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Y Mine

Publications and source records attributed to Y Mine.

At least 73 records · Page 4Linked to original sources
PubMed1990

Voltage and current clamp studies of muscarinic and nicotinic excitation of the rat adrenal chromaffin cells.

Characteristics of the muscarinic and nicotinic excitation of chromaffin cells that had been freshly isolated from the rat adrenal medullae were analyzed using voltage and current clamp techniques. A dose-dependent increase in the extracellularly recorded firing of cells was observed when 10(-6) to 10(-4) M acetylcholine (ACh) were locally applied to the cells in the vicinity of the target cell being recorded using a microinflow method. During voltage clamp recording at the resting membrane potential, ACh induced two different sequential inward currents: a transient current with a rapid rising phase (fast response) and an apparent inward current with a slow rising phase (slow response). The membrane conductance increased during the ACh-induced fast response, and it subsequently decreased during the slow response. The amplitude of the fast response decreased when the holding potential was shifted to depolarized levels, whereas the amplitude of the slow response increased with depolarization. Nicotine produced fast depolarization and a transient inward current that was reduced by the membrane depolarization. In contrast, muscarine induced a slow depolarization and an apparent inward current that increased with depolarization. Muscarine also reduced the inward K+ current that had been induced by the application of a high K+ medium to the outside of the cell at the resting membrane potential. It is suggested that muscarinic excitation is triggered by the suppression of K+ channels that are open at potentials near the resting membrane potential. The present results indicate that ACh-induced excitation of adrenal chromaffin cells involves two separate mechanisms mediated by nicotinic and muscarinic receptors.

Acetylcholine↗
PubMed1990

A patch clamp study of muscarinic excitation of the rat adrenal chromaffin cells.

A patch clamp study was performed to determine the ionic mechanisms underlying the muscarinic excitation of rat adrenal chromaffin cells. Burst-like, single-channel currents with brief openings were recorded during cell-attached or cell-free patch recording when the pipette solution contained high K+ media (70-140 mM), and the currents were recorded at potentials near the resting membrane potential. The amplitude and frequency of channel openings were dependent on the membrane potential and the K+ concentration of the external medium. Moreover, the single-channel currents observed with high K+ outside the membrane during inside-out recording were suppressed by the addition of a K+ channel blocker, tetraethylammonium, inside the membrane. These results suggest that the single K+ currents recorded in the present study had properties similar to those of the resting or muscarine-activated K+ currents in atrioventricular cells of the rabbit heart. During cell-attached patch recording with the high K+ medium in the recording pipette, muscarine at concentrations of 10(-5) to 10(-4) M dose dependently decreased the frequency of the channel openings but did not affect the current-voltage relationship or the time constants of open and close time histograms. These results indicate that muscarinic-induced suppression of K+ currents is caused by a decrease in the number of active K+ channels at the resting membrane potential.

Animals↗
PubMed1988

Nature of monocyclic beta-lactam antibiotic Nocardicin A to beta-lactamases.

Nocardicin A is the antibiotic which was first found to possess a monocyclic beta-lactam ring. This antibiotic was inactivated by the cleavage of its beta-lactam ring. The direct spectrophotometric assay was applied to measure the rate of enzymatic hydrolysis of Nocardicin A. Nocardicin A was highly stable to both chromosomal and plasmid-mediated beta-lactamases. Of the nine beta-lactam antibiotics including cefoxitin and cefuroxime, Nocardicin A was the most stable to the beta-lactamases tested excluding those from Klebsiella oxytoca and Proteus vulgaris. The latter broad-spectrum beta-lactamases hydrolyzed Nocardicin A rather intensively. Extreme stability of Nocardicin A to beta-lactamases was suggested to be due to the combination of its low affinity to the enzymes and stabilization of its monocyclic beta-lactam ring. Nocardicin A was shown to have inducing ability toward beta-lactamases.

Anti-Bacterial Agents↗
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

Degradation of host defenses against respiratory tract infection by Klebsiella pneumoniae in aged mice.

The host defense against respiratory tract infection with Klebsiella pneumoniae was much weaker in 60-week-old mice than in 4-week-old mice, but the resistance against systemic infection by intravenous and intraperitoneal challenge with K. pneumoniae in 60-week-old mice did not differ from that in 4-week-old mice. The number of alveolar macrophages at the resting stage in 60-week-old mice was the same as in 4-week-old mice, but the number of macrophages and polymorphonuclear leukocytes in the pulmonary cavity 4 h after challenge with formalinized K. pneumoniae in aerosol doubled in parallel with body weight. Phagocytosis and killing activities and superoxide anion production as measured by the Nitro Blue Tetrazolium reduction test of alveolar macrophages in 60-week-old mice were significantly weaker than in 4-week-old mice. The surfaces of the alveolar macrophages of the 60-week-old mice shrunk and a few adhered weekly to the glass plate, but the alveolar macrophages of the 4-week-old mice stretched to their full length and adhered firmly to the glass plate. These functions of alveolar macrophages clearly differed from those of peritoneal macrophages in 60-week-old mice, but those of the peritoneal phagocytes did not differ between 60-week-old and 4-week-old mice. The results suggest that the susceptibility to respiratory tract infection in 60-week-old mice is affected by a decline in the functions of alveolar macrophages rather than by the number of alveolar macrophages and exudated polymorphonuclear leukocytes in the lungs.

Aging↗
PubMed1988

Inhibitory effect of FK-565 alone and in combination with zidovudine on retroviral infection by Friend leukemia virus in mice.

The effects of route and starting time of administration on FK-565 inhibition of splenomegaly by Friend leukemia virus (FLV) were studied in mice, and the concomitant effect of FK-565 in allowing reduction of zidovudine dosage was estimated. FK-565 inhibited splenomegaly in intravenous and oral doses of 0.01 to 1 mg/kg, but time of initial dosing had little effect on this inhibition. When 0.01 or 1 mg/kg of FK-565 was given intravenously with intraperitoneal doses of 0.63, 2.5, 10 and 40m g/kg of zidovudine, the inhibition rate of splenomegaly at all doses was markedly and dose-dependently higher than when either drug was given alone, and the concomitant use of FK-565 with zidovudine enabled a 16-fold reduction of the dose of zidovudine. The survival rate and survival time after infection with massive amounts of FLV were higher when FK-565 1 mg/kg and zidovudine 20 mg/kg were given in combination than when either drug was given alone. Inhibition of FLV splenomegaly was reflected in the prolonged survival time of the infected mice.

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↗
PubMed1988

Pharmacokinetics of FK482, a new orally active cephalosporin, in animals.

The pharmacokinetic profile of FK482 was studied in mice, rats, rabbits and dogs after oral dosing and compared with that of cefixime, cefaclor and cephalexin. Considerable differences in oral absorption of FK482 were observed among the animal species. Absolute bioavailabilities of FK482 were 12.6% in mice, 15.3% in rats, 32.3% in rabbits and 72.3% in dogs. In mice and rats, the absorption of FK482 was poor, and was the lowest of the reference antibiotics. FK482 was moderately well absorbed, with higher plasma levels than cefixime in rabbits and, like cefixime, gave higher plasma levels and a longer half-life than cefaclor or cephalexin in dogs. The increase in the area under the serum concentration time curve (AUC) of FK482 was strictly proportional to the increase in dose in the range of 2.5 to 40 mg/kg in rats and dogs, and 2.5 to 20 mg/kg in rabbits and the urinary recovery rates were almost constant. All tissue concentrations of FK482 in rats and rabbits were lower than those of the reference antibiotics and reflected its lower plasma concentrations in these animals. The urinary recovery rates of FK482 were 9.8% for mice, 15.5% for rats, 45.8% for rabbits and 47.1% for dogs. The biliary recovery rate of FK482 was low; 1.4% in rats and less than 0.1% in rabbits and dogs. No active metabolites were detected in the plasma, urine or bile samples from rats, rabbits or dogs. FK482 was mainly absorbed in the jejunum, and was inactivated in the large intestine. The serum-protein binding of FK482 was almost the same as that of cefixime: 60-77% for mouse, rabbit and human serum, and 90-93% for rat and dog serum.

Administration, Oral↗
PubMed1988

[Changes in cell cycle and RNA content in cultured cancer cells treated with cis-diamminedichloroplatinum (II)].

Recent reports have shown that CDDP interacts with RNA and protein as well as DNA. We studied the alteration of cell cycle, cellular RNA content and the effect of nucleic acid metabolism on cultured cancer cells after treatment with CDDP by flow cytometry and 3H incorporation assay. The alteration of cell cycle was found to be accumulation of cells in after delay S phase in cytostatic concentrations, CDDP inhibited 3H-TdR uptake markedly at this time and 3H-UR uptake earlier. Increase in RNA content accompanied accumulation of cells in G2M phase. This increase was not a specific phenomenon caused by CDDP, because increase in RNA content was also induced by other inhibitors of DNA synthesis. It is more likely that the direct alteration of cell cycle and cellular RNA content due to action of DNA-combined CDDP rather than that of RNA-combined CDDP.

Cell Cycle↗
PubMed1988

[Metastatic calcification associated with malignancy].

From 1975 to 1986, 15 cases (2%) of metastatic calcification associated with an underlying malignancy were found in a review of 702 autopsied cases with histories of malignancy. These underlying malignancies included 7 cases of lung cancer, 6 cases of malignant lymphoma, one case of breast cancer, and one of urinary bladder cancer. Squamous cell carcinoma was of the histological type most often associated with metastatic calcification in lung cancer, and ATL in malignant lymphoma. Hypercalcemia was found in 10 (83%) out of cases, and almost all were accompanied by renal dysfunction. Calcium deposits were most frequently observed in the kidneys and the lungs. It has been suggested that metastatic calcification in the lungs and kidneys of a patient with a history of malignancy showing hypercalcemia is sometimes accompanied by respiratory and renal dysfunction, causing the patient's condition to deteriorate.

Adult↗
PubMed1988

[Studies of 5-FU concentrations associated with microangiography in colorectal cancer tissue].

In order to elucidate the effect of supplying vessels on 5-FU distribution within a tumor, the correlation between 5-FU tissue concentration and tumor microangiography was examined in 31 patients with colorectal cancer after administration of 5-FU (500 mg/day for 3 days). The 5-FU concentration at the tumor margin was significantly higher than that in the other two tissue areas (p less than 0.05). A low 5-FU concentration was noted in the central region of ulcerative cancer showing vertical invasion with vascular disarray and/or histological necrotic foci. This type of tumor also showed a low RNA index by flow cytometry. The present study indicates that the vascular change and vascular pattern of a tumor may be a major contributing factor to 5-FU transfer from the blood circulation into a tumor.

Adult↗
PubMed1986

Studies on beta-lactam antibiotics. X. Synthesis and structure-activity relationships of 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino)acetamido] cephalosporin derivatives.

The synthesis of 7 beta-([Z) -2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino) acetamido]-cephalosporins (2a-h) modified at the C-3 position of a cephem nucleus and the effect of the C-3 substituents on the antibacterial activity, oral absorptivity and therapeutic activity are discussed. The cephems (2a and 2b) having a C-3 substituent such as hydrogen or vinyl were more potent than other cephalosporins against Gram-negative bacteria. However, the cephalosporin (2f) having methylthio group at the 3-position showed the highest absorption rate in rats. These three cephalosporins (2a, b and f) exhibited equally good protective activities in mice infected. Furthermore, the serum levels of these cephalosporins (2a, b and f) were examined in dogs, and 2b and 2f showed outstanding high and prolonged serum levels.

Administration, Oral↗
PubMed1986

Synergism of cephalosporins at subinhibitory concentrations and polymorphonuclear leukocytes on phagocytic killing of Escherichia coli and its mode of action.

The interactions between subinhibitory concentrations of cephalosporins and polymorphonuclear leukocytes in the killing of a strain of Escherichia coli are described and an attempt is made to define the responsible mechanism. Ceftizoxime was the most potent agent tested. Pretreatment of the E. coli strain with subinhibitory concentrations of ceftizoxime increased the susceptibility to both; phagocytic killing activity of the polymorphonuclear leukocytes and bactericidal activities of the oxygen metabolites and the granule extracts. A most interesting result was the increased susceptibility of the ceftizoxime-treated E. coli to killing by beta-glucuronidase which normally is not bactericidal. It is suggested that the augmented killing could be due to bacteriolysis by beta-glucuronidase.

Animals↗