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Biomedical subjects

K Nishi

Publications and source records attributed to K Nishi.

At least 181 records · Page 10Linked to original sources

Intraarterial perfusion of the hindlimb with pyridoxalated hemoglobin polyoxyethylene conjugate solution in anesthetized dogs.

To evaluate the potential clinical usefulness of a modified hemoglobin, pyridoxalated hemoglobin polyoxyethylene conjugate (PHP), the hindlimb vascular bed was perfused with PHP solution while monitoring tissue oxygen tension (PtO2) in anesthetized dogs. The hindlimb region was perfused through the external iliac artery with a roller pump at a varying perfusion rate. PtO2 was measured using a PO2-monitoring probe inserted into the gracial muscle. After surgical preparation for perfusion, the iliac arterial flow rate was 19.9 +/- 5.6 ml/min, and baseline PtO2 was 38.4 +/- 1.3 mm Hg. Perfusion with autologous arterial blood with the pump increased PtO2 and perfusion pressure (PP) in a perfusion rate-dependent manner. Perfusion with PHP solution at 20 ml/min decreased PtO2 from the initial baseline level, but an increase in the flow rate to 40-55 ml/min restored or induced an elevation of PtO2. Results demonstrated that PHP solution can deliver oxygen to local tissue and maintain tissue oxygen tension at the same level as autologous arterial blood at a high enough flow rate.

Animals↗

The GCR1 requirement for yeast glycolytic gene expression is suppressed by dominant mutations in the SGC1 gene, which encodes a novel basic-helix-loop-helix protein.

The GCR1 gene product is required for maximal transcription of yeast glycolytic genes and for growth of yeast strains in media containing glucose as a carbon source. Dominant mutations in two genes, SGC1 and SGC2, as well as recessive mutations in the SGC5 gene were identified as suppressors of the growth and transcriptional defects caused by a gcr1 null mutation. The wild-type and mutant alleles of SGC1 were cloned and sequenced. The predicted amino acid sequence of the SGC1 gene product includes a region with substantial similarity to the basic-helix-loop-helix domain of the Myc family of DNA-binding proteins. The SGC1-1 dominant mutant allele contained a substitution of glutamine for a highly conserved glutamic acid residue within the putative basic DNA binding domain. A second dominant mutant, SGC1-2, contained a valine-for-isoleucine substitution within the putative loop region. The SGC1-1 dominant mutant suppressed the GCR1 requirement for enolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, phosphoglycerate mutase, and pyruvate kinase gene expression. Expression of the yeast enolase genes was reduced three- to fivefold in strains carrying an sgc1 null mutation, demonstrating that SGC1 is required for maximal enolase gene expression. Expression of the enolase genes in strains carrying gcr1 and sgc1 double null mutations was substantially less than observed for strains carrying either null mutation alone, suggesting that GCR1 and SGC1 function on parallel pathways to activate yeast glycolytic gene expression.

Alleles↗

Effect of the cytokines on the prostaglandin E2 synthesis by lens epithelial cells of human cataracts.

BACKGROUND: Lens epithelial cells (LECs) derived from human cataracts have been reported to produce various cytokines and prostaglandin E2 (PGE2) in culture. The effects of IL-1, TGF-beta, and b-FGF on the PGE2 synthesis by LECs have been studied. METHODS: A circular piece of the anterior capsule with attached LECs was obtained by capsulotomy during cataract surgery and cultured. The primary, almost confluent, cultures were used for the study. The PGE2 concentration of the culture media for 24 h was measured after the addition of recombinant human IL-1 alpha, TGF-beta 2, or b-FGF at various concentrations. The PGE2 concentration was also measured in the media to which each cytokine and rabbit polyclonal anti-human antibodies against the corresponding cytokine had been added. RESULTS: The PGE2 concentration of the culture media after addition of IL-1 alpha at the concentration of 100 or 500 pg/ml (1765 (768) and 3071 (1121) pg/10(4) cells) or TGF-beta 2 at the concentration of 10 or 100 ng/ml (689 (264) and 750 (189) pg/10(4) cells) was significantly increased compared with that in the controls (67 (20) pg/10(4) cells). These effects were suppressed by the corresponding anticytokine antibodies. Basic FGF and anti-human b-FGF showed no significant effect on the PGE2 concentration. IL-1 and TGF-beta increased but b-FGF did not affect the PGE2 synthesis by LECs in culture. CONCLUSION: IL-1 and TGF-beta may participate in postoperative inflammation after cataract surgery by increasing PGE2 synthesis by residual LECs.

Cataract↗

Types of collagen synthesised by the lens epithelial cells of human cataracts.

AIMS/BACKGROUND: Residual lens epithelial cells (LECs) undergo fibrous proliferation after cataract surgery, resulting in capsular fibrosis. The purpose of this study was to determine the types of collagen produced in cultured LECs derived from human cataract LECs. METHODS: A circular section of the anterior capsule, about 5 mm in diameter, with LECs attached was obtained by anterior capsulotomy during cataract surgery and cultured directly without dispersion of the cells in a well, on the bottom of which a disc-shaped, thin plate of poly(methyl methacrylate) had been placed. At 5 to 6 weeks of culture, the proliferated cells of the culture were stained immunohistochemically with antibodies against human collagens I-VI by the avidin-biotin-peroxidase complex method. RESULTS: Collagens I, IV, V, and VI were positive in the cultured cells. Types IV and V were strongly present in almost all the cells whereas types I and VI were only observed in a few cells. Collagens II and III were negative. CONCLUSIONS: Since the lens capsule is known to be comprised of collagen IV, collagens I, V, and VI seem to be produced newly in culture. The capsular fibrosis seen after cataract surgery in vivo as a wound healing process of the lens capsule, may contain these types of collagens. The present culture model is useful for studying secondary cataract formation.

Cataract↗

Administration of rhG-CSF increases complete remission rates after CHOP and ProMACE/CytaBOM for non-Hodgkin's lymphoma: a pilot study. Hokkaido Study Group of Malignant Lymphoma and rhG-CSF.

To evaluate the clinical effects of the administration of recombinant human granulocyte-stimulating factor (rhG-CSF) post chemotherapy for patients with advanced-staged intermediate-grade or high-grade non-Hodgkin's malignant lymphoma (NHL), we conducted this multicenter study and compared the responses between both the regimens, CHOP as a first-generation chemotherapy and ProMACE/CytaBOM as a third-generation chemotherapy, when combined with the rhG-CSF administration. In this multicenter study, where forty patients were registered, patients in both the CHOP and ProMACE/CytaBOM groups were treated with the original regimen designs without the necessity of reducing drug dosages when combined with the administration of rhG-CSF. The administration of rhG-CSF post both of the cytotoxic therapies brought about much higher rates of complete remission in both the groups (CHOP, 75 percent; ProMACE/CytaBOM, 75 percent), as compared with those of the previous study without the rhG-CSF administration. Regarding response rates according to the International prognostic factor index, the CHOP group showed a lower rate of complete remission in patients with risk factors, compared with ProMACE/CytaBOM group. This result suggested that the administration of rhG-CSF may offer one important approach for improving the first-line therapy for aggressive NHL with high risk factors.

Adult↗

Synthesis and antibacterial activity of 2-(isoxazolidinio-5-yl)carbapenem derivatives.

The synthesis and antibacterial activity of the title compounds having an isoxazolidine ring at the C-2 position are described. These derivatives were synthesized by the 1,3-dipolar cycloaddition reaction of nitrone with 2-vinyl carbapenems. This 1,3-dipolar cycloaddition reaction proceeded regioselectively to give diastereomeric isomers of 2(-isoxazolidin-5-yl)carbapenems. It was ascertained that the antibacterial activity of 1 beta-methylcarbapenem derivatives was superior to that of the corresponding 1H-carbapenem derivatives, and between the 2-(isoxazolidin-5-yl)-1 beta-methylcarbapenems the antibacterial activity of the 5'R-isomer was slightly better than that of the 5' R-isomer slightly better than that of the 5' S-isomer.

Anti-Bacterial Agents↗

Inhibitory effect of terfenadine, a selective H1 histamine antagonist, on alcoholic beverage-induced bronchoconstriction in asthmatic patients.

We wanted to evaluate the effect of terfenadine, a selective H1-receptor antagonist, on alcoholic beverage-induced bronchoconstriction. Eight patients with alcohol-induced asthma received terfenadine (60 mg, twice on the test day) or placebo, with the last dosing 2 h before the test in a double-blind, randomized, cross-over manner. On two separate study days, each subject drank the same brand and volume of alcoholic beverage (beer or Japanese saké), and bronchoconstriction was assessed as change in peak expiratory flow (PEF) over 120 min postchallenge. Inhalation challenges were performed with the same alcoholic beverage with which they had been orally challenged. The mean (SEM) percentage fall in PEF 15, 30, 45, 60, 90 and 120 min after the oral alcohol challenge was significantly reduced from 12.0 (3.1), 17.0 (1.7), 15.8 (2.3), 15.2 (3.4), 16.6 (4.8) and 14.7 (5.2)%, to 2.6 (1.8), 2.1 (1.6), 3.9 (1.2), 5.7 (2.2), 6.5 (2.6), 5.1 (1.6)%, respectively, by terfenadine. No significant bronchoconstriction was observed after the inhalation challenge. We conclude that the release of histamine makes a major contribution to alcoholic beverage-induced bronchoconstriction in Japanese asthmatic patients, and that histamine H1 antagonists may be effective in preventing alcoholic beverage-induced bronchoconstriction.

Adult↗

Population frequency of apolipoprotein E5 (Glu3-->Lys) and E7 (Glu244-->Lys, Glu245-->Lys) variants in western Japan.

Apolipoprotein (apo) E modulates the catabolism of chylomicrons and of very low density lipoprotein remnants. It has three major isoforms (apo E2, E3, E4) and some rare variants. To detect the variants of apo E, blood specimens from 1269 Japanese subjects were analyzed using isoelectric focusing with immunoblotting. The E5 and E7 variants were identified by IEF in 2 and 18 subjects, respectively. Both E5 (Glu3-->Lys) carriers were confirmed by PCR-mediated site-directed mutagenesis, and all E7 (Glu244-->Lys, Glu245-->Lys) carriers were confirmed by the amplification refractory mutation system. The relative frequencies of the epsilon 5 and epsilon 7 alleles were 0.001 and 0.007, respectively. High concentrations of total cholesterol (> 220 mg/dl) were detected in five of the subjects expressing apo E7 and one subject expressing apo E5, and eight subjects heterozygous for apo E7 showed elevated plasma triglyceride concentrations (> 150 mg/dl). In 621 healthy subjects, the mean triglyceride concentration in subjects with apo E7/3 appeared to be higher than in those with apo E3/3, but the difference was not statistically significant.

Adolescent↗

[A case of chronic persistent cough caused by gastro-esophageal reflux].

Although gastro-esophageal reflux (GER) is one of the major causes of chronic persistent cough (CPC) in the USA and in Europe, it is a rare cause of CPC in Japan. We report a rare case of CPC caused by GER, in which treatment with an H2-blocker or with a proton pump inhibitor was successful. A 65-year-old woman had complained of coughing for over 25 years. Her coughing was not alleviated by treatment with a bronchodilator (beta 2-adrenoceptor agonist), an anti-allergic agent, a corticosteroid, or a sedative. GER was considered as a possible cause of her coughing because exacerbation of the coughing was associated with the development of gastrointestinal symptoms (heartburn). Fiberoptic esophagoscopy showed esophagitis and esophageal herniation of the sliding type. Twenty four-hour monitoring of distal esophageal pH showed that the coughing occurred when the pH dropped below 4, and that the pH was less than 4 for about 7% of the whole monitoring time. An H2-blocker or a proton pump inhibitor completely eliminated the symptoms. Therefore, CPC caused by GER was diagnosed. We found that coughing could be induced by instillation of 0.1 N hydrochloric acid at the distal esophagus, and that the coughing was partially inhibited by inhalation of an anti-muscarinic agent (ipratropium bromide) and by esophageal instillation of 4% xylocaine. These data support the "reflex theory". Although CPC caused by GER is rare in Japan, we should remember that GER can be a cause of CPC even in Japanese patients.

Aged↗

[Significance of CSF biopterin and neopterin in hereditary progressive dystonia with marked diurnal fluctuation (HPD)--a clue to pathogenesis].

Hereditary progressive dystonia with marked diurnal fluctuation (HPD or dopa-responsive dystonia) is a clinical entity characterized by childhood-onset dystonia followed by parkinsonism, which shows dramatic response to levodopa. However, the same combination of the symptoms is also characteristic of some patients with juvenile parkinsonism (JP: manifesting below the age of 40), and sometimes the correct differentiation between these HPD and JP patients, in the early course of the disorder, may be difficult. In this study, therefore, we analyzed cerebrospinal fluid (CSF) biopterin (BP) and neopterin (NP) concentrations in 2 patients with HPD, 58 with idiopathic parkinsonism (IP: this group includes 25 cases with JP), 9 with dopa-nonresponsive dystonia (DNRD) and 18 controls, to search for biochemical differences among these disorders. Biopterin is the natural cofactor for tyrosine hydroxylase and NP consists of degradation products of dihydroneopterin triphosphate, which is the first intermediate in the BP biosynthesis from guanosine triphosphate (GTP). As a result, the mean BP level in the IP patients (8.5 +/- 0.3 pmol/ml; mean +/- SE) was significantly lower than those in both the controls (13.2 +/- 0.5, p < 0.001) and the DNRD patients (14.2 +/- 1.2, p < 0.001). The BP levels in the HPD patients (7.1, 5.9) were lower than the mean BP level in the IP patients. With regard to NP content, there were no significant differences in the mean NP levels among the controls (25.2 +/- 2.0 pmol/ml; mean +/- SE) and the patients with IP and DNRD (22.6 +/- 1.0, 25.2 +/- 2.2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Congenital protein C deficiency with pulmonary infarction].

A 45-year-old man was admitted with left chest pain and hemoptysis. Chest CT on admission showed multiple areas of wedge-shaped consolidation in both lung fields. A perfusion lung scintigram showed bilateral deficits in both lungs, whereas a ventilation scintigram was normal. The serum concentration and the functional activity of protein C were 41% and 42%, respectively. The same results were obtained from studies of the patient's mother and two sons, which indicated that this was a case of congenital protein C deficiency with pulmonary infarction.

Humans↗

[A case of intra-pulmonary lymph nodes presenting as multiple small nodular lesions in both lungs].

A 59-year-old man came to our hospital for further examination of multiple small nodular lesions in both lungs. Chest CT scan revealed multiple nodular lesions in rt-S6, It-S5, and It-S9 (two lesions). All of these nodules measured about 10 mm or less and those in It-S9 had spicula. Bronchoscopic examination did not yield a definitive diagnosis, so open lung biopsy was done. The open lung biopsy specimen revealed intra-pulmonary lymph nodes with anthracosis and pulmonary emphysema. Intrapulmonary lymph nodes are very difficult to distinguish from small lung tumors by radiographic examination alone, so the possibility that small nodules in the lungs may be intra-pulmonary lymph nodes should be kept in mind.

Chronic Disease↗

[Changes in intraoperative and postoperative colloid oncotic pressure after open heart surgery especially in relation to non-blood priming or blood priming].

In order to evaluate the colloid oncotic pressure (COP) is useful index of hemodynamics and respiratory recovery after open heart surgery, cardiac index (CI), pulmonary capillary wedge pressure (PCWP), (A-a) Do2 and COP were measured in 34 patients during 48 hours after the cardiopulmonary bypass (CPB). The patients were divided into non-blood priming group: 11 patients and blood priming group (23 patients). In addition, blood priming group divided into two groups, one with dopamine (more than 15 micrograms/kg/min), epinephrine or intraaortic balloon pumping (severe blood subgroup, n = 6) and the other without these treatments after open heart surgery (slight blood subgroup n = 17). The COP levels in the non-blood priming group were significantly higher than those in the blood priming group from aortic cross-clamp to 10 minutes after aortic declamping (p < 0.01). From 1 to 48 hours after CPB, COP in the non-blood priming group and slight blood subgroups was significantly higher than severe blood subgroups (p < 0.05). CI and COP-PCWP levels were significantly higher in the non-blood priming group and slight blood subgroups than those in the severe blood group (p < 0.05). It is concluded that COP is useful index of hemodynamics and respiratory recovery after open heart surgery and our priming system without blood is effective in order to eliminate the blood transfusion.

Aged↗

[Effect of clarithromycin on symptoms and mucociliary transport in patients with sino-bronchial syndrome].

The effect of clarithromycin on symptoms and on mucociliary transport (as assessed by the saccharin test) were studied in 32 patients with sino-bronchial syndrome. Before treatment with clarithromycin, the nasal clearance time was significantly longer in these patients (70.3 +/- 64.7 min, mean +/- SD) than in control subjects (11.9 +/- 5.3 min, p < 0.001). By the end of 4 weeks of treatment with oral clarithromycin (400 mg/day), nasal clearance time in the patients had improved significantly (30.4 +/- 39.5 min, p < 0.001). Before clarithromycin therapy, bacteria were found in cultures of sputum from 15 patients. After clarithromycin therapy, bacteria were found in cultures of sputum from only 3 of those 15 patients. Cough frequency, volume of sputum, and dyspnea on exertion were significantly improved by clarithromycin therapy. These findings suggest that mucociliary transport is abnormal in patients with sino-bronchial syndrome, and that clarithromycin can be clinically useful in these patients.

Adult↗

Dnacin A1 and dnacin B1 are antitumor antibiotics that inhibit cdc25B phosphatase activity.

The p80cdc25 protein is a protein phosphatase directly involved in p34cdc2 protein kinase activation by dephosphorylation. The cdc25B gene is one of three human cdc25 homologs which can complement the temperature-sensitive cdc25 mutation of Schizosaccharomyces pombe, and is expressed a high levels in human cell lines, particularly in some cancer cells. A fusion protein of glutathione-S-transferase (GST) and the catalytic domain of cdc25B protein was constructed and found to retain phosphatase activity in the manner of a p80cdc25 phosphatase by using a chromogenic substrate, p-nitrophenylphosphate. Two benzoquinoid antitumor compounds, dnacin A1 and dnacin B1, inhibited phosphatase activity in a non-competitive manner.

Antibiotics, Antineoplastic↗

The kinase inhibitor staurosporine induces G1 arrest at two points: effect on retinoblastoma protein phosphorylation and cyclin-dependent kinase 2 in normal and transformed cells.

Staurosporine (ST), a protein kinase inhibitor, at a concentration of 20 nM arrests normal diploid fibroblasts 3 h into G1 (H. A. Crissman et al., Proc. Natl. Acad. Sci. USA, 88: 7580-7584, 1991; K. Abe et al., Exp. Cell Res., 192: 122-127, 1991). ST (2 nM) induces a new G1 arrest point at 6 h into G1. Partial phosphorylation of the retinoblastoma protein was observed at the 2 nM ST arrest point, whereas the retinoblastoma protein was unphosphorylated or underphosphorylated at the 20 nM arrest point. This correlated with the activity of the cyclin-dependent kinase 2 (CDK2) and the phosphorylation of the Thr160 residue of p33CDK2. The cyclin E and cyclin D1/2 levels were reduced at the 20 nM ST arrest point. In HeLa cells that do not arrest in G1 in response to 2 or 20 nM ST, the retinoblastoma protein and CDK2 phosphorylations and CDK2 activity were not affected by ST. These results suggest that ST inhibits one or more G1-regulating protein kinases, which lie upstream of CDK2.

Alkaloids↗

Bradykinin-evoked non-specific cationic current in neuroblastoma-glioma hybrid (NG108-15) cells and its down-regulation through differentiation.

Effects of bradykinin (BK) on the membrane conductance and level of cytoplasmic free Ca2+ in undifferentiated and differentiated neuroblastoma-glioma hybrid (NG108-15) cells were studied using the nystatin-perforated patch-clamp technique and fura-2 fluorometry. Under voltage clamp at -20 mV, undifferentiated cells responded to BK at > 10(-9) M, producing a biphasic current composed of an apamin-sensitive Ca(2+)-activated K+ outward current and non-specific cationic inward current. Both current components corresponding to a biphasic elevation of [Ca2+]i were completely prevented by an intracellular perfusion with EGTA (1 mM) under conventional whole cell recording condition. Undifferentiated cells revealed almost no voltage sensitive Ca2+ current. In NG108-15 cells differentiated with 8-Br-cyclic AMP (1 mM) or rolipram (1 mM), an inhibitor of type IV phosphodiesterase, BK concentration required for the non-specific cationic current with amplitude of > 100 pA was much greater than that of undifferentiated cells. This suggests that the differentiated cells decreased BK-sensitivity in induction of the non-specific cationic current. The non-specific cationic channel is suggested to play roles as a source of Ca2+ entry in undifferentiated NG108-15 cells.

Bradykinin↗