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Biomedical subjects

S Kitano

Publications and source records attributed to S Kitano.

At least 127 records · Page 7Linked to original sources

Identification of a MAGE-2-encoded human leukocyte antigen-A24-binding synthetic peptide that induces specific antitumor cytotoxic T lymphocytes.

Because MAGE-2 gene is expressed in a wide variety of malignant tumors and HLA-A24 is the most common allele in the Japanese population and is also frequently present in Caucasians, the identification of MAGE-2-encoded peptide presented by HLA-A24 is, therefore, considered to be important in order to develop specific immunotherapy for malignant tumors using peptides as a vaccine. By using a MHC-binding assay, eight peptides derived from MAGE-2 were found to bind with sufficient affinity to the HLA-A24 molecule. When the induction of specific cytotoxic T lymphocytes (CTLs) was examined using a simplified method, the highest human lymphocyte antigen (HLA) binder (EYLQLVFGI) in these peptides was able to elicit CTLs from unseparated peripheral blood mononuclear cells in HLA-A24 healthy donors by stimulation with freshly isolated, peptide-pulsed peripheral blood mononuclear cells as antigen-presenting cells and also by using interleukin 7 and keyhole-limpet hemocyanin in a primary culture. The induced CTL could, thus, lyse HLA-A24 tumor cells expressing MAGE-2, as well as the peptide-pulsed target cells, with antigen specificity in a HLA class I-restricted manner. The identification of this peptide may, thus, be of therapeutic value in peptide-based vaccines for the treatment of several types of malignant tumors expressing MAGE-2.

Amino Acid Sequence↗

Convenient murine pneumoperitoneal model for the study of laparoscopic cancer surgery.

To investigate the effects of laparoscopic surgery on the progression of cancers, it is necessary to establish a reliable and economical animal model. We describe a convenient murine pneumoperitoneal model for the study of laparoscopic cancer surgery. Under anesthesia using diethyl ether, peritoneal cavity was insufflated with gas through an intravenous catheter placed in the left lower quadrant. Syringe pump was used for continuous gas insufflation, and intraperitoneal pressure was measured. Intraperitoneal pressure increased and reached 10 cm H2O when 15 mL of CO2 gas was injected, but fell to 1 cm H2O 5 min after stopping the injection. When the continuous flow was adjusted by syringe pump between 20 and 160 mL/hour, intraperitoneal pressure was easily maintained at 8 cm H2O for >60 min. We believe that this murine model for pneumoperitoneum may be useful for the study of laparoscopic cancer surgery.

Animals↗

A disposable sealing device (Dispo-sand) for conversion between pneumoperitoneum and minilaparotomy.

During laparoscopic procedures, minilaparotomy is a safe technique for removal of large specimens and for the performance of complicated procedures. However, it is time consuming and troublesome to close the minilaparotomy to recreate the pneumoperitoneum. We describe a new device (Dispo-sand) that enables instant conversion between pneumoperitoneum and minilaparotomy.

Disposable Equipment↗

1alpha,25-dehydroxyvitamin D3 synergism toward transforming growth factor-beta1-induced AP-1 transcriptional activity in mouse osteoblastic cells via its nuclear receptor.

The present study demonstrates 1alpha,25-dehydroxyvitamin D3 (1alpha-25-(OH)2D3) synergism toward transforming growth factor (TGF)-beta1-induced activation protein-1 (AP-1) activity in mouse osteoblastic MC3T3-E1 cells via the nuclear receptor of the vitamin. 1alpha-25-(OH)2D3 synergistically stimulated TGF-beta1-induced expression of the c-jun gene in the cells but not that of the c-fos gene. We actually showed by a gel mobility shift assay 1alpha-25-(OH)2D3 synergism of TGF-beta1-induced AP-1 binding to the 12-(O-tetradecanoylphorbol-13-acetate response element (TRE). 1alpha-25-(OH)2D3 markedly stimulated the transient activity of TGF-beta1-induced AP-1 in the cells transfected with a TRE-chloramphenicol acetyltransferase (CAT) reporter gene. Also, a synergistic increase in TGF-beta1-induced CAT activity was observed in the cells cotransfected with an expression vector encoding vitamin D3 receptor (VDR) and the reporter gene. However, the synergistic CAT activity was inhibited by pretreatment with VDR antisense oligonucleotides. In addition, in a Northern blot assay, we observed 1alpha-25-(OH)2D3 synergism of TGF-beta1-induced expression of the c-jun gene in the cells transfected with the VDR expression vector and also found that the synergistic action was clearly blocked by VDR antisense oligonucleotide pretreatment. The present study strongly suggests a novel positive regulation by 1alpha-25-(OH)2D3 of TGF-beta1-induced AP-1 activity in osteoblasts via "genomic action."

Animals↗

Identification and cloning of human G-protein gamma 7, down-regulated in pancreatic cancer.

Differentially expressed genes between normal and cancer tissues of the pancreas were investigated using differential display. Consequently, we identified a fragment cDNA that was expressed in the normal tissue but was rarely expressed in the cancer tissue. This cDNA was screened in cDNA library prepared from the normal pancreatic tissue by rapid amplification of cDNA ends (5'RACE). 859 bp of cDNA was cloned and sequenced, and the inferred amino acid sequence was found to encode a G protein gamma subunit with 98% homology to cow G protein gamma 7 and complete homology to human G protein gamma 7. The decreased expression of the G protein gamma 7 was confirmed by Northern blot assay in twelve pancreatic malignancies which included nine duct cell carcinomas, two cystoadenocarcinomas and one blastoma. Reverse transcriptase (RT)-polymerase chain reaction (PCR) assay showed no expression of G protein gamma 7 in five of six pancreatic carcinoma cell lines and two pancreatic cancer tissues. Immunohistochemical analysis also displayed positive staining in the normal tissue but no staining in the cancer tissue. The findings demonstrated that the reduced or suppressed expression of human G-protein gamma 7 may play an important role in pancreatic carcinogenesis.

Amino Acid Sequence↗

Paget's Disease of the Breast: Report of Five Cases and Review of the Japanese Literature.

Five cases of Paget's disease of the breast are presented, and 76 cases reported in the Japanese literature are analyzed. Paget's disease of the breast is often confined to the nipple-areolar complex(68%), and the duration of symptoms issometimes more than 5 years(25%). Paget's disease without palpable tumor in theunderlying breast is characterized by a low incidence of invasive ductal carcinoma(8%), lymph node metastasis(8%), and stage II or greater disease(0%). These cases indicate that Paget's disease without palpable breast tumor has less aggressive behavior and more benign course than that with palpable breast tumor, and local excision and/or radiation therapy may be an alternative to mastectomy as the initial treatment.

Journal Article↗

Sphingomyelinase and ceramide inhibit formation of F-actin ring in and bone resorption by rabbit mature osteoclasts.

Recent studies have demonstrated that ceramide plays an important role as a second messenger in many kinds of cells. However, it is not known whether apoptosis of and bone resorption by mature osteoclasts are mediated via sphingomyelinase (SMase) and ceramide. Thus, we examined the possible involvement of SMase and ceramide in the induction of apoptosis in and bone resorption by rabbit mature osteoclasts. SMase and C2-ceramide inhibited strongly F-actin ring formation of and bone resorption by the osteoclasts. However, the osteoclast apoptosis was not induced by C2-ceramide. The ceramide inhibition of the bone resorption was suppressed by DL-threodihydrosphingosine, an inhibitor of sphingosine kinase. In addition, we observed that sphingosine-1-phosphate is able to inhibit bone resorption by the osteoclasts. These results suggest an important role of the sphingomyelin pathway in bone resorption by rabbit mature osteoclasts.

Actins↗

Effect of aging on EGF-stimulated replication of specific genes in rat hepatocytes.

EGF-stimulated replication of specific genes was examined in primary hepatocyte cultures from mature (6 months) and senescent (24 months) rats. Basal and EGF-stimulated [3H]thymidine incorporation and DNA polymerase alpha activities, as well as total cellular DNA, were also assessed. The genes examined were dihydrofolate reductase (DHFR) and c-myc, as well as total mitochondrial DNA (mt DNA). Although [3H]thymidine incorporation, DNA polymerase alpha activity, total cellular DNA, DHFR, and c-myc gene specific DNA replication stimulated by EGF are reduced with age, mt DNA replication is not affected by either EGF or age. Chromosomal DNA replication is mediated mainly by DNA polymerase alpha while mt DNA replication is mediated by its own DNA polymerase gamma. Thus, the age-related decline in stimulated DNA replication appears to be associated mainly with the DNA polymerase alpha activation pathway.

Aging↗

Vasopressin antagonist improves renal function in a rat model of pneumoperitoneum.

Pneumoperitoneum (PP) is associated with oliguria and increased plasma arginine vasopressin (AVP) levels. This study investigated the role of AVP in the pathogenesis of oliguria due to PP. Anesthetized and ventilated rats (n = 12) were subjected for 1 h to carbon dioxide PP with an intra-abdominal pressure of 8 mmHg or, as control, at 0 mmHg, before the determination of plasma AVP level. Another group of rats (n = 48) subjected to PP or control conditions was pretreated with the AVP V2 receptor antagonist, OPC-31260 (5 mg/kg), or vehicle, and their renal parameters were measured. Glomerular filtration rate (GFR) was determined by inulin clearance in an additional group of rats (n = 12) subjected to PP with or without pretreatment with OPC-31260. Rats subjected to PP had higher plasma AVP levels than did controls (17.3 +/- 8.1 pg/ml vs 1.5 +/- 0. 6 pg/ml, P < 0.05). In rats pretreated with vehicle, PP decreased urine output, excretion of water, and urea nitrogen, leading to reduced serum osmolality and serum sodium levels as well as elevated blood urea nitrogen levels. OPC-31260 pretreatment improved urine output, excretion of water, and urea nitrogen, thereby preventing changes in serum osmolality, serum sodium levels, and blood urea nitrogen levels. OPC-31260 pretreatment did not affect GFR. Results suggest that plasma AVP contributes to the oliguria due to PP. OPC-31260 may be useful in treating the water retention associated with PP.

Animals↗

Clinical significance of ventricular size in shunted-hydrocephalic children.

For maintaining the intracranial buffering capacity against shunt obstruction, we tried to seek the most suitable size of the lateral ventricles in hydrocephalic children. Thirty-seven shunted-hydrocephalic children who required emergent revision of the shunt were analyzed. At the time of shunt obstruction, the lateral ventricle remained small (0.35 or less than 0.35 on the Evans' index) in 13 patients (Slit-like group), but it enlarged (more than 0.35 on the Evans' index) in 24 patients (Dilated group). The mean age in the Slit-like group was significantly older than in the Dilated group and there was no patient younger than 3 years in the Slit-like group. Compared with the Dilated group, the Slit-like group showed significantly rapid deterioration into lethargy after shunt obstruction. Also, at the time of obstruction CT scans showed a significantly higher rate of narrowing of the ambient cistern. While the shunt was working well before shunt obstruction, the Evans' index was less than 0.33 in all patients of the Slit-like group. In conclusion, because small ventricles after shunt strongly suggest the presence of ventricular tautness, the lateral ventricular size should be maintained at more than 0.33 on the Evans' index in shunted children at an age of 3 or more than 3 years.

Adolescent↗

Bone mineral density in patients taking H2-receptor antagonist.

Osteoporosis after gastrectomy is a common clinical disorder. In gastrectomized patients, decreased gastric acidity may be associated with impaired calcium absorption. This study was undertaken to determine whether patients with chronic use of H2-receptor antagonists (HRA) had demonstrable decreases in bone mineral density (BMD). Thirty-three patients taking cimetidine, ranitidine, or famotidine for more than 2 years were analyzed. We measured BMD of L2-L4 using dual energy X-ray absorptiometry (DXA). Osteoporosis (BMD less than 0.70 g/cm2) was found only in three patients (9%). As compared with healthy controls, age- and sex-matched BMD ranged from 74.4% to 132.9%, with a mean of 97.0%, and was not influenced by the period of HRA use (<5 years versus >5 years or more). Although the age- and sex-matched BMD was different among the kinds of HRA (98.6% for cimetidine, 101.3% for ranitidine, and 85.5% for famotidine), the relationship between the BMD and type of drug was not significant by multivariate analysis. These results indicate that chronic use of HRA has little influence on the degree of BMD, and suggest that decreased gastric acidity is not always associated with osteoporosis after gastrectomy.

Adult↗

Comparison of pneumoperitoneum and abdominal wall lifting as to hemodynamics and surgical stress response during laparoscopic cholecystectomy.

BACKGROUND: Impairments in hemodynamics during pneumoperitoneum (PP) have been noted. This study compared changes in hemodynamics and surgical stress response with PP and abdominal wall lifting (AWL) during laparoscopic cholecystectomy. METHODS: Twenty patients with symptomatic cholecystolithiasis were assigned to PP (n = 10) or AWL (n = 10). Cardiac output (CO), stroke volume (SV), and ejection fraction (%EF) were measured by transesophageal echocardiography. Clearances of para-aminohippurate (CPAH) and sodium thiosulfate (CSTS) were determined as measures of renal function. Levels of interleukin-6, C-reactive protein, white cell count, and neutrophil elastase were evaluated as indicators of surgical stress. RESULTS: In the PP group, CO, SV, and %EF were depressed significantly during pneumoperitoneum. Immediately after and 15 min after insufflation, the CPAH and CSTS were decreased by 78.0% and 73.8%, respectively. None of the hemodynamic parameters changed significantly in the AWL group. Surgical stress response was not different significantly between the two groups. CONCLUSIONS: In contrast to pneumoperitoneum, AWL did not alter cardiac function or renal hemodynamics. AWL may be useful in patients with cardiovascular or renal disorders.

Abdominal Muscles↗

Laparoscopic cholecystectomy in patients undergoing anticoagulant therapy.

We recently performed a laparoscopic cholecystectomy on three patients receiving preoperative oral anticoagulant therapy. The patients requiring anticoagulants for pre-existing cardiac conditions have the following risks at surgery: thromboembolism, hemorrhage, endocarditis, and cardiopulmonary dysfunction. In patients receiving anticoagulant therapy, one must thus maintain a balanced international normalized ratio of the prothrombin time to prevent thromboembolism or hemorrhage. Warfarin sodium was discontinued preoperatively in all patients. Heparin sodium was individualized according to each patient's risk of thromboembolism. As a result, these patients all underwent a laparoscopic cholecystectomy without complications. Attention was paid to achieve hemostasis in the operative field and the trocar inserted sites during the procedure. The administration of warfarin sodium was resumed on the first postoperative day in all patients. Restarting warfarin sodium early also helps to simplify postoperative management. A broad spectrum of antibiotic therapy was also used to reduce the risk of endocarditis. Each patient's cardiopulmonary function was carefully monitored. The minimal invasion experienced during a laparoscopic cholecystectomy may thus facilitate the management of gallstones in patients receiving systemic anticoagulation treatment based on the findings of this limited series.

Adult↗

Laparoscopic enucleation of a pancreatic insulinoma: report of a case.

We report herein the case of a 48-year-old Japanese woman in whom a pancreatic insulinoma was successfully treated by laparoscopic enucleation. The patient presented after developing episodic neurohypoglycemic symptoms, and an insulinoma in the pancreatic tail, 1.0 cm in diameter, was diagnosed by the results of biochemical and radiological examinations. A laparoscopic intraoperative ultrasonogram demonstrated a solitary hypoechogenic tumor in the pancreatic tail. After the tail and body of the pancreas with the spleen were mobilized, laparoscopic enucleation was performed without any complications. The total operative time was 225min and the estimated blood loss was 20 ml. Serial blood sugar measurements demonstrated a sharp rise in blood sugar levels at the time of enucleation. The patient's postoperative course was uneventful, and she was discharged on the seventh postoperative day. She has remained well for 33 months following surgery without any hypoglycemic symptoms.

Female↗

An additional variant of the persistent primitive trigeminal artery: accessory meningeal artery--antero-superior cerebellar artery anastomosis associated with moyamoya disease.

Persistent embryological carotid-basilar anastomoses are rare. There has been no report on persistent anastomosis between the accessory meningeal artery and the antero-superior cerebellar artery. We describe a 3-year-old boy with moyamoya disease manifesting such a congenital vascular anomaly, namely, a large anastomosis between the accessory meningeal artery and the antero-superior cerebellar artery associated with marked hypoplasia of the basilar artery. This persistent vascular anomaly is considered embryologically as an additional variant of the persistent primitive trigeminal artery, i.e., a "stapedo-trigemino-cerebellar" variant.

Basilar Artery↗

Laparoscopic splenopexy for pediatric wandering spleen.

Wandering spleen is an uncommon condition, showing a splenic hypermobility that results from laxity or maldevelopment of its suspensory ligament. This condition results in constant danger of splenic torsion and infarction. Wandering spleen was diagnosed in a 2-year-old girl who complained of intermittent abdominal pain, and viability of the spleen was confirmed by doppler ultrasound scan. Elective laparoscopic splenopexy was performed by anchoring the spleen wrapped in absorbable mesh. To our knowledge, this is the first reported case of laparoscopic splenopexy for wandering spleen. The authors believe that this approach is a safe and effective procedure for wandering spleen with the advantage of minimally invasive surgery.

Child, Preschool↗

Decreased circulating levels of vitamin K and 25-hydroxyvitamin D in osteopenic elderly men.

Changes in the circulating factors participating in involutional osteoporosis have been intensively investigated in women, but little is known about this in men. We investigated the possible participation of circulating factors including testosterone, vitamin D metabolites, and vitamins K1 and K2 in osteopenia in elderly men. In a group of 27 ambulatory men aged 74 +/- 10 years (mean +/- SD; range, 60 to 90), the bone mineral density (BMD) of the second to fourth lumbar vertebrae was measured by dual-energy x-ray absorptiometry (DXA) and expressed as a Z score, the age-adjusted BMD value for the Japanese population (mean +/- SD, 0 +/- 1). Although the plasma level of total testosterone significantly decreased with age in the group, it did not significantly correlate with the Z score. However, the plasma levels of 25-hydroxyvitamin D (25-OHD), phylloquinone, menaquinone-7 (MK-7), and albumin were significantly positively correlated with the Z score. Moreover, plasma 25-OHD and both phylloquinone and MK-7 were significantly positively correlated in the subjects. These observations suggest that depressed circulating levels of 25-OHD and vitamin K concomitantly and cooperatively participate in osteopenia in elderly men, which may reflect the etiology of the type II moiety of involutional osteoporosis.

Aged↗

A transient increase in endogeneous erythropoietin levels after paediatric liver transplantation.

We investigated whether liver transplantation affects endogeneous erythropoietin (EPO) synthesis. Serum EPO levels were measured before transplantation and during the peri-transplant period in ten consecutive paediatric patients who had received a liver allograft without recombinant EPO therapy. All patients were anaemic on post-operative day 1 (POD 1); however, the haemoglobin levels of three patients gradually increased and required phlebotomy on POD 5-9. The serum levels of EPO in all patients were within the normal range before surgery, but six of the ten patients had a transient increased level of EPO at 1248 h after transplantation. A transient increase of endogeneous EPO following paediatric liver transplantation may be associated with extramedullary erythropoiesis in human liver grafts.

Child↗