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Biomedical subjects

T Kitamura

Publications and source records attributed to T Kitamura.

At least 217 records · Page 12Linked to original sources

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↗

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↗

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↗

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↗

The effect of papaverine on morphologic differentiation, proliferation and invasive potential of human prostatic cancer LNCaP cells.

BACKGROUND: Intracellular cyclic adenosine monophosphate (AMP) level changes are thought to play an important role in inhibiting cell proliferation and inducing differentiation in several types of cells. It has been reported that cyclic AMP analogs induce terminal differentiation in human prostate cancer cells. Consequently, phosphodiesterase inhibitors may be useful in delineating the role of cyclic AMP in the differentiation of these cells. Therefore, the effect of phosphodiesterase inhibitors on morphologic differentiation, proliferation and invasive potential of human prostate cancer cells was investigated. METHODS: Three human prostate cancer cell lines PC-3, DU145 and LNCaP were treated with one of the phosphodiesterase inhibitors, papaverine, 3-isobutyl-1-methylxanthine (IBMX) or theophylline, for 6 days. Morphologic changes of these cells induced by phosphodiesterase inhibitors were observed by microscopy. Intracellular cyclic AMP levels in LNCaP cells were measured by radioimmunoassay using a cyclic AMP assay kit. The effect of papaverine on the proliferation and invasive potential of LNCaP cells were measured by cell counting and the Matrigel invasion chamber assay. RESULTS: Of the three agents, examined papaverine (10(-5) mol/L) is the most effective inducer of morphologic change and also raised intracellular cyclic AMP levels in LNCaP cells. However, unlike LNCaP cells, PC-3 and DU145 cells treated with phosphodiesterase inhibitors, including papaverine, showed little change in morphology. Additionally, proliferation and invasive potential of LNCaP cells were significantly inhibited by papaverine. CONCLUSION: The results suggest that papaverine induces terminal differentiation in LNCaP cells, which is correlated with an intracellular cyclic AMP-mediated pathway.

1-Methyl-3-isobutylxanthine↗

Contractile responses to alpha1-adrenoceptor agonists in isolated human male and female urethra.

OBJECTIVE: To investigate the contractile responses mediated through alpha1-adrenoceptors in human urethra and to evaluate the effectiveness of NS-49 [(R)-(-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethanesulphonanilide++ + hydrochloride], a novel alpha1-adrenoceptor agonist, against contraction of the human urethra. MATERIALS AND METHODS: The contractile responses were assessed in 10 male prostatic urethrae and six female urethrae. Antagonism was evaluated in the urethra using phenylephrine, a nonselective alpha1-adrenoceptor agonist, cumulatively applied > 20 min after applying 0.1 micromol/L prazosin or 0.1 micromol/L 5-methylurapidil, a selective alpha1A-adrenoceptor antagonist. Agonism was determined in both male and female urethrae to obtain the concentration-response curve for the agonist. RESULTS: Phenylephrine caused both male and female urethrae to contract, and showed high potency and efficacy. Prazosin antagonized these contractions with low affinity (apparent pKB of 8.30 in male urethrae). 5-Methylurapidil, also antagonized the contractions with low affinity (apparent pKB of 7.88 in male urethrae). Noradrenaline and phenylephrine caused both male and female urethrae to contract, with high potency and efficacy. A novel and selective alpha1A-and alpha1L-adrenoceptor agonist, NS-49, induced contractile responses with high potency and moderate efficacy, whereas methoxamine induced contractions with low potency and moderate efficacy. Norephedrine was a very weak contractile agonist. CONCLUSION: In the human urethra, phenylephrine-induced contractions were mediated through alpha1L-adrenoceptors and not through alpha1A-adrenoceptors. Contractions of the human urethra induced by NS-49 were also mediated mainly through alpha1L-adrenoceptors, with high potency and moderate efficacy. NS-49 may therefore be useful for the treatment of urinary stress incontinence, with minimal side-effects because it has subtype selectivity.

Adrenergic alpha-Agonists↗

Soluble E-selectin as a marker of disease activity in pustulosis palmaris et plantaris.

In this study, we investigated a possible correlation between adhesion molecules and activity of pustulosis palmaris et plantaris (PPP). Serum levels of soluble E-selectin (sE-selectin), soluble intercellular adhesion molecules 1 (sICAM-1) and tumour necrosis factor alpha (TNF-alpha) in 30 untreated PPP patients were examined, and compared with those in 20 healthy subjects. Values in 10 PPP patients were re-examined after treatment. Serum levels of sE-selectin and TNF-alpha in untreated PPP patients were significantly higher than those in healthy subjects. There was a statistically significant correlation between the disease activity and serum levels of sE-selectin in untreated PPP patients. Furthermore, disease activity of PPP was higher in patients who smoked and during the summer, with elevation of serum sE-selectin levels. Serum levels of sE-selectin were downregulated with the recovery from PPP. These results suggest that sE-selectin may play a role in the pathogenesis of PPP and could be a reliable marker of its disease activity.

Adult↗

Core 2-containing O-glycans on CD43 are preferentially expressed in the memory subset of human CD4 T cells.

Human CD4 T cells can be divided into two functionally distinct subsets: a CD45RO+ memory subset and a CD45RA+ naive subset. In an attempt to identify novel cell surface molecules on these cells, we have developed a mAb, anti-1D4. The antigen defined by anti-1D4 was preferentially expressed on the memory subset of freshly isolated peripheral CD4 T cells and 1D4+ CD4 T cells functionally corresponded to memory T cells. Retrovirus-mediated expression cloning revealed that the 1 D4 antigen is human CD43. Transfection of CHO-leu cells, which stably express human CD43, with core 2 beta-1,6-N-acetylglucosaminyltransferase (C2GnT) conferred expression of the 1D4 antigen and mRNA of C2GnT was detected by RT-PCR only in 1D4+ T cells but not in 1D4- T cells, implying that the 1 D4 antigen is composed of core 2-containing O-glycans on CD43. Reactivity with anti-1 D4 was completely abolished when cells were treated with neuraminidase, while them remained weak binding of anti-T305, a previously described mAb which also reacts with CD43 modified with core 2-containing O-glycans. Moreover, anti-1D4 markedly reacted with NIH-3T3 cells expressing human CD43 and low levels of endogenous C2GnT, whereas anti-T305 reacted slightly. These results indicate that the 1D4 antigen is distinct from the epitope defined by anti-T305 and anti-1D4 is a more sensitive probe to detect core 2-containing O-glycans than anti-T305. Taken together, our results indicate that core 2-containing O-glycans, whose expression can easily be detected with anti-1D4, are preferentially expressed in the CD45RO+ memory subset of CD4 T cells.

Animals↗

Efficiency of a new fiberoptic stylet scope in tracheal intubation.

BACKGROUND: Failed or difficult tracheal intubation is an important cause of morbidity and mortality during anesthesia. Although a number of fiberoptic devices are available to circumvent this problem, many do not allow manual control of the flexion of the tip and necessitate time-consuming preparation, special training, or the use of an external light source. To improve these limitations, the authors designed a new fiberoptic stylet scope (FSS) that has a simple form of a standard stylet with the fiberoptic view and maneuverability of its tip. This study was undertaken to prospectively evaluate the effectiveness of the FSS in tracheal intubation. METHODS: Thirty-two patients undergoing general surgery participated in this study. The authors used a standard laryngoscope only to elevate the tongue, then tracheal intubation was attempted with the glottic opening being viewed only through the FSS. The success rate, time necessary for intubation, hemodynamics, and adverse effects were recorded. RESULTS: The success rate of tracheal intubation on the first attempt using the FSS was 94% (30 of 32 patients), and the remaining two patients were intubated successfully on the second attempt. The mean time necessary for the intubation procedure was 29+/-14 s in all patients (mean +/- SD). Changes in hemodynamics during intubation were well within acceptable ranges. There were no major adverse effects, but minor sore throat (28%) and minor hoarseness (25%) on the first postoperative day. CONCLUSIONS: Tracheal intubation using the FSS proved to be a simple and effective technique for airway management.

Adult↗

Psychiatric disorders among Japanese children.

OBJECTIVE: To generate current data on the prevalence of psychiatric disorders among Japanese children, using DSM-III-R criteria. METHOD: As part of an ongoing longitudinal study in a Japanese community sample, 114 mother-child dyads were interviewed when the children were approximately 8 years old. DSM-III-R disorders of the children were diagnosed through the administration of a structured diagnostic instrument, the parent and child versions of the Child Assessment Schedule, to both the children and their mothers. RESULTS: The prevalence rate for any diagnosis was 49.1%, which is similar to that of U.S. children and adolescents. CONCLUSION: The Child Assessment Schedule is an appropriate scale for assessing the psychopathology of Japanese children, which is as prevalent as in a U.S. sample.

Adolescent↗

A computer-aided approach to the structural analysis and modification of a large circulatory system model.

The purpose of this study is to show an approach to making an intelligent support system for understanding and modifying a large circulatory system model using techniques of system analysis. Structural analysis makes it possible to visualize hierarchies of Coleman's circulatory model Human. Two techniques are successively applied for structural analysis, model reduction and graph analysis by interpretative structural modeling (ISM). First, the analysis for model reduction removes input-output relations with an input-output gain less than a given threshold, and second, the ISM technique applied to the reduced model of Human provides hierarchical directed graphs. The proposed approach: 1) enables visualization of a hierarchy graph of cause and effect relations of the large circulatory model, 2) suggests control and diagnostic information to the model by tracing back a path in the hierarchy, and 3) allows the user to modify the circulatory model. The efficiency and performance of the proposed approach demonstrates technical indications of success in analyzing and justifying experimental evidences with the online help of the system.

Algorithms↗

Immunohistochemical detection of JC virus in nontumorous renal tissue of a patient with renal cancer but without progressive multifocal leukoencephalopathy.

We performed immunohistochemical staining on the nontumorous renal tissue of 45 patients with renal cancer but without progressive multifocal encephalopathy using JCV-specific antibody. For one patient we found positive staining of the nuclei of the renal collecting ducts. Immunoelectron microscopic examination of the positive cell nuclei revealed electron-dense polyomavirus-like particles.

Antibodies, Viral↗

Monoclonal antibodies against the minimal DNA-binding domain in the carboxyl-terminal region of human immunodeficiency virus type 1 integrase.

Integrase of human immunodeficiency virus type 1 (HIVIN) consists of 288 amino acids, and its minimum DNA-binding domain (MDBD) (amino acids [aa] 220 to 270) is required for the integration reaction. We produced and characterized four murine monoclonal antibodies (MAbs) to the MDBD of HIVIN (strain LAI). Immunoblot and enzyme-linked immunosorbent assays with truncated HIVINs showed that those MAbs recognized sequential epitopes within the MDBD (aa 228 to 236, 237 to 252, 253 to 261, and 262 to 270). Their binding to HIVIN inhibited terminal cleavage and strand transfer activities but not disintegration activity in vitro. This collection of MAbs is useful for studying the structure and function of the MDBD by complementing mutational analyses and other biochemical studies.

Animals↗

An orphan G protein-coupled receptor, GPR1, acts as a coreceptor to allow replication of human immunodeficiency virus types 1 and 2 in brain-derived cells.

Twelve G protein-coupled receptors, including chemokine receptors, act as coreceptors and determinants for the cell tropisms of human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus (SIV). We isolated HIV-1 variants from T-cell-line (T)- and macrophage (M)-tropic (i.e., dualtropic) (R5-R3-X4) HIV-1 strains and also produced six HIV-1 mutants carrying single-point amino acid substitutions at the tip of the V3 region of the Env protein of HIV-1. These variants and three mutants infected brain-derived CD4-positive cells that are resistant to M-, T-, or dualtropic (R5, X4, or R5-X4) HIV-1 strains. However, a factor that determines this cell tropism has not been identified. This study shows that primary brain-derived fibroblast-like cell strains, BT-3 and BT-20/N, as well as a CD4-transduced glioma cell line, U87/CD4, which were susceptible to these HIV-1 variants and mutants and the HIV-2ROD strain, expressed mRNA of an orphan G protein-coupled receptor (GPCR), GPR1. When a CD4-positive cell line which was strictly resistant to infection with diverse HIV-1 and HIV-2 strains was transduced with GPR1, the cell line became susceptible to these HIV-1 variants and mutants and to an HIV-2 strain but not to T- or dualtropic HIV-1 strains, and numerous syncytia formed after infection. These results indicate that GPR1 functions as a coreceptor for the HIV-1 variants and mutants and for the HIV-2ROD strain in vitro.

Brain↗

Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt.

Cyclic nucleotide phosphodiesterase (PDE) is an important regulator of the cellular concentrations of the second messengers cyclic AMP (cAMP) and cGMP. Insulin activates the 3B isoform of PDE in adipocytes in a phosphoinositide 3-kinase-dependent manner; however, downstream effectors that mediate signaling to PDE3B remain unknown. Insulin-induced phosphorylation and activation of endogenous or recombinant PDE3B in 3T3-L1 adipocytes have now been shown to be inhibited by a dominant-negative mutant of the serine-threonine kinase Akt, suggesting that Akt is necessary for insulin-induced phosphorylation and activation of PDE3B. Serine-273 of mouse PDE3B is located within a motif (RXRXXS) that is preferentially phosphorylated by Akt. A mutant PDE3B in which serine-273 was replaced by alanine was not phosphorylated either in response to insulin in intact cells or by purified Akt in vitro. In contrast, PDE3B mutants in which alanine was substituted for either serine-296 or serine-421, each of which lies within a sequence (RRXS) preferentially phosphorylated by cAMP-dependent protein kinase, were phosphorylated by Akt in vitro or in response to insulin in intact cells. Moreover, the serine-273 mutant of PDE3B was not activated by insulin when expressed in adipocytes. These results suggest that PDE3B is a physiological substrate of Akt and that Akt-mediated phosphorylation of PDE3B on serine-273 is important for insulin-induced activation of PDE3B.

3',5'-Cyclic-AMP Phosphodiesterases↗

Medullary thyroid carcinoma with multiple hepatic metastases: treatment with transcatheter arterial embolization and percutaneous ethanol injection.

A 54-year-old man with medullary thyroid carcinoma in the thyroid gland was unable to undergo total thyroidectomy because the tumor had invaded the mediastinum. Radiation therapy and chemotherapy were given. Seven years later, intractable diarrhea and abdominal pain appeared, and computed tomography demonstrated hypervascular tumors in the thyroid gland and in the liver. The tumors were successfully treated with percutaneous ethanol injection to a lesion in the thyroid gland and transcatheter arterial embolization followed by percutaneous ethanol injection to tumors in the liver. Transcatheter arterial embolization and percutaneous ethanol injection may be valuable in treating medullary thyroid carcinoma.

Angiography↗