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Biomedical subjects

M Shibata

Publications and source records attributed to M Shibata.

At least 559 records · Page 31Linked to original sources
PubMed1989

Redistribution of haloperidol after electroshock: experimental evidence.

We have previously reported that plasma and red blood cell levels of haloperidol, a neuroleptic agent, significantly increased immediately after electroconvulsive shock therapy (ECT) in schizophrenic patients on long term haloperidol treatment. To elucidate the mechanism of this increase, we attempted to reproduce this phenomenon in female Wistar rats. After 4 successive days of ip administration of haloperidol (10 mg/kg body weight, once daily), rats were given ECT through corneal electrodes on the fifth day (a.c. 50 Herz, 55 mA, 2.0 sec). Haloperidol levels were determined in plasma and other major tissues using a radioreceptor assay for haloperidol distribution before and after ECT at appropriate time intervals. Plasma haloperidol level was significantly increased 1 min after ECT but tended to return to the control level (without ECT) after 5 min. A significant decrease in haloperidol concentration in tissues was not observed in any of the tissues examined including frontal cerebrum, striatum, and muscle tissues (gluteal muscles). However, the relatively high haloperidol level and the large volume of muscle tissues suggested that the muscle could be the source of the transient increase in haloperidol levels in plasma. This conclusion was also supported by the data showing no significant rise of plasma haloperidol level after ETC in rats previously given a muscle relaxant, succamethonium chloride.

Animals↗
PubMed1989

Modifying effects of simultaneous treatment with butylated hydroxyanisole (BHA) on rat tumor induction by 3,2'-dimethyl-4-aminobiphenyl, 2,2'-dihydroxy-di-n-propylnitrosamine and N-methylnitrosourea.

The modifying effects of concurrent treatment with high or low doses of butylated hydroxyanisole (BHA) on wide-spectrum carcinogen-induced carcinogenesis were studied in male F344 rats. Groups of 20 animals were treated with 2 or 0.04% BHA for 24 weeks. Starting 2 weeks after the commencement of BHA treatment, they were given s.c. injection of 50 mg/kg body weight 3,2'-dimethyl-4-aminobiphenyl (DMAB) once a week, i.g. administrations of 200 mg/kg body weight 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN) once every 2 weeks, or i.p. injection of 15 mg/kg body weight N-methylnitrosourea (MNU) once every 2 weeks for 22 weeks. Further groups of rats were treated with DMAB, DHPN, MNU, or 2 or 0.04% BHA alone. All surviving animals were killed 24 weeks after the beginning of the experiment and the target organs examined histopathologically. The BHA treatment dose-dependently decreased the incidence of DMAB-induced liver preneoplastic lesions but was associated with significant tumor induction in the forestomach (papillomas, 40%, P less than 0.01) and urinary bladder (papillomas, 53%, P less than 0.001; carcinomas, 80%, P less than 0.001), where no lesions were observed in the group given only DMAB. Concurrent administration of 2% BHA also significantly inhibited the development of alveolar hyperplasia (P less than 0.001) of the lung in DHPN-treated animals, while enhancing induction of forestomach papillomas (P less than 0.05) and simple hyperplasia in the urinary bladder. Neither MNU nor 2% BHA alone induced forestomach carcinoma or papillary or nodular hyperplasia (PN hyperplasia) in the urinary bladder. However, these lesions were observed in 100% (P less than 0.001) and 55% (P less than 0.001) of animals respectively, receiving the two compounds in combination. These results demonstrated that concurrent treatment with BHA not only inhibits but can also strongly enhance carcinogenesis depending on the organ, irrespective of whether the carcinogens act directly or require metabolism. The finding that BHA potently modified carcinogenesis at 0.04% in diet, 1/50 of the carcinogenic dose, suggests that actual dietary levels close to the human situation might play a significant role in tumor development in man.

Aminobiphenyl Compounds↗
PubMed1989

Expression of DNA polymerase alpha and Leu3a molecules in growing and saturated cultures of human leukemic cells: phenotype analysis of proliferative cells by flow cytometry.

A flow cytometric method to analyze phenotypes of proliferative cells was developed using human leukemic cell line MOLT 4. A nuclear protein, DNA polymerase alpha (pol alpha), was selected as a marker for proliferative cells, and Leu3a molecule as a cell-surface antigen phenotype marker of the cells. The procedure involved the simultaneous use of fluorescein-conjugated anti-pol alpha antibody, developed by us, and commercially available phycoerythrin-conjugated anti-Leu3a antibody. The optimal fixative for both proteins was phosphate-buffered 2% paraformaldehyde. The pol alpha-positive population in logarythmically growing MOLT 4 cells was estimated, by flow cytometry, to be ca. 95%. A sharp flow cytometry histogram with a strong pol alpha-linked fluorescence was observed. On the other hand, the pol alpha-positive population in the saturated culture was ca. 70%, with weaker pol alpha-linked fluorescence. Thus, the population of pol alpha-positive cells and the amount of pol alpha in cells was dependent on the cell density of the culture. In contrast, ca. 90% Leu3a-positive populations with similar flow cytometry histograms were seen in either growing or saturated states, suggesting that expression of Leu3a was independent of cell density. The flow cytometric method using fluorescein isothiocyanate-conjugated anti-pol alpha antibody is useful for detecting proliferative fractions of free tumor cells, such as leukemic cells. Furthermore, analysis of the phenotype of the proliferative or non-proliferative cells became easier by simultaneous labeling with antibodies against pol alpha and phenotype-specific proteins.

CD4 Antigens↗
PubMed1989

Lack of carcinogenicity of quercetin in F344/DuCrj rats.

Quercetin was administered at dietary levels of 0(control), 1.25 and 5.0% to groups of 50 male and 50 female rats for 104 weeks, and then all animals were maintained without quercetin supplement for a further 8 weeks. At 5.0% quercetin, both sexes showed growth retardation throughout the study. There were no treatment-ascribed effects regarding clinical signs, mortality, urinalyses or hematology. Although serum glucose in 5.0% quercetin-treated males was significantly decreased and some relative organ weights in 5.0% groups showed statistically significant increases, these latter changes seemed to be related to the growth retardation. An increased incidence of non-neoplastic hyperplastic polyps in the cecum was noted in the 5.0% males. The incidences of cystic changes and fibroadenomas of the mammary gland, and foci (areas) of hepatocellular alteration in the 5.0% females, and liver bile duct proliferations in the 5.0% males were significantly decreased. No proliferative lesions of the urinary bladder related to treatment with quercetin were found in any rats. The incidences of several other nonneoplastic and neoplastic lesions which demonstrated statistically significant changes appeared to be related to the growth retardation or to be within the normal range, and therefore none was considered to be significant biologically. Thus, the investigation did not demonstrate any clear carcinogenic effect of quercetin on F344 rats at dietary levels of up to 5.0%.

Animals↗
PubMed1989

Acute hydrothorax in continuous ambulatory peritoneal dialysis--a collaborative study of 161 centers.

Follow-up studies on 3,195 patients from 161 centers in Japan undergoing continuous ambulatory peritoneal dialysis (CAPD) were performed for 1-104 months to clarify the incidence as well as the clinical features of acute hydrothorax. In these studies, 50 patients (1.6%) developed this complication. Twenty-seven (54%) were men, and 23 (46%) were women, ranging in age from 6 to 79 (average 49) years. The interval between onset of CAPD and hydrothorax ranged from 1 day to 8 years. Four had left-sided, and 2 had bilateral hydrothorax, but the majority (88%) were right-sided. Dyspnea was experienced by 37 of these 50 patients, but the remaining 13 (26%) patients were asymptomatic. Hydrothorax was fully resolved in 27 of them following a brief interruption of CAPD or the combined use of small exchange volumes in a semi-sitting position and pleurodesis with tetracycline or other agents. The remaining 23 patients (46%) were switched to hemodialysis permanently. Despite recurrence, 1 patient continued successfully on CAPD. It was concluded that acute hydrothorax is one important possible complication, although the risk may be low. Constant surveillance is necessary to detect pleural effusions in patients during CAPD.

Acute Disease↗
PubMed1989

Analyses of specific and total antibody responses of rabbits to four kinds of immunogens.

As a basic study to investigate suitable conditions to immunize rabbits with drug-immunogens, two highly sensitive and accurate enzyme immunoassays (EIAs) for specific antibody to viomycin (VM) and blasticidin S (BLS) were developed using the corresponding standard antibody, the solid-phase antigens, and enzyme-labeled goat anti-rabbit immunoglobulin G (IgG) antibody as immunological reagents. The accuracy of the assay results with these newly developed EIAs was demonstrated. The new EIAs as well as two previously developed EIAs, EIA for antibody specific to neocarzinostatin (NCS) and a sandwich EIA for rabbit IgG, were applied for analyses of the changes in contents of total and specific antibodies in rabbit antisera samples collected during immunizations with four antigens. Total IgG levels increased from 7.0-9.9 mg/ml to 30-50 mg/ml in all rabbits immunized under the same immunizing schedule, despite the use of four kinds of antigens. The highest level of specific antibodies, anti-BLS, anti-VM and anti-NCS, was 0.5 mg/ml in each case.

Animals↗
PubMed1989

Comparative study of complete and incomplete Freund's adjuvants for immunization of a drug immunogen using enzyme immunoassay methods.

Highly sensitive and accurate enzyme immunoassays (EIAs), a sandwich EIA for mouse immunoglobulin G (IgG) and an enzyme linked immunosorbent assay for mouse antibody specific to viomycin (VM), were developed. Accuracy and specificity of the assay results were confirmed before their application. The changes of total IgG and antibody specific to VM in mice, immunized with a VM-immunogen with or without two types of Freund's adjuvants under various conditions, were assessed by means of the newly developed EIA methods. Both methods were very useful tools to follow the immunization processes of mice, and complete and incomplete Freund's adjuvant were found to have similar adjuvant activities for production of antibody specific to VM, judging from the amounts of anti-VM antibody formed. It seems to be important that too many booster injections should be avoided in the immunization of mice with a hapten immunogen.

Animals↗
PubMed1989

Prevention of adverse reactions following milbemycin D administration to microfilaremic dogs infected with Dirofilaria immitis.

Some adverse reactions such as shock-like reaction and dirofilarial hemoglobinuria (caval syndrome) occasionally occurred in microfilaremic dogs following milbemycin D (Milbe) administration. This study was carried out to seek the prevention of these adverse reactions. In two groups containing 16 and 9 dogs respectively which were administered either chlorpheniramine maleate (1 mg/kg) or indomethacin (2.5 mg/kg) simultaneously with Milbe (1 mg/kg), the incidence of clinical signs such as the pale color of the visible mucous membranes, respiratory disorders, caval syndrome and shock-like reaction as well as changes in clinical parameters such as RBC and WBC counts, WBC profile and serum total protein, were almost equal to that observed in the group administered Milbe alone. In 41 dogs administered prednisolone (1 mg/kg) simultaneously with Milbe (1 mg/kg), no shock-like reaction was observed. Changes in clinical parameters were different from those in the group administered Milbe alone, whereas some clinical signs of adverse reactions, including caval syndrome, were observed. These results indicated that prednisolone was effective for prevention of the shock-like reaction in microfilaremic dogs induced by Milbe.

Animals↗
PubMed1989

Lack of modifying effects of 2,2'-[(4-aminophenyl) imino] bisethanol sulfate on induction of preneoplastic gamma-glutamyl transpeptidase-positive foci in a medium-term bioassay system using F344 rats.

The modifying effects of 2,2'-[(4-aminophenyl) imino] bisethanol sulfate (4APE) on liver carcinogenesis were investigated in male F344/DuCrj rats initially treated with N-nitrosodiethylamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats were given 4APE at dietary levels of 1,000, 330 and 110 parts per million (ppm), or 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) at 600 ppm as a positive control for 6 weeks. At week 3 following DEN administration, all animals were subjected to partial hepatectomy. No adverse effects on survival and body weight were seen in rats treated with 4APE, even at the highest dietary levels. Marked growth retardation and significant increase of relative liver weight were found in animals treated with the known hepatocarcinogen 3'-Me-DAB, which demonstrated marked promoting activity as evidenced by significantly increased values for gamma-glutamyl transpeptidase (gamma-GT) positive foci as compared with the controls given DEN alone. In contrast, 4APE did not significantly increase the level of gamma-GT positive foci over that induced by DEN initiation alone. From these results, it is concluded that 4APE does not possess promoting activity for liver carcinogenesis.

Animals↗
PubMed1989

[Modifying effects of beraprost sodium (TRK-100) on N-methyl-N-nitrosourea (MNU) carcinogenesis in F344 rats].

The potential tumor-promoting effects of beraprost sodium (TRK-100), stable analogue of prostacyclin (PGI2), were investigated in rats pretreated with N-methyl-N-nitrosourea (MNU) which is a potent initiator of tumor development in a variety of organ or tissues. Male F344 rats were initially given injections of MNU (20 mg/kg b.w. i.p.) twice a week for 3 weeks, and then administered drinking water containing 6, 2, 0.7 or 0.2 ppm of beraprost sodium for the next 29 weeks. For comparison, positive control groups received N-propyl-N-nitrosourea (PNU), which is a carcinogen in hematopoietic system and small intestine on F344 rat, at the dose of 200, 50 and 12.5 ppm in their drinking water. Appropriate non-treated controls were also included. Numerous tumors were observed in many organs including the hematopoietic system, digestive tract, nervous system, Zymbal's gland (auditory sebaceous glands) and peritoneal mesothelium. However, no tumor-enhancing effects of beraprost sodium were observed. In contrast, the groups treated with PNU demonstrated increased development of tumors in the tongue, forestomach, large intestine and Zymbal's gland. These results thus indicate that beraprost sodium is not capable of modulating the development of MNU-induced tumors.

Animals↗
PubMed1989

The structure of M-GTFI, an inhibitor of glucosyltransferase from S. mutans, and its inhibitory relationship with other sulfate ester-containing inhibitors.

M-GTFI, an inhibitor of glucosyltransferase from S. mutans was produced by Micromonospora narashinoensis strain No. 731. The isolation procedure for M-GTFI was improved and established for spectroscopic analyses, and some properties of the inhibitor were investigated. The structure of M-GTFI was shown to be trisodium [2-sulphonato-(E)-9-undecenyll-oxacyclotriacont-(E)-3- en-2-one, 16, 18-bis sulphonate. The chemical structure of M-GTFI was therefore similar to that of izumenolide which is a beta-lactamase inhibitor containing sulfate ester groups in its molecule. The inhibitory characteristics of M-GTFI were parallel to that of other inhibitory compounds containing sulphate esters but the spectrum of activity was wider.

Alkanesulfonates↗
PubMed1989

[Conscious survey of dental patients. 1. Questionnaire related to general dentistry (in the case of the new patients of the Nippon Dental University Hospital)].

Increased information on dentistry in the mass media in recent years may have caused changes in patients' attitudes toward dental care. To better understand patient' attitudes, we conducted a questionnaire survey of patients on the first visit to our hospital. Of 384 responses, 196 were eligible for statistical analysis. The following findings were obtained. 1. Among the motives for visiting a dental clinic, "Manifestation of pain or symptoms" was given by majority (85.7%) of respondents, followed by "detection of abnormality" (20.4%). The percentage of patients wanting treatment of "any part suggested by the dentist" was highest (35.7%), followed by those expecting "treatment including cleaning" (30.1%). The above results indicate that patients still tend to visit a clinical after subjective symptoms appear and leave the content of treatment to the dentist. However, an increasing number of patients appear to be concerned with their oral condition and visit a clinic before manifestation of symptoms. 2. Among factors in selecting their dentist, "expertise" obtained the highest percentage, 87.2%, followed by "providing prompt treatment" (38.8%) and "trying to avoid pain" (32.1%), in that order. Dissatisfaction with dentists was described as "no explanation of treatment" in 57.1%, "lack of sympathetic attitude" in 38.3% and "easily resorts to tooth extraction" in 35.4%. These results suggest that patients expect good human relations with their dentists, sufficient explanations of treatments and sympathetic consideration, as well as expertise. 3. The majority of patients (85.7%) hoped to receive instructions on oral hygiene and to be increased interest in information above prophylaxis. Meeting their needs will remain a future issue for dentists.

Attitude to Health↗
PubMed1989

[Conscious survey of dental patients. 2. Questionnaire related to prevention (in the case of the new patients of the Nippon Dental University Hospital)].

A questionnaire on the consciousness of new patients was conducted in Nippon Dental University Hospital. Following our prior report, items regarding dental prevention were asked to 196 subjects in the present case. The results are as follows. 1. 53.1% of the subjects had experienced scaling of the teeth. However only 15.4% of them had regularly scaling. 2. 62.8% of the subjects had been given guidance in brushing and 39.8% of them had used toothbrushes by themselves in the guidance. 3. 99.5% of the subjects brushed their teeth everyday. 58.5% of them brushed twice a day. Regarding the brushing period, "3 minutes" amounded the highest radio, 33.3%. 4. Regarding the major purpose of brushing, "prevention of oral diseases" amounted to 50.5%, followed by "unknown". Namely, 23.0% of the subjects had no definite purpose of brushing. This figure suggests that the awareness on brushing was unexpectedly low. 5. 85.7% of the subjects wanted to have oral sanitation guidance and oral health management. Among them. 59.5% wanted to have "regular examination". To the question "How often can you visit our hospital except treatment?", 48.2% of the subjects answered "twice or more per year", 41.1% "a day for each examination" and 53.6% answered "60 minutes per day". Among those who wanted to have oral sanitation guidance and oral health management, only 32.7% wanted to participate in our oral sanitation class. These results indicate that many patients want to have passive management but for would start action by themselves. Thus it is the most important for dentists to carry out sufficient education and guidance under these situations.

Attitude to Health↗
PubMed1989

Involvement of protein kinase in the regulation of beta-adrenergic receptors by antidepressants.

The role of serotonin (5-HT) and protein kinases in the regulation of the beta-receptor induced by typical and atypical antidepressants was investigated. Treatment with either mianserin or maprotiline for seven days produced a significant decrease in the beta-receptor density measured 6h after the last dose. The reduction in beta-receptors disappeared within 24h. However, combined treatment of mianserin or maprotiline with either fluoxetine or 5-hydroxytryptophan significantly decreased beta-receptors even 24h after the last dose. Following treatment with p-chlorophenylalanine the reduction in beta-receptors induced by desipramine was reversible within 24h. These results demonstrate that an increase in the synaptic 5-HT availability may contribute to the prolongation of the beta-receptor down-regulation by antidepressants. The intraventricular infusion of 12-0-tetradecanoyl-phorbol-13-acetate (TPA), a potent protein kinase C (PK-C) activator for seven days caused a significant decrease in beta-receptors, while forskolin or dibutyryl cyclic adenosine monophosphate had no influence on the receptor. The TPA-induced and desipramine-induced decreases in beta-receptors were not additive, suggesting that a similar mechanism is involved. The infusion of the PK-C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) caused an inhibition of the desipramine-induced decrease in beta-receptors. It is suggested that the beta-receptor down-regulation by antidepressants might be also regulated by PK-C through 5-HT-Ca2+-inositol-phospholipid systems.

5,7-Dihydroxytryptamine↗
PubMed1989

[A case of malignant pleural mesothelioma with infectious bronchogenic cyst].

A 47-year-old man was admitted with a cough on January 4, 1986. A chest X-ray film showed a mass shadow in the left lower lung, which was revealed to be a bronchogenic cyst by CT scanning and ultrasonography. Thoracotomy was performed on March 3, 1986 because cytologic tests on the fluid in the cyst suggested malignancy. A cyst, two tumors on the diaphragm and pleural thickening were revealed. Microscopic examination showed a benign bronchogenic cyst and a mixed-type malignant mesothelioma. In spite of chemotherapy (ADR, Cis-DPP, 5-fluorouracil) and immunotherapy (OK-432, PSK), the pleural thickening progressed, as was demonstrated by CT scanning and ultrasonography. Although cardiac tamponade due to invasion by the malignant mesothelioma developed, this was improved by cardiocentesis. The patient died of pneumonia on March 28, 1987. We studied the concentration of mineral fibers in lung and tumor tissues of this case by Energy Dispersive X-ray Analyser because asbestos or non-asbestos inorganic fibers might cause malignant mesothelioma. This case of malignant pleural mesothelioma accompanied by a bronchogenic cyst is very rare.

Bronchogenic Cyst↗