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Biomedical subjects

S Suzuki

Publications and source records attributed to S Suzuki.

At least 127 records · Page 7Linked to original sources

Percutaneous absorption of non-steroidal anti-inflammatory drugs from in situ gelling xyloglucan formulations in rats.

The potential of gels formed in situ by dilute aqueous solutions of a xyloglucan polysaccharide derived from tamarind seed as sustained release vehicles for percutaneous administration of non-steroidal anti-inflammatory drugs has been assessed by in vitro and in vivo studies. Chilled aqueous solutions of xyloglucan that had been partially degraded by beta-galactosidase formed gels at concentrations of 1-2% w/w when warmed to 37 degrees C. The in vitro release of ibuprofen and ketoprofen at pH 7.4 from the enzyme degraded xyloglucan gels and the subsequent permeation of these fully ionized drugs through cellulose membranes followed root-time kinetics over a period of 12 h after an initial lag period. Diffusion coefficients were appreciably higher when the drugs were released from 1.5% w/w xyloglucan gels than when released from 25% w/w Pluronic F127 gels formed in situ under identical conditions. The difference in release rates was attributed to differences in the structure of the gels. The permeation rate of ibuprofen through excised skin was higher than that of ketoprofen when released from both gels, but of similar magnitude through cellulose membranes. Plasma concentrations of ibuprofen and ketoprofen from gels formed in situ following topical application of chilled aqueous solutions of xyloglucan and Pluronic F127 to the abdominal skin of rats were compared. The bioavailabilities of ibuprofen and ketoprofen were significantly higher when released from xyloglucan gels compared to Pluronic F127 gels. Occlusive dressing techniques had a greater enhancing effect on the bioavailability of ibuprofen when released from Pluronic gels.

Administration, Cutaneous↗

del11(p11-13) with overexpression of Wilms' tumor gene during leukemic transformation of myelodysplastic syndrome.

We report a case of leukemic transformation from myelodysplastic syndrome (MDS) with a sole chromosome abnormality of del11(p11-13). The patient had been diagnosed as having MDS (refractory anemia with excess of blast cells, RAEB) in May 1998. At that time, cytogenetic analysis of bone marrow cells showed a normal karyotype. The patient received sequential chemotherapy with low-dose cytosine arabinoside (AraC) and macrophage colony-stimulating factor (M-CSF). Complete remission was obtained with this treatment, but the disease gradually progressed after June 1999. Cytogenetical analysis showed del11(p11-13) in 6 of 40 cells analyzed at that time, and the disease had evoluted to overt leukemia in December 1999 with a gradual increase in the abnormal clone. Furthermore, mRNA of the WT1 gene located at chromosome 11p13 was overexpressed during leukemic transformation, whereas it was not detected at the time of the initial diagnosis of MDS (RAEB) in May 1998. It was thought that this chromosome deletion and overexpression of WT1 resulted in the leukemic transformation in this patient. This is the first case report of del11(p11-13) being considered to be the primary cause of leukemic transformation from MDS.

Blast Crisis↗

Organ differences in the enhancing potential of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine on carcinogenicity in the prostate, colon and pancreas.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant carcinogenic heterocyclic amine in cooked meat and fish, is speculated to be associated with human carcinogenesis. It has been shown to induce DNA adducts in a variety of organs in rodents and thus clarification of any enhancement of neoplasia is a very important subject for assessing human risk. In order to evaluate modifying effects of PhIP on carcinogenesis, several in vivo experiments in rats were performed. These featured dietary administration of PhIP at different dose levels and for different durations, and included intragastric dosing for a short period, or continuous dietary administration after initiation with other carcinogen, namely 3,2'-dimethyl-4-aminobiphenyl (DMAB) or 1,2-dimethylhydrazine (DMH). The data indicate that a short administration of PhIP is sufficient to induce prostate tumors but long-term treatment is required for effects in the colon. They also suggest tumor enhancing potential dependent on the organ, i.e. evident in the colon but not the prostate. Furthermore, promotion of colon neoplasia may depend on the initiator employed. Thus these findings suggest that the carcinogenic mechanisms of PhIP may vary in its different target organs.

1,2-Dimethylhydrazine↗

Acute gliclazide administration enhances glucose and ketone body utilization in the perfused hind limb of normal and streptozotocin-diabetic rats.

Sulfonylureas are the most commonly used oral hypoglycemic agents. Their hypoglycemic actions are produced not only by stimulating insulin secretion but also by extrapancreatic mechanisms. Some groups have already demonstrated the extrapancreatic actions of sulfonylureas on carbohydrate metabolism in the liver, fat and muscle. In this study, we showed in an in situ perfused hind limb preparation of STZ-diabetic rats that gliclazide has an acute effect on ketone body and glucose utilization.

Animals↗

Changes in the proportion of T helper 1 and T helper 2 cells in cord blood after premature rupture of membranes.

This study investigated changes in the proportion of T helper (Th)1 and Th2 cells in cord blood after premature rupture of membranes (PROM), and evaluate the effects of PROM on the intrauterine fetal immune status. The proportion of CD3-positive T cells secreting interferon (IFN)-gamma as an index of Th1 cells, and interleukin (IL)-4 as an index of Th2 cells in cord blood of 12 newborns with and without PROM, were analyzed by flow cytometry. In cord blood of newborns with PROM, the proportion of IFN-gamma secreting cells significantly increased, and the proportion of IL-4 secreting cells was rather high but not significantly higher than that of newborns without PROM. These changes eventually caused a shift in the Th1/Th2 ratio to Th1 dominance in PROM. There was no significant correlation between the proportion of IFN-gamma secreting cells and the duration of PROM before the onset of labor. These results suggest that the increase in the proportion of IFN-gamma secreting cells after PROM, which eventually cause the Th1/Th2 ratios to show the Th1 predominance, may reflect in part intrauterine fetal immune responses to PROM.

Adult↗

Urinary excretion of 8-oxo-7, 8-dihydro-2'-deoxyguanosine as a predictor of the development of diabetic nephropathy.

AIMS/HYPOTHESIS: The increased oxidative stress in diabetes is known to contribute to the progression of diabetes and its complications. We have reported a significant relation between the content of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a product of oxidative DNA damage in urine or leukocytes and the severity of diabetic nephropathy and retinopathy [1]. We investigated whether 8-oxodG in urine or leukocytes is associated with the progression of diabetic nephropathy. METHODS: We measured urinary 8-oxodG contents at entry and carried out a prospective longitudinal study to assess the progression of nephropathy over 5 years. RESULTS: There was a significant progression of diabetic nephropathy in the patients with higher excretion of 8-oxodG in urine compared with the patients with moderate or lower excretion of 8-oxodG. There was no significant association between the leukocyte 8-oxodG contents and the development of nephropathy. The multivariate logistic regression analysis suggests that the urinary 8-oxodG was the strongest predictor of nephropathy among several known risk factors. CONCLUSION/INTERPRETATION: This study provides evidence that increased oxidative stress has a primary role in the pathogenesis of diabetic nephropathy. A local enhancement of oxidative stress in diabetic kidney might explain the possible linkage between the increased urinary excretion of 8-oxodG and the development of nephropathy. 8-oxodG in urine is a useful clinical marker to predict the development of diabetic nephropathy in diabetic patients.

Age of Onset↗

Serum adenosine deaminase activity and its isoenzyme pattern in women with normal pregnancies.

Adenosine deaminase (ADA) is a purine enzyme which is essential for the proliferation, maturation and function of lymphoid cells, and congenital deficiency of this enzyme is associated with severe combined immunodeficiency disease. The activity of ADA has changed in diseases characterized by the alteration of cell-mediated immunity such as rheumatoid arthritis, systemic lupus erythematosus and tuberculosis, so ADA has been considered as a nonspecific marker of cell-mediated immunity. In this study we examined changes in serum total ADA activity and the patterns of two ADA isoenzymes, ADA1 and ADA2 in normal pregnant women, and evaluated the possible role of the alteration of cell-mediated immunity during normal pregnancy as causes of changes in ADA activity. We measured serum activities of total ADA, ADA1 and ADA2 in normal pregnant women in the third trimester (n=24) and age-matched healthy nonpregnant women (n=24). Peripheral blood lymphocytes and monocytes were also measured. In normal pregnant women, serum total ADA activity averaged 10.5 +/- 0.5 U/L, which was significantly lower than in nonpregnant women (14.0 +/- 0.5 U/L ) (p<0.05), and mean serum ADA2 activity also significantly reduced that of nonpregnant women (p<0.05). There was no significant difference in ADA1 activity in normal pregnant and nonpregnant women. The decrease in total ADA activity was accompanied by the decrease in lymphocyte count. These results suggest that reduced serum total ADA activity reflects decrease in ADA2 activity, and which may be in part associated with depressed cell-mediated immunity during normal pregnancy.

Adenosine Deaminase↗

Pneumococcal purulent genual arthritis after allogeneic bone marrow transplantation.

A 21-year-old male patient with non-Hodgkin's lymphoma (diffuse large T-cell type, clinical stage IV) received allogeneic bone marrow transplantation (BMT) from a partially HLA-mismatched unrelated donor in July 1998 and achieved complete remission. Thereafter, he suffered from chronic graft-versus-host disease (GVHD) and was continuously administered immunosuppressive drugs for a long time. Two years after the BMT, he complained of severe pain in the right knee, which was swollen, and was diagnosed as having pneumococcal purulent genual arthritis. He underwent arthroscopic synovectomy and was administered systemic and intra-articular antibiotics, leading to a gradual improvement. Streptococcal infections are often seen in patients in the late phase after allogeneic BMT because of immunodeficiency associated with chronic GVHD and hyposplenism. Most streptococcal infections are respiratory tract infections and septicemia, and there have been very few reports on cases of purulent genual arthritis. Administration of prophylactic antibiotics and control of chronic GVHD, which is a risk factor of pneumococcal infection, seem to be important to prevent purulent genual arthritis.

Adolescent↗

Down-regulation of Lsm1 is involved in human prostate cancer progression.

Elucidation of genetic alterations is an approach to understanding the underlying molecular mechanisms of progression of human prostate cancers. We have searched for genes differentially expressed in advanced prostate cancers using cDNA-representational difference analysis, and thereby isolated the Lsm1 as one of down-regulated gene. An Lsm1 expression vector was transfected into PC3 cells, normally featuring down-regulated Lsm1, and four transfectants were established. No differences in morphology or cell proliferation were evident in comparison with parent PC3 or PC3/mock-transfectants. In contrast, significant suppression of invasive potential or metastatic ability of Lsm1 transfectants was observed in the Matrigel chemoinvasion assay and in nude mice, respectively. With human prostate cancers, almost all of informative prostatectomised cases without neoadjuvant therapy showed allelic retention in the Lsm1 region, whereas refractory cancers frequently showed allelic loss in this region. No critical gene mutations were found in open reading frame of Lsm1 in prostate cancers examined by PCR-SSCP analysis, including localised and refractory cancers. These results suggest that Lsm1 is deeply involved in prostate cancer progression through its down-regulation, independent of any gene mutation.

Animals↗

Clinical manifestations, character of aneurysms, and surgical results for unruptured cerebral aneurysms presenting with ophthalmic symptoms.

OBJECTS: Cases with unruptured cerebral aneurysms presenting with visual symptoms were investigated about their site, size, symptom, operative methods and results. MATERIAL: Between 1984 and 1999, 8 cases were treated in Sendai National Hospital. One man and 7 women, mean age 66.4 years. Ophthalmic symptoms were as follows: diplopia in 6, visual acuity deterioration in 2, impaired visual field in 2 and ptosis in 3. Aneurysm location was IC cavernous in 3, IC ophthalmic in 3, ICPC in 1 and Acom in 1. Aneurysms of more than 25 mm numbered 6 cases. RESULTS: Operative methods and results were as follows: Direct clipping 3 cases, parent artery occlusion + EC/IC bypass 4 cases, Aneurysm trapping + EC/IC bypass 1 case. One patient who underwent direct clipping died following intraoperative complication. Of the remaining 7 cases, visual symptoms were improved in 4, remained unchanged in 2 cases, worsened in 1 case. CONCLUSIONS: These results suggest that in cases with unruptured large or giant aneurysms presenting with ophthalmic symptoms, especially in IC cavernous or IC ophthalmic aneurysms, parent artery occlusion + EC/IC bypass is the safest operative procedure.

Aged↗

Maternal plasma adenosine and endothelin-1 levels in twin gestation complicated by preeclampsia.

The aim of this study was to evaluate the relationship between the vascular resistance in uterine arteries and the maternal release of adenosine and endothelin-1 in twin gestations with and without preeclampsia. Uterine artery Doppler velocimetry and maternal arterial blood sampling were performed in 14 women with normal singleton gestation, nine women with singleton gestation with preeclampsia, eight women with dichorionic twin gestation without preeclampsia and six women with dichorionic twin gestation with preeclampsia at 28-34 weeks' gestation. In normal singleton gestations, the average maternal uterine arteries pulsatility index (PI), plasma adenosine and endothelin-1 levels were 0.64+/-0.07, 0.34+/-0.11 micromol/l and 1.29+/-0.31 pg/ml, respectively. In preeclamptic singleton gestations, increased vascular resistance in the uterine arteries (PI: 0.85+/-0.14, P<0.05) and the elevation of maternal arterial plasma adenosine (0.48+/-0.14 micromol/l, P<0.05) and endothelin-1 levels (1.91+/-0.55 pg/ml, P<0.05) were observed. In the normal twin gestation group, the average maternal vascular resistance of the uterine arteries (PI: 0.55+/-0.09) was lower than that in the normal singleton gestation group, while the average plasma adenosine levels (0.47+/-0.12 micromol/l) were higher than that in normal singleton gestation. On the other hand, significant increased plasma endothelin-1 concentrations (1.87+/-0.42 pg/ml) were observed in the preeclamptic twin gestation groups without changes in plasma adenosine levels or vascular resistance of uterine arteries. Our results indicate the presence of different mechanisms for the pathogenesis of preeclampsia between twin and singleton gestations.

Adenosine↗