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Biomedical subjects

N Harada

Publications and source records attributed to N Harada.

At least 487 records · Page 27Linked to original sources

[Dry cough in the elderly patients treated with angiotensin converting enzyme inhibitor].

Since dry cough has recently been recognized as a side effect of angiotensin converting enzyme (ACE) inhibitors employed in the treatment of hypertension or congestive heart failure, the incidence of dry cough in elderly patients receiving ACE inhibitors was investigated. There were 237 out-patients on either captopril, enalapril, or delapril, in August and November 1989. Questionnaires concerning dry cough and smoking were completed by 184 patients. Patients either less than 50 years of age, or with chronic pulmonary disease were excluded. The remaining 168 patients, 63 males, 105 females, with a mean age of 73 years were analyzed for the incidence of a dry cough in relation to age, sex, smoking, and type of drugs. The overall incidence of a dry cough was 21/168 (12.5%), 7/63 (11.1%) for males and 14/105 (13.3%) for females, and was less frequent with advancing age; in the 51-60 age group 4/11 (36.4%), in the 61-70 age group 5/39 (12.8%), in the 71-80 age group 9/75 (12.0%), in the 81-90 age group 3/40 (7.5%), in the 91- age group 0/3 (0%). Enalapril showed significantly higher incidence of dry cough than captopril (16/93, 17.2% vs 7/88, 8.0%, p less than 0.05). Delapril showed an incidence 4/11, 36.4%, however, 9 out of the 11 patients who were given delapril had had a history of a dry cough with captopril or enalapril, and in 4 out of these 9 patients the dry cough disappeared by replacement of captopril or enalapril by delapril.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Long-term single dose chemoprophylaxis of recurrent urinary tract infection in elderly female subjects].

To evaluate the efficacy of the single dose chemoprophylaxis of recurrent urinary tract infection (UTI) in the elderly, 20 female inpatients (mean age 81.4) who had one or more culture documented UTIs in the past 12 months were studied. They were randomly assigned to be treated for 6 months either with chemoprophylaxis (200 mg of norfloxacin) or conventional therapy (without any antimicrobials except when overt UTI occurred). After a 4 months of washout period, the protocols were exchanged with each other and next 6 months of trial was carried out. All cases were followed at least 4 months after the discontinuance of the chemoprophylaxis. The difference of efficacy between the two modalities was evaluated by periodical examinations of urine cultures, urinalysis and inflammatory markers. During chemo-prophylaxis, the frequency of the symptomatic UTI (bacteriuria greater than 10(4)/ml, pyuria greater than 5/HPF, CRP greater than +) was 0.267/patient.year which was significantly lower than during conventional therapy (2.97/patient.year, p less than 0.01). This prophylactic effect remained 4 months after the discontinuance of the drug. On the other hand, bacteriuria was persistent in more than half of patients with chemoprophylaxis. Minimal inhibitory concentration of norfloxacin for separated bacteria revealed that the resistant species steeply increased from 4 to 6 months after the beginning of chemoprophylaxia. These species disappeared 4 months after the drug was discontinued. Optimal durations of chemoprophylaxis and drug-holidays were discussed.

Aged↗

Effects of vitamin E on toxicity by minute amounts of paraquat fed continuously to rats.

The effects of vitamin E on toxicity by minute amounts of paraquat fed continuously for some period to rats were investigated. Two experiments were carried out as experiments 1 and 2. In both experiments, weaning rats were divided at first into two groups; one group was given a vitamin E-deficient diet, and the other a vitamin E-supplemented control diet (50 mg alpha-tocopherol/kg of diet). They were fed on these diets for 40 days. After that, in both experiments, the rats that had been fed the vitamin E-deficient diet were further divided into two groups, which were either given a paraquat-added diet (+PQ-E) or continuously fed the same vitamin E-deficient diet (-E). The amount of paraquat added was 250 mg of methyl viologen per kg of diet. After the addition of paraquat, these two groups were pair-fed. In experiment 1, paraquat was given to all the rats fed the vitamin E-supplemented control diet (+PQ+E). In experiment 2, rats fed the control diet were divided into paraquat-added (+PQ+E) and non-paraquat-added (+E) groups, similar to those of vitamin E-deficient rats. These two groups were also pair-fed thereafter. In both experiments, about 35 days after paraquat addition, they were sacrificed. Plasma and liver alpha-tocopherol contents were measured by HPLC, and liver peroxidation value was measured by chemiluminescence and the TBA method. And, as parameters of vitamin E deficiency, plasma pyruvate kinase and GOT activities and alpha-cysteine proteinase inhibitor (alpha-CPI) level were measured. When the analyzed values were compared between paraquat-added and the corresponding not-added control groups (+PQ-E vs. -E, +PQ+E vs. +E), the following results were obtained. In experiment 1, the values of plasma and liver alpha-tocopherol levels were significantly lower in the +PQ-E group than those of the -E group; however, liver peroxidation values and values of the three parameters of vitamin E deficiency were not different significantly. In experiment 2, the value of liver alpha-tocopherol level was significantly lower in the +PQ+E group than that of the +E group.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effects of combination therapy with pirenzepine and famotidine on tetragastrin-stimulated gastric secretion in humans.

To determine the combined effects of the H2-receptor antagonist famotidine (FAM) and M1-receptor antagonist pirenzepine (PZ) on tetragastrin-stimulated acid production, 10 mg of FAM was intravenously injected into 6 healthy volunteers, alone and in combination with 20 mg of PZ. Physiologic saline was administered separately for control purposes. Compared with physiologic saline, both FAM and the FAM + PZ combination significantly reduced gastric secretion, acidity, acid output, and pepsin secretion. Concomitant use of PZ significantly enhanced FAM-induced reduction of overall gastric secretion, but did not enhance decreases in acid output, acidity, or pepsin secretion. These results indicate that combination therapy with intravenous FAM and PZ may be more useful than monotherapy with FAM in the treatment of gastroduodenal bleeding.

Adult↗

A case of extragenital choriocarcinoma in the jejunum.

A case of extragenital choriocarcinoma which produces human chorionic gonadotropin (HCG) in the small intestine of a 48-yr-old Japanese women is reported. Only seven such cases have been reported. The patient complained of postprandial upper abdominal pain and vomiting of 5 months' duration. Nine years before, right upper lobectomy was performed because of lung undifferentiated carcinoma. Double-contrast examination of the small intestine showed irregular ulceration in the lower jejunum. Celiac angiography demonstrated a hypervascular tumor stain in the branch of the jejunal artery. The serum HCG level was elevated. Gynecological examination revealed nothing abnormal. A small intestinal neoplasm was diagnosed, and a partial resection of the jejunum was performed. Endoscopy on the operating table showed a large, irregularly shaped sessile ulcer. Histologically the tumor was diagnosed as choriocarcinoma, composed of syncytiotrophoblastic cells and cytotrophoblastic cells. Immunohistochemical staining for HCG was positive. No metastasis was present. Although extragenital choriocarcinoma in the small intestine is rare, it should be included in the differential diagnosis of small intestinal neoplasm.

Choriocarcinoma↗

Evidence for involvement of clonal anergy in MHC class I and class II disparate skin allograft tolerance after the termination of intrathymic clonal deletion.

Mechanisms of cyclophosphamide (CP)-induced tolerance to class I (D) and class II (IE) alloantigens were studied. Transplantation tolerance across H-2D plus IE Ag-barriers has been achieved when B10.Thy-1.1 (Kb,IAb,IE-,Db; Thy-1.1) mice were primed i.v. with 9 x 10(7) spleen cells plus 3 x 10(7) bone marrow cells from B10.A(5R) mice (5R; kb,IAb,IEb,Dd; Thy-1.2) and treated i.p. with 200 mg/kg of CP 2 days later. The tolerant state in the early and the late stage was confirmed by prolonged acceptance of donor-type skin grafts, and in vitro unresponsiveness to donor Ag. In the tolerant B10.Thy-1.1 mice treated with 5R cells 28 days earlier and followed by CP, intrathymic clonal deletion of V beta 11+ T cells reactive to IE-encoded antigens was observed in association with intrathymic mixed chimerism. 5R skin survived, however, even after the clonal deletion of V beta 11+ T cells terminated by 180 days after tolerance induction. V beta 11+ T cells, which reappeared in the periphery of the recipient B10.Thy-1.1 mice bearing 5R skin at this stage, were not capable of proliferating in response to receptor cross-linking with V beta 11-specific mAb. Furthermore, the CTL activity against class I (Dd) alloantigens of spleen cells from these tolerant mice was restored by the addition of IL-2 to MLC. Thus, our experiments provide direct evidence that tolerance to both class I (Dd) and class II (IEb) alloantigens by clonal allergy occurs during the termination of intrathymic clonal deletion. These results clearly show practical hierarchy of the mechanisms of transplantation tolerance.

Animals↗

Distribution of aromatase in the brain of the Japanese quail, ring dove, and zebra finch: an immunocytochemical study.

An immunocytochemical peroxidase-antiperoxidase procedure using a purified polyclonal antibody raised against human placental aromatase was used to localize aromatase-containing cells in the brain of three avian species: the Japanese quail, the ring dove, and the zebra finch. In quail and dove, immunoreactive cells were found only in the preoptic area and hypothalamus, with a high density of positive cells being present in the medial preoptic area, in the septal area above the anterior commissure, in the ventromedial nucleus of the hypothalamus, and in rostral part of the infundibulum. Immunoreactivity was weaker in zebra finches, and no signal could therefore be detected in the ventromedial and tuberal hypothalamus. The positive material was localized in the perikarya and in adjacent cytoplasmic processes, including the full length of axons always leaving a clear unstained cell nucleus. These features could be observed in more detail on sections cut from perfused brains and stained with an alkaline phosphatase procedure. The distribution of aromatase immunoreactivity was similar in the three species although minor differences were observed in the preoptic area. The localization of labelled neurons coincided with the distribution of aromatase activity as studied by in vitro radioenzyme assays on brain nuclei dissected by the Palkovits punch method. There was one striking exception to this rule: no immunoreactivity was detected in the zebra finch telencephalon, while assays had shown the presence of an active enzyme in several nuclei such as the robustus archistriatalis, the hyperstriatum ventrale pars caudale, and the hippocampus and area parahippocampalis. The origins of this discrepancy and the functional role of the aromatase observed in the axons are discussed.

Animals↗

Expression of estrogen synthetase (P-450 aromatase) during adipose differentiation of 3T3-L1 cells.

The expression of estrogen synthetase (aromatase), catalyzing a rate limiting reaction in estrogen formation, was examined in 3T3-L1 cells during adipose differentiation. The expression of another P-450 enzyme, cholesterol side-chain cleavage enzyme (P-450scc) by the cells was also studied for comparison. The level of specific mRNA for aromatase increased 17-fold during adipogenic conversion and the elevated level was maintained in fully differentiated adipocytes. The level of specific mRNA for P-450scc increased about 5-fold, mainly due to net increase of cellular RNA. Various reagents, such as dexamethasone, testosterone and 1-methyl-3-isobutylxanthine, affected the expression of specific mRNA for aromatase markedly in adipocytes but had scarcely any effect on its level in fibroblasts. In contrast, these reagents caused similar increases in the level of mRNA for P-450scc in the two types of cells. Thus the 3T3-L1 cell line during adipogenic differentiation may be a useful system for studies on the mechanism regulating aromatase gene expression.

1-Methyl-3-isobutylxanthine↗

Immunocytochemical localization of aromatase in the brain.

An immunocytochemical peroxidase-antiperoxidase procedure using a purified polyclonal antibody raised against human placental aromatase was used to localize aromatase-containing cells in the Japanese quail brain. Immunoreactive cells were found only in the preoptic area and hypothalamus, with a high density of positive cells being present in the sexually dimorphic medial preoptic nucleus, in the ventromedial nucleus of the hypothalamus and in the infundibulum. The positive material was localized in the perikarya and in adjacent cytoplasmic processes. Aromatase-containing cells were a specific marker for the sexually dimorphic preoptic nucleus. Treatment with testosterone produced a 6-fold increase in the aromatase activity of the preoptic area and a 4-fold increase in the number of immunoreactive cells in the medial preoptic nucleus. Thus, the increase in aromatase activity observed after testosterone administration is caused by a change in enzyme concentration.

Animals↗

Role of carbohydrate moiety of IL-5. Effect of tunicamycin on the glycosylation of IL-5 and the biologic activity of deglycosylated IL-5.

IL-5 is a T cell-derived lymphokine that induces B cell growth and differentiation in murine systems. In this study, we examined the role of carbohydrate moiety of IL-5 in the expression of biological function. IL-5 polypeptides translated in Xenopus oocytes were heterogeneous in terms of isoelectric point (pI 4.7 to 8.0) and m.w. (45,000 to 60,000 under nonreducing conditions) and yielded m.w. of 25,000 to 30,000 under reducing conditions. Treatment of rIL-5 with N-glycanase under reducing conditions yielded an IL-5 monomer of m.w. 12,000 to 14,000. Furthermore, deglycosylated rIL-5 that had been translated in the presence of tunicamycin showed very limited heterogeneity by two-dimensional gel electrophoresis (first dimension, nonequilibrium pH gradient electrophoresis; second dimension, SDS-PAGE). The m.w. was 27,000 to 28,000 under non-reducing conditions and migrated to m.w. 13,000 to 14,000 under reducing conditions. These results indicate that IL-5 is a glycoprotein carrying the N-glycosidically-linked carbohydrates. Treatment of IL-5 with sialidase caused the decrease in the heterogeneity in isoelectric point of IL-5. Deglycosylated rIL-5 that had been obtained from tunicamycin-treated oocytes could bind to IL-5-responding cells (T88-M), which express both high- and low-affinity IL-5 receptors, as efficient as intact rIL-5 under high-affinity conditions. Scatchard plot analysis of equilibrium binding of 35S-labeled rIL-5 to T88-M cells revealed that the dissociation constants (Kd) of glycosylated rIL-5 and deglycosylated rIL-5 were 127 pM and 110 pM, respectively. IL-5 activities determined by both B cell growth and differentiation assays were not affected by deglycosylation. These results indicate that N-linked glycoside moiety of IL-5 molecules may not play an essential role in the expression of its activity.

Animals↗

Structural characterization of the human estrogen synthetase (aromatase) gene.

The estrogen synthetase (aromatase, cytochrome P-450AROM) gene has been isolated from human genomic libraries and characterized. The restriction map of 43 positive clones obtained indicated that this enzyme is present as a single copy gene. The aromatase gene is unexpectedly large compared with other forms of the cytochrome P-450 superfamily, spanning at least 70 kilobases. The gene consists of 10 exons and its 5'-untranslated region is divided into 2 exons by an intron of more than 35 kilobases long. This organization of the first exon in the aromatase gene is unique in the cytochrome P-450 superfamily. All the exon-intron junctional sequences conform to the canonical GT/AG rule. The sequences of a TATA box and a CAAT box are present 27 and 83 base pairs upstream from the transcriptional initiation site. Within 3 kilobases upstream from the initiation site, there are no typical consensus sequences of responsive elements for glucocorticoid and c-AMP, which regulate aromatase expression.

Aromatase↗

Purification of a 130-kDa T cell glycoprotein that binds human interleukin 4 with high affinity.

The interleukin 4 (IL-4) receptor was purified from the gibbon T cell line MLA 144. These cells were found to express high numbers of human IL-4-binding proteins (5000-6000 sites/cell) with an affinity constant (Kd) similar to that measured in human cell lines (Kd = 40-70 pM). Affinity cross-linking of 125I-IL-4 to human cell lines and MLA 144 cells demonstrated the labeling of three proteins of approximately 130, 75, and 65 kDa. Human IL-4-binding sites were solubilized from MLA 144 cells using Triton X-100 and then purified by carboxymethyl chromatography, which removed 50% of the protein without loss of IL-4-binding activity. Then sequential affinity purification over wheat germ agglutinin and a single IL-4 Affi-Gel 10 column resulted in a final 8000-fold purification of the IL-4 receptor. When analyzed on a silver-stained sodium dodecyl sulfate-polyacrylamide gel, the purified receptor migrated as a single molecular species of 130 +/- 5 kDa. Identification of the 130-kDa protein as the IL-4 receptor was demonstrated by cross-linking experiments and specific binding of 125I-IL-4 to nitrocellulose membranes after electrophoretic transfer of the purified receptor on sodium dodecyl sulfate-polyacrylamide gel.

Animals↗

Spinal cord compression with paraplegia in xanthomatosis due to normocholesterolemic sitosterolemia.

A 48-year-old woman with a 30-year history of tendinous xanthomatosis developed paraplegia. The magnetic resonance image revealed extramedullary tumors. The analysis of her sera and tumors revealed increased amount of plant sterols, especially sitosterol, and the diagnosis of sitosterolemia was made. This is the first reported case of a patient with sitosterolemia who had the neurological complication of spinal cord compression due to extramedullary sitosterolemic xanthomas.

Cholesterol↗

Interleukin 4 receptors on normal human B lymphocytes: characterization and regulation.

Human interleukin 4 (IL 4) up-regulates the expression of CD23 on both resting and "in vivo" activated B cells but induces proliferation and/or differentiation only on "in vitro" activated B lymphocytes. Resting B cells express 360 high-affinity IL 4 receptors (R) per cell (Kd = 25-75 pM). Activation of resting B cells with anti-IgM antibody or Staphylococcus aureus Cowan I (SAC) results in a two-to-threefold increase of IL 4R number without alteration of IL 4R affinity for IL 4. Flow cytometric analysis of biotinylated IL 4 binding shows that IL 4R expression is up-regulated on virtually all anti-IgM-stimulated B cells, but only on a subpopulation of larger cells among SAC-activated B lymphocytes. Culturing cells for 40 h with optimal concentrations of IL 4 does not significantly affect IL 4R levels on resting and anti-IgM-preactivated B lymphocytes but triples IL 4R levels on SAC-preactivated B cells. Removal of IL 4 from cell cultures results in a two-to-fourfold increase of IL 4R levels 2 h later, suggesting an increase in IL 4R turnover. Resting and activated B cells degrade 125I-labeled IL 4 at 37 degrees C. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of IL 4 binding molecules on resting, "in vivo" activated and anti-IgM-activated B cells reveals the same three species of 130, 80-75, 70-65 kDa. Thus, IL 4 displays its different biological activities on resting and activated B cells through IL 4R of the same affinity, gross biochemical structure and ability to mediate IL 4 degradation.

B-Lymphocytes↗

Expression of human lymphotoxin in Namalwa KJM-1 cells adapted to serum-free medium.

A Namalwa cell line, KJM-1, which was adapted to serum-free medium is thought to be a good host cell line for recombinant DNA technology. We previously reported the expression of human beta-interferon (beta-IFN) in Namalwa KJM-1 (Miyaji, 1989a). The utility of Namalwa KJM-1 for expression of foreign genes was further examined. As a target gene to be expressed, human lymphotoxin (hLT) cDNA was used. It was engineered for expression in Namalwa KJM-1 using a simian virus 40 (SV40)-based expression vector pAGE107 (Miyaji, 1989a). It contains all components necessary for the expression of cDNA in mammalian cells. The expression vector was introduced into Namalwa KJM-1 by electroporation. Among the transformants, clone 7 was further examined for the expression of hLT in serum-free medium. The production level of hLT was augmented with the increase of the cell density. Thus it was further indicated that Namalwa KJM-1 is useful for production of foreign gene products.

Cell Line↗