCM. The 18 patients, (10 in New York Heart Association functional class III and 8 in class IV) were randomly assigned to 2 groups. Bisoprolol was administered as the first drug in 10 patients and diltiazem was administered in 8. Cross-over to bisoprolol was also performed in 3 patients. At the end of the study, among the 13 patients who had been given bisoprolol, 9 showed a good response (efficacy rate: 69%). In contrast, only 3 of the 8 patients who received diltiazem showed a good response (efficacy rate: 37.5%). Among the patients in NYHA class III, all 7 (100%) who were treated with bisoprolol responded but only 2 of the 4 (50%) treated with diltiazem responded (p < 0.05). Among the patients in class IV, 2 of 6 (33%) responded to bisoprolol and 1 of 4 (25%) responded to diltiazem (not significant). These results suggest that diltiazem, like bisoprolol, has a beneficial effect in patients with DCM, with a greater effect in class III patients. However, we conclude that diltiazem should usually be used as a second choice to improve heart failure in DCM, and as the first medication only in those with contraindications to beta-blocking agents.

Adolescent↗
PubMed1996

Genetic instability as a basis for transformation of human lymphocytes infected with human retrovirus.

T cell lines (Coculture-14, Coculture-5) derived from human T-cell leukemia virus type I (HTLV-I)-seronegative persons acquired interleukin-2 (IL-2)-dependent continuous growth capacity (immortalized) following in vitro HTLV-I infection. They showed structural abnormalities of chromosomes carrying proviral DNA as seen by in situ hybridization. Following ultraviolet (UV) irradiation, Coculture-5 cells achieved IL-2-independent autonomous growth (transformed) resulting in the establishment of UV-1 and UV-5 lines. They showed additional abnormalities of the same chromosomes. Cocultivation of Coculture-5 cells with IUdR-treated UV-1 cells also resulted in autonomous growth of Coculture-5 cells, giving rise to three cell lines. By ABC immunostaining with specific antibodies, expression of proteins coded for growth regulatory genes, including Ki-67, Topo II, Pol alpha, c-MYC, p53, Rb, bcl-3, bcl-2, and BM-1, was found to be variably altered in transformed cells compared with immortalized cells. These results demonstrated chromosomal instability, altered gene product expression of HTLV-I-infected human lymphocytes, and their susceptibility to transformation without exposure to an initiating carcinogen.

Cell Line, Transformed↗
PubMed1996

[Disappearance of essential neck tremor after pontine base infarction].

Mechanism of essential tremor remains unknown. Central oscillators, postulated in thalamus, inferior olive, and spinal cord are thought to be important to form rhythmicity, and finally to stimulate spinal or medullary motor cells, leading trembling muscle contraction, tremor. Among several subtypes of essential familial tremor, including hand tremor, neck tremor, and voice tremor, essential neck tremor is a common disorder, and its pathophysiology seems different from that of typical essential hand tremor, since patients with essential hand tremor are responsive to beta blocker, whereas those with neck tremor are usually not. We experienced a 41-year-old left handed woman with essential neck tremor in whom neck titubation disappeared shortly after pontine base infarct. She was our patient in the outpatient clinic with the diagnosis of essential neck tremor. The tremor developed when she was teenage, and has been localized in the neck muscles. Alcohol intake had apparently diminished it transiently. Her mother also had the tremor in her neck. She was admitted to our hospital with sudden onset of right-sided limb weakness and speech disturbance. Neurological examination showed right hemiparesis including the ipsilateral face, scanning speech, and cerebellar limb ataxia on the same side. In addition, there was no tremor in her neck. Brain MR imaging revealed a pontine base infarct at the level of middle pons, which was consistent with paramedian artery territory. The hemiparesis and speech disturbance improved almost completely after treatment, and her neck tremor has never occurred in one year follow-up. In our patient, efficacy of alcohol imply that essential neck tremor and hand tremor had same central nervous pathway including central oscillator in common, and descending cortical fibers is seemingly associated with diminishing patient's tremor. Pathophysiology of essential neck tremor was discussed with reviewing previous literature.

Adult↗
PubMed1996

Resistance to interleukin 6 in human non-small cell lung carcinoma cell lines: role of receptor components.

The role of interleukin 6 (IL-6) in regulating the growth of three human non-small cell lung carcinoma (NSCLC) cell lines (NSCLC-3, NSCLC-5, and NSCLC-7, derived from a primary lesion, a brain lesion, and lymph node metastases, respectively) was examined. Although IL-6 alone did not alter the growth of these cells, the addition of soluble IL-6 receptor (sIL-6R) led to the inhibition of proliferation of one of the NSCLC cell lines, NSCLC-5. This antiproliferative effect was neutralized by antibodies to IL-6 and the IL-6R binding and signaling component (gp130). The IL-6-related cytokines, leukemia inhibitory factor and oncostatin M, inhibited proliferation of NSCLC-5 cells but were ineffective in NSCLC-3 and NSCLC-7 cells. NSCLC-7 cells (but not NSCLC-3 or NSCLC-5 cells) secreted biologically active IL-6 and expressed IL-6R. However, antibodies to IL-6 or gp130 failed to alter the proliferation of NSCLC-7 cells. All three cell lines expressed gp130 mRNA and protein. The level of expression of gp130 protein varied in the three cell lines (NSCLC-7 > NSCLC-3 > NSCLC-5). The examination of tyrosine phosphorylation of gp130 (as an early event in IL-6 signal transduction) revealed that gp130 could be phosphorylated in all cell lines after stimulation with IL-6 and/or IL-6 + sIL-6R. These results demonstrate that the mechanisms responsible for IL-6 resistance in different NSCLC cell lines vary and involve defects at either one or more levels of the IL-6 signaling cascade. In the NSCLC-5 cell line, IL-6 resistance (which can be reversed in the presence of sIL-6R) is due to the transcriptional inactivation of the IL-6R gene. In contrast, in the other two cell lines (NSCLC-3 and NSCLC-7), defect(s) in the signaling cascade downstream of gp130 phosphorylation, together with a lack of expression of IL-6R in NSCLC-3 cells, result in IL-6 resistance.

Antigens, CD↗
PubMed1996

IgA antikeratinocyte surface autoantibodies from two types of intercellular IgA vesiculopustular dermatosis recognize distinct isoforms of desmocollin.

We previously proposed the term intercellular IgA vesiculopustular dermatosis (IAVPD) for cases showing IgA antikeratinocyte surface autoantibodies. This condition is divided into two subtypes: intraepidermal neutrophilic IgA dermatosis (IEN), showing pustule formation in the entire epidermis, and subcorneal pustular dermatosis (SPD) showing pustule formation in the uppermost epidermis. We have previously reported that serum from certain IAVPD patients reacts with bovine desmocollin (Dsc), a desmosomal cadherin. In this study we showed that two Dsc isoforms with a slightly different molecular weight were recognized by the serum from these patients. Further analysis revealed that serum from patients with the SPD type, which stained the cell surface in the uppermost epidermis with immunofluorescence, seem to react with Dsc1. By contrast, serum from patients with the IEN type, which stained the cell surface at all levels of the epidermis with immunofluorescence, seemed to react with Dsc3. This difference of distribution between the two distinct Dsc molecules may contribute to the different clinicopathological features between the IEN and SPD type of IAVPD.

Autoantibodies↗
PubMed1996

[Origin of the adenohypophysis and of the olfactory system in toads: demonstration by chimera method].

Localisation of the primordium of the olfactory system and its topographical relationships with the primordium of the hypothalamic-hypophyseal system were determined on the embryos of the toad Bufo japonicus by generating chimeric embryos. Different parts of the neural ridge and the neural plate were taken up from normal embryos and grafted on the same region of albino embryos of the same developmental stage. The melanin granules contained in the grafts permitted to trace the developmental fate. The anteriormost region of the neural ridge (ANR) was found to be the origin of all the parts of the adenohypophysis as well as some of the neurons in the preoptic region. The infundibulum differentiated from the central portion of the neural plate, just posterior to the adenohypophyseal primordium. The primordium of the olfactory system, including the olfactory sacs and the olfactory bulbs, was found to be situated on the neural ridge on both sides of the ANR. The present results showed that the central and peripheral parts of each of the two systems constitute a closely apposed cell population at the neurula stage. It seems that the periphero-central connection in these systems reflect a clonal origin of the presumptive cells. If the olfactory primordium was removed at the neurula stage, the olfactory sac regenerated from the adenohypophyseal primordium. In conclusion, these results demonstrate that the olfactory primordium is related not only topographically but also ontogenetically to the adenohypophyseal primordium.

Animals↗
PubMed1996

Neuron-glia interrelations during migration of Purkinje cells in the mouse embryonic cerebellum.

The interrelations between migratory Purkinje cells and radial glial processes were examined immunohistochemically and electron-microscopically in the fetal mouse cerebellum. Migratory Purkinje cells identified immunochemically with anti-spot 35 antibody were apposed to the presumed radial glial processes. Putative immature migratory Purkinje cells were apposed to the radial glial processes identified immunochemically with monoclonal antibody 1D11 or anti-tenascin antibody. Junctional specializations related to cell adhesion were observed at the sites of contact between the immature neurons and glial processes. Furthermore, coated vesicles and coated pits were noted in the contact region. These findings support the concept of contact guidance of migratory Purkinje cells by radial glial processes through cell adhesion, and also suggest the trophic interactions occurring at the region of contact.

Animals↗
PubMed1995

The POU domain transcription factor Brn-2 is required for the determination of specific neuronal lineages in the hypothalamus of the mouse.

We generated mice carrying a loss-of-function mutation in Brn-2, a gene encoding a nervous system specific POU transcription factor, by gene targeting in embryonic stem cells. In homozygous mutant embryos, migratory precursor cells for neurons of the paraventricular nuclei (PVN) and the supraoptic nuclei (SO) of the hypothalamus die at approximately E12.5. All homozygous mutants suffered mortality within 10 days after birth, possibly because of a complete deficiency of these neurons in the hypothalamus. Although neither developmental nor histological abnormalities were observed in heterozygous mice, the levels of expression of vasopressin and oxytocin in the hypothalamus of these animals were half these of wild-type mice. These results strongly suggest that Brn-2 plays an essential role in the determination and development of the PVN and SO neuronal lineages in the hypothalamus.

Animals↗
PubMed1995

Antithrombotic effect of a humanized anti-GPIIb/IIIa monoclonal antibody, YM207, in a photochemically induced thrombosis model in monkeys.

We investigated the antithrombotic effects of a F(ab')2 fragment of a humanized anti-platelet glycoprotein (GP) IIb/IIIa monoclonal antibody, YM207, in a platelet-rich thrombosis model. Thrombus was induced in a mesenteric venule of squirrel monkeys by irradiation with filtered light in combination with i.v. administration of a fluorescent dye (sodium fluorescein). Time to occlusive thrombus formation was significantly prolonged by i.v. bolus injection of 0.3 mg/kg of YM207. At doses of 1 mg/kg and 3 mg/kg, complete occlusion did not occur during 60 min of the observation. Platelet aggregation in platelet-rich plasma was inhibited by YM207 at doses 0.3 mg/kg or more. A good correlation was obtained between inhibition of platelet aggregation and the percentage of GPIIb/IIIa receptors blocked by YM207. Bleeding time was significantly prolonged at a dose of 3 mg/kg. Platelet counts showed no significant change. These results suggest that YM207 is effective in preventing platelet-rich thrombus formation without inducing the prolongation of bleeding time or a significant decrease in platelet count. YM207 may be a useful therapeutic agent for the treatment of thrombotic disorders.

Adenosine Diphosphate↗
PubMed1995

The sequence of a rat cDNA encoding thrombopoietin.

Overlapping cDNA clones encoding rat thrombopoietin (TPO) were isolated from liver-derived cell line cDNA libraries and the nucleotide sequences were determined. The deduced 326-amino-acid rat TPO showed significant homology to the known TPO of other species, especially in the N-terminal sequence.

Amino Acid Sequence↗
PubMed1995

Migration of dopaminergic neurons in the embryonic mesencephalon of mice.

Migration of dopamine (DA)-containing neurons and its guiding cues were histologically examined in the embryonic mesencephalon of normal mice. Cells immunoreactive (ir) for tyrosine hydroxylase (TH), a DA-synthesizing enzyme, were first detected on embryonic day 10 (E10) in the medio-basal part of the mesencephalon and were distributed throughout the entire length of the ventral mesencephalic wall at E12. By E14, TH-ir cells were located laterally along the ventral pial surface to form the primordia of the substantia nigra. Experiments with a single injection of bromodeoxyuridine, a thymidine analog, demonstrated that cells generated in the ventricular surface of the ventral mesencephalon at E11 migrated ventrally and then moved laterally to form the substantia nigra and the ventral tegmental area. Electron microscopic examination of the ventral mesencephalon of E12 mice disclosed that in the dorsal part ventrally migrating immature neurons made close contacts with the processes of radial glial cells. The expression of tenascin was transiently seen on radial glial processes between E10 and E13 coincident with the period of the ventral migration of mesencephalic DA neurons. By double immunostaining of E13 mesencephalon, ventrally migrating TH-ir cells were seen to be apposed to tenascin-bearing radial glial processes. On the other hand, laterally migrating neurons in the basal part of the mesencephalon were observed by electron microscopy to contact with tangentially arranged nerve fibers which were immunopositive for the 160 kDa neurofilament polypeptide at the light microscopic level from E10. Double immunostaining of E13 mesencephalon demonstrated that laterally migrating TH-ir cells were intermingled among neurofilament-ir fiber bundles. The cells of origin of the tangential nerve fibers were detected in the lateral part of the mesencephalon, when a fluorescent dye, 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI) was injected into the basal part of the mesencephalon of fixed E12 mice. The present results suggest that guiding cues of the radial migration of mesencephalic DA neurons represent processes of radial glial cells which express tenascin. On the other hand, tangentially arranged nerve fibers originating from the lateral part of the mesencephalon may provide a scaffolding along which the mesencephalic DA neurons subsequently migrate laterally to form the ventral tegmental area and the substantia nigra.

Animals↗
PubMed1995

Empiric determination of the transition from concentric hypertrophy to congestive heart failure in essential hypertension.

OBJECTIVES: Our aim was to determine whether there is a final transition from left ventricular hypertrophy to congestive heart failure in the late stage of essential hypertension. BACKGROUND: A theoretic model using the concept of systolic transmural nonuniform wall thickening was applied to develop a concentric two-shell geometry allowing evaluation of the mechanics of circumferential midwall fibers. METHODS: We evaluated pressure-volume data from 46 normal control subjects (control group) and 70 patients with hypertension: 33 without hypertrophy (hypertension only group), 14 with hypertrophy (hypertrophy group) and 23 with heart failure in addition to hypertrophy (heart failure group). RESULTS: End-diastolic volume index was higher in the heart failure group than in the control group (p < 0.01). Although left ventricular wall thickness and mass index were increased in both the hypertrophy and the heart failure group, concentricity indexes as assessed by ratios of left ventricular wall thickness to dimension and mass index to end-diastolic volume index were maximal in the former. Although endocardial and standard midwall fractional shortening did not differ among the control, hypertension only and heart failure groups, that of the modified midwall by concentric two-shell geometry was decreased in the hypertrophy and the heart failure groups (p < 0.05). The Hotelling T2 test and Mahalanobis distance clearly discriminated the latter two groups with end-systolic stress and modified midwall fractional shortening relation. CONCLUSIONS: A fitting segmented regression model predicted a progression to hypertrophy and identified a transition from hypertrophy to heart failure by a combination of modified midwall fractional shortening and concentricity indexes.

Adult↗
PubMed1995

Development of a sandwich enzyme-linked immunosorbent assay for the determination of human heart type fatty acid-binding protein in plasma and urine by using two different monoclonal antibodies specific for human heart fatty acid-binding protein.

We have developed a sandwich enzyme-linked immunosorbent assay (ELISA) for the determination of human heart type fatty acid-binding protein (H-FABP) in human plasma and urine using the combination of two distinct monoclonal antibodies (MAbs) directed against human H-FABP purified from human heart muscle. The total assay time of the ELISA is practically much shorter than that of the competitive enzyme immunoassay (EIA) we previously reported. The immunoreactive mass of human H-FABP was specifically measured using a horseradish peroxidase (HRPO)-labeled anti-human H-FABP MAb as an enzyme-linked MAb, and anti-human H-FABP MAb immobilized on the polystyrene microtiter plate as a solid-phase MAb, and purified human H-FABP as standard materials. The assay range of the ELISA was 0-250 ng/ml of plasma and urine. The ELISA yielded a coefficient of variation of less than 10% in inter- and intra-assays, and the good linearity was obtained in dilution test using clinical samples. Anticoagulants, except sodium fluoride and a high concentration of hemoglobin and bilirubin, did not interfere with the assay of plasma samples. A high concentration of hemoglobin, bilirubin and immunoglobulin, and contamination with seminal plasma did not interfere with the assay of urine samples. The average recovery of purified human H-FABP added to human plasma and urine samples was 98.5% and 97.0%, respectively. Myoglobin and myosin did not crossreact in the ELISA. The minimum detection limit of the ELISA was 1.25 ng/ml. The immunoreactive masses of human H-FABP in plasma and urine samples, obtained from one hundred normal healthy subjects were quantified by the sandwich ELISA. The normal mean (+/- SD) level of human H-FABP mass in plasma was 3.65 +/- 1.81 ng/ml, and that in urine was 3.20 +/- 2.70 ng/ml. In conclusion, this sandwich ELISA is a useful tool for the sensitive and precise determination of human H-FABP in human plasma and urine, and it may be used specifically for clinical investigation and diagnosis of myocardial injury.

Antibodies, Monoclonal↗