Measurement and cytologic demonstration of 5-S-cysteinyldopa for the clinical diagnosis of primary leptomeningeal melanoma.
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Adult↗
Biomedical subjects
T Ochiai
Publications and source records attributed to T Ochiai.
Acute, subchronic and chronic toxicity studies of a synthetic antioxidant, 2,2'-methylenebis(4-methyl-6-tert-butylphenol) in rats.
General toxicity studies on 2,2'-methylenebis(4-methyl-6-tert-butylphenol) (MBMBP) were conducted using male and female Wistar rats. LD50 values were greater than 5 g/kg BW by oral administration for both sexes. Diarrhea was observed until 5 days. In the subchronic test, rats were fed diet containing MBMBP at 0, 0.12, 0.6 or 3.0% for 12 weeks. Severe suppression of body weight gain was observed in both sexes of 0.6 and 3.0% groups. Death accompanied by hemorrhage from nasal cavity was observed in 0.6 and 3.0% males and 3.0% females. Dose-dependent toxicity to the liver in both sexes was observed in blood chemical analysis. Histopathologically, testicular atrophy and decrease of spermatogenesis were dose- and time-dependently observed in all treated males. Atrophy of ovaries was evident in 0.6 and 3.0% females. Thymus atrophy and bone marrow hypoplasia were observed in both sexes of 0.6 and 3.0% groups. In the chronic test, rats were fed diet containing MBMBP at 0, 0.01, 0.03 and 0.1% for 18 months. Body weight gain was only suppressed in both sexes receiving 0.1%. Histopathologically, testicular atrophy and decrease of spermatogenesis were apparent in 0.1% males. No neoplastic response by MBMBP administration was noted. NOAEL was concluded to be 0.03% in the diet (12.7 mg/kg BW/day for male rats and 15.1 mg/kg BW/day for female rats).
Administration, Oral↗
Zinc as modulator of oxygenation function and stabilizer of quaternary structure in earthworm hemoglobin.
Blood of the earthworm Pheretima hilgendorfi contains 10.7 mM Ca, 2.0 mM Mg, 75.5 mM Na, 5.9 mM K, 0.9 mM Zn and 0.3 mM Mn. Some of these cations cannot be removed completely from the blood by dialysis, and 36 atoms of Ca, 1-3 atoms of Mg and 1-2 atoms of Zn per 164 atoms of Fe were retained in purified preparation of the hemoglobin (Hb). At physiological pH, oxygen affinity and the Hill coefficient at half saturation (n1/2 value) of the Hb increased in the presence of 100 mM of Ca, Mg or Na. These effects were in the order of Ca > Mg > Na. At physiological concentration, however, the effect of each of these three cations on oxygenation was rather small. On the other hand, Zn gave a remarkable effect at less than 1 mM. This suggests a possibility that Zn acts as a primal modulator for the oxygenation function of the Hb in vivo. Oxygenation data at various pH values in the presence of each cation strongly suggest that Zn binds to a site different from those for the other three cations. Zn at a concentration of only 1 mM protected considerably the dissociation of the whole molecule to smaller components at alkaline pH and Zn thus contributes to the stabilization of the quaternary structure of the Hb.
Animals↗
Combination of immunosuppressive drugs for organ transplantation.
Several novel immunosuppressive agents have been developed in recent years. They exhibited not only remarkable immunosuppressive potency but also side effects. They are still short of the final goal in terms of immunosuppression for organ transplantation. Combination treatment is more effective and safer to use, and it will prevail in the future.
Amylases↗
High-dose chemotherapy with autologous bone marrow transplantation in the treatment of advanced gastric cancer.
BACKGROUND: Clinical usefulness of high-dose chemotherapy with autologous bone marrow transplantation (ABMT) in the treatment of gastric cancer was investigated. METHODS: Ten patients with late-stage gastric cancer (four recurrent and six primary cases) with measurable lesions were treated with high-dose combination therapy consisting of etoposide (VP-16) (1200 mg/m2), adriamycin (80 mg/m2), and cisplatin (120 mg/m2) or carboplatin (900 mg/m2) (high-dose etoposide, adriamycin, and cisplatin [EAP] therapy). Afterward, 1 x 10(7)/kg of mononuclear cells, which were prepared from autologous bone marrow before treatment and cryopreserved, were transfused intravenously. RESULTS: All patients recovered from the aplastic period without severe complications. Of nine assessable cases, partial response was observed in eight (89% response rate). CONCLUSION: High-dose EAP therapy with ABMT is recommended as adjuvant therapy accompanied with radical operation for late-stage gastric cancer.
Adult↗
Structure of the Paramecium caudatum gene encoding the B-type of the major hemoglobin component.
We have found the gene (Hb) encoding the B-type of the major hemoglobin (Hb) component in the ciliated protist, Paramecium caudatum, stock K33 of syngen 3. Gene Hb, which encodes a protein consisting of 116 amino acids (aa), had the same sequence as the A-type Hb in this species, with the exception of 10 nucleotides (nt) reflecting 5 single-aa differences. The coding region was interrupted at the position between codons 62 and 63 by one short intron, which was comparable with the second intron of plant Hb in position, phase and nt sequence. The maximum alignment of the P. caudatum Hb aa sequence with the other globin sequences from prokaryotes and lower eukaryotes indicates that these globins can be classified into two groups: one consists of protist and cyanobacterial globins of about 120 aa, and the other consists of fungal and other bacterial globins of about 150 aa having a significant homology with higher eukaryotic Hbs. These proteins share more than 25% homology with one another in each group. Our finding of the P. caudatum Hb intron corresponding to the second intron of plant Hb suggests that all of the globin-encoding genes have a common origin, and that at least two groups had already existed in the globin-encoding gene before prokaryote-eukaryote radiation.
Amino Acid Sequence↗
Effects of rapamycin in experimental organ allografting.
The immunosuppressive effect of rapamycin (RAPA), a macrolide antibiotic produced by Streptomyces hygroscopicus, was tested using allografts in the rat and dog. It was immunosuppressive at a dose of 3.0 mg/kg/day for 8 days in skin allografts and 0.1 mg/kg/day for 11 days using cardiac allografts in the rat. It prevented rejection of renal allografts in beagle dogs at a dose of 0.3 mg/kg; however, emaciation and gastrointestinal toxicity resulted in some deaths in dogs. Mucosal necrosis and vasculitis in the submucosal layer were the predominant findings at autopsy in dogs receiving RAPA. Serum amylase values rose soon after commencement of RAPA treatment. Combined drug treatment with CsA at a nonimmunosuppressive dose of 3.2 mg/kg in the rat or 2.5 mg/kg in the dog was synergistic, with a low dose of 0.1 mg/kg/week RAPA. Combined therapy of CsA and RAPA also inhibited the frequency of vasculitis and emaciation in dogs. The present data suggest that RAPA is immunosuppressive in organ allografting and that the combination of CsA and RAPA would be effective clinically.
Animals↗
Sudden cardiac death from hypertrophic cardiomyopathy and acute idiopathic (Fiedler's) myocarditis: autopsy report.
A 45-year-old man with a rapidly deteriorating heart condition died suddenly, two hours after admission, after resistance to attempts of cardiac pacing. At autopsy, the heart weighed 600g with asymmetric septal hypertrophy. Histological examination revealed an extensive and diffuse disarray of myocardial fibers in the ventricular septum and in the free wall of both ventricles. Pronounced mononuclear cell infiltrations and interstitial edema were distributed widely in both ventricles. There were few abnormal findings in the other organs. The diagnosis was hypertrophic cardiomyopathy accompanied by Fiedler's myocarditis. Such a case appears to be rare.
Cardiomyopathy, Hypertrophic↗
Effects of triple therapy of cyclosporine, FK 506, and RS-61443 on allogeneic small bowel transplantation in dogs.
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Animals↗
Pathologic characteristics of vasculitis in renal transplant recipient dogs receiving immunosuppressive agents, FK 506, rapamycin, or RS-61443.
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Animals↗
[Evaluation of immunotoxicity tests using cyclosporin A-treated rats: the International Collaborative Immunotoxicity Study II (cyclosporin A)].
Immunotoxicological effects of cyclosporin A (CsA) were studied by enhanced histopathological and functional tests in rats. Male F344 rats were orally administered with CsA in doses of 0, 2.5, 10, and 40 mg/kg/day for 28 successive days. Hematological examination revealed that the CsA treatment brought about a marked dose-dependent decrease in the number of WBCs, which was attributed to a decrease in the number of lymphocytes. In the femoral bone marrow, a significant reduction in the number of nucleated cells was observed, which was attributed to a decrease in the number of lymphocytes and erythroblasts. Histopathologically, diminution of thymic medullas, appearance of tangible body macrophages in thymic cortices, and calcification and basophilic changes in kidneys were observed in the middle and high dose groups. Immunohistological examination with anti-rat T lymphocyte antibody showed a decrease in the number of T cells at the periarterial lymphatic sheaths in the spleens. As for the functional tests, CsA treatment remarkably reduced the PFC number even in the low dose group. The Con A response of spleen cells was decreased in the middle and high dose groups. The STM response was reduced only in the high dose group. The NK activity was little affected. Thus, in the CsA-treated F344 rats, the enhanced histopathological and some functional tests which were proposed by ICICIS, were found to be useful to detect damages to the immune system.
Administration, Oral↗
Role of ICAM-1 and LFA-1 in cardiac allograft rejection of the rat.
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Animals↗
[Analysis of antigen non-specific suppressor T cells factor (TsF) which suppresses the generation of cytotoxic T lymphocytes].
Anti-mouse melanoma suppressor T cells clone (F12) secreted a functional factor (TsF) which suppresses the generation of cytotoxic T lymphocytes (CTL). Ts clone F12 secreted TsF into culture supernatant by stimulating for more than 12 hours with anti-CD3 monoclonal Ab. In syngeneic CTL induction system, TsF suppresses the generation of both anti-melanoma and anti-lymphoma CTL. Moreover, TsF suppresses allogeneic CTL not only from C57BL/6 mice but also from C3H mice. Analysis of the biochemical and physiochemical character of TsF shows that TsF is stable for variance of pH and freeze and thawing, but unstable for heat in region of 100 degrees C. and in acetonitorile. It is also suggested that the molecular weight of TsF is in the vicinity of 12,000 daltons on the analysis in high performance liquid chromatography. F12 clone secretes other suppressive cytokine, TGF-beta and INF-gamma. However, TsF seems different from these suppressive cytokine, because anti-TGF-beta serum which blocks the suppressive function of TGF-beta 1 for CTL generation does not block TsF function. Moreover, recombinant INF-gamma does not suppress the generation of CTL.
Animals↗
The unique structure of the Paramecium caudatum hemoglobin gene: the presence of one intron in the middle of the coding region.
The gene encoding hemoglobin (Hb) in the ciliated protist, Paramecium caudatum, has been cloned and sequenced. A single Hb locus was detected on an isolated genomic fragment with a size of approx. 15 kbp. This gene contained 443 bp. The 5' transcriptional regulatory region contained TATA box- and CAAT box-like sequences which resemble the structure of the promoter region in higher eukaryotic genes. The amino acid sequence deduced from the gene agreed precisely with that of the major Hb component. It was an unusual structure, much smaller than Hbs from many other organisms. Furthermore, all of the untranslated regions in this gene were also small. Particularly, one intervening sequence (intron) being only 23 bp was shorter than any other introns reported for eukaryotic genes encoding protein. The position of the intron in the P. caudatum Hb gene corresponded closely to that of the second intron which had been reported only for plant Hb genes. Possible routes for the evolution of Hb genes were discussed.
Amino Acid Sequence↗
Molecular cloning of the cDNA for the major hemoglobin component from Paramecium caudatum.
Nucleotide sequence of the cDNA for the major hemoglobin component of Paramecium caudatum was determined. An oligonucleotide was synthesized on the basis of the amino acid sequence, and the Paramecium cDNA library constructed in phage lambda gt11 was screened with it. Three positive clones, of which insert sizes were 0.4, 0.6, and 0.9 kbp, were obtained. Sequence analysis made clear that the 0.4-kbp cDNA retains a full length of the nucleotides encoding 116 amino acid residues, and that in the coding region it contains four TAA codons which are known to encode glutamine.
Amino Acid Sequence↗
Cell-cell interaction in graft rejection responses: induction of anti-allo-class I H-2 tolerance is prevented by immune responses against allo-class II H-2 antigens coexpressed on tolerogen.
The intravenous sensitization of C57BL/6 (B6) mice with class I H-2-disparate B6-C-H-2bm1 (bm1) spleen cells results in almost complete abrogation of anti-bm1 CD8+ helper (proliferative and interleukin 2-producing) T cell (Th) activities. Although an appreciable portion of CD8+ cytotoxic T lymphocyte (CTL) precursors themselves remained after this regimen, such a residual CTL activity was eliminated after the engrafting of bm1 grafts, and these grafts exhibited prolonged survival. In contrast, the intravenous sensitization with (bm1 x B6-C-H-2bm12 [bm12])F1 cells instead of bm1 cells failed to induce the prolongation of bm1 graft survival as well as bm12 and (bm1 x bm12)F1 graft survival. In the (bm1 x bm12)F1-presensitized B6 mice before as well as after the engrafting of bm1 grafts, anti-bm1 CTL responses that were comparable to or slightly stronger than those observed in unpresensitized mice were induced in the absence of anti-bm1 Th activities. bm1 graft survival was also prolonged by intravenous presensitization with a mixture of bm1 and bm12 cells but not with a mixture of bm1 and (bm1 x bm12)F1 cells. The capacity of CD4+ T cells to reject bm12 grafts was eliminated by intravenous presensitization with antigen-presenting cell (APC)-depleted bm12 spleen cells. However, intravenous presensitization with APC-depleted (bm1 x bm12)F1 cells failed to induce the prolongation of bm1 graft survival under conditions in which appreciably prolonged bm12 graft survival was induced. More surprisingly, bm1 graft survival was not prolonged even when the (bm1 x bm12)F1 cell presensitization was performed in CD4+ T cell-depleted B6 mice. This contrasted with the fact that conventional class I-disparate grafts capable of activating self Ia-restricted CD4+ as well as allo-class I-reactive CD8+ Th exhibited prolonged survival in CD4+ T cell-depleted, class I-disparate cell-presensitized mice. These results indicate that: (a) intravenous presensitization with class I- and II-disparate cells fails to reduce anti-allo-class I rejection responses that would otherwise be eliminated using only class I-disparate cells; (b) such failure is generated according to the coexpression of both classes of alloantigens on a single cell as tolerogen; and (c) allo-class II antigens coexpressed on tolerogen function to activate CD4+ as well as non-CD4+ Th leading to the generation of anti-class I effector T cell responses.
Animals↗
Disposition of beta-hexachlorocyclohexane, p,p'-DDT, and trans-chlordane administered subcutaneously to monkeys (Macaca fascicularis).
To evaluate skin lipid analysis for the accumulation level of environmental pollutants, the correlations between organochlorine pesticide residues in adipose tissue, blood, and skin lipids of monkeys were studied. The mixture of beta-hexachlorocyclohexane (beta-HCH), p,p'-DDT, and trans-chlordane was subcutaneously given to monkeys once weekly for 5 weeks at dose levels of 1 and 10 mg/kg. The chemicals distributed in adipose tissue, blood, and skin lipids were determined six times after the last dosing at intervals of 4 to 9 weeks. Oxychlordane and p,p'-DDE were detected in all tissues together with the administered chemicals. In blood and adipose tissue, trans-chlordane decreased rapidly and oxychlordane and p,p'-DDE increased gradually and then remained at constant levels. beta-HCH and p,p'-DDT in adipose tissue increased until the 12th week and then decreased in all animals. The correlation coefficients between blood and adipose tissue regardless of dose level and collection time for each chemical ranged from 0.83 to 0.94. Correlation coefficients between skin lipids and adipose tissue varied with the chemical, namely, 0.31, 0.72, 0.81, 0.81, and 0.83 for p,p'-DDE, trans-chlordane, p,p'-DDT, beta-HCH, and oxychlordane, respectively. The results indicated that skin lipid analysis may be useful for the evaluation of specific pollutants in the body burden.
Adipose Tissue↗
Hair analysis for drugs of abuse. V. The facility in incorporation of cocaine into hair over its major metabolites, benzoylecgonine and ecgonine methyl ester.
We studied the incorporation of cocaine (COC), benzoylecgonine (BE) and ecgonine methyl ester (EME) into hair from blood. At first, the time courses of three drugs in rat plasma following i.p. administration of cocaine were investigated over 360 min. AUCs of COC, BE and EME in plasma were 14.2, 60.7 and 53.4 micrograms/ml/min, respectively. In contrast, the concentrations of the three compounds in hair were 16.4, 1.7 and 0.8 ng/mg. In spite of that, the AUC of COC in plasma was much lower than that of the other two compounds in plasma, the concentration of COC in hair was much higher than that of the other two compounds. The incorporation of COC into hair was much greater than that of BE and EME. If the incorporation of drugs from blood into hair is compared by [concentration in hair]/[AUC in plasma], that of COC, BE and EME is represented by 77:1.9:1. Our results suggest that the incorporation of drugs into hair from blood unexpectedly depends upon the physical properties of each drug.
Animals↗