Search PubMed⌕ Search

Biomedical subjects

S Suzuki

Publications and source records attributed to S Suzuki.

At least 217 records · Page 12Linked to original sources

Long-term graft acceptance in rat heart transplantation by CTLA4Ig gene transfection combined with FTY720 treatment.

CTLA4Ig strongly adheres to B7 molecules on antigen-presenting cells to block intracellular signal transduction via CD28 on helper T cells, which eventually inhibits immune responses. We have demonstrated that the administration to recipient animals of adenoviral vectors containing CTLA4Ig gene (adCTLA4Ig) prolonged graft survival, although the gene expression diminished in a time-dependent manner and the grafts were finally rejected. In addition, recipient animals treated with FTY720, a new immunosuppressant, exhibited a decrease in the number of peripheral lymphocytes due to apoptosis. In this study, we performed adCTLA4Ig transfection combined with FTY720 treatment in heart-grafted rats to determine if the combination could induce a mutual effect on graft survival. The recipient animals were given injections of 1 x 10(9) plaque-forming units of adCTLA4Ig via the tail vein immediately after grafting. On the day before transplantation we administered FTY720 orally to some of these animals at a dosage of 5 mg/kg and again on the day of transplantation. The median graft survival period in the adCTLA4Ig-only group was 27 days, whereas that in the combination group was markedly prolonged to 56 days. Of 15 grafts, 5 survived indefinitely. In these groups we observed detectable levels of CTLA4Ig in the sera 49 days after grafting; the levels were always higher in the combination group than in the adCTLA4Ig-only group. As a result, this study revealed that FTY720 and adCTLA4Ig have a potent mutual effect on graft survival during rat heart transplantation. Furthermore, it is highly possible that FTY720 enhances gene expression of adCTLA4Ig, which may be related to the long-term acceptance of grafts.

Abatacept↗

Peripheral T-cell lymphoma in a patient with osteopetrosis.

Osteopetrosis is a rare genetic disorder in which the function of osteoclasts is defective, resulting in impaired bone resorption. This disease is usually accompanied by myelosuppression due to decreased marrow space and by osteomyelitis, especially in the submandibular bone. We report the case of a 72-year-old woman with an autosomal dominant form of osteopetrosis who suffered from peripheral T-cell lymphoma. Accurate clinical and pathological diagnoses and staging were difficult due to nonspecific reactive hyperplasia of the lymph nodes, even though we used several scintigraphic techniques and [18F]fluorodeoxyglucose positron emission tomography. We also paid special attention to myelosuppression and exacerbation of osteomyelitis after combination chemotherapy. Severe infectious complications were avoided by early administration of G-CSF for leukocytopenia and by continuous oral administration of antibiotics. The patient achieved complete remission after four courses of chemotherapy and this status has been maintained for 6 months.

Aged↗

Chronic eosinophilic leukemia with t(6;11)(q27;q23) translocation.

We report a rare case of chronic eosinophilic leukemia (CEL) with a chromosomal abnormality of t(6;11)(q27;q23). The patient was diagnosed as having thyroid cancer with metastases to the lung and cervical lymph nodes in 1993. Percutaneous ethanol injection therapy (PEIT), total thyroidectomy, and radiotherapy were performed. The patient was also diagnosed as having prostatic cancer with bone metastasis in July 1999, and hormonal therapy was performed. At the time of the diagnosis of prostatic cancer, leukocytosis with eosinophilia was also revealed. Thereafter, cytogenetical analysis and reverse transcriptase polymerase chain reaction (RT-PCR) analysis of bone marrow showed t(6;11)(q27;q23) translocation and MLL/AF6 fusion products, respectively. No transcripts of the BCR/ABL chimeric gene were found by RT-PCR in bone marrow. Analysis of serum cytokines revealed a slight elevation of GM-CSF but no elevation of IL-3 or IL-5. Tissue damage due to infiltration of eosinophils was not observed throughout the clinical course. On the basis of the cytogenetic and molecular abnormality, the patient was diagnosed as having CEL, rather than reactive eosinophilia due to thyroid or prostatic cancer or other reactive inflammation. This is the first case report of CEL with t(6;11)(q27;q23) translocation.

Aged↗

The platelet-sparing effect of paclitaxel is not related to changes in the pharmacokinetics of carboplatin.

PURPOSE: To determine whether the platelet-sparing effect of paclitaxel is related to changes in pharmacology of carboplatin. METHODS: A group of 32 patients with epithelial ovarian cancer were treated with intraperitoneal (i.p.) carboplatin-based chemotherapy with carboplatin alone or in combination with cyclophosphamide or paclitaxel, and the relationship between the pharmacology of serum platinum and thrombocytopenia was examined. The target AUC of i.p. carboplatin was 6.5 mg min/ml. Cyclophosphamide was administered intravenously at 400 mg/m2 after i.p. carboplatin and paclitaxel at 175 mg/m2 was given before i.p. carboplatin. RESULTS: Ten patients received i.p. carboplatin alone, 10 received cyclophosphamide and 12 received paclitaxel. The ages of the patients, body surface area, serum creatinine, platelet count before chemotherapy, and the total dose of carboplatin in each patient were similar in all groups. The measured AUC, Cmax, T 1/2, and MRT were similar in these groups. The nadir platelet counts were significantly higher (P = 0.0018) in patients treated with i.p. carboplatin with paclitaxel (12.1 +/- 4.3 x 10(4)/mm3) compared with carboplatin alone (5.2 +/- 3.3 x 10(4)/mm3) or with cyclophosphamide (5.2 +/- 4.8 x 10(4)/mm3). The percentage decrease in platelet counts was significantly lower (62.5 +/- 18.2%) in patients treated with paclitaxel than in the other two groups (81.5 +/- 12.6% carboplatin alone, 88.7 +/- 7.9% with cyclophosphamide). CONCLUSION: The addition of paclitaxel or cyclophosphamide to i.p. carboplatin did not alter the pharmacology of serum platinum. Thrombocytopenia was significantly less in patients treated with carboplatin in combination with paclitaxel. The platelet-sparing effect of paclitaxel is not related to changes in the pharmacology of carboplatin.

Age Factors↗

Spinal tanycytic ependymomas.

Three cases of spinal tanycytic ependymoma are reported, a man aged 45 years and two women aged 36 and 55 years. Each patient developed gradual paraparesis over a few months prior to admission. Magnetic resonance imaging showed an enhancing, well-circumscribed tumor in the spinal cord in each case. Histologically, the tumors consisted of monotonous proliferation of long spindle cells with markedly eosinophilic cell processes; focally forming perivascular pseudorosettes. The tumor cells were strongly immunopositive for glial fibrillary acidic protein, S-100 protein and vimentin. Ultrastructurally, in addition to massive intermediate filaments, many tumor cells showed abundant microtubules. Well-developed desmosomes and microvilli/cilia-lined microlumina were occasionally observed. The tumors were grossly totally removed and the patients remain recurrence free at 9, 9, and 2 years postoperatively. Reviewing reported cases including our three cases, tanycytic ependymoma may occur frequently in spinal cord, especially in the cervical region of the spinal cord. Since histologically it resembles pilocytic astrocytoma and schwannoma, tanycytic ependymoma should be included in the differential diagnosis of benign spindle cell tumors of the central nervous system.

Adult↗

Incidence of intrauterine complications in monoamniotic twin gestation.

We compared the incidence of intrauterine complications, such as twin-twin transfusion syndrome, between monochorionic-monoamniotic (MM) and monochorionic-diamniotic (MD) twin gestations. We retrospectively evaluated a series of 11 MM and 211 MD twin gestations managed after 22 weeks' gestation at our hospitals. One MM twin gestation was diagnosed with twin-twin transfusion syndrome based on clinical presentation of polyhydramnios and hydrops. The incidence of twin-twin transfusion syndrome in MM twin gestations (9.1%) was not measurable different from that in the MD twin gestations (7.6%, p=0.09). There were no measurable differences in the incidence of other complications, such as growth discordance >25% or intrauterine fetal demise between the two groups. MM twin gestations should be kept under close management while carefully monitoring for any circulatory imbalance between the twins.

Adult↗

Penile agenesis complicated by Potter sequence.

We present a case of penile agenesis complicated by multicystic dysplastic kidneys and urethral agenesis, which resulted in oligohydramnios, pulmonary hypoplasia and neonatal death. In this case, no external urethral opening was found, and the gastrointestinal tract showed no anomaly. Cases of penile agenesis complicated by Potter sequence with urethral agenesis should be differentiated from those with ectopic urethral openning.

Fatal Outcome↗

Basiliximab induction improves the outcome of renal transplants in children and adolescents.

Thirty-two children and adolescents received their renal transplant at the Montefiore Medical Center, in New York, between October 1996 and May 2000. Twenty-four patients received basiliximab, in addition to tacrolimus and steroids (basiliximab group). The remaining eight patients received only tacrolimus and steroids (non-basiliximab group). The 1-year patient survival rate was 100% in both groups. The 1-year graft survival rate was 87.5% for the basiliximab group and 75% for the non-basiliximab group (P=0.45). The rates of acute rejection in the basiliximab and non-basiliximab groups were 26% and 43%, respectively (P=0.36). However, in recipients with <or=3 HLA mismatches, the rate of acute rejection was zero in the basiliximab group, and 40% in the non-basiliximab group (P=0.04). The beneficial effect occurred despite the fact that tacrolimus was maintained at below the target levels. There were no adverse events directly attributable to the administration of basiliximab. There were no cases of opportunistic infections or post-transplant lymphoproliferative disease. In summary, addition of basiliximab to tacrolimus and prednisone significantly decreased the rate of acute rejection in well-matched patients. Moreover, this effect was manifest at lower, and therefore less toxic, tacrolimus levels.

Adolescent↗

Intrahepatic cholangiojejunostomy for unresectable malignant biliary tumors with obstructive jaundice.

We reviewed our experience with intrahepatic cholangiojejunostomy as a palliative therapy for patients with unresectable malignant diseases involving the ductal confluence or the common hepatic duct. Fifteen patients with malignant biliary obstruction were treated by cholangiojejunostomy at our hospital. Two patients had intrahepatic cholangiocarcinoma, 7 had gallbladder carcinoma, 5 had bile duct carcionoma, and 1 had pancreatic carcinoma. Segment III cholangiojejunostomies were performed in 14 patients and segment V cholangiojejunostomy in 1. Contraindications for surgical resection were locoregional invasion of tumors involving the proper and/or common hepatic artery and portal vein in 15 patients and the presence of hepatic metastases in 6 patients. Liver metastases were detected in 5 of the 7 patients with gallbladder carcinoma. Postoperative complications occurred in 2 patients (13%), but there was no leakage of the cholangioenteric anastomosis in our series. There was no operative mortality after cholangiojejunostomy. Of the 9 patients who survived for more than 6 months after surgery, 7 showed a significant improvement in performance status (PS) (82 +/- 10%) 3 months after the surgery compared with the preoperative PS (70 +/- 7%). Four of the 9 patients had recurrent cholangitis as a late complication, but 4 were completely free from jaundice. Median survival after cholangioenteric bypass was 9 months (range, 2-25 months). With respect to tumor location, the median survival time was 4 months (range, 2-25 months) in patients with gallbladder carcinoma and 15.5 months (range, 12-22 months) in those with bile duct carcinoma. While the median survival period after surgery was only 3 months (range, 2 to 8 months) in the 5 patients with hepatic metastases from gallbladder carcinoma, 2 patients without liver metastasis survived for 9 and 25 months after segment III cholangioenteric bypass. In conclusion, cholangiojejunostomy can provide useful palliation for malignant biliary obstruction when combined with careful patient selection.

Bile Duct Neoplasms↗

Mucinous cystadenocarcinoma of the retroperitoneum: report of a case.

Retroperitoneal mucinous cystadenocarcinomas are extremely rare. A 40-year-old Japanese woman was found to have a retroperitoneal mucinous cystadenocarcinoma of ovarian type. Both ovaries were normal. Concentrations of carcinoembryonic antigen and carbohydrate antigen 19-9 in the cyst fluid were extremely high (810,000 ng/ml and 8,082,000 IU/l, respectively). The tumor varied from benign to borderline and malignant in microscopic appearance, and the lesion was composed of mesothelium-like cells. The histologic and immunohistochemical findings suggested that the tumor developed from mucinous metaplasia of the coelomic mesothelium.

Adult↗

Replacement of the canine inferior vena cava with a seeded graft.

The patency and microscopic findings of gelatin-coated Dacron grafts seeded with endothelial cells and implanted into the inferior vena cava of dogs was evaluated. A total of 25 mongrel dogs were divided into four experimental groups according to whether or not an antiplatelet agent was administered and a seeded or nonseeded graft was implanted. In the groups not given antiplatelet therapy that were implanted with a nonseeded graft, occlusion of the graft occurred soon after surgery. In contrast, in the majority of animals implanted with a seeded graft and given antiplatelet therapy, graft patency was evident for up to 4 weeks postoperatively. In the latter animals, scanning electron microscopy 4 weeks after surgery showed the formation of confluent endothelial-like cells within 5 mm from the anastomosis, as well as insular endothelial-like cells in the central part of the graft. The simple centrifugal seeding method enables endothelial-like cells to adhere to grafts, suggesting that it may be useful in venous replacement.

Animals↗

Effect of filler size on wear resistance of resin cement.

The purpose of this study was to evaluate the effect of filler size on the wear of resin cements. Materials tested included four experimental dual-cure resin cements (Kuraray) consisting of different-sized filler particles. A rectangular box cavity was prepared on the flattened occlusal surface of extracted human molars. Ceramic inlays for the cavities were fabricated using the Cerec 2 system. The Cerec inlays were cemented with the respective cements and adhesive systems according to the manufacturer's directions. The restored surface was finished by wet-grinding with an 800-grit silicon carbide paper. Six specimens were prepared for each resin cement. Half of the specimens were subjected to a three-body wear test for 200,000 cycles, and the others were subjected to a toothbrush abrasion test for 30,000 cycles. The worn surface of each restoration was scanned by a profilometer (Surfcom 475 A) at eight different points for each restoration. The wear value was determined by measuring the vertical gap depth on the profilometric tracings. The data were statistically analyzed by one-way analysis of variance (ANOVA) and Scheffe's test. The results showed that, with increase of filler size, the wear value decreased in the toothbrush test and increased in the three-body wear test. The cement with 0.04-microm filler exhibited the lowest wear value among the materials in the three-body wear test, and the same wear value as the cement with 0.97-microm filler in the toothbrush test. Based upon the results of this study, it is concluded that the wear of resin cements was affected by the filler size as well as the mode of wear test.

Journal Article↗

Cholesteryl ester transfer protein and atherosclerosis in Japanese subjects: a study based on coronary angiography.

We undertook a cross-sectional analysis on CETP and atherosclerosis among Japanese subjects, by means of CETP mass assay, its gene polymorphism and coronary angiogram. The 110 consecutive patients who underwent coronary angiography were enrolled into the study except for those over 70 years and taking lipid-lowering drugs. Association was analyzed among plasma lipid and lipoproteins, CETP mass, its gene polymorphisms and the finding in coronary angiography. Four CETP-deficiency heterozygotes were identified and excluded from the analysis. CETP mass level showed neither significant correlation with the coronary score (CS) (r=0.06, P=0.52) nor the difference between the groups eventually diagnosed as coronary heart disease (CHD) positive and CHD negative (2.36+/-0.57 vs. 2.24+/-0.21, P=0.24). CETP mass correlated with the total and LDL cholesterol (r=0.43, P<0.001; r=0.36, P<0.001, respectively) but not with HDL cholesterol (r=0.08, P=0.40). While I405V polymorphism had no impact on CETP mass, HDL cholesterol or CS, CETP mass was low with TaqIB polymorphism (B1B1>B2B2, P<0.05) only in the low CS group (<4). Among the lipid and lipoprotein, HDL cholesterol had a greater impact than LDL cholesterol on coronary atherosclerosis. We concluded that CETP mass in plasma does not correlate with coronary atherosclerosis as whole in the non-CETP-deficient. However, the B2B2 genotype in CETP TaqIB polymorphism, only when it decreases the CETP level, may act as a protective factor against atherosclerosis. It should also be noted that CETP mass in general correlates to total and LDL cholesterol, so that it would be an indirect atherogenic parameter.

Carrier Proteins↗

Plasma adenosine levels and P-selectin expression on platelets in preeclampsia.

OBJECTIVE: To measure the correlation of plasma adenosine levels with platelet activation in women with preeclampsia. METHODS: Plasma adenosine concentration and expression of P-selectin, a marker for platelet activation, were measured in 18 normal pregnant women and 18 preeclamptic women. The effect of 8-sulfophenyltheophylline, an adenosine receptor blocker, on expression of P-selectin on platelets also was measured. RESULTS: Plasma adenosine level averaged 0.77 +/- 0.11 microM (standard error of the mean [SEM]) in women with preeclampsia, significantly higher than the mean level of 0.47 +/- 0.08 microM in women with normal pregnancies (P <.05). Expression of P-selectin on platelets averaged 7.8 +/- 1.2% in women with preeclampsia, also significantly higher than the mean level of 4.7 +/- 0.7% in normal pregnancy (P <.05). Adenosine receptor blockade significantly increased expression of P-selectin on platelets in women with preeclampsia by 26% (P <.05), which was significantly higher than the 13% increase of activation in those with normal pregnancies (P <.05). CONCLUSION: Adenosine is an established platelet activation suppressor. Increased plasma levels of adenosine in preeclampsia might partially compensate and tend to prevent further excessive platelet activation in women with preeclampsia.

Adenosine↗

Attention-dependent brief adaptation to contour orientation: a high-level aftereffect for convexity?

In contrast to the abundant literature investigating how orientation coding depends on edges defined by various image features, relatively little is known about how coding of orientation might also depend on the two distinct functional roles that oriented edges commonly play. Oriented lines can delineate outline contours of a figure or they can form texture. The results of five experiments using orientation aftereffects measured with brief tests (27 ms, backward masked; adapt-to-test interval=201 ms) provided evidence that brief stimuli (<135 ms) selectively adapt coding of contour-line orientation rather than coding of line-texture orientation. Furthermore, parametric results revealed that the rapidly adapting aftereffects for contour orientation are characterized by (1) broad orientation tuning (peaking at +/-30 degrees to +/-50 degrees from test orientation), (2) indifference as to how the contours are defined (e.g. bright lines, high-pass-filtered lines, faint lines generated by the spatial inhomogeneity of visual sensitivity), (3) rapid saturation at low contrast energy, (4) strong modulation by selective attention, and (5) relative size tolerance. These characteristics appear to parallel those of cells in the high end of the visual form processing pathway (such as inferotemporal cortex). It is thus suggested that the rapidly adapting contour orientation aftereffects reported here may be mediated by high-level neural units that encode global configurations of orientation (e.g. convexity and concavity).

Adaptation, Physiological↗

Preferential gene transfer to BBN-induced rat bladder tumor by simple instillation of adenoviral vector.

OBJECTIVES: We examined the efficacy and safety of intravesical instillation of adenoviral vectors to develop gene therapy protocols for bladder cancer. In this study, an adenoviral vector containing the beta-galactosidase gene was instilled into the rat bladder with N-butyl-N-(4-hydroxybutyl) nitrosamine-induced tumors. We evaluated the effect of the glycosaminoglycan (GAG) layer on adenoviral transduction of bladder urothelium. In addition, we determined the systemic distribution of the adenoviral vector after instillation. METHODS: An adenoviral vector containing either the beta-galactosidase or the herpes simplex virus thymidine kinase gene was transurethrally instilled into the bladder, after which efficacy of gene transfer was evaluated by staining with 5-bromo-4-chloro-3-indolyl-beta-D-galactopyraminoside, and the distribution of the gene was examined by reverse transcriptase-polymerase chain reaction. To determine the extent to which the GAG layer may have inhibited gene transfer by the adenoviral vector, prior to instillation of adenoviral vector, normal bladders were pretreated with either phosphate-buffered saline or HCl, which would destroy the mucosal GAG layer. RESULTS: We found that intravesical instillation of an adenoviral vector caused preferential gene transfer to the tumor cells and that expression of the transferred gene occurred exclusively in the bladder. Removing the GAG layer rendered the normal bladder highly susceptible to adenoviral gene transfer, indicating that GAG on normal mucosa prevented adenoviral gene transfer. CONCLUSIONS: BBN-induced bladder tumors were preferentially transduced by instillation of adenoviral vectors probably due to the lack of GAG layers on their surface. Intravesical instillation of adenoviral vectors does not result in systemic infection. These results encourage the consideration of gene therapy in the treatment of human bladder cancer.

Adenoviridae↗

Methylprednisolone ameliorates cochlear nerve degeneration following mechanical injury.

We investigated whether methylprednisolone sodium succinate can ameliorate cochlear nerve degeneration following compression injury on the cerebellopontine angle portion of the cochlear nerve, using a quantitative animal experimental model that we have developed recently. In this model, cochlear nerve degeneration after compression could be quantitatively evaluated, while cochlear ischemia induced by the compression carefully maintained below the critical limit that causes irreversible damage to the cochlea. Eleven rats were treated with methylprednisolone during the pre- and post-compression period. Two weeks after compression, the numbers of SGC were compared between the rats that received the compression without and with methylprednisolone treatment. Methylprednisolone treatment improved the survival of SGC following cochlear nerve injury statistically highly significantly in the basal turn where the traumatic stress had been less than in the other cochlear turns in our experimental setting. Although it was not statistically significant, greater survival was also observed in the other cochlear turns. The results of this experimental study indicated that at least a portion of injured cochlear nerve had been potentially treatable, and that methylprednisolone might prevent such cochlear neurons from entering into the vicious process of irreversible damaging process.

Animals↗