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T Uchida

Publications and source records attributed to T Uchida.

At least 1,153 records · Page 64Linked to original sources

Complement activation by polymer binding IgG.

It was found that immobilized IgG on polymer carriers activates complement on contact with the serum. As polymers were microspherical in this study, complement fragments bound to polymers were detected by the agglutination of the polymer microspheres with the corresponding antisera or rosette formation with cells having complement receptors. Without the immobilization of IgG, polymers having amino, carboxyl, cyano or phenyl groups activated complement in the serum, while the presence of hydroxyl and carbamoyl groups in polymers did not cause complement activation. When intact IgG was bound to poly(glyceryl methacrylate) by the use of glutaraldehyde, the IgG-polymer conjugate activated complement in spite of the inertness of the polymer itself. The polymers immobilizing F(ab')2 activated complement less than the polymers immobilizing intact IgG. When dextran aldehyde prepared by periodate oxidation of dextran was used as a binder instead of glutaraldehyde, complement activation by F(ab')2-polymer conjugate was remarkably reduced, though antibody activity for binding the antigen remained. These results should be taken into consideration in the design of an immunosorption therapy.

Animals↗

Acute viral hepatitis: morphologic and functional correlations in human livers.

The usual histologic pattern in acute viral hepatitis (AVH) includes cellular abnormalities predominantly in the perivenular (zone 3) hepatocytes and changes interpreted as representing regenerative activity in the periportal (zone 1) hepatocytes. Enzyme histochemical and ultrastructural studies of livers of 12 patients with AVH were undertaken to see whether these features support the concept of regeneration of hepatocytes in zone 1. The swollen hepatocytes in the perivenular areas were hydropic, with dilated or eccentric rough endoplasmic reticulum and decreased or vesicular smooth endoplasmic reticulum; correspondingly, the glucose-6-phosphatase activity (reflecting, when present, intact and functional endoplasmic reticulum) was markedly decreased. Succinic dehydrogenase and diphosphopyridine nucleotide diaphorase activities, representing mitochondrial enzymes, were limited to the perinuclear or pericanalicular cytoplasm of swollen hepatocytes. gamma-Glutamyl transpeptidase activity was increased. The periportal hydropic hepatocytes were small and arranged in clusters displacing sinusoids. Ultrastructurally, these hepatocytes had nearly normal organelles but scanty smooth endoplasmic reticulum. Activities of the enzymes glucose-6-phosphatase, succinic dehydrogenase, and diphosphopyridine nucleotide diaphorase were weak, although glycogen was abundant. gamma-Glutamyl transpeptidase activity was scanty in these hepatocytes. These findings from enzyme histochemical and electron microscopic studies could be interpreted as evidence of functional deterioration of perivenular swollen hepatocytes and relative functional immaturity of periportal hydropic clustered hepatocytes, suggesting regeneration of zone 1 hepatocytes.

Acute Disease↗

Chromosomal assignment of the gene for human elongation factor 2.

Elongation factor 2 (EF-2), polypeptidyl -tRNA translocase, is an essential factor for protein synthesis in eukaryotic cells and Archebacteria . We isolated diphtheria toxin-resistant human primary embryo cells that contain EF-2 that cannot be ADP-ribosylated by diphtheria toxin and Pseudomonas exotoxin A (PA toxin). Somatic cell hybrids were constructed from mouse L cells and toxin-resistant human embryo cell mutants. Forty-one hybrid clones were isolated, of which 15 clones were resistant to PA toxin. Karyotypic analysis and isozyme studies revealed that there was an absolute correlation between human chromosome 19 and resistance to PA toxin in the hybrids. On subcloning of PA toxin-resistant hybrid cells, we obtained one PA toxin-resistant hybrid subclone containing human chromosome 19 as the only human chromosome. Furthermore, the resistance to PA toxin of hybrid cell strains was lost after infection with poliovirus, for which sensitivity is conferred by human chromosome 19. It was confirmed by using two-dimensional gel electrophoresis that PA toxin resistance in hybrid cells was caused by the presence of EF-2 resistant to ADP-ribosylation by fragment A of diphtheria toxin. These facts suggest that the gene encoding EF-2 is located on human chromosome 19.

ADP Ribose Transferases↗

Entry of diphtheria toxin into cells: possible existence of cellular factor(s) for entry of diphtheria toxin into cells was studied in somatic cell hybrids and hybrid toxins.

Ehrlich ascites tumor cells were found to be very insensitive to diphtheria toxin. We formed 37 hybrids from Ehrlich tumor cells and diphtheria toxin-sensitive human fibroblasts. The effects of diphtheria toxin on protein synthesis in those hybrids were examined. The hybrids were divided into three groups on the basis of toxin sensitivity. Group A hybrids were as sensitive to diphtheria toxin as human fibroblasts, Group C were as resistant as Ehrlich tumor cells, and Group B had intermediate sensitivity. Group A hybrids had diphtheria toxin-binding sites but Group B and C had no detectable binding sites. Elongation factor-2 of all the hybrids was susceptible to ADP-ribosylation by fragment A of diphtheria toxin. Cells of Group A and B became more sensitive to CRM 45 (cross-reacting material 45 of diphtheria toxin) after they were exposed to low pH (pH = 4.5). The resistance of Group C to CRM 45 was not affected by the same treatment. Group A and B hybrids and human fibroblasts had similar sensitivities to a hybrid toxin composed of wheat germ agglutinin and fragment A of diphtheria toxin, but Group C and Ehrlich tumor cells were resistant to this hybrid toxin. All the hybrids and Ehrlich tumor cells were more sensitive to a hybrid toxin composed of wheat germ agglutinin and subunit A of ricin than were human fibroblasts. On subcloning of Group B hybrids, one Group C hybrid was obtained, but no Group A hybrid. These facts suggest that Ehrlich ascites tumor cells differ from human fibroblasts in the expression of a factor(s) that is involved in entry of fragment A of diphtheria toxin into the cytoplasm after the toxin binds to its surface receptors.

Adenosine Diphosphate Ribose↗

Giant mitochondria in the alcoholic liver diseases--their identification, frequency and pathologic significance.

Three types of giant mitochondria have been described in hepatocytes, and we have investigated their ultrastructural features and occurrence in alcoholic liver disease. Type I mitochondria are spherical, with a paucity of cristae. Type II are elongated and have long crystalline insertions. Type III are relatively smaller and often bizarre in shape, containing multiple crystalline insertions. We defined megamitochondria as spheroidal giant mitochondria with a diameter roughly more than one third of the hepatocyte nucleus and visible under light microscopy. Type I was the most common form of megamitochondria in livers with ALD. Megamitochondria were present in livers of 58 (27.8%) of 209 consecutive patients with alcoholic liver disease, compared with 1 (0.7%) of a series of 145 patients with non-alcoholic liver disease. The frequency and occurrence of megamitochondria varied in different types and/or stages of alcoholic liver disease. In particular, livers with alcoholic foamy degeneration had significantly increased frequency and numbers of megamitochondria compared to other patterns of alcoholic liver disease. The ultrastructural studies showed that hepatocytes containing Type I mitochondria frequently had other damaged organelles and extensive focal cytoplasmic degradation. Enzyme histochemistry showed the foamy hepatocytes containing Type I had markedly decreased staining for glucose-6-phosphatase and slightly decreased staining for succinic dehydrogenase activities, while the hepatocytes with Type II or III had normal staining. In general, Type I giant mitochondria seem more characteristic to alcoholic liver disease, or conditions that produce similar hepatic morphology. It is particularly seen in alcoholic foamy degeneration and may be part of decompensation of the hepatocytes, while Types II and III occurred in hepatocytes of both alcoholic and non-alcoholic patients and had preserved function.

Humans↗

Alcoholic hyalin-containing hepatocytes--a characteristic morphologic appearance.

We studied the morphologic appearance of alcoholic hyalin (AH)-containing hepatocytes in liver biopsies from 14 patients with alcoholic liver disease. Most hepatocytes had a characteristic appearance. The cells were swollen and hydropic with an intact cell membrane. The mitochondria had variable-sized cristae which were both shortened and elongated. The smooth endoplasmic reticulum was markedly decreased. The rough endoplasmic reticulum was bizarre, with detachment of the ribosomes that surrounded the AH. The hepatocytes that contained AH bodies had lost almost all the glucose-6-phosphate activity but had variable amounts of succinic dehydrogenase and diphosphopyridine nucleotide diaphorase activities. The neutrophils admixed with mononuclear cells attached themselves to the hepatocytes and then invaginated into the hepatocytic cytoplasm with focal lysis of the cell membrane mediated via the release of neutrophilic lysosomes. The distortion of protein-synthesizing organelles and decrease in glucose-6-phosphatase activity suggest that the AH-containing hepatocyte is metabolically decompensated. The final cell death may be related to the neutrophilic attack, rather than the metabolic derangement.

Biopsy, Needle↗

Fulminant hepatic and renal failure complicating Wilson's disease.

We report a case of fatal fulminant liver failure complicating Wilson's disease that is unique in several respects. The illness supervened after several years of medical noncompliance in a patient who had been previously diagnosed and successfully treated with penicillamine. Re-institution of penicillamine therapy 2 weeks prior to the fulminant decompensation failed to prevent it. Renal failure in this patient was apparently secondary to rhabdomyolysis. Addition of penicillamine to a peritoneal dialysis solution allowed chelation and removal of over 14 mg per day of copper but without apparent benefit. Exchange transfusion and high dose dexamethasone therapy (24 mg/day) were equally ineffective in reversing the liver failure. Other reported cases have also been fatal. The best treatment for fulminant Wilson's disease is prevention by diagnosis in a pre-symptomatic stage and institution of carefully supervised life-long therapy with penicillamine.

Acute Kidney Injury↗

Effect of pacemaker sites on contractile forces of the local myocardium and blood flow in the major branches of the left coronary artery in anesthetized open-chest dogs.

Decreased cardiac performance during ventricular tachycardia or ventricular pacing has been ascribed to the lack of synchrony due to altered ventricular contraction. However, the direct effect of the pacemaking site on blood flow in the major coronary arterial branches and on regional contractile forces has not been adequately examined. In this investigation, twelve dogs were used to assess coronary flow in the left anterior descending (LAD) and circumflex coronary arteries (LCx) and the regional myocardial function in response to ectopic electrical pacing. The sites were the outflow tract of the right ventricle (RV pacing), the anterior left ventricular wall supplied by the LAD (LAD pacing), and the lateral wall perfused by the LCx (LCx pacing). Strain gauge arches were transmurally fixed to myocardial segments of the anterior and lateral walls of the left ventricle. The mechanical forces generated were measured while simultaneously recording blood flow in the LAD and LCx. RV pacing diminished developed-tension similarly in both areas. LAD flow was further decreased during anterior pacing as was the developed-tension in the LAD supplied area. A similar relationship was observed between LCx flow and developed-tension in the LCx area during lateral pacing. Compared to RV pacing, anterior pacing did not affect LCx flow and local myocardial force in the lateral wall of the left ventricle, and lateral pacing did not cause further changes in LAD flow and anterior myocardial function. The decrements in blood flow were closely related to decreased myocardial function (p less than 0.01). These findings indicate that ventricular pacing decreases ventricular performance with attenuated regional myocardial function at the pacing area, in addition to causing altered ventricular contraction sequence.

Animals↗

Simple technique for measuring regional contractility by a modified strain guage arch.

A simple modification of a commercially available gauge arch, namely the addition of pins to effect mechanical couplings to heart muscle rather than suturing, results in an isometric myocardial force sensor which is easy to insert, stable and relatively atraumatic to the myocardium. Compressing the pins by means of a machinist's vernier caliper which is removed after the sensor is implanted, insures controlled muscle stretch. Tests in open-chest dogs show that force sensed by this gauge is little affected by changes in heart rate, left ventricular end-diastolic pressure or aortic pressure, but faithfully reflects the inotropic effects of isoproterenol or propranolol. Thus, the modified strain gauge arch is sensitive to changes in contractility but not to changes in preload or afterload.

Animals↗

Co-storage of adrenaline and noradrenaline with Met-enkephalin-Arg6-Gly7-Leu8 and Met-enkephalin-Arg6-Phe7 in chromaffin cells of hamster adrenal medulla.

The co-existence of catecholamines with opioid peptides in adult hamster adrenal chromaffin cells was studied by Sternberger's peroxidase-antiperoxidase (PAP) method. Paraffin embedded serial sections (3-4 microns thick) of adrenal glands perfusion-fixed with either Bouin's fluid or 4% paraformaldehyde solution were immunostained using anti-adrenaline (AP16-2), -noradrenaline (NAP1-18), -Met-enkephalin-Arg6-Gly7-Leu8 (Met-Enk-Arg-Gly-Leu: R-0171, NE2-206) and -Met-enkephalin-Arg6-Phe7 (Met-Enk-Arg-Phe: AP3-311) sera. Selective and specific immunostaining for adrenaline and noradrenaline was obtained in tissues fixed in 4% paraformaldehyde solution. Bouin's fluid gave negative or unsatisfactory results. Immunostaining with two kinds of Met-Enk-Arg-Gly-Leu (R-0171, NE2-206) and one kind of Met-Enk-Arg-Phe sera (AP3-311) was dependent upon the method of fixation used. The immunostaining in the Bouin-fixed tissues was stronger than that in the 4% paraformaldehyde-fixed ones. Secretory granules in chromaffin cells were responsible for both adrenaline- and noradrenaline-like and Met-Enk-Arg-Gly-Leu- and Met-Enk-Arg-Phe-like immunoreactivities. All adrenaline-storing (A) and noradrenaline-storing (NA) cells showed intense Met-Enk-Arg-Gly-Leu- and Met-Enk-Arg-Phe-like immunoreactivities. In the Bouin-fixed adrenal medulla, immunostaining of A cells with the two kinds of anti-Met-Enk-Arg-Gly-Leu sera (R-0171, NE2-206) was deeper than that of the NA cells. Immunostaining of A cells with the anti-Met-Enk-Arg-Phe serum (AP3-311) was apparently of the same intensity as that of NA cells. In 4% paraformaldehyde-fixed tissues, no correlation was seen between the distribution of A and NA cells and that of intensely and slightly Met-Enk-Arg-Gly-Leu and Met-Enk-Arg-Phe immunopositive cells. The "masking" of immunoreactive residues in chromaffin granules by an aldehyde-noradrenaline complex may be one of the major causes of the decreased opioid peptide-like immunoreactivity in the 4% paraformaldehyde-fixed adrenal medulla.

Adrenal Medulla↗

[Chemotherapy of advanced genitourinary carcinoma with cis-diamminedichloroplatinum].

Eighteen patients with advanced genitourinary carcinoma have been treated with cis-diamminedichloroplatinum (CDDP) since 1978, at our University Hospital. They were 3 patients with prostatic cancer, 3 patients with bladder cancer, 6 patients with testicular tumors, 5 patients with renal cell carcinoma and 1 patient with malignant pheochromocytoma. Four patients with testicular tumors were administrated CDDP, bleomycin (BLM) and vinblastine (VBL). A testicular tumor patient was given CDDP, vincristine and actinomycin-D, a bladder cancer patient was given CDDP, VBL and Pepleomycin as combined chemotherapy. The remaining 12 patients were treated only with CDDP. Five of the 6 patients with testicular tumor and a case of choriocarcinoma of left kidney showed an objective response. As side effects, bone marrow suppression was inevitable when VBL and BLM were given along with CDDP. Renal dysfunction was seen in 5 patients on whom BVP regimen was employed. Various degrees of nausea and vomiting were present in almost all patients during CDDP administration. The combination chemotherapy with CDDP appears to be effective in nonseminomatous testicular tumor. The effectiveness of CDDP against other genitourinary carcinomas may require further investigation.

Adolescent↗

[Clinical evaluation of cefmenoxime in internal medicine, with special reference to infections associated with hematological disorders].

Clinical evaluation of cefmenoxime (CMX, Bestcall) was examined in the infection associated with hematological disorders, respiratory tract and other disorders. Clinical effectiveness for severe infection of hematological disorders was 47.4% in good and 84.2% in fair response, however, in the respiratory tract infections, 89.7% in good response was obtained. Opportunistic infection due to Gram-negative bacilli are often experienced in patients with hematological disorders. It was discussed that CMX would be a good therapeutic agent against infectious diseases associated with hematological disorders because it's antibacterial spectrum would be parallel to pathogens of such disorders.

Adolescent↗