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Biomedical subjects

H Harada

Publications and source records attributed to H Harada.

At least 343 records · Page 19Linked to original sources
PubMed1995

Gene expression of retinoic acid receptors, retinoid-X receptors, and cellular retinol-binding protein I in bone and its regulation by vitamin A.

We investigated the gene expression of retinoic acid (RA) receptors (RARs) and retinoid-binding proteins, and the effect of vitamin A on gene expression in the rat tibia to understand the actions of vitamin A on bone tissue. The transcripts of all three subtypes of all-trans RAR (alpha, beta, and gamma) and two of three subtypes of retinoid-X receptor (alpha and beta) were detected by Northern blotting. Among cellular retinol-binding protein I (CRBP-I) and CRBP-II and cellular retinoic acid-binding protein I and II, only the CRBP-I gene was expressed. These results indicated that in bone, the actions of vitamin A are exerted through these nuclear receptors by regulating target gene expression, and through CRBP-I by modulating the intracellular transport of vitamin A. Moreover, using rats of various retinoid status, we investigated whether the expression of target genes for vitamin A (RAR beta and CRBP-I) is regulated by retinoic acid (RA) in the adult rat tibia. The messenger RNA levels of these genes in vitamin A-deficient rats decreased to half of those in normal rats and were quickly restored (4 h) by either all-trans-RA or 9-cis-RA. Excess RA given to normal rats doubled the messenger RNA levels of these two genes. These results verified that, like other target tissues, bone is a target for vitamin A in terms of gene expression. In addition, we examined the effect of RAs on the expression of the target genes for vitamin D, because it is possible that 9-cis-RA is involved in the transcriptional control of vitamin D receptor by forming a heterodimer complex with retinoid-X receptor. The vitamin D-regulated osteopontin gene was induced 4 h after the administration of RA regardless of retinoid or vitamin D status. RA also induced osteopontin gene expression in concert with vitamin D in normal rats. Specific inhibitors of transcription showed that gene expression may be regulated by RA at the transcriptional level. Thus, the results presented here clarified at the molecular level that bone is a target organ for vitamin A in terms of gene expression.

Animals↗
PubMed1995

Synthesis and structure-activity relationships of 4-amino-5-chloro-2-ethoxybenzamides with six- and seven-membered heteroalicycles as potential gastroprokinetic agents.

A new series of 4-amino-5-chloro-2-ethoxybenzamides 3b--f and 5--8 bearing six- and seven-membered heteroalicycles was prepared and evaluated for gastroprokinetic activity. Compounds 3b--e, derived by replacement of the morpholine oxygen of 4-amino-N-[(4-benzyl-2-morpholinyl)methyl]-5- chloro-2-ethoxybenzamide (3a) with other atoms (sulfur, nitrogen and carbon), generally exhibited a potent gastric emptying activity. N-(4-Benzyl-3-morpholinyl)methylbenzamide (5a) and its analogues 5b--e had weaker activity. However, N-(4-benzyl-3-morpholinyl)ethylbenzamide 8 was as potent as 3a. Benzamides 6a--e, having seven-membered heteroalicycles, showed fairly potent activity. Molecular superimpositions of 5a, 6a and 8 upon 3a using computer graphics suggested that the direction of the N-benzyl group greatly influences the gastric emptying activity, whereas the location of the alicyclic nitrogen is less critical.

Animals↗
PubMed1995

Development of potent serotonin-3 (5-HT3) receptor antagonists. I. Structure-activity relationships of 2-alkoxy-4-amino-5-chlorobenzamide derivatives.

A new series of 2-alkoxy-4-amino-5-chlorobenzamide derivatives bearing five- to seven-membered heteroalicyclic rings in the amine moiety was synthesized and evaluated for serotonin-3 (5-HT3) receptor antagonistic activity by assaying the ability to antagonize the von Bezold-Jarisch reflex in rats. The five- to seven-membered heteroalicycles comprise pyrrolidine, morpholine, 1,4-thiazine, piperidine, piperazine, 1,4-oxazepine, 1,4-thiazepine, azepine, and 1,4-diazepine rings. Among them, some benzamide derivatives having a 1,4-diazepine ring showed a potent 5-HT3 receptor antagonistic activity. In particular, 4-amino-5-chloro-N-(1,4-dimethylhexahydro-1H-1,4-diazepin-6- yl)-2- ethoxybenzamide (96) and the 1-benzyl-4-methylhexahydro-1H-1,4-diazepine analogue 103 showed potent 5-HT3 receptor antagonistic activity without 5-HT4 receptor binding affinity.

Animals↗
PubMed1995

Development of potent serotonin-3 (5-HT3) receptor antagonists. II. Structrue-activity relationships of N-(1-benzyl-4-methylhexahydro-1H-1,4- diazepin-6-yl)carboxamides.

Our studies on 4-amino-5-chloro-2-ethoxybenzamides led to the discovery that the N-(1,4-dimethylhexahydro-1H-1,4-diazepin-6-yl)benzamide 9 and the 1-benzyl-4-methylhexahydro-1H-1,4-diazepine analogue 10 are potent serotonin-3 (5-HT3) receptor antagonists. Structure-activity relationship (SAR) studies on the influence of the aromatic nucleus of 9 and 10 upon inhibition of the von Bezold-Jarisch reflex in rats are described. Heteroaromatic rings such as pyrrole, thiophene, furan, pyridine, pyridazine, 1,2-benzisoxazole, indole, quinoline, and isoquinoline rings showed weak 5-HT3 receptor antagonistic activity. Within this series, use of the 1H-indazole ring as an aromatic moiety led to a substantial increase of the activity; the 1H-indazolylcarboxamides 54, 57, 97, and 102 showed potent 5-HT3 receptor antagonistic activity. The optimal compound identified via extensive SAR studies was N-(1-benzyl-4-methylhexahydro-1H-1,4-diazepin-6-yl)-1H-indaz ole-3- carboxamide (54), whose effect was superior to that of the corresponding benzamide 10 and essentially equipotent to those of ondanbsetron (1) and granisetron (4).

Animals↗
PubMed1995

Antisecretory effect of leminoprazole on histamine-stimulated gastric acid secretion in dogs: potent local effect.

Leminoprazole, an acid pump inhibitor, significantly reduces basal and stimulated gastric acid secretion in rats when administered via the systemic or local route. Our aim here was to characterize the antisecretory effect of leminoprazole on gastric acid secretion in conscious dogs. Gastric acid secretion by dogs with a vagally denervated Heidenhain pouch was stimulated by intravenous histamine infusion. Leminoprazole or omeprazole (as a reference drug) was administered either intravenously or locally into the pouch before or after histamine infusion. A bolus intravenous administration of leminoprazole and omeprazole, respectively, significantly and dose-relatedly inhibited the stimulated gastric acid secretion for > 26 hr. Local application of leminoprazole, but not omeprazole, significantly inhibited the acid secretion when applied for 15 to 30 min. The duration of the local antisecretory effect observed after 30 min application was around 8-10 hr. The acid-degraded products of leminoprazole had no effect when applied to the pouch. The blood concentration of leminoprazole was very low at 1 hr after local application. These results indicate that leminoprazole suppresses the secretory function of the parietal cells of dogs, via both the intravenous and local routes. It remains unknown whether or not locally applied leminoprazole produced the acid inhibition by inhibiting the acid pump.

Animals↗
PubMed1995

Different behavior of forearm blood flow during intermittent isometric handgrip in a thermo-neutral and a hot environment.

The purpose of the present study was to evaluate the different behavior of forearm blood flow (FBF) during intermittent isometric handgrip (IIHG, 6 seconds contraction +6 seconds relaxation) in a thermoneutral versus a hot environment. Six healthy men performed three times of 5-minute period IIHG at three different work loads (10%, 20% and 30% MVC). The IIHG was performed with the right hand. The experiments of IIHG were performed at two different air temperatures (25 degrees C and 40 degrees C, RH: 50%), and an experiment without work was also carried out at 40 degrees C (RH: 50%). The physiological responses measured involved heart rate (HR), cardiac output (CO), mean arterial blood pressure (MBP), FBF, and skin blood flow (SBF). HR, CO and SBF showed higher values during IIHG at 40 degrees C than at 25 degrees C. MBP had a tendency to increase with the intensity of work load at both 25 degrees C and 40 degrees C. Since intramuscular pressure might increase during contraction periods at 20% MVC and 30% MVC at 25 degrees C, FBF was significantly higher during relaxation periods than during contraction periods. FBF showed similar values between contraction and relaxation periods at 10% MVC at both temperatures. The present study suggested that FBF was sufficient for active muscles during IIHG at 10% MVC. FBF of contraction periods was close to that of relaxation periods at 40 degrees C due to the modulation of the sympathetic outflow to the muscles and/or the decreased efficiency of the muscle pump. It was suggested that FBF showed different behaviors during HHG at 25 degrees C versus at 40 degrees C.

Adult↗
PubMed1995

Circulatory regulation during supine and sitting intermittent isometric handgrip in a hot environment.

We studied the circulatory regulation during intermittent isometric handgrip (IIHG, six seconds contraction + six seconds relaxation) in supine and sitting postures in a hot environment (40 degrees C, RH: 50%). Eight healthy male subjects performed thrice 5-minute period IIHG at three different work loads (10%, 20% and 30% MVC). The IIHG was performed with the right hand in the two postures. Heart rate (HR), cardiac output (CO), mean arterial blood pressure (MBP), forearm blood flow (FBF), skin blood flow (SBF), foot swelling (FSW) and tympanic temperature (Tty) were measured during IIHG, resting and recovery periods. During IIHG in a hot environment, HR, MBP, FSW and Tty showed higher values in the sitting than in the supine posture. FBF during relaxation showed higher values at high work load than at low work load in the two postures. FBF showed higher values in the sitting than in the supine posture, except during relaxation at 30% MVC. It was concluded that the decrements of blood volume of splanchnic organs might be greater in the sitting than in the supine posture due to sympathetic vasoconstrictor activity, and were responsible for the redistribution of blood flow. Posture had an effect on FBF because of hydrostatic pressure.

Adult↗
PubMed1995

Changes in body shape of young individuals from the aspect of adult physique model by factor analysis.

The purpose of this study was to clarify characteristics of age-related changes in body shape in adolescence, in 11- to 19-year-old boys and girls, by using previously reported physique models of adult men and women as the scale. The scale consisted of four factors obtained by factor analysis using 30 items as variables, such as the values measured for the physique, skinfold thickness and body composition. The four factors were Factor 1: body fat, Factor 2: mass, Factor 3: leg length to height ratio, and Factor 4: length, and were interpreted in the men and women in a similar manner. The subjects were 307 boys and 368 girls; all were healthy. Thirty items were measured and included the values measured for the physique, skinfold thickness and body composition, as in the men and women. Factor scores in the subjects were standardized by mean and standard deviation for each item in the adult subjects, and calculated for individuals by using the coefficient of factor score in the adult subjects. The body shapes of the boys and girls were investigated from the factor score by age calculated for each factor. The following results were obtained: 1. Factor 1 tended to gradually decrease and reached the adult level at 15 years of age in the boys.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Effects of time stress on psychophysiological responses during data entry tasks.

Six male and six female students (19-23 yrs) volunteered as subjects in the present experiment. Subjects performed the data entry tasks. A hundred and twenty single digit numbers 12 by 10 lines matrix were displayed in a random sequence on the left side of monitor. Subjects input the same numeral as these numbers one by one with clicking of the mouse on the ten keys displayed on the right side of the monitor. Each task consists of the following conditions: 1) system response time is fast or slow; 2) delete the input numerals from 120 numbers or not; 3) button flashes after input or not; and 4) the remaining time is displayed or not during performing the tasks. These tasks are programmed to be finished automatically after 200 seconds independent of the rate of completing all inputs. We measured heart rate (HR), systolic and diastolic blood pressure (SBP and DBP), skin blood flow (SBF), skin potential level (SPL), number of errors (Es), total number of input and subjective ratings concerning the degree of irritation (SR1), difficulty of input (SR2) and unpleasantness in operation (SR3). It was shown that when system response time was slow, even the average of heart rate and blood pressure were lower than fast system response time, however, the subjects felt greater emotional irritation, difficulty of input and unpleasantness in operation hence making more errors.

Adult↗
PubMed1995

Characteristics of body shape of female athletes based on factor analysis.

We examined the body shape of female athletes in comparison with female adult non-athletes by factor analysis. The subjects were 433 adult non-athletes and 464 athletes participating in 11 different sporting events. The physique, skinfold thickness and body composition of each subject were measured. The values obtained from non-athletes were analyzed by factor analysis, and the body shape of the athletes was then analyzed according to these factors. Four main factors with which 80 percent of total variance could be explained were body fat (Factor 1), mass (Factor 2), leg length to height ratio (Factor 3) and length (Factor 4), and were extracted from the values from non-athletes. The body shape of the athletes could be classified into 4 categories by cluster analysis for factor score of sporting events: less body fat and slim type, average type like non-athletes, muscular and well-balanced type, and tall and well-developed mass. Compared with non-athletes, female athletes for all sporting events had less body fat. Moreover, the athletes had a body shape suitable for their sporting events; i.e., their mass, length of leg and height.

Adult↗
PubMed1995

Serum levels of six pancreatic enzymes as related to the degree of renal dysfunction.

OBJECTIVES: Currently, serum total amylase, pancreatic isoamylase (P-amylase), lipase, trypsin(ogen), phospholipase A2 (PLA2), and elastase I are advocated to be useful in diagnosing pancreatic diseases. However, the most useful among the above six enzymes in patients with impaired renal function has not been fully clarified. We, therefore, studied the relation of the serum levels of the above enzymes and creatinine clearance (CrCl) in normal controls and patients with chronic renal insufficiency or failure. METHODS: PLA2 and elastase I were assayed by RIA, trypsin(ogen) by EIA and others by activity. Subjects were 24 healthy controls and 47 patients with impaired renal function and no apparent pancreatic diseases. RESULTS: 1) Elastase I was significantly elevated only in patients with a CrCl of 10 ml/min or less, whereas others were elevated already in patients with a CrCl below 40 ml/min; 2) in 12 patients with a CrCl between 13 and 39 ml/min, lipase tended to be less frequently raised than others, except elastase I, although the difference was statistically insignificant; 3) in 28 patients with a CrCl between 40 and 74 ml/min, lipase was less frequently elevated than others, except elastase I and PLA2; 4) in seven patients with a CrCl of 10 ml/min or below, elastase I tended to be less frequently elevated than others, although the difference was statistically insignificant; and 5) the degree of elevation was within 2.5 times the upper limits of reference values in all enzymes, except trypsin(ogen) (within 4.8 times). CONCLUSIONS: Elastase I was least vulnerable to impaired renal function followed by lipase. We, therefore, recommend combined assays of elastase I and lipase for detecting pancreatic diseases in patients with renal insufficiency. When cut-off levels are set at 2.5 times the upper limit of reference values, P-amylase or PLA2 can replace lipase.

Aged↗
PubMed1995

[Chromosomes, morphologic subtypes and their prognostic evaluation in acute non-lymphocytic leukemia].

Cytogenetic and morphological analyses were performed on 55 adult patients (34 males, 21 females) with acute non-lymphocytic leukemia (ANLL) diagnosed between 1986 and 1992, and the results were studied with regard to therapeutic response and prognosis. Eleven patients had M1 (20%), 14 had M2 (25.5%), 14 had M3 (25.5%), 7 had M4 (12.7%), 3 had M5 (5.5%), 5 had M6 (9.1%) and one had M7 (1.8%). The overall incidence of chromosomal abnormalities were 65.5% including 10 cases (18.2%) with t (8;21), 12 (21.8%) with t (15;17), 5 (9.1%) with pseudodiploid, 3 (5.5%) with hyperdiploid, 2 (3.6%) with hypodiploid and 4 (7.3%) with abnormalities of 5 or 7 chromosomes. Outcomes were analyzed in 45 patients. 36 patients (80%) achieved complete remission (CR). All 12 patients with M2 entered CR, and they showed a significantly longer median survival than M1. The median survival of 10 patients with t (8;21) was significantly longer than that of patients with t (15;17). However, therapeutic response and prognosis did not correlate with either chromosomal status (NN, AN, or AA) or with age-groups (> or = 60, < 60). These results confirmed that morphological subtypes and certain types of chromosomal abnormality are important variables in determining the prognosis of adult patients with ANLL.

Adolescent↗
PubMed1995

[Phenotypic analysis of myeloma cells].

Recent 2-color phenotypic analysis using anti-CD38 antibody reveals that plasma cells alone locate at CD38strong positive (CD38++) fraction and expression of adhesion molecules such as VLA-5 and MPC-1 can define VLA-5-MPC-1- immature, VLA-5-MPC-1+ intermediate and VLA-5+ MPC-1+ mature plasma (myeloma) cells. Furthermore, phenotypic analysis of plasma cells with anti-CD19 and -CD56 antibodies can distinguish normal (polyclonal) plasma cells from malignant (monoclonal) plasma cells; normal plasma cells from various tissues are all CD19+ CD56-, while malignant plasma cells are mostly CD19- CD56+. Therefore, this 2-color phenotypic analysis is very useful for differential diagnosis of bone marrow plasmacytosis, that is, myeloma, benign monoclonal gammopathy or polyclonal gammopathy, and furthermore contributes to understanding of differentiated stages of myeloma cells (immature, intermediate or mature myeloma cells).

Antigens, Surface↗
PubMed1995

[Association of chronic neutrophilic leukemia and myeloma with fibrillar inclusions in granulocytes].

A 57 year-old-female was incidentally found to have leukocytosis in September 1988. Physical examination revealed anemia and marked hepatosplenomegaly. Her WBC count was 33,400/microliters with 95% mature neutrophils showing toxic granules. Her neutrophil alkaline phosphatase score was 482, and serum VB12 14,600 pg/ml. Serum immunoglobulin concentrations were 582 mg/dl for IgG, 3,628 mg/dl for IgA and 48 mg/dl for IgM. IgA was determined as monoclonal origin of lambda type. Bone marrow aspiration revealed a hypercellular marrow with active granulocytopoiesis and increased plasma cells. Cytogenetic study revealed normal karyotype. The bcr rearrangement was negative for bone marrow cells. An electronmicroscopy demonstrated fibrillar inclusions in granulocytes. We diagnosed this case as a chronic neutrophilic leukemia (CNL) associated with multiple myeloma. She was treated with a course of low dose busulfan without beneficial response. She was admitted for development of huge subcutaneous hematoma of left waist in October 1990. Laboratory findings were: Hb 7.0 g/dl, WBC 55, 300/microliters, Platelets 3.3 x 10(4)/microliters, and IgA 6,607 mg/dl. She required frequent transfusions. She died of pneumonia in July 1991. The peculiar fibrillar inclusions with CNL has not been reported so far. The origin and significance of such structure remains uncertain.

Female↗