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Biomedical subjects

Y Tsuchida

Publications and source records attributed to Y Tsuchida.

At least 37 records · Page 2Linked to original sources

Intestinal motility in an in vivo rat model of intestinal ischemia-reperfusion with special reference to the effects of nitric oxide on the motility changes.

BACKGROUND: To clarify the relation between intestinal ischemia-reperfusion (IR) and dysmotility, the authors investigated changes in the motility pattern in the duodenum and jejunum in an in vivo rat model of IR when artery- (and vein-) fed jejunum was clamped transiently. The authors also studied the effect of nitric oxide on the motility changes in this model by means of the administration of L-NAME (N(G)-nitro-L-arginine methyl ester) or S-methylisothiourea sulfate (SMT). MATERIALS AND METHODS: A force transducer was sutured onto the serosal side of the duodenum or jejunum. After a 3-to 4-day recovery period, contractions were recorded during periods of preischemia, ischemia (60 minutes), and reperfusion (90 minutes). An intestinal IR was produced by clamping and releasing the mesenteric artery and vein with artery forceps. RESULTS: In the jejunum, there was a prolongation in the duration of contraction and there were decreases in the number of contractions (NC) during the IR. When treated with L-NAME, no decrease in the NC was observed during the 45 to 90 minutes after reperfusion. S-methylisothiourea sulfate did not affect the IR-induced motility changes significantly. In the duodenum, there was a prolongation in the duration of contraction and a decrease in the NC and AC only during the reperfusion. L-NAME or S-methylisothiourea sulfate inhibited the decreases in the NC during the reperfusion. CONCLUSIONS: Intestinal IR causes motility changes in the ischemic site during the IR and in the nonischemic site during the reperfusion. The IR-induced motility changes partly depend on nitric oxide production.

Animals↗

Effects of recombinant human endostatin on a human neuroblastoma xenograft.

New antitumor agents must be added to the current neuroblastoma treatment regimens to improve the clinical results. We investigated whether recombinant human endostatin (rhEndostatin), an antiangiogenic agent, is effective against human neuroblastoma in the human neuroblastoma xenograft model designated TNB9. When tumors on the back of nude mice grew to a weight of 90-95 mg, rhEndostatin 10 mg/kg/day was administered subcutaneously every day for 10 consecutive days. Mean relative tumor weight in mice administered rhEndostatin (n=5) was significantly less than that in controls (n=12) on days 2, 4, and 6 after the start of administration (p<0.01 on day 2, p<0.05 on days 4 and 6), and regression of tumor growth (TRW<1.0) was marked on day 2. The maximum inhibition rate (MIR) by rhEndostatin was 46.4%, indicating inefficacy, but it may not be appropriate to apply Battelle Columbus Laboratories criteria to this experimental model because rhEndostatin is a protein. After day 8, tumors in the experimental group increased in weight and were not statistically significantly different from those in controls. Recombinant human endostatin was used in tumors in the arterial system of the mouse in this experiment because eventually rhEndostatin, not recombinant mouse endostatin, may be used to treat advanced neuroblastoma in the clinical setting. The results show that there is little cross-reactivity of rhEndostatin with the human and mouse models and indicate that rhEndostatin could become an effective agent for the treatment of human neuroblastoma.

Animals↗

Case-control study of perinatal factors and hepatoblastoma in children with an extremely low birthweight.

BACKGROUND: There is a significant association between hepatoblastoma and low birthweight. A case-control study was conducted to reveal risk factors for hepatoblastoma in children of extremely low birthweight (< 1,000 g). METHODS: Prenatal and postnatal histories, including parental histories, of 12 hepatoblastoma cases and 75 birthweight-matched controls were compared. RESULTS: The gestational age of the hepatoblastoma cases (23-32 weeks: median 25 weeks), tended to be lower than that of the controls (23-36 weeks; median, 27 weeks; P = 0.072). The time for an infant's bodyweight to return to the same level as the birthweight also tended to be longer in hepatoblastoma cases than in controls (P = 0.055). All hepatoblastoma cases received oxygen therapy for a period of 4-508 days (median 114 days), which was significantly longer than the 0-366 days (median 62 days) in the controls (P = 0.022). Furosemide was given to all hepatoblastoma cases and was used for a significantly longer period in these infants (6460 days; median 89 days) than in the controls (0-241 days; median 44 days P = 0.027). A univariate Cox regression demonstrated that the time taken to regain bodyweight at birth and the duration of both oxygen therapy and furosemide treatment were significantly associated with the development of hepatoblastoma (hazard ratio (HR)= 1.044, P= 0.013; HR = 1.006, P= 0.001; and HR = 1.007, P= 0.001, respectively). Although there were significant correlations between the factors, a multivariate Cox regression analysis identified the duration of oxygen therapy as a significant independent risk factor (HR = 1.006, P = 0.001). CONCLUSIONS: Oxygen therapy and furosemide treatment, along with the rate of growth, are risk factors for the development of hepatoblastoma in children of extremely low birthweight, and the duration of oxygen therapy is the most important factor in predicting the development of hepatoblastoma. Further studies are necessary to determine the real reasons for the development of hepatoblastoma and to protect children of low birthweight from the development of cancer.

Case-Control Studies↗

Risk of contralateral manifestation in children with unilateral inguinal hernia: should hernia in children be treated contralaterally?

PURPOSE: This study was done to identify risk factors for metachronous manifestation of contralateral inguinal hernia in patients with unilateral inguinal hernia. METHODS: Characteristics of 156 patients with metachronous contralateral hernia were compared with those of 156 patients with unilateral hernia who were ascertained not to have presented with contralateral hernia. RESULTS: There was a tendency for the hernia to be more often on the left side in 88 of 156 patients (56.4%) with contralateral manifestation compared with 70 of 156 patients (44.9%) in the control group (P =.054). The age at hernia repair of the patients with contralateral manifestation, 1 to 120 months (median, 14 months), was significantly younger than the 1 to 149 months (median, 20 months) of the control patients (P =.016). More patients with contralateral manifestation had a family history of inguinal hernia, and the percentage, 24.4%, was significantly higher than the 14.7% in the control group (P =.046). A univariate analysis with the Cox regression models found that hernia on the left side and a positive family history were significantly associated with the metachronous manifestation of contralateral hernia (hazard ratio [HR], 1.40; P =. 037 and HR, 1.59; P =.013, respectively). CONCLUSION: The risk of metachronous manifestation of contralateral hernia is high in patients with left-side hernia and in those with a family history, and the incidence of contralateral hernia is at most 10% in these patients. The authors think that the incidence is still too low to justify routine exploration and surgery for a patent processus vaginalis. Contralateral exploration should therefore be reserved for high-risk patients in whom second anesthesia and surgery have to be avoided.

Adolescent↗

Reduced or absent expression and codon 201Gly/Arg polymorphism of DCC gene in rhabdomyosarcoma and Ewing's sarcoma/PNET family.

Genetic alterations occurring in various chromosomes have been described in many human tumors. The DCC gene was originally identified in colorectal cancer and was reported as a tumor suppressor gene that might be related to tumor metastasis. We investigated 10 cell lines and 15 fresh tumors of childhood rhabdomyosarcoma, 7 cell lines of Ewing's sarcoma, and 4 cell lines of primitive neuroectodermal tumor (PNET) for the expression and mutation of DCC gene by RT-PCR analysis and PCR-single stranded conformation polymorphism (SSCP) analysis. Twenty-five pairs of primers were used for PCR-SSCP. Six of ten (60%) cell lines of rhabdomyosarcoma and 3 of 7 (43%) cell lines of Ewing's sarcoma showed reduced or absent expression of DCC gene. There was no mobility shift within 24 exons by SSCP analysis, although 3 types of polymorphism were found at codon 201 in exon 3. Direct sequencing of different bands showed types I, II, and I/II representative of codon 201Gly, codon 201Arg, and codon 201Gly/Arg, respectively. The proportion of type I between fresh rhabdomyosarcoma and normal controls was not significant. Our results suggested that the inactivation of DCC gene may play a role in the pathogenesis of a subset of rhabdomyosarcoma and Ewing's sarcoma.

Adolescent↗

Evaluation of leukocyte dynamics in choroidal circulation with indocyanine green-stained leukocytes.

PURPOSE: To develop a new method with which to visualize leukocytes moving through the choroidal vessels of pigmented animals and enable the evaluation of leukocyte dynamics in the choroidal microcirculation. METHODS: Pigmented rabbits and monkeys were used in this study. Leukocytes, collected by centrifugal separation of autologous blood, were stained with indocyanine green (ICG) dye. The ICG-stained leukocyte fluid was injected into the vein, and the fundus image was obtained with a scanning laser ophthalmoscope. The image was recorded on videotapes and analyzed with a personal computer-based image analysis system. RESULTS: In pigmented rabbits, fluorescent leukocytes moving in the choroidal circulation were clearly visible for more than 1 hour. In monkeys, distinct fluorescent dots were seen moving approximately 50 to 200 microm in the foveal avascular zone for more than 30 minutes after the injection of the ICG-stained leukocyte fluid. Dim fluorescent dots were seen moving in the fundus. Although the movement of these dim dots was difficult to trace, they seemed to be moving in the choroidal vessels. In the rabbits, the mean flow velocity of leukocytes moving without plugging was 0.48 +/- 0.14 mm/sec in the peripheral choriocapillaris. In the monkeys, the mean flow velocity of distinct fluorescent leukocytes without plugging was 2.45 +/- 0. 48 mm/sec in the posterior choroid. CONCLUSIONS: In pigmented rabbits and monkeys, this method allows visualization of leukocytes passing through the choroidal vessels and provides a new way to investigate, noninvasively and in vivo, leukocyte dynamics in the choroidal microcirculation.

Animals↗

Incidence of intrahepatic biliary cysts in biliary atresia after hepatic portoenterostomy and associated histopathologic findings in the liver and porta hepatis at diagnosis.

BACKGROUND/PURPOSE: The association of intrahepatic biliary cysts in biliary atresia (BA) after hepatic portoenterostomy has drawn the attention of many pediatric surgeons and has become an important subject in clinical management, but the incidence and causes of this association are not well known. METHODS: During the last 14 years, we operated on 33 BA patients by hepatic portoenterostomy. Five patients could not be followed up over a 1-year period, so the remaining 28 patients had their intrahepatic structure investigated by periodic magnetic resonance imaging (MRI), and were confirmed at autopsy. The authors also reviewed the preoperative conditions of these patients and the histopathologic changes in the liver biopsy and the porta hepatis specimens taken at portoenterostomy. RESULTS: (1) Intrahepatic biliary cysts were found in 6 of the 28 patients studied (21%). Of 16 patients who were operated on after 1989 and are undergoing follow-up by MRI, 4 (25%) had cysts. (2) Five of the 6 patients with cysts had episodes of cholangitis before or at the time of discovery of the cysts, and 4 of them have had their jaundice reappear since the discovery of the cysts. (3) The intralobular spaces (ILS) with fibrosis and the number of bile ducts had increased in the group with cysts compared with those in the group without cysts. (4) The bile duct maximum size in the porta hepatis (PH) was similar in the groups with and without cysts, but a denudation of the mucosal lining cells in the duct, and a fibrosis and inflammation around the duct had increased in the group with cysts compared with those in the group without cysts. (5) Statistically, the fibrosis found in the ILS and the inflammation around the bile duct found in the PH were induced as a correlative factor affecting cyst formation. CONCLUSIONS: The association of intrahepatic biliary cysts in BA after portoenterostomy is frequent. The fibrous change in the ILS and the inflammatory process around the bile ducts might be potential causes of cyst formation.

Bile Ducts↗

A case of well-differentiated, fetal-type hepatoblastoma with very low serum alpha-fetoprotein.

Serum alpha-fetoprotein (AFP) is elevated in 96.6% of infants and children with hepatoblastoma and hepatocarcinoma. Serum AFP was of normal level in only one case of immature-type hepatoblastoma, and very low in only one case of fetal-type hepatoblastoma among 43 cases reviewed in 1986. Recently, a case of hepatoblastoma with very low serum AFP was encountered in the authors' surgical department. In October 1998, a 55-month-old girl was admitted. Her birth weight was 717 g. A large space-occupying lesion (SOL) located in the left lobe of the liver was seen by magnetic resonance imaging (MRI), and her serum AFP level was 322 ng/mL with a subfractionation pattern of the "benign liver disease" type based on reactivity with lens culnaris hemagglutinin and concanavalin A. The patient underwent successful left lobectomy, and histological examination showed that the tumor, weighing 268 g, was hepatoblastoma of the well-differentiated, fetal type. Immunohistochemistry findings for AFP were negative. A hepatic mass in infants and children with low serum AFP level indicates the presence of either well-differentiated or immature hepatoblastoma, or fibrolamellar hepatocellular carcinoma. Subfractionation of AFP may contribute to the differential diagnosis of these subtypes.

Child, Preschool↗

Development of a polyclonal antibody with defined specificity against synthetic peptides from the N-myc oncoprotein using multiple antigen peptide and hemocyanin conjugation methods.

BACKGROUND/PURPOSE: The importance of determining N-myc oncoprotein rather than genomic N-myc amplification has been emphasized in neuroblastoma, especially in an international project to register biological risk factors in all neuroblastomas. A method to raise a specific polyclonal antibody against the N-myc oncoprotein in large quantities was sought using the synthetic antigen peptide and the multiple antigen peptide (MAP) method. METHODS: Two sets of peptides, HGRGPPTAGSTAQSPG and GVAPPRPGGRQTSGGDH, conserved in the N-myc oncoprotein were synthesized. The hemocyanin-conjugated peptides and the lysine core-conjugated (multiple antigen peptide method) peptides were injected into rabbits with adjuvant. IgG fractions precipitated from the sera were purified on an affinity column coupled with these peptides, and the potency and specificity of the purified IgGs were examined by immunoblotting and immunohistochemistry in small cell lung cancer cell lines with known positivity-negativity of amplification and expression of N-myc, c-myc, and L-myc. RESULTS: Peptides conjugated to the lysine core raised more potent antibodies than those conjugated to hemocyanin. Purified IgG against GVAPPRPGGRQTSGGDH reacted positively with an N-myc-amplified lung cancer cell line, but not with N-myc-unamplified and c-myc/L-myc-amplified cell lines on either immunoblotting or immunostaining. This IgG strongly stained the nuclei of cells in a series of surgical specimens and cell lines of neuroblastoma with N-myc amplification. CONCLUSION: A polyclonal antibody specific for a synthetic peptide from the N-myc oncoprotein was thus obtained and will find wide international use.

Animals↗

Choroidal abnormalities in Behçet disease observed by simultaneous indocyanine green and fluorescein angiography with scanning laser ophthalmoscopy.

OBJECTIVE: To examine choroidopathy in patients with Behçet disease. DESIGN: Prospective clinical study. PARTICIPANTS: Thirty-three patients (63 eyes) with Behçet disease. INTERVENTION: Patients underwent simultaneous indocyanine green (ICG) and fluorescein angiography with a double detector of scanning laser ophthalmoscopy. MAIN OUTCOME MEASURES: Angiographic findings recorded on videotapes were evaluated. The relation of angiographic findings with systemic activity and aqueous inflammation was also analyzed. RESULTS: Fluorescein angiography showed leakage in varying degrees from retinal vessels in 30 patients (53 eyes, 84%). The ICG angiographic findings were choroidal vascular wall staining in 16 eyes (25%), hyperfluorescent spots in 42 eyes (66%) and hypofluorescent plaques in 22 eyes (35%), both of which were not evident with fluorescein, leakage from choroidal vessels in 3 eyes (5%), and irregular filling of choriocapillaris in 11 eyes (17%). These findings did not have a statistically significant correlation with the presence or absence of aqueous inflammation or oral aphthous ulcerations. CONCLUSIONS: The patients with Behçet disease showed choroidal abnormalities, which could be revealed only by ICG angiography, but not with funduscopy or fluorescein angiography. Simultaneous ICG and fluorescein angiography would be useful for examining choroidal lesions in Behçet disease.

Adult↗