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Biomedical subjects

H Maeda

Publications and source records attributed to H Maeda.

At least 685 records · Page 38Linked to original sources

[Teratological study of trandolapril (RU44570) in rats].

A teratogenicity study was performed in Sprague-Dawley rats treated orally with trandolapril (RU44570) at the dosage levels of 3, 30 and 300 mg/kg/day from day 7 to day 17 of pregnancy. In each group, 24 or 25 female rats were sacrificed on day 20 of pregnancy for the examination of their fetuses, and 14 or 15 female rats were allowed to litter naturally for the postnatal examination of their offspring. Clinical symptoms and mortality attributable to administration of RU44570 were not observed in the dams (P). Body weight gain and food consumption were slightly depressed in the 300 mg/kg dosage group comparing with those of control group. However, RU44570 showed no adverse effect on the fetal mortality, prenatal development or teratogenicity of the fetuses. Incidence of dilatation of renal pelvis was slightly increased in fetuses in the 300 mg/kg dosage group comparing with that of the control group. However, the offspring in each treated group showed similar incidence of this abnormality to that of the control group in more advanced age. Therefore, these changes were considered to be reversible. No adverse effects on the postnatal development of the offspring containing reproductive ability were detected. The results suggest that non-effective dose level of RU44570 is 30 mg/kg for dams, 30 mg/kg for fetuses and 300 mg/kg for development in offspring, respectively.

Abnormalities, Drug-Induced↗

[Twelve-month oral toxicity study of trandolapril (RU44570) in rats].

1) The chronic toxicity of (-)-(2S, 3aR, 7aS)-1-[(S)-N-[(S)-1- ethoxycarbonyl-3-phenylpropyl]alanyl]hexahydro-2-indolinecarboxylic++ + acid (trandolapril: RU44570), a novel angiotensin-converting enzyme blocking antihypertensive drug, was assessed in rats by oral administration for 12 months at dosage levels of 0.05, 0.25, 2.50 and 25.00 mg/kg/day, comparing with the control animals received 0.5% methylcellulose solution. Reversibility of the drug-induced changes was also examined by 3 months' withdrawal following the administration period. 2) There was no death or general symptom that was thought to be attributable to the administration of RU44570. 3) The body weight gain was significantly suppressed from 1st week to the end of administration period in male animals of the dosage groups of 2.50 mg/kg or more and from week 1 to 15 of administration in female animals of the 25.00 mg/kg dosage group. During the withdrawal period, the difference of the body weights between these groups and control was reduced and that was never statistically significant. 4) The food consumption generally tended to be lowered in male animals of the dosage groups of 2.50 mg/kg or more throughout the administration period. The values were significantly different from that of control group on almost all measurement points from week 2 to 34 of administration. The difference of the food consumption of these groups from control group tended to be smaller thereafter, although significant difference was seen sporadically. Male animals of the 0.05 and 0.25 mg/kg dosage groups also showed the tendency of decreased food consumption infrequently. There was no constant tendency of fluctuation in the food consumption among the each RU44570 treated group during the withdrawal period. 5) The water consumption increased significantly in male animals of the 25.00 mg/kg dosage group from 1st week to the end of administration period. Male animals of the 2.50 mg/kg dosage group showed similar high value of the water consumption but the degree was lesser than that of 25.00 mg/kg dosage group. Although female animals of the 25.00 mg/kg dosage group showed significantly increased water consumption from week 3 to 4 of administration, they began to show decreasing tendency from approximately week 10 of administration conversely. From week 26 of administration, the water consumption of this group significantly decreased frequently comparing with that of control group. Female animals of the 2.50 mg/kg dosage group showed similar decrease in water consumption from approximately week 26 of administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

Intracerebral arteriovenous malformation fed by the anterior ethmoidal artery--case report.

A 66-year-old male presented with a left frontal intracerebral arteriovenous malformation (AVM) fed by the anterior ethmoidal artery. The nidus was located intracerebrally, although the feeder was a dural artery, and was drained by the ascending frontal vein which showed varicose dilatation. The AVM was associated with an unruptured right anterior choroidal artery aneurysm. The AVM was removed and the aneurysm was clipped in a two-stage operation. The etiology of AVMs fed by the ethmoidal artery is still uncertain, but is probably due to a disturbance in normal embryonic development. The association with aneurysm seemed to be incidental.

Aged↗

Increased 120 kDa protein in liver cytosol of genetically obese Zucker rats.

In this study, the differences between the pattern of stained proteins from genetically obese Zucker rats and those from lean Zucker rats were analyzed using SDS-polyacrylamide gel electrophoresis. The level of the 120 kDa protein in the liver cytosol fraction of these obese rats was several times higher than that found in the lean rats. This protein was not present in the mitochondrial fractions of either strain. The level of the 120 kDa protein was decreased drastically during a 72-h fast in the obese Zucker rats. An increase in the level of this protein was induced in the lean Zucker rats through a 48-h fast followed by refeeding with a high-carbohydrate diet. However, when the lean Zucker rats were refed with a high-fat diet following the fast, no significant change was observed in the level of the 120 kDa protein. These observations strongly suggest that the elevated levels of the 120 kDa protein seen in the liver cytosol fraction of obese Zucker rats may be responsible for the observed increases in lipogenesis and pathogenesis of obesity in these rats.

Animals↗

[Spontaneous thrombosis of the pampiniform plexus--case report].

Spontaneous thrombosis of the pampiniform plexus is a extremely rare condition, with only 9 cases reported in the literature. We report here a case of this entity and demonstrate that surgical exploration should be indicated to rule out some of these other conditions, such as a tumor of the intrascrotal component, acute scrotum or inguinal herniation.

Adult↗

[Bone mineral loss in patients with chronic obstructive pulmonary disease].

Body weight loss is often observed in patients with chronic obstructive pulmonary disease (COPD). Bone mineral loss has also been reported in COPD, but the mechanisms are not well determined. To elucidate what factors influence on bone mineral content in COPD patients, we measured bone mineral content (BMC) by dual energy X-ray absorptiometry (DXA) (XR-26, Norland), pulmonary function, and ten minute walk distance (TMD) in Japanese elderly male patients with COPD. The subjects were 21 male patients with COPD (72.6 +/- 9.5 years) and 18 age-matched male normal individuals (66.5 +/- 9.5 years). COPD patients showed significantly (p < 0.05) lower BMC (1.82 +/- 0.33, 2.27 +/- 0.35 kg, respectively) compared with age-matched controls. BMC was significantly correlated with body weight and TMD (r = 0.71, r = 0.51, respectively). These results demonstrate that lower body weight and decreased exercise capacity account for the significantly lower bone mineral content of our COPD patients and that COPD patients with body weight loss may be at high risk for osteoporotic fracture.

Absorptiometry, Photon↗

[Clinical characteristics and treatment results of acute promyelocytic leukemia in children (Children's Cancer and Leukemia Study Group)].

The clinical characteristics and treatment outcome in 40 children with acute promyelocytic leukemia (APL) treated at institutions participating in the Children's Cancer and Leukemia Study Group (CCLSG) were studied retrospectively. The median age at diagnosis was 8 years old. Bleeding diathesis was the predominant presenting symptom (90%), associated with laboratory findings of disseminated intravascular coagulation. Hepatomegaly, splenomegaly and lymphadenopathy were observed in 35%, 10%, and 15% of the cases, respectively. The median WBC count was 4.25 x 10(9)/l. Anemia (hemoglobin < 8 g/dl) and thrombocytopenia (< 30 x 10(9)/l) were present in more than half of the patients. Cytogenetic studies demonstrated the characteristic 15; 17 translocation in about 90% of the patients analyzed. Induction therapy consisted of cytosine arabinoside and an anthracycline, with or without other agents. Twenty-nine patients (73%) achieved complete remission (CR) while early fatal hemorrhage was the predominant cause of induction failure. The survival rates continued to decrease (28% at 3 years, 24% at 5 years, and 7.9% at 10 years) due to late marrow relapses. Anthracycline cardiotoxicity was fatal in three patients in remission. These clinical features of childhood APL should be taken into account in the development of new protocols.

Adolescent↗

[A case of multiple colon cancer appeared after thymectomy for thymoma with myasthenia gravis].

A 62-year-old woman was admitted to our hospital because of diarrhea and melena. Thymectomy for thymoma with myasthenia gravis was carried out on this patient four years ago. Barium enema revealed four tumor shadows in the ascending and transverse colon. Multiple colon cancer was diagnosed and extended right hemicolectomy was carried out. The postoperative course was uneventful and she has been free from any symptom. In this paper, we discussed the relationship between thymoma and the incidence of nonthymic malignancy.

Adenocarcinoma↗

[Production of monoclonal antibodies against osteoclasts of rat].

In mammals, it has been difficult to collect the authentic osteoclasts on a large scale. Recently we established a culture system for forming osteoclast-like multinucleated cells (MNCs) which exhibited many characteristics of osteoclasts. MNCs instead of authentic osteoclasts were used as immunogen to establish the hybridomas which secrete monoclonal antibodies against the osteoclasts by in vitro immunization. We obtained two monoclonal antibodies, HOK 1 and HOK 2. HOK 1 showed intense immunoreactivity with MNCs, mononuclear cells and putative migratory traces of MNCs on the culture dishes, but it had weak reactivity with the stromal cells. HOK 2 also showed strong reactivity with MNCs, mononuclear cells, and the very limited area of the culture dishes just facing to one side of some MNCs. The stromal cells were faintly stained with HOK 2. In th paraffin sections of tibiae, both antibodies intensely stained osteoclasts, osteoblasts and osteocytes. The bone matrix was weakly stained by HOK 2 but not by HOK 1. The present observations indicated that HOK 1 and HOK 2 could recognize the common antigen expressed on cells both involving in the bone formation and resorption. The antigens recognized by HOK 1 and HOK 2 were shown to exist on the putative traces of motile MNCs. These antibodies would be available to investigate the mechanisms of the 'bone remodeling' as a functional marker of bone cells.

Animals↗

[Primary mediastinal tumors in children--comparison with mediastinal tumors in adults].

During the past 43 years, 628 patients with a primary mediastinal tumor underwent surgical operation in our institution. Of those patients, 106 patients (16.9%) were children of 15 yr of age or less and 522 patients (83.1%) were adults. 47 (44.3%) of the 106 children had neurogenic tumors, while 21 patients (19.8%) had a teratoma. 189 (36.2%) of the 522 adults had thymoma and 89 patients (17.1%) had teratoma. In the 106 children there were 71 benign tumor patients (66.9%) and 35 malignant tumor patients (33.1%). There were 277 (53.1%) benign and 245 (46.95) malignant tumors in the 522 adults. The adults had significantly more malignant tumors than the children (p < 0.01). In our series of malignant mediastinal tumors in children, 14 patients (13.3%) had a lymphoma and 11 patients (10.5%) had a neuroblastoma. On the other hand, in the adults, 127 patients (24.3%) had a thymoma and 66 patients (12.6%) had a lymphoma. Regarding benign mediastinal tumors, in children, 30 patients (28.5%) had a ganglioneuroma and 19 patients (18.0%) had a teratoma. In the adults, 68 patients (13.0%) had a teratoma and 62 patients (11.9%) had a thymoma. In the clinical manifestation, 51 child patients (48.1%) and 191 adult patients (36.6%) were asymptomatic. As symptoms due to compression or direct invasion to adjacent structures, dyspnea was seen in 16 child patients (15.1%), and chest pain occurred in 59 adult patients (11.3%). Dyspnea was significantly more common in children than in in adults (p < 0.01). Emergency operations were performed in children more than in adults.

Adolescent↗

Effect of phenol block on peripheral nerve: morphometric and histochemical study in rats.

Nerve degeneration and regeneration following phenol block were investigated quantitatively by coordinated morphometry and histochemistry. Retrograde axonal transport of horseradish peroxidase was used to assess functional deficits in peripheral nerves. After one side of the rat sciatic nerve was blocked by 5 or 10% phenol, horseradish peroxidase was injected into the tibial muscular compartments bilaterally at various time intervals. The number and somatic area distribution of labeled motoneurons on the blocked side were compared to the contralateral unoperated side. After phenol block, the motoneuron number that had decreased during the first 2 weeks increased significantly at 4 weeks, and then returned to the level of the control side at 8 weeks at both phenol concentrations. No difference was found in somatic area between the blocked and control side during the process of recovery. It is concluded that phenol should not be used to cause selective and irreversible nerve block.

Animals↗

[A case of gastric diverticulum difficult to differentiate from left adrenal tumor].

We report a case of gastric diverticulum difficult to differentiate from left adrenal tumor. A 58-year-old woman was admitted for the examination of right renal cyst. Ultrasonogram and abdominal CT scan revealed 3 cm mass at the upper pole of the left kidney. Operation was performed with diagnosis of left adrenal incidentaloma, but no evident tumor was explored. Postoperative X-ray of upper gastrointestine revealed the mass as a gastric diverticulum.

Adrenal Gland Neoplasms↗

The superoxide generation of neutrophils in normal and preeclamptic pregnancies.

OBJECTIVE: To determine whether preeclampsia enhances superoxide generation of neutrophils. METHODS: Samples were obtained from 12 normal nonpregnant, 15 normal pregnant, and 11 preeclamptic women. The superoxide production of neutrophils was measured by the superoxide dismutase-inhibitable reduction of ferricytochrome C at 550-540 nm using a dual-wavelength spectrophotometer. RESULTS: N-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced superoxide production of neutrophils was significantly higher in preeclamptics than in normal nonpregnant and pregnant subjects, whereas phorbol 12-myristate 13-acetate-induced superoxide production did not differ among them. When neutrophils prepared from normal nonpregnant women were preincubated with sera from the study groups, sera from preeclamptics enhanced the FMLP-induced superoxide production to about twice that of the other subjects. The serum-enhancing factor appeared to be a heat-labile protein, different from other known activators. CONCLUSION: Preeclampsia is characterized by the presence of a neutrophil activator that enhances superoxide production. This enhanced production may contribute to the pathophysiologic changes observed in preeclampsia.

Adult↗

[Rearrangements of immunoglobulin light chain and heavy chain constant region genes in B-cell malignancies].

We analyzed immunoglobulin (Ig) gene rearrangements in 69 patients with B-cell malignancies by Southern hybridization. We used 5 probes which covered JH 5'S mu and S gamma 3 loci of the Ig heavy (IgH) chain gene, and C kappa and kappa de loci of the Ig light (IgL) chain kappa gene, respectively. DNA rearrangements were observed in 68 out of the 69 patients using the JH probe. In 97% (33/34) of patients with non-Hodgkin's lymphoma (NHL), 100% (5/5) of chronic lymphocytic leukemia (CLL), 42% (10/24) of non-T cell acute lymphoblastic leukemia (non-T ALL), and in 0% (0/4) of chronic myelogenous leukemia lymphoid crisis (CML-LBC), the rearrangements were detected by C kappa and/or kappa de probes. Furthermore, the genotype of the light chain was defined by rearrangement patterns of these 2 probes. The by using the 5'S mu-probe, class switch recombinations were detected in 76% (25/33) of NHL, 20% (1/5) of CLL, 17% (4/24) of non-T ALL, and in 0% (0/4) of CML-LBC. Among them, 1 case of IgM NHL and 3 cases of double bearer NHL had rearranged on both IgH alleles by the constant region. The results of this study indicate that genotypes correspond well to phenotypes of B-cell malignancies and that the determination of genotype will be useful for making an exact diagnosis of B-cell malignancies.

DNA, Neoplasm↗

[Study on three patients with malignant glioma showing tumor reduction during maintenance therapy with MCNU].

Tumor regression occurred in three of 19 patients (15.8%) with malignant glioma during maintenance therapy using MCNU. In two patients, the tumor reduced 5 and 8 months after the initial treatment, respectively. In the remaining patient, though the maintenance therapy was interrupted for a while and consequently the tumor size increased, readministration of MCNU reduced the tumor size two months later. Therefore, since the antitumor activity of MCNU against malignant glioma seems to require a certain time depending on the case, it is recommended that MCNU be given as maintenance therapy for at least half a year.

Adult↗

Hydroxyl radical production by H2O2 plus Cu,Zn-superoxide dismutase reflects the activity of free copper released from the oxidatively damaged enzyme.

To elaborate the catalytic activity of Cu2+ of Cu,Zn-superoxide dismutase (SOD) in the generation of hydroxyl radical (.OH) from H2O2, we investigated the mechanism of inactivation of alpha 1-protease inhibitor (alpha 1-PI), mediated by H2O2 and Cu,Zn-SOD. When alpha 1-PI was incubated with 500 units/ml Cu,Zn-SOD and 1.0 mM H2O2, 60% of anti-elastase activity of alpha 1-PI was lost within 90 min. ESR spin trapping using 5,5-dimethyl-1-pyrroline N-oxide showed that free .OH was indeed generated in the reaction of Cu,Zn-SOD/H2O2; this was substantiated by the almost complete eradication of .OH by either ethanol or dimethyl sulfoxide accompanied by the generation of carbon-centered radicals. .OH production and alpha 1-PI inactivation in the H2O2/SOD system became apparent at 30 min or later. Dimethyl sulfoxide and 5,5-dimethyl-1-pyrroline N-oxide protected inactivation of alpha 1-PI significantly in this system, indicating that alpha 1-PI inactivation was mediated by .OH. SOD activity decreased rapidly during the reaction with H2O2 for the initial 30 min. Time-dependent changes in the ESR signal of SOD showed the destruction of ligands for Cu2+ in SOD by H2O2 within this initial period. Thus we conclude that inactivation of alpha 1-PI is mediated in the H2O2/Cu,Zn-SOD system via the generation of .OH by free Cu2+ released from oxidatively damaged SOD.

Cyclic N-Oxides↗

Gene structure of human indoleamine 2,3-dioxygenase.

Two genomic DNA clones that encode human indoleamine 2,3-dioxygenase (IDO) were isolated from the human genomic DNA library using the IDO cDNA as a probe, and their restriction maps and partial nucleotide sequences were determined. The human IDO gene spanned 15 kilobase pairs with ten exons. The 5' terminus of the IDO mRNA was 33 nucleotides upstream of the translation initiation codon ATG. The 5' flanking region contained ISRE, X-box, and Y-box like sequences. Southern blot analysis of the human genomic DNA indicated that the human IDO gene was present in a single copy in the genome.

Alternative Splicing↗