Biomedical subjects

T Kitamura

Publications and source records attributed to T Kitamura.

At least 199 records · Page 11Linked to original sources

PubMed1999

Lungs of patients with idiopathic pulmonary alveolar proteinosis express a factor which neutralizes granulocyte-macrophage colony stimulating factor.

Mice deficient in granulocyte-macrophage colony stimulating factor (GM-CSF) develop pulmonary alveolar proteinosis (PAP). We found that bronchoalveolar lavage fluid (BALF) from 11 patients with idiopathic pulmonary alveolar proteinosis (IPAP) suppressed the growth of peripheral blood monocytes and TF-1 cells, a cell line dependent on either GM-CSF or interleukin-3 (IL-3). The inhibitory effect of PAP-BALF occurred only when TF-1 cells were cultured with GM-CSF but not when cultured with IL-3, suggesting that PAP-BALF contains a factor that specifically interferes with GM-CSF function. 125I-GM-CSF binding to TF-1 cells was prevented in the presence of BALF from IPAP patients. Furthermore, cross-linking of 125I-GM-CSF to IPAP-BALF produced two major bands on SDS-PAGE; these bands were not observed in normal BALF. These data suggest that IPAP is caused by expression of binding factor(s) which inhibit GM-CSF function in the lung.

Binding, Competitive↗

PubMed1999

Accelerated rejection of Fas ligand-expressing heart grafts.

The Fas/Fas ligand (FasL) system plays an important role in the induction of lymphoid apoptosis and has been implicated in the suppression of immune responses. Recently, there has been renewed interest in immune privilege, as it was shown that two privileged sites (the eye and testes) constitutively express FasL, which kills lymphoid cells that invade these areas. We have established murine FasL-transgenic mice (B6) under the control of the cardiac alpha-myosin heavy chain promotor, and transplanted FasL-expressing F1(B6 x C3H/HeJ) heart grafts into syngeneic (F1) and allogeneic (C3H/HeJ) recipients. FasL-expressing F1 heart allografts placed in C3H/HeJ recipients as well as FasL-expressing F1 isografts placed in nontransgenic and FasL-transgenic F1 were more rapidly rejected, and their survival was much shorter than that of nontransgenic control F1 allografts placed in C3H/HeJ. Native control and FasL-expressing hearts looked normal in mice up to 8 wk of age on hematoxylin-eosin staining. Control heart allografts undergoing ordinally acute rejection showed moderate focal lymphocyte infiltrates, while FasL-expressing F1 allografts and isografts showed massive hemorrhage, edema, and massive neutrophil infiltration as early as 1 day after transplantation. In conclusion, FasL expression and surgical procedure (ischemia/reperfusion) were synergistic in the induction of accelerated heart graft rejection, while allogenicity was not necessary. It may be necessary to find ways of controlling neutrophilic reaction/apoptosis in infiltrating lymphocytes to use FasL in clinical organ transplantation.

Animals↗

PubMed1999

Expression of interferon receptor genes in the liver as a predictor of interferon response in patients with chronic hepatitis C.

Interferon (IFN) receptor mRNA expression patterns in the liver have been shown to correlate with the effectiveness of IFN therapy in patients with hepatitis C virus (HCV) infection. However, it is not clear to what extent this factor contributes to the short (primary)- and long (sustained)-term results of IFN treatment with respect to biochemical and virological remission. Eighty-two patients who subsequently received lymphoblastoid IFN-alpha therapy underwent liver biopsies before IFN therapy. Possible factors that might correlate with IFN response were chosen and analyzed. The primary biochemical and virological responses at the end to treatment (24 weeks) were 63% and 43% vs. 46% and 32% for sustained biochemical and virological remission at the end of follow-up (48 weeks), respectively. In univariate analysis, the absence of HCV genotype 1b, a low titer of HCV RNA, and the expression of IFN receptor mRNA were significantly correlated with sustained biochemical and virological responses to IFN therapy. Multiple logistic regression analysis showed that IFN receptor mRNA expression and the absence of genotype 1b were significant predictors of the sustained biochemical and virological effectiveness of IFN therapy. IFN receptor mRNA expression predicted a sustained virological response to IFN therapy with a positive predictive value of 100% with genotype non-1b and had a negative predictive value of 97% with genotype 1b. It is concluded that expression of IFN receptor genes in the liver is a useful index for predicting the short- and long-term efficacy of IFN therapy in patients with chronic HCV infection.

Alanine Transaminase↗

PubMed1999

Longitudinal relationship between maternal depression and infant temperament in a Japanese population.

To investigate the relationship between maternal depression and infant temperament in a Japanese population, a prospective questionnaire survey was administered in the postpartum period. Postnatal depression was assessed by Zung's (1965) Self-Rating Depression Scale on two occasions (5 days and 12 months after delivery). At 6 months and 18 months after birth, infant temperament was assessed using the Revised Infant Temperament Questionnaire (RITQ; Carey & McDevitt, 1978) and the Toddler Temperament Scale (TTS; Fullward, McDevitt, & Carey, 1984), respectively. Of the five temperamental dimensions of the RITQ and TTS, "rhythmicity" and "attention span and persistence" showed reciprocal relationships with postnatal depression. Unidirectional effects of maternal depression on infant temperament were found for "frustration tolerance" and "fear of strangers and strange situations."

Adolescent↗

PubMed1999

Isolation of oncogenes from rat mammary tumors by a highly efficient retrovirus expression cloning system.

A majority of mammary tumors induced with N-methyl-N-nitrosourea in rats contain G to A transitional mutation of c-Ha-ras at the 12th codon. Additional oncogene activation is known to be necessary for further tumor progression. To isolate novel oncogenes, we used an expression cloning system utilizing the pMX retroviral vector in combination with BOSC23 packaging cells. First, we elucidated the sensitivity of this system in the NIH 3T3 focus assay; foci were detectable even after 10(-6) dilution using v-Ha-ras, neuT, and beta-galactosidase constructs in pMX vector. This system is sensitive enough to detect low copy number cDNAs. We used the pMX/BOSC23 expression cloning system to clone novel oncogenes from rat mammary tumors harboring an activated c-Ha-ras and isolated several candidate oncogenes that caused transformation of NIH 3T3 cells and/or generated tumors when transplanted to nude mice.

3T3 Cells↗

PubMed1999

Social Support Questionnaire among psychiatric patients with various diagnoses and normal controls.

BACKGROUND: Several studies have pointed to the importance of social support in influencing the onset and course of a psychiatric disorder such as schizophrenia or depression. However, only a few have studied it across groups of patients with various psychiatric diagnoses employing a standardized assessment procedure. METHOD: We administered the Social Support Questionnaire (SSQ); a measure of social support recommended by two recent reviews on the subject, to 1,369 psychiatric outpatients visiting the 23 psychiatric hospitals and clinics all over Japan and to 178 healthy controls recruited from among employees at a general hospital. RESULTS: The original two-factor structure of the SSQ was confirmed and internal consistency reliability for the Number and Satisfaction subscales was satisfactory, with Cronbach's alphas above 0.85. When the SSQ scores were compared between psychiatric patients and healthy controls, it was found that the psychiatric patients in general reported significantly lower Number as well as Satisfaction scores than the healthy controls. When individual diagnostic categories were considered, almost all the diagnostic groups reported significantly lower Number scores, but only the patients with anxiety disorder, mood disorder, schizophrenia, and V codes reported significantly lower Satisfaction scores than the healthy controls. Compared with patients with other diagnoses, the schizophrenic patients stood out as reporting significantly lower Number and Satisfaction scores. CONCLUSION: The findings demonstrated the internal consistency reliability, factor validity, and construct validity of the SSQ among psychiatric as well as normal populations, and exemplified the feasibility of applying the SSQ as a standard measure of social support among psychiatric patients.

Adolescent↗

PubMed1999

Differences in mossy and climbing afferent sources between flocculus and ventral and dorsal paraflocculus in the rat.

Sources of mossy and climbing fiber inputs to the flocculus (FL), ventral paraflocculus (VP) and/or dorsal paraflocculus (DP) were identified in the vestibular ganglion, medulla oblongata and pons of 19 Wistar rats after 26 local injections of horseradish peroxidase, wheat-germ agglutinin-conjugated horseradish peroxidase, fast blue or diamidino yellow into the FL, VP and/or DP. There were large differences in the sources of mossy fibers to the FL and VP/DP. Labeled neurons after injections into the FL were observed mainly in the ipsilateral vestibular ganglion, bilaterally in the vestibular and prepositus hypoglossal nuclei, and in the caudal part of the nucleus reticularis tegmenti pontis. Labeled neurons were rarely observed in the pontine nuclei after localized injections into the FL. By contrast, after injections into the VP and/or DP, numerous labeled neurons were observed in the pontine nuclei with a contralateral predominance and in the rostral part of the nucleus reticularis tegmenti pontis bilaterally, but not in the vestibular nuclei in either side. Sources of climbing fibers to the FL and paraflocculus were completely contralateral to the injection side. After injection into the FL, labeled neurons were observed in the caudal dorsal cap and ventrolateral outgrowth of the inferior olivary nucleus. After injections into the VP, labeled neurons were observed mainly in the rostral dorsal cap, ventral medial accessory olivary nucleus (MAO) and caudal half of the ventral leaf of the principal olivary nucleus. After injections into the DP, labeled neurons were observed in the ventral MAO and caudal half of the ventral leaf of the principal olivary nucleus. These differences in the sources of mossy and climbing fiber inputs may suggest functional differences between the FL and VP/DP. The present results are consistent with our previous observations in monkey that the FL and VP/DP exhibit quite different mossy fiber input organizations.

Amidines↗

PubMed1999

CD95 ligand expression enhances growth of murine renal cell carcinoma in vivo.

The CD95/CD95 ligand (CD95L) system plays an important role in the induction of lymphoid apoptosis and has been implicated in the suppression of immune responses. In this system, two murine CD95L-transfected renca clones and a control renca clone transfected only with the vector were implanted into the subcapsule of the left kidney of Balb/c and Balb/c nude mice. Both CD95L-expressing and control renca clones formed macroscopic tumors in all of the Balb/c and Balb/c nude hosts 14 days after implantation. Growth of tumors of murine CD95L-transfected renca cells was significantly better than that of control renca cells in Balb/c mice, while the growth advantage of CD95L transfectants was not observed in Balb/c nude mice. Lymphocytes underwent apoptosis mainly in the periphery of the CD95L-expressing tumors but not in control tumors grown in Balb/c mice, while lymphocytes undergoing apoptosis were not observed in CD95L-expressing tumors or in control tumors grown in Balb/c nude mice. Neutrophilic recruitment was rarely observed in CD95L-expressing or control tumors. CD95L expressed on renca cells possibly suppressed immune responses against renca tumors by inducing apoptosis of the infiltrating lymphocytes. However, CD95L-expressing renca cells did not form tumors in the renal subcapsule of allogeneic C3H/HeJ mice.

Animals↗

PubMed1999

Dehydroepiandrosterone (DHEA) facilitates liver regeneration after partial hepatectomy in rats.

In this study we investigated whether or not liver regeneration is facilitated by dehydroepiandrosterone (DHEA) after partial (70%) hepatectomy in rats. Treatment with DHEA (300 mg/kg body weight) did not cause any significant increase in the expression ratio of proliferating cell nuclear antigen (PCNA) in sham-operated controls; however, in partially hepatectomized rats it caused a significant increase in the ratio in hepatocytes 24 and 36 hr after hepatectomy. In partially hepatectomized rats, DHEA treatment significantly accelerated the restoration of liver 48, 60, and 72 hr after partial hepatectomy. The restoration rate in DHEA-treated hepatectomized rats at 72 hr was 1.3-fold greater than in partially hepatectomized controls. Treatment with androstenedione (300 mg/kg body weight), the first metabolite of DHEA, did not cause any significant increase in the expression of PCNA in either sham-operated controls or partially hepatectomized rats. These results indicate that DHEA itself promotes the liver regenerative process after partial hepatectomy in rats.

Androstenedione↗

PubMed1999

Structure of depressive symptoms in pregnancy and the postpartum period.

BACKGROUND: The present study investigated the structure of depressive symptoms in the perinatal period. METHOD: The Zung Self-Rating Depression Scale (SDS) was administered to a total of 1329 women in early, middle and late pregnancy and 5 days, 1 month, 6 months, 12 months and 18 months after the delivery. RESULTS: A number of somatic items and the suicidal ideation item of the SDS made low contributions to the evaluation of the severity of depression, and as a consequence these were excluded in the principal component analysis. Three factors were interpretable as "Cognitive", "Affective insomnia" and "Attentional" emerged at all eight assessment points. The goodness-of-fit index (GFI) generated by confirmatory factor analyses (LISREL 7.20) proved sufficiently high on all eight occasions. LIMITATION: The present study investigated only one self-rating scale and the sample comprised Japanese mothers only. CONCLUSION: The three-factor model of the SDS in the perinatal period was derived from exploratory and confirmatory factor analyses. It is noteworthy that the same three-factor structure emerged at all eight collection points in the present study.

Adolescent↗

PubMed1999

Signal transduction pathways in normal human monocytes stimulated by cytokines and mediators: comparative study with normal human neutrophils or transformed cells and the putative roles in functionality and cell biology.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL) -3 induced tyrosine phosphorylation of 92-kDa protein in normal human monocytes. We identified this 92-kDa protein as STAT5, but not as STATs1, 3, and 6 nor c-fes and vav protooncogene products, and demonstrated its translocation to the nucleus, enhancement of specific DNA binding capacity, and potentiation of trancriptional activity by GM-CSF. N-formyl-methionyl-leucyl-phenylalanine (FMLP) and phorbol myristate acetate (PMA) induced tyrosine phosphorylation of 42- and 44-kDa proteins, which were identified as extracellular signal-regulated kinase (ERK), in human monocytes. In marked contrast to neutrophils and MO7e cells, GM-CSF did not induce tyrosine phosphorylation and activation of ERK in monocytes. Among upstream signaling molecules of ERK, Shc was constitutively associated with Grb2 and was not tyrosine-phosphorylated by GM-CSF and FMLP, and Sos1 and c-Raf-1 were not phosphorylated by GM-CSF, IL-3, TNF, and FMLP in monocytes, whereas all these signaling molecules were affected and/or utilized by GM-CSF in MO7e cells. In contrast to neutrophils, p38 was constitutively phosphorylated and agonist-dependent phosphorylation and activation was not detected in human monocytes. Superoxide release stimulated by FMLP was inhibited partially by PD98059 or SB203580, a specific inhibitor of ERK or p38 pathway, and was almost completely inhibited by the combination of both inhibitors, whereas PMA-induced superoxide release was resistant to these two inhibitors in monocytes. PD98059 inhibited GM-CSF-dependent proliferation of MO7e cells. Present results indicate trancriptional roles of STAT5 and functional roles of ERK and/or p38 in normal human monocytes stimulated by physiological receptor-mediated agonists GM-CSF and FMLP. Possible roles of ERK in proliferation of transformed cells were also suggested.

Adult↗

PubMed1999

Induction of germline transcription in the TCRgamma locus by Stat5: implications for accessibility control by the IL-7 receptor.

IL-7 receptor (IL-7R) plays critical roles in lymphocyte development by promoting survival and proliferation and by inducing V(D)J recombination in TCR and Ig loci. Here, we demonstrate that IL-7R-activated Stat5 binds to consensus motifs in the 5' regions of Jgamma segments and induces germline transcripts. We also show that a constitutively active form of Stat5 restores V-J recombination of TCRgamma genes and partially rescues T cell development from IL-7R(-/-) T cell precursors, especially in favor of gammadelta T cells. Therefore, this study reveals a potential role of Stat5 in T cell development and also implies that IL-7R may control the accessibility of the TCRgamma locus through Stat5-induced germline transcription.

Animals↗

PubMed1999

PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance.

Agonist-induced activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) is known to cause adipocyte differentiation and insulin sensitivity. The biological role of PPAR gamma was investigated by gene targeting. Homozygous PPAR gamma-deficient embryos died at 10.5-11.5 dpc due to placental dysfunction. Quite unexpectedly, heterozygous PPAR gamma-deficient mice were protected from the development of insulin resistance due to adipocyte hypertrophy under a high-fat diet. These phenotypes were abrogated by PPAR gamma agonist treatment. Heterozygous PPAR gamma-deficient mice showed overexpression and hypersecretion of leptin despite the smaller size of adipocytes and decreased fat mass, which may explain these phenotypes at least in part. This study reveals a hitherto unpredicted role for PPAR gamma in high-fat diet-induced obesity due to adipocyte hypertrophy and insulin resistance, which requires both alleles of PPAR gamma.

Adipocytes↗

PubMed1999

Receptors for polytropic and xenotropic mouse leukaemia viruses encoded by a single gene at Rmc1.

The onset of leukaemia caused by type C retroviruses (MLV) in mice is accelerated by the emergence of recombinant polytropic or mink cell focus-forming (MCF) viruses. Susceptibility to infection by polytropic/MCF and also by closely related xenotropic MLV has been mapped to Rmc1 on mouse chromosome 1 (refs 5-7). To identify this gene, we introduced an expression cDNA library prepared from mouse NIH3T3 fibroblasts into nonpermissive hamster cells and screened these cells for acquired susceptibility to MCF viruses encoding beta-galactosidase and G418 resistance. From hamster cell clones identified in the screen, we recovered a mouse cDNA that maps to Rmc1 and confers MCF MLV infection when expressed in nonpermissive cell lines. It encodes a membrane protein related to Syg1p (suppressor of yeast G alpha deletion; ref. 8). The receptor-binding domain of the MCF MLV envelope protein binds specifically to Xenopus laevis oocytes that express mouse Syg1, suggesting it functions as a receptor that mediates virus entry. We also obtained the cDNA encoding human SYG1. When expressed in hamster cells, it establishes infectivity by MCF MLV as well as xenotropic MLV, which do not infect laboratory mice.

3T3 Cells↗

PubMed1999

A signal sequence trap based on a constitutively active cytokine receptor.

Targeting of secreted and cell-surface proteins to the cell membrane is mediated by a short hydrophobic stretch of amino acids, termed the signal sequence. We have developed a method that detects signal sequences in cDNA fragments based on their ability to redirect a constitutively active mutant of a cytokine receptor to the cell surface, thereby permitting interleukin-3 (IL-3)-independent growth of Ba/F3 cells. Retrovirus-mediated expression of the fusions in IL-3-dependent cells was followed by selection of clones for growth in the absence of IL-3. Infection of cells with 5x10(6) viral particles in a pilot experiment led to the isolation of 150 known and 48 novel cDNA clones, and all the known cDNA clones were found to encode secreted and cell-surface proteins. In addition, we isolated type II membrane proteins, which have not been detected by existing signal sequence trap strategies.

Animals↗

PubMed1999

Reliability of childhood mental disorder: diagnoses by Japanese psychologists.

The recent entry of psychologists into psychiatric practices and schools in Japan calls for diagnostic skills, because psychiatrists are less available in such settings. We examined the reliability of the diagnoses of 10 DSM-IV childhood mental disorders by 11 Japanese psychologists, using 20 case vignettes. Most categories had good reliability (kappa), except for attention deficit hyperactivity disorder. Japanese clinical psychologists may be able to use DSM-IV reliably as a tool for diagnosis of childhood psychiatric disorders, if sufficient training is provided.

Adolescent↗

PubMed1999

A polydiagnostic study of depressive disorders according to DSM-IV and 23 classical diagnostic systems.

The classification of mood disorders is one of the most highly debated topics in modern psychiatry. The introduction of DSM-III (and its followers) has set a new standard in this controversy but little empirical evidence is available as to how the various classical diagnostic categories of mood disorders by Kraepelin, Schneider, Leonhard, Hamilton, Kielholz, Winokur and others compare with this new standard. The Intensive Prospective Study arm of the Group for Longitudinal Affective Disorders Study has studied a broad spectrum of mood disorders in 23 participating centres from all over Japan with a polydiagnostic semistructured interview called Comprehensive Assessment List of Affective disorders. In this paper we examined how the various classical diagnostic systems of depressive disorders correspond to the DSM-IV diagnoses, and found the following: (1) The classical 'neurotic' or 'psychogenic' depressions are diagnosed as major depression and not as dysthymia in DSM-IV; although dysthymia was dubbed as 'depressive neurosis' in DSM-III, its criteria were not true to the traditional usage of the term. Viewed from the other side of the coin, DSM-IV can be said to stand in the unitary tradition. (2) Some of the classical diagnostic categories such as Schneider's depressive psychopathy and Klein's acute dysphoria as well as modern ones such as Akiskal's subaffective dysthymia and Angst's recurrent brief depression were rarely seen in traditional psychiatric treatment settings. (3) Comparisons of the unique diagnostic systems such as those by Leonhard, Winokur and Berner warrant further studies on their validity.

Adult↗

PubMed1999

Precedents of perceived social support: personality and early life experiences.

In order to examine the effects of personality and early life experiences on perceived social support, a total of 97 young Japanese women were investigated. Current interpersonal relationships were measured by an interview modified from Henderson et al.'s Interview Schedule for Social Interaction (ISSI). Personality was measured by Cloninger et al.'s Temperament and Character Inventory. Early life experiences at home and outside of home were also identified in the interview. The number of sources of perceived support was correlated with self-directness, while satisfaction with perceived support was correlated with novelty seeking and with low harm avoidance. No early life experiences--early loss of a parent, perceived parenting, childhood abuse experiences, experiences of being bullied and/or other life events--showed significant correlations with the number or satisfaction of supportive people. The quantity and quality of perception of social support differ in their link to personality, and perceived social support may, to some extent, be explainable in terms of personality.

Adult↗