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Biomedical subjects

T Kamimura

Publications and source records attributed to T Kamimura.

At least 109 records · Page 6Linked to original sources
PubMed1993

Excellent activity of FK037, a novel parenteral broad-spectrum cephalosporin, against methicillin-resistant staphylococci.

FK037 exhibits potent in vitro and in vivo antibacterial activity against methicillin-resistant staphylococci. In in vitro studies, FK037 was the most active of the cephalosporins and imipenem tested against the highly methicillin-resistant staphylococci (MIC > 100 micrograms/ml). Only 2 of 57 strains of highly methicillin-resistant Staphylococcus aureus (H-MRSA) had a FK037 MIC value of 50 micrograms/ml. On the other hand, 55, 40 and 19 strains had MICs of 50 or > or = 100 micrograms/ml to cefpirome, flomoxef and imipenem, respectively. Against 13 strains of highly methicillin-resistant coagulase-negative staphylococci (H-MRCNS), FK037 inhibited all the strains at < or = 50 micrograms/ml, but there were many strains highly resistant to the reference drugs with MICs of > or = 100 micrograms/ml. The influence of culture conditions such as low temperature, high inoculum and supplementation with 4% NaCl on the anti-MRSA activity of FK037 was less than those with cefpirome, flomoxef and imipenem. The in vitro frequency of spontaneous mutant cells highly resistant to FK037 in MRSA was lower than that to cefpirome and flomoxef. These findings were supported by lack of colonies inside the inhibition zone demarcated by FK037 in a disk sensitivity test, although many colonies proliferated inside the inhibition zone demarcated by flomoxef and imipenem. The increase in MIC of FK037 against a MRSA strain during subculture in the presence of the drug was smaller than that noted with the reference drugs. FK037 had higher affinity and faster binding for the PBP 2a of MRSA than that of the reference drugs. Moreover, the capacity to induce PBP 2a was lower for FK037 than that of cefpirome but higher than that of flomoxef. In an in vitro pharmacokinetic model simulating human plasma concentrations, FK037 showed potent bactericidal activity against H-MRSA in the plasma concentrations after intravenous infusion dosing with 1.0 g. FK037 was synergistically active against H-MRSA in combination with either imipenem of fosfomycin. The in vitro post-antibiotic effect (PAE) of FK037 against H-MRSA ranged from 1.2 to 1.7 hours at one to four times the MIC. FK037 had potent therapeutic effects against lethal systemic infections and experimental local infections in mice such as pneumonia, endocarditis, subcutaneous abscess, intrauterine infection and granuloma pouch infection due to MRSA or methicillin-resistant Staphylococcus epidermidis (MRSE). FK037 was about 4, 8 and 1.5 times more effective than cefpirome, flomoxef and imipenem, respectively, against lethal systemic infections with H-MRSA.(ABSTRACT TRUNCATED AT 400 WORDS)

Abscess↗
PubMed1992

Sequence of a cDNA clone encoding a rat Reg-2 protein.

We report here the nucleotide sequence of a rat cDNA clone encoding a protein homologous to the Reg (regenerating) protein. The encoded protein, designated Reg-2, shows 60%, 78% and 61% similarities with the reported amino acid sequences of the rat, bovine and human proteins, respectively.

Amino Acid Sequence↗
PubMed1992

Conformational rigidity of specific pyrimidine residues in tRNA arises from posttranscriptional modifications that enhance steric interaction between the base and the 2'-hydroxyl group.

In order to elucidate roles of the 2'-O-methylation of pyrimidine nucleotide residues of tRNAs, conformations of 2'-O-methyluridylyl(3'----5')uridine (UmpU), 2'-O-methyluridine 3'-monophosphate (Ump), and 2'-O-methyluridine (Um) in 2H2O solution were analyzed by one- and two-dimensional proton NMR spectroscopy and compared with those of related nucleotides and nucleoside. As for UpU and UmpU, the 2'-O-methylation was found to stabilize the C3'-endo form of the 3'-nucleotidyl unit (Up-/Ump-moiety). This stabilization of the C3'-endo form is primarily due to an intraresidue effect, since the conformation of the 5'-nucleotidyl unit (-pU moiety) was only slightly affected by the 2'-O-methylation of the 3'-nucleotide unit. In fact even for Up and Ump, the 2'-O-methylation significantly stabilizes the C3'-endo form by 0.8 kcal/.mol-1. By contrast, for nucleosides (U and Um), the C3'-endo form is slightly stabilized by 0.1 kcal/.mol-1. Accordingly, the stabilization of the C3'-endo form by the 2'-O-methylation is primarily due to the steric repulsion among the 2-carbonyl group, the 2'-O-methyl group and the 3'-phosphate group in the C2'-endo form. For some tRNA species, 2-thiolation of pyrimidine residues is found in positions where the 2'-O-methylation is found for other tRNA species.(ABSTRACT TRUNCATED AT 250 WORDS)

Dinucleoside Phosphates↗
PubMed1992

Electron microscopic study of hepatitis B virus-associated antigens on the infected liver cell membrane in relation to analysis of immune target antigens in chronic hepatitis B.

To clarify the characteristics of cell surface Pre-S2 Ag, HBcAg and HBeAg immunohistochemically and to explore their relationship with a cellular immune target antigen, 31 liver biopsy specimens from chronic HBV carriers were examined by immunoperoxidase staining. By immune light microscopy, Pre-S2 Ag was detected on the liver cell membrane in 18 (58%) of the 31 cases, HBcAg in 4 cases (13%) and HBeAg in 4 cases (13%). Pre-S2 Ag frequently showed a honeycomb-like membrane expression pattern which was present regardless of liver inflammation, whereas HBcAg and HBeAg exhibited a scattered membrane expression pattern detected in areas of marked inflammation. Of the 18 cases showing a honeycomb-like Pre-S2 Ag expression, 3 concomitantly showed a scattered membrane expression pattern. Immunoelectron microscopy revealed these two distinct membrane expression patterns. In areas showing a honeycomb-like membrane expression pattern, Pre-S2 Ag was demonstrated in the intercellular space and on the basolateral membranes of hepatocytes, but was not detected on the cell membranes in areas of the intercellular space lacking an immunoreaction. Cytoplasmic expression of Pre-S2 Ag was less extensive in these hepatocytes. These findings suggest that the honeycomb-like membrane expression of Pre-S2 Ag results from attachment of extracellular antigen to the liver cell membrane. In contrast, in areas showing a scattered membrane expression pattern, Pre-S2 Ag, HBcAg and HBeAg were each detected as single-layered linear deposits along the cell membrane, but were absent in the intercellular space. Each antigen was also expressed abundantly in the cytoplasm, and the immunoproducts appeared to fuse with the cell membrane. These findings suggest that the scattered membrane expression of these antigens results from intrahepatic transfer of antigen synthesized in the liver cell to the cell membrane, possibly serving as a target for the host immune-mediated response in connection with inflammation.

Adult↗
PubMed1992

Effect of protein binding in serum on therapeutic efficacy of cephem antibiotics.

The effect of protein binding in serum of eight cephem antibiotics (ceftazidime, ceftizoxime, cefotiam, cefmetazole, cefpiramide, cefazolin, cefuzonam, ceftriaxone) on their therapeutic efficacies was examined in mice with experimentally induced intraperitoneal infections or pneumonia. The relationship among therapeutic activity, in vitro antibacterial activity, total or free (unbound) levels in serum, and homogenized whole lung levels was investigated. In the intraperitoneal infection caused by Staphylococcus aureus or Klebsiella pneumoniae, the 50% effective doses (ED50s) of the cephem antibiotics correlated with the area under the concentration-time curve (AUC) values of free levels in serum and the MICs but not with those of total levels in serum. A linear relationship was seen between 1/ED50 values and AUC of free levels in serum/MIC values. On the other hand, in mice with pneumonia caused by K. pneumoniae, the number of bacteria in the lung closely correlated with the AUC of the antibiotic concentration in lung tissue. There was a direct correlation between the levels in lung tissue and total levels in serum but not free levels in serum. The cephem antibiotics tested in this study were bound only slightly to homogenates of mouse lung. These results indicate that the effect of protein binding in serum on therapeutic efficacy against intraperitoneal infection differs from that against pulmonary infection.

Animals↗
PubMed1992

Structure-binding relationship and binding sites of cephalosporins in human serum albumin.

The binding of some cephalosporins to human serum albumin (HSA) was studied by an ultrafiltration technique. Changes in C-3 side chain resulted in marked changes in the binding to HSA, but changes in C-7 side chain did not. Cephalosporins were classified into three groups by C-3 side chain: (i) Cationic side chain with low affinity for HSA; (ii) anionic side chain with high affinity for HSA; (iii) non ionized side chain, in which binding to HSA was dependent on lipophilicity. These findings suggest that electrostatic and hydrophobic forces play a role in the binding affinity of cephalosporins for HSA. The binding of cephalosporins with high HSA affinity was displaced significantly by warfarin but not by phenylbutazone, L-tryptophan, or diazepam. The interaction of the cephalosporins with high affinity for HSA with chemically modified HSA was investigated to clarify the amino acid residues of HSA involved in the cephalosporin binding sites. The binding of the cephalosporins decreased remarkably with the modification of the tyrosine residues. These results suggest that the binding site of cephalosporins is located in the vicinity of warfarin binding site rather than benzodiazepine binding site and that tyrosine residues are involved in the cephalosporin binding site.

Binding Sites↗
PubMed1991

Hepatic lesions in alcoholic HBV carriers.

Liver biopsies were taken from 54 alcoholic HBV carriers with liver dysfunction to assess whether HBV infection or habitual drinking was the main cause of their illness. In 28 cases, ultrastructural studies were done. Results showed that 50% of the cases predominantly displayed virus-related histological changes, whereas 13% of them mainly had alcohol-related ones. Both pathological changes were evenly distributed in four cases. The remaining 15 cases showed nonspecific or other histological changes. Electron microscopy revealed that HBV core and Dane particles were seen with Mallory bodies in the same hepatocytes. Thus, we postulate that HBV-related changes are more often encountered than alcoholic ones in alcoholic HBV carriers and that HBV replication can occur even in hepatocytes bearing Mallory bodies.

Adult↗
PubMed1991

[Studies on motile-Aeromonas infection: 2). Development of a bacteriophage typing system for motile Aeromonas].

We succeeded in isolating Aeromonas-susceptible phages from river water and mud after a few years (1983-1985) of painstaking effort. For the first time in Japan, we investigated phagetypes of the bacterial strains isolated. The results obtained are summarized as follows: 1) Aeromonas-susceptible phages were isolated from 82 (40.1%) of 195 samples of river water and from 23 (25.6%) of 90 samples of river mud. By the cross-matching test of the phages isolated from the 105 samples, these were classified into 13 type groups (Groups I-XIII). 2) When 594 Aeromonas strains isolated from river water, lake water, river mud and fresh-water fish were examined using the phage group patterns developed by us, 129 (21.7%) strains classified into these phagetypes. Phagetyping was possible for 11 (15.5%) of the 71 strains isolated from river and lake water, for 29 (35.4%) of the 82 strains from river mud and for 89 (20.2%) of the 441 strains from fresh-water fish. By bacterial species, phagetyping was possible for 53 (51.5%) of the 103 strains of A. hydrophila. 21 (7.2%) of the 292 strains of A. sobria, 13 (8.8%) of the 148 strains of A. caviae and 42 (82.4%) of the 51 strains of Aeromonas spp.. Especially the phages classified as Groups I, IV and VI amounted to the majority. Thus we succeeded in isolating Aeromonas-susceptible phages which could be classified into Groups I-XIII. The results suggested the possibility of utilizing this phagetyping for analysis of the ecological distribution of genus Aeromonas.

Aeromonas↗
PubMed1991

Studies on beta-lactam antibiotics. XIX. Structure-activity relationships of cephalosporins having a thiadiazolylthiomethyl group at the C-3 side chain.

The synthesis and antibacterial activity of 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2-(hydroxy or alkoxy)iminoacetamido]cephalosporins with various thiadiazolylthiomethyl moieties at the 3-position are discussed. Of the compounds (1a-1e, 7a-7d), 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2-hydroxyiminoacetamido]-3-[(1,2 ,4- thiadiazol-5-yl)thiomethyl]cephalosporin (1d: FK312) exhibited the highest activity against Gram-positive and Gram-negative bacteria, especially, against methicillin-resistant Staphylococcus aureus. Furthermore, the pharmacokinetic profiles of the compound 1d showed longer serum levels than that of ceftriaxone in rats.

Anti-Bacterial Agents↗
PubMed1991

Point mutation, allelic loss and increased methylation of c-Ha-ras gene in human hepatocellular carcinoma.

Somatic alterations of the c-Ha-ras gene were examined in 21 Japanese patients with hepatocellular carcinoma. Restriction endonuclease analysis by double digestion with MspI and HpaII revealed that DNAs from two of 21 hepatocellular carcinoma tissues were affected by nucleotide substitution at the twelfth amino acid coding sequence of the c-Ha-ras gene. DNAs from cirrhotic noncancerous liver tissue, but not leukocytes, of one of these patients possessed the mutation, whereas DNAs from noncirrhotic liver tissue and leukocytes of the other patient did not. In one of the nine patients harboring heterozygosity for c-Ha-ras-related BamHI-fragments, the loss of one allele was demonstrated as a somatic change not only in DNA from the tumor tissue but also in DNA from the cirrhotic nontumorous tissue. In two of the 19 patients comparatively examined for digestion patterns of c-Ha-ras locus with HpaII and MspI, extensive methylation was observed as a somatic modification in both DNAs from the tumor and the cirrhotic nontumorous tissues. These results thus indicate that the genetic lesions affecting the c-Ha-ras gene do occur in human hepatocellular carcinoma and probably serve as one of the multiple steps in the process of hepatic carcinogenesis.

Adult↗
PubMed1991

[Clinical significance of antibodies against calmodulin in patients with various liver diseases].

The sera from patients with various liver diseases were investigated for the antibody against calmodulin (CaM) extracted from bovine brain by the enzyme linked immunosorbent assay. The specificity and purity of CaM were confirmed by the Western blot technique using anti-CaM antibody (anti-CaM) positive sera. IgA class antibody was frequently detected in patients with hepatocellular carcinoma (HCC), autoimmune hepatitis (AIH) and chronic active hepatitis (CAH). On the other hand, IgG class antibody was very often present in patients liver cirrhosis, AIH and acute viral hepatitis (AVH). Sixty seven percent of patients with AVH in the acute phase were positive for IgM class anti-CaM and 33% of patients with AVH in the convalescent phase positive respectively. In AVH, the titer of anti-CaM reached its peak on 26.3 days after the onset. The titer of anti-CaM in fulminant hepatitis was higher than that in AVH. Seventy percent of type A hepatitis patients were positive for IgM class anti-CaM, 33% of type B and 33% of type non-A non-B. These results suggest that the frequency and titer of anti-CaM may depend upon the type of hepatitis and the degree of liver cell injury.

Autoantibodies↗
PubMed1990

A comparison of the molecular structure of integrated hepatitis B virus genomes in hepatocellular carcinoma cells and hepatocytes derived from the same patient.

To elucidate critical genetic elements in the development of hepatocellular carcinoma associated with hepatitis B virus DNA integration, a single integrant in hepatocellular carcinoma cells and one species of multiple integrants in hepatocytes, both obtained from the same patient, were compared structurally using molecular cloning techniques. Both hepatitis B virus integrants showed similar inverted repeat sequences consisting of two defective virus genomes. The recombination of viral DNAs seemed to be mediated by short regions of base homology near the direct repeat 1 and at other regions of the virus genomes in both integrants. The virus component in the junction with host DNAs was the cohesive end region in each identical end of the viral integrant in hepatocellular carcinoma cells and in one end of the viral integrant in hepatocytes. The structure of the integrant in hepatocellular carcinoma cells was characterized by an inverted, duplicated conformation composed not only of integrated virus genomes but also of flanking cellular sequences. It was shown to be the so-called "alpha dimer" of satellite DNA. In contrast, the flanking, nonreiterated cellular DNA in the hepatocyte-derived clone did not show discernible rearrangement. These findings suggest that a common mechanism underlies the integration of hepatitis B virus DNA so that a similar organization of inverted repeat genomes is found in hepatocellular carcinoma cells and in hepatocytes. The unstable nature of cellular DNA where DNA integration occurs may be important in generating chromosome alterations found in hepatocellular carcinoma.

Adult↗
PubMed1990

A multi-center double-blind controlled trial of ursodeoxycholic acid for primary biliary cirrhosis.

A multi-center double-blind controlled trial of ursodeoxycholic acid (UDCA) for treatment of primary biliary cirrhosis (PBC) was carried out. Twenty two and 23 patients were treated with 600 mg/day UDCA and placebo, respectively, for 24 weeks. In UDCA-treated patients, fall of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma-glutamyltranspeptidase activities started within 4 weeks after start of the trial and continued throughout the trial period. The serum IgM level fell in 7 UDCA-treated patients examined but not in 10 placebo-treated patients examined. Serum bilirubin concentration showed no significant change at the end of the study in either of UDCA- and placebo-treated group of patients. There was no significant difference between these two groups with respect to the frequency of improvement of pruritus. In UDCA-treated patients, serum bile acid composition changed markedly, though its concentration showed no significant change. The percentage of total bile acid which ursodeoxycholic acid took up increased, whereas those which cholic acid, chenodeoxycholic acid and deoxycholic acid took up were decreased.

Alanine Transaminase↗
PubMed1990

Proteinaceous inhibitors of phospholipase A2 purified from inflammatory sites in rats.

We have purified two phospholipase A2 inhibitory proteins (37 and 33 kDa) from peritoneal fluid of dexamethasone-treated rats. The extracellular phospholipase A2 found in inflammatory sites differed from the exocrine phospholipase A2 in susceptibility to these endogenous inhibitors; both proteins inhibited the activity of the extracellular phospholipase A2 purified from sites of inflammation but did not affect appreciably the activity of either porcine pancreatic or Naja naja venom phospholipase A2. The amino acid sequence of the NH2-terminal portion of the purified proteins did not resemble that of lipocortins so far reported, but it was almost identical to that of parts of human or mouse complement component C3. These findings may indicate that degraded products of C3 are involved in the regulation of activity of a class of mammalian phospholipase A2.

Amino Acid Sequence↗
PubMed1990

[Studies on FK482 (Cefdinir). IV. Synthesis and structure-activity relationships of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]- 3-substituted cephalosporin derivatives].

The synthesis of 7 beta-[(Z)-2-(aminothiazol-4-yl)-2-hydroxyiminoacetamido] cephalosporins (Ia-i) modified at the C-3 position of a cephem nucleus and the effect of the C-3 substituents on the antibacterial activity and oral absorbability are discussed. The cephems (Ie, h and i) having a C-3 substituent such as 1-propenyl, ethylthio and vinylthio group as well as FK482 (cefdinir) exhibited excellent antibacterial activities against both gram-positive and gram-negative bacteria. However, those compounds showed poor absorption rate after oral administration in rats. It is concluded that the vinyl moiety at the 3-position is necessary to display fairly oral absorptivity in a series of 7 beta-[(Z)-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]c eph ems.

Animals↗