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Biomedical subjects

K Utsumi

Publications and source records attributed to K Utsumi.

At least 145 records · Page 8Linked to original sources

[Multiple cancer].

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Combined Modality Therapy↗

[An autopsy case of lymphoepithelioma-like carcinoma of the mediastinum].

A case of lymphoepithelioma-like carcinoma of the mediastinum is reported. A 67-year-old male was admitted to Tokyo Medical College Hospital, in February of 1992, for evaluation of an abnormal mediastinal shadow on chest X-ray. The mediastinal tumor was biopsied using mediastinoscopy. Histological diagnosis was undifferentiated carcinoma and radiation therapy was performed. Six months after treatment, he complained of dyspnea. Combination chemotherapy was performed. Although the tumor size decreased, he died of pneumonia. Histological findings at autopsy included nesting of large carcinoma cells with vacuolar nuclei and large nucleoli, interstitial lymphocytic infiltration similar to that of lymphoepithelioma of the epipharynx, and lymphoepithelioma-like carcinoma in the thymus. The epipharynx and thymus were, however, intact at autopsy. We found no other origins of this tumor, including the trachea and lung. This case was therefore diagnosed as lymphoepithelioma-like carcinoma of the mediastinum.

Aged↗

[Diagnosis of B-cell lymphoma of lung by kappa-lambda imaging in broncho-alveolar lavage fluid lymphocytes].

We attempted to verify the clonality of proliferating cells in broncho-alveolar lavage fluid (BALF) by using a sophisticated technique known as kappa-lambda imaging. We applied this method to BALF lymphocytes from 3 cases suspected of having primary pulmonary B-cell lymphoma, by transbronchial lung biopsy, and from 2 cases with B-cell lymphoma revealing abnormal shadows. (One was diagnosed as small cell carcinoma, the other mycotic infection). B-cell monoclonality was found in the former 3 cases, but not in the latter 2 cases. We conclude that kappa-lambda imaging in BALF lymphocytes is useful for diagnosing B-cell lymphoma of the lung.

Aged↗

Acute hepatic failure with swollen mitochondria and microvesicular fatty degeneration of hepatocytes triggered by free radical initiator.

BACKGROUND: Reye syndrome and acute fatty liver of pregnancy are characterized by acute hepatic failure associated with characteristic pathologic changes of hepatocytes, i.e., microvesicular fatty degeneration with severe mitochondrial swelling. Several animal models of these conditions have been proposed, although none has demonstrated sufficiently similar laboratory and pathologic features. EXPERIMENTAL DESIGN: A single dose of 2,2'-azobis-(2-amidinopropane) dihydrochloride, a free radical initiator, 100 mg/kg of body weight, injected intraperitoneally to BALB/c mice induced a transient decrease in hepatic energy charge, liver mitochondrial respiratory activity, and succinate dehydrogenase activity and a transient increase in blood ammonia level, suggesting hepatic failure. RESULTS: The hepatocytes displayed microvesicular fatty degeneration with severely swollen mitochondria. CONCLUSIONS: This is the first model of acute hepatic failure with microvesicular fatty degeneration of hepatocytes. It suggests a role of free radicals in the pathogenesis of certain types of acute hepatic failure.

Adenine Nucleotides↗

Embryo sex selection by a rat male-specific antibody and the cytogenetic and developmental confirmation in cattle embryos.

Embryos of mouse, rabbit, goat, sheep, and cattle were separated into 2 groups on the basis of their morphology when incubated with a male-specific antibody (qualified here as the H-Y antibody) prepared from newborn rat testis. When morula-stage embryos were cultured in the presence of this H-Y antibody, the development of roughly one half of the embryos was arrested at that stage, whereas the other half continued to develop to the blastocyst stage. The developmentally arrested group of embryos resumed their development into blastocysts when cultured in antibody-free medium. Eighty to 90% of cattle embryos whose development was unaffected by the antibody were shown to possess a female karyotype (XX), and close to 80% of those embryos whose development was arrested possessed a male karyotype (XY). Cattle embryos whose sex had been presumptively identified by development in the presence of the H-Y antibody were cryopreserved and transferred, and the sex of the calves was examined. The overt sex of the young born from sexed embryos was found to be the same as that determined by chromosomal analysis.

Animals↗

Developmental ability of enucleated bovine oocytes matured in vitro after fusion with single blastomeres of eight-cell embryos matured and fertilized in vitro.

Single blastomeres from eight-cell stage bovine embryos matured and fertilized in vitro were electrically fused with enucleated oocytes matured in vitro. In experiment 1, The percentage of these reconstituted embryos developed to the two- to eight-cell stage 48 hr after electrofusion was increased when both the eight-cell embryos and the enucleated oocytes were derived from oocytes cultured with granulosa cells (14% vs. 38%). In experiment 2, the relationship between activation of oocytes and developmental ability of reconstituted embryos was examined. Although both ethanol and electrical stimulation efficiently induced parthenogenetic activation of oocytes matured in vitro for 26-28 hr (ethanol, 89%; electrical stimulation, 73%), the ratio of the second polar body extrusion differed (80% vs. 22%). Ethanol-treated enucleated oocytes, however, were not significantly different from the early cleavage of the reconstituted embryos 48 hr after electrofusion (nontreated, 38%; treated, 43%). In experiment 3, reconstituted embryos at the two- to eight-cell stage 48 hr after the electrofusion were cocultured with granulosa cells for 6-7 days. Of 69 embryos, one developed to a morula and three developed to blastocysts.

Animals↗

Growth retardation in rats whose growth hormone gene expression was suppressed by antisense RNA transgene.

We produced four transgenic founder rats (F0) by introducing into rat embryos a fusion gene, which consisted of rat growth hormone (GH) promoter containing with four copies of thyroid hormone response element (TRE) and antisense cDNA sequences for rat GH. This transgene promoter directed 2.8-fold stimulation of CAT gene expression in transfected GH3 rat pituitary tumor cells compared with the rat GH promoter alone. Two of four transgenic rats expressed antisense RNA in the pituitary. Transgenic offspring (F1) from each founder rat exhibited dwarfism at as early as 3-4 weeks of age, and they exhibited approximately 70-85% reduced growth rate compared with their nontransgenic littermates over 56 weeks of observation. Plasma rat GH concentration was approximately 40-50% lower in transgenic F1 rats compared to their nontransgenic littermates. In these experiments, the pituitary hormone expression controlled in a complex manner was shown to be repressed by the antisense RNA transgene. Furthermore, the suppression of gene expression could be achieved by antisense RNA transgene in the rat as well.

Animals↗

Reversible priming and protein-tyrosyl phosphorylation in human peripheral neutrophils under hypotonic conditions.

Hypotonic shock enhanced both formyl-methionyl-leucyl-phenylalanine (FMLP)-induced superoxide (O2-.) generation and tyrosyl phosphorylation of cellular proteins including 120-, 115-, 83-, 63-, and 54-kDa proteins of human peripheral neutrophils. The time course of the enhancement correlated with that of tyrosyl phosphorylation of the 115-kDa protein. The "primed state" was reversed to the nonprimed resting state by changing the conditions from hypotonic to isotonic, with a concomitant decrease in tyrosyl phosphorylation. Genistein inhibited the increase in both O2-. generation and tyrosyl phosphorylation of the 120-, 115-, 63-, and 54-kDa proteins. These results suggest the involvement of tyrosyl phosphorylation of a cellular protein(s) in hypotonic shock-induced priming of neutrophils.

Amino Acid Sequence↗

Primary pulmonary B-cell lymphoma diagnosed by kappa-lambda imaging of broncho-alveolar lavage fluid lymphocytes.

A 69-year-old woman was examined due to abnormal pulmonary shadows on her chest roentgenogram. Although small lymphocyte proliferation was revealed in specimens by transbronchial lung biopsy (TBLB), immunoglobulin light chain restriction could not be seen. We attempted to verify the B-cell clonality by broncho-alveolar lavage (BAL) and a new sensitive method called kappa-lambda imaging (KLI), which was available for the detection of monoclonal B cells. Therefore, B-cell monoclonality was found. Thus, the patient was diagnosed as having primary pulmonary lymphoma (PPL). PPL may be differentiated from benign lymphoproliferative disorders such as pseudolymphoma and lymphocytic interstitial pneumonia by KLI of BAL-derived lymphocytes.

Aged↗

Effect of indomethacin and aspirin on the TNF-alpha-induced priming and protein tyrosyl phosphorylation of human neutrophils.

Receptor-mediated superoxide (O2-.)-generation in human peripheral neutrophils (HPPMN) is enhanced by various priming agents, such as granulocyte colony stimulating factor (G-CSF) and tumor necrosis factor (TNF-alpha). We previously reported that this enhancement occurred in parallel with the priming agent-induced increase in protein tyrosyl phosphorylation which is sensitive to tyrosine kinase (TK) inhibitors [Akimaru K. et al. Arch. Biochem. Biophys. 298:703, 1992]. We describe here that nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin and aspirin, modulate the priming and tyrosine phosphorylation of HPPMN. The enhancement by TNF-alpha of formylmethionyl-leucyl-phenylalanine (FMLP)-induced O2-. generation was not inhibited by 5 microM azide, whereas that of FMLP-induced luminol chemiluminescence (LCL) was sensitive. Enhancement of FMLP-induced O2-. generation and LCL by priming agents was inhibited by both aspirin and indomethacin in a concentration dependent manner. This inhibition by the NSAIDs was much stronger than that for FMLP-induced O2-. generation without priming. The half-inhibition dose of indomethacin and aspirin were 50 microM and 1.5 mM, respectively. The priming-induced enhancement of tyrosyl phosphorylation of some neutrophil proteins, such as that of 108 and 115 kDa, was also inhibited by aspirin and indomethacin in a dose-dependent manner. However, dose dependent inhibition of the enhanced O2-. generation by the NSAIDs was not completely similar to that of enhanced tyrosyl phosphorylation. However, PKC-mediated O2-. generation, which has little sensitivity to TNF-alpha or G-CSF, was rather stimulated by the NSAIDs. These findings suggest that aspirin and indomethacin inhibit also the early steps of neutrophil activation as reflected by their ability to inhibit priming and the related tyrosyl phosphorylation of neutrophil proteins.

Animals↗

Increase in cell responses and protein phosphorylation of neutrophils induced by synthetic diacylglycerols.

Diacylglycerols (DG) induced various stimulation-coupled responses of guinea pig peritoneal neutrophils (GPPMN), such as superoxide (O2-.) generation, luminol chemiluminescence response (LCL) and membrane depolarization. These activities induced by L-alpha-1,2-dioctanoyl glycerol (diC8) are quite similar to those induced by phorbol 12-myristate 13-acetate (PMA). The effects of diC8 were much stronger than those of L-alpha-1-oleoyl-2-acetylglycerol (OAG) and no effect was produced by L-alpha-1,2-dioleoyl glycerol (DO). Concentrations of diC8 and OAG for maximal O2-. generation were 1 and 10 microM, respectively. However, rat brain Ca(2+)- and phospholipid-dependent protein kinase (PKC) was activated by all DGs used, and the concentrations of OAG, DO and diC8 for half maximum stimulation were 0.2, 1.0 and 2.0 microM, respectively. Discrepancies between the concentrations of DGs required for O2-. release and PKC activation might be due to differences in their affinity for and permeability in the membrane. The generation of active oxygen and the PKC activity were both sensitive to PKC inhibitors, such as 1-(5-isoquinolinesulfonyl)-2-methyl-piperazine (H-7) and staurosporine. ID50 of H-7 and staurosporine for the inhibition of diC8-induced O2-. release were 150 nM and 10 nM, respectively. By contrast, staurosporine does not inhibit diC8 induced membrane depolarization. Phosphorylation of cytoplasmic proteins, such as the 47 kDa protein, was increased by DGs and this phosphorylation was also inhibited by H-7 or staurosporine. The capacities of stimulating the rates of 47 kDa protein phosphorylation were in the order diC8 > OAG > DO. These results suggest the involvement of protein phosphorylation in DG-induced O2-. generation. However, a part of the O2-. generation induced by high concentration of DG might have occurred via a PKC-independent pathway.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

[Early detection of chronic obstructive pulmonary disease by following individual annual changes in lung function].

The possibility of early detection of chronic obstructive pulmonary disease (COPD) was investigated among subjects whose lung function could be followed for more than ten years. Ten subjects aged 60 or more were selected from among about 1500 cases using the following diagnostic criteria; (1) subjects had complained of exertional dyspnea (2) chest X-ray abnormalities were suggestive of COPD (3) FEV1.0% was under 55%. Data on FVC/height, FEV1.0/height and FEV1.0% of these subjects were available for the previous ten years. Individual linear regression equations were estimated. Average annual changes of cases of obstruction were compared with those of normal cases, and individual deviations from the normal standard range were observed. Declines of the regression lines were as follows; FEV1.0/height: normal case--0.016 +/- 0.017, obstruction cases--0.038 +/- 0.018 (L/m/yr), FEV1.0%: normal cases 0.164 +/- 0.627, obstruction cases--1.522 +/- 0.638 (%/yr). Significant differences were observed between the normal and the obstruction cases (p < 0.01). FEV1.0% of all obstruction cases was under--2 SD of that of normal subjects. All individual FEV1.0% regression lines of the obstruction cases were outside +/- 2 RSD of the normal standard range more than 5 years before the onset of symptoms. Following individual annual changes in lung function was considered to be useful for the early detection of COPD.

Adult↗