Biomedical subjects

T Kawakami

Publications and source records attributed to T Kawakami.

At least 73 records · Page 4Linked to original sources

PubMed2001

X-linked dilated cardiomyopathy with a large hot-spot deletion in the dystrophin gene.

A 36-year-old Japanese man was hospitalized with coughing and exertional dyspnea (NYHA class I). He was diagnosed as having congestive heart failure, and was treated with diuretics and a beta-adrenergic blocking agent. He responded well to the treatment and his symptoms completely disappeared within a few days. Based on his clinical, laboratory, and molecular genetic findings, he was diagnosed as having X-linked dilated cardiomyopathy (XLDCM). He was found to have a large deletion in the dystrophin gene, involving exons 45-55. This is the first report on a Japanese XLDCM patient with a mutation in the central hot-spot region of this gene.

Adult↗

PubMed2001

Acute changes in bronchoconstriction influences exhaled nitric oxide level.

In previous studies the exhaled nitric oxide (NO) level of asthma patients was investigated only in association with bronchial inflammation, and whether the degree of bronchoconstriction itself influences the exhaled NO level has never been investigated. We therefore evaluated the effect of inhalation of a bronchoconstrictor (methacholine) or a bronchodilator (salbutamol) on the exhaled NO level of healthy volunteers and asthma patients. The exhaled NO level of the healthy volunteers decreased after methacholine inhalation. The exhaled NO level of patients with mild or moderate persistent asthma, who had no asthma attacks on the day of measurement, increased after salbutamol inhalation, and the exhaled NO level of asthma patients during asthma attacks increased after salbutamol inhalation followed by intravenous drip infusion of aminophylline. It is suspected that large amounts of NO are trapped in the lung distal to the constricted airway, contributing little to the exhaled NO level at the mouth. However, we expect that the trapped NO is exhaled at a larger fraction after the dilatation of the constricted small airway, thereby increasing the exhaled NO level at the mouth. In conclusion, the results of this study suggest that acute changes in bronchoconstriction themselves influence the exhaled NO level independently of the change in NO synthase activity associated with airway inflammation.

Adult↗

PubMed2001

Prognostic impact of CD45 antigen expression in high-risk, childhood B-cell precursor acute lymphoblastic leukemia.

To evaluate the clinical implications of CD45 expression in acute childhood lymphoblastic leukemia (ALL), we measured the CD45 expression of blast cells from 133 untreated patients with childhood B-precursor ALL (n = 118) or T-ALL (n = 15). CD45 expression (> or = 20%) was detected in all 15 cases (100%) of T-ALL, and 101 cases (86%) of B-precursor ALL. In 122 cases, the fluorescence intensity of the CD45 expression was measured as a relative value; the ratio of average linear values (RALV) of CD45 on the blasts to that on CD3-positive T-lymphocytes from the same specimen. The expression was more intense in the T-ALL cases than in the B-precursor ALL cases (RALV, mean +/- SE: T-ALL 0.230 +/- 0.04 vs. pro-B ALL 0.150 +/- 0.012/pre-B ALL 0.153 +/- 0.019, p < 0.05). However, the intensity of the CD10, CD19, CD20 and CD34 antigen immunoreactivity did not correlate with the CD45 expression. Patients with hyperdiploidy (chromosome number > 50) showed significantly lower levels of CD45 expression than patients with t(1;19) or normal karyotypes (RALV, mean +/- SE: 0.081 +/- 0.022 vs. 0.133 +/- 0.03/0.143 +/- 0.019, p < 0.05). Other clinical features such as age, gender and WBC count did not correlate with CD45 expression. The prognostic implications of CD45 expression were studied in non-high-risk (low-risk + intermediate-risk) (n = 60) and high-risk patients (n = 52) with B-precursor ALL who had been treated with the risk-directed protocol of ALL-941 trial. Although CD45 expression did not correlate with the event-free survival (EFS) of the non-high-risk patients, there was a significant correlation between the expression levels and the EFS of the high-risk patients: the 3-year EFS rate of the CD45low group (n = 26, RALV = 0.017-0.132) was 88 +/- 7% versus the CD45high group (n = 26, RALV = 0.133-0.450) at 34 +/- 24% (p < 0.05). These results show that the levels of expression of the CD45 antigen on leukemic lymphoblasts are significantly correlated with the clinical features and prognosis of childhood ALL.

Antigens, CD↗

PubMed2001

Gene expression of angiogenesis related factors in glioma.

Angiogenesis plays an important role in growth and proliferation of cancer. Various angiogenic and angiostatic factors regulate angiogenesis. In this study, we examined gene expression of the angiopoietin family including angiopoietin 1 (Ang1) and angiopoietin 2 (Ang2) in 39 gliomas and 5 glioma-xenografts by RT-PCR. Ang1 and Ang2 genes were expressed in 54%, and 77% of gliomas, respectively. The expression of Ang1 was significantly correlated with the expression of Ang2. Both Ang1 and Ang2 were shown to be expressed in the glioma cells. Ang2 gene expression was correlated with VEGF gene expression. Angiopoietin molecules may synergistically cooperate in growth and vascularization in glioma.

Angiopoietin-1↗

PubMed2001

Interleukin 10 expression is correlated with thrombospondin expression and decreased vascular involvement in colon cancer.

Interleukin 10 (IL-10) is an immuno-suppressive cytokine produced by T-lymphocytes, and a regulatory molecule for angiogenesis in various cancers. We examined IL-10 gene expression in 53 colon cancer patients who underwent surgical resection. IL-10 gene expression was correlated with TSP1 and TSP2 gene expression (P=0.0049, P=0.0285). Colon cancer with IL-10 gene expression (19/53) showed significantly decreased venous involvement (P=0.0433). The mean vessel counts in the colon cancers with IL-10 gene expression were significantly lower than those without IL-10 gene expression (P<0.001). These results suggested that IL-10 stimulates angiostatic factor gene expression, and results in suppression of venous involvement.

Adenocarcinoma↗

PubMed2001

[Perioperative management of three patients with streptococcal toxic shock syndrome].

We report the perioperative management of three patients with streptococcal toxic shock syndrome (STSS) caused by group A streptococcal infection. Three of two patients survived but one patient died from multiple organ dysfunction in spite of vigorous treatments. These patients required the treatments including administration of antibiotics, circulatory and respiratory care, surgical debridement, anticoagulant therapy for disseminated intravascular coagulation and hemofiltration. The early diagnosis and surgical intervention play a key role in the successful management of this syndrome because it has a rapid course and frequent fatal outcome. The anesthetic management of these patients should be targeted to maintain perfusion of the vital organs and to control the blood clotting disorders.

Adult↗

PubMed2001

[A case of fatal herpes encephalitis presenting massive cerebral hematoma].

A 53-year-old woman was admitted to the hospital because of headache and disturbance of consciousness. She was afebrile. No inflammatory reaction was identified on serologic examination. Radiological findings showed acute-subacute, massive intracerebral hemorrhage in the right temporal lobe, compressing the brain stem contra-laterally. On the day of admission, she underwent a right temporal craniotomy for the removal of the mass lesion. The resected brain tissue demonstrated a small hemorrhage and edema accompanied by the infiltration of lymphoid cells into the subarachnoid space. Several days after surgery, the patient became lethargic and showed urinary incontinence. Late onset of fever and CSF findings suggested she was suffering from viral encephalitis. Serological findings, however, disclosed no antibody production against HSV, HZV, or CMV. For the diagnosis, a biopsy of the brain was carried out and herpes encephalitis was subsequently proved. Unfortunately, her condition deteriorated quickly and she died without anti-viral treatment.

Aged↗

PubMed2001

Metabolism of 99mTc-ethylcysteinate dimer in infarcted brain tissue of rats.

UNLABELLED: Brain SPECT with 99mTc-ethylcysteinate dimer (99mTc-ECD) reveals a subacute cerebral infarct as a hypoactive area, even in the presence of postischemic hyperperfusion. The brain retention of 99mTc-ECD depends on hydrophilic conversion mediated by enzymes, and impaired enzymatic trapping is hypothesized to depress the retention efficiency in the infarcted region. The aim of this study was to determine whether the metabolic rate of 99mTc-ECD is actually reduced in infarcted brain tissue. METHODS: In 50 mmol/L phosphate buffer (pH 7.4), 99mTc-ECD was incubated for 30 min with homogenates of rat brain tissue with and without triphenyltetrazolium chloride (TTC) staining. The ratio of polar products was determined by thin-layer chromatography as a function of incubation time, and metabolic rates were obtained. Permanent focal ischemia was induced by occlusion of the right middle cerebral artery (MCA) in rats. The brain was removed 24 h after MCA occlusion, and the infarcted area was defined by TTC staining. The metabolic rate of 99mTc-ECD was determined in homogenates of infarcted tissue, contralateral noninfarcted tissue, and tissue sampled from sham-operated rats. The infarct volume was measured by direct and indirect methods to assess volume expansion caused by edema, and the metabolic rate in infarcted tissue was corrected for the effect of edema. RESULTS: TTC staining had no effect on the metabolic rate of 99mTc-ECD. The metabolic rates in the infarcted tissue were 0.222%/min +/- 0.054%/min and 0.285%/min +/- 0.064%/min before and after correction for edema, respectively. These rates were significantly lower than those in the contralateral noninfarcted tissue (0.426%/min +/- 0.028%/min) and the tissue sampled from the sham-operated rats (0.439%/min +/- 0.031%/min). No substantial difference in rates was observed between the contralateral tissue and the tissue from the sham-operated rats. CONCLUSION: The results of this study showed that infarction decreases the activity of enzymes that mediate the hydrophilic conversion of 99mTc-ECD in the brain and suggest that reduced metabolic activity is related to decreased accumulation of 99mTc-ECD in hyperperfused infarcts.

Animals↗

PubMed2001

Expression patterns of cancer testis antigens in testicular germ cell tumors and adjacent testicular tissue.

PURPOSE: The human cancer-testis antigens (CTAs) are a group of tumor specific antigens recognized by cytotoxic T lymphocytes whose expression occurs in human malignancies as well as in normal testicular tissue. We studied a series of CTA gene transcripts in testicular germ cell tumors of various histological types to test the hypothesis that the expression of CTA in testicular germ cell tumors reflects developmental stages of tumorigenesis rather than constitutive tumor antigens recognized by cytotoxic T lymphocytes. MATERIALS AND METHODS: Total RNA was obtained from 31 primary and 3 metastatic testicular germ cell tumors, and 11 parenchymal tissues adjacent to the testicular germ cell tumors. We performed an expression study of the CTA genes MAGE-A, MAGE-B, GAGE, PAGE-1, HOM-MEL-40 (SSX2), NY-ESO-1, LAGE-1 and SCP-1 in these samples using reverse transcriptase-polymerase chain reaction. RESULTS: The results showed that expression patterns of CTA genes depended on the histological differentiation of the testicular germ cell tumors. Overall CTA expression was more common in seminomas than in nonseminomatous germ cell tumors. Specifically all 13 seminomas (100%) demonstrated the positive expression of MAGE-B1 and MAGE-B2, while 3 of 17 nonseminomatous germ cell tumor samples (18%) showed positive expression of these genes. All 5 teratomatous elements (100%) had homogenous null expression with regard to all CTA genes examined. In addition, we detected deficiencies in CTA expression in 7 of 11 parenchymal tissues adjacent to the testicular germ cell tumors (64%). CONCLUSIONS: These data support the idea that CTA transcripts in testicular germ cell tumors serve as developmental footprints of testicular germ cell tumors rather than as constitutive tumor antigens recognized by cytotoxic T lymphocytes.

Antigens, Neoplasm↗

PubMed2001

Significant correlation between interleukin 10 expression and vascularization through angiopoietin/TIE2 networks in non-small cell lung cancer.

The expression of interleukin 10 (IL-10) is correlated with clinical prognosis in non-small cell lung cancer [NSCLC (H. Hatanaka et al., ANN: ONCOL:, 11: 815--819, 2000)]. However, the effects of IL-10 expression on vascularization in NSCLC are not apparent. We examined the gene expression of IL-10/IL-10 receptor and various angiogenic/angioinhibitory factors in 95 NSCLC samples to determine the correlation between IL-10 production and vascularization. Vascular endothelial growth factor, angiopoietin [Ang (Ang-1 and Ang-2)], thrombospondin, brain-specific angiogenesis inhibitor 1, vascular endothelial growth factor receptors (KDR and flt-1), and Ang receptor (TIE2) gene expression were evaluated by reverse transcription-PCR. The cellular localization of these factors and vascularity in the cancer stroma were examined immunohistochemically. Seventy-eight (82.1%) and 93 (97.9%) of these 95 NSCLCs were positive for IL-10 and IL-10 receptor, respectively. Ang-1, Ang-2, and TIE2 gene expression was seen in 76 (97.4%), 73 (93.6%), and 78 (100%) of 78 IL-10-positive NSCLCs, respectively, and was significantly correlated with IL-10 gene expression (P < 0.0088, <0.0008, and 0.0305, respectively; Fisher's exact method). The localizations of Ang-1, Ang-2, and TIE2 were confirmed within tumor cells immunohistochemically. Vascular number and measurement area were significantly higher in the IL-10-positive NSCLCs (33.500 +/- 9.299/microm(2) and 4.742 +/- 1.287%) as compared with IL-10-negative NSCLCs (10.611 +/- 2.839/microm(2) and 0.718 +/- 0.331%; Mann-Whitney U test, P = 0.0039). The IL-10 expression did not show any significant correlation with the expression of other factors. These results suggested that tumor-produced IL-10 promotes stromal vascularization through expression of Ang-1, Ang-2, and TIE2.

Angiogenesis Inhibitors↗

PubMed2001

[The effect of obesity on spinal anesthesia for cesarean section].

To evaluate the effect of obesity on spinal anesthesia for cesarean section, we retrospectively studied 90 parturients who had undergone cesarean section, dividing the patients into 2 groups: obesity group (body mass index > 30, n = 41); control group (body mass index < 30, n = 49). Total surgical time and anesthetic time were longer in the obesity group than in the control group. The amount of ephedrine administered was also greater in the obesity group than in the control group. However, there were no significant differences in time for spinal tap and the incidence of hypotension between the two groups. Spinal anesthesia for cesarean section in obese patients may be an acceptable method.

Adult↗

PubMed2001

How a small enterprise improved the conditions of night and shift work using local resources.

A small oxygen factory in Cantho Province located in the Mekong Delta Area in the southern part of Vietnam was studied to provide practical support measures to improve night and shift work. A direct observation study and a fatigue symptom survey during the work were conducted. The factory applied discontinuous two-shift systems in two teams. Depending on customers' demands, they frequently prolonged oxygen production until midnight. The study results showed work-related risks such as carrying heavy oxygen cylinders, workers' sleepiness during the night work, and increased fatigue feelings among production operators. Based on the study results, better strategies for night and shift work schedules such as regular work hours minimizing overtime and night work were discussed with the managers and workers. A follow-up visit three months later confirmed many improvements undertaken in the factory. Better work arrangements for night and shift workers were made including local lighting, resting corners, filling the height gaps on the work floors, and clear work instructions. Prolonged mid-night shift was stopped. It was concluded that local small enterprises in Vietnam have much potential to improve their conditions of shift and night work once practical support measures based on their local practice is given.

Accidents, Occupational↗

PubMed2001

Support measures to improve night and shift work conditions in Thailand: a case study in a glass factory.

The present study aimed to examine the working conditions of shift workers in a multinational enterprise in Thailand and to identify practical support measures for improvements. A multinational, glass-manufacturing factory employing 1,500 workers was selected as the research site. Three shift systems in three teams were adopted. A direct observation study and a fatigue feeling monitoring study were carried out to compare the differences between different shifts. A 10-day time-budget study was conducted for 30 shift workers to know their work and sleep patterns. The direct observation study identified safety and health risks during the night work periods. The risks included insufficient lighting, height gaps on the floor, excessive exposure to heat, inappropriate workstations, and sleepiness and fatigue feelings among shift workers. Working consecutive double shifts and overtime work was often seen. An advisory meeting was held based on the study findings to assist managers and workers in improving their working conditions. A follow-up visit six months later confirmed that the glass factory implemented several improvements to help night and shift workers. It was concluded that the direct observation methods associated with the time-budget study were helpful for identifying practical action points and strengthening workplace initiatives.

Adult↗

PubMed2000

Effects of substance P and calcitonin gene-related peptide on axonal transport in isolated and cultured adult mouse dorsal root ganglion neurons.

Substance P and calcitonin gene-related peptide (CGRP) released from primary sensory neurons are known to play important roles in nociception and nociceptive transmission. In the present study, we attempted to clarify the roles of these neuropeptides in the regulation of axonal transport in sensory neurons. Cells were isolated from adult mouse dorsal root ganglia and cultured in F-12 medium containing fetal bovine serum for 48 h until their neurites were grown. These isolated and cultured DRG cells were mostly (>98%) small (diameter <25 microm) and medium (diameter, 25-40 microm) in size, and were immunoreactive for substance P and CGRP (85.9 and 66. 0% of total cells, respectively). Video-enhanced microscopy was applied to observe particles transported within neurites. Application of substance P (100 nM) decreased the number of particles transported in both anterograde and retrograde directions in each of DRG neurons tested (n=5). The instantaneous velocities of individual particles transported in anterograde and retrograde directions were also reduced by substance P. In contrast, alpha-CGRP (100 nM) increased the number of particles transported in both directions in each of DRG neurons tested (n=5), and also increased the instantaneous velocities of particles transported bidirectionally. Application of beta-CGRP (100-1000 nM) did not elicit any effect on axonal transport. Therefore, axonal transport in sensory neurons seems to be modulated by substance P and alpha-CGRP, both of which can be derived from its own and adjacent sensory neurons.

Animals↗

PubMed2000

Akt-dependent cytokine production in mast cells.

Cross-linking of FcepsilonRI induces the activation of three protein tyrosine kinases, Lyn, Syk, and Bruton's tyrosine kinase (Btk), leading to the secretion of a panel of proinflammatory mediators from mast cells. This study showed phosphorylation at Ser-473 and enzymatic activation of Akt/protein kinase B, the crucial survival kinase, upon FcepsilonRI stimulation in mouse mast cells. Phosphorylation of Akt is regulated positively by Btk and Syk and negatively by Lyn. Akt in turn can regulate positively the transcriptional activity of interleukin (IL)-2 and tumor necrosis factor (TNF)-alpha promoters. Transcription from the nuclear factor kappaB (NF-kappaB), nuclear factor of activated T cells (NF-AT), and activator protein 1 (AP-1) sites within these promoters is under the control of Akt activity. Accordingly, the signaling pathway involving IkappaB-alpha, a cytoplasmic protein that binds NF-kappaB and inhibits its nuclear translocation, appears to be regulated by Akt in mast cells. Catalytic activity of glycogen synthase kinase (GSK)-3beta, a serine/threonine kinase that phosphorylates NF-AT and promotes its nuclear export, seems to be inhibited by Akt. Importantly, Akt regulates the production and secretion of IL-2 and TNF-alpha in FcepsilonRI-stimulated mast cells. Altogether, these results revealed a novel function of Akt in transcriptional activation of cytokine genes via NF-kappaB, NF-AT, and AP-1 that contributes to the production of cytokines.

Animals↗

PubMed2000

Redundant and opposing functions of two tyrosine kinases, Btk and Lyn, in mast cell activation.

Protein-tyrosine kinases play crucial roles in mast cell activation through the high-affinity IgE receptor (FcepsilonRI). In this study, we have made the following observations on growth properties and FcepsilonRI-mediated signal transduction of primary cultured mast cells from Btk-, Lyn-, and Btk/Lyn-deficient mice. First, Lyn deficiency partially reversed the survival effect of Btk deficiency. Second, FcepsilonRI-induced degranulation and leukotriene release were almost abrogated in Btk/Lyn doubly deficient mast cells while singly deficient cells exhibited normal responses. Tyrosine phosphorylation of cellular proteins including phospholipases C-gamma1 and C-gamma2 was reduced in Btk/Lyn-deficient mast cells. Accordingly, FcepsilonRI-induced elevation of intracellular Ca2+ concentrations and activation of protein kinase Cs were blunted in the doubly deficient cells. Third, in contrast, Btk and Lyn demonstrated opposing roles in cytokine secretion and mitogen-activated protein kinase activation. Lyn-deficient cells exhibited enhanced secretion of TNF-alpha and IL-2 apparently through the prolonged activation of extracellular signal-related kinases and c-Jun N-terminal kinase. Potentially accounting for this phenomenon and robust degranulation in Lyn-deficient cells, the activities of protein kinase Calpha and protein kinase CbetaII, low at basal levels, were enhanced in these cells. Fourth, cytokine secretion was severely reduced and c-Jun N-terminal kinase activation was completely abrogated in Btk/Lyn-deficient mast cells. The data together demonstrate that Btk and Lyn are involved in mast cell signaling pathways in distinctly different ways, emphasizing that multiple signal outcomes must be evaluated to fully understand the functional interactions of individual signaling components.

Agammaglobulinaemia Tyrosine Kinase↗

PubMed2000

TCR/CD3-Induced activation and binding of Emt/Itk to linker of activated T cell complexes: requirement for the Src homology 2 domain.

Expressed in mast and T cells/inducible T cell tyrosine kinase (Emt/Itk), a Tec family protein tyrosine kinase, is critical for the development and activation of T lymphocytes. The mechanism through which Emt/Itk mediates its effector functions is poorly understood. In this study, we show that the Emt/Itk Src homology 2 (SH2) domain is critical for the transphosphorylation and activation of Emt/Itk catalytic activity that is mediated by TCR/CD3 engagement. Furthermore, we find that the Emt/Itk SH2 domain is essential for the formation of TCR/CD3-inducible Emt/Itk-LAT complexes, whereas the SH3 domain and catalytic activity are not required. The Emt/Itk-linker of activated T cells (LAT) complexes are biologically important because Jurkat T cells with deficient LAT expression (JCaM2) fail to increase Emt/Itk tyrosine phosphorylation upon TCR/CD3 stimulation. Confocal microscopy reveals that in activated cells, LAT complexes colocalize with TCR/CD3. The present data suggest that upon TCR/CD3 engagement, the Emt/Itk SH2 domain mediates the formation of a molecular complex containing Emt/Itk, LAT, and TCR/CD3; this complex is essential for Emt/Itk activation and function.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Regulation of protein kinase CbetaI by two protein-tyrosine kinases, Btk and Syk.

Two protein-tyrosine kinases, Bruton's tyrosine kinase (Btk) and Syk, and members of the protein kinase C (PKC) subfamily of serine/threonine kinases play crucial roles in signal transduction through antigen receptors in B lymphocytes and high-affinity IgE receptors (FcepsilonRI) in mast cells. The present study provides genetic, biochemical, and pharmacological evidence that, on FcepsilonRI stimulation, Syk regulates Btk, and Btk selectively regulates the membrane translocation and enzymatic activity of PKCbetaI among the conventional PKC isoforms (alpha, betaI, and betaII) expressed in mast cells. Syk/Btk-mediated PKCbetaI regulation is involved in transcriptional activation of the IL-2 and tumor necrosis factor alpha genes through the JNK pathway induced by FcepsilonRI stimulation. Accordingly, FcepsilonRI-induced production of these cytokines is inhibited by specific inhibitors of Btk and Syk, as well as broad-specificity inhibitors of PKC and a selective inhibitor of PKCbeta. Specific regulation of PKCbetaI by Btk is consistent with the selective association of Btk with PKCbetaI. Components of this signaling pathway may represent an attractive set of potential targets of pharmaceutical interference for the treatment of allergic and other immunologic diseases.

Agammaglobulinaemia Tyrosine Kinase↗