[A clinicopathologic study on islets of Langerhans in cases of chronic dialysis].
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Biomedical subjects
Publications and source records attributed to K Suda.
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The 46,XY,del(5)(q31),del(12)(p11) and 46,X,-Y,del(5)(q31),del(12)(p11), +mar clones were found in the bone marrow cells of a 64-year-old Japanese man with chronic myelomonocytic leukemia (CMML). Although the 5q- anomaly has been reported to occur in various hematologic disorders, a literature survey of CMML cases revealed that the present case is the first instance of CMML with the 5q- anomaly. The possible significance of the chromosome findings is discussed.
Yeast cytochrome c oxidase subunit IV (an imported mitochondrial protein) is made as a larger precursor with a transient pre-sequence of 25 amino acids. If this pre-sequence is fused to the amino terminus of mouse dihydrofolate reductase (a cytosolic protein) the resulting fusion protein is imported into the matrix space, and cleaved to a smaller size, by isolated yeast mitochondria. We have now fused progressively shorter amino-terminal segments of the subunit IV pre-sequence to dihydrofolate reductase and tested each fusion protein for import into the matrix space and cleavage by the matrix-located processing protease. The first 12 amino acids of the subunit IV pre-sequence were sufficient to direct dihydrofolate reductase into the mitochondrial matrix, both in vitro and in vivo. However, import of the corresponding fusion protein into the matrix was no longer accompanied by proteolytic processing. Fusion proteins containing fewer than nine amino-terminal residues from the subunit IV pre-piece were not imported into isolated mitochondria. The information for transporting attached mouse dihydrofolate reductase into mitochondria is thus contained within the first 12 amino acids of the subunit IV pre-sequence.
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Bile pancreatitis was studied both macropathologically and histopathologically in cases with an abnormal pancreatic choledochoductal junction, in which free communication between the pancreatic duct and the common bile duct occurred. The intraductal pressure of the pancreatic duct is normally higher than that of the bile duct, therefore, the pancreatic juice flows into the bile duct. In this study, we found squamous carcinoma cells from an adeno-squamous cell carcinoma of the gall-bladder in the main pancreatic duct. Hence, the possibility of bile reflux into the pancreatic duct was also considered. Outstanding findings, such as degeneration and disappearance of the pancreatic ductal epithelium, intraluminal aggregation of bacilli, and diffuse interlobular fibrosis were found in four of 15 cases with an abnormal junction. Similar ductal alterations and diffuse fibrosis were found neither in the controls nor in the remaining 11 cases. Therefore, it appears that pancreatic disorders due to the reflux of bile occurs in the presence of bacteria.
A histopathologic study on hemosiderin deposition in the pancreas was performed. This study included three patients with primary hemochromatosis and 25 patients with aplastic anemia who were receiving blood transfusions. In the three patients with primary hemochromatosis, hemosiderin deposition was present in the acinar tissue, interstitium, islets of Langerhans, and ductal epithelium but occurred predominantly in the acinar tissue. Fibrosis was also found in the interlobular and intralobular areas in a diffuse and irregular manner. A micronodular arrangement of the acinar tissue was present in the atrophic exocrine pancreas. In patients with aplastic anemia who were receiving blood transfusions, the distribution and the quantity of hemosiderin approximately increased in accordance with the volume of blood given. Atrophy of the acinar tissue, interstitial fibrosis, and micronodular formation in the exocrine pancreas occurred in those patients who received a large volume of blood. Therefore, micronodular formation in the exocrine pancreas was one of the characteristic findings in patients with primary hemochromatosis and in patients with aplastic anemia who had received blood transfusions over a long period.
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To isolate nuclear genes specifying imported mitochondrial proteins, a yeast genomic clone bank was screened by an RNA hybridization-competition assay. This assay exploited the fact that mRNAs for imported mitochondrial proteins are enriched in polysomes which are bound to the mitochondrial surface in cycloheximide-inhibited yeast cells. Clones selectively hybridizing to these enriched mRNAs were further screened by hybrid-selected translation and immunoprecipitation with monospecific antisera against individual mitochondrial proteins. Thirty-six clones were isolated which contained complete or partial copies of 16 different genes for imported mitochondrial proteins. Several of these clones caused expression of the corresponding precursor polypeptide in Escherichia coli or over-expression of the corresponding mature protein in yeast. The gene for the matrix enzyme citrate synthase was sequenced; the derived amino acid sequence of the precursor polypeptide revealed an amino-terminal extension containing basic but no acidic residues.
Cytochrome c1 is a component of the mitochondrial respiratory chain in most eukaryotes. The protein is coded by nuclear DNA, synthesized as a larger precursor outside the mitochondria and then cleaved to the mature form in two successive steps during its import into the mitochondria. We have cloned the structural gene for yeast cytochrome c1 by functional complementation of a cytochrome c1-deficient yeast mutant with a yeast genomic library in the yeast-Escherichia coli 'shuttle' vector YEp 13. The complete nucleotide sequence of the gene and of its 5'- and 3'-flanking regions was determined. The deduced amino acid sequence of the yeast cytochrome c1 precursor reveals an unusually long transient amino-terminal presequence of 61 amino acids. This presequence consists of a strongly basic amino-terminal region of 35 amino acids, a central region of 19 uncharged amino acids and an acidic carboxy-terminal region of seven amino acids. This tripartite structure of the presequence resembles that of the precursor of cytochrome c peroxidase and supports a previous suggestion on the import pathways of these two precursors.
The anti-tumour effect of mouse interferon (IFN) on an intracranially transplanted 203-glioma in C 57BL mice and the natural killer (NK) activity of spleen cells were studied. As a clinical trial, five patients with glioblastomas were treated with human fibroblast IFN and the anti-tumour effect of IFN and the NK activity of peripheral blood lymphocytes were also studied. The NK activity increased after the beginning of IFN therapy but there was no remarkable anti-tumour effect of IFN in both mouse and human studies. There was no marked correlation between the increased NK activity and the anti-tumour effect of IFN in this study.