Biomedical subjects

K Morimoto

Publications and source records attributed to K Morimoto.

At least 181 records · Page 10Linked to original sources

PubMed1998

Collaboration of antibody and inflammation in clearance of rabies virus from the central nervous system.

To investigate the involvement of various cellular and humoral aspects of immunity in the clearance of rabies virus from the central nervous system, (CNS), we studied the development of clinical signs and virus clearance from the CNS in knockout mice lacking either B and T cells, CD8+ cytotoxic T cells, B cells, alpha/beta interferon (IFN-alpha/beta) receptors, IFN-gamma receptors, or complement components C3 and C4. Following intranasal infection with the attenuated rabies virus CVS-F3, normal adult mice of different genetic backgrounds developed a transient disease characterized by loss of body weight and appetite depression which peaked at 13 days postinfection (p.i.). While these animals had completely recovered by day 21 p.i., mice lacking either B and T cells or B cells alone developed a progressive disease and succumbed to infection. Mice lacking either CD8+ T cells, IFN receptors, or complement components C3 and C4 showed no significant differences in the development of clinical signs by comparison with intact counterparts having the same genetic background. However, while infectious virus and viral RNA could be detected in normal control mice only until day 8 p.i., in all of the gene knockout mice studied except those lacking C3 and C4, virus infection persisted through day 21 p.i. Analysis of rabies virus-specific antibody production together with histological assessment of brain inflammation in infected animals revealed that clearance of CVS-F3 by 21 days p.i. correlated with both a strong inflammatory response in the CNS early in the infection (day 8 p.i.), and the rapid (day 10 p.i.) production of significant levels of virus-neutralizing antibody (VNA). These studies confirm that rabies VNA is an absolute requirement for clearance of an established rabies virus infection. However, for the latter to occur in a timely fashion, collaboration between VNA and inflammatory mechanisms is necessary.

Animals↗

PubMed1998

Cardiovascular and humoral responses to sustained muscle metaboreflex activation in humans.

The cardiovascular and humoral responses to sustained muscle metaboreflex activation were examined in eight male volunteers while they performed two 24-min exercise protocols. Each of these consisted of six 1-min bouts of isometric handgrip exercise (the left and right hands being used alternately) at 50% of maximal voluntary contraction; after each bout, there was either 3-min postexercise occlusion (occlusion protocol) or 3-min rest (control protocol). In the occlusion protocol, mean arterial blood pressure was approximately 25 mmHg higher than during the control protocol, indicating that the muscle metaboreflex was activated during occlusion. During the control protocol, plasma renin activity, plasma vasopressin, and adrenocorticotropic hormone values were not significantly different from the values at rest. During the occlusion protocol, however, plasma renin activity, plasma vasopressin, and adrenocorticotropic hormone were all significantly increased at 25 min. These data demonstrate that, in humans, the sustained activation of the muscle metaboreflex causes the secretion of several hormones originating from different regions.

Adult↗

PubMed1998

[Amyloidogenic peptides such as beta-amyloid, amylin and calcitonin strongly enhance the susceptibility of rat hippocampal neurons to excitatory amino acids in vivo].

We have previously shown that in vivo injection of beta-amyloid (beta 1-40, beta 25-35) with non-toxic amounts of ibotenic acid, an excitatory amino acid, causes synergistic and drastic neuronal degeneration in rat hippocampus. It was, however, yet not clear whether the neuronal degeneration in vivo was associated with their primary amino acid sequences, their secondary beta-structure or their activities to suppress MTT reduction activity in vitro. In addition to beta-amyloid, other amyloidogenic peptides such as human amylin or calcitonin are known to deposit extracellularly in systemic and peripheral amyloidosis. In this study, we measured the activity of amyloidogenic peptides (beta 1-40, human amylin and calcitonin) to suppress cellular MTT reduction activity in vitro and their synergistic neurodegeneration with ibotenic acid in vivo. All amyloidogenic peptides, but not non-amyloidogenic peptides (beta 40-1, BSA), suppressed the MTT reduction activity in HeLa cells and in the primary cultured neurons in vitro, and also produced the synergistic neuronal cell loss in rat hippocampal region by enhancing the toxicity of ibotenic acid in vivo. The deposits of amyloidogenic peptides at the injection sites were thioflavin S fluorescence positive, suggesting the fibrillary beta-structures. These results indicate that the neurodegeneration in vivo by amyloidogenic peptides is strongly associated with their fibrillary beta-structure and their activity to suppress MTT reduction activity in vitro.

Amyloid↗

PubMed1998

Lifestyle and periodontal health status of Japanese factory workers.

The present study investigated the association of lifestyles to periodontal health status of workers in a manufacturing company in Japan. In a annual health checkup, periodontal health status was assessed by using the Community Periodontal Index (CPI) criteria and analysed by modified Miller's CPI score. Lifestyle information was also obtained by a self-administered questionnaire. Bivariate and multivariate analyses were used to examine the relationship between lifestyle and oral health care variables and 2 indicators of periodontal health status. These were the modified Miller's CPI score and the probability of subjects in the upper 25th percentile of CPI distribution as an indicator of poor periodontal health. The modified Miller's CPI score was found to increase with age, but to vary according to the workers' lifestyles. In bivariate analyses, significant variables were age, smoking, alcohol consumption, toothbrushing frequency, toothbrushing method, and use of interdental cleaners. In multivariate analyses, age, smoking, and use of interdental cleaners had significantly independent effects. Amount of smoking or alcohol consumption was associated with periodontal health status. Excessive use of alcohol may contribute to the development of periodontal disease, although further investigations are required to confirm this finding. The data from this study indicate that lifestyles which include smoking and insufficient oral health care have an independent association with periodontal disease.

Adult↗

PubMed1998

Effects of dietary biotin on enhanced sucrose intake and enhanced gustatory nerve responses to sucrose seen in diabetic OLETF rat.

We used the sucrose preference test and taste nerve recording to investigate the effect of dietary biotin on the abnormal sucrose taste sensitivity and preferences seen during the course of diabetes mellitus. For this, we used Otsuka Long-Evans Tokushima fatty (OLETF) rats. The chorda tympani nerve (CT nerve) response to sucrose (> 1 M) was of greater relative magnitude in OLETF rats than in non-diabetic control (Long-Evans Tokushima Lean, LETO) rats, but the responses to other basic taste stimuli (such as HCl, quinine-HCl and L-glutamic acid) did not differ between the two groups. In behavioral experiments using a two-bottle preference test, solution intake for sucrose (> 50 mM) was higher in OLETF rats than in LETO rats. The neural responses to sucrose (1.5-2 M) in OLETF rats were lower when given a biotin-high diet (BH-OLETF) than when given a biotin-basal diet (BB-OLETF), but this was not true of the other basic tastes. However, there were no significant differences between BH-OLETF and BB-OLETF rats in terms of sucrose solution intake. These findings suggest that the enhanced sugar sensitivity observed in OLETF rats is probably the result of a genetic difference between OLETF and LETO rats, though the discrepancy can be modified by the dietary biotin level.

Animals↗

PubMed1998

[Study on evaluating methods for the quality control of glycoprotein products. (II)--Erythropoietin products. Part 2].

Using recombinant human erythropoietin (rh-EPO) from three different sources, the usefulness of HPAEC-PAD (high-pH anion exchange chromatography with pulsed amperometric detection) for evaluation of carbohydrate moieties of rh-EPO products was evaluated. It is well known that in vivo bioactivity and metabolic fate of EPO are dependent on the number of sialic acids and the degree of branching in the carbohydrate moieties. Here we show that HPAEC analysis reveals differences in the number of sialic acids as well as in the structure of desialylated N-glycans among the rh-EPO products. Therefore, HPAEC is useful for evaluation of the quality of rh-EPO products.

Carbohydrate Sequence↗

PubMed1998

Relevance of both daily hassles and the ALDH2 genotype to problem drinking among Japanese male workers.

The effects of genetic polymorphisms in the ALDH2 and ADH2 genes and stress levels, as assessed by the daily hassles scale on the prevalence of problem drinkers, were investigated in males in a Japanese occupational population. The frequency of problem drinkers was estimated by the Kurihama Alcoholism Screening Test (KAST). The prevalence of those with a high KAST score (> or =0.0) was significantly higher in ALDH2*1/*1 (18.4%) than in ALDH2*1/*2 (4.8%). Multiple logistic regression analysis revealed significant contributions by levels of alcohol consumption, the ALDH2 genotype, and daily hassles to the prevalence of those with a high KAST score. When we analyzed the data for each ALDH2 genotype, heavier alcohol consumption (> or =28.8 ml/day), older age (> or =40 years old), and very high daily hassles levels (> or =20) significantly increased the prevalence of problem drinkers in ALDH2*1/*1. On the contrary, no variables other than heavier alcohol consumption influenced the prevalence in ALDH2*1/*2. In summary, the present study revealed significant contributions of both daily hassles and the ALDH2 genotype to the increase of problem drinkers in an occupational population. Health promotion activities to prevent from alcohol dependence should focus on ALDH2*1/*1, especially those of middle age, and should include stress management as a part of their activities.

Adolescent↗

PubMed1998

[An early phase II clinical study of S-1 in patients with breast cancer. S-1 Cooperative Study Group (Breast Cancer Working Group)].

An early phase II clinical study of S-1 in patients with advanced or recurrent breast cancer was undertaken by a cooperative study group (Breast Cancer Working Group) of 14 institutes in Japan. S-1 was administered twice daily at 75 or 50 mg (dose FT)/body for 28 consecutive days with 14 days rest (one course). Twenty-eight patients were enrolled, 27 were eligible for the study, and 25 were evaluable for efficacy. Four complete responses and seven partial responses were obtained, and the response rate was 40.7% (11/27) [ninety percent confidence interval for this response was 26.7-56.4%]. The major adverse reactions observed were myelosuppression represented by leukopenia 44.4% (12/27), neutropenia 40.7% (11/27), RBC decreased 37.0% (10/27), hemoglobin decreased 29.6% (8/27), anorexia 55.6% (15/27), nausea/vomiting 48.1% (13/27), and fatigue 33.3% (13/27). The results suggested that the efficacy and safety of S-1 were effective against advanced or recurrent breast cancer. The objective of study judged should be investigated in a late phase II clinical study.

Adult↗

PubMed1998

[Steady state and disappearance of the metabolites of miproxifene phosphate in the treatment of breast cancer].

We gave miproxifene phosphate to six patients with recurrent breast cancer and to one patient with advanced breast cancer. This drug was orally administered at a daily dose of 20 mg in the morning, and serial blood samples were obtained just before the drug administration. Treatment was discontinued in 16 days in the patient with advanced breast cancer. Tumor response was 2 PR and 4 NC (3MR) with an efficacy rate of 29%. Adverse effects of grade 2, such as anorexia, nausea or vomiting and fatigue with grade 3 flushing and chilling were observed in the one patient with advanced breast cancer. This climacteric syndrome disappeared after cessation of administration. In one of the patients with recurrent breast cancer, a calf muscle cramp was observed. Steady plasma levels were observed in one week or two for miproxifene and in 2 to 8 weeks for desmethyl miproxifene, which were active metabolites of miproxifene phosphate. The half lives of these metabolites for disappearance were calculated in three patients. That of miproxifene was 27 to 36 hours and that of desmethyl miproxifene was 156 to 202 hours. Miproxifene phosphate is a promising drug for breast cancer, and the results of pharmacokinetics of active metabolites will suggest the time to obtain maximum efficacy and for it to disappear.

Adult↗

PubMed1998

[Plasma cell leukemia (IgG kappa) presenting bilateral neurosensory hearing loss and left sixth cranial nerve plasy].

A 30-year-old man who had been given a diagnosis of IgG-kappa multiple myeloma by another hospital and treated with melphalan, prednisone, and cyclophosphamide 6 months earlier, was admitted to our hospitaly in July 1994 because of progressively impaired hearing in both ears, vertigo, and worsening fatigue. Peripheral blood examination showed a white blood cell count 25,000/microliter, with 77.5% atypical plasma cells. Examination at the time of hospitalization also revealed retinal hemorrhages and serum hyperviscosity. The diagnosis was plasma cell leukemia with hyperviscosity syndrome. Subsequent treatment consisted of vincristine, doxorubicine, and prednisone and repeated plasmapheresis. This resulted in a partial response and a reduction of serum viscosity but no reversal of hearing loss. One month after admission, left sixth cranial nerve plasy was demonstrated. Cranial computed tomography studies disclosed a tumoral mass in the sphenoid sinus. The patient received local radiotherapy and intensive chemotherapy, but exhibited no notable alleviation of his cranial nerve palsy. He died of septicemia and progressive disease in August 1994. This case was rare in that it involved plasma cell leukemia and bilateral neurosensory hearing loss associated with serum hyperviscosity and sixth cranial nerve plasy due to plasmacytoma within the sphenoid sinus.

Abducens Nerve↗

PubMed1998

[Manifestation of Chiari II symptoms following peritoneal shunt tube extension].

A 5-year-old boy with hydrocephalus and a lumbar myelomeningocele underwent extension of peritoneal tube of ventriculoperitoneal (VP) shunt system. Prior to the operation he had been able to walk independently with the use of braces, to speak complex sentences and to sing songs. After the surgery, he lost consciousness and became critically ill with irregular respiration. He was artificially ventilated for 10 days, and then recovered, with sequelae of right facial paresis and slight dysarthria. T1 weighted magnetic resonance image showed high intensities of the medial part of the inferior lobe of the cerebellum and medulla oblongata, which were interpreted as representing edema. This case illustrates that Chiari II malformation can become symptomatic after a VP shunt trouble.

Acute Disease↗

PubMed1998

[A case of congenital toxoplasmosis confirmed by detection of Toxoplasma gondii in placenta].

We report a case of congenital toxoplasmosis with a prenatal diagnosis of fetal hydrocephalus. A CT scan performed at birth revealed ventricular dilation with calcification. The serum and CSF Toxoplasma specific IgM were elevated. The diagnosis was confirmed by the presence of Toxoplasma cysts in the placenta, and detection of the Toxoplasma SAG1 gene by a polymerase chain reaction (PCR) (placenta, positive; CSF, negative). Signs of active central nervous system infection, such as the decreased CSF glucose, and elevated CSF protein, neuron specific enolase and LDH, resolved after initiation of treatment with pyrimethamine and sulfazoxine. A PCR test using the placental tissue may be useful for the rapid diagnosis of congenital toxoplasmosis.

Adult↗

PubMed1998

[Severe hemolytic anemia with tear drop red cells as initial manifestation of Wilson's disease].

A 16-year-old girl was admitted for a detailed examination of hemolytic anemia in November 1995. Initial laboratory findings included a total bilirubin concentration of 1.46 mg/dl, hemoglobin of 9.1 g/dl, and a reticulocyte count of 89/1000 percent. The plasma haptoglobin concentration was below 10 mg/dl. A blood smear showed many dacryocytes and a few echinocytes and codocytes. GOT was 71 IU/l; GPT, 44 IU/l; and LDH, 812 IU/l; the results of a hepaplastin test were 45% of normal. On further investigation, the level of serum ceruloplasmin was found to be 4 mg/dl, and of serum copper, 43 micrograms/dl. Urinary copper excretion was markedly increased, at 345 micrograms per day. Slit-lamp examination of both corneas revealed obvious Kayser-Fleischer rings. A liver biopsy sample showed fibrosis histologically and an elevated copper concentration of 535 micrograms/g dry weight and 183 micrograms/g wet weight. In family studies, the patient's asymptomatic 5-year-old sister was observed to have metabolic abnormalities consistent with Wilson's disease. These findings suggested that the patient's hemolytic anemia with red cell deformities was due to abnormal copper metabolism associated with Wilson's disease.

Adolescent↗

PubMed1998

[Hydromyelia associated with spinal lipoma].

We studied morphological changes of hydromyelia complicated with spinal lipoma of infants who were untethered. Since the MRI was introduced, early detection of spinal lipoma with lumbosacral skin abnormalities has become possible. We have experienced 44 surgical cases of spinal lipoma. Out of 36 such cases, 25 (69.4%) had hydromyelia, and hydromyelia of 9 patients was found to be of the terminal ventricle type. As many as 36% of spinal lipoma patients with hydromyelia concurrently had terminal-type hydromyelia, which was considered to fall under a specific category of congenital hydromyelia. At the stage of embryogenesis of the spinal cord, the caudal cell mass undergoes vacuolization, canalization and retrogressive differentiation, and during this process, the terminal ventricle with ependymallined cells becomes morbid. Though the morphological changes of hydromyelia after surgery as untethering were varied, hydromyelia of 9 patients became smaller after untethering, and hydromyelia of 8 expanded but attenuated afterwards, totaling 17 (68.0%). However, 5 had an expanding tendency and 3 did not show any morphological changes during the follow-up period (20.6-26.9 months) by MRI.

Child↗

PubMed1998

Nitrogen dioxide compromises defence functions of the airway epithelium.

The effect of nitrogen dioxide (NO2) exposure on airway epithelial defence functions, such as ciliary activity, mucociliary transport velocity and junctional barrier function, remains to be elucidated. Our study investigates the effect of 24-h exposure to 3.0 ppm of NO2 on the airway epithelial defence functions in the healthy rabbit. Fifty-two healthy rabbits were exposed to 3.0 ppm of NO2 (NO2 group) or pure air (control group) for 24 successive hours in exposure chambers. After completion of the exposure sequence, the ciliary activity in the trachea was examined by a photoelectric method, the mucociliary transport velocity in the trachea by an endoscopic method and epithelial permeability of the trachea to fluorescein isothiocyanate-dextrans (FD-70s; molecular weight: 70,000 daltons) by an in vitro tracheal sac method. In the NO2 group, all epithelial defence functions, including ciliary activity, mucociliary transport velocity and epithelial permeability were significantly inferior to those in the control group. Although there was considerable overlap in the parameters examined between the two groups, approximately two-thirds of the animals were susceptible to 24-h exposure to 3 ppm of NO2. Dysfunction of both the junctional barrier and the mucociliary system could allow easier entry of allergen molecules to the airway parenchyma, where immunocomponent cells exist. NO2 might be involved to some extent in the clinical manifestation of airway allergic disorders through epithelial dysfunction.

Air Pollutants↗

PubMed1998

[Effects of selegiline hydrochloride on intracellular Ca2+ contents in cultured neuronal cells].

The effects of Selegiline hydrochloride (Selegiline HCl) on the intracellular Ca2+ contents of primarily cultured rat striatal, mesencephalic neuronal cells and PC-12 cells were examined by the use of a Ca2+ imaging analyzer. In the former two cell types, Selegiline HCl (10(-5)-10(-6) M) induced a transient inflow of extracellular Ca2+ through the voltage-dependent N-type Ca2+ channel. In addition, all cells indicating an increase in the intracellular Ca2+ content were found to be catecholaminergic neurons which showed a positive reaction with anti-tyrosine hydroxylase antibodies. Furthermore, a transient intracellular influx of Ca2+ was observed in the NGF-pretreated PC-12 cells. From these results, it is suggested that Selegiline HCl elicits various functions, including antioxidation, activation of neurotrophic factor biosynthesis and neuronal protection probably via an unidentified specific proteins of tyrosine hydroxylase-positive neurons.

Animals↗

PubMed1997

A variant of the HL-60 cell line expressing a high level of PTP1C exhibits increased susceptibility to differentiation by phorbol 12-myristate 13-acetate.

A variant of the HL-60 cell line, HL-60/MCSFR4D2, has been found to express twice the amount of PTP1C as compared to the parental HL-60 cell line by immunoblotting and immunoprecipitation. Differentiation of the variant cells after phorbol 12-myristate 13-acetate (PMA) treatment was examined by the appearance of adherence. In 1% fetal calf serum (FCS), 20% of HL-60/MCSFR4D2 cells exhibited adherence after treatment with 0.5 ng/ml PMA for 48 h, 60% exhibited adherence after treatment with 1.0 ng/ml PMA and 80% exhibited adherence after treatment with 5.0 ng/ml PMA, while HL-60 cells exhibited only a slight response. Furthermore, antisense PTP1C oligonucleotides decreased the PMA-induced adherence of HL-60/MCSFR4D2 cells. These results suggest that the high-expression of PTP1C in HL-60 cells may be involved in the enhancement of susceptibility to macrophage-like differentiation by PMA.

Cell Adhesion↗

PubMed1997

BW1003C87, phenytoin and carbamazepine elevate seizure threshold in the rat amygdala-kindling model of epilepsy.

We examined the anticonvulsant effects of BW1003C87 (5-(2,3,5-trichlorophenyl)-2,4-diaminopyrimidine ethane sulphonic acid), which is structurally related to the new antiepileptic drug, lamotrigine, and compared its effects to those of the conventional antiepileptic drugs, phenytoin and carbamazopine, using the rat amygdala-kindling model of epilepsy. BW1003C87 (2.5-10 mg/kg, i.p.) had potent and long-lasting (48 h after single administration) effects on amygdala-kindled seizures. The effects of BW1003C87 were completely reversed when the stimulus intensity was increased to 2 or 3 times the threshold determined. Since the same effects on seizure threshold were obtained for phenytoin and carbamazepine in the present study and for lamotrigine in our previous study, we propose that the principal mechanism of these antiepileptic drugs, which act primarily on voltage-sensitive Na+ channels, is significant elevation of the seizure threshold in epileptogenic foci and that BW1003C87 has a profile similar to that of these drugs.

Amygdala↗