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Biomedical subjects

M Tanabe

Publications and source records attributed to M Tanabe.

At least 181 records · Page 10Linked to original sources

trk A gene expression in neuroblastoma. The clinical significance of an immunohistochemical study.

BACKGROUND: Neuroblastomas display a spectrum of morphologic and cytologic features of neural cells, and the prognosis of patients with these tumors varies widely. Expression of trk A in these tumors, as documented by Northern blot analysis, is associated with a favorable prognosis. To examine the expression of trk A at the cellular level in individual tumors and apply the results to routine clinical use, the authors designed this immunohistochemical study using an antibody with a predetermined specificity on formalin fixed, paraffin embedded tumor sections. METHODS: Expression of trk A and Ha-ras genes in 105 neuroblastomas was examined by avidin-biotin-complex immunoperoxidase staining. N-myc gene amplification was examined in 81 of the tumors by Southern blot analysis. RESULTS: Immunohistochemical expression in tumors correlated strongly with a favorable prognosis for trk A expression (P < 0.0001) and for Ha-ras expression (P < 0.0001). N-myc amplification was found in neuroblastomas with low expression of trk A and of Ha-ras genes. Kaplan-Meier analysis resulted in a favorable outcome associated with high trk A expression and no N-myc amplification, and a poor outcome associated with low trk A expression and demonstrable N-myc amplification (P < 0.0001). Univariate analysis showed that immunohistochemical expression of trk A at the time of diagnosis was a powerful predictor of the patient's prognosis, as were N-myc amplification and Ha-ras expression. trk A expression even correlated significantly with prognosis when the analysis was restricted to Stages III and IV tumors. CONCLUSIONS: Immunohistochemical detection of the trk A gene product in tumor cells is strongly predictive of a favorable prognosis for patients with neuroblastomas. The coexpression of trk A and Ha-ras genes with clinical behavior of the tumor may indicate close linkage of these genes in the nerve growth factor signal transduction system. Prognostic evaluation at diagnosis based on such molecular and genetic information should be important clinically.

Adolescent↗

Variable chimerism, graft-versus-host disease, and tolerance after different kinds of cell and whole organ transplantation from Lewis to brown Norway rats.

The bidirectional paradigm of tolerance involving reciprocal host vs. graft and graft vs. host reactions was examined after Lewis (LEW)-->Brown Norway (BN) transplantation of different whole organs (liver, intestine, heart, and kidney) or of 2.5 x 10(8) LEW leukocytes obtained from bone marrow, spleen, lymph nodes, and thymus. The experiments were performed without immunosuppression or under 14 daily doses of postoperative tacrolimus, which were continued in weekly doses to 100 days in a "continuous treatment" subgroup, and to 27 days in a short treatment group. Without immunosuppression, all organs and cell suspensions failed to engraft or were acutely rejected. GVHD (usually fatal) was always caused when either the long or short treatment was used for recipients of intestinal grafts and cell suspensions of spleen and lymph nodes. In contrast, both immunosuppressive protocols allowed engraftment of bone marrow cells, liver, heart, and kidney without clinical GVHD, whereas thymus cell suspensions and small doses of whole blood neither engrafted nor caused GVHD. At 100 days, now drug-free for 73 days, the liver, bone marrow, and heart recipients were tolerant in that they accepted all challenge LEW heart and/or liver grafts for 100 more days despite in vitro evidence of donor-specific reactivity (split tolerance). At 200 days, histopathologic studies of the challenge livers were normal no matter what the priming graft. However, the still-beating challenge hearts had a spectrum from normal to severe chronic rejection that defined the tolerogenicity of the original primary grafts: liver best-->bone marrow next-->heart least. Both the GVHD propensity and tolerogenicity in these experiments were closely associated with recipient tissue chimerism 30 and 100 days after the experiments began. The tissue chimerism was invariably multilineage, but the GVHD outcome was associated with T cell over-representation. These observations provide guidelines that should be considered in devising leukocyte augmentation protocols for human whole organ recipients. The results are discussed in relation to the historical tolerance studies of Billingham, Brent, and Medawar; Good; Monaco; and Calne.

Animals↗

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↗

Uterine atrophy in chronic murine toxoplasmosis due to ovarian dysfunction.

Uterine atrophy is a conspicuous finding in Nya:NYLAR female mice chronically infected with Toxoplasma gondii. Administration of 17B-estradiol to infected mice induced a vigorous uterotropic response, i.e., an increase in uterine weight, in endometrial hypertrophy and proliferation, and in the activity of three estrogen-regulated uterine enzymes. These findings rule out a parasite-induced refractoriness of the uterus to estrogen and point to ovarian dysfunction (hypogonadism) as the immediate cause of the uterine atrophy.

Adenylate Kinase↗

Intraoperative radiotherapy for gliomas.

Intraoperative radiotherapy (IORT) was performed in 20 of 36 patients with glioma; 11 glioblastomas, 7 malignant astrocytomas, 2 benign astrocytomas. Twenty or 25 Gy of irradiation was delivered in a single fraction intraoperatively, followed by external beam irradiation. The electron beam energy was selected so that the 80% isodose line fell at 2 or 3 cm below the residual tumor surface. Median survival time of IORT group was 14 months and that of the control group was 10 months. Difference of survival curve was significant. There were 6 incidences of complication caused by IORT; 1 radionecrosis, 1 convulsion, 1 abscess, and 3 severe brain edemas. IORT is suited for the treatment of malignant gliomas.

Adult↗

Hypersensitivity pneumonitis in a pearl nucleus worker.

A 37-year-old woman had worked for 4 years in a shell-processing factory where considerable airborne dust was produced cutting and polishing fresh water shells into pearl nuclei. She had a dry cough and dyspnea. Transbronchial lung biopsy showed noncaseating granulomas and cellular intraalveolar infiltrates. High-resolution lung computed tomography (HRCT) showed diffuse small nodules and ground-glass opacities. Hypersensitivity pneumonitis caused by shell dust should be considered in the appropriate clinical setting in a patient with the appropriate radiographic abnormalities.

Adult↗

Age-related profile of neuroblastoma: a comparison of tumors detected by mass-screening with those detected clinically.

Infants with neuroblastoma are known to have a favorable prognosis compared to those over 1 year of age. However, there is little biological information about the age-related heterogeneity of neuroblastoma. We evaluated the biological profile comparing cases detected by mass screening with those detected clinically. A total of 238 patients with neuroblastoma were classified into four groups according to their age at diagnosis. Patients in group A were 0-5 months of age (n = 31). Patients in group B were detected clinically and were 6-11 months of age (n = 25). Patients in group C were 6-11 months of age and were detected by mass-screening (n = 97). Patients in group D were more than 12 months of age (n = 85). The age-related heterogeneity was evaluated by Kaplan-Meier survival analysis, several clinical markers (neuron specific enolase, ferritin, vanillylmandelic acid and homovanillic acid) at diagnosis, tumor Ha-ras p21 expression and tumor N-myc amplification. Infant neuroblastoma had unique features in comparison to neuroblastoma diagnosed over 12 months of age. Clinical outcome of the patients in groups A and C was quite favorable. Even patients with stage III or IV disease in group A had a favorable prognosis. However, stage IVs disease in group A was not necessarily associated with a good prognosis and the early death after diagnosis was also characteristic. The biological profile of tumors in group C was similar to that in group A but different from the profile in groups B and D. Tumors in group B had a biological profile intermediate between groups A and D.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Species-specific PCR detection of malaria parasites by microtiter plate hybridization: clinical study with malaria patients.

A simple and convenient PCR method that amplifies the 18S rRNA genes has been developed for the purpose of detecting and differentiating four species causing malaria in humans. The advantage of the assay is that the biotinylated PCR product is visualized following hybridization with specific probes which are immobilized on plate wells (microtiter plate hybridization). This method has been previously evaluated in a field study and was found to be sensitive and specific for the detection of Plasmodium falciparum and Plasmodium vivax. In the current study, the microtiter plate hybridization PCR method was evaluated by using blood specimens from malaria patients. All of 36 cases of falciparum malaria, 26 of 27 cases of vivax malaria, all of 11 cases of ovale malaria, and 2 cases of malariae malaria were diagnosed species specifically by the PCR method. There were four smear-negative, PCR-positive cases that seemed to correspond to the convalescent stage of malaria. In contrast, 30 cases for which the diagnosis of malaria has been excluded on the basis of microscopy and clinical courses showed negative PCR results. By comparing parasite densities and PCR results following antimalarial treatment of some patients, it was revealed that the PCR results largely paralleled the parasite densities and that PCR could detect as few as 10 parasites per microliter of blood. We conclude that this PCR method is highly sensitive and specific for the detection of all four parasite species and can serve as a useful supplement to microscopy for the clinical management of malaria.

Animals↗

The DNA-binding properties of two heat shock factors, HSF1 and HSF3, are induced in the avian erythroblast cell line HD6.

Avian cells express three heat shock transcription factor (HSF) genes corresponding to a novel factor, HSF3, and homologs of mouse and human HSF1 and HSF2. Analysis of the biochemical and cell biological properties of these HSFs reveals that HSF3 has properties in common with both HSF1 and HSF2 and yet has features which are distinct from both. HSF3 is constitutively expressed in the erythroblast cell line HD6, the lymphoblast cell line MSB, and embryo fibroblasts, and yet its DNA-binding activity is induced only upon exposure of HD6 cells to heat shock. Acquisition of HSF3 DNA-binding activity in HD6 cells is accompanied by oligomerization from a non-DNA-binding dimer to a DNA-binding trimer, whereas the effect of heat shock on HSF1 is oligomerization of an inert monomer to a DNA-binding trimer. Induction of HSF3 DNA-binding activity is delayed compared with that of HSF1. As occurs for HSF1, heat shock leads to the translocation of HSF3 to the nucleus. HSF exhibits the properties of a transcriptional activator, as judged from the stimulatory activity of transiently overexpressed HSF3 measured by using a heat shock element-containing reporter construct and as independently assayed by the activity of a chimeric GAL4-HSF3 protein on a GAL4 reporter construct. These results reveal that HSF3 is negatively regulated in avian cells and acquires DNA-binding activity in certain cells upon heat shock.

Animals↗

[Changes in physique and obesity of school children in an elementary school observed from the Meiji era to the Showa era].

Data on height and weight were collected at an elementary school in Fukui Prefecture from 1889 through 1934 (observation period). During the observation period, the school area, consisting of a mountainous region and a plain region, was not changed. Using these data, analysis showed that there were: (1) differences in physique between children from the mountainous region and those from the plain region, which was suggested by the school teachers during the observation period, (2) chronological changes in physique, (3) chronological changes in the features of the height velocity curve in the analysis when school children at the same school born in the 1980s were used as a control, (4) chronological changes in the balance of weight to height and (5) changes in the prevalence of obesity. The results were as follows: (1) during the observation period, the physiques of children in the mountainous region were consistently inferior to those in the plain region, (2) during the period, the average physique of the school children aged 12 was consistently inferior to the overall average for Japanese pupils of the same age, (3) during the observation period, the onset of the adolescent growth spurt was later by one year compared with that of current controls, (4) the ratio of weight to height stratified by 3cm intervals during the observation period was almost the same as that in current controls, (5) during the observation period, the prevalence of obesity in boys (6%) was lower than that in current controls (10%). However, the obesity prevalence in girls during the period was higher than that in the controls. However, this findings might be associated with wearing kimono during measurement. By contrast, these differences have recently disappeared. These results suggest that there were consistent differences in physique that persisted between regions in the school area and in Japan as a whole across several eras.

Body Constitution↗

[Comparison of 99mTc-technegas scintigraphy and high resolution CT in pulmonary emphysema].

This study was undertaken to assess the usefulness of technetium-99m technegas scintigraphy axial images (technegas) compared with high resolution CT (HRCT) in 12 patients with pulmonary emphysema. All patients were male adult and heavy smokers and their mean age was 65. All patients inhaled 505 MBq technegas in several tidal volume breaths in the supine position without breath holding. SPECT imaging was performed by a Picker model Prism 2000. HRCT was performed after technegas. The technegas images showed different degree of changes from areas of heterogeneity to hot spots or defects. In emphysema, HRCT images showed low attenuation areas varying in size and number. In 4 of 12 patients, the degree of abnormal findings on technegas increased according to the degree of abnormal findings on HRCT. In the remaining 8 patients, however, more detailed findings were shown by technegas than by HRCT. There was no patients in which HRCT showed a greater changes than on technegas. HRCT can demonstrate low attenuation areas, even less than 5 mm in diameter. Moreover previous reports showed that aerosol inhalation would also demonstrate the airway disease. Assessment of the degree of involvement revealed by both methods indicated the superiority of technegas over HRCT. We conclude that technegas can represent the ventilation involvement easily more than HRCT in pulmonary emphysema.

Aged↗

[Prediction of postoperative pulmonary function using 99mTc-MAA perfusion lung SPECT].

In order to predict postoperative pulmonary function, 99mTc-MAA perfusion lung SPECT and spirometry were performed preoperatively in 52 patients with resectable primary lung cancer; 44 underwent lobectomy, eight pneumonectomy. Local pulmonary function (called local effective volume) was evaluated according to the degree of radionuclide distribution of each voxel in the SPECT images. The total effective volume was defined as the sum of the local effective volume, and the residual effective volume was the total effective volume excluding loss after operation. Predicted pulmonary function (VC and FEV1.0) was calculated by the following formula: Predicted value = preoperative value x percent of the residual effective volume. Postoperative pulmonary function was predicted in the same patients by means of 99mTc-MAA perfusion lung planar scintigraphy and X-ray CT. The patients were reinvestigated with spirometry at one and four months after surgery, and the values were compared with the predicted values. The correlations between the predicted values using SPECT and measured postoperative pulmonary function were highly significant (VC: r = 0.867, FEV1.0: r = 0.864 one month after operation; VC: r = 0.860, FEV1.0: r = 0.907 4 months after operation). The predicted values calculated using SPECT were accurate compared with the predicted values calculated using planar scintigraphy or X-ray CT. The patients with predicted FEV1.0 of less than 0.8 liter required home oxygen therapy. This method is valuable for the prediction of postoperative pulmonary function before the surgical procedure.

Adult↗

[Differential diagnosis of solitary pulmonary nodules by computerized statistical analysis using CT number].

There have been previous reports on the differentiation of benign pulmonary nodules from malignant ones using CT number. However, most of the nodules were without calcification, and diagnosis could be made only in limited cases. In the present study we established new multiple variables such as relative high density over the 75th percentile, inner gradient number (inner irregular rate), edge gradient number (edge irregular rate) and increased area rate (IAR). They are automatically calculated from CT data by computer. These variables are transformed into relative values, enabling comparisons of nodules without a standard reference phantom. With IAR, pulmonary nodules were classified into three types: type 1 (IAR 1.0-1.4), a high-density solid mass with well-defined margin; type 2 (IAR 1.4-2.0) between type 1 and type 3; and type 3 (IAR > 2.0) a low-density infiltrated mass with ill-defined margin. We studied 52 cases with solitary pulmonary nodules, whose diagnoses were confirmed either histologically or on follow-up. There were 34 benign nodules and 18 primary lung cancers. Using step-wise multiple regression with three variables, 42 of 52 cases were correctly diagnosed. Twenty-four of 28 type 1 cases and all 14 of type 2 cases were correctly diagnosed. This computer analysis is considered to be useful in distinguishing between benign and malignant solitary pulmonary nodules.

Aged↗

[A case of Sjögren's syndrome and systemic lupus erythematosus complicated with necrotizing angiitis of the gallbladder].

A 71 year-old man with Sjogren's syndrome and systemic lupus erythematosus was admitted to our hospital because of abdominal pain and fever. Laboratory investigation showed an ESR of 76 mm/hr, elevation of CRP and marked leukocytosis. Abdominal ultrasound and CT scan showed enlargement of the gallbladder and intravesicular sludge without stones. With a clinical diagnosis of acute cholecystitis and pan-peritonitis, the surgical procedures including cholecystectomy were performed. Histological examination of the gallbladder showed a presence of necrotizing angiitis of small arteries. The postoperative course was uneventful with daily administration of 10 mg of prednisolone.

Acute Disease↗

[Results of radiotherapy for stage III uterine cervical carcinomas and preliminary study of combined radiotherapy and transarterial infusion chemotherapy].

This is a retrospective analysis of 55 patients with stage III carcinoma of the uterine cervix treated with radiation from November 1984 through December 1991. Eleven of the patients were treated with radiation and transarterial infusion chemotherapy (TAI), using cis-platinum and pepleomycin. The 3- and 5-year cumulative survival rates for all patients were 61% and 58%, respectively, and the 3-year cumulative survival rate for the group with combined radiation and TAI was 47%. According to initial failure site, the locoregional recurrence rate was 36.8%, and that for para-aortic lymph node metastasis and distant metastasis was 31.6%. The failure pattern was similar between the irradiation only group and the group with combined radiation and TAI. The incidence of intestinal complications of grades 1 and 2 was 20%. Irradiation combined with TAI did not increase the incidence of complications.

Adult↗

[Evaluation of liver function in carbon tetrachloride-damaged rabbits by dynamic SPECT: comparison of 99mTc-GSA and 99mTc-Sn colloid].

Technetium-99m-DTPA-galactosyl human serum albumin (99mTc-GSA) is a new ligand that binds specifically to asialoglycoprotein receptors in hepatocytes. We performed liver dynamic SPECT using 99mTc-GSA and 99mTc-Sn colloid in nine normal control rabbits and 17 chronically CCI4-damaged rabbits (total 29 examinations), and also performed liver function tests (ICGR15, Alb, etc). Using the obtained dynamic SPECT data, we analyzed the liver kinetics of 99mTc-Sn colloid using a one-compartment model (hepatic blood flow [K]) and 99mTc-GSA using a two-compartment model (hepatic blood flow and receptor binding [K1], catabolism [K2]). As the CCl4-treated period increased, K1 decreased most significantly. K1 showed the most significant statistical correlation with the results of liver function tests, ICGR15 (p < 0.0001), Alb, PT, HP, Bil and GPT. Further, only K1 showed a correlation with the hepatic fibrosis of the HAI score. From the present results, liver dynamic SPECT using 99mTc-GSA may be said to provide a novel method for the evaluation of hepatic functional reserve.

Animals↗