Biomedical subjects

N Kato

Publications and source records attributed to N Kato.

At least 631 records · Page 35Linked to original sources

PubMed1993

Splenic hemangiosarcoma with sinus endothelial differentiation.

A case of primary splenic hemangiosarcoma where the tumors entirely replaced the spleen is reported. Histologically, the splenic tumors consisted of two major components: (i) solid and nodular areas, in which spindle cells (SC) were arranged in interlacing fascicles; and (ii) vasoformative areas, in which vascular lining cells (VC) closely resembled normal splenic sinus endothelial cells (SSEC) in shape. Both SC and VC were immunoreactive with the markers of vascular endothelial cells (EC) including SSEC, JC70, von Willebrand factor, OKM5, vimentin MAb and Ulex europaeus-1 lectin. The tumor cells were positive for OKM5 MAb as well as normal SSEC and sheathed arterial EC, but other vascular EC in normal spleen were negative. Enzyme-histochemically, the tumor cells and normal SSEC revealed naphthol AS-D acetate esterase activity but no reaction for ALPase, whereas normal vascular EC other than SSEC in the spleen were positive for the latter but negative for the former. These studies revealed that the tumor cells expressed the same phenotype as normal SSEC. To the present author's knowledge this is the first report demonstrating sinus endothelial differentiation of splenic hemangiosarcoma, enzyme- and immuno-histochemically.

Aged↗

PubMed1993

Experimental studies of cis-diamminedichloroplatinum (II) and cis-diammine-1, 1-cyclobutandicarboxylate platinum (II) combination therapy for malignant gynecologic tumors.

A comparative exploration of the optimum regimens for CDDP and CBDCA therapy of malignant gynecologic tumors was conducted using both in vitro and in vivo approaches. In vitro, CBDCA exerted less cytotoxicity with short-time exposure, but over a longer time was as effective as CDDP. Pharmacokinetic studies demonstrated rapid binding of all administered CDDP to protein, while free-Pt was seen for many hours after CBDCA treatment. These results suggest that the gradual action of CBDCA leads to the appearance of cytotoxicity, and that in clinical use CBDCA affects the tumor cells for a long time. To increase the active dose of platinum, treatment with high doses of CDDP, or CBDCA, or the two platinum compounds with different pharmacokinetic behavior in combination, was designed for optimal therapeutic protocols. In the CDDP-alone treatment animals, renal toxicity was apparent with the increase in dose level. However, in the combination CDDP-and-CBDCA treatment animals, the total dose level could be elevated without causing toxicity. In the drug-sensitivity test, the combination therapy also exerted strong activity. The fact that the combined CDDP-and-CBDCA therapy appears to exert greater anti-tumor effects without any increment in adverse toxicity of these drugs is clinically promising.

Adenocarcinoma↗

PubMed1993

The effect of lipopolysaccharide on the disposition of xanthines in rats.

The effect of lipopolysaccharide (LPS) isolated from Klebsiella pneumoniae O3 on the pharmacokinetic behaviour and metabolism of the xanthines, theophylline and 1-methyl-3-propylxanthine (MPX), which are mainly metabolized by the liver, was investigated in rats. LPS was infused at 0.25 mg kg-1 over a period of 20-30 min, 2 h before the administration of theophylline (10 mg kg-1) or MPX (2.5 mg kg-1). Concentrations of both xanthines in plasma and concentrations of the parent drug and metabolites in urine were measured by HPLC. Model-independent methods were applied to estimate the pharmacokinetic parameters for both xanthines. No significant changes in the pharmacokinetic parameters or metabolism of theophylline were observed in rats pretreated with LPS. However, the total body clearance and volume of distribution of MPX were significantly increased by pretreatments with LPS. Significant decreases in the binding capacity and number of binding sites on the albumin molecule were observed in the presence of LPS. Changes occurring in the protein binding behaviour as a result of the introduction of LPS is a primary factor which not only increases the volume of distribution but also increases total body clearance. These results indicate that LPS has no effect on the pharmacokinetics and metabolic pathway of theophylline although it changes the disposition of MPX due to decreases in the extent of the protein binding of MPX which is highly bound to protein.

Animals↗

PubMed1993

Influence of a bacterial lipopolysaccharide on the pharmacokinetics of tobramycin in rats.

The effects of Klebsiella pneumoniae O3 lipopolysaccharide on the renal handling and distribution characteristics of the aminoglycoside tobramycin were investigated in rats. Tobramycin (2 mg kg-1) and inulin (100 mg kg-1) were administered intravenously 2 h after administration of 50, 250 or 500 micrograms kg-1 lipopolysaccharide. Lipopolysaccharide delayed the disappearance of tobramycin from plasma in a dose-dependent manner. A dose-dependent decrease in systemic clearance of tobramycin was observed, although the elimination rate constant and fraction of urinary recovery of unchanged drug were not significantly different in any group. Lipopolysaccharide significantly decreased the central compartment volume of distribution of tobramycin, but did not influence the steady-state volume of distribution. A dose-related increase in the ratio of the rate constant of transfer to the peripheral compartment to the rate constant of transfer from peripheral compartment to central compartment was observed. The glomerular filtration rate was significantly decreased by pretreatment with 250 micrograms kg-1 lipopolysaccharide and the clearance ratio was decreased by 20%, indicating that lipopolysaccharide increases the tubular reabsorption of tobramycin. Our findings suggest that K. pneumoniae O3 lipopolysaccharide modifies the glomerular filtration rate and tubular reabsorption without change in the terminal half-life and that drug distribution characteristics from the rapidly-distributing compartment to the peripheral compartment were altered without expansion of the extracellular fluid volume.

Animals↗

PubMed1993

[Identification of enterotoxin-producing Clostridium perfringens by the polymerase chain reaction].

Polymerase chain reaction was applied to identify enterotoxin-producing Clostridium perfringens by amplifying a segment of the C. perfringens enterotoxin gene. All of the four enterotoxin-positive reference strains tested were PCR positive while an enterotoxin-negative strain was PCR positive. All 17 clostridial strains (16 species) other than C. perfringens were PCR negative. With clinical strains isolated from various clinical specimens in Japan, Korea, and Thailand, all three enterotoxin-positive isolates were PCR positive and all 82 enterotoxin-negative isolates were PCR negative. PCR results for amplifying a region containing the initiation codon of the C. perfringens enterotoxin gene also demonstrated complete agreement with enterotoxin producibility. These results suggested that the PCR assay is a rapid and simple test for identifying the enterotoxin-producing C. perfringens without using any cultures and spore treatments.

Base Sequence↗

PubMed1993

In vitro activity of FK037, a new parenteral cephalosporin, against anaerobic bacteria.

The activity of FK037, a new parenteral cephalosporin, was compared with those of cefpirome, ceftazidime, and flomoxef against 322 recent clinical isolates of anaerobic bacteria. A fastidious facultative anaerobe, Gardnerella vaginalis, was also studied. FK037 inhibited 90% of isolates of Peptostreptococcus anaerobius, Peptostreptococcus asaccharolyticus, Clostridium perfringens, Mobiluncus spp., G. vaginalis, and Porphyromonas gingivalis at < or = 0.78 micrograms/ml. The MICs of FK037 for 50 and 90% of Bacteroides fragilis isolates were 25 and > 200 micrograms/ml, respectively; the activity of FK037 was comparable to those of cefpirome and ceftazidime but lower than that of flomoxef. The activity of FK037 against Fusobacterium nucleatum, Fusobacterium varium, and Bilophila wadsworthia decreased when inoculum size was increased from 10(6) to 10(8) CFU/ml. Little influence of inoculum size on the activity of FK037 was observed for other isolates tested. Medium pH affected the activity of FK037 against F. varium (MICs at pHs 5 and 7, 3.13 and 100 micrograms/ml, respectively) and Bacteroides gracilis (MICs at pHs 5 and 7, 12.5 and 1.56 micrograms/ml, respectively) but not against other organisms tested. FK037 was less resistant than flomoxef to hydrolysis by beta-lactamase group 2e derived from B. fragilis GAI 0558 and GAI 10150.

Bacteria, Anaerobic↗

PubMed1993

Plasmid-mediated AmpC-type beta-lactamase isolated from Klebsiella pneumoniae confers resistance to broad-spectrum beta-lactams, including moxalactam.

Klebsiella pneumoniae NU2936 was isolated from a patient and was found to produce a plasmid-encoded beta-lactamase (MOX-1) which conferred resistance to broad spectrum beta-lactams, including moxalactam, flomoxef, ceftizoxime, cefotaxime, and ceftazidime. Resistance could be transferred from K. pneumoniae NU2936 to Escherichia coli CSH2 by conjugation with a transfer frequency of 5 x 10(-7). The structural gene of MOX-1 (blaMOX-1) was cloned and expressed in E. coli HB101. The MIC of moxalactam for E. coli HB101 producing MOX-1 was > 512 micrograms/ml. The apparent molecular mass and pI of this enzyme were calculated to be 38 kDa and 8.9, respectively. Hg2+ and Cu2+ failed to block enzyme activity, and the presence of EDTA in the reaction buffer did not reduce the enzyme activity. However, clavulanate and cloxacillin, serine beta-lactamase inhibitors, inhibited the enzyme activity competitively (Kis = 5.60 and 0.35 microM, respectively). The kinetic study of MOX-1 suggested that it effectively hydrolyzed broad-spectrum beta-lactams. A hybridization study confirmed that blaMOX-1 is encoded on a large resident plasmid (pRMOX1; 180 kb) of strain NU2936. By deletion analysis, the functional region was localized within a 1.2-kb region of the plasmid. By amino acid sequencing, 18 of 33 amino acid residues at the N terminus of MOX-1 were found to be identical to those of Pseudomonas aeruginosa AmpC. These findings suggest that MOX-1 is a plasmid-mediated AmpC-type beta-lactamase that provides enteric bacteria resistance to broad-spectrum beta-lactams, including moxalactam.

Amino Acid Sequence↗

PubMed1993

Alterations in pharmacokinetics and protein binding behavior of cefazolin in endotoxemic rats.

The possible alterations in the pharmacokinetics and protein binding behavior of the beta-lactam antibiotic cefazolin (CEZ) were investigated in endotoxemic rats induced by Klebsiella pneumoniae O3 lipopolysaccharide (LPS). LPS (250 micrograms/kg of body weight) was infused for 20 to 30 min 2 h before an intravenous administration of CEZ (20 mg/kg). Significant decreases in systemic clearance and renal clearance of CEZ were observed in LPS-treated rats without any changes in fraction of urinary excretion in unchanged CEZ (> 0.8). The volume of distribution at steady state showed a tendency to increase. The protein binding parameters of CEZ, the binding capacity, and number of binding sites on the albumin molecule were decreased by LPS, whereas the dissociation constant did not change. Significant decreases in systemic and renal clearances for unbound CEZ were observed in LPS-treated rats. The glomerular filtration rate estimated as inulin clearance was also decreased by LPS. The ratio of renal clearance of unbound CEZ to glomerular filtration rate (clearance ratio) dropped to 70% of that in control rats, and the net tubular secretion of CEZ was also dramatically reduced. The present study suggests that LPS has an effect on the pharmacokinetics of CEZ by changes which occur in renal handling and protein binding.

Animals↗

PubMed1993

Enhancement of extracapsular polysaccharide synthesis in Klebsiella pneumoniae by RmpA2, which shows homology to NtrC and FixJ.

We determined the complete nucleotide sequence of a 2.1-kb HindIII-EcoRI fragment that was cloned from a resident large plasmid of Klebsiella pneumoniae Chedid, a highly virulent and mucoviscous strain of the O1:K2 serotype. This fragment encoded an ability to enhance K2 capsular polysaccharide synthesis in K. pneumoniae, and a 636-bp open reading frame (rmpA2) was found. The 411-bp rmpA reported to be involved in the virulence and mucoid phenotypes of K. pneumoniae by Nassif et al. (Mol. Microbiol. 3:1349-1359, 1989) was a part of rmpA2. Eighty percent homology in nucleotide sequence was found between rmpA2 and rmpA in the corresponding regions. The central domain of the deduced amino acid sequence of RmpA2 showed considerable homology to the central domains of NtrC of K. pneumoniae and Escherichia coli, to which the sigma factor of RNA polymerase binds. The C-terminal domain of RmpA2 also demonstrated considerable homology with the putative helix-turn-helix motifs of LuxR of Vibrio fischeri and FixJ of Rhizobium meliloti. Moreover, RmpA2 also showed some homology in its N- and C-terminal regions to those of RcsA, a transcriptional activator for colanic acid synthesis in E. coli. On the other hand, a sequence upstream of rmpA2 was found to be highly homologous to insertion sequence 3 of members of the family Enterobacteriaceae. Southern hybridization analysis suggested that rmpA2 exists on the large plasmids of all mucoviscous virulent K2 strains but not on those of the slightly mucoviscous avirulent strains. Freeze substitution electron microscopy and fluorescent-antibody staining with anti-K2 serum revealed that K. pneumoniae Chedid has a dense and thick capsule (180 nm) with dense extracapsular substance, whereas K. pneumoniae K2-215, one of the slightly mucoviscous and avirulent strains, has a capsule which is looser and thinner (120 nm) than that of strain Chedid and no extracapsular substance. Introduction of rmpA2 into K2-215 as well as reference strains K. pneumoniae K9 and K72 resulted in a change of the colony phenotype to highly mucoviscous through abundant production of extracapsular substance which reacted with anti-K2, -K9, or -K72, respectively, as did their parental strains. From these results, it is suggested that RmpA2 belongs to the family of transcriptional regulators and confers a highly mucoviscous phenotype on cells of various serotypes of K. pneumoniae by enhancing extracapsular polysaccharide synthesis.

Amino Acid Sequence↗

PubMed1993

Typing of Clostridium difficile by western immunoblotting with 10 different antisera.

Western blotting (immunoblotting) with antisera against each of 10 reference serogroups was evaluated as a means of typing Clostridium difficile. A total of 164 clinical isolates of C. difficile were tested. Variations in band profiles in each serogroup were used to type isolates into subserogroups. This technique was useful for an epidemiological investigation.

Antibodies, Bacterial↗

PubMed1993

Molecular epidemiology of a variant of coxsackievirus A24 in Taiwan: two epidemics caused by phylogenetically distinct viruses from 1985 to 1989.

In order to know the phylogenetic relationship and the route of transmission of a variant of coxsackievirus A24 (CA24v), an agent that caused four sequential outbreaks of acute hemorrhagic conjunctivitis from 1985 to 1989 in Taiwan, the nucleotide sequence variations in the virus-encoded proteinase 3C region (549 nucleotides) were studied with 19 isolates. The prototype strain (EH24/70), four isolates from Japan, and two isolates from Hong Kong were used for comparison. The nucleotide sequences of the Taiwan strains from the 1985-1986 and 1988-1989 epidemics were closely related within each epidemic, while they were more distantly related between strains from two epidemics. Phylogenetic analysis by the unweighted pairwise grouping method of the arithmetic average revealed that the 19 Taiwan isolates had diverged into two groups, 1985-1986 and 1988-1989 groups. The time at which these two groups diverged was estimated to be around May 1982, more than 3 years prior to the first appearance of the CA24v epidemic in Taiwan. On each occasion, the viruses caused a 2-year epidemic and then disappeared. The Taiwan isolates from 1985 to 1986 were closely related to the Japan isolates from 1985 to 1986 and the Taiwan isolates from 1988 to 1989 were phylogenetically close to the 1989 Japan isolates, indicating that Taiwan and Japan had two common-source outbreaks. However, none of the 1988 Taiwan isolates were phylogenetically close to the 1988 Japan or Hong Kong isolates. The evidence revealed that Taiwan has had two repeated but discontinuous introductions of CA24v since its first appearance in Taiwan in 1985. None of the other CA24v strains have been detected so far.

Base Sequence↗

PubMed1993

Chimeric hepatitis B virus core particles with parts or copies of the hepatitis C virus core protein.

Either parts or multiple copies of the core gene of hepatitis C virus (HCV) were fused to the 3' terminus of the hepatitis B virus (HBV) core gene with 34 codons removed. As many as four copies of HCV core protein (720 amino acids) were fused to the carboxy terminus of truncated HBV core protein (149 amino acids) without preventing the assembly of HBV core particles. Chimeric core particles were sandwiched between monoclonal antibody to HBV core and that to HCV core, thereby indicating that antigenic determinants of both HBV and HCV cores were accessible on them. Proteolytic digestion deprived chimeric core particles of the antigenicity for the HCV core without affecting that of the HBV core, confirming the surface exposure of HCV core determinants. The density of HCV core determinants on chimeric core particles increased as copies of fused HCV core protein were increased. Hybrid core particles with multiple HCV core determinants would be instrumental as an antigen probe for detecting class-specific antibodies to the HCV core in patients with acute and chronic hepatitis C and for simultaneous detection of antibodies to HBV core and those to HCV core in donated blood.

Amino Acid Sequence↗

PubMed1993

Humoral immune response to hypervariable region 1 of the putative envelope glycoprotein (gp70) of hepatitis C virus.

We recently found that alterations of amino acids in hypervariable region 1 (HVR1) of the putative envelope glycoprotein (gp70) of hepatitis C virus (HCV) occurred sequentially in the chronic phase of hepatitis at intervals of several months. This finding suggests that mutations in HVR1 are involved in the mechanism of persistent chronic HCV infection involving escape from the immunosurveillance system. To explore this possibility, we examined the humoral immune response to HVR1 with our assay system, in which immunoprecipitation was carried out with sera from patients by using an HVR1 (27-amino-acid) dihydrofolate reductase fusion protein synthesized by in vitro transcription and translation. Results showed that HVR1 contains a sequence-specific immunological epitope that induces the production of antibodies restricted to the specific viral isolate. Furthermore, analysis of the kinetics of the appearance of antibodies in two patients with chronic hepatitis, with whom successive alterations of amino acids of HVR1 have been observed, showed that the titers of anti-HVR1 antibodies usually reached maximal levels several months after the isolation of HCV having the specific sequence of HVR1. This observation suggests that anti-HVR1 antibodies are involved in the genetic drift of HVR1 (minor antigenic variation) by immunoselection. However, the coexistence of HVR1 as an antigen and its specific antibody was sometimes observed. The possibility that HVR1 acts as a neutralizing epitope is discussed.

Adult↗

PubMed1993

Two distinct proteinase activities required for the processing of a putative nonstructural precursor protein of hepatitis C virus.

Gene products of hepatitis C virus (HCV), a possible major causative agent of posttransfusion non-A, non-B hepatitis, are considered to be produced from a precursor polyprotein via proteolytic processing mediated by either host cell or viral proteinases. The presence of HCV serine proteinase has been proposed from analyses of amino acid sequence homology. To examine the processing mechanism of the HCV precursor polyprotein, the amino-terminal region of the putative nonstructural protein region of the HCV genome, containing the serine proteinase motif, was expressed and analyzed by using an in vitro transcription/translation system and a transient expression system in cultured cells. Two distinct proteinase activities which function in the production of a 70-kDa protein (p70) from the precursor polyprotein were detected. One of these proteinase activities, which cleaved the carboxyl (C)-terminal side of p70, required the presence of the serine proteinase motif, which is located in the amino (N)-terminal region of p70. That suggested that the predicted HCV serine proteinase was functional. The other activity, which was responsible for the cleavage of the N-terminal side of p70, required the expression of the region upstream and downstream of that cleavage site, including the p70 serine proteinase domain. From the results of pulse-chase analysis, using proteinase inhibitors coupled with a point mutation analysis, the latter activity was proposed to be a novel zinc-dependent metalloproteinase.

Amino Acid Sequence↗

PubMed1993

Mass screening for prostate cancer and the bias relating to survival rate.

Since 1981 we have been studying prostate cancer (Pca) by mass screening (MS) in the Gunma Prefecture, Japan. From 1981 to 1990, 9,067 subjects (total 15,451) were examined in connection with this project and 121 subjects were diagnosed as having Pca. The presence of Pca in 87 cases was confirmed at their initial MS (initial group); 34 cases were confirmed either the year after or several years after the first MS (repeat group). To evaluate the significance of MS for Pca, in this group of patients, the effects of 'lead time bias', 'self-selection bias' and 'length bias' on the survival rate were compared to Pca patients detected in the hospitals of the Gunma Prefecture during the same period. The survival curves of MS cases for each stage of the disease were better than those of the controls. Only in stage D was there a significant difference between the two groups. However, this MS curve decreased from the 4th year in the same manner as the control curve from the start. The clinical characteristics (age, pathological differentiation, prostatic acid phosphatase, gait disturbance, erythrocyte sedimentation rate, chronic disease, and pain in the patients with stage D disease) were compared between both groups. All characteristics studied, except age, in the MS group were clinically more favorable compared to those of the controls for each stage or in total. Moreover, the relative survival rate of subjects examined by MS was greater than 1.0. No significant difference was found in stage distribution between the initial group and the repeat group.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗

PubMed1993

Relief of acute lower limb ischemia with percutaneous fenestration of intimal flap in a patient with type III aortic dissection--a case report.

Acute right lower limb ischemia developed in a patient with type III aortic dissection. Aortography revealed complete occlusion of the right common iliac artery by dissecting intima. Immediately percutaneous transfemoral fenestration with angioplasty balloon catheter was performed and marked improvement was obtained in clinical symptoms and angiographic findings. Unfortunately the patient died of rupture of the thoracic aorta about eleven hours after the procedure. The cause of death was not thought to be related to this procedure. The authors conclude that percutaneous fenestration should be considered as the treatment of choice for visceral or limb ischemia due to acute aortic dissection.

Aortic Dissection↗

PubMed1993

Appearance of a regenerating (reg) gene protein in pancreatic islets of remission BB/Wor//Tky rats.

Remission of diabetes, i.e. significant amelioration from absolute insulin-dependency, has been sometimes observed in diabetic BB/Wor//Tky rats which were treated with insulin. In remission BB/Wor//Tky rats, plasma glucose levels improved to near normal level and insulin content was also preserved as much as that between diabetic and non-diabetic rats. In this process, we hypothesized that autoimmune insulitis was suppressed and remaining islet B-cells was restored from severe destruction by recovering in number and/or function. While, recently, a novel regenerating (reg) gene, identified in the regenerating pancreatic islets of surgical models, is reported to be related to the replication of pancreatic B-cells in vitro. Based on these findings, we histologically investigated whether the reg protein could be actually expressed or not in the islets from remission BB/Wor//Tky rats. As expected, reg protein was observed in the islets from remission BB/Wor//Tky rats mainly in accordance with pancreatic B-cells. Thus, the present findings suggested that the regeneration of pancreatic B-cells represented by the expression of reg protein might be, at least in part, relevant to remission induced by insulin therapy in spontaneously occurring Type 1 diabetes in BB/Wor//Tky rats.

Animals↗

PubMed1993

The role of intraabdominal pressure in venous blood drainage from the prostate into the vertebral vein system.

We investigated venous blood drainage from the prostate into the vertebral vein system by cineangiography in five mongrel dogs and measured intraabdominal pressure and venous blood pressure in the dog or human to study the role of intraabdominal pressure in the drainage. The averages of intraabdominal pressure and caudal vena caval pressure in the dog were 32.2 +/- 3.0 and 12.8 +/- 1.3 mmHg, respectively, in the supine position, and 39.2 +/- 3.0 and 23.8 +/- 4.0 mmHg, respectively, in the head-up tilt position, when the radiopaque medium injected into the dorsal penile vein appeared in the vertebral vein system. Intraabdominal pressure in the head-up tilt position was significantly higher than that in the supine position when the venous drainage into the vertebral veins happened. In eight continuous ambulatory peritoneal dialysis patients, intraabdominal pressure showed 8.1 +/- 2.4 mmHg in the supine position, 24.6 +/- 4.3 mmHg in the sitting position, and 30.4 +/- 4.9 mmHg in the standing position at rest. During voluntary contraction of the abdominal muscles, the pressure was increased up to 50.6 +/- 21.6 mmHg in the supine position, 69.3 +/- 19.8 mmHg in the sitting position, and 73.8 +/- 19.8 mmHg in the standing position. These pressure values in the human were significantly higher than those observed at the time when the radiopaque medium appeared in the vertebral veins in both supine and head-up tilt positions in the canine. These results suggest that the increase of intraabdominal pressure causes inflow of prostatic venous blood into the vertebral veins via the inferior vena cava, common iliac vein, or internal iliac vein.

Abdomen↗