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Biomedical subjects

H Uchida

Publications and source records attributed to H Uchida.

At least 91 records · Page 5Linked to original sources

Hepatic lymphocyte transplantation in hyperbilirubinemic gunn rats.

Hepatic lymphomyeloid cells (HLCs) are thought to contain liver stem cells. We investigated whether HLCs generated enzyme-producing cells in vivo. HLCs from normal Wistar/Shi rats and rats in which liver ischemia was induced using a portal clamp 4 days previously were studied histopathologically and characterized using flow cytometry. Splenic lymphocytes obtained from these animals were compared as a control. The proliferative activity of HLCs and splenic cells from both groups was also tested by stimulation with concanavalin A. HLCs contained a significantly higher number of NK-T cells and OV6+ cells compared with the splenic cells. The HLCs from rats in which liver ischemia was induced tended to have greater proliferative activity than those from normal rats, while the proliferative activity of splenic lymphocytes was impaired by liver ischemia. The HLCs obtained from Wistar/Shi rats with liver ischemia were then injected into hereditary hyperbilirubinemic Gunn rats to determine whether the HLCs generated enzyme-producing cells. After injection of these stimulated HLCs, the titer of serum bilirubin in the recipient rats was markedly reduced over a long time course (6.80+/-0.93 to 4.87+/-0.22 mg/dl after 1 month and 3.52+/-1.33 mg/dl after 6 months). The results of the present study indicate that HLCs have different populations than splenic cells, and ischemia-reperfusion of the liver increased their proliferative activity. HLC transplantation successfully reduced high bilirubin levels over a long time course.

Animals↗

Cellular activities of 20K- and 22K-hGH do not necessarily correlate with their binding affinities for rat GH receptor.

Even though 20K human growth hormone (20K-hGH) has 3-10% binding affinity for the rat liver and adipose tissue microsomes as compared to 22K-hGH, it was also reported that 20K-hGH has the same potency as 22K-hGH in the hypophysectomized rat weight gain assay. In order to investigate the reason why such controversial data exist, we have studied 20K- and 22K-hGH using the rat GH receptor extracellular domain (rGHR-ECD) and full-length rGHR. When we examined the complex formation of rGHR-ECD with 20K- and 22K-hGH in gel filtration assay, 20K-hGH formed no complex while 22K-hGH formed a 1:1 complex. Next, rGHR cDNA was introduced into Ba/F3 cells and CHO-K1 cells, and stable transfectants (Ba/F3-rGHR and CHO-rGHR) were established. In the proliferation of Ba/F3-rGHR cells, 20K-hGH had 10-fold lower activity than 22K-hGH, which is consistent with their affinities for rGHR. But surprisingly, in the Spi2.1 gene promoter activation in CHO-rGHR cells, 20K- and 22K-hGH had the same activity, which was found not only in stable CHO-rGHR clones but also in CHO-K1 cells transiently expressing rGHR. In conclusion, these results indicate that cellular activities of 20K- and 22K-hGH do not necessarily correlate with their binding affinities for rGHR.

Adipose Tissue↗

Aortic stent-grafting with transrenal fixation: use of newly designed spiral Z-stent endograft.

PURPOSE: To evaluate the feasibility and efficacy of a newly designed stent-graft placed across the renal arteries for exclusion of abdominal aortic aneurysms (AAAs) with short or tortuous proximal necks. METHODS: Among a group of AAA patients treated with endovascular grafting, 5 had tortuous proximal necks and 13 had necks <20 mm (mean 13 mm). In these 18 cases, a 2- to 3-cm uncovered segment of the stent-graft was placed transrenally using a catheter inserted into the renal artery as a guide for graft margin positioning. A newly designed stent-graft was constructed from a custom-made spiral Z-stent covered with a thin-walled Dacron material; the endografts were deployed through 16-F (aortoaortic model) or 18-F sheaths (bifurcated devices). Renal function was assessed by preoperative and postoperative measurement of urea nitrogen and creatinine. Aneurysm exclusion and renal artery patency were evaluated during follow-up using spiral computed tomography and angiography. RESULTS: The stent-grafts were correctly placed at the intended site in all 18 patients. Renal function was not affected except transiently in 1 patient who developed bilateral renal artery stenoses 24 hours after the procedure; Palmaz stents were deployed in each renal artery to reestablish satisfactory blood flow. Of the 33 renal arteries crossed by the bare stent-graft segment, all were patent over a mean 14-month follow-up (range 7-24), including the patient with Palmaz stents implanted for postprocedural renal stenosis. Complete aneurysm exclusion was maintained in 15 (83%) of 18 patients; proximal leaks persisted in 3 patients, including 2 with severely angled proximal necks. CONCLUSIONS: Transrenal placement of the uncovered leading edge of custom-made spiral Z-stent-based endografts appears feasible and clinically effective in the treatment of AAAs with short or tortuous proximal necks.

Aged↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1998). I. Susceptibility distribution].

The frequencies of bacterial isolation and susceptibilities to antimicrobial agents were investigated on 538 bacterial strains isolated from patients with urinary tract infections (UTIs) in 9 hospitals during the period of June 1998 to May 1999. Of the above bacterial isolates, Gram-positive bacteria accounted for 30.3% and Gram-negative bacteria accounted for 69.7%. Susceptibilities of several isolated bacteria to antimicrobial agents were as follows; against Enterococcus faecalis isolated from patients with UTIs, vancomycin (VCM), ampicillin (ABPC) and imipenem (IPM) had strong activities. Among E. faecalis strains, those with low susceptibilities to all drugs have increased in 1998, compared with those in 1997. VCM showed the highest activity against MRSA isolated from patients with UTIs. The MICs of VCM for all 34 strains were equal to or lower than 2 micrograms/ml. Arbekacin (ABK) was also active against MRSA with the MIC90s of 2 micrograms/ml. Against Escherichia coli and Klebsiella pneumoniae, all drugs except penicillins were active. Particularly, meropenem (MEPM) showed the highest activity with the MICs of 0.125 micrograms/ml or below. Almost all the drugs except minocycline (MINO) showed high activities against Proteus mirabilis. Against Pseudomonas aeruginosa, all drugs were not so active, with the MIC90s of 16 micrograms/ml or above. MEPM, IPM and gentamicin (GM) showed high activities against Serratia marcescens. Generally, it seemed that resistant strains of S. marcescens had decreased since 1996.

Anti-Bacterial Agents↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1998). II. Background of patients].

Clinical background was investigated on 449 patients with urinary tract infections (UTIs) from whom 591 bacterial strains were isolated in 9 hospitals during the period from June, 1998 through May, 1999. About distribution of age and sex of patients and type of infections, among males, patients less than 50 years old were few, and uncomplicated UTIs without indwelling catheters was most frequent. Among females, patients less than 20 years old were few, and uncomplicated was most frequent. Escherichia coli was the most frequently isolated in uncomplicated UTIs, and the higher the ages of patients, the higher were became the isolation frequencies of Enterococcus faecalis, Proteus spp. and Klebsiella spp. In complicated UTIs with indwelling catheters and without indwelling catheters, the types of pathogens had no relation with ages. The complication of infections had decreased E. coli but that had increased Proteus spp., Pseudomonas aeruginosa and Staphylococcus aureus. Until last year, use of antibiotics had decreased pathogens isolated from patients with uncomplicated UTIs drastically in our study. But, pathogens isolated after antibiotics had increased in 1998. As for surgical procedures and types of causative organisms in UTIs, E. faecalis were more isolated when surgical procedures were experienced, and E. coli were more isolated when they were not in uncomplicated and complicated UTIs without indwelling catheters. In complicated UTIs with indwelling catheters, types of causative organisms had no relationship with surgical procedures.

Adult↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1998). III. Secular changes in susceptibility].

Susceptibilities to various antimicrobial agents were examined for Enterococcus faecalis, Staphylococcus aureus, Echerichia coli, Klebsiella spp. and Pseudomonas aeruginosa that were isolated from patients with urinary tract infections (UTIs) in 9 hospitals during June 1998 to May 1999, and the results were compared with those obtained during the same period from 1990 to 1997 in uncomplicated UTIs and complicated UTIs. Among E. faecalis strains, those with low susceptibilities to almost drugs have increased in the latest period. All 5 S. aureus strains isolated from uncomplicated UTIs were the most susceptible to gentamicin (GM). Over 50% of S. aureus strains isolated from complicated UTIs were susceptible to GM, and on the contrary the resistant strains have increased with the MIC90 of 256 micrograms/ml or above. Among S. aureus strains isolated from complicated UTIs, those with low susceptibilities to arbekacin (ABK) have increased in the latest period compared to those during period of 1996-1997, and the MIC90s of them have changed into the lower state from 1 microgram/ml in 1996-1997 to 4 micrograms/ml in 1998. S. aureus strains have continued high susceptibilities to vancomycin (VCM). The susceptibilities to minocycline (MINO) of E. coli showed MIC90: 4 micrograms/ml in 1997, but those have returned in the latest period in uncomplicated UTIs. The MIC90s of ofloxacin (OFLX) to E. coli isolated from uncomplicated and complicated UTIs have been lower 2-3 classes in the latest period than those in 1997. Among Klebsiella spp. strains isolated from uncomplicated UTIs, those with low susceptibilities to almost cephems had increased in 1997, but few of them were detected in the latest study. The sensitive strains of P. aeruginosa to almost drugs have increased during the latest period. The MIC50s of cefozopran (CZOP) and OFLX against P. aeruginosa were the best in our history. The sensitive strains of P. aeruginosa to ceftazidime (CAZ) have increased and its percentage was 30%. Piperacilline (PIPC), cefoperazone (CPZ), GM and OFLX resistant P. aeruginosa strains have increased in the latest period.

Anti-Bacterial Agents↗

[Experimental study of esophageal covered stent for prevention of migration: use of clay to simulate stenosis of the esophagogastric junction or anastomosis site].

PURPOSE: An inner-covered Spiral Z-stent (IC-SZ) developed by our group was examined for its effectiveness in preventing migration by experimental comparison with commercially available esophageal covered stents. MATERIALS AND METHODS: The following six types of stents were used: inner-covered Spiral Z-stents with diameters of 16 mm (small IC-SZ) and 19 mm (large IC-SZ), outer-covered Spiral Z-stent (OC-SZ), covered Wallstent, covered Ultraflex stent, and Cook Z-stent. Experimental models were prepared using clay to simulate stenosis of the esophagogastric junction or anastomosis site due to tumor, and each stent was placed in the clay. After the stent had been fully expanded with a balloon catheter, one of its ends was pulled until the stent migrated out of the clay, and the traction force was measured. The inner cavity of the stent placed in the clay was observed using an endoscope. RESULTS: The mean maximal traction force required to pull the stents out of the clay were as follows, in decreasing order: 4.14 +/- 0.39 kg for the large IC-SZ, 4.12 +/- 0.83 kg for the small IC-SZ, 3.64 +/- 0.44 kg for the Cook Z-stent (p < 0.05), 3.34 +/- 0.62 kg for the covered Ultraflex stent (p < 0.05), 1.53 +/- 0.43 kg for the OC-SZ (p < 0.01), and 0.56 +/- 0.16 kg for the covered Wallstent (p < 0.01). The force required to pull out the large IC-SZ stent was the greatest, showing a significant difference from the values for the other four types of stents (excluding the small IC-SZ). Observation using an endoscope revealed that the wire of the IC-SZ stent was almost entirely embedded in the clay, whereas the wires of other stents were not. CONCLUSION: The IC-SZ stent may be less likely to migrate than other esophageal covered stents.

Biomechanical Phenomena↗

[Secular trends of sex ratios at birth in Japan].

OBJECTIVE: To describe secular trends of change in sex ratio at birth in Japan during the 100 years from 1899 to 1998. METHODS: Data on sex ratios (number of males to females at birth by prefecture) from 1899 to 1998 were obtained from the vital statistics of Japan. We used moving averages (9-years averages) to minimize the effects of yearly fluctuation on the sex ratio and calculated simple linear regression coefficients to examine trends in change for the period between 1925 and 1969 and between 1970 and 1998. RESULTS: The male: female sex ratio in Japan increased during the period through 1925 to about 1970 and thereafter decreased. The increase was the case for all prefectures with few exception, while these but Fukushima, Ibaraki, Fukui, Yamanashi and Kumamoto demonstrated subsequent decrease. The prefectures with strong decrease in the sex ratio from about 1970 at largely distributed facing the Sea of Japan; e.g. Akita, Toyama, Ishikawa, Kyoto, Shimane and Fukuoka. CONCLUSION: Our study confirmed a decline in the male: female sex ratio at birth in recent decades in Japan as a whole and in most prefectures. Although we do not know whether this is an effect of environmental pollution due to chemical substances, monitoring of secular trends in sex ratios should be continued with due attention to counsel to government.

Birth Rate↗

[Clinical evaluation of the Heidelberg Retina Tomograph II].

PURPOSE: To evaluate the usefulness of Heidelberg Retina Tomograph (HRT) II prototype, which is an easily handled model for routine optic disc examination in glaucoma clinics. METHODS: Ten eyes of 10 normal volunteers and 18 eyes of 18 open-angle glaucoma patients followed at Gifu University were studied. The reproducibility of three consecutive optic disc measurements with a 15 degrees x 15 degrees field using HRT II and with a 10 degrees x 10 degrees field using HRT (version 2.01) were evaluated by the same examiner on the same day. We also examined the correlation of the main topographic parameters (disc area, cup area, cup/disc area ratio, rim area, cup volume, rim volume, cup shape measure) between HRT II and HRT. RESULTS: The mean (+/- standard deviation) reproducibility of optic disc measurements with HRT II and HRT were 17.5 +/- 7.6 microns and 19.3 +/- 9.6 microns, respectively. This difference was not significant. All topographic parameters obtained from HRT II and HRT (R = 0.86-0.98, p < 0.01) showed statistically significant correlations with each other. CONCLUSION: The HRT II has high reproducibility of measurements and reliable stereometric parameters comparable to the conventional HRT.

Glaucoma, Open-Angle↗

Correlation between gamma-ray-induced G2 arrest and radioresistance in two human cancer cells.

PURPOSE: The correlation between radioresistance and gamma-ray-induced G2 arrest was examined in two human cancer cell lines, HeLa (cervical carcinoma) and MeWo (melanoma). METHODS AND MATERIALS: Cellular radioresistance was examined by a colony formation assay and Hoechst 33342 staining. G2 arrest induced by gamma-rays was examined by flow cytometry, and the accumulation of cyclin B1 and cdc2 proteins was analyzed using Western blotting. RESULTS: HeLa was more resistant (10% survival dose[D10] = 10 Gy) than MeWo (D10 = 4 Gy) to gamma-rays. In HeLa, cell cycle analysis showed that G2 arrest was induced 10 or 24 h after irradiation of 10 or 4 Gy, respectively. In contrast, no clear G2 arrest in MeWo was observed after irradiation. Western blot analysis showed that cell cycle regulators, cyclin B1 and cdc2, were accumulated in HeLa but not in MeWo. The accumulation of cyclin B1 and cdc2 reached peak levels 24-34 h after irradiation of 10 Gy, and 24 h after irradiation of 4 Gy. In addition, Hoechst staining revealed similar increase in apoptotic bodies with time after irradiation in HeLa and MeWo at isosurvival doses. CONCLUSION: Radioresistance of these human cancer cells is closely correlated with gamma-ray-induced G2 arrest, and cyclin B1 and cdc2 are possible regulators of G2 arrest.

Apoptosis↗

Selectivity of dihydropyridines for cardiac L-type and sympathetic N-type Ca2+ channels.

The blocking effects of cilnidipine and other dihydropyridines on L-type cardiac Ca2+ channels (I(Ca,L)) and N-type sympathetic Ca2+ channel currents (I(Ca,N)) were studied using a whole-cell patch-clamp technique. At -80 mV, cilnidipine had little inhibitory effect below concentrations of 1 microM on I(Ca,L) (IC50 value; 17 microM). However, 1 microM cilnidipine strongly shifted the steady-state inactivation curve of I(Ca,L) toward negative potentials without changing the current-voltage relationship. Each action of cilnidipine was characterized by a high affinity for the inactivated channel in preference to the resting channel. The IC50 values of dihydropyridines for I(Ca,L) were in the range between 0.01 and 10 microM, and those for I(Ca,N) were between 3 and 30 microM. Cilnidipine had the strongest affinity for I(Ca,N) among the dihydropyridines tested. These results suggest that cilnidipine did not cause hypotension-evoked tachycardia deficiency by depression of cardiac L-type channels but by sympathetic N-type channels blockade.

Animals↗

Chronopharmacology for deoxyspergualin: toxicity and efficacy in the rat.

BACKGROUND: Deoxyspergualin (DSG), a potent immunosuppressive drug, has been clinically used as a rescue therapy for acute graft rejection. However, DSG has severe adverse effects that limits its use. Here, we examined the optimized therapeutic protocol for DSG using chronopharmacological profiles of it. METHODS: First, a dosing time-dependent difference in the toxicity and efficacy of DSG was determined using a heterotopic heart transplantation model. Second, chronokinetics of DSG were examined to reveal the mechanism for dosing time-dependent differences in the effect. RESULTS: In rats treated with DSG at the active period, bone marrow suppression and damage of small intestine were significantly severe. However, no significant difference was found in cardiac allograft survival and pharmacokinetics according to the timing of drug administration. CONCLUSIONS: The toxicity of DSG varied with the dosing time, whereas its efficacy did not. The chronopharmacological approach may provide merits for immunosuppressive therapy with DSG in clinical organ transplantation.

Animals↗

Three distinct domains in TEL-AML1 are required for transcriptional repression of the IL-3 promoter.

A cytogenetically cryptic (12;21) translocation is the most common molecular abnormality identified in childhood acute lymphoblastic leukemia (ALL), and it generates a chimeric TEL-AML1 protein. Fusion of the Helix-Loop-Helix (HLH) (also called the pointed) domain of TEL to AML1 has been suggested to convert AML1 from a transcriptional activator to a repressor. To define the structural features of this chimeric protein required for repression, we analysed the transcriptional activity of a series of TEL-AML1 mutants on the AML1-responsive interleukin-3 (IL-3) promoter, a potentially relevant gene target. Our results demonstrate that TEL-AML1 represses basal IL-3 promoter activity in lymphoid cells, and deletion mutant analysis identified three distinct domains of TEL-AML1 that are required for repression; the HLH (pointed) motif contained in the TEL portion of TEL-AML1, and both the runt homology domain (Rhd) and the 74 amino acids downstream of the Rhd that are present in the AML1 portion of the fusion protein. Although AML1B (and a shorter AML1 isoform, AML1A) have transcriptional activating activity on the IL-3 promoter, fusion of the AML1 gene to the TEL gene generates a repressor of IL-3 expression. Consistent with this activity, freshly isolated human ALL cells that contain TEL-AML1 do not express IL-3.

Child↗

Influence of tacrolimus on bile acid and lipid composition in continuously drained bile using a rat model. Comparative study with cyclosporine.

Cholestatic effects have been reported for cyclosporine (CsA), but information is still limited for tacrolimus (TCR). The purpose of this study was to investigate the influence of TCR on biliary bile acid and lipid composition as compared with CsA, using a continuously bile-drained rat model. Adult male Wistar rats received TCR (0.4 mg/kg, 1 mg/kg, and 4 mg/kg) or CsA (2.5 mg/kg, 10 mg/kg, and 25 mg/kg) by intramuscular injection (i.m.) daily for 10 days. On day 7, the common bile duct of all rats was cannulated, then bile was continuously collected for the following 3 days. Bile flow, bile acid secretion rate (BASR), and biliary lipids secretion were measured for each of the groups. TCR increased bile acid-dependent flow (BADF) but with no statistical significance. However, this agent did not influence total bile flow and biliary lipids secretion, while bile acid-independent flow (BAIF) was significantly reduced and bile acid synthesis (mainly cholic acid, CA, synthesis) was increased. In contrast, CsA was cholestatic, showing a tendency to reduce both BADF and BAIF. BASR was dose-dependently suppressed, especially in chenodeoxycholic acid (CDCA). Furthermore, biliary lipids secretions were also significantly decreased under a higher dose of CsA. TCR increased BADF with no influence on total bile flow, having a stimulating effect on CA production, although CsA dose-dependently diminishes CDCA production and consequently reduced bile secretion. Our results suggest that TCR is a less effective agent on cholestasis as compared to CsA.

Animals↗

A pair of invertedly repeated genes in Chlamydomonas reinhardtii encodes a zygote-specific protein whose expression is UV-sensitive.

Uniparental inheritance of the chloroplast genome has been observed in a wide variety of green plants. In Chlamydomonas this phenomenon, which can be selectively inhibited by UV irradiation of mt(+) gametes, has been shown cytologically to be due to the preferential degradation of mt(-)-derived chloroplast nucleoids in young zygotes. The zygote-specific pair of zys1 genes, zys1A and zys1B, is expressed earliest among five genes isolated from a "10-min" zygote library. We report here that the ZYS1 protein, which is encoded by the invertedly duplicated zys1 gene, accumulates in zygotes and is localized in nuclei. In addition, when mt(+) gametes (but not mt(-) gametes) are UV-irradiated before mating, only very limited accumulation of ZYS1 protein can be detected in the resulting zygotes.

Algal Proteins↗

Sequence analysis of alleles at a microsatellite locus D14S299 (wg1c5) and population genetic comparisons.

In order to increase the discriminating power of DNA analysis in personal identification, we evaluated the forensic utility of the microsatellite locus D14S299 (wg1c5) in the Japanese population and also in the Chinese and Caucasian populations. Twelve different alleles were identified in length by gel electrophoresis with silver staining. The major alleles in Japanese were sequenced and designated as the numbers of the variable repeats (GGAT or GGAA). There were five variable regions and extensive homoplasy was found. However, the allele fragment lengths were in 4 bp increments and no "interalleles" were found. The estimated heterozygosity and the polymorphism information content (PIC) were 0.726 and 0.689, respectively in Japanese. Those in Chinese (0.743 and 0.704) were similar to those in Japanese, while those in Caucasians (0.812 and 0.781) were much higher. After adjacent alleles were combined to yield at least five entries, statistical analysis was performed. The power of discrimination (PD) was 0.887 in Japanese, 0.895 in Chinese and 0.935 in Caucasians and no significant deviations from the Hardy-Weinberg equilibrium were found in the three populations. We retyped all apparently homozygous samples using an alternative pair of flanking primers and found them to be true homozygotes. D14S299 appears to be a useful STR locus for forensic practice.

Asian People↗