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Biomedical subjects

K Kishi

Publications and source records attributed to K Kishi.

At least 217 records · Page 12Linked to original sources

Diffuse panbronchiolitis in rheumatoid arthritis.

The association of progressive obliterative bronchiolitis (OB) with rheumatoid arthritis (RA) is uncommon but has been reported previously. Diffuse panbronchiolitis (DPB) is a unique inflammation principally affecting the respiratory bronchioli and has been reported mainly in Japanese adults. Recently, DPB has also been noted in patients with RA in Japan. Therefore, there might be considerable overlap in clinical features between DPB and OB associated with RA in Japan. The aim of this study was to evaluate the clinicopathological characteristics of bronchiolitis in patients with RA. Three RA patients clinically diagnosed as having DPB were evaluated. All patients underwent chest radiographs, pulmonary function tests (PFT) and post mortem examination. Clinical features in all patients were a history of productive cough, exertional dyspnoea, wheezing and/or coarse crackles. Chest radiographs showed small nodular shadows up to 2 mm in diameter with bronchiolectasis throughout both lungs in all patients. The PFT revealed marked obstructive impairment in all patients. All patients died of progressive respiratory failure. Pathologically, two out of the three cases were confirmed as DPB, while the remaining one case was confirmed as OB, because the primary obstructive lesions were in the respiratory bronchioli in the former and in the membranous bronchioli and the proximal small bronchi in the latter. Thus, the clinical features of DPB and OB were strikingly similar, but the histopathological features revealed distinct differences. This study demonstrated that there was considerable overlap in clinical features between diffuse panbronchiolitis and obliterative bronchiolitis associated with rheumatoid arthritis, suggesting that diffuse panbronchiolitis might be a new manifestation of rheumatoid arthritis. The differentiation of these two disease entities is significant in making decisions on their therapeutic modality and is possible by analysing the precise histopathological findings of the lung.

Aged↗

Left postpneumonectomy syndrome successfully treated with endobronchial stent.

We describe a case of left pneumothorax-induced left postpneumonectomy syndrome in the absence of anatomical anomalies developing at 10 years after the operation. We placed an endobronchial stent into the right truncus intermidius and the procedure resulted in recovery of the syndrome. We consider endobronchial stent placement as an effective treatment for postpneumonectomy syndrome, especially when surgical management is not feasible.

Aged↗

Mechanism of increased serum cytokeratin 19 fragment levels in patients with diabetic nephropathy as a model of chronic renal failure.

We examined serum and urinary cytokeratin 19 fragment (CYFRA 21-1) levels in patients with diabetic nephropathy as a model of chronic renal failure, to investigate the mechanism of increased serum CYFRA 21-1 levels in chronic renal failure. Serum and urinary CYFRA 21-1 levels in non-insulin-dependent diabetes mellitus (NIDDM) patients with abnormal urinary immunoglobulin G (IgG) levels (>1.1 mg/g x Cr, n=126) were higher than those with normal urinary IgG levels. In NIDDM patients with normal urinary IgG levels (n=81); the urinary albumin or transferrin levels were not related to serum or urinary CYFRA 21-1 levels. We speculate that the increased serum CYFRA 21-1 levels contribute to metabolic abnormality in the kidney itself rather than the decreased urinary excretion per se, and that increased urinary CYFRA 21-1 levels are found in advanced cases of diabetic nephropathy with destruction of the size barrier.

Albuminuria↗

Bradykinin directly triggers GLUT4 translocation via an insulin-independent pathway.

Physical exercise induces translocation of GLUT4 from an intracellular pool to the cell surface in skeletal muscles and increases glucose uptake via an insulin-independent pathway. However, the molecular mechanism remains to be identified. Some studies have suggested that bradykinin is locally released from contracting muscles and may be responsible for GLUT4 translocation and the increase of glucose transport in skeletal muscles. To determine whether bradykinin directly triggers GLUT4 translocation, we established L6 myotubes, 3T3-L1 adipocytes, and Chinese hamster ovary cells stably expressing c-myc epitope-tagged GLUT4 (GLUT4myc) and bradykinin B2 receptors. We found that bradykinin directly triggered GLUT4myc translocation and increased the rate of glucose uptake in a dose-dependent manner in these cells. The translocation with bradykinin occurred even after pretreatment with an islet-activating protein, wortmannin, and phorbol 12,13-dibutyrate. The signaling pathway does not seem to be mediated by Gi, phosphatidylinositol 3-kinase, or protein kinase C. It is insulin-independent and via trimeric G-protein Gq. Bradykinin is probably one of the factors responsible for exercise-stimulated glucose uptake in skeletal muscles.

3T3 Cells↗

Two novel screening methods for selecting monoclonal antibodies which specifically inhibit DNase I enzyme activity.

Two novel screening methods, single radial enzyme diffusion and the DNA-cast polyacrylamide gel electrophoresis, for selecting monoclonal antibodies which detect human deoxyribonuclease I (DNase I) enzyme activity are described. The former was adopted for initial screening to select potential objective antibodies from numerous hybridoma culture supernatants, because it was easy to perform and a powerful mass-screening tool. The latter was utilized for the subsequent precise selection of the antibodies in the supernatants selected after preliminary screening by the former, because it was clearly more accurate and sensitive, although the procedure was slightly more complicated. The consecutive use of these two methods resulted in the isolation of 25 anti-human DNase I antibodies, all of which specifically inhibited the activity of human DNase I.

Antibodies, Monoclonal↗

Expression of deoxycytidine kinase (dCK) gene in leukemic cells in childhood: decreased expression of dCK gene in relapsed leukemia.

Competitive RT-PCR was used to determine the quantitative variation in the expression of deoxycytidine kinase (dCK) gene in childhood leukemic cells. The degree of dCK gene expression varied over a 50-fold range. In two cases in which both primary and relapsed leukemic cells were analysed, decreased expression of dCK gene was found in relapsed leukemic cells. The sequence variation analysis using bisbenzimide/polyethylene glycol electrophoresis demonstrated no sequence alteration of dCK cDNA in all cases. These results indicate that the expression of dCK gene varies in patients and suggests decreased expression of the dCK gene as one of the mechanisms responsible for clinical resistance to ara-C.

Adolescent↗

Hematopoietic cytokine-dependent differentiation to eosinophils and neutrophils in a newly established acute promyelocytic leukemia cell line with t(15;17).

We recently established an acute promyelocytic leukemia (APL) cell line (HT93) that has the capacity to differentiate into neutrophils and eosinophils in response to all-trans retinoic acid (ATRA) and human hematopoietic cytokines. The cells had a myeloblastic morphology, were positive for surface CD33, CD34, and CD56, and showed the following karyotypes: 46, XY, t(1;12)(q25;p13), 2q+, t(4;6)(q12;q13), and t(15;17)(q22;q11). When the cells were cultured with ATRA, they showed nuclear segmentation and developed secondary granules consisting in part of neutrophils and eosinophils. In the presence of ATRA and granulocyte colony-stimulating factor (G-CSF), the cells showed polymorphonuclear neutrophil differentiation accompanied by expression of surface CD11b, CD15, CD10, positive activity for neutrophil alkaline phosphatase (NAP), and NAP mRNA expression. In cultures with ATRA and granulocyte-macrophage colony-stimulating factor (GM-CSF), IL (interleukin)-3, or IL-5, HT93 showed remarkable eosinophil maturation at day 8 as determined by luxol fast blue staining, in addition to expression of eosinophil peroxidase and major basic protein. These results indicate that HT93 is an APL cell line with the ability to differentiate into neutrophils and eosinophils, and that these lineages are dependent on the CSF added. HT 93 should prove to be a useful model in analyzing the effects of hematopoietic cytokines on proliferation, differentiation, and maturation of hematopoietic progenitors.

Alkaline Phosphatase↗

Implications of heat shock/stress proteins for medicine and disease.

Heat shock/stress proteins (HSPs) are crucial for maintenance of cellular homeostasis during normal cell growth and for survival during and after various cellular stresses. The HSP70 family functions as molecular chaperones and reduces stress-induced denaturation and aggregation of intracellular proteins. In addition to the chaperoning activities, HSP70 has been suggested to exert its protective action by protecting mitochondria and by interfering with the stress-induced apoptotic program. The biochemical and functional properties of HSPs observed in cultured cells may be relevant to organs and tissues in whole animals. The activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nerve system elicits the stress response in selected peripheral tissues; the HSP70 expression in the vasculature and stomach increases resistance against hemodynamic stress and stress-induced mucosal damage, respectively. Gastric mucosa pretreated with mild irritants acquires a tolerance against subsequent mucosal-damaging insults. This phenomenon is known as "adaptive cytoprotection". Transient ischemia also induces ischemic tolerance in the brain and heart, which is called "ischemic preconditioning". The heat shock response is believed to contribute to the acquisition of the tolerance. The therapeutic applications of chaperone inducers that induce HSPs without any toxic effect are also introduced.

Animals↗

[The relationship of carcinoembryonic antigen and neutrophils to pulmonary function in healthy smokers].

We evaluated the relationship of carcinoembryonic antigen (CEA) and neutrophils to pulmonary function in healthy smokers. Smokers in whom levels of CEA were greater than 5.0 ng/ml (n = 70) and in whom CEA levels were 5.0 ng/ml or less (n = 693) had significantly higher mean concentrations of leukocytes and neutrophils than non-smokers (n = 651) (leukocytes: 6,883 +/- 1,889/mm3 or 5,581 +/- 1,457/mm3 vs. 4,507 +/- 1,111/mm3, p < 0.01; neutrophils: 4,389 +/- 1,542/mm3 or 3,343 +/- 1,164/mm3 vs. 2,700 +/- 884/mm3, p < 0.01). Differences in the ratio of vital capacity to the predicted vital capacity (%VC) were not significant. In addition, the ratio of forced expiratory volume in one second to forced vital capacity (FEV 1.0%) in smokers with CEA levels greater than 5.0 ng/ml was decreased compared with smokers with CEA levels of 5.0 ng/ml or less and in non-smokers (90.2 +/- 8.4% vs. 93.3 +/- 6.7% or 92.9 +/- 6.5%, p < 0.01). These results suggest that in healthy smokers high serum CEA levels are related to a decreased FEV 1.0%.

Adult↗

Detection of the two short tandem repeat loci (HumTPO and HumLPL) in Japanese populations using discontinuous polyacrylamide gel electrophoresis.

Two short tandem repeat (STR) systems, HumTPO and HumLPL, were investigated in 218 unrelated Japanese living in Gunma and Fukui Prefectures by means of discontinuous, horizontal polyacrylamide gel electrophoresis and silver staining. Five and six alleles were identified at the HumTPO and HumLPL loci, respectively. No deviations from the Hardy-Weinberg equilibrium or differences in genotype frequency were found between the two Japanese populations in the two systems. Our detection methods offered several advantages including time-saving and safe electrophoretic procedures, and fast and easy silver-staining, in comparison with standard and conventional STR analysis using vertical polyacrylamide gel electrophoresis.

Electrophoresis, Polyacrylamide Gel↗

[Experimental study of percutaneous hot ethanol injection therapy (PHEIT) by continuous heating device for hepatocellular carcinoma].

Percutaneous ethanol injection therapy (PEIT) is widely used as a local treatment for hepatocellular carcinoma (HCC). However, because only a small amount of ethanol can be used in one PEIT session and because the antitumor effect is limited, this modality is indicated only when there are three or fewer tumors and when the tumor diameter is < or = 3 cm. To obtain a more potent and certain antitumor effect, we have devised a new treatment called percutaneous hot ethanol injection therapy (PHEIT), and developed a Continuous Heating Device with which ethanol can be heated and locally injected at a specified temperature. The continuous Heating Device is composed of three major components: a syringe heater, a needle thermocontroller, and a needle tip thermosensor. A disposable syringe filled with liquid is inserted into the syringe heater, which heats the liquid to a desired temperature by adjusting the voltage. The needle thermocontroller is a puncture guide needle to which a heating device has been attached. The needle-tip thermosensor constantly measures, displays and records the temperature of the liquid at the needle tip during injection. Also, because the Continuous Heating Device is a closed-circuit system, there is no risk of accidental a fire, which ensures procedural safety. It is also possible to use this device to safely heat and inject a variety of other liquids, such as physiological saline and anticancer agents and thus contribute to the widespread development of ultrasound-guided injection therapy.

Animals↗

Evaluation of aspartic acid racemization ratios in the human femur for age estimation.

Levels of D-aspartic acid (D/L ratio) in cranial non-collagen proteins (acid-soluble peptide fractions) have been reported to increase with age. We isolated total amino acid fractions from the femur and separately isolated acid-insoluble collagen fraction and acid-soluble peptide fractions; then D/L ratios were measured from each fraction by gas chromatography. We evaluated the applicability of their D/L ratios for age estimation based on their correlation coefficient. A sex-related difference was observed in the D/L ratio. In particular, aged females showed a low ratio, suggesting an association with bone disorders. In males, the D/L ratios of acid-soluble peptide fraction showed the highest correlation rate (r = 0.969) with age, and those of total amino acid fraction showed the highest correlation rate (r = 0.633) with age in females. Without separation of male and female, the D/L ratios of total amino acid fraction showed the highest value (r = 0.853). The D/L ratio of acid-soluble peptide fractions differed according to the size of bone powder particles, being higher for larger particle sizes. These results suggest that the application of D/L ratio from total amino acid fraction is the most effective method for estimating age using the human femur. However, care is necessary when studing cadavers that might be females.

Adolescent↗

[Chronic thromboembolic pulmonary hypertension associated with initial pulmonary involvement in Takayasu arteritis].

A 37-year-old non-smoking woman was admitted to our hospital because of nocturnal coughing and exertional dyspnea after using an ultrasonic humidifier. Chest roentgenograms and computed tomography showed many ground-glass opacities in the right upper lobe and left upper lung field. Her symptoms were alleviated and erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels returned to normal following the administration of prednisolone (40 mg/day). The same symptoms subsequently recurred, and ESR and CRP levels increased proportionately to a decreased dosage of prednisolone. In addition, chest computed tomography showed new opacities in the left lower lobe. Transbronchial lung biopsy specimens revealed multiple stenotic or obstructive changes in the small pulmonary arteries by organizing thromboemboli, with no vasculitis. The diagnosis of chronic thromboembolic pulmonary hypertension was made on the basis of multiple defects from lung perfusion scintigraphy, irregular or tapering of the pulmonary arteries detected by pulmonary arteriograms, and increased pulmonary pressure measured by echocardiography. We propose that the pulmonary thromboembolism observed in this case was related to the initial pulmonary involvement of Takayasu arteritis, since the patient's symptoms, ESR and CRP levels all improved markedly following the administration of prednisolone.

Adult↗

The placenta is not the main source of leptin production in pregnant rat: gestational profile of leptin in plasma and adipose tissues.

The gestational profiles of leptin in plasma, adipose tissue and placenta were investigated in rats. Leptin in plasma and the adipose tissue of the maternal compartment increased as pregnancy advanced and remained high during the latter half of pregnancy (approximately 2-fold compared with the non-pregnant state), followed by a rapid decrease just before parturition. Leptin in fetal plasma and amniotic fluid was first detectable on day 19 and then increased to levels comparable to those in maternal plasma of non-pregnant and day 21 pregnant rats. The total amount of mRNA in maternal adipose tissues significantly increased as pregnancy advanced and reached about 2.5-fold of those of non-pregnant rats on day 19 of pregnancy, followed by a marked decrease on day 3 of lactation. Placentae and decidual tissues did not show any expression of leptin mRNA on day 12 and 19 of pregnancy. These results indicate that the placenta is not a major source of leptin production in rats and also suggest the physiological significance of leptin in rat pregnancy.

Adipose Tissue↗

Correlation between serum cytokeratin 19 fragment and tissue polypeptide antigen levels in patients with non-small cell lung cancer.

We evaluated the correlation between serum cytokeratin 19 fragment (CYFRA 21-1) and tissue polypeptide antigen (TPA) levels in 57 non-small cell lung cancer patients. There was a significant correlation between serum CYFRA 21-1 and TPA levels for each clinical stage and TNM (T, primary tumor; N, regional lymph node involvement; M, occurrence of distant metastasis) subcategory (range of r-value = 0.809-0.998, P < 0.01). High correlations between serum CYFRA 21-1 and TPA levels were found in eight patients both before and after the surgery, in 22 patients before and after chemotherapy and in another 27 patients who could not complete the scheduled chemotherapy (range of r-value = 0.856-0.998, P < 0.0001). However the positive rate of CYFRA 21-1 was higher than that of TPA (61% vs. 53%, P < 0.05). CYFRA 21-1 would yield better diagnostic results for non-small cell lung cancers than TPA, though these tumor markers are both cytokeratin-associated tumor markers.

Aged↗

Pepsinogen C gene product is a possible growth factor during gastric mucosal healing.

We isolated, by the subtraction cloning method, a pepsinogen C (PGC) gene fragment (the sequence between the 968th and 1179th base pairs) from a rat gastric mucosal cDNA library as a cDNA clone encoding a substance that promotes growth of the normal rat gastric mucosal cell line RGM1. Northern blot analysis revealed that PGC gene expression was enhanced not only in acetic acid-induced chronic gastric ulcers but also in indomethacin-induced gastric mucosal lesions. PGC gene expression was also increased in the Helicobacter felis-infected stomachs. Thus, the PGC gene may play a role in gastric epithelial cell growth during gastric mucosal healing.

Acetic Acid↗

Rabbit DNase I: purification from urine, immunological and proteochemical characterization, nucleotide sequence, expression in tissues, relationships with other mammalian DNases I and phylogenetic analysis.

DNase I from rabbit urine was purified approx. 3600-fold to apparent homogeneity with a 41% yield by affinity chromatography utilizing DNA-cellulose; the purity of the final preparation was assessed by SDS/PAGE, lack of contamination by other nucleases and production of a monospecific antibody against the enzyme. Although the proteochemical and enzymological properties of the purified enzyme resembled those of other mammalian DNases I, the enzymic activity of rabbit DNase I was less efficiently inhibited by monomeric actin than was that of human DNase I, probably due to substitution of an amino acid residue involved in actin binding (Tyr-65 to Phe). The effects of specific antibodies to human, rabbit and rat DNases I on the activities of the corresponding purified enzymes revealed that human DNase I lies between the rat and rabbit enzymes with regard to its immunological properties. An 1158 bp full-length cDNA encoding rabbit DNase I was constructed from the total RNA of rabbit pancreas using a combination of reverse transcriptase-PCR and rapid amplification of cDNA ends, followed by sequencing. This identified a 17- or 21-amino-acid signal sequence, with the mature enzyme containing 260 amino acids and a single N-glycosylation site at Asn-18. The amino acid sequence deduced from the cDNA sequence exactly matched that determined proteochemically from the purified enzyme up to residue 20. A systematic survey of DNase I distribution as measured by both enzymic activity and DNase I gene transcripts in 12 rabbit tissues showed the pancreas and parotid gland to produce equivalent levels, higher than those in other tissues. Enzymic activity and DNase I gene expression levels in each tissue correlated well. The results of phylogenetic and sequence identity analysis, immunological properties and tissue-distribution patterns of DNase I indicated a closer relationship between the rabbit and human enzymes than for other mammalian DNases I. Furthermore, differences between the enzymic activities expressed in mammalian parotid gland and pancreas suggest that the distribution of DNase I in mammalian tissue is species-specific.

Amino Acid Sequence↗