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Biomedical subjects

K Kondo

Publications and source records attributed to K Kondo.

At least 289 records · Page 16Linked to original sources
PubMed1997

Inhibitory effect of prostaglandin E1 on intimal thickening following photochemically induced endothelial injury in the rat femoral artery.

The inhibitory effect of prostaglandin E1, which has an anti-platelet action and a vasodilating action via intracellular cyclic AMP elevation, was studied on intimal thickening in the rat femoral artery. A segment of the femoral artery was occluded by a platelet and fibrin-rich thrombus due to photochemical reaction between systemically administered Rose Bengal and transluminal green light which causes endothelial injury followed by platelet adhesion and aggregation at the site of photochemical reaction. Three weeks after endothelial injury, intimal thickening occurred at the irradiated site. Prostaglandin E1 (0.3 microgram/kg per min), administered as a continuous infusion 10 min before photochemical reaction significantly (P < 0.05) prolonged the time to occlusion of the femoral artery. In a separate experiment, prostaglandin E1 (0.3 microgram/kg per min) administered as a continuous infusion for 7 days just after endothelial injury significantly (P < 0.05) inhibited intimal thickening compared with a control group. In cultured rat-derived vascular smooth muscle cells, prostaglandin E1 produced concentration-dependent inhibition of migration and proliferation, stimulated by platelet-derived growth factor. These results suggest that prostaglandin E1 may be effective in preventing vascular restenosis after vascular surgery and angioplasty.

Alprostadil↗
PubMed1997

Smoking cessation increases the resistance of low-density lipoprotein to oxidation.

The effects of smoking cessation on the susceptibility to oxidation of low-density lipoprotein (LDL) was investigated in 14 men who quit smoking for 3 months. LDL was isolated and susceptibility of LDL to V-70 (4-methoxy-2,4-dimethylvalerinitrile)-mediated oxidation was assessed by measuring conjugated diene production at 234 nm, the lag phase being a measure of the resistance of LDL to oxidation. The mean duration of the lag phase became 1.9-fold longer after 3 months (P < 0.001). The result suggests that the increase in resistance of LDL to oxidation contributes to the reduction of the risk of coronary heart disease by smoking cessation.

Adult↗
PubMed1997

Systemic inflammatory responses in acute coronary syndrome: increased activity observed in polymorphonuclear leukocytes but not T lymphocytes.

BACKGROUND: Local inflammation within the coronary arteries is involved in the pathogenesis of acute coronary syndrome. However, the contribution of a systemic inflammatory response to the pathogenesis of this syndrome has not been well characterized. Accordingly, we investigated systemic inflammatory responses in patients with acute coronary syndrome. METHODS: A total of 83 patients with ischemic heart disease (15 with stable exertional angina and 68 with acute coronary syndrome) were studied. The luminol-dependent chemiluminescence (CL) response of polymorphonuclear leukocytes (PMNs), which reflects their ability to generate oxygen species, was used as a marker for PMN activation. Soluble interleukin-2 receptor (sIL-2R) levels were measured to assess T-lymphocyte activation. RESULTS: CL counts of whole blood from patients with acute coronary syndrome were twice those of patients with stable angina (2.38 +/- 0.22 vs 1.10 +/- 0.17 x 10(6) counts, P < 0.05). A comparison of CL counts between patients with unstable angina and those with acute myocardial infarction revealed no significant differences. T-lymphocyte activity, measured by serum sIL-2R, was significantly lower in patients with acute coronary syndrome than those with stable angina (214.3 +/- 11.5 vs. 358.3 +/- 115.7 U/ml, P < 0.05). CONCLUSIONS: This investigation shows that there is a systemic increase in PMN activity and a decrease in T-lymphocyte activity in patients with acute coronary syndrome. This contrasts with the pattern of cellular activation seen at sites of local inflammation within atherosclerotic plaques, suggesting that two independent inflammatory processes (local and systemic) may be involved in the pathogenesis of this syndrome.

Acute Disease↗
PubMed1997

Comparative studies of circulating KL-6, type III procollagen N-terminal peptide and type IV collagen 7S in patients with interstitial pneumonitis and alveolar pneumonia.

KL-6, a MUC1 mucin preferentially expressed in regenerating type 2 pneumocytes, has been reported to be a sensitive serum marker for evaluating the disease activity of interstitial pneumonitis (IP). Type III procollagen N-terminal peptide (PIIIP) and type IV collagen 7S (7S collagen) have also been reported to be useful in the serological evaluation of the activity. Their levels were measured and their serodiagnostic values were compared simultaneously in patients with IP and alveolar pneumonia. The study population was 45 patients with IP and 12 patients with alveolar pneumonia. Serum KL-6 levels were measured by a specific enzyme immunoassay, and both serum PIIIP and 7S collagen concentrations by their correspondent radioimmunoassay kits. There were no significant difference of serum C-reactive protein level, which was evaluated as an indicator of inflammatory process, between IP and alveolar pneumonia patients. In IP, the abnormally elevated rate of KL-6 [80% (36/45)] was significantly higher than those of PIIIP [40% (18/45)] and 7S collagen [40% (18/45)]. In alveolar pneumonia, the rate of KL-6 [0% (0/12)] was significantly lower than those of PIIIP [33% (4/12)] and 7S collagen [25% (3/12)]. There were no significant correlations among serum levels of the markers. These observations indicate that the serodiagnostic value of KL-6 for IP is superior to that of PIIIP and 7S collagen, and that KL-6 has a characteristic to discriminate IP from alveolar pneumonia.

Antigens↗
PubMed1997

High frequency of p53 protein expression in thymic carcinoma but not in thymoma.

Thymic epithelial tumours are broadly classified into thymomas and thymic carcinomas. Although both tumours occasionally show invasive growth, they exhibit different clinical and biological findings. The oncogene and anti-oncogene in thymic epithelial tumours have not been evaluated fully. We investigated the expression of p53 protein by immunohistochemical analysis using the anti-p53 polyclonal antibody (CM-1) in 17 thymomas and 19 thymic carcinomas. We also examined p53 gene (exon 5-8) mutation in 18 thymic carcinomas by using polymerase chain reaction-single-strand conformation polymorphism methods and direct sequencing. Of the thymoma cases, only one invasive thymoma showed focal nuclear staining. Fourteen of the 19 thymic carcinomas (74%) showed nuclear staining. Point mutations of the p53 gene were recognized in only 2 of the 18 thymic carcinomas (11%). One was the mutation C to T transition in the first letter of codon 222 in exon 6, which results in the amino acid substitution from proline to serine. Another was a silent mutation. p53 protein accumulation is highly frequent in thymic carcinomas but not in thymomas, and gene mutation is uncommon in thymic carcinomas.

Adult↗
PubMed1997

High-level expression of a sweet protein, monellin, in the food yeast Candida utilis.

We describe the heterologous expression of monellin in the yeast Candida utilis. A single-chain monellin gene was expressed under the control of the glyceraldehyde-3-phosphate dehydrogenase [correction of decarboxylase] gene promoter from C. utilis. A promoter-deficient marker gene allowed high-copy-number integration of vectors into either the rDNA locus or the URA3 gene locus. Monellin was produced at a high level, accounting for > 50% of the soluble protein. No significant decrease in the production level of monellin was detected in transformants after 50 generations of nonselective growth.

Amino Acid Sequence↗
PubMed1997

Pharmacokinetics and safety of JTP-4819, a novel specific orally active prolyl endopeptidase inhibitor, in healthy male volunteers.

AIMS: To investigate the pharmacokinetics and safety profile of JTP-4819, (-)-(2S)-1-benzylaminocarbonyl-[(2S)-2-glycoloylpyrrolidinyl ]-2-pyrrolidinecarboxamide, a novel specific orally active prolyl endopeptidase (PEP) inhibitor. METHODS: JTP-4819 was given orally to 28 healthy male volunteers at single doses of 30 mg (n = 6), 60 mg (n = 6), 120 mg (n = 6) and placebo (n = 3) and multiple doses of 60 mg three times daily (n = 5) and placebo (n = 2) for 7 days to investigate its safety and pharmacokinetics following a preliminary safety evaluation of 3, 10 and 30 mg doses in six healthy volunteers. With the single dose of 60 mg, a cross-over study was conducted to examine the effect of food on the bioavailability of the drug. The concentrations of JTP-4819 in plasma and urine were determined by electrospray ionization-liquid chromatography/mass spectrometry (ESI-LC/MS) method. RESULTS: In the multiple-dose study, the cholinesterase activity was gradually increased and reached above the normal range on days 4 to 8 in all five subjects given JTP-4819 and gradually returned to normal range after completion of dosing. The elevation of plasma cholinesterase activity was considered to be an action of JTP-4819, but this remains to be verified. There were no other abnormal findings in objective symptoms and laboratory findings including blood pressure, heart rate, electrocardiogram, body temperature, haematology, blood chemistry and urinalysis. The Cmax of JTP-4819 at 30, 60 and 120 mg in fasting state were 474, 887 and 1,649 ng ml-1, respectively, at 1 h after administration, and the t1/2 was about 2 h. AUC increased in proportion to the given doses. The cumulative urinary recoveries within 24 h were approximately 66%, Cmax, AUC, t1/2 and urinary recovery were not affected by food intake. In the multiple-dose study, there was no drug accumulation trend in plasma. CONCLUSIONS: These results indicate that JTP-4819 has acceptable pharmacodynamic and pharmacokinetics profiles for clinical use without any serious adverse events as we verified in healthy young male volunteers.

Administration, Oral↗
PubMed1997

The genomic analysis of human DAN gene.

DAN gene is shown to be localized at human chromosome 1p36.11-p36.13, which resides within the consensus deletion observed in neuroblastoma. In the present study, we have isolated the genomic DNA containing the entire human DAN gene and determined its nucleotide sequence. Structural analysis revealed that DAN gene is composed of four exons and spans approximately 15 kb. Its overall structure was basically the same as that of rat DAN gene. Two distinct transcription initiation sites (major and minor) were identified by the primer extension experiment. Putative TATA and CAAT-like elements are present 38 and 366 bp upstream from the major transcription start site, respectively, however, no apparent TATA-like sequence was found in the upstream region of the minor transcription start site. The 400-bp region immediately upstream from the major transcription initiation site was strongly GC-rich (79% GC). Genomic Southern experiments demonstrated that the allelic loss of DAN gene might occur in neuroblastoma. Interestingly, there exist two dinucleotide repeats, (CA)7 and (CA)8, in the first intron of DAN gene, raising the possibility to distinguish two alleles of DAN gene in some of the cancer cells.

Base Composition↗
PubMed1997

Fatty acid synthesis of an eicosapentaenoic acid-producing bacterium: de novo synthesis, chain elongation, and desaturation systems.

The fatty acid synthesis systems of a Shewanella sp., strain SCRC-2738, that produces a large amount of eicosapentaenoic acid were investigated. Two kinds of fatty acid synthesis system, de novo synthesis and chain elongation ones, were detected in the cytosol. The de novo synthesis system required an acyl carrier protein, and produced palmitoyl- and palmitoleoyl-acyl carrier proteins as final products. The chain elongation system also required an acyl carrier protein, and produced an acyl-acyl carrier protein as a product, using palmitoyl-, palmitoleoyl-, stearoyl-, and oleoyl-CoAs as primers but not eicosanoyl- or eicosenoyl-CoA. There were an anaerobic pathway and an aerobic desaturation one for the production of unsaturated fatty acids. Eicosapentaenoic acid seemed to be produced through the aerobic desaturation pathway and not through the anaerobic one, since the latter pathway produced n-7 type monoenoic fatty acids, which are different from eicosapentaenoic acid in the position of the double bond. The desaturase utilized an acyl-acyl carrier protein as a substrate, and this activity increased in the presence of ferredoxin and ferredoxin NADP+ reductase. Thus, Shewanella sp., strain SCRC-2738, has novel characteristics as to both fatty acid chain elongation and desaturation systems.

Acetyl Coenzyme A↗
PubMed1997

Effects of pemirolast and tranilast on intimal thickening after arterial injury in the rat.

We previously reported that tranilast, an antiallergic agent, reduced intimal thickening after endothelial injury in rats. In this study, to verify whether or not antiallergic agents inhibit intimal thickening, we investigated the effect of pemirolast on intimal thickening after endothelial injury and compared its effect with that of tranilast. Administration of two antiallergic agents, pemirolast (0.1, 1, and 10 mg/kg, p.o.) and tranilast (300 mg/kg, p.o., daily), was begun 2 days before endothelial injury and continued until the animals were killed. Endothelial injury in the rat femoral artery was induced by a photochemical reaction between localized irradiation by green light and intravenously administered rose bengal. To evaluate intimal hyperplasia, we measured the cross-sectional area of the intima 21 days after endothelial damage. Pemirolast at doses of 0.1, 1, and 10 mg/kg reduced the intimal area to 2.10 +/- 0.33, 1.36 +/- 0.19, and 1.35 +/- 0.18 (x0.01 mm2), respectively, and tranilast showed a tendency to reduce the intimal area, which was 1.86 +/- 0.35 x 0.01 mm2, compared with findings for controls (2.83 +/- 0.49 x 0.01 mm2). In rat A10 vascular smooth-muscle cells, we investigated the effects of antiallergic agents on migration by using a modified Boyden chamber assay and on proliferation by using the bromodeoxyuridine-incorporation assay. Two antiallergic agents inhibited in a concentration-dependent manner both migration and proliferation of smooth muscle cells stimulated by platelet-derived growth factor. These results suggest that antiallergic agents directly inhibit migration of smooth-muscle cells to the intima from the media and proliferation in the intima, and that pemirolast has more potent antihyperplastic action than does tranilast. Antiallergic agents may be effective in preventing restenosis after coronary angioplasty.

Animals↗
PubMed1997

Immunocytochemistry of apoptosis induced by bromodeoxyuridine in human leukemic HL-60 cells.

Various antitumor drugs which target tumor cells in the S-phase of the cell cycle induce apoptosis in HL-60 cells. The present study shows that apoptosis is inducible in HL-60 cells by continuous exposure to bromodeoxyuridine (BrdU), an S-phase specific reagent and a thymidine analogue. The localization of BrdU in the apoptotic cells was visualized with immunogold particles using an anti-BrdU monoclonal antibody. After 3 days of treatment with 20 microM BrdU, cells ceased to grow and their viability was significantly decreased. Morphologically, nuclear segmentation and cytoplasmic maturation were observed in many viable cells, and the dead cells showed typical features of apoptosis. The nuclear DNA of apoptotic cells was visualized by the immunocytochemical detection of BrdU with post-embedding immunogold staining. The condensed chromatin of the apoptotic cells was highly labeled with immunogold particles, while the nucleolus was sparsely labeled. The chromatin could be traced with BrdU-immunocytochemistry even after disappearance of the nuclear envelope. These results indicated that apoptosis in HL-60 cells was induced by incorporation of BrdU into DNA of the S-phase cells. Using BrdU-immunocytochemistry, the localization of nuclear DNA in apoptotic cells was visualized and the changes of nuclear structures were followed during the progression of apoptosis.

Apoptosis↗
PubMed1997

Trial of electrolyzed strong acid aqueous solution lavage in the treatment of peritonitis and intraperitoneal abscess.

Electrolyzed strong acid aqueous solution is acidic water that contains active oxygen and active chlorine and possesses a redox potential. We performed peritoneal and abscess lavages with an electrolyzed strong acid aqueous solution to treat 7 patients with peritonitis and intraperitoneal abscesses, who were seen in our department between December 1994 and April 1995. The underlying disease was duodenal ulcer perforation in 4 of these 7 patients and gastric ulcer perforation, acute enteritis, and intraperitoneal perforation of pyometrium in 1 patient each. Irrigation was performed twice a day. Microbiological studies of the paracentesis fluid were negative in 3 cases, and the irrigation period was 2-4 days. Anaerobic bacteria were isolated in 3 of the 4 positive cases (Bacteroides in 2, Prevotella in 1), and a fungus (Candida) was isolated in the remaining patient. The period of irrigation in these patients ranged from 9 to 12 days, but conversion to a microorganism negative state was observed in 3-7 days.

Abdominal Abscess↗
PubMed1997

Safety and pharmacokinetics of CS-834, a new oral carbapenem antibiotic, in healthy volunteers.

CS-834, (+)-[pivaloyloxymethyl (4R,5S,6S)-6-[(R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[[(R)-5-oxopyrroli din-3-yl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate], is an ester-type oral carbapenem prodrug, and an active metabolite is R-95867, which has antibacterial activity. CS-834 was administered orally to healthy male volunteers at single doses of 50, 100, 200, and 400 mg and at a multiple dose of 150 mg three times a day for 7 days to investigate its safety and pharmacokinetic profiles. Other studies were conducted to examine the effect of food intake on the bioavailability of CS-834 and also the effect of the coadministration of probenecid on the pharmacokinetics of CS-834. In the fasting state, the concentration of R-95867 in plasma reached maximum levels from 1.1 to 1.7 h after the oral administration of CS-834, followed by a monoexponential decrease. The maximum concentrations of R-95867 in serum (C[max]s) after the administration of CS-834 at doses of 50, 100, 200, and 400 mg were 0.51, 0.97, 1.59, and 2.51 microg/ml, respectively. The half-lives (t1/2s) were almost constant, approximately 0.7 h. The areas under the concentration-time curves (AUCs) were proportional to the doses, ranging from 50 to 400 mg x h/ml. The cumulative recoveries in urine were approximately 30 to 35% until 24 h after drug administration. The C(max), AUC, t1/2, and recovery in urine were not affected by food intake. Probenecid coadministration prolonged the t1/2, and it increased the C(max) and AUC for R-95867 by approximately 1.5- and 2.1-fold, respectively. The multiple-dose study showed no change in the pharmacokinetics from those for the single doses and no drug accumulation in the body. A mild transient soft stool was observed in one volunteer in the study with a single dose of 400 mg. In the multiple-dose study, mild transient soft stools were observed in six volunteers, one volunteer had mild transient diarrhea, and one volunteer had elevated serum glutamic oxalacetic transaminase and serum glutamic pyruvic transaminase levels (1.4- and 2.8-fold compared with the upper limits of normal, respectively). There were no other abnormal findings for objective symptoms or laboratory findings, including blood pressure, heart rate, electrocardiogram, body temperature, hematology, blood chemistry, and urinalysis.

Administration, Oral↗
PubMed1997

Characterization of the genes encoding the three-component membrane-bound alcohol dehydrogenase from Gluconobacter suboxydans and their expression in Acetobacter pasteurianus.

The three-component membrane-bound alcohol dehydrogenase (ADH) of Gluconobacter suboxydans IFO12528 was purified, and the NH2-terminal amino acid sequence of each subunit was determined. On the basis of the amino acid sequences, the genes adhA, encoding the 72-kDa dehydrogenase, adhB, encoding the 44-kDa cytochrome c-553 (a CO-binding cytochrome c), and adhS, encoding a 15-kDa protein, were cloned and the amino acid sequences of their products were deduced from the nucleotide sequences. The dehydrogenase and cytochrome genes were clustered with the same transcription polarity, as is the case in species of Acetobacter, another genus of acetic acid bacteria. These AdhA and AdhB subunits showed similarity in amino acid sequence to those from Acetobacter spp., whereas AdhS showed no similarity to the corresponding subunit of the ADH complex of Acetobacter pasteurianus. Consistent with this, adhS of G. suboxydans could not complement a defect in the corresponding subunit of A. pasteurianus. When the adhA-adhB gene cluster of G. suboxydans was expressed in an ADH-deficient mutant of A. pasteurianus, the transformant showed distinct ADH activity. The ADH complex was purified to near homogeneity and consisted of two subunits, the dehydrogenase and the cytochrome c subunits derived from G. suboxydans, without any other subunit. These data suggested that AdhS, the smallest subunit of ADH, from G. suboxydans is not essential for ADH activity in A. pasteurianus, in contrast to the essential role of A. pasteurianus AdhS, which is required for correct assembly of the dehydrogenase and cytochrome c subunits on the membrane.

Acetobacter↗
PubMed1997

Characterization of an insertion sequence, IS12528, from Gluconobacter suboxydans.

A novel insertion sequence element, IS12528, was found to be associated with inactivation of the alcohol dehydrogenase by insertion in the adhA gene, which encodes the primary dehydrogenase subunit of the three-component membrane-bound alcohol dehydrogenase complex in Gluconobacter suboxydans. Cloning and sequencing analyses revealed that IS12528 was 905 bp in length and had a terminal inverted repeat of 18 bp. In addition, IS12528 was found to generate a 3-bp duplication (TMA, where M represents C or A) at the inserted site upon transposition. IS12528 encoded one long product of 274 amino acids that was rich in basic amino acids. This protein showed significant homology with putative transposases of the IS1031 family isolated from Acetobacter xylinum, which belongs to another genus of acetic acid bacteria. IS12528-like sequences were distributed in a wide variety of acetic acid bacteria, as determined by Southern hybridization and PCR. These observations suggest that IS12528 is one of the insertion sequences that are responsible for genetic instability leading to deficiencies in various physiological properties in a variety of acetic acid bacteria.

Acetobacter↗
PubMed1997

Osmoregulation of plasma vasopressin in three cases with adrenal insufficiency of diverse etiologies.

Neurohypophyseal function was studied by hypertonic saline infusion with plasma vasopressin measurement in 3 patients with adrenal insufficiency before and after cortisol replacement. Although each patient had different causes of adrenal insufficiency, all showed impaired water excretion before replacement. The first patient with isolated adrenocorticotropin deficiency had marked hyponatremia and inappropriate vasopressin secretion which was normalized after replacement, indicating vasopressin hypersecretion during hypoadrenocorticism. The second patient had combined anterior and posterior pituitary deficiency due to postpartum hypopituitarism and showed completely absent vasopressin secretion, with her polyuria being masked before cortisol replacement, suggesting a vasopressin-independent intrarenal mechanism of antidiuresis. The third patient with panhypopituitarism due to a pituitary tumor also had preexisting diabetes insipidus with defective vasopressin secretion. In this case, however, plasma vasopressin was found to be elevated when adrenal insufficiency and hyponatremia subsequently developed. Together, these results indicate that vasopressin hypersecretion does occur during adrenal insufficiency, but that the accompanying urinary diluting defect may be attributable either to vasopressin-dependent or to vasopressin-independent mechanisms.

Adrenal Insufficiency↗
PubMed1997

The cessation of fluoridated water administration and the fluoride distribution profiles in rat molar cementum.

The aim of this work was to obtain further information about the origin of fluoride profiles in cementum. Fluoride was administered to rats at varying doses (0.50, 100 ppm F in drinking water) and for different durations (4, 13 and 25 weeks). Fluoride distribution across the full thickness of molar cementum in rats was measured by means of an abrasive micro-sampling technique. The average fluoride concentrations in cementum increased significantly with increasing dose and duration of fluoride administration. The relative reduction of the average fluoride concentrations after cessation of fluoride administration was 94.2-36.5% at 50 ppm F and 62.2-49.2% at 100 ppm F in the outer layers (1-60 microns) and 91.5-24.1% at 50 ppm F and 74.1-7.6% at 100 ppm F in the middle (61-120 microns) layers of the cementum, respectively. The reduction rates were more closely related to the time intervals following cessation rather than fluoride concentrations in drinking water or specificity within the cementum. Two factors which may influence this are new cementum formation after withdrawal of fluoride and some fluoride release from cementum surfaces when the fluoride supply stopped. It was concluded that the cessation of fluoride administration reduced the fluoride concentration on the outer layers of cementum differing from bone where reduction occurs across the entire thickness.

Analysis of Variance↗