Search PubMed⌕ Search

Biomedical subjects

T Uchida

Publications and source records attributed to T Uchida.

At least 523 records · Page 29Linked to original sources
PubMed1994

Completely or nearly identical hepatitis B virus strains replicate between patients with acute or fulminant hepatitis B and their respective infectious sources.

Five patients with acute hepatitis B and four with fulminant hepatitis B were selected for sequencing of the precore/core gene of the virus strains. Furthermore, identical sequencing was done with the HBV of the infectious sources, i.e., the sexual partner in eight cases and a natural child (chronic carrier) infecting the mother in one case. Of the subjects responsible for the infection, four were healthy HBV carriers, three suffered from chronic hepatitis B, and one from acute and one from fulminant hepatitis B. The nucleotide sequences of HBV from both the patients and the implicated sources of infection exhibited perfect identity of the precore region and perfect or high identity of the core region. The completely or nearly identical strain of virus seemed to proliferate successively in the patients following the transmission from the infecting individuals regardless of sequence variations and infectious status. In two cases a peculiar pattern of infection and disease was found: In one married couple the husband, during the incubation period of acute hepatitis B, infected his wife, who developed fulminant hepatitis. In another married couple, both partners ultimately developed fulminant hepatitis (the wife being the source of the infection).

Acute Disease↗
PubMed1994

Evolution of the hepatitis B virus gene during chronic infection in seven patients.

We analyzed the evolution of the precore/core gene of hepatitis B virus (HBV) over a period of 6 to 11 years in seven patients with chronic HBV infection, who exhibited a variety of clinical features. Sequence analysis revealed the following results: (1) HBeAg to anti-HBe seroconversion was correlated roughly with the occurrence of precore-defective mutants, and several years appeared to be required for complete replacement of wild types by mutants; (2) core gene mutations preceded precore-defective mutations and tended to increase with time, although not cumulatively. They occurred not only during serum alanine aminotransferase (ALT) elevations but also after ALT returned to normal; (3) ALT fluctuations appeared to subside with complete replacement of the wild type by the mutant type and/or substantial accumulation of core gene mutations; (4) unexpectedly, the anti-HBe-positive "healthy" carrier was found to harbor the wild type precore gene, as did the HBeAg-positive "healthy" carrier; however, the core gene of the former evolved at a rapid rate; and (5) a partial deletion was recognized in the core gene at the onset of fatal hepatic failure in one patient. Thus, the precore/core mutation was closely related with the clinical features in the patients.

Adolescent↗
PubMed1994

Skin permeability of various drugs with different lipophilicity.

The in vitro and in vivo skin permeability of 16 drugs with a wide span of lipophilicity (log P ranging from -0.95 to 4.40) was evaluated with an ethanol/panasate 800 (tricaprylin) (40/60) system as a lipophilic vehicle. The ethanol/panasate 800 (40/60) binary vehicle remarkably improved the in vitro skin permeability of the drugs across excised hairless mouse skin compared with ethanol or panasate 800 as single vehicles. The in vivo skin permeability of the large majority of the drugs across abdominal rat skin also showed high permeation rates and short lag times. The relationship between lipophilicity and skin permeability of the drugs from the ethanol/panasate 800 (40/60) binary vehicle indicated parabolic shapes with their peaks at much greater hydrophilic range (log P: -0.88 for in vitro, -0.83 for in vivo) compared with other past references (log P: 2-3). The results suggest that the lipophilicity of a drug is a main factor for prediction of the skin permeability of the drug and that the ethanol/panasate 800 (40/60) lipophilic binary vehicle would be a good candidate as a vehicle for future clinical application of hydrophilic drugs.

Animals↗
PubMed1994

Immunoperoxidase staining of hepatitis C virus in formalin-fixed, paraffin-embedded needle liver biopsies.

The localization of hepatitis C virus (HCV) in the liver has not been well clarified. We report successful indirect immunoperoxidase staining of the HCV core antigen using polyclonal antibodies raised in rabbits and conventional formalin-fixed, paraffin-embedded needle biopsy sections of liver. The core antigen was distributed in a fine granular pattern diffusely, perisinusoidally, or focally within the hepatocellular cytoplasm of livers from patients with HCV infection. The staining tended to show a more heterogeneous pattern in terms of intensity and distribution in cases of more advanced disease. Hepatocellular carcinoma cells were also frequently stained. HCV immunostaining will provide important information on the pathogenesis and treatment of HCV-related liver diseases.

Adult↗
PubMed1994

Inhibition by Brefeldin A of the envelopment of nucleocapsids in herpes simplex virus type 1-infected Vero cells.

Inhibition by Brefeldin A (BFA) of the multiplication of herpes simplex virus (HSV) type 1 in Vero cells was characterized quantitatively. The yield of infectious progeny virus decreased exponentially with increasing concentrations of BFA while the yield of enveloped virus particles decreased less steeply to the level of approximately one fifth of the yield in the untreated cells; the level then remained constant even at higher BFA concentrations. The yield of nucleocapsids was not markedly affected by the drug. These results suggest that there are two different (i.e., BFA-sensitive and -insensitive) pathways for the formation of enveloped particles in the HSV-1-infected cells and that the infectious progeny virus arises exclusively from the BFA-sensitive pathway. Addition of BFA at various times after infection showed that the agent inhibited the increase in the amount of enveloped particles and of infectious progeny virus immediately after the addition. Single-step growth experiments suggested that, even in the presence of mature viral envelope proteins and of nucleocapsids, the increase in the amount of enveloped particles was completely inhibited by the addition of BFA at a late stage of infection. These results are consistent with the concept that the Golgi complex, the most BFA-sensitive organelle, is the major envelopment site of HSV-1 nucleocapsids leading to the formation of the infectious progeny virus.

Animals↗
PubMed1994

Effects of membrane lipid peroxidation by tert butyl hydroperoxide on the sodium current in isolated feline ventricular myocytes.

Membrane lipid peroxidation is known to play a pivotal role in the genesis of coronary reperfusion arrhythmias in both experimental and clinical settings. To elucidate the electrophysiological mechanisms underlying these arrhythmias, the effects of tert butyl hydroperoxide (TBH) on the Na+ current (INa) in isolated feline ventricular myocytes were studied using whole-cell patch clamp techniques under 100% O2 bubbling. This agent at 20 mM inhibited INa from 2.2 +/- 1.3 to 1.7 +/- 1.0 nA (P < 0.01, n = 7) without changing time courses of INa inactivation. Twenty millimoles TBH shifted the steady-state inactivation curve for INa from -77.4 +/- 1.7 to -81.3 +/- 1.8 mV when measured at INa half inhibition voltage (P < 0.01, n = 7), but did not affect the slope factor. The kinetics of INa recovery from inactivation remained unchanged. These findings suggest that lipid peroxidation in the membrane by TBH reduces INa conductance and voltage-dependent INa availability, most likely as a result of structural damage to the Na+ channels.

Animals↗
PubMed1994

Variations of hepatitis B virus precore/core gene sequence in acute and fulminant hepatitis B.

Variations of the hepatitis B virus (HBV) precore/core sequence has been shown to play a role in the development of active liver disease in chronic hepatitis B. Whether this is also an important viral factor in the pathogenesis of acute and fulminant hepatitis B is unknown. To determine the precore/core gene sequence in patients with acute and fulminant hepatitis B, 11 patients with fulminant hepatitis B and seven patients with acute hepatitis B were studied. The sequences of precore/core gene were determined by direct sequencing of the polymerase chain reaction amplicons generated from the HBV isolated from patients' serum. For the 11 patients with fulminant hepatitis B, the precore/core regions were successfully amplified in 10 patients. Eight patients exhibited precore stop codon mutations. In addition, nine of the 10 fulminant hepatitis B patients had frequent nucleotide substitutions with corresponding changes in the predicted amino acid sequences in the mid-core and the 5' terminus region of the core gene. In contrast, precore stop codon mutants were not detected, and variations of the HBV core gene were minimal in patients with acute hepatitis B. The association of HBV precore mutants and HBV core gene variations with fulminant hepatitis B and not acute hepatitis B suggested that these variations may be important in modulating the clinical course of HBV infection.

Acute Disease↗
PubMed1994

Clinical assessment of a continuous intraarterial blood gas monitoring system.

We evaluated the clinical performance of a continuous intraarterial blood gas monitoring (CIABG) system which includes a fluorometric intravascular sensor. Seventeen patients undergoing elective surgery were monitored perioperatively with the CIABG system (PB3300; Puritan Bennett, Carlsbad, CA). Conventional laboratory blood gas analyses (BGA) were performed simultaneously whenever indicated, and the values were compared with those obtained from the CIABG system. Monitoring time ranged from 24 to 72 hr. The biases (average error between PB3300 and BGA) of pH, PCO2 and PO2 were 0.003 pH unit, -2.8 mmHg, and 0.9 mmHg in the operating room (OR), and 0.005 pH unit, 3.9 mmHg, and 8.5 mmHg in the intensive care unit (ICU), respectively. The precision (standard deviation of the bias) of pH, PCO2 and PO2 were 0.030 pH unit, 2.1 mmHg, and 29.9 mmHg in the OR and 0.035 pH unit, 3.8 mmHg, and 14.7 mmHg in the ICU, respectively. Although the PB3300 system was clinically useful as a trend monitor, the system's precision and reliability were unacceptable for estimation of true blood gas values.

Adult↗
PubMed1994

Leukotriene D4-induced mucosal damage during long observation periods in vitro.

The effect of leukotriene D4 (LTD4) on human paranasal sinus mucosa was investigated for over 1 hour up to 24 hours using a VTR system at 2,500 X in vitro. Ethmoidal sinus mucosal specimens were incubated in tissue culture, and after exposure to LTD4 the mucosal surface profile was viewed under an inverted phase-contrast microscope equipped with a VTR system on a TVscreen. LTD4-induced ultrastructural alterations, ciliostasis, alterations consisted of a coarse profile and epithelial cell exfoliation. Ciliary activity was photoelectorically measured on the screen hourly. The mucosal specimens were morphologically examined before and after exposure to LTD4 by transmission electron microscopy. LTD4 inhibited ciliary activity in a time- and dose-dependent manner at concentrations ranging from 10(-6)M to 10(-10)M, whereas LTE4 had a minimal effect on the mucosa even at the concentration of 10(-6) M. Irrigation of the mucosa with culture medium after 5-min of exposure to 10(-8) M LTD4 delayed appearance of ciliary inhibition and alteration of the mucosal surface profile, but had no effect after 15-min exposure. These effects of LTD4 on the mucosa were blocked by preincubation with the LT antagonists, FPL-55712 and Ly-171883. These results demonstrate the cytotoxic effect of LTD4 on human airway epithelium in vitro.

Cilia↗
PubMed1994

Lunar base CELSS design and analysis.

This paper describes the conceptual development of a hybrid biological-physical/chemical (P/C) life support system model for a lunar outpost. It presents steps that lead to loop closure and determines mass flow characteristics for an inedible biomass enzyme reactor and an activated sludge bioreactor. Computer modeling techniques were used to determine that the cellulose reactor has the design capabilities to provide significant increases in the plant harvest index. Activated sludge was found to fit design demands for a small, continuous-flow, steady-state system. Systems analysis and component sizing for these two bioreactors and information regarding supporting bioregenerative and physical/chemical components are presented.

Biomass↗
PubMed1994

Cryotherapy for postoperative pain relief following knee arthroplasty.

Ninety consecutive patients undergoing primary knee arthroplasty received local cryotherapy 72 hours after surgery for pain relief. Thermal-pad circulating temperatures were randomly assigned to 50 degrees, 60 degrees, or 70 degrees F (room temperature). Pain relief was monitored using patient-controlled analgesia machines. The amount of morphine received and number of attempts per hour were statistically analyzed with relation to temperature group, age, sex, weight, side, and diagnosis. The amount of morphine injected was positively correlated to the number of attempts per hour and moderately correlated to body weight. There was no correlation between thermal-pad temperature or any other parameter and the amount of morphine injected after surgery.

Aged↗
PubMed1994

Malignant fibrous histiocytoma of the bladder with focal rhabdoid tumor differentiation.

A case of primary malignant fibrous histiocytoma of the bladder is presented. This tumor involving the bladder is rare and the unusual histological features in the present case caused significant delay in accurate diagnosis. Since early diagnosis and aggressive surgical resection are essential to the effective treatment of this neoplasm, physicians should continually bear in mind the possibility of this malignant tumor whenever the pathological diagnosis is inconclusive.

Aged↗
PubMed1994

Dose and load studies for subcutaneous and oral delivery of poly(lactide-co-glycolide) microspheres containing ovalbumin.

Poly(lactide-co-glycolide) microspheres containing different loads of OVA (0.05, 0.1, 0.5 and 1.0% w/w) were manufactured by a w/o/w emulsion/solvent evaporation method. Low load efficiencies of less than 20% were observed. Normal size distributions with mean volume diameters ranging from 3.7 to 4.7 microns were obtained for different batches. The in vitro release of OVA from different loaded microspheres showed an expected burst release with all batches. The in vivo dose study (1, 10, 25, 50 micrograms of OVA) was performed by subcutaneous and oral inoculation in mice by single (0 week) or double (0 and 3 weeks) administration of PLGA 50/50 microspheres containing 0.1% OVA. Subcutaneous administration showed an immune response (serum Ig levels by ELISA) statistically (Fisher's paired t-test; P < 0.05) above OVA saline negative controls at 3, 6 and 12 weeks after administration. Oral administration of microspheres produced statistically higher systemic immune responses at the higher doses. Single and double inoculation orally and subcutaneously produced similar serum antibody levels. The in vivo load study was performed by subcutaneous and oral administration to mice of 25 micrograms OVA contained in various loaded (0.05, 0.1, 0.5 and 1.0% w/w) microspheres. Serum immune responses at 3, 6, and 12 weeks after inoculation were statistically above OVA saline controls and were inversely proportional to the OVA load using either route. This observation suggested a relationship between the number of microspheres delivered and the in vivo serum response. Single subcutaneous administration of 0.05 or 0.1% OVA loaded PLGA 50/50 microspheres induced larger immune responses compared with complete Freund's adjuvant.

Administration, Oral↗
PubMed1994

Uchida rat (rSey): a new mutant rat with craniofacial abnormalities resembling those of the mouse Sey mutant.

A new mutant rat with small eyes (rSey) which was found in the course of breeding Sprague-Dawley rats is described. Genetic analysis demonstrates that rSey is inherited as an autosomal dominant mutation. Heterozygotes (rSey/+) have small eyes, while homozygotes (rSey/rSey) do not develop lens and nasal placodes, resulting in lack of eyes and the nose and perinatal death. rSey does not affect any other cranial regions including the maxilla, mandible, hyoid arch and otic vesicles. The genetics and phenotype of the mutant rat closely resemble the Sey mutation in the mouse, suggesting that rSey is the rat counterpart of the Sey mouse. Tissue recombination studies indicate that ectoderm from homozygotes (rSey/rSey) never differentiates into lens tissue even if it is cultured with normal optic vesicles from rSey/+ or +/+ embryos. In contrast, lens differentiation occurs when ectoderm from rSey/+ or +/+ as well as rSey/rSey embryos. These results suggest that the failure of head ectoderm from rSey/rSey embryos to differentiate into lens results from defects in the early differentiation signaling from the neural plate or underlying mesenchyme before the optic vesicle grows out to contact the head ectoderm.

Abnormalities, Multiple↗
PubMed1994

Localization and developmental changes of tau protein kinase I/glycogen synthase kinase-3 beta in rat brain.

tau protein kinase I (TPKI) purified from bovine brain extract has been shown to phosphorylate tau and to form paired helical filament (PHF) epitopes and was found recently to be identical to glycogen synthase kinase -3 beta (GSK-3 beta). Before elucidating a role of TPKI/GSK-3 beta in PHF formation, it is necessary to investigate the normal function of the enzyme. To study the distribution and developmental changes of the enzyme, specific polyclonal antibodies were prepared against TPKI and GSK-3 alpha. Immunoblot analysis demonstrated that TPKI was nearly specifically localized in the brain of adult rats. The level of TPKI in the rat brain was high at gestational day 18, peaked on postnatal day 8, and then decreased rapidly to a low level, which was sustained up to 2 years. Immunohistochemistry indicated primarily neuronal localization of TPKI. Growing axons were stained most intensely in the developing cerebellum, but the immunoreactivity became restricted to the gray matter in the mature tissue. Parallel fibers had a high level of TPKI and also stained intensely for tau. These findings indicate that tau is one of the physiological substrates of TPKI and suggest that the enzyme plays an important role in the growth of axons during development of the brain.

Animals↗
PubMed1994

Virus and bacteria enhance histamine production in middle ear fluids of children with acute otitis media.

Histamine levels were measured in 677 middle ear fluid (MEF) samples from 248 children (aged 2 months to 7 years) with acute otitis media (AOM); of these, 116 (47%) had documented viral infection. Histamine content was higher in bacteria-positive than in bacteria-negative MEF samples (P = .007) and higher in samples from patients with viral infection than in those from patients with no viral infection (P = .002). Bacteria and viruses together had an additive effect on histamine content in MEF. Histamine concentration in the initial MEF sample tended to be higher in patients with persistent otitis than in those with good response to treatment (P = .14). Results suggest that viruses, bacteria, or both induce histamine production, which leads to increased inflammation in the middle ear. Antihistaminic drugs may be beneficial. Large, prospective, controlled trials of the effects of antihistamine as an adjunct therapy in bacterial and viral AOM are required before recommendations can be made.

Acute Disease↗
PubMed1994

Regulation of choline kinase R: analyses of alternatively spliced choline kinases and the promoter region.

The previous report described the cloning kinase R1 cDNA [Uchida, T. and Yamashita, S. (1992) J. Biol. Chem. 267, 10156-10162]. A new cDNA, for choline kinase R2, was isolated from rat liver cDNA libraries. This transcript was thought to be generated by alternative splicing. Ribonuclease protection analysis revealed the presence of a third choline kinase. Three transcripts were detected in all of the examined rat tissues at different levels. Southern blot analysis demonstrated a single copy of choline kinase R gene. The genomic DNA containing the first exon and its flanking regions of choline kinase R gene was isolated and characterized. A number of transcription start sites, determined by ribonuclease protection and primer extension analyses, were found. The most 3' site, 193 base pairs upstream of the initiation codon and common in liver and testis, was the main site in liver. Some transcription start sites were detected only in testis. Choline kinase R gene showed features not only of a typical housekeeping gene but also of a gene regulated through a variety of putative cis-acting motifs. 3-Methylcholanthrene and carbon tetrachloride increased all of three transcripts to various levels, and enhanced transcription from the same start site, which scarcely gave a detectable product in normal liver.

Alternative Splicing↗