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Biomedical subjects

H Morita

Publications and source records attributed to H Morita.

At least 73 records · Page 4Linked to original sources
PubMed2001

A new method for tolerance induction: busulfan administration followed by intravenous injection of neuraminidase-treated donor bone marrow.

The portal venous (p.v.) administration of foreign cells induces donor-specific tolerance. Recently, we have demonstrated that the p.v. administration of donor cells elicits donor-specific tolerance across major histocompatibility complex barriers. In the present study, utilizing the intrahepatic tolerance-inducing system, we have established a new method for organ transplantation using both busulfan ([Bu] to provide a sufficient "space" for the donor hematopoietic cells to expand in the recipient) and neuraminidase ([Neu] to enhance the trapping of i.v.-injected cells in the liver). Radiolabeled bone marrow cells (BMCs) were found to exclusively accumulate in the livers of the recipients as a result of the Neu treatment. Furthermore, hematopoietic progenitors (forming hematopoietic foci) in the accumulated BMCs were retained in the recipient livers for at least 18 days. C57BL/6 (B6) mice that had been transplanted with skins of BALB/c mice immediately after the injection of BALB/c BMCs showed a 90% skin graft survival rate over 400 days as a result of using the combination of injecting 50 mg/kg Bu into the B6 mice and treatment of the BALB/c BMCs with 0.25 U/ml Neu (50 Bu + 0.25 Neu). However, the survival rate significantly decreased when either the Bu or Neu treatment was omitted. In tolerant recipients, microchimerism was observed in the various hematolymphoid organs. T cells collected from the tolerant recipients suppressed proliferative responses to the donor-alloantigens but enhanced the production of Th2 and Th3 cytokines. These findings suggest that the enhanced retention of donor BMCs in the recipient livers as a result of the Bu and Neu treatments efficiently induces tolerance induction. Therefore, this "single-day protocol" would be of great advantage for human organ transplantation.

Animals↗
PubMed2001

Effects of pCO(2) on the CSF turnover rate in T(1)-weighted magnetic resonance imaging.

The cerebrospinal fluid (CSF) secretion of rat was monitored by longitudinal relaxation time-weighted magnetic resonance imaging (T(1)-weighted MRI) in combination with a ventricular injection of a T(1)-relaxation reagent: gadolinium-diethylene triamine-N,N,N',N",N"-pentaacetic acid (Gd-DTPA). A cannula was inserted in the left lateral ventricle, and 5 microl of 8.5 mM Gd-DTPA was injected as a CSF marker. Changes in the image intensity of the CSF were measured every 30 s, and the turnover rate of CSF (k) in the left lateral ventricle was obtained from the dilution of Gd-DTPA, based on the assumption of a single compartment model. In the control conditions, k was 0.158 +/- 0.009 min(-1) at an arterial blood CO(2) tension (pCO(2)) of 38.6 +/- 2.2 mmHg (n = 10), which corresponds to the CSF secretion rate of 3.6 microl min(-1). The k value was decreased (0.078 +/- 0.010 min(-1), n = 4) by a carbonic-anhydrase inhibitor (acetazolamide). The turnover rate was decreased by hypocapnia (0.094 +/- 0.019 min(-1), pCO(2) = 24.7 +/- 2.9 mmHg, n = 4), and it increased gradually and reached a plateau level as a result of hypercapnia (0.194 +/- 0.011 min(-1), pCO(2) = 104.5 +/- 7.1 mmHg, n = 10). These results suggested that CO(2) upregulates the secretion of CSF in the rat.

Animals↗
PubMed2001

[Gene therapy for cardiomyopathy].

Cardiac transplantation has become accepted therapy for a number of patients with severe cardiomyopathy. The cellular cardiomyoplasty is expected as an alternative therapy for cardiomyopathy. The experimental foundation was laid for the approach to cellular cardiomyoplasty--the molecular and cellular treatment of cardiomyopathy by augmentation, regeneration or replacement of cardiomyocytes--by experiments in cardiac gene transfer and transgenic animals. Recently, cardiomyocyte has been reported to be generated from embryonic stem cell or marrow stromal cell in vitro. However, differentiation from non-cardiomyocyte to cardiomyocyte cannot be controlled completely yet. It is now under investigation mainly in an experimental setting. For successful gene therapy, not only characterization of proper targets but also elimination of undesirable side effects are indispensable.

Animals↗
PubMed2001

Platelets exposed to elevated levels of endogenous thrombopoietin in vivo have a reduced response to megakaryocyte growth and development factor in vitro.

Thrombopoietin (TPO), or megakaryocyte growth and development factor (MGDF), has been shown to potentiate the sensitivity of normal human platelets to various agonists in vitro. The present study investigated the functional and biochemical properties of platelets from mice rendered thrombocytopenic by sublethal irradiation with regard to the reactivity to recombinant murine MGDF (rmMGDF) in vitro. During the course of reversible thrombocytopenia following irradiation, platelets from irradiated mice which had lower platelet counts and reciprocally higher plasma TPO levels showed lower reactivity to rmMGDF in agonist-induced platelet aggregation. Intravenous injections of recombinant soluble murine c-Mpl (sMpl), which has the ability to capture TPO, after irradiation restored the reactivity of platelets at the platelet nadir to rmMGDF. On the other hand, platelets prepared from normal mice 3 h after a single intravenous injection of pegylated rmMGDF did not respond to rmMGDF. There was a marked decrease in c-Mpl and Janus kinase 2 (JAK2) in platelets from irradiated mice at the platelet nadir. Similar results were observed with platelets from mice administered pegylated rmMGDF. JAK2 was only moderately decreased, however, in platelets from mice given sMpl after irradiation. These results indicate that exposure of platelets to increased endogenous TPO levels in vivo in thrombocytopenic mice leads to a reduction in the platelet reactivity to rmMGDF in vitro. Further, these results suggest that the c-Mpl-mediated signaling pathway, which is essential for the priming effect of rmMGDF, is defective in thrombocytopenic murine platelets.

Animals↗
PubMed2001

[A case of paroxysmal nocturnal hemoglobinuria combined with focal segmental glomerular sclerosis].

A 81-year-old woman was admitted to our hospital because of edema and massive proteinuria on September 26, 1995. On admission, the palpebral conjuctiva were slightly anemic, and edema of the eyelids and legs was observed. Laboratory findings were as follows, urine protein(3+), occult blood(3+), WBC 2,600/microliter, Hgb 10.0 g/dl, reticulocytes 20@1000, TP 5.0 g/dl, Alb 2.7 g/dl, T-Cho 376 mg/dl, TG 194 mg/dl, LDH 763 U/l, haptoglobin < 93 mg/dl, Ham's test(+), sugar water test(+), and indirect coombs (+). The erythrocytes of this patient showed a negative population consisting of double negative erythrocytes evaluated by flow cytometric two-color analysis using monoclonal antibodies specific to CD55 and CD59. From these findings, the diagnosis of paroxysmal nocturnal hemoglobinuria(PNH) was made. The patient showed nephrotic syndrome and a renal biopsy was performed. The histological findings of renal biopsy showed focal and segmental sclerosis and adhesion of glomerular tufts. Interstitial fibrosis with atrophic tubules and lymphocyte infiltration were also observed. There was no specific staining of immunoglobulins and complement by immunofluorescence. The diagnosis of focal segmental glomerular sclerosis(FSGS) was made. There have been only three case reports of glomerular disease in patients with PNH, such as purpura nephritis, IgA nephropathy and membranous nephropathy. The complication of FSGS and PNH is every rare and there has been no report of FSGS in a case with PNH. The onset of PNH resulted from the loss of CD55 and CD59, which was critical in the onset of FSGS in the present case.

Aged↗
PubMed2001

Lack of association between the platelet glycoprotein Ia C807T gene polymorphism and myocardial infarction in Japanese. An approach entailing melting curve analysis with specific fluorescent hybridization probes.

The platelet-collagen receptor, glycoprotein Ia/IIa (integrin alpha2beta1) plays a fundamental role in the adhesion of platelets to fibrillar collagen, an event leading to platelet activation and thrombus formation and contributing to the pathogenesis of thrombotic disease. Further, glycoprotein Ia/IIa receptor density and function may be associated with two linked and silent polymorphisms (807C/T and 873G/A) within the glycoprotein Ia gene. We tested the extent to which these polymorphisms serve as genetic markers of myocardial infarction in a Japanese population. A case-control study was carried out using 210 Japanese myocardial infarction patients and 420 age- and sex-matched controls. Genotyping was accomplished using PCR followed by melting curve analysis with specific fluorescent hybridization probes. The 807CC, CT, TT genotypes linked perfectly to the 873GG, GA, AA genotypes, respectively. Allele frequencies of the 807T (873A) variant were similar in the control and patient groups (0.373 vs. 0.352). The 807T and 873A variants of platelet glycoprotein Ia gene are common and in a perfect linkage in the Japanese population, but it appears unlikely that the 807T (873A) variant represents a useful marker of increased risk for myocardial infarction.

Adult↗
PubMed2001

[A case report of chronic chyluria probably due to Bancroftian filariasis, which showed hypoproteinemia].

Proteinuria is commonly observed in patients with chyluria due to Bancroftian filariasis. However, whether or not hypoalbuminemia is caused by chyluria alone is still a matter of debate. This is because various forms of glomerulonephritis are complicated in such patients. Herein, we report a case we have recently encountered. A 72-year-old male was admitted to our division for further evaluation of nephrotic syndrome. He was from the Southernmost part of Japan, where Bancroftian filariasis has been epidemic, and had developed persistent chyluria over a period of nearly 50 years. There was no other past history of illness except for diabetes mellitus(DM) pointed out 3 months prior to admission. The physical and laboratory examinations on admission fulfilled the diagnostic criteria for nephrotic syndrome. Lymphoscintigraphy showed an intense tracer accumulation in both kidneys. A renal biopsy was performed. At the light microscopic level, the glomeruli looked normal. Edema of the tubulointerstitium was noted. At the electron microscopic level, effacement of podocyte foot processes was not observed. Immunofluorescent study did not show glomerular deposition of immunoglobulins and complements. He also had persistent microscopic hematuria. Automated urinary sediment analysis by real-time confocal scanning laser microscopy revealed red blood cells of the non-glomerular type. Taken together, these findings strongly indicated that hypoalbuminemia of this patient was caused by chyluria alone. In conclusion, a report of the present case provides strong evidence that hypoalbuminemia of a patient with Bancroftian filariasis could be caused by chyluria alone.

Aged↗
PubMed2001

Comparative effect of theophylline and aminophylline on theophylline blood concentrations and peripheral blood eosinophils in patients with asthma.

The comparative effects of a new theophylline preparation (Theodrip) and aminophylline on blood concentrations of theophylline were examined in 74 patients with asthma. Subjects were intravenously administered 200 mg of Theodrip or 250 mg of aminophylline for 1 h. The mean increases in blood theophylline concentration after Theodrip or aminophylline administration were 8.80 +/- 1.80 mg/l and 8.81 +/- 2.15 mg/l, respectively. In addition, these patients were divided into four groups based on baseline theophylline concentrations before infusion of Theodrip or aminophylline: i) naïve patients (not administered theophylline); ii) those with a baseline theophylline concentration of 0-5 mg/l; iii) those with a baseline theophylline concentration of 5-10 mg/l; iv) those with a baseline theophylline concentration of 10-15 mg/l. Mean increases in blood theophylline concentration after administration of Theodrip in each group were similar to those after aminophylline administration. We found no significant differences between Theodrip and aminophylline. However, when the comparative effects of Theodrip and aminophylline on peripheral blood eosinophil counts were examined, Theodrip, but not aminophylline, reduced blood eosinophil counts. With acute exacerbations of bronchial asthma, it is expected that Theodrip, but not aminophylline, may have an antiinflammatory effect. In conclusion, it is suggested that Theodrip is a more useful drug than aminophylline in patients with acute exacerbations of bronchial asthma.

Adult↗
PubMed2001

Differential clearance and induction of host responses by various administered or released lipopolysaccharides.

The clearance and activity of different types of lipopolysaccharide (LPS) released during infection with Gram-negative bacteria were investigated. When highly purified preparations differing in their specific endotoxin activity were administered intravenously to mice, the clearance of rough (R)-form LPS preparations from Salmonella minnesota and Escherichia coli was much faster than that of a smooth (S)-form LPS preparation from Salmonella abortus equi, but slower than that of lipo-oligosaccharides (LOS) preparations from Bordetella pertussis and Helicobacter pylori. After intraperitoneal infection with 10(7) and 10(8) CFU E. coli O111:B4, relatively high levels of LPS were detected dose-dependently in the plasma of infected mice and persisted for a long time. In addition, plasma sCD14 levels in infected mice were higher than in LPS-administered mice. These results indicate that continuously higher levels of plasma LPS followed by stronger host responses occur during infection and suggest that these differences between LPS-administered and infected mice should be taken into consideration when analyzing host responses induced by LPS.

Animals↗
PubMed2001

[Study on the effects of walking on functional fitness in aged patients with the hand-arm vibration syndrome].

PURPOSE: This article reports the effectiveness of mild walking exercise for maintaining functional fitness in aged patients with the hand-arm vibration syndrome (HAVS). SUBJECTS AND METHODS: Fifty-two patients suffering from vibration syndrome, for which they received annual compulsory examination from December 1998 to March 1999 at the San-in Rosai Hospital, were examined. They all were male, with a mean age (standard deviation) of 69.1 (7.3) years, and were randomly allocated to an intervention group (N = 26) and a control group (N = 26). The goal of the intervention was to achieve and maintain at least 30 minutes of walking a day. Functional fitness was assessed by a sitting and standing test, a zigzag walking test, a hand working test with a pegboard for dexterity, and a self-care working test proposed by the Physical Fitness Research Institute, Meiji Life Foundation of Health and Welfare. RESULTS: There were no significant differences between the two groups regarding baseline characteristics. The proportions of subjects with regular exercise habits after the intervention were 84.6% (22/26) and 53.8% (14/26) in the intervention and control groups, respectively, the difference being significant. The total scores for functional fitness were improved in the intervention, while decline was noted in the control group. Sitting and standing and self-care working ability were also improved in the intervention group as against the deterioration with age in the control group. CONCLUSIONS: Our findings show to some extent that intervention using mild exercise, walking for 30 min, is effective for aged patients with HAVS to maintain and improve functional fitness.

Aged↗
PubMed2001

[Adult form of acid maltase deficiency presenting with pattern of muscle weakness resembling facioscapulohumeral dystrophy].

We report a 61-year-old female patient with adult form of acid maltase deficiency showing many clinical similarities to facioscapulohumeral muscular dystrophy (FSHD). She developed difficulty in raising her right arm in her thirties followed by leg weakness. She had the typical features of FSHD, including bilateral scapular winging sparing the levator scapulae and deltoid muscles, and Beevor's sign. Muscle involvement was asymmetrical. Facial muscles were not affected, while the neck flexor was weak. No muscle shortening or joint contracture was observed. On muscle CT, the lumbar paravertebral, gluteal and thigh muscles were replaced by adipose tissue, while the rectus femoris, gracilis, and sartorius muscles were spared. Serum creatine kinase level was not elevated. Muscle biopsy showed some vacuoles and many granular inclusions with high acid phosphatase activity. Acid maltase activity was very low in both muscle and cultured skin fibroblasts. Absence of shortening of affected muscles appears to be the characteristic finding suggesting metabolic myopathies with minimal fibrosis, rather than FSHD.

Diagnosis, Differential↗
PubMed2000

Enzymatic formation of unnatural aromatic polyketides by chalcone synthase.

Substrate specificity of recombinant chalcone synthase (CHS) from Scutellaria baicalensis (Labiatae) was investigated using chemically synthesized aromatic and aliphatic CoA esters. It was demonstrated for the first time that CHS converted benzoyl-CoA to phlorobenzophenone (2,4,6-trihydroxybenzophenone) along with pyrone by-products. On the other hand, phenylacetyl-CoA was enzymatically converted to an unnatural aromatic polyketide, phlorobenzylketone (2, 4,6-trihydroxyphenylbenzylketone), whose structure was finally confirmed by chemical synthesis. Furthermore, in agreement with earlier reports, S. baicalensis CHS also accepted aliphatic CoA esters, isovaleryl-CoA and isobutyryl-CoA, to produce phloroacylphenones. In contrast, hexanoyl-CoA only afforded pyrone derivatives without formation of a new aromatic ring. It was noteworthy that both aromatic and aliphatic CoA esters were accepted in the active site of the enzyme as a starter substrate for the complex condensation reaction. The low substrate specificity of CHS thus provided further insight into the structure and function of the enzyme.

Acyltransferases↗
PubMed2000

Syntheses and structural analysis of 10-monoxy- and -dioxy-5-N-substituted iminothianthrene derivatives and the stereochemical change on their sulfur atom under acidic and thermal conditions.

5-(N-p)-Toluenesulfonyl)iminothianthrenes, whose sulfur atoms are oxidized to a sulfoxide or sulfone at the 10-position, were hydrolysed readily in high yield to N-unsubstituted-sulfilimines by using concentrated H2SO4. During hydrolysis, 10-monoxy-5-N-unsubstituted-sulfilimines were obtained as a separable mixture of the cis and trans isomers. The stereochemical interconversion of these compounds was studied under both hydrolytic and thermal conditions and their structures were elucidated by using X-ray crystallography.

Journal Article↗
PubMed2000

Presynaptic control of transmission along the pathway mediating disynaptic reciprocal inhibition in the cat.

In cat lumbar motoneurones, disynaptic inhibitory postsynaptic potentials (IPSPs) evoked by stimulation of antagonist motor nerves were depressed for at least 150 ms following conditioning stimulation of flexor (1.7-2 times threshold (T)) and ankle extensor (5T) nerves. The aim of the present study was to investigate the possibility that this depression is caused by presynaptic inhibitory mechanisms acting at the terminals of group I afferent fibres projecting to the Ia inhibitory interneurones and/or the terminals of these interneurones to the target motoneurones. Conditioning stimulation of flexor, but not ankle extensor, nerves evoked a depression of the monosynaptic Ia excitatory postsynaptic potentials (EPSPs) recorded intracellularly in Ia inhibitory interneurones. This depression lasted between 200 and 700 ms and was not accompanied by a depression of the monosynaptic EPSPs evoked by stimulation of descending pathways. These results suggest that flexor, but not ankle extensor, group I afferent fibres can modulate sensory transmission at the synapse between Ia afferent fibres and Ia inhibitory interneurones. Conditioning stimulation of flexor muscle nerves, extensor muscle nerves and cutaneous nerves produced a long-lasting increase in excitability of the terminals of the Ia inhibitory interneurones. The increase in the excitability of the terminals was not secondary to an electrotonic spread of synaptic excitation at the soma. Indeed, concomitant with the excitability increase of the terminals there were signs of synaptic inhibition in the soma. The unitary IPSPs induced in target motoneurones following the spike activity of single Ia inhibitory interneurones were depressed by conditioning stimulation of muscle and cutaneous nerves. Since the conditioning stimulation also evoked compound IPSPs in those motoneurones, a firm conclusion as to whether unitary IPSP depression involved presynaptic inhibitory mechanism of the terminals of the interneurones could not be reached. The possibility that the changes in excitability of the Ia interneuronal terminals reflect the presence of a presynaptic inhibitory mechanism similar to that operating at the terminals of the afferent fibres (presynaptic inhibition) is discussed.1. In cat lumbar motoneurones, disynaptic inhibitory postsynaptic potentials (IPSPs) evoked by stimulation of antagonist motor nerves were depressed for at least 150 ms following conditioning stimulation of flexor (1.7-2 times threshold (T)) and ankle extensor (5T) nerves. The aim of the present study was to investigate the possibility that this depression is caused by presynaptic inhibitory mechanisms acting at the terminals of group I afferent fibres projecting to the Ia inhibitory interneurones and/or the terminals of these interneurones to the target motoneurones. Conditioning stimulation of flexor, but not ankle extensor, nerves evoked a depression of the monosynaptic Ia excitatory postsynaptic potentials (EPSPs) recorded intracellularly in Ia inhibitory interneurones. This depression lasted between 200 and 700 ms and was not accompanied by a depression of the monosynaptic EPSPs evoked by stimulation of descending pathways. These results suggest that flexor, but not ankle extensor, group I afferent fibres can modulate sensory transmission at the synapse between Ia afferent fibres and Ia inhibitory interneurones. Conditioning stimulation of flexor muscle nerves, extensor muscle nerves and cutaneous nerves produced a long-lasting increase in excitability of the terminals of the Ia inhibitory interneurones. The increase in the excitability of the terminals was not secondary to an electrotonic spread of synaptic excitation at the soma. Indeed, concomitant with the excitability increase of the terminals there were signs of synaptic inhibition in the soma. The unitary IPSPs induced in target motoneurones following the spike activity of single Ia inhibitory interneurones were depressed by conditioning stimulation

Action Potentials↗