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T Sugano

Publications and source records attributed to T Sugano.

At least 91 records · Page 5Linked to original sources
PubMed1994

The capacity of the malate-aspartate shuttle differs between periportal and perivenous hepatocytes from rats.

The capacity of the malate-aspartate shuttle was evaluated in periportal (PP-H) and perivenous subfraction of rat hepatocytes (PV-H). The rate of glutamine production from alanine was 34-fold higher in PV-H than in PP-H. Statistically significant differences between PP-H and PV-H were found for the activities of lactate dehydrogenase and pyruvate kinase but not for the activities of NAD(+)-malate dehydrogenase, aspartate aminotransferase, and mitochondrial alanine aminotransferase. The rate of glucose production from sorbitol and the rate of ethanol utilization were higher in PP-H than in PV-H. In the presence of phenazine methosulfate (PMS), the increments in these rates were significantly greater in PV-H than in PP-H. The capacity of malate-aspartate shuttle in the presence of alanine was significantly higher in PP-H than in PV-H but in the presence of asparagine was similar in PP-H and PV-H. The results suggest that the capacity of malate-aspartate shuttle distributes heterogeneously along liver lobules with the dominance in periportal zone and that the difference of the capacity may result from the difference in the transport of aspartate across the mitochondrial membrane.

Alanine↗
PubMed1994

Different antibody response to a neutralizing epitope of human cytomegalovirus glycoprotein B among seropositive individuals.

The amino-terminal portion of human cytomegalovirus glycoprotein B (HCMV-gB) was expressed as a fusion protein to analyze the neutralizing epitope recognized by human monoclonal antibody C23 and the humoral immune response to this epitope. The linear neutralizing epitope was further localized to the peptide within 17 amino acids (position 68-84) which were conserved between two HCMV laboratory strains. Ten out of 17 HCMV-seropositive human sera contained the antibody against this epitope. Although seven sera were negative for reacting with the fusion protein, the viruses isolated from the same patients retained the epitope. The immunogenicity of the epitope and the possible application of C23 human monoclonal antibody for passive immunization against HCMV infections are discussed.

Amino Acid Sequence↗
PubMed1994

Pharmacokinetics of a new human monoclonal antibody against cytomegalovirus. Third communication: correspondence of the idiotype activity and virus neutralization activity of the new monoclonal antibody, regavirumab in rat serum and its pharmacokinetics in rats and monkeys.

TI-23 consists of lyophilized regavirumab (monoclonal antibody C23, MCA C23), a new human monoclonal antibody against cytomegalovirus (CMV), human serum albumin (HSA) and amino acetic acid. The pharmacokinetics of MCA C23 was studied in rats and monkeys, and virus neutralization activity was investigated after intravenous administration of TI-23 in rats. MCA C23 idiotype activity (antigenicity against idiotype antibody) was not affected by heat treatment. The rat serum obtained after injection of TI-23 showed a potent inhibition activity of plaque formation. A good correlation (r = 0.873) was observed between idiotype activity and the inhibition activity of plaque formation in the diluted serum samples. After single or repeated injection of TI-23 to cynomolgus monkeys, the MCA C23 concentration in plasma was determined by an immunological method. 1 h after single injection, 60.8 +/- 5.1 micrograms/ml of MCA C23 was detected in plasma, then the plasma level decreased with an elimination half-life of 20.5 +/- 6.2 days and the AUC value was 18.3 +/- 3.4 mg.h/ml. In the repeated administration experiment (2 mg/kg/week, 5 times), the MCA C23 plasma concentration reached a steady state (74.4 +/- 11.8 micrograms/ml) at 24 h after the fourth injection. The elimination half-life after the final injection was similar to that after the single injection.

Animals↗
PubMed1994

[Evaluation of bactericidal activity of arbekacin in mixed culture with MRSA and Pseudomonas aeruginosa using an in vitro pharmacokinetic simulation system].

The bactericidal activities of arbekacin (ABK), vancomycin (VCM), gentamicin (GM) and netilmicin (NTL) in mixed culture with Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa were examined using an in vitro computer programmed pharmacokinetic simulation system and also the protective effect of these agents on systemic infection in neutropenic mice was examined. In a mixed culture of S. aureus No. 235 (MRSA) and P. aeruginosa E7, ABK showed a strong bactericidal activity and an inhibition of regrowth against both bacteria, and GM and NTL showed similar effects. On the other hand, VCM showed a bactericidal activity against S. aureus No. 235, but not against P. aeruginosa. In the protective study, ABK was evidently more effective than GM, NTL or VCM against a systemic mixed infection of mice with S. aureus No. 235 and P. aeruginosa E7. In brief, the ED50 values of ABK, VCM, GM and NTL were 19.5, > 100, 40.5 and 45.2 mg/kg, respectively.

Aminoglycosides↗
PubMed1994

U.v.-induced nuclear accumulation of p53 is evoked through DNA damage of actively transcribed genes independent of the cell cycle.

Induction of p53 in u.v.-irradiated primary human fibroblasts was monitored by immunostaining and Western blotting. Minimum u.v. doses required for induction of nuclear accumulation of p53 (minimum response dose: MRD) were estimated in various cells with different DNA repair capacities. The MRD in repair deficient xeroderma pigmentosum (XP) group A cells is eightfold lower than in normal cells, indicating that nuclear accumulation of p53 is related to DNA repair capacity. Cells from patients with another u.v.-sensitive disorder, Cockayne syndrome (CS), which have normal repair capacity for the overall genome but have a specific defect in preferential repair of lesions in active genes, have the same low MRD as of XP-A cells. Furthermore, the MRD in XP-C cells, which have normal preferential repair but have defects in overall genome repair, is as high as that of normal cells. DNA damage induced by X-ray is repaired at similar rates in normal, XP and CS cells. In contrast to u.v.-irradiation, the minimum dose of X-rays that induces nuclear accumulation of p53 is the same in these cells. Inhibition of transcription with alpha-amanitin evokes nuclear accumulation of p53 both in normal cells and in XP cells. These results strongly suggest that u.v.-induced nuclear accumulation of p53 is evoked through DNA damage of actively transcribed genes. Nuclear accumulation of p53 is observed in any phase of the cell cycle at both low and high u.v. doses.

Amanitins↗
PubMed1993

A microneutralization enzyme immunoassay for antibody to human cytomegalovirus.

We have developed a relatively rapid, sensitive and quantitative microneutralization assay for antibody to human cytomegalovirus (HCMV). Cell monolayers in 96-well microtiter plates inoculated with pre-incubated virus-antibody mixtures were fixed after 3 days. Infectious foci were stained with peroxidase-labeled human monoclonal antibody to a 64 kDa immediate early antigen of HCMV, and the plates were read at OD450. The 50% neutralization titer of the antibody was calculated. A study with 20 human sera and a human monoclonal antibody which neutralizes virus showed that this microneutralization enzyme immunoassay is more sensitive than, and as quantitative as, the conventional plaque reduction assay for antibody to HCMV. The neutralizing antibody titers of each sample measured by these two methods showed good correlation (n = 19, r = 0.884). Thus, this new assay is a useful and valid alternative to the conventional method for mass screening of sera and hybridoma fluids, and considerably more rapid.

Antibodies, Monoclonal↗
PubMed1993

The bone mineral density change with aging of Japanese women measured by single energy X-ray absorptiometry and dual energy X-ray absorptiometry.

The calcaneus bone mineral density of 473 Japanese women was measured by single energy X-ray absorptiometry (SXA) and the vertebrae bone mineral density of 198 Japanese women was measured by dual energy X-ray absorptiometry (DEXA). The calcaneus bone mineral density of Japanese women starts decreasing from age 30, and the rate of decrease accelerates from the age of 50. The vertebrae bone mineral density starts decreasing from the age of 35, and a conspicuous decrease can be seen from the age of 50 as well. Because bone deterioration of Japanese women is thought to start earlier than Caucasian, the necessity of osteoporosis screening before menopause was suggested. A high positive correlation (r = 0.804) between calcaneus bone mineral density and vertebrae bone mineral density was found, and a high degree of precision of SXA was shown.

Absorptiometry, Photon↗
PubMed1993

Induction of the acrosome reaction in human spermatozoa by human zona pellucida and effect of cervical mucus on zona-induced acrosome reaction.

OBJECTIVES: To investigate the induction of the acrosome reaction in human spermatozoa by the zona pellucida (ZP), cumulus oophorus, and cervical mucus (CM), and to examine the effect of cumulus oophorus and CM on the zona-induced acrosome reaction. DESIGN, PATIENTS, MAIN OUTCOME MEASURES: The acrosome status of spermatozoa from healthy donors that were cultured with salt-stored human ZP, cumulus oophorus, and/or cervical mucus was assessed using fluoresceinated pisum sativum agglutinin. RESULTS: The acrosome reaction rate after sperm attachment to the zona for 6 hours was 35.7% +/- 17.7%, which was higher than controls (2.8% +/- 1.9%). The acrosome reaction was not observed after passage through cumulus oophorus or CM; however, the acrosome reaction rate of spermatozoa passed through CM after the attachment to zona was 51.6% +/- 6.8%, a higher value in comparison with spermatozoa that had not passed through CM (25.6% +/- 9.4%). CONCLUSION: These data indicate that human ZP are capable of inducing the acrosome reaction in human spermatozoa; however, cumulus oophorus and CM are unable to do so. The data further provide evidence that CM promotes the zona-induced acrosome reaction in human spermatozoa.

Acrosome↗
PubMed1993

Inhibition of varicella-zoster virus (VZV) glycoprotein expression by a human monoclonal antibody against VZV glycoprotein III.

Effects of human monoclonal antibodies (MAbs) against varicella-zoster virus (VZV) glycoproteins (gp) on VZV glycoprotein expression were analyzed by flow cytometry. Human embryonic fibroblast (HEF) cells were inoculated with cell-free VZV and cultured in the presence of human MAbs. While human MAbs directed against gpI (V2) and -II (V1) did not affect VZV expression, a human MAb against gpIII (V3) inhibited expression of VZV gpI, -II, -III, and -IV. V3 also inhibited spread of VZV from infected to uninfected cells. Interferon-alpha, -beta, and -gamma and tumor necrosis factor-alpha were able to synergize with V3 and inhibit VZV gp expression. These results suggest that human MAb V3 may be useful for passive prophylaxis against VZV infection and for treatment of severe VZV infection.

Antibodies, Monoclonal↗
PubMed1993

Adaptive changes in zonation for gluconeogenic capacity in liver lobules of cold-exposed rats.

The rate of gluconeogenesis from lactate increased in perfused livers after exposure of rats to cold for 5 days, and it returned to the control rate after 20 days [M. Shiota, T. Tanaka, and T. Sugano. Am. J. Physiol. 249 (Endocrinol. Metab. 12): E281-E286, 1985.]. The relationship between the increased gluconeogenic activity and its zonal distribution in liver lobules was studied in cold-exposed rats that had been starved for 24 h by examination of preparations enriched for periportal hepatocytes (PP-H) and for perivenous hepatocytes (PV-H), which had been isolated by the digitonin-collagenase perfusion technique. In the control group, the rate of gluconeogenesis from lactate or alanine was three times higher in PP-H than in PV-H. The rate of gluconeogenesis from these substrates in PP-H was not changed by exposure of rats to cold. The rates of PV-H increased to the level in PP-H after 5 days of exposure of rats to cold and then returned to the control rates after 20 days. The rate of gluconeogenesis from fructose was not altered in either preparation of cells by cold treatment of rats. The change in gluconeogenic capacity in PV-H caused by exposure of rats to cold was unrelated to changes in the activity of the malate-aspartate shuttle and of pyruvate kinase. The increased capacity in mitochondrial respiration was observed in both preparations of cells by cold treatment of rats for 5 days. The activity of phosphoenolpyruvate carboxykinase was higher in PP-H than in PV-H in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1993

Responses to catecholamines in perfused livers of hypothalamic-lesioned rats.

The responses of hepatic glycogenolysis to catecholamines in ventromedial hypothalamus (VMH)-lesioned male rats were examined in perfused livers. Seven days after bilateral electrical lesioning of the VMH, the livers were perfused. Isoproterenol, a beta-agonist, stimulated greater glucose production in VMH-lesioned rats than in controls (32.8 vs. 5.6 mumol glucose.h-1.g liver-1), while responses to phenylephrine, an alpha-agonist, decreased significantly compared with controls (44.4 vs. 69.8 mumol glucose.h-1.g liver-1). There were no significant differences in responses of livers to glucagon and vasopressin between control and VMH-lesioned rats. Adrenodemedullation showed the same effect on beta-responses as lesions in the VMH, but no effect on alpha-responses. Plasma epinephrine levels were not detectable with the high-performance liquid chromatography analysis in VMH-lesioned rats. The periodicity of plasma corticosterone levels was observed in both VMH-lesioned and control rats, although daytime increases in plasma corticosterone were blocked by VMH lesions. These results suggest that the lesions in the VMH cause changes in the levels of adrenergic receptor and that the increase in beta-responses is caused mostly by the reduction of plasma epinephrine.

Adrenalectomy↗
PubMed1993

Tissue-type plasminogen activator (t-PA) lysis of aortic and mitral valve thrombosis.

Valve thrombosis is one of the most serious complications after prosthetic valve replacement. We report the use of tissue-type plasminogen activator (t-PA) in the treatment of a patient with thrombosed aortic and mitral valves. Thrombolysis resulted in immediate hemodynamic improvement and resolution of congestive heart failure, thereby avoiding surgical intervention. Based on our experience, thrombolysis with t-PA is an effective alternative in the treatment of thrombosed prosthetic valves.

Adult↗