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Biomedical subjects

K Tsuchiya

Publications and source records attributed to K Tsuchiya.

At least 91 records · Page 5Linked to original sources

A potent antiviral effect on hepatitis C viral dynamics in serum and peripheral blood mononuclear cells during combination therapy with high-dose daily interferon alfa plus ribavirin and intravenous twice-daily treatment with interferon beta.

Hepatitis C virus (HCV) is known to infect and replicate within peripheral blood mononuclear cells (PBMC), thereby enabling the direct evaluation of antiviral mechanisms by analyzing HCV dynamics in PBMC. To address potential molecular differences associated with distinct antiviral regimens, we studied HCV dynamics in both serum and PBMC in 44 patients with HCV genotype 1b and high viral load who were randomly assigned to the following 4 different treatment groups: 1) combination therapy with 6 MU daily of interferon alfa 2b (IFN-alpha2b) plus 800 mg of ribavirin; 2) monotherapy with 6 MU daily of IFN-alpha2b; 3) monotherapy with twice-daily intravenous administration with 3MU of IFN-beta; and 4) monotherapy with daily intravenous administration with 6 MU of IFN-beta. HCV-RNA levels were measured serially using highly sensitive real-time detection polymerase chain reaction (PCR). HCV dynamics in both the serum and PBMC showed a "biphasic" pattern. The exponential decay slopes of the second phase were significantly higher in the combination or twice-daily dosing regimen groups compared with groups 2 or 4 (0.10 +/- 0.08 vs. 0.02 +/- 0.09 or 0.16 +/- 0.09 vs. 0.02 +/- 0.04 day(-1); P <.05 or P <.0005, respectively). Moreover, the viral half-lives in the second phase were significantly shorter in these groups (73.2 +/- 42.5 vs. 240.1 +/- 120.7 or 56.0 +/- 44.6 vs. 361.6 +/- 293.5 hours; P <.05 or P <.05, respectively). Additionally, the slope of HCV decline in PBMC tended to be higher in the combination regimens, as compared with monotherapy. Taken together, our data on HCV dynamics provide molecular insight into utilization of combination or twice-daily dosing regimens to increase rates of sustained viral eradication of HCV.

Adult↗

Open carpal tunnel decompression in long-term haemodialysis patients [corrected].

This retrospective study assessed the treatment of 91 cases of carpal tunnel syndrome in long-term haemodialysis patients. One group of patients underwent an enlargement reconstruction of the flexor retinaculum with synovectomy and the other group was treated with a conventional carpal tunnel release. There were no major changes or differences between the outcomes of the two groups. However, there was an earlier functional recovery of grip strength and a lower recurrence rate in the enlargement plasty with synovectomy group.

Aged↗

Assessment of systemic adverse reactions induced by ophthalmic beta-adrenergic receptor antagonists.

To assess quantitatively the risks of ophthalmic beta-blocking agents for cardiovascular and respiratory adverse reactions, we analyzed the binding kinetics of beta-blocking agents to the beta-1 and beta-2 adrenoceptors. The relationship between the occupancies for beta-1 and beta-2 adrenoceptors and the effects on the exercise pulse rate or the forced expiratory volume in one second (FEV1) after topical administration of carteolol, befunolol, timolol and betaxolol was analyzed using a ternary complex model. The beta-1 and beta-2 receptor occupancies after ophthalmic administration were calculated to be quite high as well as those after oral administration. The maximum occupancies for beta-1 and beta-2 receptors after ordinary ophthalmic administration were 52% and 88% for carteolol, 52% and 61% for befunolol, 62% and 82% for timolol, and 44% and 3% for betaxolol, respectively. Concave relationships were obtained between a decrease in exercise pulse rate and the beta-1 receptor occupancy and between a decrease in FEV1 and beta-2 receptor occupancy, respectively. Nasolacrimal occlusion was estimated to decrease the exercise pulse rate and FEV1 by 65% and 50%, respectively. The beta-1 and beta-2 adrenoceptor occupancies were proved to be the most appropriate indicators for cardiac and pulmonary adverse reactions evoked by ophthalmic beta-blocking agents.

Administration, Oral↗

Substantia nigra in progressive supranuclear palsy, corticobasal degeneration, and parkinsonism-dementia complex of Guam: specific pathological features.

Disease-specific findings in the substantia nigra were examined in cases of progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and parkinsonism-dementia complex of Guam (PDC); diseases in which the patients exhibit dementia and parkinsonism, with neurofibrillary tangles (NFTs) and glial tangles composed of hyperphosphorylated tau. Loss of pigmented neurons was extremely severe in these 3 diseases, and decrease of the nonpigmented neurons was severe in PSP and CBD. On the other hand, in PDC the decrease of the nonpigmented neurons was different in each patient. Topographically, in PSP the nonpigmented neurons were particularly depleted in the ventral part and relative preservation of the pigmented neurons was observed in the medial part at the level examined. Many NFTs were observed in PDC. Although the number of NFTs was small, many pretangles were seen in the neurons in CBD. Granular and hazy astrocytic inclusions were identified exclusively in PDC. Numerous argyrophilic neuropile threads were identified in CBD and PSP, but these were few in PDC. Many foamy spheroid bodies as well as coiled bodies were observed in PSP and CBD, but only a few were observed in PDC. In conclusion, PDC is a disease that is distinctly different from PSP and CBD. It is possible to differentiate between PSP and CBD by the occurrence of many pretangles in CBD, but some similarities between these 2 diseases indicate the existence of common pathological mechanisms.

Adult↗

Surgical therapy for dialysis-related spondyloarthropathy: review of 30 cases.

Surgical therapy for dialysis-related spondyloarthropathy was investigated regarding its spinal manifestation. Between August 1985 and May 1998, 31 operations were performed on 16 male and 14 female patients; of these, 17 had cervical and 13 had lumbar spinal disorders. The average patient age was 59 years. The average period of hemodialysis was 14.8 years. Twenty-eight of 30 patients had cystic bone lesions and 24 had carpal tunnel syndrome. Four major postoperative complications occurred: death from paralysis and respiratory distress, severe kyphosis from the collapse of the grafted bone, deep infection from instrumentation, and wire breakage and bone fusion failure. Postoperative results with an average follow-up period of 2.7 years were good in 19 cases (63%), fair in 8 cases (27%), and poor in 3 cases (10%). As yet, surgical intervention for dialysis-related spondyloarthropathy is still regarded as a noncurative treatment; furthermore, the anterior approach to the cervical spine has a high risk for postoperative complications.

Aged↗

Determination of glomerular filtration rate per unit renal volume using computerized tomography: correlation with conventional measures of total and divided renal function.

PURPOSE: Previous studies suggest that functional computerized tomography (CT) can measure glomerular filtration rate (GFR) per unit renal volume. We compared this index with conventionally determined GFR measurements. MATERIALS AND METHODS: A total of 16 men and 8 women 63.3 +/- 14.9 years old (range 31 to 88) were studied using with contrast enhanced CT. A single slice of kidney was scanned sequentially after bolus injection (0.5 to 1.0 ml. per second(-1)) of 20 ml. iopamidol (300 mg. iodine per ml.(-1)). GFR per volume of kidney was calculated using a Patlak graphical analysis, and this index was multiplied by renal volume on CT to yield global GFR (ml. per minute(-1)). Divided function was also calculated. GFR and divided renal function were calculated in all cases from radioisotope renography with 99m diethylenetetraminepentaacetic acid. In 12 subjects in whom 24-hour urine collection was possible GFR was also calculated from creatinine clearance. RESULTS: A strong correlation was observed between divided renal function, expressed with respect to the right kidney calculated from CT (52.7 +/- 14.8%, range 19.9% to 97.4%) and by radioisotope renography (51.7 +/- 14.6%, range 18.9% to 92.6%, r = 0.97, p <0.0001). A strong correlation (r = 0.92, p <0.0001) was also seen between global GFR determined by CT (80.1 +/- 43.9 ml. per minute(-1), range 38.2 to 197.9) and creatinine clearance (72.4 +/- 47.5, range 14.6 to 168.5), and was stronger than the correlation between the radioisotope and creatinine clearance method (r = 0.67, p = 0.02) in the same patients. CONCLUSION: Functional CT using nonionic contrast material can measure GFR normalized to renal volume and is an accurate alternative to conventional methods of renal function evaluation.

Adult↗

Phthalates rapidly increase production of reactive oxygen species in vivo: role of Kupffer cells.

The role of oxidants in the mechanism of tumor promotion by peroxisome proliferators remains controversial. The idea that induction of acyl-coenzyme A oxidase leads to increased production of H(2)O(2), which damages DNA, seems unlikely; still, free radicals might be important in signaling in specialized cell types such as Kupffer cells, which produce mitogens. Because hard evidence for increased oxidant production in vivo after treatment with peroxisome proliferators is lacking, the spin-trapping technique and electron spin resonance spectroscopy were used. Rats were given di(2-ethylhexyl) phthalate (DEHP) acutely. The spin trapping agent alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone was also given and bile samples were collected for 4 h. Under these conditions, the intensity of the six-line radical adduct signal increased to a maximum value of 2.5-fold 2 h after administration of DEHP, before peroxisomal oxidases were induced. Furthermore, DEHP given with [(13)C(2)]dimethyl sulfoxide produced a 12-line electron spin resonance spectrum, providing evidence that DEHP stimulates (*)OH radical formation in vivo. Furthermore, when rats were pretreated with dietary glycine, which inactivates Kupffer cells, DEHP did not increase radical signals. Moreover, similar treatments were performed in knockout mice deficient in NADPH oxidase (p47(phox) subunit). Importantly, DEHP increased oxidant production in wild-type but not in NADPH oxidase-deficient mice. These data provide evidence for the hypothesis that the molecular source of free radicals induced by peroxisome proliferators is NADPH oxidase in Kupffer cells. On the contrary, radical adduct formation was not affected in peroxisome proliferator-activated receptor alpha knockout mice. These observations represent the first direct, in vivo evidence that phthalates increase free radicals in liver before peroxisomal oxidases are induced.

Animals↗

Lyme disease Borrelia spp. in ticks and rodents from northwestern China.

In May 1999, field surveys of Lyme disease spirochetes were conducted around the Tianshan Mountains in Xinjiang Uygur Autonomous Region in northwestern People's Republic of China. Ixodes persulcatus ticks were obtained in a Tianchi Lake valley with primary forest, while the tick fauna was poor in the semidesert or at higher altitudes in this region. Species identities were confirmed by molecular analysis in which an internal transcribed spacer sequence was used. Of 55 adult ticks, 22 (40%) were positive for spirochetes as determined by Barbour-Stoenner-Kelly culture passages. In addition, some rodents, including Apodemus uralensis (5 of 14 animals) and Cricetulus longicaudatus (the only animal examined), and some immature stages of I. persulcatus (4 of 11 ticks) that had fed on A. uralensis were positive for spirochetes. Based on 5S-23S rRNA intergenic spacer restriction fragment length polymorphism analysis and reactivity with monoclonal antibodies, 35 cultures (including double isolation cultures) were identified as Borrelia garinii (20 isolates, including 9 Eurasian pattern B isolates and 11 Asian pattern C isolates), Borrelia afzelii (10 pattern D isolates), and mixed cultures (5 cultures, including isolates that produced B. garinii patterns B and C plus B. afzelii pattern D). These findings revealed that Lyme disease pathogens are distributed in the mountainous areas in northwestern China even though it is an arid region, and they also confirmed the specific relationship between I. persulcatus and genetic patterns of Borrelia spp. on the Asian continent.

Animals↗

Impact of nephron-sparing surgery on quality of life in patients with localized renal cell carcinoma.

OBJECTIVES: The aim of the study is to evaluate the impact of nephron-sparing surgery on postoperative quality of life (QOL) in patients with localized renal cell carcinoma, compared with radical nephrectomy. METHODS: From 1986 to 1996, a total of 66 patients with localized small renal cell carcinoma <4 cm in diameter and a functioning contralateral renal unit underwent radical nephrectomy (n = 51) or nephron-sparing surgery (n = 15). Of these, 50 patients evaluated various dimensions of QOL using standardized self-rating questionnaires, EORTC QLQ-C30. RESULTS: There is no significant difference in 5-year overall survival between the nephron-sparing surgery group and the radical nephrectomy group. With regard to postoperative QOL, patients who underwent nephron-sparing surgery showed a significantly higher score on physical function than patients treated with radical nephrectomy (p<0.05). Nephron-sparing surgery was additionally superior to radical nephrectomy in terms of fatigue, sleep disturbance, pain and constipation. CONCLUSION: Selected patients with localized, small, unilateral renal cell carcinoma and a normal contralateral kidney will benefit from nephron-sparing surgery.

Adult↗

Molecular cytogenetic analysis of the highly repetitive DNA in the genome of Apodemus argenteus, with comments on the phylogenetic relationships in the genus Apodemus.

The DNA of Apodemus argenteus was digested with DraI, and the resultant DraI fragment of highly repetitive DNA was isolated and analyzed by DNA filter hybridization, cloning, sequencing, and fluorescence in situ hybridization (FISH). Southern blot hybridization and nucleotide sequencing revealed that most of the DraI fragment consisted of a 230-bp repeating unit and contained no sex-chromosome-specific nucleotide sequences. The DraI fragment included the CENP-B box-like sequence, with a strong homology to the human CENP-B box sequence. FISH revealed that the DraI fragment was specific to all pericentromeric C-band-positive regions, as well as to the C-block of the X chromosome. No hybridization signals were obtained from A. speciosus, A. peninsulae peninsulae, A.p. giliacus, A. agrarius, A. sylvaticus, A. semotus, or Mus musculus when the DraI fragment was used as probe. Peptide nucleic acid (PNA)-FISH using the CENP-B box-like sequence in the DraI fragments as probe suggested that this nucleotide sequence was also specific to all pericentromeric C-heterochromatic regions of A. argenteus chromosomes. Zoo-blot hybridization using DraI-digested genomic DNA from three species of Apodemus (namely, A. argenteus, A. speciosus, and A. peninsulae) and from Mus musculus strongly suggested that the consensus DraI fragment contained nucleotide sequences that were species-specific for A. argenteus. These results also suggest that A. argenteus is phylogenetically distant from other Apodemus species examined, as well as the possibility that the DraI fragment might be related directly to the delayed quinacrine mustard fluorescence of many pericentromeric C-heterochromatic regions of the chromosomes in A. argenteus.

Animals↗

Electron paramagnetic resonance study on free radical scavenging and/or generating activity of dopamine-4-O-sulfate.

The free radical scavenging and/or generating activity of dopamine-4-O-sulfate was examined and compared with that of dopamine. In humans, dopamine mostly exists in two isomeric forms of sulfate ester conjugates as metabolites; i.e., dopamine-3-O-sulfate and dopamine-4-O-sulfate in the circulation. Dopamine is generally believed to be oxidized by molecular oxygen or another reactive oxygen species under physiological conditions, to form oxidized dopamine derivatives that are cytotoxic. However, it is not known whether dopamine conjugates are generated on interaction with reactive oxygen species or not. In the present study, we measured the susceptibility to oxidization of dopamine-4-O-sulfate by using electron paramagnetic resonance (EPR) spectroscopy and optical absorption spectrometry. Dopamine was easily oxidized and dopamine-derived radicals appeared, whereas dopamine-4-O-sulfate was not oxidized under physiological conditions. Furthermore, dopamine-4-O-sulfate did not react with a strong oxidizing agent, sodium periodate. These results suggest that dopamine-4-O-sulfate has resistance against autoxidation, and seems to be a stable metabolite of dopamine.

Dopamine↗

[Strain-, sex- and species-related differences of acetohexamide reductase and 20 beta-hydroxysteroid dehydrogenase activities in liver microsomes of experimental animals].

We examined physiological and genetic factors affecting acetohexamide reductase (AHR) and 20 beta-hydroxysteroid dehydrogenase (20 beta-HSD) activities in liver microsomes of experimental animals. Pronounced strain-related differences were found in both activities of AHR and 20 beta-HSD present in liver microsomes of male rats. Among rat strains tested in this study, even though a Wistar-Imamichi (WIM) rat strain was taken to lack AHR activity, it exhibited a significant 20 beta-HSD activity. These findings appeared to be in conflict with our conclusion reported so far, which AHR and 20 beta-HSD present in liver microsomes of male rats are identical enzymes. Thus the reason for this discrepancy was discussed. Furthermore, AHR and 20 beta-HSD activities were little or not observed in liver microsomes of female rats or male experimental animals other than the rat, indicating the existence of sex- and species-related differences in these two enzyme activities.

20-Hydroxysteroid Dehydrogenases↗

Antioxidants inhibit JNK and p38 MAPK activation but not ERK 1/2 activation by angiotensin II in rat aortic smooth muscle cells.

Angiotensin II (Ang II) induces vascular smooth muscle cell (VSMC) hypertrophy, which results in several cardiovascular diseases. Ang II-induced cellular events have been mediated, in part, by reactive oxygen species (ROS) which also involve activation of mitogen-activated protein (MAP) kinases. Although it has been proposed that the therapeutic administration of antioxidants is useful for vascular diseases, the precise mechanisms which regulate ROS-sensitive signaling events have not been well characterized. Thus, we hypothesized that antioxidants may affect ROS-mediated MAP kinases activation induced by Ang II. The present findings showed that Ang II stimulated rapid and significant activation of ERK 1/2, JNK and p38 MAPK in cultured rat aortic smooth muscle cells (RASMC). Ang II-induced ERK 1/2 activation was not affected by all antioxidants examined, whereas JNK was sensitive to all antioxidants. In contrast, p38 MAPK activation was inhibited by DPI and ascorbic acid concentration-dependently, but by NAC only at high concentration. DETC and Trolox C had no effects on p38 MAPK activation by Ang II. We further examined the effects of antioxidants on Ang II-induced increases in oxygen consumption as an index of ROS generation in RASMC. DPI strongly inhibited Ang II-induced increases in oxygen consumption. DETC also inhibited Ang II-induced oxygen consumption, whereas ascorbic acid markedly augmented it. These findings suggest that the inhibitory effects of antioxidants on MAP kinases activation in VSMC are attributable, in part, to their modulating effects on ROS generation by Ang II in VSMC. Thus, inhibition of MAP kinases by antioxidants may imply their usefulness for relief of cardiovascular diseases.

Acetylcysteine↗

Dynamic computer tomography is useful in the differential diagnosis of juxtaglomerular cell tumor and renal cell carcinoma.

We compared dynamic computer tomographic CT images of 3 cases of juxtaglomerular (JG) cell tumor with those of 8 cases of renal cell carcinoma (RCC). The JG cell tumor was visualized as a low- to high-density area in case 1, a low-density area in case 2, and a low- to iso-density area in case 3 before contrast enhancement. None of the JG cell tumors were stained during the early phase (1 min), but all were stained moderately during the late phase (5 min) after contrast enhancement. Although all cases of RCC were visualized as a low- to iso-density area before contrast enhancement, they were intensely stained during the early phase with significant washout during the late phase. The present results suggest that the dynamic CT scan is useful in the differential diagnosis of the JG cell tumor and RCC.

Adenocarcinoma↗

FLAIR MR imaging for diagnosing intracranial meningeal carcinomatosis.

OBJECTIVE: The purpose of this study was to compare unenhanced and contrast-enhanced fluid-attenuated inversion recovery (FLAIR) imaging with other sequences to visualize meningeal carcinomatosis. MATERIALS AND METHODS: Unenhanced FLAIR images were compared with spin echo T2-weighted and contrast-enhanced FLAIR images in five patients with documented meningeal carcinomatosis and four patients with suspected meningeal carcinomatosis. Comparisons were also made between contrast-enhanced T1-weighted and FLAIR images. RESULTS: In six patients, the unenhanced FLAIR images showed areas of abnormal hyperintensity within the sulci that were not noted on the spin-echo T2-weighted images. In all patients, the contrast-enhanced FLAIR images also showed meningeal enhancement, periventricular enhancement, or both. The contrast-enhanced T1-weighted and FLAIR images were equivalent in their depiction of abnormal enhancement in five of the nine patients; contrast-enhanced FLAIR images were superior in three patients. CONCLUSION: Unenhanced FLAIR images are of more value than spin-echo T2-weighted images for the diagnosis of intracranial meningeal carcinomatosis. Contrast-enhanced FLAIR images can sometimes surpass contrast-enhanced T1-weighted images in their quality.

Female↗

Some biological and biochemical activities of resormycin, a novel herbicidal antibiotic.

Biological and biochemical activities of resormycin were studied using unicellular green algae, Selenastrum capricornutum (abbreviated as Selena.), as a test organism. Resormycin inhibited the growth in vitro of Selena. more strongly in the dark than in the light. A weaker but more photo-stable derivative, (+/-)-2,3-dihydro-resormycin, showed more long-lasting activity against Selena. in the light. Resormycin started killing Selena. only after exposure for 2 days and longer, even at high concentrations. Resormycin at concentrations near IC50 rapidly inhibited incorporation of 3H-leu, but not 3H-UR or 3H-TdR, into the TCA insoluble fraction of Selena. Herbicidal activity of resormycin was confirmed using some crops and weeds.

Antifungal Agents↗