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Biomedical subjects

T Kishimoto

Publications and source records attributed to T Kishimoto.

At least 145 records · Page 8Linked to original sources

Forced expression of terminal deoxynucleotidyl transferase in fetal thymus resulted in a decrease in gammadelta T cells and random dissemination of Vgamma3Vdelta1 T cells in skin of newborn but not adult mice.

The repertoire of lymphocyte receptor genes encoded in a germline is further diversified by a number of processes, including the template-independent addition of nucleotides (N regions) by means of terminal deoxynucleotidyl transferase (TdT). Normally, mouse gammadelta T cells in the early fetal thymus, whose T-cell receptor (TCR) genes lack N regions and are encoded by Vgamma3-Jgamma1 and Vdelta1-Ddelta2-Jdelta2 with canonical junctions (invariant Vgamma3Vdelta1), are thought to be the precursors of dendritic epidermal T cells (DETC). We generated mutant mice whose endogenous TdT promoter was replaced with the lck promoter through homologous recombination. These mutant mice expressed TdT in fetal thymus, had abundant N regions and infrequent canonical junctions in gamma and delta rearrangements, and showed a decreased number of gammadelta T cells. Various Vgamma3Vdelta1 T cells, most of which had N regions in their TCR genes, were found to disseminate in the skin of newborn mutant mice, whereas normal numbers of DETCs with the invariant Vgamma3Vdelta1 rearrangement were observed in adult mutants. These data demonstrate that the regulation of TdT expression during fetal development is important for the generation of gammadelta T cells, and that Vgamma3Vdelta1 T cells, which have various junctional sequences in their TCR genes, randomly disseminate in skin, but invariant Vgamma3Vdelta1 T cells have a great advantage for proliferation in skin.

Animals↗

Cytokines and their receptors in cardiovascular diseases--role of gp130 signalling pathway in cardiac myocyte growth and maintenance.

Interleukin (IL)-6-related cytokines share gp130 as the signal-transducing protein. Cardiac myocytes produce various kinds of cytokines including IL-6 and cardiotrophin-1. Activation of gp130 transduces hypertrophic and cytoprotective signals in cardiac myocytes via JAK/STAT, MAP kinase and PI-3 kinase pathways. Besides various well-established mechanisms by which cardiac growth and myocardial remodeling are regulated, gp130 signalling may be a newly discovered mechanism that regulates these events in association with cytoprotective effect in myocardial diseases.

Animals↗

Renal cell carcinoma in an L-shaped kidney.

A 64-year-old man with a chief complaint of an asymptomatic abdominal mass was diagnosed as having a renal cell carcinoma in his L-shaped kidney. He was successfully treated with partial nephrectomy following selective embolization of the feeder artery. It is thought to be the first reported case of renal cell carcinoma occurring in an L-shaped kidney.

Angiography↗

Comparative study of transurethral laser prostatectomy versus transurethral electroresection for benign prostatic hyperplasia.

BACKGROUND: Transurethral resection of the prostate (TURP) is the gold standard treatment for benign prostatic hyperplasia (BPH). Recently, less invasive transurethral laser prostatectomy, such as visual laser ablation (VLAP) or interstitial laser coagulation (ILCP), have been developed. Herein, we investigated the efficacy of VLAP and ILCP compared to TURP. METHODS: A total of 80 patients with BPH were treated: 20 patients by VLAP, 30 patients by ILCP and 30 patients by TURP. All patients were followed up for 12 months after their operations. Treatment outcomes were evaluated by four different criteria: (i) the International Prostatic Symptom Score (I-PSS), (ii) the maximum flow rate (Qmax), (iii) postvoided residual urine volume before treatment and one, three, six and 12 months after treatment, and (iv) prostatic volume before operation and three and six months postoperatively. RESULTS: The I-PSS, Qmax and residual urine volume were significantly improved compared to baseline levels and the improvement continued for 12 months in the three groups: for I-PSS (P<0.001 in the VLAP group and P<0.0001 in the ILCP and TURP groups), Qmax (P<0.001 in the VLAP and ILCP groups, and P<0.0001 in the TURP group), residual urine volume (P<0.01 in the VLAP group and P<0.0001 in the ILCP and TURP groups). Significant reduction of the prostatic volume was recorded only in the ILCP and TURP groups (P<0.001). CONCLUSION: Visual laser ablation and ILCP can be good alternative treatments for BPH. Visual laser ablation provides good outcomes in patients with small-sized BPH and with risk factors such as heart disease or anticoagulation therapy.

Aged↗

A comparative study of terazosin and tamsulosin for symptomatic benign prostatic hyperplasia in Japanese patients.

OBJECTIVE: To compare the efficacy and safety of an incremental-dose regimen of terazosin (1-2 mg daily) and a fixed-dose regimen of tamsulosin (0.2 mg daily), on Japanese patients with symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: This multicentre, single-blind, randomized trial compared terazosin and tamsulosin over 4 weeks, in 61 patients with symptomatic BPH randomly assigned to terazosin (n = 31) or tamsulosin (n = 30). Terazosin 0.5 mg twice daily was administered for 2 weeks, followed by 1 mg twice daily for 2 weeks. Tamsulosin (0.2 mg) was administered once daily for 4 weeks. Symptoms were evaluated using the International Prostate Symptom Score (IPSS), and quality of life (QOL) was assessed subjectively before treatment, and again after 2 and 4 weeks of treatment. Objective measurements taken before and after the treatment period were the maximum (Qmax) and average (Qave) urinary flow rates, and the percentage residual urine volume. Improvement was defined as a 25% decrease from baseline in IPSS, > 1 point increase in QOL score, and > 2.5 mL/s increase in Qmax. Adverse reactions potentially related to the study drugs were recorded throughout the treatment period. RESULTS: Both terazosin and tamsulosin produced statistically significant improvements in subjective and objective variables. Neither treatment affected systolic or diastolic blood pressure or pulse rate. Adverse reactions were noted in four patients (three in the terazosin group and one in the tamsulosin group). However, there was no statistically significant difference in the incidence of adverse effects between the groups. CONCLUSIONS: Despite the limitations of small sample size and relatively short treatment periods, terazosin and tamsulosin were equally effective in the treatment of symptomatic BPH in Japanese patients, using relatively lower doses than those used in Western countries.

Adrenergic alpha-Antagonists↗

Astrocyte differentiation of fetal neuroepithelial cells by interleukin-11 via activation of a common cytokine signal transducer, gp130, and a transcription factor, STAT3.

The interleukin (IL)-6 family cytokines utilize membrane glycoprotein gp130 in common as a critical signal-transducing receptor component. IL-11, a cytokine initially identified as a plasmacytoma growth factor, belongs to this family. We show here that IL-11 and its cognate receptor components are expressed in fetal mouse neuroepithelial cells. We also show that after 4 days of culture with IL-11, cells with typical astrocytic morphologies expressing glial fibrillary acidic protein (GFAP; a marker for astrocytes) come out. This differentiation process is totally dependent on the gp130-mediated signal-transduction pathway involving activation of a latent cytoplasmic transcription factor, STAT3 (for signal transducer and activator of transcription 3), because (a) IL-11-induced astrocyte differentiation is not observed when neuroepithelial cells prepared from gp130-deficient mice were used, (b) stimulation of neuroepithelial cells by IL-11 rapidly induces tyrosine-phosphorylation of STAT3, and (c) transfection of neuroepithelial cells with a dominant-negative form of STAT3 inhibits IL-11-induced activation of the GFAP gene promoter. We have further identified, in the GFAP promoter region, a STAT3 site at which nucleotide substitutions almost completely abolished the IL-11-induced GFAP promoter activation. Taken together, it is suggested that IL-11 contributes to astrocytogenesis in fetal brain via activation of gp130 and STAT3.

Animals↗

Persimmon leaf extract and astragalin inhibit development of dermatitis and IgE elevation in NC/Nga mice.

BACKGROUND: We previously found that persimmon leaf extract contains antiallergic substances that inhibit histamine release by human basophilic cell line KU812 in response to cross-linkage of FcepsilonRI. OBJECTIVES: The purpose of this study was to identify substances in the persimmon leaf extract that are responsible for the effect and to examine their in vivo effects on the allergic mouse model. METHODS: HPLC analysis of persimmon leaf extract was done to measure its content. Inhibitory activity of persimmon leaf extract or its major constituent of flavonoids (astragalin) on the histamine release by KU812 cells was examined. To investigate the effects of these substances in vivo, models of passive cutaneous anaphylaxis and atopic dermatitis mice (NC/Nga) were used. RESULTS: Persimmon leaf extract or astragalin inhibited histamine release from KU812 in response to cross-linkage of FcepsilonRI. Oral intake of both substances dose dependently inhibited passive cutaneous reactions. Moreover, oral administration of these substances to NC/Nga atopic dermatitis-model mice led to a striking suppression of the development of dermatitis, scratching behavior, and serum IgE elevation. Histologic analyses revealed that infiltration of inflammatory cells, especially degranulated mast cells, thickening of the epidermis, and prominent hyperkeratosis, were significantly reduced. Immunologic studies showed that the capacity of spleen T cells to produce both IL-4 and IL-13, but not IFN-gamma, was downregulated by means of oral intake of these substances. CONCLUSION: This study demonstrates a novel activity of astragalin and the dramatic effect of persimmon leaf extract and astragalin on atopic dermatitis-model mice.

Administration, Oral↗

Reconstruction of hip abduction using free muscle transplantation: a case report and description of the technique.

The authors describe a free-functioning latissimus dorsi muscle transplantation for reconstruction of hip abduction. A radical "buttockectomy" was performed on a 62-year-old patient with recurrent soft-tissue sarcoma. The patient received a muscle transplantation immediately after resection of the tumor. Until recovery of the muscle, a complete absence of hip abductors resulted in a marked lurch in the patient's gait, requiring him to use walking aids. Reinnervation of the muscle was confirmed via electromyography 6 months after surgery. Hip abduction was restored along with muscle recovery, and walking support was no longer required. Although the strength of the muscle was not sufficiently powerful to overcome gravity fully, the latissimus dorsi muscle improved markedly the performance of an otherwise unstable hip. This patient demonstrates that microsurgical reconstruction is of great value in enhancing the functional outcome of a salvaged limb after tumor surgery.

Biomechanical Phenomena↗

p53 status in multiple human urothelial cancers: assessment for clonality by the yeast p53 functional assay in combination with p53 immunohistochemistry.

Multifocal synchronous or metachronous tumor development is a common observation in human urothelial cancer cases. However, the underlying mechanism has remained obscure. We have employed a new tool to investigate the p53 gene status, the yeast p53 functional assay, in combination with immunohistochemistry in a total of 50 tumor samples from 32 cases with urothelial cancers, including 8 with multiple synchronous tumor development and 2 demonstrating metachronous tumors. p53 mutations were found in 13 cases (9 with missense mutations, 3 with deletion, 1 with splicing mutation) by the yeast p53 functional assay. p53 protein overexpression was seen in all 9 cases with missense mutations, but in only one of the 4 cases with nonsense mutations. Two tumors without p53 mutation also showed positive p53 immunoreactivity. Overall, p53 abnormalities including mutations and/or protein overexpression were found in 15 (47%) cases. p53 abnormalities were significantly more frequent in non-papillary and in high grade tumors. Loss of the wild type allele in addition to a p53 mutation was suggested in 8 of the 15 (53%) cases. All 4 cases with mutations in multiple synchronous tumors had identical p53 mutations in the separate urothelial cancers, strongly suggestive of monoclonality. The one case with multiple metachronous tumors, in contrast, was characterized by variation in the p53 status, indicative of different clonal origins. In conclusion, combined assessment for p53 status as used here (yeast p53 functional assay plus immunohistochemistry) may provide insights into the molecular mechanisms of urothelial carcinogenesis.

Adult↗

Chemopreventive effects of bovine lactoferrin on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced rat bladder carcinogenesis.

Chemopreventive effects of bovine lactoferrin (bLF), which is found at high concentrations in colostrum, on rat bladder carcinogenesis were investigated using a rat bladder medium-term bioassay. In experiment 1, a total of 80 F344 male rats, 6 weeks old, were divided into 5 groups. Groups 1 and 2 were treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in the drinking water for 8 weeks and after a 1-week interval, received dietary supplementation with 2% and 0.2% bLF, respectively. Group 3 received 0.05% BBN for 8 weeks and then no treatment. Group 4 was administered 2% bLF alone from week 9, without prior carcinogen exposure. Group 5 was maintained without any treatment throughout the experiment. All rats were killed at the end of week 36. Group 1 demonstrated a significantly decreased multiplicity of the bladder tumors (carcinomas and papillomas) as compared with group 3. Maximum cut surface areas of bladder tumors were also significantly decreased in groups 1 and 2 compared with group 3. No bladder tumors were observed in groups 4 or 5. In experiment 2, a total of 60 rats were divided into two groups (30 rats each); both were treated with 0.05% BBN for 4 weeks and after a 1-week interval, one received 2% bLF (group 1) and the other, basal diet (group 2) for 4 weeks. Group 1 demonstrated a tendency for decrease of the 5-bromo-2'-deoxyuridine (BrdU) labeling index. bLF was detected in the urine of rats fed bLF by ELISA as well as western blot analysis. The findings indicate that 2% bLF can inhibit BBN-induced rat bladder carcinogenesis, and that this may be due to bLF in the urine.

Acetyltransferases↗

Anti-interleukin 6 receptor antibody treatment in rheumatic disease.

Interleukin 6 (IL6) is a pleiotropic cytokine with a wide range of biological activities. IL6 transgene into mice gives rise to the abnormalities such as hypergammaglobulinaemia, thrombocytosis, infiltration of inflammatory cells into the tissues, mesangial cell proliferation of the kidney as well as splenomegaly and lymphadenopathy, which are predictable by the biological functions of IL6 shown in vitro. Continuous overproduction of IL6 is observed in patients with some immune-inflammatory diseases such as Castleman's disease and rheumatoid arthritis that are frequently associated with similar abnormalities to those of IL6 transgenic mice, strongly suggesting the involvement of IL6 in the human diseases. Successful treatment of the model animals for immune-inflammatory diseases with anti-IL6 receptor (IL6R) antibody thus indicates the possible application of IL6 blocking agents to treat the IL6 related immune-inflammatory diseases of humans. In this review, the new therapeutic strategy for Castleman's disease and RA using humanized antibody to human IL6 receptor, MRA, is discussed.

Animals↗

Brain-derived neurotrophic factor-induced phosphorylation of neurofilament-H subunit in primary cultures of embryo rat cortical neurons.

Phosphorylation of the neurofilament-H subunit (NF-H) was investigated in rat embryonic brain neurons in culture. A portion of the NF-H was phosphorylated in vivo at embryonic day 17 when brain neurons were prepared. When the neurons were isolated and cultured, the NF proteins disappeared once and then reappeared over the next several days in the following order: (1) NF-L/NF-M, (2) dephosphorylated NF-H and (3) phosphorylated NF-H. Phosphorylation of NF-H began around 4 days after cell plating, at about the time of synapse formation. Treatments that appeared to modulate the timing of synapse formation also affected the timing of NF-H phosphorylation: (1) earlier phosphorylation was observed at higher neuronal cell density, (2) earlier phosphorylation was observed in neurons cultured on a coating substrate that promotes rapid neurite extension and (3) phosphorylation was suppressed when neurite extension was inhibited by brefeldin A. Three possible synapse formation-induced events, excitation, cell-cell contact through adhesion proteins and elevated concentrations of neurotrophic factors, were examined for their possible involvement in generating the signal for NF-H phosphorylation. Neither excitation nor cell contact enhanced NF-H phosphorylation. Neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) stimulated phosphorylation of NF-H. The BDNF-stimulated phosphorylation was inhibited by an anti-BDNF antibody and K252a, an inhibitor of BDNF receptor TrkB tyrosine kinase. Among known NF-H kinases of cyclin-dependent kinase 5 (CDK5), external signal-regulated protein kinase (ERK) and stress-activated protein kinase (SAPK), CDK5 and SAPK showed an increase in kinase activity or an active form with a time course similar to NF-H phosphorylation in control culture. On the other hand, BDNF stimulated the kinase activity of CDK5 and induced appearance of an active form of ERK transiently. These results suggest a possibility that synapse formation induces NF-H phosphorylation, at least in part, through activation of CDK5 by BDNF.

Animals↗

Ser787 in the proline-rich region of human MAP4 is a critical phosphorylation site that reduces its activity to promote tubulin polymerization.

p34cdc2 kinase-phosphorylation sites in the microtubule (MT)-binding region of MAP4 were determined by peptide sequence of phosphorylated MTB3, a fragment containing the carboxy-terminal half of human MAP4. In addition to two phosphopeptides containing Ser696 and Ser787 which were previously indicated to be in vivo phosphorylation sites, two novel phosphopeptides, containing Thr892 or Thr901 and Thr917 as possible phosphorylation sites, were isolated, though only in in vitro phosphorylation. The role of phosphorylation at Ser696 and Ser787, which were differently phosphorylated during the cell cycle (Ookata et al., (1997). Biochemistry, 36: 15873-15883), was investigated in MT-polymerization, using MAP4 Ser to Glu mutants, which mimic phosphorylation at each site. Mutation of Ser787 to Glu strikingly reduced the MAP4's MT-polymerization activity, while Glu-mutation at Ser696 did not. These results suggest that Ser787 could be the critical phosphorylation site causing MTs to be dynamic at mitosis.

Amino Acid Sequence↗

Percutaneous balloon pericardiotomy by the use of Inoue balloon for the management of recurrent cardiac tamponade in a patient with lung cancer.

A 32-year-old man with lung cancer involving pericarditis carcinomatosa underwent pericardiotomy, using an Inoue balloon dilating catheter, to create a non-surgical pericardial window. The procedure was performed from the thoracic wall to the left pleural effusion and parietal pericardium under local anesthesia. The effects of non-surgical pericardial window had been maintained until this patient died from his primary disease. It is concluded that percutaneous balloon pericardiotomy is helpful in the management of massive pericardial effusions particularly in patients with malignancies and poor clinical condition

Adenocarcinoma↗

The characteristics of fatigue symptoms and their association with the life style and the health status in school children.

In order to evaluate the characteristics of fatigue symptoms and their association with the life style and the health status, we examined using data accumulated by the longitudinal surveys from 1992 to 1998, in 118 six-year primary school children and 129 second-year junior high school children. The complaints of "drowsiness and dullness", such as "become drowsy" (71%), "give a yawn" (59%) and "want to lie down" (51%), respectively, were most frequently observed. The proportion of these complaints was high before the first morning class, but decreased when the children leave school. Notably, the complaints of "difficulty in concentration" annually have increased. Children with undesirable eating habits, particularly those who often eat salty foods, or poor life style, such as staying up late at night tended to have more complaints of fatigue symptoms. By correlation analysis, these complaints were significantly related to the obesity degree, blood pressure, HDL cholesterol and atherogenic index. These results support the hypothesis that fatigue symptoms increase or are associated with life style and health status. Consequently, it is necessary to improve the life style such as dietary habits and rhythm of life for the reduction of fatigue symptom.

Child↗

Chromosome mapping and expression of human tip49 family genes.

TBP-interacting protein 49 (TIP49) was originally identified as a TBP-binding protein, and two related proteins are encoded by individual genes, tip49a and b. Although the function of this gene family has not been elucidated, they are supposed to play a critical role in nuclear events because they interact with various kinds of nuclear factors and have DNA helicase activities. At least, TIP49a has been suggested to act as an autoantigen in some patients with autoimmune diseases. In this study, we investigated the chromosome positions of this family of genes. Human tip49a and tip49b genes were mapped on 3q21 and 19q13.2, respectively. Consistent with the notion that tip49 family genes are essential for cell growth, Northern blot analysis demonstrated that both genes are expressed ubiquitously in human tissues. It is worthy of notice that the testes contained large amounts of the both transcripts. These results are consistent with our previous results from tissue distribution analysis for of TIP49 proteins.

ATPases Associated with Diverse Cellular Activitie↗

[Color Doppler ultrasonography in the diagnosis of the acute scrotum].

PURPOSE: To determine the value of color Doppler ultrasonography (CDUS) in the diagnosis of acute scrotum. MATERIALS AND METHODS: 10 patients referred to our hospital with acute scrotal pain were included in this study. All patients were evaluated with CDUS after the initial clinical examinations. Blood flow of the involved testis was compared semiquantitatively to that of the opposite testis. Patients with a diagnosis of testicular torsion by CDUS underwent surgical exploration. Patients with CDUS diagnosis of epididymitis were treated with intravenous antibiotics. RESULTS: Of the 10 patients evaluated, CDUS diagnosed 5 patients with testicular torsion and 5 patients with epididymitis. All cases of torsion were confirmed intraoperatively. 2 cases with no intratesticular blood flow on CDUS had necrotic testes and underwent orchiectomy with orchiopexy of the contralateral testes. A case with absent flow and 2 cases with decreased flow had bilateral orchiopexy. CDUS findings of normal or increased flow were present in all patients with epididymitis. No cases of testicular atrophy were encountered on long-term follow up in patients with epididymitis. CONCLUSION: CDUS is helpful in detecting the perfusion of the testis as well as in getting anatomical information. CDUS is a very useful device which causes a minimal burden to the patient with acute scrotum. In most cases it will rapidly provides us the correct information although it may not be regarded as the definitive adjunct.

Acute Disease↗