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Biomedical subjects

Y Kasahara

Publications and source records attributed to Y Kasahara.

At least 19 recordsLinked to original sources

Fas-independent and nonapoptotic cytotoxicity mediated by a human CD4(+) T-cell clone directed against an acute myelogenous leukemia-associated DEK-CAN fusion peptide.

The mechanism underlying the cytotoxicity mediated by a human CD4(+) cytotoxic T-lymphocyte (CTL) clone directed against a peptide derived from the acute myelogenous leukemia-associated fusion protein, DEK-CAN, was investigated. A DEK-CAN fusion peptide-specific CD4(+) Th0 CTL clone, designated HO-1, was established from the peripheral blood lymphocytes of a healthy individual. HO-1 exerted direct but not "innocent bystander" cytotoxicity within 2 hours. The cytotoxicity mediated by HO-1 was completely Ca2+-dependent. Because HO-1 lysed peptide-loaded Fas-deficient target cells derived from a patient with a homozygous Fas gene mutation, its cytotoxicity appeared to be mediated by a Fas-independent pathway. In addition, its cytotoxicity was only partially inhibited by treatment with concanamycin A and strontium ions, which are inhibitors of the perforin-based cytotoxic pathway. Although membrane-bound type of tumor necrosis factor-alpha (TNF-alpha) was expressed on HO-1, an anti-TNF-alpha antibody had no effect on HO-1-mediated cytotoxicity. HO-1 expressed mRNA for apoptosis-inducing mediators, including perforin, granzyme B, Fas ligand, TNF-alpha, and lymphotoxin; however, no DNA fragmentation was detected in target cells incubated with HO-1 by 5-[125I]Iodo-2'-deoxyuridine release assay and agarose gel electrophoresis of DNA. Although it has been suggested that the Fas/Fas ligand system is the main pathway by which CD4(+) CTL-mediated cytotoxicity is exerted in murine systems, HO-1 produced peptide-specific and HLA-restricted cytotoxicity via a Fas-independent and nonapoptotic pathway. The present study thus describes a novel mechanism of cytotoxicity mediated by CD4(+) CTL.

Acute Disease

Electromyographic examination of jaw muscles in relation to symptoms and occlusion of patients with temporomandibular joint disorders.

Clinical/occlusal scores and jaw-muscle EMGs were recorded in 24 TMD symptomatic (group S) and 20 normal (group N) subjects to evaluate the significance of EMG parameters and their clinical associations. Results indicated: (1) integrated EMG activity (IEMG) was larger at the rest position (RP) in anterior temporalis (Ta) but smaller at maximal voluntary clenching (MVC) in masseter (Ma) and Ta, and the ratios of IEMG at 70%MVC to the corresponding bite force (70%BF) were greater in group S; (2) mean power frequency (MPF) were almost the same in both groups but its shift was more rapid in group S; (3) silent period duration (SPD) was longer in group S; (4) asymmetry indices for SPD and silent period latency (SPL) were larger in group S; (5) muscle pain was associated negatively with IEMG at MVC and 70%BF but positively with IEMGs at RP and 70%MVC, and impaired jaw movements were associated negatively with the above EMG values; (6) muscle pain was positively associated with SPD in Ma, while joint pain and sound showed positive and negative associations with SPD, respectively; (7) associations between occlusion and EMG parameters were found more in group N. These findings verify: (1) jaw elevators in TMD may have hyper-tonic activities and a weak functional efficiency; (2) jaw muscles in TMD may become easily fatigued following a functional effort, and less relaxed following a muscle twitch; (3) the severity of pain could not be reflected in EMG activities, but impaired jaw movement may increase tonic activity and decrease functional effort; (4) TMD symptoms may alter the functional adaptation of jaw-muscle activities and occlusion.

Adaptation, Physiological

Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency.

The first known human case of heme oxygenase-1 (HO-1) deficiency is presented in this report. The patient is a six-year-old boy with severe growth retardation. He has been suffering from persistent hemolytic anemia characterized by marked erythrocyte fragmentation and intravascular hemolysis, with paradoxical increase of serum haptoglobin and low bilirubin. An abnormal coagulation/fibrinolysis system, associated with elevated thrombomodulin and von Willebrand factor, indicated the presence of severe, persistent endothelial damage. Electron microscopy of renal glomeruli revealed detachment of endothelium, with subendothelial deposition of an unidentified material. Iron deposition was noted in renal and hepatic tissue. Immunohistochemistry of hepatic tissue and immunoblotting of a cadmium-stimulated Epstein-Barr virus-transformed lymphoblastoid cell line (LCL) revealed complete absence of HO-1 production. An LCL derived from the patient was extremely sensitive to hemin-induced cell injury. Sequence analysis of the patient's HO-1 gene revealed complete loss of exon-2 of the maternal allele and a two-nucleotide deletion within exon3 of the paternal allele. Growth retardation, anemia, iron deposition, and vulnerability to stressful injury are all characteristics observed in recently described HO-1 targeted mice. This study presents not only the first human case of HO-1 deficiency but may also provide clues to the key roles played by this important enzyme in vivo.

Animals

Developmental changes and functional properties of human memory T cell subpopulations defined by CD60 expression.

The present study was undertaken to examine developmental changes of T cells expressing CD60 and their functional properties. Three-color immunofluorescence analysis revealed that the CD60 antigen was preferentially expressed on a proportion of memory (CD45RO+) CD4+ T cells, but less on memory CD8+ T cells, while this antigen is undetectable in naive (CD45RO-) T cells. A frequency of memory CD4+ T cells expressing CD60 in the peripheral blood was negligible in newborns and gradually increased with advancing age. CD60+ memory CD4+ T cells showed stronger proliferative responses to PPD and produced higher levels of IL-4 and IL-10 than CD60- ones, whereas production of IL-2 and IFN-gamma was similarly found in both cell subpopulations. In addition, it was shown that efficient helper activity for Ig production by B cells was predominated in CD60+ memory CD4+ T cells. These results suggest that CD60 may be primarily expressed on the functionally differentiated memory effector cells among circulating CD45RO+ CD4+ T cells.

Adolescent

Prevention of severe hepatic injury by interferon-alpha in chronic active hepatitis lacking HBeAg (mutant strain) in a patient with malignant lymphoma.

Multidrug chemotherapy with concomitant interferon (IFN)-alpha was performed in a patient with chronic hepatitis lacking the hepatitis Be antigen and malignant lymphoma (ML). Levels of trans-aminases and DNA polymerase (DNA-P) values increased after the fifth course of chemotherapy. Therapy with IFN-alpha for 9 weeks induced a remission in liver disease and complete remission of ML was obtained with subsequent chemotherapy. It was possible to prevent severe liver damage by administering IFN immediately after the elevation of DNA-P. Early introduction of IFN may be effective in the prevention of fulminant hepatic failure from hepatitis from a precore mutant after chemotherapy.

Hepatic Encephalopathy

Dimensions of schizophrenic positive symptoms: an exploratory factor analysis investigation.

Current psychopathology classifies schizophrenic positive symptoms into four groups: delusions, hallucinations, formal thought disorder, and catatonic symptoms. The present study explores the factor structure of different positive symptoms to refine this classification. The 35 positive symptoms of 429 psychiatric patients, consecutively admitted to any of 95 mental hospitals, with diagnosis of the ICD-10 F20 schizophrenia, were studied. After excluding those items with a base rate of 10% or less, factor analysis yielded six factors. The first factor was loaded by most of Schneider's first-rank symptoms and two specific auditory hallucinations; the second by all the catatonic symptoms and incoherence; the third by bodily delusions/hallucinations; the fourth by delusions of persecution and reference; the fifth by grandiose and religious delusions; and the sixth by visual and miscellaneous hallucinations. The finding that schizophrenic positive symptoms may have more than four dimensions suggests the need for reclassification of schizophrenic symptoms and for reconsideration of evidence-based diagnostic criteria for the disorder.

Adolescent

Role of carotid body in pressure response of pulmonary circulation in rats.

We investigated how signals arising from peripheral chemoreceptors could affect pulmonary vasculature in rats. Effects of the hypoxic exposure (10%) on mean pulmonary arterial pressure (mPAP), abdominal aortic flow (Q) and the estimated total pulmonary vascular resistance (mPAP/Q) were determined in anesthetized, artificially ventilated, carotid sinus nerve intact or chemodenervated rats. The pressor response of PAP to hypoxia seen in intact rats changed to the depressor response after chemodenervation. Hypoxia elicited a decrease in Q and an increase in mPAP/Q in both intact and chemodenervated rats. Selective carotid body stimulation by the intra-carotid injection of sodium cyanide (NaCN) in normoxia elicited an immediate but transient increase in PAP and Q before and after bilateral vagotomy. The peak change in PAP slightly preceded that in Q. These responses to NaCN were completely abolished by chemodenervation. These results indicate that the immediate chemoreflex contributes to the short-term regulation of pulmonary vasculature in rats.

Animals

Direct antiglobulin test negative autoimmune hemolytic anemia associated with autoimmune hepatitis.

A case of direct antiglobulin test(DAT)-negative autoimmune hemolytic anemia (AIHA) associated with autoimmune hepatitis (AIH) is presented. A 54-year-old female was admitted with liver dysfunction and anemia. AIH was diagnosed based on the diagnostic criteria of the International Autoimmune Hepatitis Group. The patient was DAT-negative, and exhibited all the clinical features of warm type AIHA and elevated levels of red blood cell-associated IgG. Marked improvement of subjective symptoms, the return to normal of hematological and liver test values, and a decrease in the level of RBC-associated IgG were observed after the start of corticosteroid therapy. Although an association of AIH and AIHA is rarely reported, the measurement of RBC-associated IgG is recommended in cases of AIH with DAT-negative anemia, as both disorders are autoimmune in nature.

Anemia, Hemolytic, Autoimmune

Dysfunctional parenting as a risk factor to lifetime depression in a sample of employed Japanese adults: evidence for the 'affectionless control' hypothesis.

BACKGROUND: Although many case-control studies have replicated an association between dysfunctional parenting and a lifetime diagnosis of depression, few epidemiological studies have explored the association. In addition, little is known about the association in non-western countries. METHODS: Using logistic regression analyses, additive and interactive contributions of parental child-rearing behaviours, as measured by the Parental Bonding Instrument (PBI), toward the risk for having a lifetime diagnosis of major depressive disorder were explored in 418 employed Japanese adults. The diagnosis was provided by using the Inventory to Diagnose Depression, lifetime version. The analyses were conducted for male and female subjects separately. RESULTS: Parental care rather than parental protection was primary in predicting lifetime depression in both male and female subjects. An interactive combination of low care and high protection ('affectionless control') was a significant risk factor for lifetime depression in male respondents' reporting child-rearing behaviours of both parents and female respondents' reporting paternal child-rearing behaviours. Model improvements when entering the PBI scores were larger in male subjects than in female subjects. CONCLUSIONS: The results suggested that a combination of low care and over-protection increases a risk to lifetime depression even in a non-clinical sample; that an association between dysfunctional parenting (particularly low care) and the development of depression is independent of culture; and that Japanese boys are more sensitive than Japanese girls to dysfunctional parenting as regards the development of depression.

Adolescent

Successful treatment of Epstein-Barr virus-associated natural killer cell large granular lymphocytic leukaemia using allogeneic peripheral blood stem cell transplantation.

We report a case of natural killer cell large granular lymphocytic (NK-LGL) leukaemia successfully treated with allogeneic peripheral blood stem cell transplantation (allo-PBSCT). The peripheral blood (PB) revealed an abnormal expansion of LGL that were CD3-, CD16- and CD56+, and had natural killer activity. In situ EBER-1 hybridization of the PB mononuclear cells showed the presence of Epstein-Barr virus (EBV) in the LGL as well as in lymphocytes infiltrating the tonsils and colon. Southern blotting with an EBV-terminal repetitive sequence probe demonstrated clonal proliferation of EBV+ cells. The patient received allo-PBSCT from his HLA-matched sister with a conditioning regimen involving the use of cyclophosphamide and fractionated total body irradiation. The patient promptly recovered trilineage haematopoiesis without graft-versus-host disease, and has been in complete remission without therapy for 10 months since allo-PBSCT, suggesting that allo-PBSCT could eradicate the NK-LGL leukaemic cells.

Adolescent

Personality differences in the Munich Personality Test between patients with major depression and panic disorder.

This study attempted to determine whether patients with major depression and panic disorder could be differentiated by personality features, measured by the Munich Personality Test (MPT). One of the six MPT personality dimensions, 'rigidity', was developed in relation to the 'melancholic type of personality', which may be a specific personality feature of depressive subjects. We therefore hypothesized that the MPT might be sensitive to possible personality differences between patients with major depression and panic disorder. Sixty-six patients with major depression and 27 patients with panic disorder, taken from consecutive intakes at an outpatient unit, were compared in terms of six personality dimensions of the MPT. The results demonstrated that rigidity could significantly differentiate the two patient groups, even after the possible confounding effects on the personality assessments were statistically partialled out. The MPT was suggested to be powerful for describing distinctive personality features of depressive subjects from anxiety subjects.

Adult

Gustatory responses to amino acids in the chorda tympani nerve of C3H mice.

Integrated neural responses to various amino acids were recorded from the chorda tympani (facial) nerve in C3H mice. The basic amino acids hydrochlorides L-Arg-HCl and L-Lys-HCl evoked large magnitude integrated taste responses, similar to that for NaCl, and had estimated electrophysiological thresholds of 0.0001 M. No significant difference was indicated between the response magnitudes for the L- and D-forms of the basic amino acid hydrochlorides; however, responses to the basic amino acid hydrochlorides cross-adapted with NaCl. Responses to neutral L-amino acids (Ser, Ala, Gly), which taste sweet to humans, showed higher thresholds (>0.0003 M), similar to that for sucrose, and did not cross-adapt with basic amino acid hydrochlorides or with NaCl. Responses to the neutral amino acids L-Ser and L-Ala were larger than those to their D-amino acid enantiomers. The acidic amino acids L-Asp and L-Glu showed concentration-response functions different from that for HCl. Both acidic amino acids were more stimulatory than HCl at the same pH, although the responses to them were cross-adapted by HCl, indicating a pH effect. A comparison of the stimulatory effectiveness among amino acid derivatives and analogues suggested that the alpha-amino group is essential for the stimulatory effectiveness of neutral amino acids.

Adaptation, Physiological

Novel Fas (CD95/APO-1) mutations in infants with a lymphoproliferative disorder.

Fas is an apoptosis-signaling receptor important for homeostasis of the immune system. In this study, Fas-mediated apoptosis and Fas mutations were analyzed in three Japanese children from two families with a lymphoproliferative disorder characterized by lymphadenopathy, hepatosplenomegaly, pancytopenia, hypergammaglobulinemia and an increase in TCR alphabeta+ CD4- CD8- T cells. Apoptosis induced by anti-Fas mAb was defective in both activated T cells and B cells, and granulocytes from these patients. Truncated Fas receptor lacking the cytoplasmic death domain caused by a point mutation in the splice region of intron 7 were demonstrated in two siblings. A homozygous point mutation in the splice acceptor of intron 3 was found in the Fas gene of the third patient, which resulted in the skipping of exon 4 and complete loss of Fas expression. Corresponding to these mutations, soluble Fas concentrations were decreased and reciprocally soluble Fas ligands were increased in patients' sera. Interestingly, co-stimulation by immobilized anti-Fas mAb in T cells from the two siblings was comparable to that seen in normal T cells. These results suggest that Fas-mediated apoptosis plays a pivotal role in immunological homeostasis in vivo, especially regarding clonal deletion of immune cells in humans.

Apoptosis

Role of EDRF in pulmonary circulation during sustained hypoxia.

The pulmonary artery pressure (PAP) response to hypoxia is characterized by an initial vasoconstriction followed by vasodilation. Pulmonary vessels can release endothelium-derived relaxing factor (EDRF), which is considered to be nitric oxide (NO), but the role of EDRF in the regulation of normal and hypoxic pulmonary vascular tone is still uncertain. We designed this study to address the in vivo role of EDRF in vasodilation during sustained hypoxia. We studied the effects of an EDRF-synthesis inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), on the pulmonary vascular response to sustained hypoxia (10% O2, 20 min) in normoxic (N) and chronically hypoxic (CH) rats. Biphasic PAP response was observed in N rats, whereas PAP was unchanged in CH rats during sustained hypoxic exposure. The L-NAME-induced PAP increase during normoxia was greater in CH than in N rats, suggesting that basal EDRF plays an important role in attenuating the severity of pulmonary hypertension in CH rats. Administration of L-NAME increased the initial increment in PAP by acute hypoxia and shifted the PAP response upward throughout sustained hypoxia, while still showing the biphasic pattern, in N rats. In contrast, PAP increased acutely and remained elevated with little recovery in the late phase in CH rats. The inducible NO synthase messenger RNA (mRNA) expression and protein showed greater increases in the lungs of CH than in N rats. These results suggest that EDRF release during sustained hypoxia may partly contribute to the roll-off in PAP response during sustained hypoxia in N rats, and that augmented EDRF may prevent a further increase in PAP during chronic hypoxia.

Alkalosis

Identification and expression of the Bacillus subtilis fructose-1, 6-bisphosphatase gene (fbp).

The Bacillus subtilis fbp gene encoding fructose-1,6-bisphosphatase (FBPase) was originally identified as yydE. The fbp gene was expressed at a fairly constant level in cells undergoing glycolysis or gluconeogenesis. fbp transcription was initiated 94 bp upstream of the translation initiation codon, resulting in a 2.4-kb monocistronic transcript. Interestingly, B. subtilis FBPase exhibited no significant similarity to other FBPases in protein sequence databases.

Bacillus subtilis

Functional properties of jaw and tongue muscles in rats fed a liquid diet after being weaned.

Decreased masticatory demands due to liquid or soft diets cause a reduction in the growth of craniofacial bones and in the development of feeding musculature, but the effects on masticatory function and jaw/tongue muscle activities are unclear. The present study was undertaken to test the hypotheses that a liquid diet feeding after weaning affects the critical-period programming of mastication and the motor performances of jaw and tongue muscles. Thirty-six male Wistar rats were divided into two equals groups at weaning and fed either a solid (solid-diet group) or a liquid (liquid-diet group) diet until they reached 50 days of age. Electromyograms (EMG) of the masseter, medial pterygoid, temporalis, anterior digastric, styloglossus, and genioglossus were recorded while animals were naturally ingesting ordinary pellets, apple cubes, and a liquid diet. It was found that: (1) a more irregular chewing rhythm, a shorter chewing sequence, and a longer chewing cycle were found in the liquid-diet group, but there were no differences observed during lapping/licking between the two groups; (2) during the chewing cycles, the EMG onset of each muscle in relation to that of the masseter in the liquid-diet group was similar to that in the lapping/licking cycles in both groups; (3) the activities of jaw elevators (masseter, medial pterygoid, and temporalis) during the chewing cycles were significantly higher in the liquid-diet group; and (4) the increase in the EMG activities of jaw elevators during pellet chewing compared with apple cube chewing was significantly weaker in the liquid-diet group, whereas such an enhancement was found simultaneously in the styloglossus in the solid-diet group, and in the anterior digastric in the liquid-diet group. These findings verify that: (1) the motor output of jaw and tongue muscles may be altered in rats fed a liquid diet after being weaned; (2) the feeding of a liquid diet to rats after being weaned may obstruct the functional transition from suckling to mastication; and (3) jaw elevators that develop without motor learning of mastication are inefficiency when performing functionally.

Analysis of Variance

Alleviation of monocrotaline-induced pulmonary hypertension by antibodies to monocyte chemotactic and activating factor/monocyte chemoattractant protein-1.

Administration of monocrotaline (MCT) causes pulmonary vascular lesions consisting of monocyte/macrophage infiltration in the early phase and medial thickening in pulmonary arteries and arterioles associated with pulmonary hypertension (PH) in the later phase. However, the molecular mechanism of monocyte/macrophage infiltration and its roles remain elusive. Herein, we have evaluated the role of a potent monocyte chemotactic and activating chemokine/monocyte chemoattractant protein-1 (MCAF/MCP-1) in MCT-induced PH in rats. A single injection of MCT induced PH at Day 21, as evidenced by increases in the ratio of right ventricular to left ventricular and septum weights (RV/LV+S) and right ventricular systolic pressure (RVSP). A significant increase in macrophage number in lungs started at Day 14, reaching a maximum at Day 21. MCAF/MCP-1 levels in bronchoalveolar lavage fluids were elevated significantly at Day 14 and remained high until Day 28, whereas plasma MCAF/MCP-1 levels increased at Day 7, returning to normal levels by Day 21. Immunoreactive MCAF/MCP-1 proteins were mainly detected in macrophages in alveoli and in perivascular regions of pulmonary arterioles and venules. Intravenous administration of anti-MCAF/MCP-1 antibodies with MCT significantly decreased macrophage infiltration and eventually reduced the increases in RV/LV+S and RVSP, as well as medial thickening of pulmonary arterioles. Thus, MCAF/MCP-1 is essentially involved in MCT-induced PH by recruiting and activating macrophages.

Animals