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Biomedical subjects

R Nakaya

Publications and source records attributed to R Nakaya.

At least 19 recordsLinked to original sources

Elevated plasma tissue factor antigen level in patients with disseminated intravascular coagulation.

The plasma tissue factor (TF) antigen level was measured in patients with disseminated intravascular coagulation (DIC). The plasma TF antigen was detected in normal volunteers, and it was significantly higher in DIC patients than in non-DIC patients. However, in some patients with DIC, the plasma TF antigen level was within the normal range. The plasma TF antigen level in patients with DIC significantly decreased after therapy, but it was not correlated with organ failure or outcome. The plasma TF antigen level in patients with DIC was not correlated with other hemostatic markers. The plasma TF antigen level tended to be higher in DIC patients with nonlymphoid leukemia than in those with lymphoid tumor. TF might be implicated in the occurrence and progression of DIC.

Antigens↗

Regulation of asialoglycoprotein receptor synthesis by inflammation-related cytokines in HepG2 cells.

The asialoglycoprotein receptor (AGPR) is responsible for the catabolism of acute phase proteins. The effects of inflammation-related cytokines on the expression of AGPR were investigated in HepG2 cells derived from a human hepatoblastoma cell line. Binding studies, using a [125I]-labeled asialo-orosomucoid ligand, revealed that AGPR numbers on cell surfaces were increased by interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF). In cells treated with IL-1, IL-6, or TNF, immunohistochemical staining with an anti-AGPR monoclonal antibody demonstrated augmented expression. Pulse labeling analysis, using [35S]-labeled methionine, showed newly synthesized AGPR in both the precursor and the mature forms. When IL-1, IL-6, and TNF were added to the culture medium, total synthesis of AGPR (sum of the mature and precursor forms) was increased. In addition, the relative proportion of the synthesized precursor form of AGPR was higher in cytokine-treated than in untreated cells, suggesting that these cytokines augment the synthesis of AGPR, particularly in the stage prior to glycosylation.

Acute-Phase Proteins↗

Ethanol inhibits asialoglycoprotein receptor synthesis but augments its mRNA expression in a human hepatoma cell line.

The effect of ethanol on the expression of asialoglycoprotein receptor protein and its mRNA was studied in a human hepatoma cell line, HepG2. The number of asialoglycoprotein receptors on the cell surface was decreased to 60% of the control level, without a loss in affinity, by incubating the cells with 100 mM ethanol. The decrease in cell surface asialoglycoprotein receptors was paralleled by a decrease in total receptor numbers, including intracellular and surface receptors. The internalization of asialoglycoprotein was also diminished, to 44% of that in control cells. The decreases in cell surface receptors and total receptor numbers were partially restored by 2 mM 4-methylpyrazole, suggesting that ethanol metabolites participated in the diminution of asialoglycoprotein receptor expression. However, the steady-state expression of asialoglycoprotein receptor mRNA was increased in ethanol-treated cells and further augmented by a longer ethanol exposure. These paradoxical results, i.e., the decrease of asialoglycoprotein receptor protein and the increase of its mRNA expression, suggest that the reduction in the asialoglycoprotein receptor protein is a post-transcriptional event and that a possible feedback regulatory mechanism may control asialoglycoprotein receptor gene transcription and/or impair the degradation of its mRNA.

Alcohol Dehydrogenase↗

Production and characterization of specific asialoglycoprotein receptor antibodies.

Monoclonal antibodies (MoAbs) were produced by immunizing BALB/c mice with asialoglycoprotein receptor (AGPR) purified from human liver. The purity of AGPR was confirmed by SDS-polyacrylamide gel electrophoresis and by amino acid sequence. An enzyme-linked immunoassay revealed 24 monoclonal antibodies which reacted with human AGPR. By Western blot analysis, all antibodies recognized the 46 kDa human AGPR under the non-reduced conditions and four MoAbs recognized reduced protein. Two MoAbs reacted with AGPR derived from rat, rabbit and mouse liver under both non-reduced and reduced conditions, suggesting that we could obtain antibodies which reacted with AGPR epitopes shared by different species. In immunohistochemical studies, 30201-MoAb reacted with human liver tissue but not with other tissues. This antibody immunoprecipitated two major bands of 46 kDa and 39 kDa from [35S]-methionine metabolically labeled human hepatoma HepG2 cells. The determinant recognized by 30201-MoAb is a common epitope of AGPR which is present in different species and in both the precursor and maturation forms of the receptor.

Amino Acid Sequence↗

Reduced susceptibilities of Shigella sonnei strains isolated from patients with dysentery to fluoroquinolones.

Seven clinical isolates of Shigella sonnei with reduced susceptibilities to fluoroquinolones (sparfloxacin, ciprofloxacin, and ofloxacin) were obtained. The MICs of fluoroquinolones against these S. sonnei strains were 16 to 32 times higher than those obtained against typical strains that are highly susceptible to these agents. The kinetics of [14C]ofloxacin accumulation in these clinical strains were not different from those in the fully susceptible strains. However, DNA synthesis was much less inhibited by ofloxacin in the strains with reduced susceptibility. Analysis of the in vitro activity of the partially purified DNA gyrase from these isolates showed that the decreased quinolone susceptibility of the S. sonnei strains was likely due to mutation of the DNA gyrase subunit A gene.

Anti-Infective Agents↗

[Successful treatment with combination chemotherapy of BHAC-AMP in a case of acute myelofibrosis developed from myelodysplastic syndrome with multiple chromosomal aberrations].

A 62 year old male patient was previously admitted to another hospital in February 1989 because of palpitation. Peripheral blood examination revealed pancytopenia. Although the number of nucleated cells in the bone marrow aspirate was in the normal range. It contained 2.2% of blastic cells and dysplastic cells. He was diagnosed to be myelodysplastic syndrome with refractory anemia. He subsequently received repeated blood transfusions and other symptomatic treatments as an outpatient until 1990. When he was admitted to our hospital because of severe pancytopenia. The numbers of WBC, RBC, and platelets were 2,000/microliters, 134 x 10(4)/microliters, 2.9 x 10(4)/microliters respectively. Bone marrow aspiration resulted in dry tap, and biopsy at the iliac bone showed remarkable fibrosis with marked decrease of normal hematopoietic cells. Chromosome analysis revealed multiple aberrations such as 47XY, +8, 13q-, 14p+, 48XY, +8, +9, 13q+. The patient was treated with BHAC-AMP combination chemotherapy. After 3 cycles of the therapy, pancytopenia was improved and chromosomal aberration disappeared. This case was considered to be an acute myelofibrosis developed from myelodysplastic syndrome and worth to reporting with a review of literature, because drastic combination chemotherapy was extremely effective.

Aclarubicin↗

Type 1 pili enhance the invasion of Salmonella braenderup and Salmonella typhimurium to HeLa cells.

The relationship between type 1 pili-associated adhesion and invasion to HeLa cells by Salmonella braenderup and S. typhimurium was studied. When the clinical isolates of these strains were grown in L-broth, they showed both type 1 pili formation and mannose-sensitive adhesion to HeLa cells. On the other hand, the type 1 pili-defective mutants, which were obtained either by repeated subcultures on L-agar plates or by the transposon Tn1-insertion mutagenesis of the S. braenderup and S. typhimurium strains, concomitantly lost mannose-sensitive adhesion to HeLa cells. When the HeLa cells were incubated with Salmonella, the type 1 piliated strains invaded the HeLa cells with much higher infection rate than did the type 1 pili-defective strains. The invasion of type 1 piliated strains to HeLa cells was markedly inhibited in the presence of D-mannose. The infectivity of the strain, which lost type 1 pili but still had mannose-resistant adhesion, was slightly higher than that of the strains defective in both mannose-sensitive and mannose-resistant adhesion. These results suggested that type 1 pili have a role in enhancing the invasion of S. braenderup and S. typhimurium to HeLa cells.

Acute Disease↗

[In vitro antimicrobial activity of DR-3355, a new quinolone antibacterial agent, against clinical isolates of enteritis-causing bacteria].

We determined the minimum inhibitory concentration (MIC) of DR-3355, a newly developed quinolone-derivative antibacterial agent, against clinical isolates of various bacterial species from enteritis patients, and compared them with those of ofloxacin (OFLX), ciprofloxacin (CPFX), nalidixic acid (NA), ampicillin (ABPC), kanamycin (KM). MIC90 of DR-3355 against 94 strains of Shigella spp. and 5 strains of Escherichia coli, 36 strains of Salmonella spp., 22 strains of Vibrio cholerae, 5 strains of Vibrio parahaemolyticus, and 19 strains of Campylobacter jejuni were 0.05, 0.10, 0.0025, 0.39, and 0.78 micrograms/ml, respectively. These values were 1/2 of that of OFLX, and two times of that of CPFX. MIC90 of DR-3355, OFLX and CPFX against C. jejuni were 0.78 micrograms/ml. MIC90 of DR-3355 against isolates from enteritis patients except for Vibrio spp., were 1/30 to 1/60 of those of NA, ABPC, and KM.

Bacteria↗

[Lumbago as a presentation of B-cell lymphoma invading psoas muscle].

A 73-year-old male had severe lumbago and right inguinal lymphadenopathy. A CT scanning of his abdomen showed marked enlargement of right psoas and erector spinae muscles. The biopsies of the lymph node and the muscles revealed non-Hodgkin's lymphoma of follicular mixed type with muscle invasion. THP-COPE therapy was begun. The swelling of the muscles diminished and the lumbago resolved rapidly. It was reported that clinically prominent infiltration of of lymphoma in skeletal muscle was rarely and psoas muscle was for the most part. We have to consider that psoas muscle invasion of lymphoma cause hard to cure lumbago.

Aged↗

[Effect of DQ-2556, a new cephalosporin derivative, on fecal microflora].

A new cephalosporin derivative antibacterial agent, DQ-2556, was administered intravenously to 4 healthy adult male volunteers at 2 grams per dosage 2 times a day for 5 days, and degrees of effects of drug concentrations on the fecal microflora were investigated. 1. The total viable count remained unchanged during the study period due to the minimal change in the number of members of the family Bacteroidaceae, which were the most dominant organisms. In one of the volunteers, however, the total count was remarkably reduced immediately after the end of administration of the drug. 2. Among the obligate anaerobes, most of the organisms decreased except members of the family Bacteroidaceae. A marked increase of lecithinase-positive clostridia was noted in 2 volunteers. 3. The number of aerobes, including facultative anaerobes, members of the family Enterobacteriaceae were suppressed but bacilli and yeasts showed slight increases. In many cases, increases in enterococci were also observed. 4. DQ-2556 was not detected in the feces from any of the volunteers during the study period. 5. Neither Clostridium difficile nor its toxin D-1 was detected in any of the volunteers. 6. Diarrhoea or other side-effects were not noted in any of the volunteers.

Adult↗

The effect of levofloxacin, an optically-active isomer of ofloxacin, on fecal microflora in human volunteers.

Following oral administration of levofloxacin (LVFX, (S)-(-)-Ofloxacin; formerly designated as DR-3355) at 200 mg per dose 3 times a day for 7 days to 6 healthy male volunteers, degrees of disturbance of the fecal microflora and fecal drug concentrations were examined. The total viable count remained unchanged during the study period due to the minimal change in the number of members of the family Bacteroidaceae, the most predominant organisms. Most of the aerobes including facultative anaerobes were suppressed by LVFX with only a slight increase in yeasts. In particular, the members of the family Enterobacteriaceae were reduced to below the detection limit on and after day 3 through the time of discontinuation of the drug in all subjects but one. Among the obligate anaerobes, peptostreptococci and bifidobacteria decreased or disappeared in some volunteers, but no significant changes were observed in other anaerobes. Neither Clostridium difficile nor its toxin D-1 was detected in any of the volunteers. No side effects attributable to the drug were observed. During administration, LVFX was detected in the feces at high concentrations which correlated well with the decrease of susceptible members of flora as well as to their detection rate.

Adult↗

The 106-kilobase plasmid of Salmonella braenderup and the 100-kilobase plasmid of Salmonella typhimurium are not necessary for the pathogenicity in experimental models.

Among 1.041 clinical isolates (77 serovars) of Salmonella which had been derived from cases with acute enterocolitis, 601 (58%) contained one or more plasmids. Large serovar-specific plasmids were seen in 95 of 307 isolates (31%) of Salmonella typhimurium, in 34 of 34 isolates (100%) of Salmonella enteritidis and in 36 of 38 isolates (94.7%) of Salmonella braenderup: the sizes of which were 100, 60 and 106 kilobases (kb), respectively. In order to determine the role of these plasmids in pathogenicity for enterocolitis, the plasmids were eliminated from some strains of S. braenderup and S. typhimurium and the pathogenicity of the plasmid-less strains was compared with that of the parent strains by invasiveness to HeLa cells, fluid accumulation in the rabbit ligated ileal loop, lesion of mucosal tissue and the Sereny test. The virulence of all the plasmid-less strains was as strong as that of the plasmid-bearing strains in these pathogenicity assay systems. We therefore concluded that the 106-kb plasmid of S. braenderup and the 100-kb plasmid of S. typhimurium are not necessary for their pathogenicity in the experimental models: invasiveness to HeLa cells, fluid accumulation in the rabbit ligated ileal loop, and Sereny test.

Animals↗

[In vitro antimicrobial activity of rokitamycin, a macrolide antibacterial agent, against clinically isolated strains of Campylobacter and other enteritis-causing bacteria].

We determined the minimum inhibitory concentrations (MICs) of rokitamycin (TMS-19-Q, RKM), a macrolide antimicrobial agent, against strains of various bacterial species isolated from enteritis patients, and compared them with those of josamycin (JM), erythromycin (EM) and ofloxacin (OFLX). MIC90 of RKM against 147 strains of Campylobacter jejuni, and each 25 strains of Shigella spp., Salmonella spp. and diarrheagenic Escherichia coli were 1.56, 200, 800 and 200 micrograms/ml, respectively. There was only one RKM resistant (MIC greater than 100 micrograms/ml) C. jejuni strain, while most of the strains of the other species were resistant to RKM. MIC values of the other drugs were all similar to those of RKM. MIC90 of OFLX against 147 strains of C. jejuni was 0.78 micrograms/ml, lower than other drugs.

Campylobacter↗

A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice.

Acute and chronic experimental ulcerative colitis models were produced in mice by providing them with drinking water containing synthetic dextran sulfate sodium. Mice that developed acute colitis showed signs of diarrhea, gross rectal bleeding, and weight loss within 6-10 days after ingesting 3%-10% dextran sulfate sodium. On postmortem examination, multiple erosions and inflammatory changes including crypt abscesses were found on the left side of the large intestine. Mice that developed chronic colitis showed signs of erosions, prominent regenerations of the colonic mucosa including dysplasia, shortening of the large intestine, and frequent formation of lymphoid follicles after 5 administration cycles, where each cycle was composed of 7 days' consumption of drinking water containing 5% dextran sulfate sodium followed by 10 days' consumption of distilled water. The population of intestinal microflora, Bacteroides distasonis and Clostridium spp., increased significantly in mice with acute and chronic ulcerative colitis. Further, morphological studies suggest that the administered dextran sulfate sodium was partially phagocytized by macrophages in the colonic mucosa.

Acute Disease↗

Cytotoxic component(s) of Klebsiella oxytoca on HEp-2 cells.

A cytotoxic component(s) was detected in culture filtrates of Klebsiella oxytoca isolated from patients with antibiotic-associated hemorrhagic colitis. Eleven of 12 isolates exhibited cytotoxicity on HEp-2 cells. The cytotoxic activity of K. oxytoca strain MH43-1 was stable for the treatment of 60 C for 30 min, but inactivated by the treatment of 100 C for 15 min. This cytotoxicity was not destroyed by the treatment with trypsin or pronase, and the component was filtrable through a membrane filter which cut off molecular weight 5,000.

Cells, Cultured↗

[Estimate of aztreonam (AZT) hydrolyzing enzymes from clinically isolated AZT-resistant gram-negative bacilli].

The MICs of Aztreonam (AZT) against 590 clinical isolates of Gram-negative bacilli were determined. About 13.4% (79 strains) of the isolates were AZT-resistant (MIC; 12.5 micrograms/ml less than or equal to). The resistance pattern against various beta-lactams and the effects on MICs of combination of Clavulanic acid (CVA) and AZT against AZT resistant strains suggested that AZT was inactivated by either type of IV (K1), Va (OXA1), or PSE2 beta-lactamases.

Aztreonam↗

In-vitro activity of DR-3355, an optically active isomer of ofloxacin, against bacterial pathogens associated with travellers' diarrhoea.

The in-vitro activity of DR-3355, the S-(-)-isomer of ofloxacin, was determined against bacterial pathogens associated with travellers' diarrhoea. DR-3355 was highly active against isolates of enteropathogenic Escherichia coli (MIC90 0.05 mg/l), Salmonella spp. (MIC90 0.10 mg/l), Shigella spp. (MIC90 0.10 mg/l), Campylobacter jejuni (MIC90 0.39 mg/l) and Vibrio parahaemolyticus (MIC90 0.39 mg/l). The activity of DR-3355 against these bacteria was generally two- to eight-fold greater than that of ofloxacin and equal to, or only two-fold less than, that of ciprofloxacin with the exception of isolates of C. jejuni, which were two-fold less susceptible to ciprofloxacin than to DR-3355.

Anti-Bacterial Agents↗