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Biomedical subjects

Shigeru Saito

Publications and source records attributed to Shigeru Saito.

At least 145 records · Page 8Linked to original sources
PubMed2002

Protective effect of taurine against renal interstitial fibrosis of rats induced by cisplatin.

This study was undertaken to investigate the effect of taurine on the infiltration of macrophages and the progression of renal interstitial fibrosis in the kidneys of rats treated with cisplatin (CDDP). Male rats in different groups were treated as follows: (1) saline as control, (2) CDDP and (3) CDDP plus taurine in drinking water. At weeks 2, 4 and 6 after the fifth CDDP injection, we examined platinum content, the kinetics of macrophages and the areas of fibrosis. In the histologic analyses, fibrotic areas were found to have developed around dilated or atrophic tubules in the corticomedullary junction in the kidneys of CDDP-treated rats, while CDDP-plus-taurine-treated rats showed a reduction of the extent and magnitude of damage. These findings reflect the fact that the percentage of fibrotic areas in the kidney of CDDP-plus-taurine-treated rats was significantly lower than in that of CDDP-injected rats throughout the recovery period ( P<0.05). Compared with normal rats, the macrophages in CDDP-injected rats showed significant increases in number at weeks 2, 4 and 6 ( P<0.05). In contrast, the number of macrophages in CDDP-plus-taurine-treated rats was significantly smaller than that of CDDP-injected rats. These results suggested that taurine suppressed the increase of infiltrating macrophages, and led to the attenuation of renal interstitial fibrosis ( P<0.05).

Animals↗
PubMed2002

Cooperative binding of c-Myb and Pax-5 activates the RAG-2 promoter in immature B cells.

The recombination activating gene-1 (RAG-1) and RAG-2 are expressed specifically in immature lymphoid cells undergoing the recombination of antigen receptor genes. The regulation of murine RAG-2 promoter was studied and it was revealed that the -41/-17 RAG-2 promoter region, which is conserved between humans and mice, was indispensable for the RAG-2 promoter activity in B-cell lines. The region contained 2 cis elements that bound c-Myb and Pax-5. Mutation in the c-Myb-binding site in the promoter reduced the promoter activity in B-cell lines. Cooperative activation of the RAG-2 promoter was seen by a combination of c-Myb and Pax-5 in a human embryonic kidney cell line (293T), via their synergistic DNA-binding. Deletion experiments showed that the C-terminus of c-Myb was responsible for their interaction. Furthermore, the dominant-negative c-Myb mutant suppressed the activation of the RAG-2 promoter in a pre-B-cell line as well as in 293T cells. These results suggest that cooperative binding of c-Myb and Pax-5 to the RAG-2 promoter is one of the mechanisms to direct the restricted expression of the RAG-2 in immature B cells.

Animals↗
PubMed2002

The molarless condition in aged SAMP8 mice attenuates hippocampal Fos induction linked to water maze performance.

The involvement of dysfunctional teeth in senile hippocampal activity was evaluated by examining, in aged SAMP8 mice, the effect of cutting off the upper molars (molarless condition) on hippocampal induction of the protein product, Fos, of the immediate early gene, c-fos, and on spatial performance in a water maze. The molarless condition caused a reduction in the number of Fos-positive cells in the hippocampal CA1 region, in which Fos immunoreactivity was localized in the cell nuclei. This effect was more pronounced the longer the molarless condition persisted. The suppression of both learning ability and Fos induction in the CA1 induced by the molarless condition was considerably reduced by restoring the lost molars with artificial crowns. Taken together with the plethora of research showing a relationship between stress, aging and hippocampal function and our past findings [Brain Res. 1999; 826: 148-53; Behav. Brain Res. 2000;108: 145-55; Exp. Gerontol. 2001; 36:283-95], the present results suggest the detrimental effects of a reduction in chewing on hippocampal processing in aged SAMP8 mice that would be linked with stress induced by the molarless condition.

Aging↗
PubMed2002

Usefulness of hydrophilic coating on arterial sheath introducer in transradial coronary intervention.

Radial artery spasm is one of the major problems during transradial coronary intervention (TRI). The sheath introducer with hydrophilic coating may reduce the incidence of spasm and reduce the difficulty in removing it from the radial artery under the situation of spasm artery spasm. After we compared the friction resistance between the sheath introducer with hydrophilic coating and that without coating (nine samples each) in vitro, the sheath introducers with and without hydrophilic coating were randomly used in 37 and 36 patients, respectively, who underwent elective TRI with a 6 Fr introducer sheath. Hydrophilic coating of sheath introducer reduced friction resistance by 70% (P < 0.00001) in in vitro model and facilitated sheath removal after finishing TRI (P = 0.0003). Hydrophilic coating of sheath introducer is useful in TRI.

Catheterization, Peripheral↗
PubMed2002

G-protein coupled receptor kinase 2 is altered during septic shock in rats.

BACKGROUND: One of the key mechanisms leading to beta-adrenergic receptor-specific desensitization is the phosphorylation of agonist-occupied receptors by the specific beta-adrenergic receptor kinase (GRK2). The present study examines whether GRK2 is altered during septic shock in rats. MATERIALS AND METHODS: Male Wistar rats (7 weeks) weighing between 250 and 300 g were anesthetized with pentobarbital (10 mg/kg ip). Escherichia coli endotoxin (10 mg/kg in 0.3 mL of saline) or saline (0.3 ml) was injected intravenously via the dorsal vein. Hemodynamic parameters and humoral mediators were measured at 2 h after the administration of endotoxin. The hearts were immediately excised to examine beta-adrenergic receptor density and GRK2 level. We also studied the inotropic response to isoproterenol at the same time in other animals. RESULTS: Myocardial beta-adrenergic receptor density in the membrane fraction was decreased after an intravenous administration of 10 mg/kg LPS (LPS group: baseline value; 82 +/- 11 fmol/mg protein; 120 min after LPS; 58 +/- 11 fmol/mg protein, P < 0.05). GRK2 levels in the membrane and cytosolic fraction of the control group did not change. In the LPS group, GRK2 levels in the membrane fraction were increased at 60 and 120 min after the treatment (60 min; control, 4.5 +/- 0.4; pithed control, 4.4 +/- 0.6; LPS group, 6.2 +/- 0.3; pithed LPS group, 5.5 +/- 0.4; 120 min: control, 4.4 +/- 0.3; pithed control, 4.9 +/- 0.7; LPS group, 7.1 +/- 0.3; pithed LPS group, 5.9 +/- 0.4; densitometric unit, respectively: P < 0.05). CONCLUSIONS: GRK2 levels in the membrane fraction are increased during septic shock in rats. GRK2 might play a role in the impairment of the beta-adrenergic receptor signal transduction system.

Adrenergic beta-Agonists↗
PubMed2002

Treatment for patients with postmenopausal osteoporosis who have been placed on HRT and show a decrease in bone mineral density: effects of concomitant administration of vitamin K(2).

We have been using hormone replacement therapy (HRT) as the treatment of choice for menopausal symptoms and osteoporosis. Estrogen increases bone mineral density (BMD) for 2 or 3 years, and only maintains BMD thereafter. In the present study, we investigated whether BMD improved with HRT in combination with vitamin K(2). Ninety-four patients with postmenopausal osteoporosis were studied. All patients were placed on HRT for more than 1 year. Ten patients whose BMD had increased up to a plateau and showed a decreasing trend thereafter while they were receiving HRT were placed on HRT in combination with vitamin K(2). The long-term BMD (L(2)-L(4)) profiles of those receiving HRT alone, and the effects of HRT in combination with vitamin K(2) on the BMD profiles were examined. The rate of change in BMD (mean +/- SE) of all patients who underwent HRT alone was 2.9 +/- 1.2% 1 year after the initiation of HRT, 4.6 +/- 1.2% 2 years later, and 5.4 +/- 1.2% 3 years later. The BMD in these patients, which reached a peak increase after 3 years, no longer increased from the following year. When vitamin K(2) was administered concomitantly to 10 patients for 12 months because of the decrease in BMD, their BMD (mean +/- SE) increased significantly, from 0.734 +/- 0.021 g/cm(2) to 0.783 +/- 0.026 g/cm(2) ( P < 0.03; paired- t test). We conclude that HRT in combination with vitamin K(2) significantly improved BMD that was on the decrease after HRT alone. Therefore, as a supplementary drug for postmenopausal osteoporosis, vitamin K(2) is a good therapeutic option for patients who are placed on HRT.

Bone Density↗
PubMed2002

Macrophage colony-stimulating factor restored chemotherapy-induced granulocyte dysfunctions: role of IL-8 production by monocytes.

We evaluated the influence of M-CSF treatment on granulocyte functions in patients with ovarian cancer. Eighteen patients with ovarian cancer received two consecutive courses of chemotherapy (16 cases, CAP therapy and two cases, CP therapy) at 4-week intervals. M-CSF (8 million U/day) was infused for 7 days starting from the next day after chemotherapy. Superoxide anion production by isolated peripheral blood granulocytes, their phagocytosis, and expression of cell adhesion molecules such as CD11a, CD11b, and CD18 on granulocytes were measured by flow cytometry. Cytokine (IL-8, G-CSF, and GM-CSF) levels in peripheral blood monocyte (PBM) culture supernatants were measured by enzyme-linked immunosorbent assay in 5 out of 18 cases. The levels of CD11a, CD11b and CD18 expression on peripheral blood granulocytes and superoxide anion production by granulocytes were significantly suppressed by chemotherapy without CSF support. The levels of CD11a and CD18 expression on granulocytes were significantly enhanced by administration of M-CSF. When M-CSF was added to cultured PBM, the level of IL-8 in the supernatant increased with the concentration of M-CSF. When IL-8 was added to cultured granulocytes, the levels of CD18 expression on granulocytes and superoxide anion production by granulocytes were significantly increased. These observations suggest that M-CSF enhances the production of IL-8 from monocytes in vivo, thereby improving chemotherapy-induced granulocyte dysfunction.

Adult↗
PubMed2002

Induction of apoptosis mediated by fas receptor and activation of caspase-3 in MRL-+/+ or MRL-lpr/lpr murine oocytes.

The molecular mechanisms leading to ovarian follicular atresia in the typical pathways of programmed cell death remain to be clarified. Here we have demonstrated that the apoptotic signalling pathway in MRL-+/+ (MRL/+) murine oocytes is through the Fas receptor followed by the activation of caspase-3. In contrast, we found that the aberrant expression and dysfunction of the mutant Fas receptor in MRL-lpr/lpr (MRL/lpr) murine oocytes caused by insertion of the early transposable element (ETn) into the Fas gene were associated with an inability to activate the caspase cascade (especially caspase-3) and to induce nuclear DNA fragmentation. These findings indicate that the induction of apoptosis in MRL/lpr murine oocytes did not occur in the presence of a defective Fas receptor lacking the death domain to trigger the caspase cascade, suggesting a failure to induce ovarian follicular atresia.

Animals↗
PubMed2002

Interleukin 2 receptor gamma chain (gamma(c)) knockout mice show less regularity in estrous cycle but achieve normal pregnancy without fetal compromise.

PROBLEM: Implication of cytokines in pregnancy suggested but remains to be established. We studied the effect of cytokines on reproductive functions such as ovulation and pregnancy, with mutant mice lacking interleukin 2 receptor gamma (IL-2Rgamma), the so-called common gamma chain (gamma(c)), which is shared among receptors for multiple cytokines such as IL-2, IL-4, IL-7, IL-9 and IL-15. METHOD OF STUDY: Regularities of estrous cycles were observed by vaginal smear. Ovaries stimulated with postmenopausal serum gonadotropin (PMSG) were examined for the ovarian capacities. The uteri at 13 days of gestation were used for histological analysis of the maternal-fetal interface. RESULTS: The estrous cycles in gamma(c) knockout (gamma(c) KO) mice were irregular compared with wild-type mice, although, the mutants could become pregnant. No uterine natural killer (uNK) cell was found in the uterus at 13 days of pregnancy, and poor decidual formation and thickness of blood vessel walls were observed. Apparent differences were not seen in the numbers and weight of the fetuses between wild type and mutant animals, and fetuses were not compromised throughout pregnancy. CONCLUSIONS: The gamma(c) KO mice showed irregular estrous cycle but they could carry out normal pregnancy despite lacking uNK and cytokines actions of IL-2, 4, 7, 9 and 15.

Animals↗
PubMed2002

Prostaglandin D2 and reproduction.

This review highlights recent studies investigating the role of prostaglandin (PG)D2 in reproduction. PGD2 induces sleep, allergic responses, inhibition of platelet aggregation, and relaxation of vascular and non-vascular smooth muscle, and has some roles in reproduction. Two types of PGD2 synthase are known. Lipocalin-type PGD synthase is present in cerebrospinal fluid, seminal plasma and may play an important role in male reproduction. Another PGD synthase, hematopoietic PGD synthase is present in the spleen, fallopian tube, endometrial gland cells, extravillous trophoblasts and villous trophoblasts, and perhaps plays an important role in female reproduction. Recent studies demonstrate that PGD2 is probably involved in multiple aspects of inflammation through its dual receptor systems, DP and CRTH2. CRTH2 but not DP is a chemo-attractant receptor for PGD2. Interestingly, CRTH2 is a most reliable marker for the detection of human T helper type 2 (Th2) and T cytotoxic type 2 (Tc2) cells, and the percentages of CRTH expressing CD4+-T cells and CD8+-T cells were significantly higher in the decidua especially at the implantation site, suggesting that Th2 and Tc2 cells recruit into the materno-fetal interface, in a PGD2-mediated manner. PGD2 has a very unique effect to inhibit antigen presentation by inhibition of dendritic cell (DC) migration through DP but not CRTH2. PGD2 might appear to contribute to the maintenance of pregnancy by controlling the Th1/Th2 balance and antigen presentation by DCs through its dual receptor systems, CRTH2 and DP.

Animals↗
PubMed2002

A Th2 chemokine, TARC, produced by trophoblasts and endometrial gland cells, regulates the infiltration of CCR4+ T lymphocytes into human decidua at early pregnancy.

PROBLEM: A chemokine receptor, CCR4 preferentially expressed on type 2 helper T (Th2-type) cells, and its ligand, thymus and activation regulated chemokine--(TARC/CCL)--play important roles in the recruitment of Th2-type cells. We examined the distribution of CCR4 expressing CD4+ and CD8+-T cells in human decidua at early pregnancy, and localized TARC in the decidual tissue and chorionic tissue. METHOD OF STUDY: Decidual tissue was obtained by legal abortion. The percentages of CCR4 expressing CD4+ and CD8+-T cells were analyzed by flow cytometry. Localization of TARC protein was evaluated by immunofluorescence staining. The expression of TARC mRNA in the choriocarcinoma cell line and endometrial cell line was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). RESULT: The percentages of CCR4+ cells in CD4+-T cells and CD8+-T cells were significantly increased in human early pregnancy decidua compared with those in peripheral blood. An another marker of human Th2 and Tc2 cells, CRTH2 molecules was also expressed on CCR4+ CD4+-T cells and CCR4+ CD8+-T cells. In addition, we found that trophoblasts, uterine epithelial cells and endometrial gland cells produce TARC by immunohistochemical staining and the RT-PCR method. CONCLUSION: Our findings imply that TARC secreted in decidua mediates the infiltration of CCR4+ T-cell migration into the fetomaternal interface, decidua, resulting in the maintenance of pregnancy.

Adult↗
PubMed2002

Interleukin-12 secretion by peripheral blood mononuclear cells is decreased in normal pregnant subjects and increased in preeclamptic patients.

PROBLEM: It has been reported that T-helper (Th) 2 dominance in normal pregnancy shifts to Th1 dominance in preeclampsia. Peripheral blood mononuclear cell (PBMC) production of interleukin (IL)-12, which induce Th1 responses, has not been compared between these clinical states. METHOD OF STUDY: Peripheral blood mononuclear cell from 35 non-pregnant women, 35 healthy pregnant women, 12 mildly preeclamptic patients, and 15 severely preeclamptic patients were cultured for 24 hr. IL-12 secretion was determined by enzyme-linked immunosorbent assay (ELISA). Th1/Th2 ratios in PBMC were determined flow-cytometrically, and the amounts of HLA-DR and CD14 expression on the monocytes were obtained by flow cytometry. RESULTS: Peripheral blood mononuclear cell from healthy pregnant subjects secreted less IL-12 than non-pregnant women. PBMC from severely preeclamptic patients secreted more IL-12 than those from healthy pregnant subjects, while IL-12 secretion in mild preeclampsia resembled secretion in normal pregnancy. Th1/Th2 ratios correlated were positively with IL-12. Increased HLA-DR antigens and reduced CD14 expression, suggesting monocyte activation, were observed in preeclamptic patients, although monocyte counts were unchanged. CONCLUSION: Decreased IL-12 secretion by PBMC may cause Th2 dominance in normal pregnancy, while increased IL-12 secretion by activated monocytes may cause Th1 dominance in preeclampsia.

Adult↗
PubMed2002

Physical condition among middle altitude trekkers in an aging society.

The number of alpine accidents has markedly increased among elderly trekkers in an aging society, Japan. We evaluated the physical condition of 176 trekkers by interview and physical examination on a popular middle altitude mountain. Heart rate, noninvasive blood pressure and arterial oxygen saturation (SpO2) were measured using a portable life monitor. It was revealed that more than 70% of the trekkers were over 50. Seventy-five percent of trekkers over 70 had some pre-existing medical problems. Systolic and diastolic blood pressure before the start of trekking, increased with age. However, such age-dependent differences were not apparent at the summit hut. SpO2 values decreased slightly but significantly with age. In conclusion, many elderly people enjoy nonchallenging middle altitude trekking in an aging society. Alpine accidents caused by health problems tend to arise more frequently in this population. Alpine rescue teams should be well-prepared for the alpine accidents of elderly trekkers.

Adolescent↗
PubMed2002

Accumulation of CRTH2-positive T-helper 2 and T-cytotoxic 2 cells at implantation sites of human decidua in a prostaglandin D(2)-mediated manner.

T-helper (Th) 2-type cytokines predominate in decidua, plausibly accounting for protection of a semiallograft, the embryo and placenta, from attack by the maternal immune system. However, localization of Th2 and T-cytotoxic (Tc) 2 cells in decidua has not been reported, presumably because of the difficulty in detecting intracellular cytokines in tissues. Here, by staining tissues for a novel surface maker of Th2/Tc2, the chemoattractant receptor-homologous molecule CRTH2, which is expressed on Th2 cells, we show that CRTH2(+) Th2 cells and CRTH2(+) Tc2 cells are significantly increased at the materno-fetal interface (implantation site) in decidua. We also show that trophoblast, uterine epithelium and endometrial glands all express haematopoietic-type prostaglandin (PG) D(2) synthase (hPGDS). Since CRTH2 is a chemoattractant receptor for PGD(2) and mediates PGD(2)-dependent migration of blood Th2 cells, our findings suggest that Th2 and Tc2 cells may be recruited to the materno-fetal interface, at least in part in a PGD(2)-mediated manner.

Cell Separation↗
PubMed2002

The neurotoxicity of local anesthetics on growing neurons: a comparative study of lidocaine, bupivacaine, mepivacaine, and ropivacaine.

UNLABELLED: Local anesthetics can be neurotoxic. To test the hypothesis that exposure to local anesthetics produces morphological changes in growing neurons and to compare this neurotoxic potential between different local anesthetics, we performed in vitro cell biological experiments with isolated dorsal root ganglion neurons from chick embryos. The effects of lidocaine, bupivacaine, mepivacaine, and ropivacaine were examined microscopically and quantitatively assessed using the growth cone collapse assay. We observed that all local anesthetics produced growth cone collapse and neurite degeneration. However, they showed significant differences in the dose response. The IC(50) values were approximately, 10(-2.8) M for lidocaine, 10(-2.6) M for bupivacaine, 10(-1.6) M for mepivacaine, and 10(-2.5) M for ropivacaine at 15 min exposure. Some reversibility was observed after replacement of the media. At 20 h after washout, bupivacaine and ropivacaine showed insignificant percentage growth cone collapse in comparison to their control values whereas those for lidocaine and mepivacaine were significantly higher than the control values. Larger concentrations of the nerve growth factor (NGF) did not improve this reversibility. In conclusion, local anesthetics produced morphological changes in growing neurons with significantly different IC(50). The reversibility of these changes differed among the four drugs and was not influenced by the NGF concentration. IMPLICATIONS: Local anesthetics induce growth cone collapse and neurite degeneration in the growing neurons. Mepivacaine was safer than lidocaine, bupivacaine, and ropivacaine for the primary cultured chick neurons.

Amides↗
PubMed2002

Pre-ictal bispectral index has a positive correlation with seizure duration during electroconvulsive therapy.

UNLABELLED: Propofol anesthesia increases the seizure threshold of patients receiving electroconvulsive therapy. Excessive neuronal suppression could result in an unacceptably short seizure. We sought to identify the correlation between the pre-ictal bispectral index (BIS) score and seizure duration in patients receiving electroconvulsive therapy under propofol anesthesia. BIS was monitored in 38 psychotically depressed patients. Anesthesia was induced by a bolus injection of 1 mg/kg of propofol. The duration of muscular and electroencephalographic seizure was measured during the therapy. The BIS immediately before the electrical shock was 54 +/- 13. Both muscular and electroencephalographic seizure durations had a positive correlation with pre-ictal BIS (r = 0.68 and 0.73, respectively; P < 0.01). After the electrically induced seizure, BIS decreased to 30 +/- 8, reflecting post-ictal suppression. BIS scores when the patients had awakened after the seizure had a wide variation (range, 29-81; mean, 45; SD, 13). In conclusion, seizure duration has a positive correlation with BIS immediately before electrical shock; however, BIS may not be an accurate predictor of awakening after electrical shock. IMPLICATIONS: Pre-ictal bispectral index had a positive correlation with seizure duration and could be useful to prevent an unacceptably short seizure in electroconvulsive therapy under propofol anesthesia.

Adult↗
PubMed2002

Slow rewarming has no effects on the decrease in jugular venous oxygen hemoglobin saturation and long-term cognitive outcome in diabetic patients.

UNLABELLED: The purpose of this study was to examine the effects of rewarming rate on internal jugular venous oxygen hemoglobin saturation (SjvO(2)) during the rewarming period, and long-term cognitive outcome in diabetic patients. We studied 30 diabetic patients scheduled for elective coronary artery bypass graft surgery. As a control, 30 age-matched nondiabetic patients were identified. The diabetic patients were randomly divided into two groups: the Slow Rewarming group (n = 15) (mean rewarming speed: 0.22 degrees +/- 0.07 degrees C/min, mean +/- SD) or the Standard Rewarming group (Standard group) (n = 15) (mean rewarming speed: 0.46 degrees +/- 0.09 degrees C/min, mean +/- SD). After the induction of anesthesia, a fiberoptic oximetry catheter was inserted into the right jugular bulb to monitor SjvO(2) continuously. Hemodynamic variables and arterial and jugular venous blood gases were measured at nine time points. All patients underwent a battery of neurologic and neuropsychologic tests on the day before the operation and at 4 mo after surgery. The SjvO(2) values in the Standard group were decreased during the rewarming period compared with at the induction of anesthesia (P < 0.05). There was a significant difference in the SjvO(2) value in the Control group between standard rewarming and slow rewarming during rewarming periods (Standard Control group: 51% +/- 8%, Slow Control groups: 58% +/- 5%) (P < 0.05). However, there was no difference in the SjvO(2) value in diabetic patients between standard rewarming and slow rewarming during the rewarming period. The rewarming rates (odds ratio: 0.8; 95% confidence interval: 0.5-1.3; P = 0.6) had no correlation with cognitive impairment at 4 mo after the surgery. Diabetes (odds ratio: 1.6; 95% confidence interval: 0.9-2.6; P = 0.04) was a factor in relation to cognitive impairment at 4 mo after the surgery. We concluded that a slow rewarming rate had no effects on the reduction in SjvO(2) value and long-term cognitive outcome in diabetic patients. IMPLICATIONS: We examined the effects of rewarming rate on internal jugular venous oxygen hemoglobin saturation in diabetic and nondiabetic patients during the rewarming period and long-term cognitive outcome. Slow rewarming could not prevent the frequency of the reduction in internal jugular venous oxygen hemoglobin saturation and adverse cognitive outcome in diabetic patients.

Aged↗