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Biomedical subjects

N Ohnuma

Publications and source records attributed to N Ohnuma.

At least 55 records · Page 3Linked to original sources

Antitumor vaccine effect of irradiated murine neuroblastoma cells producing interleukin-2 or granulocyte macrophage-colony stimulating factor.

We have examined vaccination effects of cytokine-producing murine neuroblastoma cells (C1300). C1300 cells retrovirally transduced with interleukin-2 (IL-2) or granulocyte macrophage-colony stimulation factor (GM-CSF) gene were established. Their in vitro proliferation rates and the class I expression of major histocompatibility complex were not different from those of wild-type cells. Five-Gy irradiation of the respective cytokine producers slightly reduced the in vitro cell growth but treatment with 15 Gy significantly impaired the proliferation. In contrast, the secretion of both cytokines from the respective transduced cells was retained compared with the cell growth. We immunized syngeneic mice with irradiated wild-type cells as a control or cytokine-producing cells and challenged the mice with unirradiated wild-type cells. The control mice developed tumors of the challenged wild-type cells, on the contrary, the mice which had received irradiated IL-2 or GM-CSF producers did not. Thus, IL-2- or GM-CSF-expressing syngeneic tumor cells can be potentially used as a tumor vaccine by inducing protective immunity against low immunogenic neuroblastomas in the inoculated hosts.

Animals↗

[TNM classification--pediatric tumors].

The clinical and postsurgical TNM classifications (cTNM and pTNM) for neuroblastoma (NB), nephroblastoma (WT) and soft tissue sarcomas were presented in 1982 by the TNM Committee in UICC in collaboration with SIOP. The Japanese TNM Committee proposed new pTNM systems (J-pTNM) for NB and WT, and new cTNM and pTNM system for primary liver carcinoma in infants and children (HT). These pTNMs were based on the staging systems developed by the Malignant Tumor Committee of the Japanese Society of Pediatric Surgeons. The proposal of subdivision of M category in NB was presented for testing the new telescopic ramifications of TNM. The TNM for HT was added as a new classification recommended for testing. The effectiveness of these TNM systems was assessed using NB, WT and hepatoblastoma (HB) cases which were registered in collaborating institutes. The analyses suggested that pTNM, especially the J-pTNM system in NB, WT and HT were effective for the assessment of prognoses, although cTNM systems were not enough to assess the extent of the disease.

Child↗

The role of ERCP in biliary atresia.

BACKGROUND: It is not easy to discriminate between infantile hepatitis and biliary atresia in spite of several diagnostic tests including laboratory analyses, ultrasound, and hepatobiliary scans. ERCP is the most useful procedure for visualization of the extrahepatic biliary system, but ERCP is still an uncommon procedure in children. METHODS: ERCP examination was performed in 52 infants with biliary atresia (10 with infantile hepatitis, 5 with congenital biliary dilatation, 3 with paucity of intrahepatic bile duct, 2 with duodenal atresia, and 1 with postoperative jaundice of hepatoblastoma) aged from 8 days to 300 days (mean, 71 days). RESULTS: ERCP was successful in 47 with biliary atresia, in 9 with infantile hepatitis, and 10 with another disease. Liver biopsy was performed in 1 infant with hepatitis in whom the cannulation failed; in 9 with hepatitis in whom the cannulation was successful, exploratory laparotomy could be avoided. The ERCP findings in 46 patients with biliary atresia (excluding 1 in whom evaluation could not be performed because of poor x-ray quality) were classified into four patterns. CONCLUSIONS: A success rate of ERCP examinations in infants was 88%, so ERCP is recommended to make a correct decision regarding the need for surgery in cholestatic disorders.

Biliary Atresia↗

Detection of tumor thrombus in children using color Doppler ultrasonography.

Color Doppler ultrasonography (CDUS), which provides information regarding both the tissue and the blood flow simultaneously in real time, is a relatively new and noninvasive technique for the evaluation of organ perfusion. The authors investigated the usefulness of CDUS in the detection of tumor thrombus in 34 children who had malignant tumor (21 neuroblastomas, 2 Wilms' tumors, 5 hepatoblastomas, 2 rhabdomyosarcomas, and 4 others) who underwent CDUS between April 1992 and March 1995 in our department. The CDUS showed tumor thrombus in four patients (11.8%). Three thrombi (in one patient each with neuroblastoma, Wilms' tumor, and hepatoblastoma) were situated in the inferior vena cava, and one (in a patient who had hepatoblastoma) in the portal vein. Each tumor thrombus was monitored and followed up using CDUS every month during the entire clinical course; two of the four thrombi remained despite intensive treatments. The authors have found CDUS to afford rapid and noninvasive detection of tumor thrombus, and it proved useful not only in the detection of tumor thrombus but also in its follow-up in these children who had malignant tumor.

Child, Preschool↗

Endoscopic variceal ligation using a clipping apparatus in children with portal hypertension.

BACKGROUND AND STUDY AIMS: Endoscopic variceal sclerotherapy (EVS) is a procedure frequently used to control bleeding from esophageal varices in adults. The use of EVS has been restricted in children due to the associated risks. The present paper describes the safety and efficacy of a new apparatus for endoscopic variceal ligation with clipping (EVLC). PATIENTS AND METHODS: Endoscopic variceal ligation using a clipping apparatus (HX-3 L, Olympus, Tokyo, Japan), was carried out in 12 children with portal hypertension (four with extrahepatic portal vein obstruction and eight with congenital biliary atresia; four boys and eight girls, age range 2-14 years). A total of 417 variceal clipping procedures were carried out in 56 separate EVLC sessions; 118 esophageal varices and 65 gastric fundic varices were ligated using 417 clips. Initially, the EVLC sessions were repeated at approximately monthly intervals until the varices were eradicated, but the interval was gradually extended to twice a year or once a year. RESULTS: Varices were successfully ligated at the first attempt in 414 (99.3%) of the 417 clipping procedures. The esophageal varices were initially eradicated in all patients. The follow-up period ranged from nine to 48 months, and complete variceal eradication or reduction of the grade of the varices was obtained in 11 of the 12 patients after initial eradication during this period. CONCLUSIONS: These data indicate that EVLC offers advantages in the treatment of patients with esophageal varices combined with gastric fundic varices.

Adolescent↗

Endoscopic retrograde cholangiopancreatography (ERCP) in biliary tract disease of infants less than one year old.

We performed a total of 75 examinations with endoscopic retrograde chlangiopancreatography (ERCP) in 73 infants aged from 8 days to 300 days (mean 71 days) between 1977 and 1995. ERCP examination was performed with a prototype duodenoscope and was successful in 47 of 52 examinations in biliary atresia, 9 of 11 in neonatal hepatitis, all 4 in paucity of intra-hepatic bile duct, 4 of 5 in congenital biliary dilatation, 1 of 2 in duodenal stricture, and 1 case of in postoperative jaundice of hepatoblastoma. In 46 infants with biliary atresia, excluding one in whom the findings could not be evaluated due to poor x-ray image quality, we distinguished the following four patterns of ERCP findings: Pattern 1, only the pancreatic duct could be demonstrated and no bile duct was visualized (76%); Pattern 2, only a part of the distal common bile duct with the pancreatic duct was visualized (2%); Pattern 3, the entire length of the common bile duct with the pancreatic duct was visualized without the gallbladder and the common hepatic duct (4%); and Pattern 4, the common bile duct and the gallbladder with the pancreatic duct were visualized without the common hepatic duct (18%). In all of these 46 patients, laparotomy, an operative cholangiogram, and histological evaluation of the biliary duct were performed. In 9 neonates with neonatal hepatitis, the biliary tract was opacified and biliary atresia was excluded. Laparotomy was thus avoided in these neonates. There was no complication caused by either ERCP or by anesthesia.

Anesthesia↗

[Long-term effects of a selective alpha 1-adrenergic inhibitor on right and left ventricular masses in patients with chronic pulmonary disease].

We examined the effect of one year of treatment with the selective alpha 1-adrenergic inhibitor doxazosin on right ventricular mass (RV mass), left ventricular mass (LV mass), and arterial blood gases. The subjects were 24 outpatients (18 men and 6 women, mean age 68.3 +/- 9.4 years) with chronic pulmonary disease complicated by hypertension who were clinically stable. One year of drug therapy was associated with significant decreases both in systolic pressure (159 +/- 15.2 vs 125.8 +/- 14.1 mmHg, p < 0.05, n = 24), and in LV mass index (101.0 +/- 13.4 vs 97.6 +/- 11.8 gm-2, p < 0.05), n = 24). We obtained the RV mass index by multiplying the thallium score RV/LV count and the LV mass index obtained by echocardiography. One year of drug therapy was associated with a significant increase in RV mass index (42.9 +/- 31.2 vs 53.6 +/- 30.5 gm-2, p < 0.05, n = 8). Vital capacity decreased (2.18 +/- 1.95 vs 1.95 +/- 0.57 l, p < 0.05, n = 24), but PaO2 improved (77.3 +/- 17.2 vs 82.2 +/- 2.4 mmHg, p < 0.05, n = 24). These data indicate that doxazosin can decrease blood pressure and can depress the left ventricle with no adverse effect on oxygenation in patients with chronic pulmonary disease complicated by hypertension. The worsening of RV hypertrophy may have been caused by a mechanism different from the one that caused LV hypertrophy, and by an increase in the work load on the right ventricles secondary to lung deterioration.

Adrenergic alpha-Antagonists↗

[Effect of percutaneous transluminal mitral commissurotomy on pulmonary function and on the pulmonary vasculature].

We evaluated the therapeutic effect of percutaneous transluminal mitral commissurotomy (PTMC) on pulmonary function, and the damage caused to pulmonary vasculature by transient occlusion of the mitral valve during PTMC in patients with mild mitral stenosis. Pulmonary function tests were done and serum thrombomodulin was measured in 6 patients before and after PTMC. The mean pulmonary arterial pressure and mean pulmonary arterial wedge pressure decreased significantly from the control values, and the decreases were proportional to the increase in the area of the mitral valve. VC, %VC, and DLco were in the normal range before and after PTMC but PEFR, FEV1%, FEV1, V50, V25, and V50/V25 were significantly higher after PTMC. Change in the area of the mitral valve correlated with the changes in FEV1% (r = 0.841), in V50 (r = 0.624), and in V25 (r = 0.697). The serum thrombomodulin levels before and after PTMC did not differ. We conclude that pulmonary dysfunction in patients with mild mitral stenosis MS is mainly due to an obstructive ventilatory defect, and that PTMC can correct this dysfunction without damaging the pulmonary vasculature.

Aged↗

Evaluation of patients with advanced neuroblastoma surviving more than 5 years after initiation of an intensive Japanese protocol: a report from the Study Group of Japan for Treatment of Advanced Neuroblastoma.

In January 1985, a single protocol consisting of cyclophosphamide, vincristine, tetrahydropyranyl adriamycin, and cis-platinum for the treatment of advanced neuroblastoma was begun nationwide in Japan and was found to improve clinical results significantly in terms of 2- or 3-year survival rate. Between January 1985 and December 1988, 113 eligible patients (7 infants younger than 12 months of age with stage IVA disease and 106 patients aged 12 months or older with stage III or IV disease) were enrolled and followed up for 5 years or more after initiation of treatment, as of March 1994. In this study, the usefulness of the protocol for the treatment of advanced neuroblastoma was evaluated with survival rates in relation to age, tumor site, stage, and N-myc amplification for patients surviving more than 5 years after initiation of the protocol. Fifty of the 113 patients were alive 5 years or more after initiation of the treatment, 39 without any episodes of disease recurrence. Fourteen (70%) of 20 patients with stage III, 6 (50%) of 12 with stage IVB, and 24 (30%) of 81 with stage IVA disease were alive and disease-free 5 years after initiation of the protocol. Twenty (56%) of 36 patients without N-myc amplification were alive at 5 years after initiation of the protocol. Only one patient who was alive without evidence of the disease at 5 years had recurrence afterward.

Antineoplastic Combined Chemotherapy Protocols↗

Histopathologic analysis of bone marrow and bone metastasis in murine neuroblastoma.

To elucidate the development of bone metastasis in human neuroblastoma, bone marrow and bone metastases were analysed histologically in a hematogeneous metastasis model of murine neuroblastoma. The bone marrow metastasis occurred initially in the bone marrow sinusoid where tumor cells adhered and extravasated to bone marrow parenchyma, resulting in the formation of nodular lesions in the medullary cavity. The nodular lesions eventually progressed to diffuse lesions segmentally occupying the medullary cavity. During the establishment of the diffuse lesions, tumor cells invaded cancellous bone and/or bone cortex, resulting in bone metastasis. Such nodular or diffuse bone marrow metastatic lesions occurred sporadically in a variety of bones. To improve the results of treatment for neuroblastoma, the characteristics of the bone marrow and the bone metastases demonstrated in this study should be considered in the diagnosis and treatment of this disease.

Animals↗

Renal impairment after surgical resection of neuroblastoma.

Postoperative renal impairment was observed in 6 of 58 patients with neuroblastoma treated between November 1982 and March 1994. To clarify the clinical characteristics of these patients (renal-impairment group), they were compared with 26 patients treated during the same period who did not have renal impairment (no-impairment group). The incidence of primary retroperitoneal tumor and invasion of the hilum renalis was clearly higher in the renal-impairment group than in the group with no impairment. However, no significant difference was observed with respect to age, tumor laterality, or stage of disease. The results of postoperative biochemical examinations showed that the serum concentrations of lactic dehydrogenase were significantly higher in the renal-impairment group. In the group with renal impairment, the mean maximal body temperatures on the first, second, and third postoperative days were 38.7 degrees C, 38.6 degrees C, and 38.1 degrees C, respectively. These were higher than those of the no-impairment group. For patients with these risk factors, intraoperative prophylactic measures and early postoperative renal blood flow evaluation (in anticipation of postoperative renal impairment) are considered necessary.

Adrenal Gland Neoplasms↗

Deletion polymorphism in the angiotensin I converting enzyme (ACE) gene as a genetic risk factor for sarcoidosis.

BACKGROUND: Genetic control of serum angiotensin I converting enzyme (SACE) levels has been suggested. A study was undertaken to elucidate the role of this polymorphism in sarcoidosis. METHODS: Three hundred and forty one unrelated healthy controls and 103 consecutive patients with sarcoidosis participated in the study. SACE levels and an insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene were studied in each subject and new reference intervals for SACE activity for each genotype were determined. The difference in genotype and allele frequencies between controls and patients was analysed and odds ratios were calculated to estimate the relative risk. RESULTS: A significant association was seen between ACE gene polymorphism and SACE levels in both patients and controls. The new reference intervals for each genotype discriminated abnormal SACE levels in patients more accurately, especially those with genotype II. In women the frequencies of allele I were 0.68 (allele D 0.32) in controls and 0.58 (allele D 0.42) in patients, and the difference between the two female groups was significant (p < 0.05). Thus, an excess of genotype ID or DD was observed in female patients (odds ratio 2.18; 95% confidence interval 1.18 to 4.01; p = 0.01). CONCLUSIONS: These findings suggest that ACE gene polymorphism is associated with SACE levels in both patients with sarcoidosis and controls. ACE gene polymorphism should be further evaluated as a candidate marker for an increased risk of sarcoidosis.

Adult↗

Treatment combined with bone marrow transplantation for advanced neuroblastoma: an analysis of patients who were pretreated intensively with the protocol of the Study Group of Japan.

One hundred and ten patients with advanced neuroblastoma were treated with the protocol of the Study Group of Japan between January 1985 and March 1991. Patients received six cyclic courses of regimen A1, consisting of cyclophosphamide (1,200 mg/m2), vincristine (1.5 mg/m2), tetrahydropyranyl adriamycin (40 mg/m2), and cisplatin (90 mg/m2). Primary tumors and regional lymph node metastases were removed some time during the first six cycles of regimen A1. After six cycles of A1, the patients were divided into three groups. Patients in group 1 received alternating treatment with regimen B (cyclophosphamide and ACNU) and intensified A1, and those in group 2 were treated with alternating administration of regimen C (cyclophosphamide and DTIC) and intensified A1. Patients in group 3 were treated with supralethal therapy and bone marrow transplantation (BMT). Event-free survival rates at five years were 38.8% in the chemotherapy group (groups 1 and 2) and 50.0% in the transplant group (group 3). Because of the study design that was not in truly randomized fashion and because of the small number of patients in each risk group, it is indicated, though not concluded, that the transplant group had a better prognosis than the chemotherapy group in the cases with stage III disease or with amplified N-myc oncogene, based on the statistical calculations. Differences in survival rates for patients who underwent BMT when complete remission (CR) was achieved and for those who achieved CR but who did not undergo marrow transplant were statistically insignificant. BMT-related death occurred in 3 of 31 cases (9.7%) undergoing marrow transplant, and the causes of the death included hemorrhagic pneumonia, myocardial disturbance and hemorrhagic uremia.

Antineoplastic Combined Chemotherapy Protocols↗

Bone marrow metastasis of neuroblastoma analyzed by MRI and its influence on prognosis.

Bone marrow metastases (BM mets) of neuroblastoma were analyzed by magnetic resonance imaging (MRI). BM mets were demonstrated in 45 femurs of 23 patients with neuroblastoma by MRI. They were classified into two patterns, nodular (N) type and diffuse (D) type, on MRI, with an incidence of 16% (7/45) and 84% (38/45), respectively. No bone metastases (B mets) were accompanied by N type BM mets, whereas all of them were accompanied by D type BM mets. The rate of disappearance of N type BM mets after chemotherapy was 100% (7/7) and was significantly higher than that (26%, 10/38) of D type BM mets. The rate of disappearance (58%, 11/19) of BM mets in bones without associated B mets was also significantly higher than that (23%, 6/26) of BM mets in bones with associated B mets. BM mets present in bones with B mets tended to persist after chemotherapy. The survival rate of patients with residual BM mets after chemotherapy was significantly lower than that of patients without residual BM mets. This suggests that powerful systematic chemotherapy and additional targeted therapy to lesions remaining after chemotherapy are needed to improve the cure rate of patients with advanced neuroblastoma.

Bone Marrow↗

Association between high serum total IgE levels and D11S97 on chromosome 11q13 in Japanese subjects.

The genetic linkage of atopy to chromosome 11q13 through maternally derived alleles has been previously reported. Linkage analysis in Japanese families did not confirm the existence of a major gene for atopy at this locus under the model of autosomal dominant inheritance. However, we observed a significant association between serum total IgE levels and genetic markers at this locus both in 14 Japanese atopic families and in 120 unrelated Japanese subjects. We detected eight alleles at the D11S97 locus and eight alleles in the CA/GT repeat region in the fifth intron of the Fc epsilon RI beta gene. A significantly increased frequency of the D11S97/PstI 0.96 kb allele was observed in the chromosomes of the subjects with high serum total IgE levels both in the family study (p < 0.001) and in the population study (p < 0.05). However, multipoint linkage analysis again did not show any evidence for the existence of a major gene regulating atopy on chromosome 11q13 with location scores to -35 under the model of maternal inheritance. Evidence against linkage was confirmed by the non-parametric linkage analysis, using the affected pedigree member method. Also, there was no substitution of isoleucine for leucine in the fourth transmembrane domain of Fc epsilon RI beta (Leu181), which was reported to be responsible for a subset of atopy in the British population. Therefore, the association of serum total IgE levels with chromosome 11q13 indicates that a gene or genes at this locus may contribute to the expression of high IgE levels in the Japanese population as well as in the British population, but the heterogeneity of the genetic regulation of serum total IgE levels is evident between the two populations.

Adolescent↗

Expression of neuronal src mRNA as a favorable marker and inverse correlation to N-myc gene amplification in human neuroblastomas.

Neuron-specific src mRNA, which is expressed in human brain tissue by alternative splicing, is associated with neural differentiation. Neuronal c-srcNI expression may be associated with the ability of neuroblastomas to mature; furthermore, c-srcN2 mRNA is induced in chemically differentiated neuroblastoma cells in vitro. The prognosis of a patient with a neuroblastoma is strongly affected by the ability of the tumor to differentiate in vivo. In order to clarify the relationship between neuronal src mRNA expression and the clinical outcome of a neuroblastoma, we analyzed the expression of src mRNA in neuroblastoma tissues from 28 patients by SI-nuclease-protection assay. N-myc gene amplification was also examined by Southern blot hybridization. The clinical significance of neuronal src mRNA expression and its relevance to N-myc gene amplification was also investigated. A high ratio (more than 10%) of c-srcN2 mRNA expression was observed in all early-stage tumors and in advanced neuroblastomas with a favorable prognosis. In contrast, in advanced neuroblastomas with an aggressive clinical phenotype, c-srcN2 mRNA expression was found at a low ratio (below 10%). Genomic amplification of the N-myc gene and expression of c-srcN2 mRNAs were inversely correlated. When combined with other prognostic markers such as N-myc gene amplification, the expression of c-srcN2 mRNA may be a new biological marker to predict the prognosis of patients with neuroblastomas.

Blotting, Southern↗

[Crystal morphological and habit investigations of crystalline drugs. III. Sulfamethizole, levodopa and phenobarbital].

Crystal morphology and habit analyses necessary for a pharmaceutical technique have been studied by a polarizing microscope for tiny crystals of sulfamethizole, levodopa and phenobarbital listed in the Japanese Pharmacopoeia XII. Measurement of key refractive indices by an immersion method has been tried semiautomatically using photographs and the kit of immersion oils produced at 0.005 intervals, and a decision of an orientation of the section has been also carried by conoscope using photos. From the orthographic projections produced by the habit analysis of the colored photo as mentioned in the previous reports morphological and optical properties were clarified.

Crystallization↗