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Biomedical subjects

T Kitamura

Publications and source records attributed to T Kitamura.

At least 235 records · Page 13Linked to original sources
PubMed1999

Phlebosclerosis of the colon with positive anti-centromere antibody.

A 56-year-old woman with symptoms of chronic bowel disease presented a peculiar calcification of the mesenteric vein of the ascending to transverse colon on barium enema study. The resected colon was hard and black. Histo-pathologic examinations demonstrated fibrous change of the colon with a calcified and hyaline-deposited mesenteric vein. No cell infiltration was observed. These findings were compatible with phlebosclerosis and also with systemic sclerosis. Positive anti-centromere antibody and Raynaud's phenomenon, hallmarks of a variant systemic sclerosis, the CREST syndrome were observed. We therefore speculated that the pathogenesis of the phlebosclerosis of the colon is related to the CREST syndrome.

Autoantibodies↗
PubMed1999

Temporal variation of validity of self-rating questionnaires: improved validity of repeated use of Zung's Self-Rating Depression Scale among women during the perinatal period.

It has been reported that Zung's Self-Rating Depression Scale (SDS) loses its validity in predicting cases of depression when used repeatedly. The validity of SDS was tested against the subject's Research Diagnostic Criteria (RDC) diagnoses of major/minor depressive disorders in 120 pregnant women four times throughout the perinatal period. Different sets of predictive SDS items were found at different time points. We developed an 'RDC-like' algorithm from SDS items. Though varying in sensitivity, we found that this formula yielded low, but stable, positive predictive values and constantly high negative predictive values. We suggest that the RDC-like algorithm is a better alternative for screening depression among perinatal women.

Adult↗
PubMed1999

[An elderly case of juvenile muscular atrophy in the unilateral upper extremity with tremor in both hands].

A 75-year-old man had noticed muscle atrophy and weakness of his right hand and forearm at the age of 25. The symptoms slowly progressed and then stopped. Right hand tremor appeared at about age 40. There was no symptom in his left upper extremity, and his gait was normal. He now shows severe muscle atrophy in his right hand and forearm. There was distally dominant weakness of the right upper extremity and his hand grip was 0 kg on the right and 25 kg on the left. On admission there was no weakness in the bilateral lower extremities. He had postural tremor in both hands and fingers. The tendon reflexes were hypoactive in the upper extremities and normal in the lower extremities. Abnormalities in the superficial sensation were unremarkable, whereas vibration sensation in both the upper and lower extremities was mildly disturbed. Electromyography revealed chronic denervation, especially in the right upper extremity. The sensory nerve conduction study results and somatosensory evoked potentials in the upper extremities were normal. Cervical MRI demonstrated spondylotic changes, canal stenosis from the C5 to C7 levels, and compression of the spinal cord. His hand tremor was dominant on the right with a peak frequency of about 7 Hz. Tremor frequency and power were decreased by mechanical load. Hirayama's disease (juvenile muscular atrophy of unilateral upper extremity) was the most probable diagnosis, although aging might have produced various additional abnormalities. The tremor seen in this patient showed characteristics of enhanced physiological tremor.

Aged↗
PubMed1999

Biological role of HGF/MET pathway in renal cell carcinoma.

PURPOSE: Several lines of evidence show that hepatocyte growth factor (HGF) and its receptor MET play a significant role in the progression of various cancers including renal cell carcinoma (RCC). Our objectives were to evaluate the gene expression of HGF and MET in RCC, and to examine the effect of HGF on the biological activities of cultured RCC cells. MATERIALS AND METHODS: We examined the gene expression of HGF and MET in 27 primary RCC tumors by quantitative competitive RT-PCR. The effects of HGF on in vitro chemoinvasion assay and the expression of matrix metalloproteinase-9 (MMP-9), and the induction of Fas-induced apoptosis were studied by transfection of HGF cDNA to cultured RCC cells, Caki-1. RESULTS: HGF mRNA and MET mRNA were detected in all surgical specimens. The level of expressed HGF mRNA was proportional with the volume of tumor (r = 0.50, p = 0.015). Caki-1 cells overexpressing HGF cells showed enhanced in vitro invasiveness in the chemoinvasion assay and increased activity of 92 kDa type IV collagenase (MMP-9). The sensitivity to Fas-induced cell death was reduced in HGF transfectants, which was reversed by the presence of anti-HGF antibody. CONCLUSIONS: HGF enhanced the invasive properties of cultured RCC cells and inhibited Fas-induced apoptosis in vitro. Both HGF and MET mRNA were expressed in RCC tissues tested. Our results indicate that HGF/MET pathway may have a significant role in the progression of RCC.

Apoptosis↗
PubMed1999

[Mode of onset and two years outcome of a broad spectrum of affective disorders].

In recent years emphasis has tended to be placed on assessing and diagnosing low-grade affective disorders. If mild affective symptoms are also considered a broad spectrum of affective disorders, this spectrum can be seen, not only in the manifestation of major symptoms of such illnesses as manic-depressive illness, but also in symptoms of various mental disorders. The present study was undertaken to analyze the clinical features of a broad spectrum of affective disorders in a prospective follow-up study. Ninety mentally ill patients who visited our outpatient clinic were followed for 2 years, to investigate the mode of onset, the course and outcome of their disorders. Using a semistructured interview method specially developed for this survey, these patients were divided into a broad spectrum of affective disorder group and the other groups. Forty-nine patients were allocated to a spectrum of affective disorder group characterized by four-day (or longer) persistence of at least one of the following symptoms, depressed mood, loss of interest or elevated, expansive, or irritable mood. Of the forty-nine patients there were only two patients with manic symptoms. And the forty-seven patients with depressive symptoms were compared with the other groups as a main subject. The other groups were composed of eighteen patients with psychotic symptoms (the psychotic group) and 23 patients with neurotic symptoms (the neurotic group). The psychotic and neurotic groups did not satisfy the criteria shown above. There was no significant differences in male-to-female ratio or age between these three groups. When the mode of onset of symptoms were compared, the percentage of cases in whom symptoms could be identified early (within 10 days after onset) was 64.4% in the depressive group, 41.2% in the psychotic group and 30.4% in the neurotic group. The percentage of cases who remitted 2 years later was 70.2%, 38.9%, 45.5% in the depressive group, psychotic and neurotic groups, respectively. The GAS score (mean +/- SD), assessed 2 years later, was 76.2 +/- 12.5, 62.8 +/- 11.7, 78.2 +/- 9.9 points for these three groups, respectively. These results suggest that a broad spectrum of depressive disorders develops more acutely and patients with this spectrum are more likely to recover from symptoms and in function. Thus, the course of disorders was more favorable in the depressive group than in the psychotic group or the neurotic group.

Adult↗
PubMed1999

Suppression of laser-induced choroidal neovascularization by oral tranilast in the rat.

PURPOSE: To determine whether tranilast administered to pigmented rats inhibits formation of choroidal neovascularization induced by diode-laser photocoagulation. METHODS: Female Brown Norway rats were used. On day 0, choroidal neovascularization was induced by diode-laser photocoagulation, using a setting of 75 microm spot size, 0.1 second's duration, and 100 mW intensity. Tranilast (200 or 600 mg/kg per day) was administered orally twice daily for 14 days. Indomethacin (1 and 5 mg/kg per day) was administered orally once a day for 14 days. Choroidal neovascularization was evaluated on days 7 and 14 by fundus photography and fluorescein angiography. Late-phase fluorescein angiography was scored according to four grades. The animals were killed on day 14, and the lesions were evaluated histologically. RESULTS: In the vehicle-treated group, 34 of 35 burns (97%) showed fluorescein staining and late leakage on day 14. Choroidal neovascularization was identified by light microscopy in all the lesions that showed fluorescein staining and late leakage. The score of fluorescein staining was reduced in rats given 200 mg/kg per day or 600 mg/kg per day (P < 0.01) of tranilast. The thickness of the laser-induced lesions was reduced in a dose-dependent manner by tranilast, a significant difference was observed with 600 mg/kg per day (P < 0.05). Oral indomethacin treatment did not reduce fluorescein staining on day 14. CONCLUSIONS: Tranilast inhibits the development of choroidal neovascularization in this experimental model.

Administration, Oral↗
PubMed1998

Expression and functional analysis of a hemopoietic progenitor antigen, NJ-1 (114/A10), in the megakaryocytic lineage.

To analyze the functions of molecules expressed in hemopoietic progenitor cells, we obtained several monoclonal antibodies by immunizing Wistar rats with antigens from a murine immature leukemic cell line, DA-1. Here, we characterize one antibody designated NJ-1, which recognizes a 145-kd molecule, and identify the cDNA encoding the NJ-1 antigen by retrovirus-mediated expression cloning. Sequence analysis of the cDNA reveals that it is identical to a previously reported cDNA encoding a surface molecule of 573 amino acids recognized by monoclonal antibody 114/A10. Our studies show that expression of NJ-1 antigen is upregulated in a murine megakaryoblastic cell line, L8057, when it differentiates into a megakaryocytic lineage in response to 12-O-tetradecanoyl phorbol-13-acetate. Overexpression of NJ-1 antigen in L8057 cells inhibits cell adhesion to fibronectin, suggesting that it may act as a negative regulator of cell adhesion in the megakaryocytic lineage.

Animals↗
PubMed1998

Childhood parental loss and schizophrenia: evidence against pathogenic but for some pathoplastic effects.

Childhood parental loss has been associated with a number of psychiatric disorders in adulthood. The present article aims to examine, firstly, the etiologic relationship between early parental loss and later development of schizophrenia and, secondly, the pathoplastic effect of the former on the symptomatology of the latter. We have administered semi-structured interviews inquiring into psychopathology and early separation experiences to a representative sample of first-visit patients to the 31 hospitals and clinics all over Japan (n=1963) and also to a community sample in a small city in Japan (n=218). When 225 patients diagnosed with schizophrenia according to DSM-III-R criteria were compared with 122 healthy control subjects without any lifetime psychiatric disorder, controlled for sex and age, there was no statistically significant difference in the rates of childhood parental loss (death or separation). As regards the pathoplastic effects, it was found that schizophrenic men were less likely to present with negative symptoms if they had experienced separation from the father, and were more likely to show panic attacks if they had experienced separation from the mother. Schizophrenic women were more likely to present with hallucinations if they had suffered any loss of the father. Childhood parental loss is not pathogenic of schizophrenia but appears to exert some pathoplastic influences on its presenting symptoms.

Adult↗
PubMed1998

Senescence marker protein-30 (SMP30) rescues cell death by enhancing plasma membrane Ca(2+)-pumping activity in Hep G2 cells.

Senescence marker protein-30 (SMP30) has been reported to decrease with aging in the rat liver. SMP30 has been also suggested to play a role as a Ca(2+)-binding protein localized in cytosol of hepatocytes. To elucidate the functional significance of SMP30, we have generated Hep G2 cell lines that stably express large amounts of SMP30 by transfection with human SMP30 cDNA. Using these cell lines, in view of the intracellular Ca2+ homeostasis, we then investigated cytosolic free Ca2+ concentration ([Ca2+]i) and Na(+)-independent Ca2+ efflux from the cells after extracellular ATP stimulation. Although stimulation of cells with ATP caused transient [Ca2+]i increase in both SMP30 and mock transfectants, rate of decrease after peak in [Ca2+]i was enhanced 2-fold by transfection of SMP30. Correspondingly, Ca2+ efflux was significantly increased in SMP30 transfectants compared with mock transfectants. In addition, more SMP30 transfectants survived than mock transfectants when cell death was induced by Ca2+ ionophore treatment. These results suggest that SMP30 regulates [Ca2+]i by modulating plasma membrane Ca(2+)-pumping activity, and thus down-regulation of SMP30 during aging may contribute to deterioration of cellular functions.

Animals↗
PubMed1998

A novel hepatic stellate (Ito) cell-derived protein, epimorphin, plays a key role in the late stages of liver regeneration.

Limited data exist regarding morphogenesis and differentiation during liver regeneration. We examined the role of epimorphin on liver regeneration. After 70% partial hepatectomy, mouse liver was collected on days 1, 3, 7, and 14 for immunohistochemistry and the detection of epimorphin mRNA and connexin 32. Using primary cultured rat hepatocytes, morphogenesis and differentiation of cells were tested with or without epimorphin. Seven days after cell inoculation, the expression of connexin 32 and the cell-cell communication was tested as a marker of differentiation. Epimorphin was detected exclusively in hepatic stellate cells. Connexin 32 was detected only in hepatocytes. After partial hepatectomy, epimorphin mRNA was detected on day 3 and peaked at day 7, followed by protein expression. Connexin 32 expression showed a similar time course. Cultured hepatocytes formed multicellular spheroids in an active epimorphin-coated culture dish and showed positive dye coupling, whereas the cell-cell communication was lost without active epimorphin. Because epimorphin was expressed late in liver regeneration, it might play a role in morphogenesis and differentiation.

Animals↗
PubMed1998

Requirement of the serine-threonine kinase Akt for heat treatment-induced activation of p70 S6 kinase.

p70 S6 kinase plays an important role in growth factor-induced translational control and in cell cycle progression. Although the mechanism of p70 S6 kinase regulation is not fully understood, phosphorylation of serine and threonine residues of the enzyme is essential for its activation. The possible role of the serine-threonine kinase Akt in the activation of p70 S6 kinase induced by exposure of cells to heat has now been investigated. Overexpression of a mutant Akt1 (Akt-AA) in which the phosphorylation sites (Thr308 and Ser473) targeted by growth factors are replaced by alanine was shown to exert a dominant negative effect on Akt activation induced by platelet-derived growth factor (PDGF) or by heat treatment in CHO cells. Akt-AA also inhibited p70 S6 kinase activation induced by these stimuli. However, Akt-AA had no effect on the activation of p70 S6 kinase induced by 12-O-tetradecanoylphorbol 13-acetate, which did not stimulate Akt activity in these cells. These data suggest that Akt is required for heat treatment-induced activation of p70 S6 kinase.

Adenoviridae↗
PubMed1998

Induction of synaptosomal-associated protein-23 kD (SNAP-23) by various cytokines.

Cytokines manifest their function through regulation of gene expression. We searched for immediate-early cytokine responsive genes by the mRNA differential display technique using interleukin-3 (IL-3)-dependent OTT-1 cells, and have isolated a novel cDNA which encodes 210 amino acids and shows 87% amino acid identity to human SNAP-23 (synaptosomal-associated protein of 23 kD). The message for this protein (mouse SNAP-23) was induced in OTT-1 cells by IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5. The experiment using C-terminal deletion mutants of the common beta subunit (betac) of IL-3/GM-CSF/IL-5 receptors showed that expression of SNAP-23 was associated with the Ras-Raf-MAPK pathway, but not with the JAK-STAT pathway. Moreover, SNAP-23 was induced in response to a wide variety of cytokines, including IL-2, IL-3, IL-5, IL-10, stem cell factor, G-CSF, GM-CSF, leukemia inhibitory factor, and erythropoietin. Constitutive expression of SNAP-23 was seen in various tissues, including heart, lung, kidney, liver, spleen, and small intestine. Possible involvement of SNAP-23 in cytokine signal transduction is discussed.

Amino Acid Sequence↗
PubMed1998

Interleukin-12 induces tyrosine phosphorylation of an 85-kDa protein associated with the interleukin-12 receptor beta 1 subunit.

Interleukin-12 (IL12) is a heterodimeric cytokine composed of p35 and p40 subunits and having multiple immunomodulatory effects on T cells as well as on natural killer cells. Two subunits, beta 1 and beta 2, consisting of the functional IL12 receptor complex, have been recently identified as members of the hemopoietin receptor superfamily, bearing strong homology to gp130. In the present study, we attempted to further characterize the biochemical nature of the IL12 receptor complex and to delineate IL12-triggered signal transduction pathways. To this end, we established a Jurkat transfectant (JIL12R beta 1t) highly expressing the recombinant human IL12 receptor beta 1 subunit. Using this transfectant, we identified an 85-kDa protein (p85) which is associated with the beta 1 subunit and appears to be a cell surface protein, but is distinct from the beta 2 subunit (130 kDa). p85 was also detected in PHA-activated T cells. Importantly, p85 was rapidly tyrosine phosphorylated upon stimulation of both JIL12R beta 1t cells and PHA-activated T cells with IL12. These results suggest that p85 is a component of the IL12 receptor complex and may play a significant role in mediating IL12-dependent signals.

Animals↗
PubMed1998

Involvement of Bruton's tyrosine kinase in FcepsilonRI-dependent mast cell degranulation and cytokine production.

We investigated the role of Bruton's tyrosine kinase (Btk) in FcepsilonRI-dependent activation of mouse mast cells, using xid and btk null mutant mice. Unlike B cell development, mast cell development is apparently normal in these btk mutant mice. However, mast cells derived from these mice exhibited significant abnormalities in FcepsilonRI-dependent function. xid mice primed with anti-dinitrophenyl monoclonal IgE antibody exhibited mildly diminished early-phase and severely blunted late-phase anaphylactic reactions in response to antigen challenge in vivo. Consistent with this finding, cultured mast cells derived from the bone marrow cells of xid or btk null mice exhibited mild impairments in degranulation, and more profound defects in the production of several cytokines, upon FcepsilonRI cross-linking. Moreover, the transcriptional activities of these cytokine genes were severely reduced in FcepsilonRI-stimulated btk mutant mast cells. The specificity of these effects of btk mutations was confirmed by the improvement in the ability of btk mutant mast cells to degranulate and to secrete cytokines after the retroviral transfer of wild-type btk cDNA, but not of vector or kinase-dead btk cDNA. Retroviral transfer of Emt (= Itk/Tsk), Btk's closest relative, also partially improved the ability of btk mutant mast cells to secrete mediators. Taken together, these results demonstrate an important role for Btk in the full expression of FcepsilonRI signal transduction in mast cells.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1998

High-dose-rate intracavitary brachytherapy in the management of cervical and vaginal intraepithelial neoplasia.

PURPOSE: To assess the effectiveness of high-dose rate intracavitary brachytherapy (HDR-ICR) in patients with grade 3 cervical intraepithelial neoplasia (CIN-3) and grade 3 vaginal intraepithelial neoplasia (VAIN-3). METHODS AND MATERIALS: This was a retrospective analysis in 20 patients with CIN-3 (n = 14) or VAIN-3 (n = 6), average age 61.9 years, managed with HDR-ICR at Kanagawa Cancer Center. Two patients with CIN-3 with microinvasive foci and 11 other patients with CIN-3 were treated with HDR-ICR for cervical lesions. Six patients with CIN-3 after hysterectomy received HDR-ICR for recurrent or residual VAIN-3 lesions. One patient received radiation therapy for both CIN-3 and VAIN-3 lesions. All these patients but one were postmenopausal. RESULTS: Seventeen patients were treated with HDR-ICR alone, and three with combined external radiation therapy. The dose was calculated at Point A located 2 cm superior to the external os and 2 cm lateral to the axis of the intrauterine tube for intact uterus. For lesions of the vaginal stump, the dose was calculated at a point 1 cm superior to the vaginal apex or 1 cm beyond vaginal mucosa. In the 14 patients treated for CIN-3 lesions, the mean total dose of HDR-ICR was 26.1 Gy (range 20-30). Six patients received HDR-ICR for VAIN-3 lesions with mean dose of 23.3 Gy (range 15-30). At follow-up (mean 90.5 months; range 13-153), 14 patients were alive and 6 had died owing to nonmalignant intercurrent disease. No patient developed recurrent disease. Rectal bleeding occurred in three patients, but this symptom subsided spontaneously. Moderate and severe vaginal reactions were noted in two patients, in whom the treatment had included the entire vagina. CONCLUSIONS: HDR-ICR can be employed as the primary management strategy for postmenopausal women with CIN-3. In intraepithelial neoplasia involving the vaginal wall after hysterectomy, HDR-ICR should be considered as an alternative to total vaginectomy.

Adult↗