Biomedical subjects
Publications and source records attributed to M Kurata.
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Two-particle correlations of direct photons were measured in central 208Pb+208Pb collisions at 158A GeV. The invariant interferometric radii were extracted for 100<K(T)<300 MeV/c and compared to radii extracted from charged pion correlations. The yield of soft direct photons, K(T)<300 MeV/c, was extracted from the correlation strength and compared to theoretical calculations.
Propeptides of papain-like cysteine proteinases such as papain, cathepsins B, L and S are potent inhibitors of their cognate cysteine proteinases with Ki values in the nanomolar range, and they exhibit highest inhibition selectivity for enzymes from which they originate. Recent studies have identified novel inhibitor proteins that are homologous to the proregions of papain-like cysteine proteinases. Mouse activated T-lymphocytes express cytotoxic T-lymphocyte antigen (CTLA-2), which is homologous to the proregion of mouse cathepsin L. CTLA-2 exhibits inhibitory activities to several cysteine proteinases. We have also identified a similar propeptide-like cysteine proteinase inhibitor, Bombyx cysteine proteinase inhibitor (BCPI), in the silkmoth Bombyx mori. BCPI is a slow and tight binding inhibitor of cathepsin L-like cysteine proteinases with Ki values in picomolar range, and the inhibition is highly selective towards these proteinases just like the propeptides. Recent genome analyses have shown the expression of similar propeptide-like proteins in Drosophila and rat, suggesting the presence of a novel class of cysteine proteinase inhibitors in a variety of organisms. Studies of the gene structures and phylogenetic analysis have shown that genes of the propeptide-like cysteine proteinase inhibitors have emerged from ancestor genes of their parental enzymes.
The clinicopathological features of 10 patients with primary mediastinal large B-cell lymphoma (PMLBCL) are described. The patients were aged 19 to 63 years, with a median age of 25.5 years. There were 5 men and 5 women. All patients presented with chest symptoms, and 6 presented with superior vena cava syndrome. Nine patients had bulky mediastinal tumors. The disease was confined within the thorax and contiguous lymph nodes, although multiple liver tumors were observed in 1 patient. Laboratory findings included high lactate dehydrogenase levels and elevated C-reactive protein levels. The soluble interleukin 2-receptor level was high in 6 patients tested. A comparative study of PMLBCL and nodular sclerosis-type Hodgkin's disease (NS-HD) with a mediastinal mass revealed substantial overlap in clinical features. Histopathological examination of biopsy specimens of PMLBCL revealed clusters of CD20+ large cells; however, CD30+ Hodgkin/Reed-Sternberg-like cells were occasionally seen, raising the potential to misdiagnose PMLBCL as NS-HD. The patients with PMLBCL were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), biweekly CHOP, or MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisolone, and bleomycin) regimen, and 6 received consolidation radiotherapy to the involved field. With the exception of 1 patient who was primarily refractory to therapy, 9 patients (90%) achieved complete response and 7 (70%) remain in continuous remission with a mean follow-up of 24 months.
Bombyx cysteine proteinase inhibitor (BCPI) is a novel cysteine proteinase inhibitor. The protein sequence is homologous to the proregions of certain cysteine proteinases. Here we report the mechanism of its inhibition of several cysteine proteinases. BCPI strongly inhibited Bombyx cysteine proteinase (BCP) activity with a K(i) = 5.9 pM, and human cathepsin L with a K(i) = 36 pM. The inhibition obeyed slow-binding kinetics. The inhibition of cathepsin H was much weaker (K(i) = 82 nM), while inhibition of papain (K(i) > 1 microM) and cathepsin B (K(i) > 4 microM) was negligible. Following incubation with BCP, BCPI was first truncated at the C-terminal end, and then gradually degraded over time. The truncation mainly involved two C-terminal amino acid residues. Recombinant BCPI lacking the two C-terminal amino acid residues still retained substantial inhibitory activity. Our results indicate that BCPI is a stable and highly selective inhibitor of cathepsin L-like cysteine proteinases.
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Chromosomal translocation involving the BCL6 gene affects not only immunoglobulin (Ig) genes but also a number of non-Ig genes as partners. The molecular anatomy of the BCL6 gene rearrangements in 39 cases with diffuse large B-cell lymphoma (DLBCL) by long-distance polymerase chain reaction-based assays was determined. The results showed that Ig genes were affected in 21 cases; non-Ig genes, 15 cases; a deletion of more than a 1-kb segment, 2 cases; and a point mutation, 1 case. Comparative studies between the 21 cases with Ig gene partners and the 17 cases with non-Ig gene partners, including 2 cases with the deletion, showed that the overall survival of the latter group of patients was significantly inferior to that of the former (P = .0440), and the estimated 2-year overall survival rates were 58.3% vs 17.6% (P = .005). Non-Ig/BCL6 fusion is a poor prognostic indicator of DLBCL, and DLBCL with BCL6 translocation could be subclassified according to the individual partner locus and/or gene. (Blood. 2000;96:2907-2909)
Three-particle correlations have been measured for identified pi(-) from central 158A GeV Pb+Pb collisions by the WA98 experiment at CERN. A substantial contribution of the genuine three-body correlation has been found as expected for a mainly chaotic and symmetric source.
BCL6 translocations involve not only immunoglobulin (IG) genes but also a number of non-IG loci as partners. Junctional sequences of three IG/BCL6 translocations were readily obtained by long-distance PCR. In cases where partner loci were not determined, we developed a long-distance inverse PCR method, which amplifies unknown fragments flanked by known BCL6 sequences. Using these two long-distance PCR-based approaches, we cloned junctional areas of BCL6 translocations from a total of 58 cases of B-cell tumors. Nucleotide sequencing and database searches revealed that 30 cases involved IGs as partners: IG heavy chain gene in 22, IG kappa light chain gene in 1, and IG lambda light chain gene in 7. In contrast, 23 cases affected non-IG loci, including the H4 histone gene, heat shock protein genes HSP89alpha and HSP90beta, and PIM-1 proto-oncogene. On der(3) chromosomes, complete sets of the promoters of these partner genes replaced that of BCL6 in the same transcriptional orientation. These results suggest that BCL6 gene affected by the translocation is transcriptionally activated by a variety of stimuli, including cell cycle control, changes in the physical environment, and response to cytokines. Break points on BCL6 occurred within the major translocation cluster, and we identified a 120-bp hyper-cluster region a short distance from the 3' end of exon 1. Gel mobility-shift assay suggested the presence of a protein(s) that bound to this particular region.
We have identified a novel mouse gene named pancortin that is expressed dominantly in the mature cerebral cortex. This gene produces four different species of proteins, Pancortin-1-4, sharing a common region in the middle of their structure with two variations at the N-terminal (A1 or A2 part) and C-terminal (C1 or C2 part) sides, respectively. In the present study, we showed that expression of mRNAs for A2-Pancortins (Pancortin species that contain the A2 part, i.e., Pancortin-3 and -4) is more dominant than that of mRNAs for A1-Pancortins (Pancortin species that contain the A1 part, i.e., Pancortin-1 and -2) in the prenatal mouse cerebral neocortex. Using western blot analysis, we found that substantial amounts of both A2-Pancortins were present in the prenatal cerebral neocortex and P19 cells after inducing neuronal differentiation. A2-Pancortins were still present in the cerebral neocortex of the adult, although their mRNAs were hardly detected. In contrast, the amount of A1-Pancortins did not increase after the third postnatal week in spite of their intense gene expression. Furthermore, we showed that recombinant Pancortin-3, one of the A2-Pancortins, was a secreted protein, in contrast to Pancortin-1 (one of the A1-Pancortins). These results suggest that A2-Pancortins are extracellular proteins essential for neuronal differentiation and that their molecular behavior is distinct from that of A1-Pancortins.
Glutathione reductase (GR) activity and flavin concentration were studied in systemic tissues (brain, heart, lung, liver, spleen, stomach, pancreas, muscle, kidney, testis) and blood components (erythrocytes and plasma) from male guinea-pigs. GR activity and the flavin concentration were high in kidney and liver, and low in muscle. GR activity in erythrocytes was found in a range of tissues, but flavin concentration in erythrocytes was lower than in any tissues. GR was saturated with flavin adenine dinucleotide (FAD) in almost all tissues, but not in muscle or erythrocytes.
A 51-year-old Japanese woman, initially diagnosed with T-lineage (CD2+, CD7+, CD3-, CD4-, CD8-) lymphoblastic lymphoma with t(4;11)(q21;p15), relapsed with acute myelomonocytic leukemia with the identical chromosomal abnormality. Southern-blot analysis revealed clonal rearrangements of an immunoglobulin heavy chain gene (JH) and T-cell receptor genes (J delta 1, J gamma 1, C beta 1) at first presentation, but germ line configurations of these genes at relapse. Leukemias with t(4;11)(q21;p15) may involve a hematopoietic progenitor capable of multilineage differentiation.
A 71-year-old woman, in whom the herniation of right-sided diaphragm was diagnosed, was admitted to our hospital on ambulance car complaining of increasing right-sided chest pain and worsening of dyspnea. She was given emergency laparotomy. The transverse colon and omentum pushed the liver backward. The tight adhesion between transverse colon and diaphragm was released by using thoracotomy additionally. In pleural cavity, there was prolapsing transverse colon which was not covered with peritonium and was caused by the rupture of right-sided diaphragm. The necrotic transverse colon was resected about 30 cm length. We considered that the rupture was caused not by external injury but by inflammation after plication for diaphragm eventration three years and ten months before.
t(9;14)(p13;q32), a subtype of 14q32 translocation, plays an essential role in the development of lymphoplasmacytoid lymphoma. t(9;14)(p13;q32) Causes juxtaposition of the PAX-5 gene on 9p13 and the IgH gene on 14q32, leading to the deregulation of the PAX-5 gene. We report a case of primary splenic lymphoma with a t(9;14). The histological diagnosis was diffuse large B-cell lymphoma without plasmacytoid differentiation. The lymphoma cells showed a complex karyotype including a t(9;14). Southern blot analysis localized the breakpoint of the PAX-5 gene within a couple of kb regions upstream of the exon 1A, although the involvement of the PAX-5 gene with the immunoglobulin heavy chain gene could not be confirmed.
Prothrombin time (PT) and activated partial thromboplastin time (APTT) were studied under excessive sodium citrate using the plasma from rats and beagle dogs. Addition of sodium citrate into the plasma caused a prolongation of PT and APTT. The prolongation was dependent on the concentration of sodium citrate or calculated hematocrit. The degree of prolongation was more severe in rats than in dogs, and in APTT than in PT. These results suggest that an artificial prolongation of PT and APTT occurs under excessive sodium citrate (e.g., elevated hematocrit), and that the degree differs between species and between parameters.
The usefulness of cellular size measurement for differentiating erythroid and myeloid cells was investigated using rat and canine bone marrow film prepared by the Cytospin method and Wright-Giemsa staining. 1. In the erythroid series, basophilic and polychromatic erythroblasts were distinguishable in terms of cellular diameter; i.e., 99% of rat and 95% of canine polychromatic erythroblasts were distributed in a range < or = 9.5 microns, at which basophilic erythroblasts did not exist. 2. In the myeloid series, myelocytes and metamyelocytes were to some extent distinguishable by their diameters; in rats, myelocytes (75% of the population) were > or = 13.5 microns, and metamyelocytes (61%) < or = 11 microns; and in dogs, myelocytes (45%) were > or = 16 microns, and metamyelocytes (66%) < or = 12 microns. 3. With regard to the metamyelocytes and myelocytes existing in the same range, their nuclear sizes (width) allowed further differentiation; in rats, the nuclear width of myelocytes (87%) was > or = 5 microns, and that of metamyelocytes (84%) < 5 microns; and in dogs, myelocytes (96%) > or = 7 microns, and metamyelocytes (88%) < 7 microns. The present results indicate that cellular size, together with nuclear size, contribute to distinguish the active mitotic group from less- or non-mitotic group in erythroids and myeloids, thus being helpful for toxicological evaluation on chemicals.
A 77-year-old man hospitalized in a bedridden state for cerebral infarction and left hemiparesis experienced the sudden onset of dyspnea and cyanosis. Chest X-ray films detected a foreign object in the hilum of the left lung. Emergency bronchoscopy revealed a dental crown lodged in the second carina. It was not possible to remove the crown with bronchoscopy forceps. The patient suffered severe respiratory failure the following day. Bronchoscopy again was performed, and the foreign object was removed with basket-type forceps. It was the patient's first molar, covered with a crown. The patient's respiratory failure was caused by atelectasis of the left lower lobe and overinflation, of the right lung, both of which resulted from postoperative edema of bronchial mucous membrane. Dental foreign objects do not cause pulmonary atelectasis or pneumonia as easily as other types of bronchial foreign objects. Therefore, there is usually enough time for thorough examination prior to removal procedures. It is important to accurately identify the shape of the foreign object, choose appropriate forceps, and successfully remove the object in the first operation. Moreover, adequate dental treatment of caries and loose teeth is important as a means of preventing dental foreign objects, especially in elderly people and bedridden patients.
Strain differences in erythrocyte glutathione (GSH) metabolism were studied in five inbred strains of Syrian hamster. Significant strain differences were found in the GSH level, rate of GSH regeneration, and the activity of hexokinase (HK). The rate of GSH regeneration did not correlate with the activity of HK. A gender difference was observed in the activity of HK. Our results indicate the possibility that Syrian hamster would be a model for studying the strain differences in the erythrocyte GSH metabolism.