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Biomedical subjects

K Kondo

Publications and source records attributed to K Kondo.

At least 415 records · Page 23Linked to original sources

Use of the double-stapling technique in esophageal surgery.

This study was conducted to examine the effectiveness of the double-stapling technique (DST) for performing esophageal anastomoses. A total of 17 patients, 10 with esophageal cancer and 7 with gastric cancer, underwent esophageal anastomosis employing this technique. Of the ten patients who underwent esophageal operations, eight received esophageal-gastric tube anastomosis, one esophageal-colon and colon-residual stomach anastomosis, and one pharyngeal-gastric tube anastomosis, while all seven of the patients who underwent operations for gastric cancer received esophagojejunostomy. Thus, a total of 18 anastomoses were performed. No problems were encountered during the anastomoses, and no leakage occurred in any of the patients. Thus, we conclude that DST is a safe and easy technique for performing esophageal anastomosis, especially intrathoracic or intramediastinal anastomoses.

Anastomosis, Surgical↗

A new method of estimating the distribution of muscle fiber conduction velocities.

A computer-assisted method of estimating the distribution of muscle fiber conduction velocities is described. An electrode array composed of 2 stimulating and 4 recording electrodes is used to record surface muscle action potentials (MAPs) in response to direct muscle stimulation. The velocity distribution and the single muscle fiber action potential (SFAP) are calculated from the recorded MAPs by an iterative method of estimation. The estimation is based on the assumption that the spatial orientation of each muscle fiber viewed from the recording electrodes is the same along the muscle fibers and a MAP is recorded as a linear summation of all SFAPs. The accuracy of this estimation is demonstrated using simulated MAPs. The method is also tested on MAPs containing simulated amplifier noise, stimulus artifact, and errors in distance between electrodes. Finally we applied this method to MAP recordings of the biceps brachii in 23 healthy subjects. The velocity distribution was successfully estimated in 20 cases. The average of the estimated distributions was smaller than that described by previous workers. The reasons for the difference are discussed.

Adult↗

Pathogenesis of adenocarcinoma induced by gastrojejunostomy in Wistar rats: role of duodenogastric reflux.

The pathogenetic effect of duodenogastric reflux of the development of gastric stump carcinoma was studied experimentally. In this animal model, 95 male Wistar rats were subjected to a specially designed gastrojejunostomy to divert the duodenal contents into the resected stomach through the afferent and efferent loop. The rats were fed normally without any carcinogen administration. The incidence of adenocarcinomas around the anastomosis of afferent loop was 0% at 10 weeks, 18.8% at 20 weeks and 34.4% at 40 weeks, so the incidence was apt to rise in parallel with passing of the weeks. At 40 weeks, the rats had a significantly higher incidence of adenocarcinoma in the gastric mucosa around the afferent loop than around the efferent loop (P < 0.05). Of particular interest is that invasive growth of the cancerous tissue into the liver was observed in one animal. Polypoid lesions called 'atypical hyperplasia' in the present study were similar to gastritis cystica polyposa of humans. The development of adenocarcinoma was found to be intimately connected with atypical hyperplasia, which might be promoted by repeated destruction and regeneration by duodenogastric reflux. These results suggest that the direct contact of the duodenal juice with the gastric mucosa induces carcinoma in the anastomotic lesion. From the clinical perspective, our findings suggest that a surgical technique that minimizes the duodenogastric reflux should be chosen.

Adenocarcinoma↗

Frequent genetic instability in small intestinal carcinomas.

To determine whether genetic instability plays a part in the development of digestive tract carcinomas, we analyzed 3 microsatellite loci isolated from tumors and surrounding normal tissue samples obtained during surgery. The polymerase chain reaction (PCR) technique was used to assess differences between tumor and matched normal DNAs. Replication errors (RERs) were observed in 3 of the 29 cases (10%) of gastric carcinoma and in 11 of the 72 cases (15%) of colorectal carcinoma. None of the 13 (0%) esophageal carcinoma cases showed any RER, but 5 of the 11 cases of small intestinal carcinoma (45%) had RERs, a significantly frequent finding. These results suggest that genetic instability plays an important role in the pathogenesis of small intestinal carcinomas.

Colorectal Neoplasms↗

Bronchial hyperresponsiveness and airway neutrophil accumulation induced by interleukin-8 and the effect of the thromboxane A2 antagonist S-1452 in guinea-pigs.

Interleukin-8 (IL-8) has been shown to be a chemotactic factor for neutrophils, T-lymphocytes and eosinophils, but it is unknown whether the IL-8-induced inflammatory cell accumulation into the airways can cause the bronchial hyperresponsiveness (BHR) characteristic of asthma. IL-8 at a dose of 0.5 or 5 micrograms/kg was administered intranasally to guinea-pigs twice a week for 3 weeks. One day after the last administration, animals were anesthetized and artificially ventilated through tracheal cannula and lateral pressure at the cannula (Pao) was measured as an overall index of airway responses to increasing concentrations of inhaled histamine (25, 50, 100, and 200 micrograms/ml). The IL-8 treatment significantly enhanced bronchial responsiveness to histamine in a dose-dependent manner (ANOVA P < 0.01). The provocative concentration of histamine causing a 100% increase in Pao (PC100) at a dose of 0.5 and 5 micrograms/kg of IL-8 was 68.1 (GSEM 1.12) and 35.6 (GSEM 1.25) micrograms/ml, respectively. The latter was significantly (P < 0.01) lower than that in control animals treated with PBS (93.3 [GSEM, 1.14] micrograms/ml). The IL-8 treatment also induced a significant influx of neutrophils, but not eosinophils, in bronchoalveolar lavage (BAL) fluid (18.3 +/- 8.8 and 30.6 +/- 8.3% in animals treated with 0.5 and 5 micrograms/kg, respectively, of IL-8 vs 3.6 +/- 0.7% in phosphate buffered saline-(PBS)-treated animals). Furthermore, we examined the effect of the thromboxane receptor antagonist S-1452 (0.01 or 0.1 mg/kg, i.p. 24 and 1 h before anesthesia) on this IL-8 induced BHR. S-1452 significantly inhibited the BHR dose-dependently (ANOVA P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

Evaluation of soluble IL-6 receptor concentration in serum and epithelial lining fluid from patients with interstitial lung diseases.

We measured soluble IL-6 receptor (sIL-6R) levels in serum and bronchoalveolar lavage fluids (BALF) from patients with interstitial pneumonia of unknown etiology (IP) (n = 17), sarcoidosis (n = 8) and normal control subjects (n = 10), to investigate its role in pulmonary diseases. Soluble IL-6R was determined by an ELISA. The volume of epithelial lining fluid (ELF) in BALF was estimated using an urea method. We found that levels of sIL-6R in serum, BALF, and ELF from patients with IP or sarcoidosis were significantly higher than those from normal subjects. Furthermore, levels of sIL-6R in BALF or ELF were significantly correlated with those of albumin, indicating that sIL-6R, together with albumin, may enter ELF as a result of the increased permeability caused by pulmonary inflammation. Thus most of the sIL-6R in ELF would be from serum, and relatively small amounts of it might be produced locally. However, sIL-6R levels in ELF, but neither serum nor BALF, were significantly correlated with levels of C-reactive protein in patients with IP. These results suggest that both systemic and local production of sIL-6R are increased, and raised sIL-6R is involved in the modulation of systemic and local inflammatory responses in patients with IP and sarcoidosis.

Adult↗

Cold-shock induction of a family of TIP1-related proteins associated with the membrane in Saccharomyces cerevisiae.

TIP1 is the first known cold-shock- and heat-shock-induced gene in Saccharomyces cerevislae. Here it is demonstrated that a TIP1 homologue, TIR1, which had been previously cloned as SRP1 (serine-rich protein), is strongly induced by a downshift in growth temperature from 30 to 10 degrees C. We further cloned TIR2, which is transcribed at a low basal level but is increased strongly by cold shock and, to a lesser extent, by heat shock. The predicted protein sequence of TIR2 demonstrates remarkable homology to TIR1 (72.2%) and is also homologous with TIP1 (49%). TIP1, TIR1 and TIR2 are rich in both serine and alanine residues and each contains serine-rich tandem repeats. The proteins contain putative N-terminal signal peptides as well as hydrophobic C-terminal sequences, indicating that the proteins may be membrane bound. The predicted protein sequences are also consistent with extensive O-mannosylation as well as glycosyl-phosphatidyl inositol (GPI) membrane anchoring. Cell fractionation analysis as well as studies using a yeast strain that is conditionally deficient in glycosylation demonstrate that TIP1 is a heavily modified membrane-associated protein. Single, double combinations and triple mutants were created and none demonstrated any obvious phenotype, indicating that this family of genes is not essential for normal growth.

Amino Acid Sequence↗

Cloning, sequencing, and characterization of the gene encoding the smallest subunit of the three-component membrane-bound alcohol dehydrogenase from Acetobacter pasteurianus.

The membrane-bound alcohol dehydrogenase (ADH) of Acetobacter pasteurianus NCI1452 consists of three different subunits, a 78-kDa dehydrogenase subunit, a 48-kDa cytochrome c subunit, and a 20-kDa subunit of unknown function. For elucidation of the function of the smallest subunit, this gene was cloned from this strain by the oligonucleotide-probing method, and its nucleotide sequence was determined. Comparison of the deduced amino acid sequence and the NH2-terminal sequence determined for the purified protein indicated that the smallest subunit contained a typical signal peptide of 28 amino acids, as did the larger two subunits. This gene complemented the ADH activity of a mutant strain which had lost the smallest subunit. Disruption of this gene on the chromosome resulted in loss of ADH activity in Acetobacter aceti, indicating that the smallest subunit was essential for ADH activity. Immunoblot analyses of cell lysates prepared from various ADH mutants suggested that the smallest subunit was concerned with the stability of the 78-kDa subunit and functioned as a molecular coupler of the 78-kDa subunit to the 48-kDa subunit on the cytoplasmic membrane.

Acetobacter↗

Structure and functional analysis of a marine bacterial carotenoid biosynthesis gene cluster and astaxanthin biosynthetic pathway proposed at the gene level.

A carotenoid biosynthesis gene cluster for the production of astaxanthin was isolated from the marine bacterium Agrobacterium aurantiacum. This cluster contained five carotenogenic genes with the same orientation, which were designated crtW, crtZ, crtY, crtI, and crtB. The stop codons of individual crt genes except for crtB overlapped the start codons of the following crt genes. Escherichia coli transformants carrying the Erwinia uredovora carotenoid biosynthesis genes provide suitable substrates for carotenoid biosynthesis. The functions of the five crt genes of A. aurantiacum were determined through chromatographic and spectroscopic analyses of the pigments accumulated in some E. coli transformants carrying various combinations of the E. uredovora and A. aurantiacum carotenogenic genes. As a result, the astaxanthin biosynthetic pathway is proposed for the first time at the level of the biosynthesis genes. The crtW and crtZ gene products, which mediated the oxygenation reactions from beta-carotene to astaxanthin, were found to have low substrate specificity. This allowed the production of many presumed intermediates of astaxanthin, i.e., adonixanthin, phoenicoxanthin (adonirubin), canthaxanthin, 3'-hydroxyechinenone, and 3-hydroxyechinenone.

Amino Acid Sequence↗

A transformation system for the yeast Candida utilis: use of a modified endogenous ribosomal protein gene as a drug-resistant marker and ribosomal DNA as an integration target for vector DNA.

We have developed a transformation system for the yeast Candida utilis. A novel strategy was applied to construct the transformation system, since auxotrophic mutants which could be used as hosts for transformation are not available. A gene encoding the ribosomal protein L41 was cloned from C. utilis, which is sensitive to cycloheximide, and used as a marker gene conferring cycloheximide resistance after modification of its amino acid sequence. The marker gene was constructed by substitution of the proline codon at position 56 with the glutamine codon by in vitro mutagenesis, as it had been reported previously that the 56th amino acid residue of L41 is responsible for the cycloheximide sensitivity of various organisms (S. Kawai, S. Murao, M. Mochizuki, I. Shibuya, K. Yano, and M. Takagi, J. Bacteriol. 174:254-262 1992). The ribosomal DNA (i.e., DNA coding for rRNA) of C. utilis was also cloned and used as a multiple-copy target for the integration of vector DNA into the genome, which resulted in a high transformation efficiency. Transformants were obtained by electroporation with a maximum efficiency of approximately 1,400 transformants per 1 microgram of linearized DNA carrying the gene for cycloheximide resistance and part of the ribosomal DNA. No transformants were obtained with intact plasmids. Multiple copies of the linearized plasmid were integrated into the host chromosome by homologous recombination. Southern analysis of the transformants in which vector DNA was integrated at the L41 gene locus indicated that there are two copies of gene for the L41 protein per cell, suggesting that C. utilis is diploid. Transformants were obtained from a variety of C. utilis strains, indicating that this method is applicable to the transformation of other C. utilis strains, even though there is significant heterogeneity in chromosomal karyotypes among these strains.

Amino Acid Sequence↗

Fluoride distribution of rat molar cementum in relation to age and fluoride levels in the drinking water.

The present study was undertaken to determine the fluoride distribution profile in rat molar cementum with age in relation to fluoride in drinking water. Fifty-four female Wistar rats were used for the experiment. Before the experiment 6 rats were killed under chloroform anesthesia at 4 weeks of age as controls. The remaining 48 rats were divided into two groups: a control group given distilled water and the other group given water containing 100 ppm fluoride ad libitum. Six rats from each group were killed at the ages of 6, 12, 24, and 48 weeks. The fluoride distribution in the molar cementum was analyzed from the surface to the cementodentinal junction by abrasive microsampling. The fluoride concentrations in molar cementum from control rats on distilled water remained relatively constant until 24 weeks. A small increase then occurred between 24 and 48 weeks. The fluoride concentration in cementum from rats drinking water containing 100 ppm fluoride increased markedly with age, both in outer and inner regions of the molar cementum for all rats. On the other hand, the fluoride concentration in the cementum of older rats drinking water with 100 ppm fluoride was significantly higher in the outer than in the inner region of the cementum. It was concluded that the fluoride distribution in rat molar cementum may increase throughout life in relation to the fluoride level in the drinking water.

Age Factors↗

Angiotensin converting enzyme as a genetic risk factor for coronary artery spasm. Implication in the pathogenesis of myocardial infarction.

It has been reported that individuals with the D allele of an insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene are at greater risk for myocardial infarction (MI), especially among subjects normally considered to be at low risk. However, little is known about the mechanism by which the ACE polymorphism affects the risk of MI. Coronary artery spasm (CAS) is considered to be one possible mechanism for developing MI. We therefore examined the ACE polymorphism relation to CAS to determine if this was the mechanism by which the DD genotype influences MI. We studied 150 angiographically assessed Japanese males, all more than 60 yr old. CASs were detected using intracoronary injection of ergonovine maleate. Subjects were divided into three groups: those with CAS (group 1), those without CAS, but with fixed organic stenosis (group 2); and those without CAS and no organic stenosis (group 3). DD subjects were significantly represented in group 1 when compared with groups 2 (P = 0.002) and 3 (P = 0.026). These results suggest that the DD genotype relates to the greater risk for MI in the patients with CAS.

Aged↗

Mobility inhibition and nematocidal activity of asarone and related phenylpropanoids on second-stage larvae of Toxocara canis.

The in vitro effect of asarone, the nematocidal principle of the rhizome of Acorus calamus, on second-stage larvae of Toxocara canis is composed of two independent actions: one is a fast acting inhibition of the larval mobility and the other is a slow acting larvicidal action. Mobility of the larvae was rapidly inhibited when they were incubated with asarone. Dye exclusion assay revealed that larvae were alive at this stage, and their mobility was restored after the first inhibition, suggesting that this effect was temporary and reversible. However, when the mobility decreased again during prolonged incubation, the cellular viability of larvae disappeared, showing that they were killed by the compound. The above two-stage effect of asarone was almost identical in two geometrical isomers ((E)- and (Z)-asarone). Di- and tri-methoxypropenyl or propylbenzenes carrying two methoxy groups at a vicinal position on a benzene ring showed, more or less, a two-stage effect of this type. These two actions were suggested to be separable by an appropriate modification of the structure.

Allylbenzene Derivatives↗

Radiofrequency catheter ablation for the treatment of common atrial flutter in humans.

Endocardial catheter ablation has been recently been proposed for the treatment of arrhythmias originating in the right atrium. In this study, we used this technique in 5 patients with paroxysmal common atrial flutter and 3 patients with paroxysmal uncommon atrial flutter. Various antiarrhythmic agents had failed to prevent the recurrence of these episodes. In each procedure, we used a large-tip 7 F quadripolar catheter electrode that was introduced via the femoral vein into the lower part of the right atrium. The two distal electrodes were used to record double-spike potentials or fragmented electrograms. A unipolar electrogram recording from a distal electrode of the same catheter was also used to identify local activation. The targets for ablation were sites which showed double-spike potential and fragmented electrogram 40-60 msec earlier than the onset of the F wave. Application of radiofrequency (RF) energy (25-40 watts) (3-17 applications) terminated atrial flutter and prevented reinduction of atrial flutter in the 5 patients with common atrial flutter. However, atrial flutter could not be terminated with the application of RF energy in the 3 patients with uncommon atrial flutter. The sites at which ablation was successful were located inferior or posterior to the coronary sinus ostium between the inferior vena cava and the tricuspid valve annulus, and were characterized by double-spike potentials and fragmented electrograms with activation times > or = 40 msec before the onset of the F wave. This area may represent the exit site from the area of slow conduction, since pacing from this site showed concealed entrainment of the F wave, and a local electrogram to the onset of the F wave coincided with the pacing spike to the onset of the F wave. Follow-up of these 5 patients (19.4 +/- 10.4 weeks) revealed recurrence of the original atrial flutter in 1 patient and a new type of atrial flutter in 1 patient. The other 3 patients have been episode-free, although an antiarrythmic agent was given for the treatment of paroxysmal atrial fibrillation in 2 patients. We conclude that the application of RF energy to the presumed critical area in the atrial flutter reentrant circuit seems to be effective in terminating and preventing common atrial flutter. Long-term follow-up is required for the recurrence of atrial flutter.

Adolescent↗

[Inhibitory effects of prostaglandin E1.alpha-cyclodextrin (PGE1.CD) on dimethylnitrosamine-induced acute liver damage in rats].

The effects of PGE1.CD on dimethylnitrosamine (DMN)-induced acute liver damage with intravascular coagulation in rats were biochemically and histopathologically investigated. PGE1.CD was administered i.v. from 30 min before to 24 hr after DMN-intoxication (pretreatment) and from 30 min after or from 4 hr after to 24 hr after DMN-intoxication (post-treatment). Pretreatment with PGE1.CD (0.2-2 micrograms/kg/min) dose-dependently suppressed the decrease of platelet counts and the elevation of blood biochemical parameters (PT, HPT, GOT, GPT, LDH, LAP, T-Bil) caused by DMN-intoxication. PGE1.CD (0.5 microgram/kg/min and over) significantly suppressed the DMN-induced histopathological changes (occurrence of hemorrhage and necrosis). Post-treatment with PGE1.CD (2 micrograms/kg/min) also suppressed the liver damage. Furthermore, pretreatment with PGE1.CD (2 micrograms/kg/min) not only suppressed the disruption of hepatocytes, but also prevented the damages of sinusoidal endothelial cells and lysosomal membrane, and it reduced the increase of lipid peroxidation. PGE1.CD (1 microgram/kg/min and over) significantly suppressed the decrease of hepatic tissue blood flow caused by DMN-intoxication. These results demonstrate that PGE1.CD has therapeutically efficacy against DMN-induced acute liver damage in rats; Therefore, it will be clinically useful for the treatment of severe hepatitis such as fulminant hepatitis with intravascular coagulation in the sinusoid.

Acute Disease↗

[Prostacyclin mimetics with non-prostanoid structures].

In searching for new drugs, we have developed receptor binding assays for prostanoids. Among the various compounds that we have tested, we have found that hydronaphthalene derivatives can interact with some prostanoid receptors. Modification of such compounds produced several pure prostacyclin agonists (ONO-AP-227 and ONO-AP-437) and a unique prostacyclin agonist with inhibitory activity against thromboxane synthase (ONO-AP-500-02). These compounds showed specific binding to the IP receptor with Ki values less than 0.2 microM, without binding to EP and TP receptors. These compounds also inhibited human platelet aggregation with IC50 values of 0.03-0.24 microM. These compounds inhibited ex vivo platelet aggregation in dogs or rats in the dose range of 1 to 30 mg/kg. Furthermore, ONO-AP-500-02 inhibited ex vivo thromboxane formation at doses similar to those inhibiting platelet aggregation in rats. These results, taken together, suggest that chemical syntheses of compounds targeting prostanoid receptors can produce unique prostanoid agonists or antagonists, and rational syntheses might be possible for compounds with different pharmacological actions such as inhibition of thromboxane synthase.

Acetates↗