Biomedical subjects

H Kumashiro

Publications and source records attributed to H Kumashiro.

At least 19 recordsLinked to original sources

PubMed2001

OPC-8212, a quinoline derivative, counteracts the reduction in type III collagen mRNA due to lipopolysaccharides in cultured rat cardiac fibroblasts.

Fibrillar collagen plays an essential role in ventricular remodeling, which is a major prognostic factor in various heart diseases. Inflammatory cytokines, including tumor necrosis factor alpha (TNFalpha), have been reported to play a role in various heart diseases and OPC-8212, a quinolinone derivative, has been demonstrated to reduce TNFalpha production. No studies have examined the effects of OPC-8212 on collagen metabolism in connection with inflammatory cytokine and growth factors. Using lipopolysaccharides as a tool to enhance TNFalpha, we examined the effects of OPC-8212 on the expression of type III collagen mRNA [alpha1(III)] in cultured neonatal rat cardiac fibroblasts. We also measured the concentration of TNFalpha and transforming growth factor beta (TGFbeta) in the cultured medium. Northern blot analysis revealed that LPS reduced the expression of alpha1(III) mRNA, and OPC-8212 counteracted this reduction (on average 25% above the reduced level by LPS stimulation). LPS enhanced the TNFalpha concentration in the medium, and OPC-8212 inhibited this enhancement. LPS increased the TGF-beta1 concentration in the cultured medium, while OPC-8212 did not affect this increase. In summary, OPC-8212 counteracted the reduction in type III collagen mRNA expression by LPS accompanied by suppression of the increase in TNFalpha.

Animals↗

PubMed1999

Establishment of a long-surviving murine model of myocardial infarction: qualitative and quantitative conventional microscopic findings during pathological evolution.

Ongoing basic molecular analyses are being performed in mice, and a simple long-surviving murine model of myocardial infarction (MI) would be very useful in this regard. Although a few studies have induced MI in mice by coronary artery ligation, the induction involves a complex technique and has a relatively high mortality rate. In addition, the identification of the basic pathological sequence is essential to the interpretation of experimental results. We developed a simple technique for the induction of MI in mice and examined qualitative and quantitative conventional microscopic findings during the pathological evolution over a 28-day observation period. Male BALB/c mice weighing approximately 25-30 g were anesthetized and then ventilated with a positive pressure ventilator. The heart was exposed by thoracotomy. Left coronary artery occlusion was performed by thermocoagulation using a thermocoagulation knife at the level of the tip of the left atrium. After establishing this surgical method, we used it to induce MI in 71 mice. The operative and postoperative mortality rates of this model were 5.6% (4/71) and 12.6% (9/71), respectively. In 3 (5.2%) of the 58 surviving mice, the area of infarct was not sufficient. The infarct area in the remaining 55 mice was 40 +/- 9% of the entire perimeter of the left ventricle. Conventional microscopic examinations with hematoxylin-eosin and Masson-trichrome staining disclosed that all of the characteristic histopathological features of MI occurred 1-2 days earlier than those in rats. Our surgical technique provides a sufficient infarct area, with an acceptable mortality rate. The present study clarified the histopathological sequence in this long surviving murine MI model.

Animals↗

PubMed1999

Effect of trazodone in a single dose before bedtime for sleep disorders accompanied by a depressive state: dose-finding study with no concomitant use of hypnotic agent.

This was the first dose-finding study of trazodone that was designed to be free of the concomitant use of hypnotics, in which the drug was administered in a single dose for sleep disorders combined with a depressive state. As a result, trazodone at the dosage of 50-100 mg/day improved sleep disorders, particularly at the 100 mg/day dosage. It was confirmed that trazodone improved sleep disorders combined with a depressive state when it was administered in a single dose before bedtime with no concomitant hypnotics.

Adult↗

PubMed1998

Sequential changes in the localization of the type IV collagen alpha chain in the infarct zone: immunohistochemical study of experimental myocardial infarction in the rat.

Collagen, as a component of the extracellular matrix, have a role in the healing process after myocardial infarction (MI). For type IV collagen, a major structural protein present in the basal membrane of myocytes, six alpha chains [alpha 1 (IV)-alpha 6(IV)] have been identified. We examined the sequential changes in the appearance and localization of the alpha 1 (IV)-alpha 5(IV) after experimental MI in rats. Hearts were excised from 1 day to 8 weeks after permanent left coronary artery ligation. Immunohistochemical staining with monoclonal antibodies was performed. On day 3, staining for both alpha 1(IV) and alpha 2(IV) first appeared, forming a wavy pattern in the infarct peripheral zone, and the staining was not restricted to the cell membrane. The staining intensity and distribution for both alpha 1(IV) and alpha 2(IV) in the peripheral zone then gradually increased, reaching a maximum around day 7. The distribution progressed from the peripheral to the central zone of the infarct for 1-2 days, reaching the center point after 2 weeks. The staining distribution gradually decreased after reaching the maximum, but the staining had not completely disappeared at 8 weeks. In contrast, no positive staining for alpha 3(IV), alpha 4(IV) or alpha 5(IV) was observed at any time during the 8-week observation period. Thus, the present results demonstrated that in rats, type IV collagen consisting of alpha 1 and alpha 2 chains appears in the infarct zone at a relatively early phase after MI, indicating that type IV collagen composed of alpha 1 and alpha 2 chains contributes to infarct healing.

Animals↗

PubMed1998

A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome).

Wolfram syndrome (WFS; OMIM 222300) is an autosomal recessive neurodegenerative disorder defined by young-onset non-immune insulin-dependent diabetes mellitus and progressive optic atrophy. Linkage to markers on chromosome 4p was confirmed in five families. On the basis of meiotic recombinants and disease-associated haplotypes, the WFS gene was localized to a BAC/P1 contig of less than 250 kb. Mutations in a novel gene (WFS1) encoding a putative transmembrane protein were found in all affected individuals in six WFS families, and these mutations were associated with the disease phenotype. WFS1 appears to function in survival of islet beta-cells and neurons.

Adult↗

PubMed1998

Expression of type XVII collagen alpha 1 chain mRNA in the mouse heart.

The type XVII collagen alpha 1 chain has been identified as a component of the type I hemidesmosome, and is thus thought to play a role in extracellular matrix (ECM) maintenance and signal transduction between the cell and the ECM. We examined the expression of type XVII collagen alpha 1 chain mRNA in the mouse heart by Northern blot analysis and determined the sequential changes of its expression in different developmental stages of the heart using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Northern blotting: Total RNA was extracted from 10 adult mouse hearts by the guanidine/cesium method. Hybridization was performed with mouse cDNA for alpha 1 (XVII) collagen. RT-PCR: Total RNA was extracted from 7 embryos, 4 neonates and 8 adult mice. Reverse transcription was performed using oligo-dT primer and MMLV. Amplification was carried out in alpha 1 (XVII) collagen and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). GAPDH served as an internal control. Northern blotting revealed a 5.6 kb signal that was identical to that of the alpha 1 (XVII) of skin and transformed keratinocyte reported previously. The sequences of the PCR products were also identical to those reported. The normalized expression ratios of alpha 1 (XVII) were 0.91 +/- 0.20 in the embryonic heart, 0.36 +/- 0.20 in the neonatal heart and 0.96 +/- 0.21 in the adult heart. In conclusion, we identified the expression of type XVII collagen alpha 1 chain mRNA in the mouse heart, suggesting that the type I hemidesmosome is located in the heart. The results of the RT-PCR at different developmental stages of the heart suggest that type XVII collagen contributes not only to cardiogenesis in the embryonic stage but also to maintenance of architecture and function in the adult heart.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1998

Localization of type IV collagen alpha chain in the myocardium of dilated and hypertrophic cardiomyopathy.

A total of 6 alpha chains [alpha 1 (IV) to alpha 6 (IV)] have been identified in type IV collagen. We examined the localization of these chains in the myocardium of patients with dilated (DCM) and hypertrophic (HCM) cardiomyopathy. The localization of alpha 1 (IV)-alpha 6 (IV) in biopsy specimens of 5 patients with DCM and 4 with HCM was examined using immunohistochemistry with monoclonal antibodies. Both alpha 1 (IV) and alpha 2 (IV) immunostaining formed thin homogeneous outlines around myocytes in control hearts. In the DCM specimens, alpha 1 (IV) and alpha 2 (IV) immunostaining formed thick and irregular patterns around myocytes. Staining for alpha 1(IV) and alpha 2 (IV) was also observed in some enlarged intercellular spaces. In 3 DCM hearts, moderate staining for alpha 1 (IV) and alpha 2 (IV) was observed in small replacement fibrotic lesions. In large replacement fibrotic lesions, no alpha 1 (IV) or alpha 2 (IV) staining was observed. In the HCM specimens, alpha 1 (IV) and alpha 2 (IV) staining formed thick homogeneous patterns around myocytes. In the enlarged intercellular spaces, no alpha 1 (IV) or alpha 2 (IV) staining was observed. No labeling for alpha 3 (IV)-alpha 6 (IV) was observed in any heart examined. In conclusion, the present results demonstrate that type IV collagen consisting of alpha 1 and alpha 2 chains appears in the fibrotic lesions of DCM, indicating its contribution to the development of fibrotic changes in the myocardium of DCM patients. In contrast, type IV collagen was restricted to the myocyte membrane in the HCM hearts. Fibrotic processes in the intercellular spaces may differ between DCM and HCM hearts.

Adult↗

PubMed1995

Effects of Antidepressants and antipsychotics on the 5HT2 receptor-mediated signal transducing system in human platelets.

The IC50 values of the antidepressants amoxapine, mianserin, desipramine, clomipramine and imipramine, and the antipsychotics spiroperidol, chlorpromazine, levomepromazine and haloperidol for 3H-ketanserin binding, 5HT-induced intracellular Ca2+ increase, 5HT-induced shape change and 3H-paroxetine binding in human platelets were measured and the correlations of each parameter were examined. Results were as follows. Both the antidepressants and the antipsychotics had inhibitory effects on 3H-ketanserin binding, 5HT-induced intracellular Ca2+ increase and 5HT-induced shape change and there were significant positive correlations between the IC50 values of these three parameters. On the other hand, there were no significant correlations between the IC50 values in 3H-paroxetine binding and those in the other three parameters. These results suggest that 3H-ketanserin binding, 5HT-induced intracellular Ca2+ increase and 5HT-induced shape change are useful and reliable tools for the assessment of the effects of the antidepressants and the antipsychotics on the 5HT2 receptor-mediated signal transducing system in human platelets.

Adult↗

PubMed1994

Reverse Shapiro's syndrome. A case of agenesis of corpus callosum associated with periodic hyperthermia.

OBJECTIVE: Investigation of the mechanism of the idiopathic periodic hyperthermia associated with agenesis of the corpus callosum. SETTING: Tertiary care referral center. PATIENT: Fourteen-year-old girl who was the first case of reverse Shapiro's syndrome (ie, agenesis of the corpus callosum associated with periodic hyperthermia, as opposed to hypothermia as described in the original report by Shapiro et al). INTERVENTION: Magnetic resonance imaging scans, endocrinological examinations for hypothalamus, electroencephalograms, and levodopa therapy. MAIN OUTCOME MEASURE: Body temperature. RESULT: No neurologic or physical abnormalities were noted beside the callosal agenesis. Neuroimaging examinations could not reveal any structural abnormality of the diencephalon. Endocrinological examinations and electroencephalograms were found to be normal. The hyperthermia returned to normal by a small dose of levodopa, but a larger dose reversed the hyperthermia to hypothermia. CONCLUSIONS: These observations suggest that the hyperthermia observed in this case may have been caused by the dopaminergic denervation of the hypothalamic thermoregulatory center, resulting in the supersensitivity of its dopaminergic receptors.

Adolescent↗

PubMed1994

Serial changes of n-isopropyl-p-iodoamphetamine single photon emission computed tomography in two epileptic psychotics.

Serial changes of single photon emission computed tomography (SPECT) in two epileptic psychotics are reported. One patient had a decreased blood flow of the left temporal lobe with schizophrenia-like symptoms, and the other patient had a decreased blood flow of the right temporal lobe with depressive symptoms. In each case, these abnormal findings disappeared following recovery from a psychotic state. It might be suggested that the psychotic state of an epileptic patient influences the SPECT findings.

Adult↗

PubMed1993

Ipsilateral hemiconvulsive seizure after unilateral injection of procaine into the substantia innominata of amygdaloid-kindled rats.

The effects of procaine injected into the substantia innominata (SI) and the amygdala (AM) were compared in AM-kindled rats. Intra-SI injection of procaine (ipsilateral to the kindled AM) caused immediate contralateral hemiparesis lasting for about 30 min, associated with EEG amplitude reduction. When the kindled AM was stimulated at the previously established generalized seizure triggering threshold (GST), 8/15 animals had ipsilateral hemiconvulsive seizure 5 min after the injection. In all the animals, afterdischarge was readily produced with a significant reduction in its duration. When procaine was injected into the kindled AM, there was no paresis or EEG change. AM stimulation at the GST did not evoke afterdischarge 5 min after the injection, although the kindled seizure was reactivated by a more intense stimulus. After 24 hr, all the animals, regardless of the site of procaine injection, responded to GST stimulation with a kindled seizure. The data suggest that: (1) the effect of intra-SI procaine is not due to drug diffusion to the kindled AM, and (2) the kindled AM can gain access to the contralateral hemispheric motor mechanism without participation of the ipsilateral SI.

Amygdala↗

PubMed1993

Hypothalamic-pituitary-adrenal axis function in children with attention-deficit hyperactivity disorder.

Examined hypothalamic-pituitary-adrenal axis (HPA axis) function in 30 children with attention-deficit hyperactivity disorder (ADHD) by measuring the diurnal variation and response to the dexamethasone suppression test (DST) of saliva cortisol. Normal diurnal saliva cortisol rhythm was found in only 43.3% of the ADHD children. DST showed suppression in 46.7% of the ADHD children. An abnormal diurnal rhythm and nonsuppression to the DST were more frequent in the severely hyperactive group than in the mildly were more frequent in the severely hyperactive group than in the mildly hyperactive group of children with ADHD. These results suggest abnormalities in HPA axis function in some children with ADHD, especially those exhibiting severe hyperactivity.

Attention Deficit Disorder with Hyperactivity↗

PubMed1992

Anticonvulsant effect of liposome-entrapped superoxide dismutase in amygdaloid-kindled rats.

Amygdaloid-kindled rats received intravenous human copper-zinc superoxide dismutase (CuZn-SOD) either in free form or entrapped within liposomes (SOD-L), at 5, 10 or 20 mg/kg. The animals were stimulated at the generalized seizure-triggering threshold 5 min, 2 h and then every 24 h after the drug was given, until 5 consecutive stage 5 seizures were induced. Free CuZn-SOD had little or no effect. However, SOD-L, particularly at 10 mg/kg, had a prolonged anticonvulsant effect, although there was great individual variation in the onset and duration of seizure suppression. This effect of SOD-L may be due to the ability of liposomes to act as a depot for the sustained release of drugs.

Amygdala↗

PubMed1992

An ESR-CT imaging of the head of a living rat receiving an administration of a nitroxide radical.

Three-dimensional ESR imaging of a living rat has been performed by an L-band ESR system, which is composed of an L-band ESR spectrometer, a field gradient coil, and a data processor. The imaging was carried out by Lauterbur's method. A nitroxide, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (Carbamoyl-PROXYL), was used as an imaging agent in saline solution at a concentration of 0.2 M and administered intraperitoneally to obtain a constant concentration in the head for about an hour. It took about 40 min to obtain one set of ESR-CT images. The cross-sectional images were made, both as coronal and horizontal images. In the images of the rat head the nitroxide-rich region was clearly distinguished from the deficient region. The nitroxide-deficient areas corresponded well to the brain of the rat.

Animals↗

PubMed1992

Effect of haloperidol on cyclic AMP and inositol trisphosphate in rat striatum in vivo.

To investigate the effect of haloperidol (HAL) on second messengers in the brain striatum, the concentrations of cAMP and inositol trisphosphate (IP-3) were measured in the striatum of rats in vivo after intravenous administration of HAL, and their concentrations were compared with the severity of catalepsy and changes in dopamine (DA) metabolism in the striatum. Catalepsy developed both in the animals treated with 5 mg/kg and those with 0.5 mg/kg of HAL, but it appeared earlier, and the period of severe catalepsy was longer in the former than in the latter. In the animals treated with 5 mg/kg of HAL, DOPAC and HVA began to increase at 20 min after administration, and their percent increases were correlated with the severity of catalepsy. In the 5 mg/kg animals, both cAMP and IP-3 increased. The IP-3 showed a delayed peak but a greater increase as compared with the cAMP. In the 0.5 mg/kg animals, only IP-3 increased. These findings suggest that HAL might affect not only the adenylate cyclase system but also the phosphoinositide response in the striatum. Moreover, the changes in the phosphoinositide response might be secondarily induced by the blocking of D-2 receptors by HAL.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1992

Plasma ratios of tryptophan and tyrosine to other large neutral amino acids in manic-depressive patients.

The plasma ratio of each neutral amino acid (tryptophan (TRP), tyrosine (TYR), valine, isoleucine, leucine (LEU) or phenylalanine) to the sum of the other neutral amino acids was measured in 16 manic and 14 depressed patients. In the manics, there was a correlation between the psychomotor activity and the plasma TRP and LEU ratios. In the depressives, the depressed mood, retardation and global severity were correlated with the TRP ratio. The zotepine responders showed an increase in the TRP ratio after treatment. In the mianserin responders, the TYR ratio, which was high before the treatment, decreased to the normal range after the treatment. But, the plasma amino acid ratios remained unchanged in the patients treated with lithium carbonate or amitriptyline. These results suggest that, in manic-depressive illness, there might be abnormalities in the metabolism of neutral amino acids, mainly of TRP and TYR, and that the plasma TRP and TYR ratios might be important indicators for determining the efficacy of some drugs.

Adolescent↗

PubMed1992

5HT2 receptor-mediated function in depressed patients: investigation by measuring 5HT-induced shape change of blood platelets.

The 5HT-induced shape change (5HT-SC) of blood platelets, which had been suggested to reflect the 5HT2 receptor-mediated function of the central nervous system (CNS), was examined in patients with depression before or after antidepressant therapy. The degree of 5HT-SC did not differ between patients before treatment (n = 17) and healthy controls (n = 26). In patients after treatment (n = 12), in whom depression had been improved but drug therapy was continued, 5HT-SC in a concentration of 10(-5) M 5HT was observed more potently than that in healthy controls or untreated patients (p less than 0.05 and p less than 0.05, respectively). In 4 patients in whom 5HT-SC was measured before and after mianserin treatment, 5HT-SC increased after the treatment. These results suggest that the 5HT2 receptor-mediated function in the CNS may not be damaged in patients with depression, and that the 5HT2 receptor-mediated function in the CNS may be enhanced by antidepressants.

Adult↗

PubMed1992

Serial changes of SPECT in periodic synchronous discharges in a case with Creutzfeldt-Jakob disease.

We conducted serial EEG and SPECT studies on one female with Creutzfeldt-Jakob disease (CJD). In an analysis of EEG, a periodic synchronous discharge (PSD) was observed in the middle of the third stage (terminal stage) of Bernoulli's classification. The frequency of PSD was the highest at the beginning of the third stage, followed by a gradual decrease and disappeared at the end of the third stage. In the middle of the third stage, SPECT disclosed blood flow differences between the cerebrum and other regions (the cerebellum and the brainstem), while no such difference was observed by SPECT at the end of the third stage. It was suggested that the appearance of PSD requires the presence of a pathological change in the cerebrum precedent to other regions.

Aged↗