Regulation of glutathione transferase P gene during hepatocarcinogenesis of the rat.
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Animals↗
Biomedical subjects
M Sakai
Publications and source records attributed to M Sakai.
The N-terminal transactivation domain of rat estrogen receptor is localized in a hydrophobic domain of eighty amino acids.
In order to determine the transactivation domain(s) of the rat estrogen receptor (rat ER), we made a number of rat ER deletion mutants and transfected the mutant plasmids into COS7 cells together with an estrogen-responsive reporter plasmid, ERE-tk(197)-CAT, which contained the estrogen response element of Xenopus vitellogenin A2 gene. We have identified and localized the N-terminal transactivation domain of the rat ER to a hydrophobic region extending from Ala 59 to Glu 140.
Animals↗
330-keV electron line in e++Th interactions.
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Journal Article↗
Genetic studies on experimental autoimmune gastritis induced by neonatal thymectomy using recombinant inbred strains between a high-incidence strain, BALB/c, and a low-incidence strain, DBA/2.
Thymectomy on day 3 after birth induced autoimmune gastritis (AIG) at the age of 2 months in 51-73% of BALB/c mice, and in only 3-5% of DBA/2 mice. AIG was detected by histological and serological (immunofluorescence staining for detecting anti-parietal cell autoantibody) examination. However, autoantibody was weakly positive in almost all of these DBA/2 mice when measured by ELISA using extract of murine gastric mucosa as the antigen. To investigate genetically the mechanism controlling the incidence of AIG, II recombinant inbred strains established by brother-sister mating of (BALB/c x DBA/2) F2 mice (C x D2 strains) were used. Among 26 markers tested, the Mls-1 locus on BALB/c chromosome 1 and the Hc locus coding a complement component (C5) on BALB/c chromosome 2 were found to be associated with high susceptibility to AIG. However, if one or both of the loci were of DBA/2 origin, mice showed medium or low susceptibility to AIG. For further analysis, F1, F2 and back-cross generations of these two strains were tested, but segregation of a single susceptibility or insusceptibility gene was not obtained. Taken together, it seems probable that two or more genes are involved in the induction mechanism of AIG. We did not detect C5 deposition in AIG lesions, nor complement-dependent cytotoxic antibody to parietal cells in serum from AIG mice. However, injection of irradiated spleen cells of DBA/2 mice into BALB/c mice thymectomized on day 3 augmented the incidence of AIG from 71 to 100%, but not that of oophoritis (33%). A relationship between Mls-1a determinants and the pathogenesis of AIG was further suggested from the fact that V beta 6 TcR-expressing T cells increased in number in AIG-bearing compared with normal BALB/c mice.
Animals↗
[Isolation of enteropathogenic microorganism from patients with infection of the digestive tract during 1976 to 1988 in Tenri Hospital].
Enteropathogenic microorganisms isolated from feces of 9,393 patients with diarrhea or enteritis in our hospital between 1976 and 1988 were analyzed. As the result of the examination of 5,443 outpatients, 1,811 strains of pathogens were isolated from 1,686 cases (31.0%). Several species including Salmonella spp., Escherichia coli serotype, Vibrio parahaemolyticus, were isolated before 1978, and the incidence of pathogens was low (14.8%). For the 10-year period since 1979, the incidence markedly increased to 34.4%, and the number of pathogens isolated also increased to about twice that before 1978. The main cause of the increase was Campylobacter species. The major pathogens detected since 1979 were Campylobacter spp., E. coli serotype, Salmonella spp., V. parahaemolyticus, etc., but Rota virus, Clostridium difficile, Aeromonas spp., Vibrio fluvialis, etc. have also been detected, showing an increase in the number and diversity of the detected pathogens. As the result of the examination of 3,950 inpatients, 835 strains of pathogens were isolated from 800 cases (20.3%). The incidence of C. difficile was the highest, 423 of 800, followed by E. coli serotype, Salmonella spp., Campylobacter spp., V. parahaemolyticus and Aeromonas spp., in that order. All the inpatients from whom C. difficile was isolated manifested diarrhea or enteritis after administration of antimicrobial agents. The pathogens causing communicable disease were Salmonella spp. serovar Typhi, Salmonella spp. serovar Paratyphi A, Shigella flexneri, Shigella sonnei and Entamoeba histolytica, which were isolated from 5, 1, 3, 2 and inpatients, respectively.
Adolescent↗
Ethanol acutely and reversibly suppresses excitation-contraction coupling in cardiac myocytes.
We used adult rat cardiac myocytes to examine the acute effects of 0.1-5.0% (vol/vol) ethanol (ETOH) on 1) the cytosolic [Ca2+] (Cai) transient measured as the change in indo 1 fluorescence at 410/490 nm and contraction elicited by electrical stimulation of single cells and 2) the sarcoplasmic reticulum (SR) Ca2+ content in cell suspensions. During stimulation at 1 Hz, clinically relevant ETOH correlations (0.1-0.15% [vol/vol]) caused a 10-15% decrease in the contraction amplitude, measured by myocyte edge tracking, without decreasing the Cai transient that initiates contraction. At higher ETOH concentrations (1-5% [vol/vol]), ETOH caused profound contractile depression and also reduced the magnitude of the Cai transient. These effects were reversed within minutes of ETOH washout. Addition of norepinephrine (10 microM) to the bathing solution or an increase in bathing [Ca2+] in the continued presence of ETOH could also reverse its effects. The relation of the amplitude of the Cai transient to the contraction amplitude measured across a range of bathing [Ca2+] was shifted by ETOH, such that for a given Cai transient a marked reduction in contraction amplitude occurred. In unstimulated myocyte suspensions, ETOH (1-5% [vol/vol]) caused a concentration-dependent depletion of SR Ca2+ content, manifested as a diminution in the Cai increase elicited by caffeine in the presence of extracellular EGTA and no added Ca2+. Thus, in rat cardiac myocytes a reduction in the myofilament Ca2+ response, possibly due to a decrease in myofilament Ca2+ sensitivity, is a mechanism for contractile depression due to clinically relevant ETOH concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Study on fluidized melt-granulation. I. Examination of the factors on the granulation].
The purpose of this study is to develop a new granulation method by using a fluidized-bed granulator, which requires a nucleus with a low melting point as a binder. This method was named as fluidized melt-granulation. The technique is very simple and useful. In this paper, the granulation mechanism and the effect of the physico-chemical properties of raw materials on the growth of the granules were investigated. The results were as follows: (1) The mixture of the nucleus and the other powder particles was heated up to the melting point of the nucleus by hot inlet air, immediately resulting in the generation of the adhesion of the powders on the melted nucleus. The granules grew as the melted material immersed into the void space among the adhered particles. (2) The lower the viscosity of the melted nucleus was, the faster the granule grew. (3) The shape and the size of the nucleus affected those of the products. (4) The optimum mixing ratio between the nucleus and the granulated materials existed and it depended on the ratio between the surface areas of these materials.
Adjuvants, Pharmaceutic↗
Development of frozen-thawed demi-embryos and production of identical twin calves of different ages.
The percentages of morphologically transferable embryos obtained from frozen-thawed demi-embryos which were embedded with or without agar, and from those with or without zonae pellucidae were 26.3% (5/19), 36.4% (8/22), 39.5% (15/38) and 40.0% (22/55), respectively. No significant differences were observed between these groups. Development to calves of frozen-thawed demi-embryos with or without zonae pellucidae was 25.0% (3/12) and 26.7% (4/15), respectively. There was also no significant difference between them. On the trial for production of identical twin calves of different ages, the pregnancy rates of fresh and frozen demi-embryos after transfer were 69.2% (9/13) and 11.1% (1/9), respectively. Out of 13 fresh demi-embryos and 9 frozen demi-embryos transferred, only one pair of identical twin male calves of different ages were produced. This frozen-thawed demi-embryo was stored for 43 days in liquid nitrogen before thawing and transfer. These twin calves were confirmed to be identical by blood typing. Although these calves had different birth dates, their growth rates indicated similar developmental patterns. We suggest that it is possible to produce identical twin calves of different ages. This possibility would be useful for predicting the sex, milk producing ability and progeny test of a pair of demi-embryos before a decision to transfer the other half of a pair is made.
Animals↗
Effects of aging on the cardiopulmonary receptor reflex in hypertensive patients.
In order to evaluate the effects of aging on cardiopulmonary receptor function in hypertensive patients, hemodynamic responses after unloading were studied in middle aged and older hypertensive patients. Twenty-one hypertensive patients were divided into 2 groups according to age. The younger group consisted of 9 patients less than 65 years old (mean age: 57.2 years) and the older group contained 12 patients more than 65 years old (77.2 years). Following 10 min rest, deactivation of cardiopulmonary receptors was obtained by reducing central venous pressure through the application of graded negative pressures of -10, -20, and -40 mmHg to the lower body. Blood pressure, pulse rate, and forearm blood flow were measured at baseline and at each level of negative pressure. Furthermore, plasma norepinephrine and plasma renin activity levels were measured at baseline and at -40 mmHg. Forearm blood flow was measured by venous occlusive plethysmography using a Silastic strain gauge applied around the forearm. Forearm peripheral vascular resistance was calculated by dividing the mean arterial pressure by the forearm blood flow. Baseline mean blood pressure, pulse rate, and peripheral vascular resistance were similar in both age groups. Following lower body negative pressure (LBNP), mean blood pressure and pulse rate did not change, suggesting the selective deactivation of cardiopulmonary receptors. The increase in peripheral vascular resistance at LBNP of -40 mmHg in the older group (20.0 +/- 6.2) was significantly lower than that in the younger group (15.5 +/- 8.9, p less than 0.05). Furthermore, the increase in peripheral vascular resistance after LBNP was inversely related to age (Y = -0.32X + 38.8, r = -0.43, p less than 0.05). Increases in plasma norepinephrine and plasma renin activity in the older group were not different from those in the younger group. It is concluded that the sensitivity of cardiopulmonary baroreceptor function in hypertensive patients deteriorates with increasing age.
Aged↗
Cross-correlation function in the analysis of auditory brainstem response in spinocerebellar degeneration.
Cross-correlation functions were derived from the analysis of auditory-evoked brainstem response (ABR) and compared with measurements of wave latency and computed tomography findings in the assessment of ABR findings in spinocerebellar degeneration (SCD). Gender-specific normative ABR templates were produced from 30 normal males and 30 normal females separately. The cross-correlation indices used were the correlation coefficient at time 0, the maximal correlation coefficient and the latency delay in milli-seconds. The technique was applied to 33 patients with SCD. The incidence of abnormal cross-correlation functions (81.8%) was greater than the incidence of abnormal ABR peak latencies assessed according to gender (75.8%) which, in turn, was more common than the abnormal peak latencies assessed conventionally (69.7%). Moreover, the incidence of abnormal cross-correlations and latencies in Menière's disease was much lower (less than 8%). These results suggest that the evaluation of ABR waveform characteristics with cross-correlation functions using normative ABR templates of the same gender contributes to the precise detection of abnormality in the brainstem auditory pathway.
Adult↗
[Systolic anterior motion of the anterior mitral leaflet and/or the chordae tendinae in the elderly].
Systolic anterior motion of the anterior mitral leaflet and asymmetric septal hypertrophy (ASH) are characteristic features of hypertrophic obstructive cardiomyopathy (HOCM) on an echocardiogram. Among 9,670 patients over 60 years old examined by echocardiography from January, 1984 to October, 1990, 55 patients showed systolic anterior motion of the anterior mitral leaflet and/or the chordae tendinae (SAM). We investigated clinical features and morphological features of the left ventricle on an echocardiogram in the 55 patients with SAM. They were classified into three groups according to the degree of SAM. Thirty eight cases (group I) had no mitral and/or chordal-septal contact, 10 (group II) had brief contact (less than 30% on the echocardiographic systole) and 7 (group III) had prolonged contact (greater than or equal to 30%). Ages ranged from 60 to 99 with a mean age of 78.2 years. There were 19 males and 36 females and there was a predominance of females in each group. Thirty five cases had hypertension and 34 left ventricular hypertrophy on electrocardiograms. One case of group I, 3 of group II and 7 of group III had a clinical diagnosis of HOCM. In comparison with each group, the incidence of LVH (SV1 + RV5 greater than or equal to 35 mm) was 52% in group I, 90% in group II and 83% in group III and that of LVH (SV1 + RV5 greater than or equal to 70 mm) was 29%, 20% and 67%, respectively. On echocardiographic examination, the diastolic descent rate of the anterior mitral leaflet in the 3 groups was 36.1 +/- 13.1 mm/sec, 19.4 +/- 13.1 mm/sec and 10.7 +/- 11.8 mm/sec (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
[Phase spectral analysis of auditory brainstem response in cats].
In order to apply the phase spectral analysis of auditory brainstem response (ABR) to the clinical diagnostic test, the following studies in cats were performed. At first, the phase spectra of normal ABRs were investigated under adequate stimulus intensities. In addition the component synchrony measures (CSM) of ABRs were calculated at each stimulus level. Moreover the waveforms and phase spectra of ABRs were investigated before and after the destructions of cochlear nerve and brainstem auditory pathways in cats. The results were as follows; (1) In normal ABRs, the phase spectra were mainly composed of three frequency components at 0-300Hz (component A), 300-900Hz (component B) and 900-1500Hz (component C). The CSMs of component A represented the degree of synchrony for a slow component of the ABR and the CSMs of components B and C represented the degree of synchrony for a fast component. (2) A decrease in stimulus intensity resulted in a decrease in each average of the CSMs of the three components. (3) A greater decrease of the CSM occurred if ipsilateral destruction was performed in a peripheral lesion. Lesions of the auditory pathway were followed by a decrease of the CSM of component C to contralateral stimulation. These results suggest that the phase spectral analysis of ABRs has significant clinical value in the detection of brainstem lesions.
Animals↗
[Intrapleural administration of pirarubicin in the treatment of malignant pleural effusion].
Pirarubicin, a new antineoplastic antibiotic of anthracycline derivative, was injected into the pleural cavity in 15 patients with malignant pleural effusion. The dose of pirarubicin was 40 mg or 80 mg/body. All 15 patients were evaluable for both efficacy and toxicity. Since one evaluable patient received two courses of intrapleural administration of pirarubicin, we evaluated a total of 16 courses. Overall response rate was 81.3% with 7 CR cases, 6 PR cases and 3 NR cases. As toxicities, transient elevation of fever was observed in 81.3%, chest pain in 37.5%, appetite loss in 18.8%, nausea in 12.5% and bone marrow suppression in 6.3% of 16 courses, but no alopecia was observed. Between 40 mg group (n = 8) and 80 mg group (n = 8), no significant difference was observed in response rate, response duration, survival duration or toxicities except for fever. Fever over 38 degrees C was observed in all (100%) the 80 mg group, which was significantly higher than 50% in the 40 mg group. Response duration in cases with fever over 38 degrees C (n = 12) was significantly longer than in cases with maximum fever under 38 degrees C (n = 4). Intrapleural administration of pirarubicin was considered to be effective for the treatment of malignant pleural effusion without severe toxicities.
Adenocarcinoma↗
Gastric mucosal hexosamine content in various liver diseases.
Since gastric mucosal lesions are frequently encountered in patients with liver disease, we measured the levels of gastric mucosal hexosamine. In chronic hepatitis patients, hexosamine levels were reduced in both the antrum and corpus as compared with those in normal controls, while values in the advanced liver cirrhosis group (total bilirubin greater than 5 mg/dl) were lower than in the less advanced group. Although the presence or absence of esophageal varices had no influence on hexosamine, higher concentrations were found in patients with the red color sign (+) in comparison with those with negative red color sign (-). One month after endoscopic injection sclerotherapy of esophageal varices, hexosamine did not change, but decreases were seen in both the antrum and corpus at 3 months. We observed an increase in gastric mucosal blood flow after treatment with teprenone, a new antiulcerative agent, in normal controls. Gastric mucosal hexosamine increased significantly after teprenone treatment in both chronic hepatitis and liver cirrhosis groups. From these results, we conclude that hexosamine has a defensive action against gastric lesions in various liver diseases.
Anti-Ulcer Agents↗
[JUN-family proteins as transcriptional regulators].
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Genes, Regulator↗
[Pharmacokinetic and clinical studies on flomoxef in mature and premature infant].
Pharmacokinetic and clinical studies of flomoxef (FMOX) in neonates and premature infants were conducted, and the results obtained are summarized below. 1. Plasma concentrations of FMOX at 15 minutes after one shot intravenous injection of 20 mg/kg to 6 cases were in a rang of 33.0-69.9 micrograms/ml and half-lives (T 1/2's) were between 0.68 and 4.89 hours. The plasma concentration of FMOX at 15 minutes after one shot intravenous injection of 40 mg/kg to 1 case was 79.9 micrograms/ml and the half-life (T 1/2) was 2.45 hours. Drug concentrations in plasma upon 1-hour intravenous drip infusion were 71.1-114.0 micrograms/ml and T 1/2's were 1.64-3.41 hours. T 1/2 tended to be couse shorter as ages of babies increased. 2. Urinary excretion rates in the first 6 hours after one shot intravenous injection of FMOX 20 mg/kg to 1 case and 1-hour intravenous drip infusion of FMOX 40 mg/kg to 2 cases were 60.4%, and 27.2 and 55.3%, respectively. 3. Clinical effects of FMOX against 12 cases of bacterial infections were excellent in 6 cases, good in 5 cases and poor in 1 case, thus the clinical efficacy rate was 91.7%. FMOX was also given to 6 cases for prophylaxis and prophylactic effects were observed in all the cases. 4. No adverse effects were observed in the 21 cases examined, but elevations of S-GOT and S-GPT were found in 1 case. The abnormal laboratory test results were probably due to this drug.
Bacterial Infections↗
A human skeleton from the Ohguruwa remains.
In 1941, the Ohguruwa remains were discovered at the Mizuho sports ground site in Nagoya. They date from about 3000 B.C., which is the early Jomon era. When the stadium was reconstructed in 1980, four human skeletons were found. Three of them, however, were in poor condition and moreover, were incomplete. However, the second skeleton was in good condition and could almost be reconstructed, and this skeleton (No. 2) was used for our study. It was found in the classic posture with arms and legs folded. Some pieces of a dog's skeleton were also discovered near the No. 2 skeleton's chest. This particular skeleton generally showed characteristics typical of the Jomon era. It had a stout structure and was judged to be a middle aged male because of the following features. There was considerable attrition of the occlusal surfaces on the remaining teeth. The teeth were worn flat, probably owing to the hard food and to their use as a tool. Both canines and first premolars of the upper and lower arches had been extracted in accordance with the custom of the time. Typical caries and localized periodontal breakdown were not observed, although there was horizontal alveolar bone loss, especially in the anterior regions. The mastoid process was extremely large and prominent. The lateral prominence of the mandible was developed. Analysis of lateral cephalogram revealed that the mandible was in the anterior position. The angles of SNA, SNB and ANB were 89.6 degrees, 89.2 degrees and 0.4 degrees, respectively. The skeletal pattern was definitive Class III. The adaptive changes in the teeth, their supporting tissues, temporomandibular joints and the related muscles--the harmonious masticatory system--were all estimated.
Cephalometry↗
[Evaluation of carboplatin administration into the serous cavity in the treatment of malignant effusion].
Carboplatin, a new analogue of cisplatin, was administered into the serous cavity in nine primary lung cancer patients with malignant effusion, consisting of six malignant pleural effusions, two malignant pericardial effusions and one malignant ascites. Clinical effects, toxicities and pharmacokinetics were studied. The doses of carboplatin were 300 mg/m2 in seven patients, 200 mg/m2 in one patient and 1,100 mg/body in one patient. In seven evaluable patients, consisting of four non-small cell lung cancers and three small cell lung cancers, the response rate was 85.7% with 3 CR cases, 3 PR cases and 1 NR case. As toxicities, thrombocytopenia was observed in 57.1%, leukopenia in 57.1%, anemia in 71.4%, anorexia in 42.9%, nausea or vomiting in 28.6%, and low grade fever in 14.3%. However local pain, renal or liver dysfunction were not observed. The pharmacokinetics of free platinum concentration was analyzed with a two-compartment model (t1/2 beta = 18.60 hours) and 14.8% of total platinum remained free in effusion 24 hours after intracavitary administration. A high level of free platinum in effusion was maintained over a long period after carboplatin administration. This method was considered to be effective for the treatment of malignant effusion from the viewpoint of pharmacokinetics and less toxicity.
Aged↗