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T Kamimura

Publications and source records attributed to T Kamimura.

At least 127 records · Page 7Linked to original sources
PubMed1990

[Studies on FK482. II. Synthesis and structure-activity relationships of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-substituted acetamido]-3-vinyl-3-cephem-4-carboxylic acid derivatives].

Various 7 beta-[2-(2-aminothiazol-4-yl)-2-substituted acetamido]-3-vinyl-3-cephem-4-carboxylic acid derivatives (Ia--e, IIa--g) were synthesized in order to find a new orally active cephalosporin improving the antibacterial activity of cefixime (CFIX) against Staphylococcus aureus. These derivatives include three types of alpha-substituted 2-(2-aminothiazol-4-yl)acetyl side chain; i) mono or non substituted acetyl moiety, ii) carboxyalkoxyimino acetyl moiety, iii) phosphonomethoxyimino and hydroxyimino acetyl moiety. Their structure-activity relationships and urinary recoveries in rats were studied. As a result, the compound with a hydroxyimino acetyl side chain (IIg, FK482) showed good oral absorption and excellent antibacterial activity against both gram-positive and gram-negative bacteria and was selected as a candidate for clinical trial.

Animals↗
PubMed1990

[Studies on FK482 (Cefdinir). III. Synthesis and structure-activity relationships of 7 beta-[(Z)-2-aryl-2-hydroxyiminoacetamido]-3-vinyl-3- cephem-4-carboxylic acid derivatives].

The synthesis, antibacterial activity and oral absorption of the 7 beta-[(Z)-2-aryl-2-hydroxyiminoacetamido]-3-vinylcephalosporins (Ia--e) are described. All of these compounds exhibited excellent activity against Staphylococcus aureus. Against Gram-negative bacteria FK482 exhibited more excellent activity than the other compounds (Ia--e). These compounds except Ie showed good oral absorption. The relationship between the oral absorption rates and the lipophilicity of these cephalosporins is discussed.

Animals↗
PubMed1990

[Results of trapezoid rotation test in guinea pigs with unilateral endolymphatic hydrops].

Obliteration of the right endolymphatic sac was performed by Kimura's method in 57 guinea pigs with normal hearing and vestibular function. However, 43 animals exhibited postoperative cerebellopontile disturbance and labyrinthitis detected by gait test, ABR test and histological examination. The remaining 14 guinea pigs were evaluated periodically by the trapezoid rotation test. Two weeks after the operation, 11 of these 14 guinea pigs exhibited prolonged right beating nystagmus based on the labyrinthine preponderance of impaired side (Lpi). In addition, endolymphatic hydrops was histological detected in the labyrinth on the operation side. A positive relation was observed between the degree of endolymphatic hydrops and the degree of Lpi. Lpi at 4 weeks after the operation was markedly lower than that at 2 weeks (P = 0.05). Therefore, the degree of Lpi was thought to be influenced by the rate of hydrops development. These results corresponded with the clinical findings that the degree of Lpi increases prior to vertiginous episodes in Meniere's patients.

Animals↗
PubMed1990

Alzheimer amyloid beta-protein precursor in sperm development.

We prepared antisera to both the N and C termini of amyloid beta-protein precursor (APP). Both antisera labeled 110 to 140 kd proteins from rat testis by immunoblotting. Northern blot analysis using oligonucleotide probes complementary to respective APPs showed that APPs expressed in rat testis contained Kunitz-type protease inhibitor domains. Immunocytochemically brain APP was localized in neurons and their processes. During sperm formation, APPs labeled by both antisera were localized only in acrosome and the growing tail of spermatids in the seminiferous tubules. This shows that APPs appear only in particular phases of spermatogenesis, that is, in the morphologic change phase from spermatid to mature sperm. Amyloid beta-protein precursors in testis may play a role in cellular differentiation or morphologic change.

Amyloid beta-Peptides↗
PubMed1989

Propagation of hepatitis A virus in hybrid cell lines derived from marmoset liver and Vero cells.

To establish monkey liver cell lines with a high susceptibility to hepatitis A virus (HAV), marmoset (Saguinus labiatus) liver cells were fused with Vero cells deficient in hypoxanthine-guanine phosphoribosyltransferase and the resulting hybrid cells were selected in HAT medium. Of four hybrid cell lines obtained (S. 1a/Ve-1 to -4), three (S. 1a/Ve-1, -3 and -4) were equally susceptible to HAV infection. When inoculated with a virus isolated from marmoset liver tissue (10% liver tissue extract) or a faecal virus (10% stool extract) from a human hepatitis A patient, all susceptible cell lines showed a significant elevation of viral antigen activity as seen in radioimmunoassay and/or immunofluorescent antibody assays, at 4 to 6 weeks post-infection (p.i.) with the liver-derived inoculum and at 6 to 8 weeks p.i. with the stool-derived inoculum. In S. 1a/Ve-1 cells, a representative of the susceptible hybrid cell lines, full adaptation of HAV (liver tissue virus concentrate) to cell culture was attained after four serial passages. Thereafter, the virus grew to a plateau titre of 10(8.5) TCID50/ml at 7 days p.i. in a growth experiment. The infected cells showed no cytopathic effects but eventually a persistent infection was established when a saturated level of virus growth was reached.

Animals↗
PubMed1989

Ultrastructural localization of Pre-S2 polypeptides in the liver tissues of patients with chronic hepatitis B virus infection.

Pre-S2 polypeptides in the liver tissue were investigated by immunoperoxidase staining in 26 patients with chronic hepatitis B virus (HBV) infection positive for HBeAg. Pre-S2 polypeptides were detected in the liver of 25 patients, in 17 of whom Pre-S2 polypeptides were localized both on the hepatocyte membrane and in the cytoplasm, and in eight of whom only in the cytoplasm. The localization pattern of Pre-S2 polypeptides was not correlated with the histological findings but with the replicative status of HBV. In cases with a high level of DNA-polymerase in the serum or with both nuclear and cytoplasmic expression of HBcAg in the liver, Pre-S2 polypeptides were more frequently expressed both on the hepatocyte membrane and in the cytoplasm (P less than 0.05). Membranous expression of Pre-S2 polypeptides was speculated to be linked to active replication of HBV in the hepatocytes. Under immune electron microscopy, Pre-S2 polypeptides were observed on the plasma membrane, membranes and cisternae of endoplasmic reticulum (ER), or perinuclear space. Moreover, Pre-S2 polypeptides were detected on the tubular structures and the intracisternal particles about 40 nm in diameter considered to represent HBV. These findings suggest that the immunoreactions of Pre-S2 polypeptides in the liver tissue are similar to those of HBsAg, indicating that Pre-S2 polypeptides play an important role in the immunocharacteristics of HBsAg.

Hepatitis B↗
PubMed1989

[Studies on motile-Aeromonas infection: incidence of motile-Aeromonas in river mud, river water and fresh-water fish].

During the period from October 1982 to July 1984, a total of 1,157 specimens that consisted of 132 river and lake water, 514 river and lake muds, and 511 fresh-water fish caught in both Tama River and Sagami River were examined the presence of the organisms. Of them, 132 (100%) river and lake waters, 304 (59.1%) river and lake muds, and 462 (90.4%) intestinal contents of fresh-water fish were found to have harbor a mean concentration of 1.3 x 10(3)/l, 1.6 x 10(6)/g, and 1.1 x 10(6)/g of motile-Aeromonas respectively. However, nonseasonal variation was observed in the incidence of the organisms throughout the period of investigation. When attempts were made to classify the isolates by the method described Popoff et al., 17 (14.2%) of 120 water-isolates were typed as A. hydrophila, 33 (27.5%) as A. sobria and 35 (29.2%) as A. caviae respectively. And the rest of the 35 (29.2%) remained untypable. As for the 176 mud-isolates, 38 (21.6%) were typed as A. hydrophila 23 (13.1%) as A. sobria and 41 (23.3%) as A. caviae respectively. And the rest of 74 (42.0%) remained untypable. Some efforts were made on the 1,056 strains obtained from fresh-water fish, and 182 (17.2%) were typed as A. hydrophila, 332 (31.4%) as A. sobria and 206 (19.5%) as A. caviae respectively. And the rest of the 336 (31.8%) remained untypable.

Aeromonas↗
PubMed1989

Synthesis and biological activity of 7 alpha-hydroxyethyl-1-oxacephem derivatives.

A series of 7 alpha-hydroxyethyl-1-oxacephems (1) was synthesized. The main focus of this study was to investigate biological activity relationships between 1-oxacephems (1) and the corresponding cephems (2). Replacement of the sulfur atom of 2 by the oxygen atom caused an enhancement of antibacterial activity, although the antibacterial activity of 1 was not high enough. Additionally 1 showed beta-lactamase inhibitory activity, especially against cephalosporinase. However, the potency was lower than that of 2.

Anti-Bacterial Agents↗
PubMed1989

Histologic studies on the hepatic lesions induced by graft-versus-host reaction in MHC class II disparate hosts compared with primary biliary cirrhosis.

By light and electron microscopic examinations, histologic changes in the liver of mice with graft-versus-host reaction (GVHR) were analyzed. To induce GVHR, C57BL/6 (B6) spleen cells were injected into (B6Xbm1)F1, (B6Xbm12)F1, and (bm1Xbm12)F1 mice. In (B6Xbm12)F1 recipient mice, bile duct changes resembling chronic non-suppurative destructive cholangitis (CNSDC) and a formation of epithelioid granulomas were observed during the course of GVHR. An epithelioid granuloma in the liver of (B6Xbm1)F1 or (bm1.Xbm12)F1 recipients was not detected. By electron microscopy, the bile duct epithelia were seen to be in close contact with infiltrating cells, and marked alterations of their cytoplasm and microvilli were demonstrated; ie, vacuolation of the cytoplasm, deterioration of microvilli, and bleb formation were frequently observed in the liver of class II-disparate hosts. Concerning the basement membrane, no marked changes characteristic of primary biliary cirrhosis (PBC), such as many-layered basement membranes containing osmium positive substance, were detected. Because the major histocompatibility complex (MHC) class II-disparate system was used in our experimental system in the GVHR, the antigen expressed on the bile duct might be a target and be associated with the formation of the initial hepatic lesions in PBC such as CNSDC and epithelioid granuloma formation. Thus, GVHR across the MHC class II antigen is believed to play an important role in the development of PBC.

Animals↗
PubMed1988

Hepatic lesions induced by graft-versus-host reaction across MHC class II antigens: an implication for animal model of primary biliary cirrhosis.

To induce graft-versus-host reaction (GVHR), C57B1/6 (B6) spleen cells were injected into (B6 x bm1)F1, (B6 x bm12)F1, and (bm1 x bm12)F1 mice. Since the strains bm1 and bm12 are mutant at the H-2Kb and I-Ab regions of major histocompatibility complex (MHC), respectively, we can assess MHC class I- or class II-different GVHR. As reported earlier, immunological perturbations assessed by the number of immunoglobulin-producing cells and immune complex deposition in renal glomeruli were demonstrated in MHC class II-different GVHR. A conspicuous finding in this report is that epithelioid granuloma formation was observed in the portal area and around the central vein of liver of (B6 x bm12)F1 mice injected with B6 spleen cells. The epithelioid granuloma formation was not observed in (B6 x bm1)F1 nor (bm1 x bm12)F1 recipient mice. Degenerative changes resembling chronic nonsuppurative destructive cholangitis in primary biliary cirrhosis were also observed in the bile duct epithelium in (B6 x bm12)F1 and (bm1 x bm12)F1 mice. These lesions were already obvious at the 2 week postinjection of donor cells and were continuously observed up to 10 weeks when immunological perturbations subsided. Thus, class II-disparate GVHR in this experimental system might provide a novel animal model of protracted disease, primary biliary cirrhosis.

Animals↗
PubMed1988

Novel plasmid-mediated beta-lactamase from Escherichia coli that inactivates oxyimino-cephalosporins.

A highly cephem-resistant Escherichia coli strain, FP1546, isolated from the fecal flora of laboratory dogs previously administered beta-lactam antibiotics was found to produce a beta-lactamase, FEC-1, of 48-kilodalton size and pI 8.2. FEC-1 hydrolyzed cefuroxime, cefotaxime, cefmenoxime, and ceftriaxone, as well as the enzymatically less-stable antibiotics cephaloridine, cefotiam, and cefpiramide. Of the oxyimino-cephalosporins, ceftizoxime was fairly stable to FEC-1. FEC-1 differed notably from chromosomal E. coli cephalosporinase, especially in its broad-spectrum substrate profile and its high inhibition by clavulanic acid, sulbactam, and imipenem. A conjugation study revealed that FEC-1 was encoded by a 74-megadalton plasmid, pFCX1. This may be the first instance of a plasmid-mediated oxyimino-cephalosporinase from E. coli.

Animals↗
PubMed1988

In vitro antibacterial activity of FK482, a new orally active cephalosporin.

FK482 is a new orally active cephem antibiotic which offers some advantages over the commercially available oral beta-lactam antibiotics. It displayed a broad spectrum of activity in vitro against stock strains of Gram-positive and Gram-negative aerobes and anaerobes. FK482 was more active in vitro than cefixime (CFIX), cefaclor (CCL) or cephalexin (CEX) against clinical isolates of Gram-positive organisms such as methicillin-sensitive Staphylococcus aureus, coagulase-negative Staphylococci including Staphylococcus epidermidis and strains of the Streptococcus group. Moderate activity was found against methicillin-resistant S. aureus and Enterococcus faecalis. Against clinical isolates of many Gram-negative species, including opportunistic pathogens, FK482 had good in vitro activity similar or slightly inferior to that of CFIX but superior to that of CCL or CEX. However, it was clearly inferior to CFIX in activity against Serratia marcescens, and was inactive against Pseudomonas aeruginosa. Strains of S. aureus resistant to methicillin were moderately susceptible to FK482. All tested strains of Klebsiella pneumoniae resistant to CCL and CEX were susceptible to FK482, as were all the strains of Escherichia coli, Proteus mirabilis, Haemophilus influenzae and Branhamella catarrhalis resistant to amoxicillin (AMPC). FK482, like CFIX, was relatively stable to all type of beta-lactamases except Bacteroides fragilis and its stability was superior to that of CCL or CEX. The antibacterial activity of FK482 against CSH2 strains containing ampicillin-resistance plasmids was not affected by the presence of the ampicillin resistance determinants. FK482 showed higher affinity for the penicillin-binding proteins (PBPs) (3, 2 and 1) of S. aureus than did CFIX, CCL and CEX. FK482 also showed very high affinity for the PBPs (2 and 3) of E. faecalis and PBPs (3, 1a, 4, 2 and 1 bs) of E. coli. The bactericidal activity of FK482 against S. aureus was almost as strong as that of AMPC and superior to that of CCL or CEX. Against Gram-negative bacteria such as E. coli, K. pneumoniae and P. mirabilis, FK482 was similar to CFIX and superior to CCL and CEX in bactericidal activity.

Administration, Oral↗
PubMed1988

In vivo antibacterial activity of FK482, a new orally active cephalosporin.

The therapeutic activities of orally administered FK482 were compared with those of reference antibiotics against systemic and local infections with a variety of bacteria in mice and rabbits. In systemic infections in mice, oral FK482 was almost as effective as oral cefaclor (CCL) and more effective than oral cephalexin (CEX) against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis infections. However, FK482 afforded superior protective activity when given subcutaneously against E. coli infection in mice, and this activity was more potent than that of subcutaneously given CCL. In comparison with CCL, the reason that the in vivo activity of orally given FK482 against mouse systemic infections was weaker than had been anticipated from its potent in vitro activity was due to its poor oral absorption in mice. In local infections in rabbits, a species in which FK482 was better absorbed than in mice, FK482 was more effective than CCL, CEX or amoxicillin (AMPC). Against pneumonia induced by S. aureus or Streptococcus pyogenes, FK482 was as effective as AMPC and more effective than CCL in reducing the number of viable bacteria in the lungs of infected rabbits. In the oral treatment of experimental ascending pyelonephritis in rabbits, FK482 was superior to CCL and AMPC against methicillin-resistant S. aureus infection, as effective as AMPC and more effective than CCL against Enterococcus faecalis infection, and as effective as cefixime (CFIX) and more effective than CCL and AMPC against E. coli infection in reducing the number of viable bacteria in the kidneys and urine.

Administration, Oral↗