Biomedical subjects

T Kitamura

Publications and source records attributed to T Kitamura.

At least 163 records · Page 9Linked to original sources

PubMed2000

Pituitary stone--case report.

A 50-year-old male with acromegalic features presented with a pituitary stone in a growth hormone-secreting adenoma. Endocrinological examination showed "low growth hormone acromegaly." The serum growth hormone level responded to the thyrotropin-releasing hormone test and was not suppressed by oral glucose loading. Neuroimaging revealed an adenoma including a large calcification (pituitary stone) located in the right lateral wing. The adenoma with stone was totally removed by transsphenoidal surgery. The patient regained almost normal response of serum growth hormone. Histological examination showed the stone was composed of thick calcification surrounded by necrotic adenoma tissue and chronic hemorrhage. Large intratumoral pituitary stone is very rare, although calcification is sometimes observed in the adenoma capsule. The long history of this disease and previous apoplexy within the tumor may have caused the pituitary stone in this patient.

Acromegaly↗

PubMed2000

[Antigen-specific T cells transduced with interleukin-10 ameliorate experimentally induced arthritis without impairing the systemic immune response to the antigen].

For the treatment of rheumatoid arthritis, efficient drug delivery methods to the inflamed joints need to be developed. Since T cells expressing an appropriate autoantigen-specific receptor can migrate to inflamed lesions, it has been reasoned that they can be employed to deliver therapeutic agents. In order to examine the ability and efficiency of such T cells as a vehicle, we employed an experimentally induced model of arthritis. Splenic T cells from DO 11.10 T cell receptor transgenic mice specific for OVA were transduced with murine IL-10. Adoptive transfer of the IL-10-transduced DO 11.10 splenocytes ameliorated OVA-induced arthritis, in spite of the presence of around 95% non-transduced cells. Using GFP as a marker for selection, the number of transferred cells needed to ameliorate the disease was able to be reduced to 10(4). Preferential accumulation of the transferred T cells was observed in the inflamed joint, and the improvement in the disease was not accompanied by impairment of the systemic immune response to the antigen, suggesting that the transferred T cells exert their antiinflammatory task locally, mainly in the joints where the antigen exists. In addition, IL-10-transduced DO 11.10 T cells ameriolated mBSA-induced arthritis when the arthritic joint was co-injected with OVA in addition to mBSA. These results suggest that T cells specific for a joint specific antigen would be useful as a therapeutic vehicle in rheumatoid arthritis for which the arthritic autoantigen is still unknown.

Animals↗

PubMed2000

Patients' desire to participate in decision-making in psychiatry: a questionnaire survey in Japan.

Japanese national sentiment has been described as paternalistic, which has potentially wide-ranging implications for the manner in which psychiatric patients should participate in medical decision-making. To examine the extent and possible determinants of the desire to participate in medical decision-making among Japanese people, we distributed a packet of questionnaires to 747 (nonmedical) university students and 114 of their parents. The questionnaires included an imaginary case vignette of psychotic depression. The participants were asked whether they would want various types of medical information, i.e., diagnosis, aetiology, treatment, outcomes, medical charts, etc., disclosed to them were they in such a psychiatric condition. Also included was the 1995 Scale for Independent and Interdependent Construal of the Self by Kiuchi. More than half of the participants wanted all the types of medical information disclosed to them. Those participants who wanted to have all types of information disclosed to them (n = 413) as compared to those who did not want to know at least one type of information (n = 445), tended to be male and to have an educational background in psychiatry (9.7% vs 5.4%) as well as an assertive attitude as indicated by a higher score on Independence on the Scale for Independence and Interdependent Construal of the Self. These results suggest that the Japanese in this sample are more likely to want to make an autonomous contribution to the psychiatric decision-making process and that less desire for information can be predicted by some demographic and personality factors.

Adolescent↗

PubMed2000

Reliability and validity of the Japanese version of the Temperament and Character Inventory.

The Temperament and Character Inventory was translated into Japanese, and, to confirm the psychometric properties of the inventory, three samples were recruited from a nonpatient population. In nonpatient population A (N = 555), the full version (240 items) of the inventory with dichotomous measuring, along with the General Health Questionnaire and the Social Desirability Scale, were distributed to the subjects. Factor analyses of the subscales showed that the factor structure of the inventory was consistent with Cloninger's theory. Correlations of the scale scores with the General Health Questionnaire and the Social Desirability Scale scores were almost negligible, indicating that the scale is resistant to the current psychopathology and response bias. In this and the other two university student samples (ns = 395 and 377), Cronbach coefficients alpha of the scale scores were substantially high except for the short version (125 items) of the inventory with dichotomous measures. The Japanese version of the inventory appears to have internal reliability and content and construct validity in a Japanese population.

Adolescent↗

PubMed2000

[The effects of sleep position change in sleep apnea syndrome].

Changing the sleep position from supine to non-supine is a simple but effective treatment for some patients with sleep apnea syndrome. In the present study, we compared the clinical data for good responders (GRs), those who responded well to the sleep position change, with those for poor responders (PRs), and also evaluated the effect of surgical treatment on the positional improvement of ventilation in the PR group. Forty-one adult patients with sleep apnea syndrome (mean age: 47.1 years, mean obesity index: 125.8%) were divided into two groups based on their polysomnographic responses to sleep position change. Thirty-two patients were classified as the GR group, whose apnea-hypopnea index (AHI) in the non-supine position declined to less than half of their AHI in the supine position, and nine whose non-supine AHI remained greater than half of their supine AHI were classified as the PR group. The AHI and the desaturation index (DI) for the PR group were significantly higher than those for the GR group, and the obesity index was also higher in the PR group. For the eight PRs who had surgical therapy, their polysomnographic data improved much more in the non-supine position than in the supine position. Of six patients whose total AHI was still 10 or more after surgery, four changed into GRs. The combination of surgery and sleep position change seemed to be an effective treatment even for patients with a little improvement before surgery.

Female↗

PubMed2000

Color Doppler sonography for evaluating response to transcatheter arterial embolization and percutaneous ethanol injection therapy and for detecting recurrence of hepatocellular carcinoma.

Eighty-six patients (mean age, 63 years) with 92 hepatocellular carcinomas (2.0 cm or greater in diameter; mean +/- SD, 3.5 +/- 1.6 cm) underwent color Doppler sonography before and after transcatheter arterial embolization and after subsequent percutaneous ethanol injection for (1) identification of pulsatile flow in the residual tumor area after transcatheter arterial embolization, (2) evaluation of therapeutic effectiveness of combined transcatheter arterial embolization and percutaneous ethanol injection, and (3) detection of recurrence during follow-up evaluation. Before and 2 weeks after transcatheter arterial embolization, color Doppler sonography revealed pulsatile flow in 76 (82.6%) and 43 (46.7%)lesions, respectively. After percutaneous ethanol injection, tumor stains in these lesions completely disappeared on digital subtraction angiography (gold standard). During follow-up study (3 to 45 months), digital subtraction angiography revealed recurrence in 73 patients (38 local recurrences and 19 new lesions [2.0 cm or greater]), whereas color Doppler sonography revealed pulsatile flow in 76.3% (local) and 63.2% (new) (not significant). Color Doppler sonography was useful for complying with our three objectives, especially for detecting local recurrence during follow-up evaluation.

Aged↗

PubMed2000

Constitutively active STAT5A and STAT5B in vitro and in vivo: mutation of STAT5 is not a frequent cause of leukemogenesis.

We recently identified several constitutively active forms of signal transducers and activators of transcription 5 (STAT5) using polymerase chain reaction-driven random mutagenesis followed by retrovirus-mediated expression screening. All constitutively active STAT5 showed constitutive phosphorylation on their tyrosine residues and induced factor-independent growth in a mouse interleukin-3-dependent cell line, Ba/F3. Sequence analysis of these active STAT5 revealed two important mutations: S710F and N642H. The N642H mutation localized in the SH2 domain was able to induce autonomous growth of Ba/F3 cells by itself, whereas S710F in the effector domain was able to induce autonomous growth of Ba/F3 cells in concert with a second mutation including H298R and E150G. Recently, constitutive activation of STAT5 has been reported in patients' leukemic cells and is implicated in leukemogenesis. We attempted to clarify whether leukemic cells harbored activating mutations primarily in STAT5 proteins, and analyzed the sequence of STAT5 derived from 49 leukemic patients. No mutations were found, however, in the regions surrounding S710 and N642 of STAT5A and corresponding residues of STAT5B. We also cloned full-length cDNAs for STAT5s from three patients whose leukemic cells exhibited constitutive tyrosine phosphorylation of the STAT5 protein and expressed the derived STAT5 proteins in Ba/F3 cells. However, none of these clones exhibited constitutive tyrosine phosphorylation or gave rise to FI proliferation of Ba/F3 cells. These results indicate that constitutive activation of STAT5 is a secondary event in most leukemias.

Animals↗

PubMed2000

Alcohol enhances lipopolysaccharide-induced increases in nitric oxide production by Kupffer cells via mechanisms dependent on endotoxin.

BACKGROUND: Ethanol causes both tolerance and sensitization of Kupffer cells. Accordingly, this study examines the effect of acute ethanol consumption on nitric oxide (NO) production from Kupffer cells with or without lipopolysaccharide (LPS) treatment. METHODS: Rats were given ethanol (4 g/kg body weight) intragastrically, and Kupffer cells were isolated 2 and 24 hr later. Some rats were treated for 4 days with 150 mg/kg/day of polymyxin B and 450 mg/kg/day of neomycin to prevent growth of intestinal bacteria, the primary source of endotoxin in the gastrointestinal tract. After addition of LPS, NO was measured by the Griess reaction. RESULTS: Two hours after ethanol administration, LPS-induced NO production by Kupffer cells was diminished by 50% but was enhanced 2-fold at 24 hr. Sterilization of the gut with antibiotics blocked this enhancement. CONCLUSIONS: Kupffer cells isolated from rats early after ethanol exhibited tolerance to LPS, whereas sensitization was observed later. It is likely that sensitization to Kupffer cell is caused by gut-derived endotoxin.

Animals↗

PubMed2000

Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) in hematopoietic cells.

Hematopoietic cell growth and differentiation are controlled by a number of cytokines. Ligand stimulation induces rapid phosphorylation of the tyrosine residues of the cytokine receptor and a variety of cellular molecules. Among them, Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) have recently been found to play a unique role in cytokine receptor-mediated intracellular signaling and hematopoietic cell development. Abnormal signaling of the JAK-STAT pathway results in hematopoietic disorders, including severe combined immunodeficiency and leukemia.

Animals↗

PubMed2000

Magnetic stimulation of the sacral roots for the treatment of stress incontinence: an investigational study and placebo controlled trial.

PURPOSE: We designed an investigational study and placebo controlled trial to evaluate the potential efficacy of magnetic stimulation of the sacral roots for the treatment of stress incontinence. MATERIALS AND METHODS: A total of 75 patients with stress incontinence were studied. A 15 Hz. repetitive magnetic stimulation of the sacral roots with 50% intensity output and duration of 5 seconds per minute was applied for 30 minutes. Urodynamic investigations under magnetic stimulation were performed in 13 patients to evaluate acute effects to lower urinary tract function. There were 62 women (mean age 58 years) enrolled in a placebo controlled study to investigate the short-term efficacy of magnetic stimulation. The number of leaks for 3 days, amount of urine loss on a pad test and quality of life score were evaluated before and 1 week after stimulation. RESULTS: The urodynamic investigations revealed an apparent elevation of urethral closure pressure induced by stimulation (mean 8.2 +/- 3.0 cm H2O, p = 0.0000004) and a significant increase in bladder capacity after stimulation (mean 40.0 +/- 51.0 ml., p = 0.0152). In the placebo controlled study the number of leaks and amount of urine loss on a pad test significantly decreased more in the active than in the sham stimulation group (p = 0.0023 and 0.0377, respectively). The quality of life score significantly improved in the active stimulation group (p = 0.0006) in contrast to no significant improvement in the sham stimulation group. The improvement rate in the active stimulation group was 74%, which was significantly higher than the 32% in the sham stimulation group (p = 0.0009). No adverse effects were noted in any patients. CONCLUSIONS: These results suggest that magnetic stimulation of the sacral roots may be useful for the treatment of stress incontinence. Further studies are needed to evaluate the long-term efficacy of this potential treatment.

Adult↗

PubMed2000

Higher prevalence and viral load of TT virus in saliva than in the corresponding serum: another possible transmission route and replication site of TT virus.

Although TT virus (TTV) is transmissible by blood or blood products, many patients with no history of transfusion of blood and blood products have been shown to be infected, suggesting other possible routes of transmission. To investigate the transmission routes and replication sites of TTV, 85 paired saliva and serum samples were studied by semi-nested polymerase chain reaction. The prevalence of TTV DNA was 38% (32/85 samples) and 21% (18/85) in saliva and serum, respectively. Fifteen patients had TTV DNA both in saliva and serum. Six out of fifteen patients had significantly higher viral titers in saliva than in serum, but none had higher titer in serum than in saliva. When the 222 base-pair nucleotide sequences of PCR products amplified from the samples were analyzed, 12 patients had the same genotype/subtype in saliva and serum and exhibited high homology (96-100%). The other 3 had different genotypes/subtypes in saliva and serum, and the homology was 61.9-87.2%. Mixed infection was observed both in saliva and serum. Further studies are required to determine if a subgroup of TTV has tropism to saliva. The high prevalence and viral load of TTV in saliva suggest that salivary fluid may be a possible route of transmission of TTV and that TTV might replicate not only in liver tissue but also in other tissues such as oropharyngeal tissues and/or salivary glands.

Aged↗

PubMed1999

A novel glycosyltransferase with a polyglutamine repeat; a new candidate for GD1alpha synthase (ST6GalNAc V)(1).

The fifth type GalNAcalpha2,6-sialyltransferase (mST6GalNAc V) was cloned from a mouse brain cDNA library. mST6GalNAc V exhibited type II transmembrane topology containing a polyglutamine repeat, which showed 42.6% and 44.8% identity to mouse ST6GalNAc III and IV, respectively. Northern blot analysis revealed that the mST6GalNAc V gene was specifically expressed in forebrain and cerebellum. mST6GalNAc V exhibited GD1alpha synthetic activity from GM1b the same as mST6GalNAc III and IV. The activity ratio of GM1b toward fetuin and the expression pattern were completely different among the three ST6GalNAcs. Interestingly, the polyglutamine repeat number was different from that of inbred mice. We report the first glycosyltransferase with a polymorphic polyglutamine repeat.

Amino Acid Sequence↗

PubMed1999

Regulation of nuclear translocation of forkhead transcription factor AFX by protein kinase B.

The regulation of intracellular localization of AFX, a human Forkhead transcription factor, was studied. AFX was recovered as a phosphoprotein from transfected COS-7 cells growing in the presence of FBS, and the phosphorylation was eliminated by wortmannin, a potent inhibitor of phosphatidylinositol (PI) 3-kinase. AFX was phosphorylated in vitro by protein kinase B (PKB), a downstream target of PI 3-kinase, but a mutant protein in which three putative phosphorylation sites of PKB had been replaced by Ala was not recognized by PKB. In Chinese hamster ovary cells (CHO-K1) cultured with serum, the AFX protein fused with green fluorescence protein (AFX-GFP) is localized mainly in the cytoplasm, and wortmannin induced transient nuclear translocation of the fusion protein. The AFX-GFP mutant in which all three phosphorylation sites had been replaced by Ala was detected exclusively in the cell nucleus. AFX-GFP was in the nucleus when the cells were infected with an adenovirus vector encoding a dominant-negative form of either PI 3-kinase or PKB, whereas the fusion protein stayed in the cytoplasm when the cells expressed constitutively active PKB. In CHO-K1 cells expressing AFX-GFP, DNA fragmentation was induced by the stable PI 3-kinase inhibitor LY294002, and the expression of the active form of PKB suppressed this DNA fragmentation. The phosphorylation site mutant of AFX-GFP enhanced DNA fragmentation irrespective of the presence and absence of PI 3-kinase inhibitor. These results indicate that the nuclear translocation of AFX is negatively regulated through its phosphorylation by PKB.

Animals↗

PubMed1999

Idiopathic pulmonary alveolar proteinosis as an autoimmune disease with neutralizing antibody against granulocyte/macrophage colony-stimulating factor.

Idiopathic pulmonary alveolar proteinosis (I-PAP) is a rare disease of unknown etiology in which the alveoli fill with lipoproteinaceous material. We report here that I-PAP is an autoimmune disease with neutralizing antibody of immunoglobulin G isotype against granulocyte/macrophage colony-stimulating factor (GM-CSF). The antibody was found to be present in all specimens of bronchoalveolar lavage fluid obtained from 11 I-PAP patients but not in samples from 2 secondary PAP patients, 53 normal subjects, and 14 patients with other lung diseases. It specifically bound GM-CSF and neutralized bioactivity of the cytokine in vitro. The antibody was also found in sera from all I-PAP patients examined but not in sera from a secondary PAP patient or normal subjects, indicating that it exists systemically in I-PAP patients. As lack of GM-CSF signaling causes PAP in congenital cases and PAP-like disease in murine models, our findings strongly suggest that neutralization of GM-CSF bioactivity by the antibody causes dysfunction of alveolar macrophages, which results in reduced surfactant clearance.

Autoantibodies↗

PubMed1999

STAT5 as a molecular regulator of proliferation, differentiation and apoptosis in hematopoietic cells.

Signal transducers and activators of transcription (STATs) play key roles in growth factor-mediated intracellular signal transduction. In the present study using a constitutively active STAT5 mutant, we show that STAT5 has pleiotropic functions regulating cell proliferation, differentiation and apoptosis in an IL-3-dependent Ba/F3 cell line. The mutant STAT5 possessed constitutive tyrosine phosphorylation and DNA binding activity, induced expression of bcl-xL and pim-1 in the absence of IL-3 in Ba/F3 cells, and rendered Ba/F3 cells factor-independent. Unexpectedly, IL-3 treatment of the factor-independent Ba/F3 cells expressing the constitutively active STAT5 resulted in apoptosis within 24 h, or differentiation followed by cell death. In these cells, mRNA expression of growth inhibitory genes downstream of STAT5 such as CIS, JAB/SOCS-1/SSI-1, and p21(WAF1/Cip1) was highly induced, correlating with prolonged hyper-phosphorylation of the mutant STAT5 after IL-3 stimulation. Of the STAT5-regulated genes, we found that constitutive expression of JAB/SOCS-1/SSI-1 was sufficient to induce apoptosis of Ba/F3 cells, while p21(WAF1/Cip1) could induce differentiation of these cells. In contrast, constitutive expression of pim-1 was sufficient to induce IL-3-independent growth of Ba/F3 cells. These findings suggest that a single transcription factor regulates cell fate by varying the intensity and duration of the expression of a set of target genes.

Animals↗

PubMed1999

Dominant negative forms of Akt (protein kinase B) and atypical protein kinase Clambda do not prevent insulin inhibition of phosphoenolpyruvate carboxykinase gene transcription.

Transcriptional regulation of phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme in hepatic gluconeogenesis, by insulin was investigated with the use of adenovirus vectors encoding various mutant signaling proteins. Insulin inhibited transcription induced by dexamethasone and cAMP of a chloramphenicol acetyltransferase (CAT) reporter gene fused with the PEPCK promoter sequence in HL1C cells stably transfected with this construct. A dominant negative mutant of phosphoinositide (PI) 3-kinase blocked insulin inhibition of transcription of the PEPCK-CAT fusion gene, whereas a constitutively active mutant of PI 3-kinase mimicked the effect of insulin. Although a constitutively active mutant of Akt (protein kinase B) inhibited PEPCK-CAT gene transcription induced by dexamethasone and cAMP, a mutant Akt (Akt-AA) in which the phosphorylation sites targeted by insulin are replaced by alanine did not affect the ability of insulin to inhibit transcription of the fusion gene. Akt-AA almost completely inhibited insulin-induced activation of both endogenous and recombinant Akt in HL1C cells. Furthermore, neither a kinase-defective mutant protein kinase Clambda (PKClambda), which blocked insulin-induced activation of endogenous PKClambda, nor a dominant negative mutant of the small GTPase Rac prevented inhibition of PEPCK-CAT gene transcription by insulin. These data suggest that phosphoinositide 3-kinase is important for insulin-induced inhibition of PEPCK gene transcription and that a downstream effector of phosphoinositide 3-kinase distinct from Akt, PKClambda, and Rac may exist for mediating the effect of insulin.

Cell Line↗

PubMed1999

Requirement for Akt (protein kinase B) in insulin-induced activation of glycogen synthase and phosphorylation of 4E-BP1 (PHAS-1).

The roles of Akt (protein kinase B) and the atypical lambda isoform of protein kinase C (PKClambda), both of which act downstream of phosphoinositide 3-kinase, in the activation of glycogen synthase and phosphorylation of 4E-BP1 (PHAS-1) in response to insulin were investigated. A mutant Akt (Akt-AA) in which the phosphorylation sites targeted by growth factors are replaced by alanine was shown to inhibit insulin-induced activation of both Akt and glycogen synthase in L6 myotubes. Expression of a mutant Akt in which Lys179 in the kinase domain was replaced by aspartate also inhibited insulin-induced activation of glycogen synthase but had no effect on insulin activation of endogenous Akt. A kinase-defective mutant of PKClambda (lambdaDeltaNKD), which prevents insulin-induced activation of PKClambda, did not affect the activation of glycogen synthase by insulin. Insulin-induced phosphorylation of 4E-BP1 was inhibited by Akt-AA in Chinese hamster ovary cells. However, lambdaDeltaNKD had no effect on 4E-BP1 phosphorylation induced by insulin. These data suggest that Akt, but not PKClambda, is required for insulin activation of glycogen synthase and for insulin-induced phosphorylation of 4E-BP1.

Amino Acid Sequence↗

PubMed1999

Transplacental administration of diethylstilbestrol (DES) causes lesions in female reproductive organs of Donryu rats, including endometrial neoplasia.

The effects of transplacental administration of diethylstilbestrol (DES) on female reproductive organs were investigated using Donryu rats. The animals were given subcutaneous injections of DES dissolved in olive oil at doses of 0.01 or 0.1 mg/kg on days 17 and 19 of gestation. In female offspring, clinical signs, body weights and estrous cycles were continuously assessed until all survivors were killed at month 18. A low mean litter size and shortening of period of pregnancy were recognized in the 0.1 mg/kg group. Disorder and/or suspension of the estrous cycle (so called persistent estrus) also appeared very early in the 0.1 mg/kg group. Macroscopically, the incidences of hypoplasia of the oviduct, cystic dilatation of the uterus and small size of the uterine cervix were higher in the 0.1 mg/kg group than those in the control group. Histologically, in the ovary, the incidence and degree of atrophy were increased in both 0.01 and 0.1 mg/kg groups. In the uterus, total incidences of endometrial hyperplasias were about the same in all groups. However, endometrial adenocarcinomas were dose-dependently increased in the treated groups, the incidence in the 0.1 mg/kg group being significant, compared to that in the control. In the vagina, mucification was more prominent in the treated animals, especially at the higher dose, but no tumors were observed. The present results indicate that prenatal exposure to DES can produce uterine adenocarcinomas in rats, as reported earlier for mice, although its carcinogenic activity is not so strong. Increase of endometrial adenocarcinoma incidence might depend on hormonal imbalance resulting from the ovarian atrophy due to transplacental treatment of DES.

Adenocarcinoma↗