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S Shigeta

Publications and source records attributed to S Shigeta.

At least 217 records · Page 12Linked to original sources

Effects of postnatal low-levels of exposure to styrene on behavior and development in rats.

Three groups of rats were exposed by inhalation to either clean air (control group) or styrene monomer at 25 and 50 ppm (styrene-exposed groups) for 7 h/day, 6 day/week, from 1 to 48 days of age. Compared to control group, Styrene-exposed groups showed significant delay in the following developmental indices: body weight gain, appearance of pinna detachment and incisor eruption. With respect to open-field activity, the styrene groups indicated longer latency to enter the field, less number of squares crossed and fewer rearings than those of controls. In the avoidance behavior aspect, the styrene groups attained less achievement level in avoidance rates than that of the control group. Dose-related trends were found between the two exposed groups in body weight increment, exploratory and avoidance behavior. Sex differences were seen on these factors also. These results suggest that at postnatal exposure of low-levels to styrene affects behavior and development in rats.

Animals↗

Mechanism of selective inhibition of varicella zoster virus replication by 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil.

To investigate the mechanism of action of 1-beta-D-arabinofuranosyl-(E)-5-(2-bromovinyl)uracil (BV-araU) on varicella zoster virus (VZV) replication, we examined the metabolism of the drug in VZV-infected cells using 14C-labeled BV-araU. [14C]BV-araU was taken up by the cells infected with thymidine kinase-positive (TK+)VZV, but not so much by TK- VZV-infected or mock infected cells. Most of the radioactivity in TK+ VZV-infected cells that were incubated with [14C]BV-araU was recovered from their acid-soluble fraction, and little from their acid-insoluble fraction. By high performance liquid chromatographic assay of the acid-soluble fraction, it was proved that BV-araU was metabolized to its 5'-monophosphate, diphosphate, and triphosphate only in TK+ VZV-infected cells. The radioactivity was not detected in VZV nucleocapsids or in VZV DNA and cellular DNA isolated from TK+ VZV-infected cells, even if BV-araU was added at a 1000 times higher concentration than the 50% inhibitory dose for VZV replication in vitro. Furthermore, it was enzymatically proved that [14C]BV-araU was selectively and effectively phosphorylated to BV-araU monophosphate by VZV TK and that affinity of BV-araU triphosphate for VZV DNA polymerase was the quite strong. From these results, it can be concluded that marked inhibition of VZV replication by BV-araU is due to selective phosphorylation of BV-araU in the TK+ VZV-infected cells and strong inhibition of VZV DNA synthesis by BV-araU triphosphate, without detectable incorporation into VZV DNA.

Antiviral Agents↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1986). III. Secular changes in susceptibility].

Changes in the susceptibility of various infectious microorganisms to antimicrobial agents from 1982 to 1986 were evaluated. The microorganisms investigated were Escherichia coli, Klebsiella spp., Citrobacter spp., Enterobacter spp., Proteus spp., Serratia marcescens and Pseudomonas aeruginosa isolated from patients with urinary tract infections. We compared susceptibilities of microorganisms obtained from simple urinary tract infections with those from complicated infections with or without indwelling catheter. Among penicillins, mecillinam (MPC) showed the strongest activity against E. coli obtained from the patients: 3.13 to 6.25 micrograms/ml of MPC inhibited the growth of over 90% of the isolates. Among the second and the third generation cephalosporins, cefotiam and cefmenoxime (CMX) showed the strongest activity and the growth of isolates was inhibited at concentrations of 0.39 to 0.78 microgram/ml and below 0.10 to 0.20 microgram/ml, respectively. The activities of penicillins against Klebsiella spp. were weak. CMX showed strong activity against Klebsiella spp; 91.7% of the isolates from patients with simple infections were inhibited at 0.39 microgram/ml of the agent; 90.7% and 91.6% of isolates from patients with complicated infections with or without indwelling catheter were inhibited at 0.78 microgram/ml and 1.56 microgram/ml of the agent, respectively. Gentamicin (GM) also showed strong activity against isolates from patients with simple infections and weaker activity against isolates from patients with complicated infections with the catheter; 0.78 microgram/ml of ofloxacin (OFLX) inhibited the growths of 90% of the isolates from these patients. Penicillins showed weak activity against Citrobacter spp. obtained from the patients. Among the second and the third generation cephalosporins, CMX and latamoxef (LMOX) showed strong activities against the Citrobacter isolates; about 50% of the isolates were inhibited at 0.20 microgram/ml of either agent. 1.56 microgram/ml of minocycline inhibited the growth of 75 to 90% of the isolates and 1.56 microgram/ml of OFLX inhibited the growth of 93 to 100% of the isolates. Against isolates of Proteus spp. penicillins also showed weak activities. Among them, however, piperacillin (PIPC) inhibited the growth of over 90% of the isolates at concentrations ranging from 0.78 to 1.56 micrograms/ml. Among the second and third generation cephalosporins, CMX and LMOX showed strong activities; 0.20 microgram/ml of CMX inhibited the growth of 94.4%, 90.4%, and 83.1% of isolates from the 3 types of the patients, respectively. 0.20 microgram/ml of LMOX inhibited the growth of 94.4%, 91.8%, and 88.3% of the isolates, respectively. Enterobacter spp. showed resistance to the beta-lactam antibiotics.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗

Critical period of brain development in learning caused by lead exposure in rats.

Three groups of rats (group a, b and c) with high and stable avoidance, and low variability, named Tokai High Avoiders (THA) strain. (a) via placenta from the 13th day of gestation, through maternal milk during lactation and per os after weaning (group Pb-gestation), (b) through maternal milk during lactation and per os after weaning (group Pb-birth), (c) per os after wearing (group Pb-weaning). The pre- and postnatal lead exposure induced apparent delays in speed of learning acquisition and broke the uniformity in avoidance rate in both males and females. Postnatal lead exposure caused slight delays in speed of learning acquisition in males alone. In the post wearing period defect in learning due to lead exposure could be observed in both males and females. No apparent difference was present in the development of pups among the lead exposed groups and control. From these results, it could be deduced that the most sensitive period of brain development in learning affected by lead exposure was the pre- and early postnatal period in the rat.

Age Factors↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1986). I. Susceptibility distribution].

Susceptibilities to various antibacterial and antibiotic agents of bacterial strains isolated from urinary tract infections at 8 hospitals in Japan from July to October in 1986 are summarized as follows. 1. Enterococcus faecalis was susceptible to sulfamethoxazole/trimethoprim (ST) and imipenem (IPM) with MIC90s of 0.78 and 1.56 microgram/ml. Minocycline had the strongest activity against Staphylococcus aureus; the MICs for all strains tested were lower than 0.39 microgram/ml. The MIC80s of dicloxacillin, and arbekacin (HBK) were 0.20 and 0.78 microgram/ml, respectively. Among the cephems, the MIC80 of flomoxef was 25 micrograms/ml, whereas those of cefmenoxime (CMX) and cefotiam (CTM) were 50 micrograms/ml. 2. Escherichia coli was most susceptible to ofloxacin (OFLX) among the oral antibacterial and antibiotic agents tested. OFLX showed the minimum inhibitory concentration against 90% (MIC90) of the 274 strains of E. coli tested to be lower than 0.10 microgram/ml. The antibacterial activities of the third generation cephems such as CMX and latamoxef (LMOX) were the strongest among the injectable antibiotics tested. The MIC90s of CMX and LMOX were lower than 0.10 and 0.20 microgram/ml, respectively. CTM and cefmetazole, the second generation cephems, were also highly active against E. coli with MIC90s of 0.39 and 1.56 micrograms/ml, respectively. 3. Among the oral antibacterial and antibiotic agents tested, OFLX was the most active against Klebsiella pneumoniae. Its MIC90 was 0.78 microgram/ml. Among the injectable antibiotics tested, CMX was the strongest with an MIC90 of 0.20 microgram/ml; MIC90 of CTM and LMOX were 0.39 microgram/ml. 4. The tested antibacterial and antibiotic agents were generally less active against Citrobacter freundii than against other bacteria. The MIC80 of OFLX was 0.39 microgram/ml. Gentamicin (GM) and ST were slightly active against C. freundii. Among the cephems, CMX had the MIC80 of 25 micrograms/ml. 5. Enterobacter cloacae was less susceptible to the cephems tested. OFLX, GM, and mecillinam were active against this bacteria with MIC80s of 0.78, 0.78 and 1.56 micrograms/ml, respectively. 6. Among the oral antibacterial and antibiotic agents and penicillins examined, piperacillin (PIPC) was the most active against Proteus mirabilis. Its MIC90 was 0.39 microgram/ml. Those of sulbenicillin, cefaclor, ampicillin, OFLX, and ST were 0.78, 0.78, 1.56, 3.13 and 3.13 micrograms/ml, respectively. CMX was highly active against P. mirabilis with an MIC90 of less than or equal to 0.10 microgram/ml; LMOX followed with an MIC90 of 0.20 microgram/ml among the injectable antibiotics tested. CTM was also active against this bacterium; the MIC90 was 0.39 microgram/ml. 7. The antibacterial and antibiotic agents were generally only slightly active against Proteus vulgaris.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1986). II. Background of patients].

From July to October in 1986, hospital data on 717 isolates of causative microorganism from patients with urinary tract infections and background information on 562 patients were collected. The urinary tract infections were divided into 3 groups; simple infections and complicated infections with or without the use of indwelling catheter. We investigated such factors as the patients' sex, age, and drug treatments, and the isolates obtained from the infections. From 1981 to 1986, about 25% of the patients with simple infections were males and about 60 to 70% among those with complicated infections were males each year. During these 6 years, no noticeable changes occurred in sex and age distributions of patients with any type of the infections, but the species of isolates changed remarkably. In 1982 and 1983, the isolation rates of Enterococcus faecalis (Streptococcus spp. or Streptococcus faecalis) obtained from the patients were about 8% in both of male and female patients. In 1984, the rate in females increased to 17.9%. In 1985, the rates in males and females were 14.9% and 7.6%, respectively. Similar rates were also observed in 1986: 16.1 and 7.4%. The isolation rate of Staphylococcus aureus in 1982 was 0.7%, as was in 1983. In however, increased to 1.7% in 1984 and to 3.2% in 1985. It was 2.5% in 1986. The isolation rate of Gram-positive bacteria was 11.1% in 1982; it increased to 18.9% in 1983 and to over 20% between 1984 to 1986. Among Gram-negative bacteria, the isolation rate of Pseudomonas aeruginosa form patients with complicated urinary tract infections with a catheter was high and over 20% in both 1985 and 1986. When antibacterial agents were administrated for 3 days, changes in number of species of isolates tended to be more pronounced in complicated infections with or without the use of catheter than in simple infections. According to date obtained in 1986, when antibiotic agents were administered for 8 or more days, the changes were definitely more drastic in complicated infections than in simple ones. An upmost care in the selection of antibiotic drugs according to their antibacterial spectra and activities, therefore, appears necessary, and an attention should be paid on future changes in species of bacteria isolated from infections.

Adolescent↗

Neurobehavioral analysis of high-rate Sidman avoidance rat strain.

The neurobehavioral characteristics of the Tokai High-Avoider (THA) rats, which had an innate high-avoidance ability, were clarified by comparing with the Wistar rats from which the THA rat strain had been derived. THA rats performed superior learning and displayed small individual differences of learning performance, not only in the Sidman avoidance task, which had already been used in selective breeding, but also in two different tasks, namely water maze and two-way shuttle avoidance. No apparent difference was present in development, circadian rhythm, and open-field activity between the two strains. On the other hand, sensitivity of the THA rat to electric shock or to heat stress was less than that of the Wistar rat. From these results, it might be considered that the high and uniform avoidance performance exhibited in the THA rat was caused by an innately acquired ability but not by sensitivity to the shock or developmental differences.

Animals↗

Mechanism of inhibitory effect of glycyrrhizin on replication of human immunodeficiency virus (HIV).

Glycyrrhizin (GL) achieved a dose-dependent inhibition of the replication of human immunodeficiency virus type 1 (HIV-1) in MOLT-4 (clone No. 8) cells within the concentration range of 0.075 to 0.6 mM. Within this concentration range, GL also effected a dose-dependent reduction in the protein kinase C (PKC) activity of MOLT-4 (clone No. 8) cells. A well-known PKC inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), also proved inhibitory to HIV-1 replication in MOLT-4 (clone No. 8) cells. PKC inhibition may thus be considered as one of the mechanisms by which GL inhibits HIV-1 replication. In addition, GL may also owe its anti-HIV-1 activity, at least in part, to an interference with virus-cell binding, since the compound at 1.2 mM partially inhibited the adsorption of radiolabeled HIV-1 particles to MT-4 cells. At this concentration GL also suppressed giant cell formation induced by co-culturing MOLT-4 (clone No. 8) cells with MOLT-4/HTLV-IIIB cells, whereas the PKC inhibitor H-7 failed to do so.

Adsorption↗

Rapid down-regulation of protein kinase C in (Chediak-Higashi syndrome) beige mouse by phorbol ester.

Protein kinase C(PKC) activity in macrophages and polymorphonuclear leukocytes was assayed in beige mouse, the model of Chediak-Higashi syndrome, control C57BL/6 and the heterozygous (+/bg) mice. Regarding enzyme activity in the cytosolic and membrane fractions of these cells, there was no difference between beige mouse and the control. After short-term activation by TPA, the translocated membrane-bound PKC activity in beige mouse decreased rapidly compared with that in control mouse. However, the cytosolic PKC activity decreased at just the same pace as the control. The change in [3H] PDBu binding paralleled the changes in PKC activity. An increase in Ca2+/phospholipid-independent protein kinase by TPA was notable in the membrane fraction of beige mouse. The increase in the kinase activity was abolished and the PKC activity recovered to normal level by the addition of calpain inhibitor, leupeptin, to the incubation of cells along with TPA. Therefore, these findings suggest that a rapid decrease in membrane-bound PKC activity in beige mouse by TPA stimulation is associated with calpain.

Animals↗

Modulation of protein kinase C activity during inhibition of tumor cell growth by IFN-beta and -gamma.

We investigated the effects of human interferon(IFN)-beta and -gamma on protein kinase C activity in human HEp-2 and KHm-14 tumor cells during IFN-induced inhibition of cell growth. Cytosolic protein kinase C activity in both cell lines was strikingly decreased following treatment with either IFN-beta or -gamma. In the particulate fraction, IFN-gamma decreased protein kinase C activity within 1 hr but it reappeared after 24 hr, whereas IFN-beta decreased the activity during the inhibition of cell growth. Furthermore, phorbol-12,13-dibutyrate(PDBu)-binding activity was altered in parallel with the changes in protein kinase C activity induced by the IFNs. In summary, we showed that IFN-beta and -gamma cause long-term modulation of protein kinase C activity in these cultured tumor cells.

Cell Division↗

Low-density lipoprotein oxidized by polymorphonuclear leukocytes inhibits natural killer cell activity.

We studied the effect of low-density lipoprotein (LDL) oxidized by opsonized zymosan-stimulated polymorphonuclear leukocytes (PMN) on natural killer (NK) cell activity. Oxidized LDL inhibited NK cell activity in a dose-dependent manner, whereas normal LDL left it unaffected. However, oxidized LDL did not inhibit antibody-dependent cell-mediated cytotoxicity (ADCC). Moreover, a positive correlation was observed between the amount of thiobarbituric acid-reacting substances (TBARS) on the sample of oxidized LDL and the degree of inhibition of NK cell activity. We also showed that oxidized LDL suppressed the binding capacity of purified large granular lymphocytes (LGL) to target cells without changing the lytic activity. These results therefore suggest that activated PMN can modulate NK cell activity by oxidizing LDL.

Antibody-Dependent Cell Cytotoxicity↗

A potent inhibitor of protein kinase C inhibits natural killer activity.

A potent inhibitor of protein kinase C(PKC), 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), dose-dependently inhibited natural killer (NK) activity in large granular lymphocytes (LGL) pretreated at 37 degrees C for 30 min. However, neither N-(2-aminoethyl)-5-isoquinolinesulfonamide dihydrochloride (H-9), which inhibits more effectively cyclic nucleotide-dependent protein kinases than other kinases, nor N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride (HA1004), which was used as a control for H-7, reduced NK activity. The inhibitor effect of H-7 was not due to changes in effector cell viability or target cell binding. We also found that H-7 suppresses PKC activity in both the cytosol and membrane fractions of LGL. From these findings, PKC is considered to play an essential role in the lytic mechanism of NK cell-mediated cytolysis.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Comparative activities of several nucleoside analogs against influenza A, B, and C viruses in vitro.

A set of 20 nucleoside analogs were examined for their inhibitory effects on the cytopathogenicity and growth of influenza virus type A, B, and C strains in Madin-Darby canine kidney (MDCK) cells. Among the compounds evaluated, pyrazofurin, 3-deazaguanine, ribavirin, carbodine, and cyclopentenyl cytosine inhibited viral cytopathogenicity at concentrations that were lower than those found cytotoxic for the MDCK cells. No differences were observed in the 50% effective doses (based on inhibition of viral cytopathogenicity) of these five compounds for a number of influenza virus type A (subtypes H1N1 and H3N2), B, and C strains. Pyrazofurin showed the lowest 50% effective dose (0.15 microgram/ml), which was about 20- to 30-fold lower than those of the other four compounds. The selectivity indices of the five compounds, calculated as the ratio of the 50% cytotoxic dose (determined by trypan blue exclusion) to the 50% effective dose, were greater than 100. When the selectivity indices were calculated as the ratios of the 50% inhibitory doses for cellular RNA synthesis to the 50% effective doses, they were greater than 100 for ribavirin, pyrazofurin, and 3-deazaguanine but less than 2 for carbodine and cyclopentenyl cytosine. All five compounds inhibited the growth of influenza virus types A and B in MDCK cells at a concentration which was well below their cytotoxicity threshold for MDCK cells and, therefore, deserve further exploration for their potential in the treatment of influenza virus type A, B, and C infections.

Cells, Cultured↗

[Changes in blood toluene concentrations in rats under various kinds of exposure conditions and physical loads].

The present experiment was conducted under the assumption that exposure conditions (time of exposure, concentration of exposed substances and working intensity) should be taken into account in estimating the level of invasion of injurious substances into the human body. Experiments were carried out on rats under various exposure conditions of toluene and the toluene concentration in the blood was monitored for the estimation of its intake. The results were as follows; 1. It was confirmed that toluene concentration in blood increased and plateau-time was delayed in proportion to increase in exposure concentration. 2. Light exercise (5.0, 7.0 m/min) increased toluene concentration in blood and it was proportioned to intensity of physical exercise. 3. Light daily exercise (2.7 m/min) for six days increased toluene concentration in blood gradually day after day when compared to exposure without exercise, though the exposure conditions were the same every day. It is thus considered that physical exercise is one of the very important factors in estimation of exposure.

Animals↗

Serum and urine concentrations of oral bromovinyldeoxyuridine in humans as monitored by a bioassay system based on varicella-zoster virus focus inhibition.

A simple and sensitive bioassay method for measuring (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) concentrations in human serum and urine has been established. This method is based on the inhibitory effect of BVDU on varicella-zoster virus (VZV) focus formation in vitro. The minimal concentration of BVDU that could be detected in serum by this method was 0.2 microgram/ml. Following a single oral administration of 250 mg BVDU, serum BVDU concentrations of 1.2-2.2 micrograms/ml were attained 1 hr later; at 5 and 7 hr, serum BVDU levels were below 0.2 microgram/ml. Upon repeated administration of 125 mg BVDU at 8 hr intervals, the serum BVDU concentrations reached 0.7-1.1 microgram/ml at 2 hr after the fourth administration. These concentrations are approximately 300-450-fold higher than the 50% inhibitory dose of BVDU for VZV in vitro. Urinary BVDU concentrations were on average 10 to 20 times higher than the serum BVDU concentrations.

Adult↗

In vitro activity of (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine against newly isolated clinical varicella-zoster virus strains.

The highly potent and selective anti-DNA virus agent (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA] was found to inhibit in vitro the replication of a number of clinical varicella-zoster virus strains within the concentration range of 0.63-5.7 ng/ml. With a mean 50% inhibitory concentration of 1.8 ng/ml and selectivity index of 29000, (S)-HPMPA is one of the most potent and most selective varicella-zoster virus inhibitors discovered to date.

Adenine↗