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T Uchiyama

Publications and source records attributed to T Uchiyama.

At least 55 records · Page 3Linked to original sources
PubMed2001

Roles of the exposed aromatic residues in crystalline chitin hydrolysis by chitinase A from Serratia marcescens 2170.

Four exposed aromatic residues, two in the N-terminal domain (Trp-69 and Trp-33) and two in the catalytic domain (Trp-245 and Phe-232) of Serratia marcescens chitinase A, are linearly aligned with the deep catalytic cleft. To investigate the importance of these residues in the binding activity and hydrolyzing activity against insoluble chitin, site-directed mutagenesis to alanine was carried out. The substitution of Trp-69, Trp-33, or Trp-245 significantly reduced the binding activity to both highly crystalline beta-chitin and colloidal chitin. The substitution of Phe-232, which is located closest to the catalytic cleft, did not affect the binding activity. On the other hand, the hydrolyzing activity against beta-chitin microfibrils was significantly reduced by the substitution of any one of the four aromatic residues including Phe-232. None of the mutations reduced the hydrolyzing activity against soluble substrates. These results clearly demonstrate that the four exposed aromatic residues are essential determinants for crystalline chitin hydrolysis. Three of them, two in the N-terminal domain and one in the catalytic domain, play vital roles in the chitin binding. Phe-232 appeared to be important for guiding the chitin chain into the catalytic cleft. Based on these observations, a model for processive hydrolysis of crystalline chitin by chitinase A is proposed.

Base Sequence↗
PubMed2001

SPECT imaging of the dopamine transporter with [(123)I]-beta-CIT reveals marked decline of nigrostriatal dopaminergic function in Parkinson's disease with urinary dysfunction.

We studied a correlation of urinary dysfunction with nigrostriatal dopaminergic deficit in Parkinson's disease (PD) by single-photon emission computed tomography (SPECT) imaging of dopamine transporter with [123I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane (beta-CIT). Eleven patients were enrolled in the study, including four men and seven women, with a mean age of 64 years. Seven patients had urinary symptoms 1-5 years after the onset of motor disorder, which included nighttime frequency in six, urinary retardation in four, daytime frequency in one and urge urinary incontinence in one. Using a SPECT camera, the ratio specific to nondisplaceable [123I]-beta-CIT uptake, designated as "striatal V3" was obtained in the caudate, anterior and posterior putamen 24 h after the tracer injection. The striatal V3 was compared in patients with and without urinary dysfunction, and between men and women, using unpaired Student's t-test. Correlation of motor dysfunction and duration of illness with urinary dysfunction, was also analyzed. In the patients, there was a reduction of [123I]-beta-CIT binding in the striatum on both sides, particularly in the putamen contralateral to the affected body side. The striatal V3 of the caudate (p<0.01, Rt; p<0.05, Lt), anterior putamen (p<0.05, Rt) and posterior putamen (p<0.05, Rt) in patients with urinary dysfunction was significantly reduced than those without urinary dysfunction. No sex difference was seen in reduction of [123I]-beta-CIT binding. Urinary dysfunction in PD was more common in patients with higher Unified Parkinson's Disease Rating Scale (UPDRS) score, higher Hoehn-Yahr grade, but not in those with longer duration of disease, although there was no statistical significance. It is likely that our results reflect the association of urinary dysfunction and degeneration of the nigrostriatal dopaminergic cells in PD.

Aged↗
PubMed2001

Stable operation of a 300-m laser interferometer with sufficient sensitivity to detect gravitational-wave events within our galaxy.

TAMA300, an interferometric gravitational-wave detector with 300-m baseline length, has been developed and operated with sufficient sensitivity to detect gravitational-wave events within our galaxy and sufficient stability for observations; the interferometer was operated for over 10 hours stably and continuously. With a strain-equivalent noise level of h approximately 5x10(-21)/sqrt[Hz], a signal-to-noise ratio of 30 is expected for gravitational waves generated by a coalescence of 1.4M-1.4M binary neutron stars at 10 kpc distance. We evaluated the stability of the detector sensitivity with a 2-week data-taking run, collecting 160 hours of data to be analyzed in the search for gravitational waves.

Astronomy↗
PubMed2001

Caspase-3 activation by lysosomal enzymes in cytochrome c-independent apoptosis in myelodysplastic syndrome-derived cell line P39.

In most cases, apoptosis is considered to involve mitochondrial dysfunction with sequential release of cytochrome c from mitochondria, resulting in activation of caspase-3. However, we found that etoposide induced apoptosis in P39 cells, a myelodysplastic syndrome-derived cell line, without the release of cytochrome c. Furthermore, in etoposide-treated P39 cells, no changes in mitochondrial membrane potential (delta psi m) were detected by flow cytometry. Flow cytometry using a pH-sensitive probe demonstrated that lysosomal pH increased during early apoptosis in P39 cells treated with etoposide. A reduction in the ATP level preceded the elevation of lysosomal pH. In addition, specific inhibitors of vacuolar H+-ATPase induced apoptosis in P39 cells but not in HL60 cells. Although etoposide-induced activation of caspase-3 was followed by DNA ladder formation in P39 cells, E-64d, an inhibitor of lysosomal thiol proteases, specifically suppressed etoposide-induced activation of caspase-3. Western blotting analysis provided direct evidence for the involvement of a lysosomal enzyme, cathepsin L. These findings indicate that lysosomal dysfunction induced by a reduction in ATP results in leakage of lysosomal enzymes into the cytosolic compartment and that lysosomal enzyme(s) may be involved in activation of caspase-3 during apoptosis in P39 cells treated with etoposide.

Anti-Bacterial Agents↗
PubMed2001

Micturitional disturbance in subacute myelo-optico-neuropathy (SMON).

BACKGROUND: Micturitional disturbance is known to occur in subacute myelo-optico-neuropathy (SMON). However, its pathophysiology is uncertain and few data are available concerning urodynamic findings. We described our results of micturitional histories and urodynamic studies in patients with SMON. METHODS: A history of urinary symptoms was obtained from six patients with SMON (two men, four women; age, 49-72 years, mean 60 years; duration of illness, 14-25 years, mean 19 years). All patients underwent urodynamic studies including measurement of post-micturition residuals, urethral pressure profilometry, cystometry and simultaneous sphincter electromyography. RESULTS: All patients had micturitional symptoms including voiding symptoms in four, filling symptoms in four and urge urinary incontinence in a patient. Urodynamic studies revealed an increased maximum urethral closure pressure in two of four patients studied, decreased bladder volume at first sensation in two, detrusor hyperreflexia in three, absent bulbocavernosus reflex in a patient, and none had detrusor-sphincter dyssynergia or post-micturition residuals. Repeated urodynamic study (10 years after initial study) in a patient with detrusor hyperreflexia showed the same findings. CONCLUSION: Our results indicate that supranuclear pelvic nerve dysfunction to be mainly responsible for the micturitional disturbance in patients with SMON.

Aged↗
PubMed2001

Machado-Joseph disease associated with an absence of fungiform papillae on the tongue.

The authors report the case of a family with Machado-Joseph disease (MJD) associated with sensory and autonomic disturbances-particularly the absence of fungiform papillae on the tongue and taste buds. Sural nerve biopsy showed a loss of myelinated fibers. Autonomic function tests showed bladder-bowel dysfunction, hypohidrosis, and low coefficients of variation of R-R intervals on electrocardiogram. These findings may be another possible variant or previously unrecognized symptoms in MJD.

Adult↗
PubMed2001

Functional uncoupling of T-cell receptor engagement and Lck activation in anergic human thymic CD4+ T cells.

Human thymic CD1a-CD4+ T cells in the final stage of thymic maturation are susceptible to anergy induced by a superantigen, toxic shock syndrome toxin-1 (TSST-1). Thymic CD4+ T-cell blasts, established by stimulating human thymic CD1a-CD4+ T cells with TSST-1 in vitro, produce a low level of interleukin-2 after restimulation with TSST-1, whereas TSST-1-induced adult peripheral blood (APB) CD4+ T-cell blasts produce high levels of interleukin-2. The extent of tyrosine phosphorylation of the T-cell receptor zeta chain induced after restimulation with TSST-1 was 2-4-fold higher in APB CD4+ T-cell blasts than in thymic CD4+ T-cell blasts. The tyrosine kinase activity of Lck was low in both thymic and APB CD4+ T-cell blasts before restimulation with TSST-1. After restimulation, the Lck kinase activity increased in APB CD4+ T-cell blasts but not in thymic CD4+ T-cell blasts. Surprisingly, Lck was highly tyrosine-phosphorylated in both thymic and APB CD4+ T-cell blasts before restimulation with TSST-1. After restimulation, it was markedly dephosphorylated in APB CD4+ T-cell blasts but not in thymic CD4+ T-cell blasts. Lck from APB CD4+ T-cell blasts bound the peptide containing the phosphotyrosine at the negative regulatory site of Lck-505 indicating that the site of dephosphorylation in TSST-1-activated T-cell blasts is Tyr-505. Confocal microscopy demonstrated that colocalization of Lck and CD45 was induced after restimulation with TSST-1 in APB CD4+ T-cell blasts but not in thymic CD4+ T-cell blasts. Further, remarkable accumulation of Lck in the membrane raft was observed in restimulated APB CD4+ T-cell blasts but not in thymic CD4+ T-cell blasts. These data indicate that interaction between Lck and CD45 is suppressed physically in thymic CD4+ T-cell blasts and plays a critical role in sustaining an anergic state.

Adult↗
PubMed2001

Neurogenic failures of the external urethral sphincter closure and relaxation; a videourodynamic study.

Urinary urgency and voiding difficulty are common features in neurological diseases, which can be attributed to dysfunction of the urethral sphincter and the detrusor. However, little is known about dynamic sphincter behaviour in neurological diseases. The present study aimed at investigating neurogenic failures of the external urethral sphincter closure and relaxation by videourodynamic study. We recruited 44 neurological patients with urinary urgency and frequency, 27 men and 17 women, mean age 61 years, and 28 of them had voiding difficulty as well. None had abnormal finding of digital examination or ultrasound echography of the pelvic organs. Using triple-lumen 7F catheter under X-ray fluoroscope, we measured detrusor pressure, external urethral sphincter pressure (Pura) and external sphincter EMG in all patients. We also performed pressure-flow study and obtained the Abram-Griffiths (AG) number, a numerical grade of obstruction. During filling 30 had detrusor hyperreflexia. EMG-cystometry showed uninhibited external sphincter relaxation (UESR) in eight patients, seven of whom had detrusor hyperreflexia as well. Patients with UESR showed an abnormal reduction of Pura, mean reduction 64 +/- 27 cmH2O (mean +/- standard deviation). During UESR the Pura and EMG activity fluctuated, and fluoroscopic image showed bladder neck opening in four with extreme urge sensation, including one without detrusor hyperreflexia. During an attempt of voiding three patients with voiding difficulty had detrusor-external sphincter dyssynergia (DESD) with detrusor contraction and eight had unrelaxing external sphincter without detrusor contraction. Fluoroscopic image showed an incomplete or absent urethral opening at the external sphincter. Four of them had severe straining on voiding together with intermittent increment of EMG activity without a normal funneling of the bladder neck. The mean reduction of Pura during voiding was 6.4 +/- 6.7 cmH2O and 5.0 +/- 9.5 cmH2O (in women and men, respectively) with DESD or unrelaxing external sphincter which was less than 39 +/- 25 cmH2O and 53 +/- 47 cmH2O in those without (P < 0.01). The mean AG number was 15 +/- 21 and 51 +/- 19 (for women and men, respectively) with DESD or unrelaxing external sphincter which was larger than 6.2 +/- 34 and 35 +/- 22 in those without (P < 0.05). In conclusion, UESR and DESD/unrelaxing external sphincter could be a factor for urinary urgency and voiding difficulty in neurological patients, evidence of central dysregulation affecting the Onuf's nucleus and its fibres to the external urethral sphincter.

Adolescent↗
PubMed2001

Urinary dysfunction in Brown-Séquard syndrome.

Brown-Séquard syndrome (BS) is a rare but well documented condition of the spinal cord hemisection, comprising hemiparesis with crossed superficial sensory disturbance. However, little is known of micturitional function in BS, although some patients with BS are troubled with severe voiding difficulty and urinary incontinence. We performed urinary questionnaire and urodynamic studies in eight patients with BS, including seven men and one woman, mean age of 41 years. Detailed questionnaire showed that five of the eight patients (63%) had micturitional symptoms, including voiding difficulty in three, urinary retention in two, urinary frequency in two and urge urinary incontinence in one. Urodynamic abnormalities were noted in all five patients with micturitional symptoms, including post-micturition residuals in four (average 149 mL), high urethral closure pressure in two, increased bladder volume at first sensation in one, detrusor hyperreflexia in four, detrusor areflexia on voiding in three and unrelaxing sphincter on voiding in four. Three asymptomatic patients showed normal urodynamic finding. Micturitional symptoms were more common in patients with severe motor paresis (100%) than in those with mild motor paresis (40%), and there was no relation between micturitional disturbance with superficial or deep sensory disturbance. A combination of treatments for the underlying disorders with alpha-adrenergic blocking agent and clean, intermittent self-catheterization ameliorated the urinary dysfunction in all patients together with neurological dysfunction. In conclusion, micturitional disturbance was not uncommon in our patients with BS, particularly in those with severe motor paresis, which could ameliorate by appropriate therapies.

Adult↗
PubMed2001

Primary mediastinal large B-cell lymphoma: a comparative study with nodular sclerosis-type Hodgkin's disease.

The clinicopathological features of 10 patients with primary mediastinal large B-cell lymphoma (PMLBCL) are described. The patients were aged 19 to 63 years, with a median age of 25.5 years. There were 5 men and 5 women. All patients presented with chest symptoms, and 6 presented with superior vena cava syndrome. Nine patients had bulky mediastinal tumors. The disease was confined within the thorax and contiguous lymph nodes, although multiple liver tumors were observed in 1 patient. Laboratory findings included high lactate dehydrogenase levels and elevated C-reactive protein levels. The soluble interleukin 2-receptor level was high in 6 patients tested. A comparative study of PMLBCL and nodular sclerosis-type Hodgkin's disease (NS-HD) with a mediastinal mass revealed substantial overlap in clinical features. Histopathological examination of biopsy specimens of PMLBCL revealed clusters of CD20+ large cells; however, CD30+ Hodgkin/Reed-Sternberg-like cells were occasionally seen, raising the potential to misdiagnose PMLBCL as NS-HD. The patients with PMLBCL were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), biweekly CHOP, or MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisolone, and bleomycin) regimen, and 6 received consolidation radiotherapy to the involved field. With the exception of 1 patient who was primarily refractory to therapy, 9 patients (90%) achieved complete response and 7 (70%) remain in continuous remission with a mean follow-up of 24 months.

Adult↗
PubMed2001

Gamma/delta T cells provide innate immunity against renal cell carcinoma.

Host immune function plays a certain role against the development of renal cell carcinomas (RCCs), but the mechanism is not entirely understood. Human gamma/delta (gamma/delta) T cells defend the body against infection. In this study, we clarify the role of gamma/delta T cells in the surveillance system against RCCs by analyzing the gamma/delta T cells in peripheral blood mononucleocytes (PBMs) and tumor infiltrating lymphocytes (TILs) from 41 patients with RCCs. The results showed that the number of gamma/delta T cells expressing V gamma 2 and V delta 2 in variable elements of TCR was elevated in the PBMs in 10 patients, but not in any of 32 healthy individuals. The proportion of patients with an elevated number of gamma/delta T cells (> 10%) increased with cancer stage. The level of the gamma/delta T cells decreased after surgery. The gamma/delta T cells in the TILs were more activated than those in the PBMs. Evaluation of the junctional diversity of TCR V gamma 2 and V delta 2 chains showed that the increased peripheral blood gamma/delta T cells were oligoclonal rather than polyclonal. Taken together, our findings suggest that gamma/delta T cells recognize certain RCC-related antigens and play a role in the surveillance system against RCCs.

Adult↗
PubMed2001

Effects of dioxins and polychlorinated biphenyls (PCBs) on thyroid function in infants born in Japan--the second report from research on environmental health.

Dioxins (PCDD + PCDF) and polychlorinated biphenyl (PCB) are potentially hazardous compounds and have structural similarity to thyroid hormones. Our research group on "Dioxins and PCB in Human Milk" was organized in 1997 and has been active for the past three years. We collected breast milk from 80 mothers living in Tokyo, Saitama, Ishikawa and Osaka Prefecture in Japan at 5, 30, 150, 300 postpartum days and measured PCDDs, PCDFs and PCBs during 1998-1999. We added another 20 prefectures and cities during 1999-2000. Breast milk was obtained from 415 mothers at 30 postpartum days (breast-feeding group). Blood was taken from infants who were breast-fed at the age of 1 year for evaluation of thyroid and immune functions. Blood was also taken from 53 infants who were bottle-fed (bottle-feeding group) as a control. Serum T4, T3, FT4 and TSH levels in the breast-feeding (n = 337) and bottle-feeding (n = 53) groups were within normal ranges and were not significantly different between the two groups. Although there were a large geographic differences of dioxins and co-PCB content in breast milk, there were no differences in serum T4, T3, FT4, TSH levels and no significant correlation between the mean serum levels of TSH and TEQ in breast milk. There was a significant correlation between serum TSH at 1 year of age and that from blood on dried filter paper TSH at 5 days of age. We concluded that dioxin intake from breast milk in Japanese infants did not impair thyroid function. However, long-term effects remain to be evaluated.

Adult↗
PubMed2001

Recurrent septicemia caused by Streptococcus canis after a dog bite.

Human infection with Streptococcus canis is extremely rare. We describe herein a case of septicemia with cellulitis caused by S. canis in a 75-y-old woman, which developed 2 weeks after a dog bite. Macrorestriction analysis with pulsed-field gel electrophoresis demonstrated that the organism had been transmitted by means of a dog bite to her hand.

Aged↗
PubMed2001

Heterogeneous breakpoints on the immunoglobulin genes are involved in fusion with the 5' region of BCL2 in B-cell tumors.

The 5' flanking region of the BCL2 gene (5'-BCL2) is a breakpoint cluster of rearrangements with immunoglobulin genes (IGs). In contrast to t(14;18)(q32;q21) affecting the 3' region of BCL2, 5'-BCL2 can fuse to not only the heavy chain gene (IGH), but also two light chain gene (IGL) loci. We report here cloning and sequencing of a total of eleven 5'-BCL2 / IGs junctional areas of B-cell tumors, which were amplified by long-distance polymerase chain reaction-based assays. The breakpoints on 5'-BCL2 were distributed from 378 to 2312 bp upstream of the translational initiation site and, reflecting the alteration of regulatory sequences of BCL2, 5'-BCL2 / IGs-positive cells showed markedly higher levels of BCL2 expression than those of t(14;18)-positive cells. In contrast, the breakpoints on the IGs were variable. Two 5'-BCL2 / IGH and two 5'-BCL2 / IGLkappa junctions occurred 5' of the joining (J) segments, suggesting operation of an erroneous variable (V) / diversity (D) / J and V / J rearrangement mechanism. However, two other 5'-BCL2 / IGH junctions affected switch regions, and the kappa-deleting element, which is located 24 kb downstream of the constant region of IGLkappa, followed the 5'-BCL2 in another case. One 5'-BCL2 / IGLkappa and two 5'-BCL2 / IGLlambda junctions involved intronic regions where the normal recombination process does not occur. In the remaining one case, the 5'-BCL2 fused 3' of a Vlambda gene that was upstream of another Vlambda / Jlambda complex carrying a non-producing configuration, indicating that the receptor editing mechanism was likely involved in this rearrangement. Our study revealed heterogeneous anatomy of the 5'-BCL2 / IGs fusion gene leading to transcriptional activation of BCL2, and suggested that the mechanisms underlying the formation of this particular oncogene / IGs recombination are not identical to those of t(14;18).

Base Sequence↗
PubMed2001

Replacement of the V3 region of gp120 with SDF-1 preserves the infectivity of T-cell line-tropic human immunodeficiency virus type 1.

Interaction between the human immunodeficiency virus type 1 (HIV-1) envelope and the relevant chemokine receptors is crucial for subsequent membrane fusion and viral entry. Although the V3 region of gp120 is known to determine the cell tropism as well as the coreceptor usage, the significance of the binding of the V3 region to the chemokine receptor has not been fully understood. To address this issue, we adopted the pseudotyped virus infection assay in which the V3 region of the T-cell line-tropic (T-tropic) NL4-3 envelope was replaced with a portion of stromal cell-derived factor 1 (SDF-1), the ligand of CXCR4. The V3 region of the NL4-3 envelope expression vector was replaced with three different stretches of SDF-1 cDNA. Expression of each chimeric envelope protein was confirmed by immunoprecipitation and Western blotting. Luciferase reporter viruses were prepared by cotransfection of the pNL4-3.Luc.E(-)R(-) vector and each chimeric envelope expression vector, and the infection assay was then carried out. We showed that pseudotyped viruses with one of the chimeric envelopes, NL4-3/SDF1-51, could infect U87.CD4.CXCR4 but not U87.CD4 or U87.CXCR4 cells and that this infection was inhibited by the ligand of CXCR4, SDF-1beta, by anti-human SDF-1 antibody, or by an anti-CD4 antibody, Leu3a, in a dose-dependent manner. Furthermore, chimeric NL4-3/SDF1-51 gp120 significantly inhibited binding of labeled SDF-1 to CXCR4. It was suggested that replacement of the V3 region of the NL4-3 envelope with SDF-1 preserved the CD4-dependent infectivity of T-tropic HIV-1. These results indicate that binding between the V3 region and the relevant coreceptor is important for viral entry, whether its amino acid sequence is indigenous to the virus or not.

Amino Acid Sequence↗
PubMed2001

Videourodynamic and sphincter motor unit potential analyses in Parkinson's disease and multiple system atrophy.

OBJECTIVES: Urinary dysfunction is a prominent autonomic feature in Parkinson's disease (PD) and multiple system atrophy (MSA), which is not only troublesome but also a cause of morbidity in these disorders. Recent advances in investigative uroneurology offer a better insight into the underlying pathophysiology and appropriate management for urinary dysfunction. METHODS: twenty one patients with PD (15 men, six women, mean age 64 (49-76), mean disease duration 4 years (1-8 years), median Hoehn and Yahr grade 3 (1-4), all taking 300 mg/day of levodopa (100-500 mg)) and 15 with MSA (eight men, seven women, mean age 59 (48-72), mean disease duration 3 years (0.5-6 years)) were recruited. Videourodynamic and sphincter motor unit potential analyses in the patients with PD and MSA were carried out, looking for distinguishing hallmarks that might be useful in the differential diagnosis of these two diseases. RESULTS: Urinary symptoms were found in 72% of patients with PD and in 100% with MSA. Filling phase abnormalities in the videourodynamic study included detrusor hyperreflexia in 81% of patients with PD and 56% with MSA, and uninhibited external sphincter relaxation in 33% of patients with PD and 33% of those with MSA. However, open bladder neck at the start of filling was not seen in patients with PD but was present in 53% of those with MSA, suggestive of internal sphincter denervation. Sphincter motor unit potential analysis showed neurogenic motor unit potentials in 5% of patients with PD and in 93% of those with MSA, suggestive of external sphincter denervation. On voiding, detrusor-external sphincter dyssynergia was not seen in patients with PD but was present in 47% of those with MSA. Pressure-flow analysis showed that the Abrams-Griffiths number, a grading of urethral obstruction (outflow obstruction >40), in PD (40 in women and 43 in men) was larger than that in MSA (12 in women and 28 in men). Weak detrusor in PD (66% of women and 40% of men) was less common than that in MSA (71% of women and 63% of men). Postmicturition residuals >100 ml were absent in patients with PD but were present in 47% of patients with MSA. CONCLUSION: Patients with PD had less severe urinary dysfunction with little evidence of internal or external sphincter denervation, by contrast with the common findings in MSA. The findings of postmicturition residuals >100 ml, detrusor-external sphincter dyssynergia, open bladder neck at the start of bladder filling, and neurogenic sphincter motor unit potentials are highly suggestive of MSA.

Aged↗