[Electron microscopic study on the pilar carcinoma with disseminated metastases and infundibulo-trichilemmal differentiation].
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Biomedical subjects
Publications and source records attributed to Y Mishima.
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Mouse and human cell extracts (S100) can support an accurate and efficient transcription initiation on homologous ribosomal RNA gene (rDNA) templates. The cell extracts were fractionated with the aid of a phosphocellulose column into four fractions (termed A, B, C and D), including one containing a major part of the RNA polymerase I activity. Various reconstitution experiments indicate that fraction D is an absolute requirement for the correct and efficient transcription initiation by RNA polymerase I on both mouse and human genes. Fraction B effectively suppresses random initiation on these templates. Fraction A appears to further enhance the transcription which takes place with fractions C and D. Although fractions A, B and C are interchangeable between mouse and human extracts, fraction D is not; i.e. initiation of transcription required the presence of a homologous fraction D for both templates. The factor(s) in fraction D, however, is not literally species-specific, since mouse D fraction is capable of supporting accurate transcription initiation on a rat rDNA template in the presence of all the other fractions from human cell extract under the conditions where human D fraction is unable to support it. We conclude from these experiments that a species-dependent factor in fraction D plays an important role in the initiation of rDNA transcription in each animal species.
A Eco RI 6.6 kb DNA fragment containing the 3'-end of 28S ribosomal RNA gene of the mouse was detected by Southern blot hybridization, and cloned in a lambda-phage vector. The site of transcription termination and the processed 3'-end of 28S RNA were determined on the cloned fragment and the surrounding nucleotide sequence determined. The 3'-terminal nucleotides of mouse 28S RNA are similar to those of yeast, Drosophila and Xenopus although the homology was lost drastically beyond the 3'-end of 28S RNA. 45S precursor RNA terminated at 30 nucleotides downstream from the 3'-end of 28S RNA gene. A structure of a dyad symmetry with a loop was found immediately prior to the termination site of 45S RNA. The rDNA termination site thus shares some common features with termination sites recognized by other RNA polymerases.
The transcription initiation site of the human ribosomal RNA gene (rDNA) was located by using the single-strand specific nuclease protection method and by determining the first nucleotide of the in vitro capped 45S preribosomal RNA. The sequence of 1,211 nucleotides surrounding the initiation site was determined. The sequenced region was found to consist of 75% G and C and to contain a number of short direct and inverted repeats and palindromes. By comparison of the corresponding initiation regions of three mammalian species, several conserved sequences were found upstream and downstream from the transcription starting point. Two short A + T-rich sequences are present on human, mouse, and rat ribosomal RNA genes between the initiation site and 40 nucleotides upstream, and a C + T cluster is located at a position around -60. At and downstream from the initiation site, a common sequence, T-AG-C-T-G-A-C-A-C-G-C-T-G-T-C-C-T-CT-T, was found in the three genes from position -1 through +18. The strong conservation of these sequences suggests their functional significance in rDNA. The S1 nuclease protection experiments with cloned rDNA fragments indicated the presence in human 45S RNA of molecules several hundred nucleotides shorter than the supposed primary transcript. The first 19 nucleotides of these molecules appear identical--except for one mismatch--to the nucleotide sequence of the 5' end of a supposed early processing product of the mouse 45S RNA.
A 10B-dopa analogue, 10B1-para-boronophenylalanine (10B1-BPA) has been found to have a marked melanoma killing effect as expressed by the Do value, 0.9-1.2 X 10(12) n/cm2. The Do value of the neutron alone is 2.8 X 10(12) n/cm2. After the introduction of high LET irradiation into radiotherapy, its higher energy deposition in the target cancer cells is one of the major problems currently to be solved. This can be achieved by our thermal neutron capture therapy in the order of cellular dimensions when we have highly tumor-seeking 10B-compounds available. Our present evidence seems to indicate that our new 10B1-BPA can highly concentrate 10B into melanoma cells, to as much as 11 times the level of the medium in the in vitro system.
The effect of dopa, cysteine, and glutathione on 5-S-cysteinyldopa (5-S-CD) genesis in melanoma cells cultured in normal and tyrosine- and cysteine-free media has been studied. In normal media only melanotic melanoma cells have been found to secrete 5-S-CD into the medium. In the presence of dopa and cysteine, both, media incubated with and without cells have been found to produce 5-S-CD. In the presence of dopa and glutathione, however, cell-free media did not show the presence of 5-S-CD. In contrast melanoma cell-cultured media has been found to contain large quantities of this amino acid. The optimum condition for maximum production of 5-S-CD via glutathione-dependent pathway has been found to be at the dopa concentration of 10(-5) M when glutathione is present at the concentration of 10(-5) M in the culture medium. Thus dopa concentration with regards to glutathione is 1:1 on the molar basis which is twice the dopa concentration required in in vitro noncellular tyrosinase system. It is suggested that higher dopa requirement in our melanoma cell culture system reflects the co-existence of eu- and pheomelanin synthesis taking place according to their genetically predetermined proportions.
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The clinical efficacy of ticlopidine, a platelet aggregation inhibitor, was evaluated in a double-blind placebo-controlled study on 193 patients with ischemic ulcers due to chronic arterial occlusion. In the group treated with ticlopidine, significantly better efficacy was noted over the placebo group in terms of judgment on overall improvement by doctors in charge as well as by the committee assessing with color slide films. The drug was particularly effective for the treatment of patients with occlusion in the arteries on the distal side and for the ischemic ulcer with relatively small size. In the group with ticlopidine, granulation was significantly improved compared to the placebo group. Those patients who had pain due to arterial occlusion on the distal side were significantly improved by this agent. The mean diameters of ulcers were clearly reduced. Therefore, this agent could possibly be claimed as an effective remedy against the main symptoms of chronic arterial occlusion. The frequencies of side effects and abnormalities in laboratory tests were comparable in the group treated with ticlopidine to those of the group with placebo. It was, therefore, concluded that this agent has an outstanding clinical value as a conservative treatment in chronic arterial occlusion.
In general malignant histiocytosis (MH) presents with fever, lymphadenopathy, general fatigue and malaise. Although facial involvement with MH has been mentioned previously, the present report emphasizes the significance and frequency of facial involvement in MH. The patient was 51-year-old woman who presented with fever, general fatigue, diplopia, and numbness on the right side of the face. A roentgenogram of the face showed parasinusitis. Histologic findings of the biopsy from the sinuses showed infiltration by atypical histiocytes. She died two months after onset of symptoms. Autopsy revealed a systemic neoplastic proliferation of atypical histiocytes diagnostic of MH. Facial involvement in MH is discussed with a review of reported cases and our own cases with MH.
Effect of dexamethasone of the growth of two T-cell acute lymphoblastic leukemia (T-ALL) cell lines, JM and TALL-1 and an American Burkitt lymphoma cell line, Ramos, of B-cell type was examined. While the growth of both TALL-1 and Ramos cell lines was significantly inhibited by dexamethasone at the concentration of 10(-7) M, JM cell line was markedly resistant at the high concentration of 10(-5) M of dexamethasone. The assay of glucocorticoid receptors showed that a small amount of the binding site was found in both T-cell leukemia cell lines, JM and TALL-1 and that a moderate amount of the binding site was found in Ramos cell line. Thus, glucocorticoid sensitivity (growth inhibition of these leukemia-lymphoma cell lines by dexamethasone) did not correlate with either the number of glucocorticoid receptor or with surface membrane markers of the target cells. This result suggests further marked heterogeneity of leukemic cells.
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Glycosylation inhibitors, glucosamine or tunicamycin, have been found to be specific inhibitory modulators for melanogenesis, which is accentuated generally in malignant melanoma cells. Exposure to glucosamine (1 mg/ml) or tunicamycin (0.2 to 0.4 micrograms/ml) induces a marked pigment loss within melanoma cells in vitro with a decrease in their grown curves. This melanogenic inhibition occurs without a substantial decrease in the synthesis of DNA, RNA, and protein in comparison with a specific, marked suppression of carbohydrate synthesis as revealed by suppressed mannose incorporation into these cells. Assay of tyrosinase of glucosamine- or tunicamycin-induced unpigmented melanoma cells has revealed a selective and marked decrease in the melanosome-rich large-granule fraction, but no substantial decrease in the total activity of remaining subcellular fractions. Electrophoresis of tyrosinase in the 30,000 X g supernatant fraction demonstrates an increase in the T1 form of soluble tyrosinase, while a disappearance of or marked decrease in membrane-bound tyrosinase, T3, is seen in the small- and large-granule fractions. Glycoprotein synthesis in the melanogenic subcellular compartments of pigment cells seems to play an integral role in melanogenesis which is principally enhanced in their carcinogenic status.
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To study the gastrointestinal hormones in hyperthyroidism and the interrelations with the thyroid hormones, the preprandial serum gastrin and motilin were measured by radioimmunoassay in 104 patients before and after the treatments. The following results were obtained: 1) Serum gastrin concentration in hyperthyroidism was significantly higher than that of the control, and when the patients reached euthyroidism or hypothyroidism after the treatments, the gastrin concentrations in the serum decreased to the normal level. There was a positive correlation between the thyroid hormones and the serum gastrin. 2) Serum motilin concentration in hyperthyroidism was slightly lower than that of the control. As the patients reached the euthyroid or hypothyroid state after the treatments, an increasing tendency of motilin was observed, though the change was not significant. There was a slightly negative correlation in gastrin versus motilin and also in T4 versus motilin.