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T Wada

Publications and source records attributed to T Wada.

At least 325 records · Page 18Linked to original sources
PubMed1998

Interplay between positive and negative elongation factors: drawing a new view of DRB.

DRB is a classic inhibitor of transcription by RNA polymerase II (pol II). Although it has been demonstrated that DRB inhibits the elongation step of transcription, its mode of action has been elusive. DRB also markedly inhibits human immunodeficiency virus (HIV) transcription, by targeting the elongation which is enhanced by the HIV-encoded transactivator Tat. Two factors essential for DRB action have recently been identified. These factors, positive transcription elongation factor b (P-TEFb) and DRB sensitivity-inducing factor (DSIF), positively and negatively regulate pol II elongation, and are likely to be relevant to the function of Tat. In this review, we summarize the recent findings on these factors, and discuss a possible model for the molecular mechanism of DRB action.

Dichlororibofuranosylbenzimidazole↗
PubMed1998

Gene transfer of RANTES elicits autoimmune renal injury in MRL-Fas(1pr) mice.

We report that the beta-chemokine RANTES, a chemoattractant for macrophages and T cells, is up-regulated in the MRL-Fas(1pr) kidney prior to injury, but not normal kidneys (MRL-++, C3H-++) and increases with progressive injury. Furthermore, we establish an association between RANTES expression in the kidney and renal damage using a gene transfer approach. Tubular epithelial cells genetically modified to secrete RANTES infused under the renal capsule incites interstitial nephritis in MRL-Fas(1pr), but not MRL-++ or C3H-++ mice. RANTES recruits predominantly macrophages (M phi) and CD4+ and CD8+ T cells. In contrast, gene transfer of CSF-1, another molecule up-regulated simultaneously with RANTES in MRL-Fas(1pr) kidneys, promotes the influx of M phi, CD4+ T cells and the unique double-negative (DN) T cells (CD4-, CD8-), which are prominent in diseased MRL-Fas(1pr) kidneys. Thus, RANTES and CSF-1 recruit distinct T cell populations into the MRL-Fas(1pr) kidney. In addition, delivery of RANTES and CSF-1 into the kidney of MRL-Fas(1pr) mice causes an additive increase in pathology. We suggest that the complementary recruitment of T cell populations by RANTES (CD4, CD8) and CSF-1 (CD4, DN) promotes autoimmune nephritis in MRL-Fas(1pr) mice.

Animals↗
PubMed1998

Effects of D-glucose and starvation upon the cyclic ADP-ribose content of rat pancreatic islets.

Rat pancreatic islets were found to display a much lower content of immunoreactive CD38 and a much lower ADP-ribosyl cyclase activity than rat spleen or brain. Cyclic ADP-ribose was also measured by a radioimmunological procedure in rat pancreatic islets. In fed rats, the cyclic ADP-ribose content appeared higher after isolation of the islets in the presence of 2.8 mM D-glucose rather than in the absence of the hexose, progressively increased during incubation of the islets for 5-60 min at 37 degrees C, but failed to be affected by the concentration of D-glucose (zero to 20.0 mM) in the incubation medium. In rats fasted for 24 hours, the cyclic ADP-ribose islet content also increased during incubation, but again failed to be affected by the concentration of D-glucose in the incubation medium. Although these findings indicate that the islet cyclic ADP-ribose content is influenced by nutritional and environmental factors, they do not support the view that the insulinotropic action of D-glucose involves major change in the islet cell content of the cyclic nucleotide.

ADP-ribosyl Cyclase↗
PubMed1998

Identification of the gene loci that predispose to rheumatoid arthritis.

We have searched the human genome for genes that predispose to rheumatoid arthritis (RA) using fluorescence-based microsatellite marker analysis and affected sib-pair linkage study. A panel of 41 Japanese families, each with at least two affected siblings, was typed for genome-wide 358 polymorphic microsatellite marker loci. Markers were amplified by the PCR using fluorescence-tagged primers and sized based on the difference of CA repeats on DNA. Linkage analysis was made using maximum lod score (MLS). The MLS for D1S214 and D8S556 was 3.27 and 3.33, while the MLS for the HLA-DRB1 region was <3.0. According to detailed analysis by single-point analysis using MAPMAKER/SIBS, the MLS for D1S253 and D1S214 was 3.77 and 3.58. The MLS by multipoint analysis was 6.13 for D1S253. The MLS for D8S556 by single-point analysis was 4.20. The MLS for DXS1232 was 2.35 by single-point analysis, whereas the MLS for the region 2 cM right to DXS1232 and the region between DXS1227 and DXS1200 was 3.03 and 2.93 by multi-point analysis. Three principal chromosome regions of linkage, D1S253/214, D8S556 and DXS1232, have been identified which we call RA1, RA2 and RA3 for RA disease loci.

Arthritis, Rheumatoid↗
PubMed1998

Novel Fas (CD95/APO-1) mutations in infants with a lymphoproliferative disorder.

Fas is an apoptosis-signaling receptor important for homeostasis of the immune system. In this study, Fas-mediated apoptosis and Fas mutations were analyzed in three Japanese children from two families with a lymphoproliferative disorder characterized by lymphadenopathy, hepatosplenomegaly, pancytopenia, hypergammaglobulinemia and an increase in TCR alphabeta+ CD4- CD8- T cells. Apoptosis induced by anti-Fas mAb was defective in both activated T cells and B cells, and granulocytes from these patients. Truncated Fas receptor lacking the cytoplasmic death domain caused by a point mutation in the splice region of intron 7 were demonstrated in two siblings. A homozygous point mutation in the splice acceptor of intron 3 was found in the Fas gene of the third patient, which resulted in the skipping of exon 4 and complete loss of Fas expression. Corresponding to these mutations, soluble Fas concentrations were decreased and reciprocally soluble Fas ligands were increased in patients' sera. Interestingly, co-stimulation by immobilized anti-Fas mAb in T cells from the two siblings was comparable to that seen in normal T cells. These results suggest that Fas-mediated apoptosis plays a pivotal role in immunological homeostasis in vivo, especially regarding clonal deletion of immune cells in humans.

Apoptosis↗
PubMed1998

Purification and characterization of a membrane-associated ganglioside sialidase from bovine brain.

A membrane-associated ganglioside-hydrolyzing sialidase was purified to apparent homogeneity from bovine brain. The enzyme was solubilized with Triton X-100 plus sodium cholate from the particulate fraction and purified over 100,000-fold by sequential chromatography on DEAE-cellulose, octyl-Sepharose, heparin-Sepharose, Sephacryl S-200, MonoQ, RCA-agarose, thiol-activated Sepharose, and ganglioside-affinity Sepharose. The final enzyme preparation exhibited a specific activity of 4,851.3 micromol/h/mg protein and an apparent molecular mass of 52 kDa on SDS-polyacrylamide gel electrophoresis. The enzyme preferentially hydrolyzed gangliosides other than GM1 and GM2 but demonstrated hardly any activity against glycoproteins and oligosaccharides. Gangliosides GD3, GD1a, and GT1b were much better substrates than GM3 and GD1b in the presence of Triton X-100, but the latter became more sensitive to the sialidase with addition of sodium cholate. The enzyme was activated by dithiothreitol, strongly inhibited by 4-hydroxy-mercuribenzoate, and firmly adsorbed to thiol-activated Sepharose, indicating that free sulfhydryl groups are essential for its catalytic activity. Subcellular fractionation experiments revealed that the enzyme is mainly located in the synaptosomal fraction.

Animals↗
PubMed1998

Diffuse brain damage caused by acute twin-twin transfusion during late pregnancy.

BACKGROUND: Monoamniotic twinning is a relatively rare event with increased antenatal and perinatal mortality. We describe a brain damage detected in a surviving monoamniotic twin after intrauterine death of the co-twin at 37 weeks of gestation. RESULTS: Severe entanglement and knotting of the umbilical cords was apparent at the time of delivery and a portion of the cord to the dead twin was narrowed significantly. It was suggested that transfer of blood occurred across placental anastomoses from the survivor to the dead fetus, resulting in transient but severe hypovolemia in the survivor. It is difficult to prevent this type of brain damage because the course of acute twin-twin transfusion is very rapid and the damage has already occurred by the time the death of the twin is diagnosed. CONCLUSIONS: We suggest that elective delivery should be considered in cases of monoamniotic twin pregnancies with additional risk factors.

Adult↗
PubMed1998

Characterization of the MexC-MexD-OprJ multidrug efflux system in DeltamexA-mexB-oprM mutants of Pseudomonas aeruginosa.

Expression of the multidrug efflux system MexC-MexD-OprJ in nfxB mutants of Pseudomonas aeruginosa contributes to resistance to fluoroquinolones and the "fourth-generation" cephems (cefpirome and cefozopran), but not to most beta-lactams, including the ordinary cephems (ceftazidime and cefoperazone). nfxB mutants also express a second multidrug efflux system, MexA-MexB-OprM, due to incomplete transcriptional repression of this operon by the mexR gene product. To characterize the contribution of the MexC-MexD-OprJ system to drug resistance in P. aeruginosa, a site-specific deletion method was employed to remove the mexA-mexB-oprM region from the chromosome of wild-type and nfxB strains of P. aeruginosa. Characterization of mutants lacking the mexA-mexB-oprM region clearly indicated that the MexC-MexD-OprJ efflux system is involved in resistance to the ordinary cephems as well as fluoroquinolones and the fourth-generation cephems but not to carbenicillin and aztreonam. Rabbit polyclonal antisera and murine monoclonal antibody against the components of the MexA-MexB-OprM system were prepared and used to demonstrate the reduced production of this efflux system in the nfxB mutants. Consistent with this, transcription of the mexA-mexB-oprM operon decreased in an nfxB mutant. This reduction appears to explain the hypersusceptibility of the nfxB mutant to beta-lactams, including ordinary cephems.

Animals↗
PubMed1998

Augmented renal sympathetic nerve activity by central command during overground locomotion in decerebrate cats.

We examined whether the cerebrum is essential for producing the rapid autonomic adjustment at the onset of spontaneous overground locomotion. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), heart rate (HR), and electromyogram of the forelimb triceps brachialis were measured when freely moving, decerebrate cats spontaneously produced overground locomotion, supporting body weight. Decerebration was performed at the level of the precollicular-premammillary body. RSNA increased 95 +/- 14 impulses/s (68 +/- 10% of baseline value) at the onset of spontaneous locomotion, which was followed by rises in MAP and HR (7 +/- 1 mmHg and 18 +/- 2 beats/min, respectively). Concomitantly with the MAP rise, RSNA declined toward control values and then increased again during the subsequent period of locomotion. The same rapid increase in RSNA at the onset of locomotion was observed after sinoaortic denervation and vagotomy. It is concluded that some central site(s), other than the cerebrum and the rostral part of the diencephalon, can generate the centrally induced autonomic adjustment at the onset of spontaneous overground locomotion, which is independent of arterial baroreceptor and vagal afferents.

Afferent Pathways↗
PubMed1998

Accumulation of carbonyls accelerates the formation of pentosidine, an advanced glycation end product: carbonyl stress in uremia.

Advanced glycation end product (AGE) formation is related to hyperglycemia in diabetes but not in uremia, because plasma AGE levels do not differ between diabetic and nondiabetic hemodialysis patients. The mechanism of this phenomenon remains elusive. Previously, it was suggested that elevation of AGE levels in uremia might result from the accumulation of unknown AGE precursors. The present study evaluates the in vitro generation of pentosidine, a well identified AGE structure. Plasma samples from healthy subjects and nondiabetic hemodialysis patients were incubated under air for several weeks. Pentosidine levels were determined at intervals by HPLC assay. Pentosidine rose to a much larger extent in uremic than in control plasma. Pentosidine yield, i.e., the change in pentosidine level between 0 and 4 wk divided by 28 d, averaged 0.172 nmol/ml per d in uremic versus 0.072 nmol/ml per d in control plasma (P < 0.01). The difference in pentosidine yield between uremic and control plasma was maintained in samples ultrafiltrated through a filter with a 5000-Da cutoff value and fortified with human serum albumin (0.099 versus 0.064 nmol/ml per d; P < 0.05). Pentosidine yield was higher in pre- than in postdialysis plasma samples (0.223 versus 0.153 nmol/ml per d; P < 0.05). These results suggest that a large fraction of the pentosidine precursors accumulated in uremic plasma have a lower than 5000 Da molecular weight. Addition of aminoguanidine and OPB-9195, which inhibit the Maillard reaction, lowered pentosidine yield in both uremic and control plasma. When ultrafiltrated plasma was exposed to 2,4-dinitrophenylhydrazine, the yield of hydrazones, formed by interaction with carbonyl groups, was markedly higher in uremic than in control plasma. These observations strongly suggest that the pentosidine precursors accumulated in uremic plasma are carbonyl compounds. These precursors are unrelated to glucose or ascorbic acid, whose concentration is either normal or lowered in uremic plasma. They are also unrelated to 3-deoxyglucosone, a glucose-derived dicarbonyl compound whose level is raised in uremic plasma: Its addition to normal plasma fails to increase pentosidine yield. This study reports an elevated level of reactive carbonyl compounds ("carbonyl stress") in uremic plasma. Most have a lower than 5000 Da molecular weight and are thus partly removed by hemodialysis. Their effect on pentosidine generation can be inhibited by aminoguanidine or OPB-9195. Carbonyl stress might contribute to AGE modification of proteins and thus to clinically relevant complications of uremia.

Aged↗
PubMed1998

Vector autoregressive modeling analysis of frequently sampled oral glucose tolerance test results. 1. A new method for quantifying insulin resistance and secretion.

To elucidate abnormalities in the feedback relationships between plasma glucose and plasma insulin levels in diabetic patients, we have introduced the vector autoregressive modeling method as a new for tool feedback analysis. This technique was applied to plasma glucose and insulin level data from a series of 977 frequently-sampled oral glucose tolerance tests (FS-OGTT). Neither special instruments nor medications were used in FS-OGTT. We were able to predict the degree of the plasma glucose response occurring after an impulse-like increase in plasma insulin at 1 mU/mL, as well as the plasma insulin response triggered by an impulse-like increase in plasma glucose at 1 mg/dL, in the form of "impulse response curves". The predicted impulse response curve of glucose to insulin gradually changed from negative to positive with incremental changes in the fasting plasma glucose level, reflecting increased insulin resistance. Furthermore, the response of insulin to glucose decreased in a stepwise fashion with the incremental changes in the fasting plasma glucose level. Our findings confirm the usefulness of impulse response curves as clinical indicators. In addition, analytical data point to a possible contribution of excessive hepatic glucose production to the pathogenesis of the insulin resistance in non-insulin-dependent diabetes mellitus.

Administration, Oral↗
PubMed1998

Vector autoregressive modeling analysis of frequently sampled oral glucose tolerance test results. 2. Insulin resistance and secretion after gastrectomy.

Using the method of vector autoregressive modeling (VAR) analysis of frequently sampled oral glucose tolerance test (OGTT) results, we evaluated abnormalities in the feedback relationships between plasma glucose and insulin in gastrectomized patients to assess insulin secretion capacity and insulin resistance following gastrectomy. VAR modeling analysis was applied to the plasma glucose and insulin level data from the frequently-sampled 75g-OGTT results of 38 subjects who had undergone total or subtotal gastrectomy and 977 controls without gastrectomy. After gastrectomy, the predicted response of insulin to a glucose challenge was excessive in normal subjects and those with slightly impaired glucose tolerance. Furthermore, the glucose response to insulin was clearly positive in gastrectomized subjects with moderately to severely impaired glucose tolerance, i.e., diabetics, indicating strong insulin resistance. The insulin resistance in this situation cannot be explained by decreased peripheral glucose disposal. Our results suggest that the lowered glucose tolerance which follows gastrectomy results from disturbance of the hormonal relationship between pancreas and intestine (entero-insular axis), which causes increased intestinal glucose absorption, and the insulin resistance which occurs in response to hyperinsulinemia in patients with normal fasting plasma glucose. Disturbance of the entero-insular axis may cause not only increased glucose absorption but also hyperglucagonemia, both of which contribute to hyperglycemia in diabetic patients after gastrectomy.

Administration, Oral↗
PubMed1998

[Bladder cancer in patients over 80 years old].

We studied 86 patients with bladder cancer who were 80 years old and over. All were studied at the time of their first presentation for treatment in our hospital. About 40% of then were somewhat limited in performing usual daily activities before the first treatment, and they could not come to the hospital by themselves. Tumors in patients were larger, of higher grade and more invasive than those in younger patients. Transurethral resection of the bladder tumor (TUR-Bt) was done in 94% of patients with a superficial tumor and in 56% of those an invasive tumor. The recurrence rates after TUR-Bt for superficial tumor were 48%, 64% and 89% in 1 year, 3 years and 5 years, respectively. Recurrence rates were significantly different in younger patients. Overall cancer related survival rates were 86%, 60%, and 56% in 1 year, 3 years and 5 years, respectively. The outcome were significantly worse in patients over 80 years old than in those under 79 years old. To improve the outcome of treatment for bladder cancer in patients over 80 years old, cooperation among doctors, patients and families was important.

Aged↗
PubMed1998

[Functional hearing loss in children who were not aware of their hearing loss].

We investigated one hundred and fourteen ears of 60 children (8 males, 52 females, aged from 6 to 13 years) with diagnoses of functional hearing loss (FHL), and were not aware of their own hearing loss. Forty nine (81.7%) of 60 cases examined were detected by school screening tests, 6 (10.0%) were referred to our hospital because their families noticed poor hearing responses, and 5 (8.3%) were enrolled because they complained of otalgia or discomfort in the ear. Forty (66.7%) showed only pure tone threshold loss without complications, and the remaining 20 associated nonorganic disorders. In addition, our investigation found 11 cases (18.3%) with nonorganic otalgia, 5 (8.3%) with functional visual disturbance, 1 (1.7%) with enuresis nocturna who refused to attend school, 1 with tinnitus, 1 with vertigo, and 1 with tic. Moreover, 11 (18.3%) of the 60 cases were suspected of being in conflict with school and/or home. The Type V Békésy pattern, which is frequently observed in FHL and it has clinical utility to distinguish FHL from other types of organic hearing loss, was detected in 44 ears (38.6%). Fifty two (45.6%) of 114 ears showed normal pure-tone thresholds during the clinical course. Sixteen (14.0%) ears needed more than 1 year for thresholds to normalize. These findings suggest that some FHL cases without awareness of their hearing loss resemble psychogenic hearing loss. In such cases, otolaryngologists should carefully check the patient's individual circumstances, and when appropriate, refer patients for psychiatric consultation.

Adolescent↗
PubMed1998

[A clinical study of decreased bone density in the patients treated with long-term luteinizing hormone releasing hormone analogue (LHRH-a)--the risk of iatrogenic osteoporosis due to treatment of carcinoma of prostate].

BACKGROUND: It is well known that androgens play an important role in bone metabolism and male hypogonadism induce osteoporosis. Luteinizing hormone-releasing hormone analogue (LHRH-a) which is essential for conservative therapy of prostatic carcinoma (CaP) ultimately reduces circulating testosterone to castration levels. The purpose of this study was to determine the risk of decrease of bone mineral density in men receiving LHRH-a for CaP. PATIENTS AND METHODS: Fifty-three man with CaP aged 63 to 95 years (mean 75.5 years) were included in this study. Seven patients received LHRH-a with estrogen drug, forty-six patients received LHRH-a with or without anti androgen drug. To estimate patient's bone density we use the second metacarpal bone density using a microdensitometry method. RESULTS: Blood level of sex hormone of the forty-six patients who were received LHRH-a without estrogen, was the same as that of castration. Patients who were treated more than twelve months had less bone density than patients who were treated less than eleven months. As the duration of medical castration period was prolonged, patients bone density were reduced. Whereas seven patients who received estrogen drug did not find a decrease of bone density regardless of duration of treatment period. CONCLUSIONS: Hypogonadism induced LHRH-a also reduce bone density, so there is a risk of iatrogenic osteoporosis caused by therapy for CaP with LHRH-a. Patients with osteoporosis easily suffer from a much complicated and pernicious bone fracture, so we should measure bone density of male patients same as female treated with LHRH-a for a long-term.

Aged↗