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Biomedical subjects

H Harada

Publications and source records attributed to H Harada.

At least 379 records · Page 21Linked to original sources

A schizophrenic patient who developed extreme hypothermia after an increase in the dose of haloperidol: a case report.

A patient with chronic schizophrenia, who had been treated for a long time with chlorpromazine, haloperidol, levodopa, benserazide hydrochloride, diazepam and biperiden, developed extreme hypothermia (about 32 degrees C) when the dose of haloperidol was increased because of a deterioration of the patient's mental symptoms. No other physical manifestations were observed, except bradycardia. The turnover of noradrenaline in the cerebrospinal fluid and blood was increased in association with the hypothermia in this patient. A hypothesis about the involvement of monoamine imbalance in changes in body temperature is discussed.

Antipsychotic Agents↗

Structure and regulation of the human interferon regulatory factor 1 (IRF-1) and IRF-2 genes: implications for a gene network in the interferon system.

Interferon regulatory factor 1 (IRF-1) and IRF-2 are structurally similar DNA-binding factors which were originally identified as regulators of the type I interferon (IFN) system; the former functions as a transcriptional activator, and the latter represses IRF-1 function by competing for the same cis elements. More recent studies have revealed new roles of the two factors in the regulation of cell growth; IRF-1 and IRF-2 manifest antioncogenic and oncogenic activities, respectively. In this study, we determined the structures and chromosomal locations of the human IRF-1 and IRF-2 genes and further characterized the promoters of the respective genes. Comparison of exon-intron organization of the two genes revealed a common evolutionary structure, notably within the exons encoding the N-terminal portions of the two factors. We confirmed the chromosomal mapping of the human IRF-1 gene to 5q31.1 and newly assigned the IRF-2 gene to 4q35.1, using fluorescence in situ hybridization. The 5' regulatory regions of both genes contain highly GC-rich sequences and consensus binding sequences for several known transcription factors, including NF-kappa B. Interestingly, one IRF binding site was found within the IRF-2 promoter, and expression of the IRF-2 gene was affected by both transient and stable IRF-1 expression. In addition, one potential IFN-gamma-activated sequence was found within the IRF-1 promoter. Thus, these results may shed light on the complex gene network involved in regulation of the IFN system.

Animals↗

Regulation of pemphigus and desmosomal antigen expression by keratinocyte differentiation.

We studied in vivo binding sites of pemphigus antibodies and the expression of pemphigus and desmosomal antigens by keratinocytes in various culture periods. Both pemphigus vulgaris (PV) and pemphigus foliaceus (PF) antibodies mainly bound to the desmosomal areas of the lesional skin. Desmoglein and PV antigens co-localized on the cultured normal human keratinocytes in both monolayers and stratified areas. PF antigens, frequently together with involucrin and suprabasal keratins, were expressed by stratified keratinocytes. The Western blotting study demonstrated two different desmogleins with molecular sizes of 130 and 150 kD. The 130-kD desmoglein bore PV antigenic epitopes. The 150-kD band increased in volume as cultured keratinocytes stratified. PV antigen expression on the 130-kD desmoglein precedes PF antigen formation occurring in keratinocyte differentiation.

Antigen-Antibody Reactions↗

Synthesis and biological activities of the optical isomers of (+/-)-4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2- morpholinyl]methyl]benzamide (mosapride).

The enantiomers, (S)-(-)-1 and (R)-(+)-1, of (+/-)-4-amino-5-chloro-2-ethoxy- N-[[4-(4-fluorobenzyl)-2-morpholinyl]methyl]benzamide (mosapride) [(+/-)-1], a new and selective gastroprokinetic agent, were prepared from optically active [4-(4-fluorobenzyl)-2-morpholinyl]methylamines (S)-(-)-4 and (R)-(+)-4, respectively. The requisite (S)-(-)-4 and (R)-(+)-4 were prepared by optical resolution of [4-(4-fluorobenzyl)-2-morpholinyl]methyl p-toluenesulfonate [(+/-)-5] using (-)- and (+)-N-(p-toluenesulfonyl)glutamic acids, followed by amination of the tosyloxy groups of (R)-(-)-5 and (S)-(+)-5, respectively. The absolute configurations of (R)-(-)-5 and (S)-(+)-5 were determined on the basis of an asymmetric synthesis of (R)-(-)-5 from (S)-(+)-benzyl glycidyl ether [(S)-(+)-11]. Mosapride and its enantiomers, (S)-(-)-1 and (R)-(+)-1, were essentially equipotent in serotonin 5-HT4 receptor agonistic activity on the electrically evoked contractions in isolated guinea pig ileum.

Animals↗

[Effects of handgrip work and heat load on heart rate variability].

The purpose of the present study was to evaluate cardiac sympathetic (SNS) and parasympathic (PNS) nervous system activities during isometric continuous and intermittent handgrip with power spectrum analysis of heart rate variability (HRV). Eight healthy men performed work at 10% maximum voluntary contraction. The sequence of tests included three different work patterns: 1) the continuous handgrip for 30 min, 2) the intermittent handgrip (10 sec contraction +5 sec relaxation) for 45 min, 3) the intermittent handgrip (10 sec contraction +10 sec relaxation) for 60 min. These experiments were performed at two different heat loads (25 degrees C and 40 degrees C, R.H. 50%). To evaluate HRV, low frequency component (0.03-0.15Hz: LFP) and high frequency component (0.15-0.5Hz: HFP) power were calculated. The SNS and PNS activities were evaluated by LFP/HFP and HFP/(HFP + LFP), respectively. Summary of the results was shown below. 1) The change of the SNS and PNS activities were not significant among the different work patterns, due to the lower work load in the present experiment. 2) The increase of HR at 25 degrees C was mediated primarily by the decrease of the PNS activities during the work periods. 3) The effects of heat loads on the SNS and PNS activities were significant. Briefly, at the same work pattern, the SNS activities at 40 degrees were higher than those at 25 degrees C, but the PNS activities at 40 degrees C were lower than those at 25 degrees C.

Adult↗

[Localized muscular load to different work patterns and heat loads during handgrip].

The physiological responses and the magnitude of perceived fatigue (MPF) were estimated from eight healthy men during isometric continuous and intermittent handgrip at 10% maximum voluntary contraction (MVC). The physiological responses involved electromyogram (EMG), heart rate (HR), mean blood pressure (MBP) and forearm blood flow during contraction (FBFC) and relaxation (FBFR). The sequence of tests included three different work patterns: 1) continuous handgrip for 30 min, 2) intermittent handgrip (10 sec contraction +5 sec relaxation) for 45 min, 3) intermittent handgrip (10 sec contraction +10 sec relaxation) for 60 min. These experiments were performed on two different heat loads (25 degrees C and 40 degrees C, H.R. 50%). The results were as follows: 1) The localized muscle fatigue in the forearm was observed during the work periods. 2) The mean frequency of EMG was higher at 40 degrees C than 25 degrees C. 3) FBFR was significantly lower than FBFC at 40 degrees C. 4) MPF and MBP were little influenced by the heat load. 5) MPF correlated well with both HR and MBP.

Adult↗

[Responses of electroencephalogram to different odors].

The responses of electroencephalogram (EEG) to different odors and their densities were studied on four men and two women at rest while sitting. The odors examined were citrus, floral and lavender, and their densities were 100 ppb and 200 ppb. The odors were released for ten minutes from a duct to fill the room completely. The subjective estimation indicated that citrus had a tendency to be the most comfortable odor in this study, but it was not significant. To evaluate changes of EEG, the power spectra of frequency-fluctuation of alpha wave (Fz) and the rate of alpha, beta, and beta/alpha wave (Oz, Fz) were calculated. The rate of alpha wave (Oz) in the period of giving out the citrus at 100 ppb was significantly (p < 0.05) higher than that of the lavender. The rate of beta wave (Oz) in the period of giving out the floral at 200 ppb was significantly (p < 0.05) higher than that of the lavender. The regression coefficient of the power spectra of frequency-fluctuation of alpha wave in the period of giving out the lavender at 100 ppb was significantly higher than those in the other periods of the experiment. The regression coefficient of the power spectra of frequency-fluctuation of alpha wave for lavender given out at 200 ppb was significantly (p < 0.01) higher than those for the other odors given out. It seems that the regression coefficient of the power spectra of frequency-fluctuation of alpha wave can be used for the evaluation of psychophysiological responses.

Adult↗

Classification of body shape of male athletes by factor analysis.

The purpose of this study was to evaluate the body shape of athletes in comparison with adult non-athletes by factor analysis. The subjects were 210 male adult non-athletes and 485 male high school age and adult athletes participating in 13 different sporting events. Physique, skinfold thickness and body composition of each subject were measured. Measured values from adult non-athletes were analyzed by factor analysis, and body shape of the athletes was then analyzed according to these factors. The results are summarized as follows: 1. Four main factors, that is, body fat, mass, leg length to height ratio and length, which could explain 88.5 percent of total variance, were extracted from the measured values from adult non-athletes. 2. Similarity of body shape between sporting events was analyzed by cluster analysis. Body shape of the athletes could be classified into 3 categories: muscular and well-balanced type; rich muscular and large-built type; and rich muscular and long-torso type. Compared with adult non-athletes, male athletes had less body fat and greater mass except for long-distance runners. The present results suggested that the athletes had body shapes suitable to their sporting events.

Adult↗

[A case of Swyer-James syndrome--a morphological study with inflated fixed lung].

Morphological features of Swyer-James syndrome were studied in a specimen obtained during left pneumonectomy. A 67-year-old woman was admitted because her left lung was hyperlucent and contained a solitary nodule. Primary lung adenocarcinoma complicated with Swyer-James syndrome was diagnosed, and left pneumonectomy done. The left upper lobe was inflated and fixed for morphological study. The volume of the specimen was obviously lower than normal but the bronchial branching was normal. Macroscopically, the specimen had irregular bronchial walls, bronchiectatic changes, and dilation of distal air spaces, similar to panlobular emphysema. Microscopically, there was scarring in periarteriolar regions that suggested bronchiolitis obliterans, enlargement of distal airspaces, and an abnormally low number of capillaries. These findings suggest hypoplasia of the lung due to abnormal lung growth after birth.

Aged↗

Malignant T cell lymphoma associated with sarcoidosis.

We report an unusual case of non-Hodgkin T cell lymphoma associated with sarcoidosis. A 44-year-old woman was histologically diagnosed as having sarcoidosis in 1966. Diffuse interstitial lung disease and erythematous skin nodules disappeared following steroid therapy. Twenty years after sarcoidosis onset erythematous nodosum recurred and biopsy specimens revealed non caseating epithelioid granuloma. Thirty-seven months later a malignant T cell lymphoma developed in the skin portion where sarcoid lesions recurred. We discuss the possible relationship between the sarcoid inflammatory process and the development of a malignant T cell clone as origin of the T cell lymphoma.

Adult↗

Accelerated exon skipping of IRF-1 mRNA in human myelodysplasia/leukemia; a possible mechanism of tumor suppressor inactivation.

The transcription factor IRF-1 has been shown to function as a tumor suppressor. Here we report that a significant proportion of the IRF-1 mRNA detected in normal human hematopoietic cells and cultured cell lines lacks exon 2 (containing the AUG initiation codon) and 3 as a result of exon skipping. Surprisingly, when we examined the bone marrow and peripheral mononuclear cells from patients with myelodysplastic syndrome (MDS) or leukemia secondary to MDS, we could still detect the exon-skipped form but little or none of the intact IRF-1 mRNA. This appears to be the result of accelerated exon skipping since we could find no mutations within the exons and splicing junctions from these patients. The exon-skipped form of IRF-1 lacking exons 2 and 3 displayed neither DNA binding nor tumor suppressive activities. Thus this accelerated exon skipping may cause the inactivation of IRF-1 and thereby contribute to the development of human hematopoietic malignancies.

Cell Line↗

[A successful case of PA debanding after percutaneous transluminal angioplasty for restenosis of coarctation complex].

A 11-year-old boy, who had undergone the initial surgical repair for Coarctation complex at 6 months of age was readmitted to our hospital for radical correction. The initial repair at 6 months of age was patch angioplasty of coarctation, PDA division and PA banding. When he was 5 years old, a cardiac catheterization revealed spontaneous closure of VSD, restenosis of coarctation and RV outflow tract stenosis due to PA banding. This time he was treated with 2 steps of procedures. The first step was percutaneous transluminal angioplasty for restenosis of coarctation. Then RV outflow tract repair was performed at the second step. Postoperative course was uneventful.

Angioplasty, Balloon↗

Double burst stimulation with submaximal current.

The present study evaluated responses to double burst stimulation (DBS) at supramaximal and submaximal currents in 30 adult patients. Usually, DBS is applied with supramaximal stimulation, but this may be quite uncomfortable for the awake patient. Therefore, the authors investigated whether it is possible to obtain an accurate assessment of significant residual neuromuscular blockade if the stimulus current is reduced to 30 mA. In all patients, neuromuscular response to DBS three three (DBS3.3), DBS three two (DBS3.2) and train-of-four (TOF) stimulation at supramaximal and/or submaximal currents was recorded using a mechanomyograph, and the ratios of the fourth to the first twitch (T4/T1) induced by TOF stimulation at supramaximal current, and the height of the second response to the first (D2/D1) induced by DBS at 30 mA and supramaximal current were calculated. The relations between control T4/T1 ratios determined by supramaximal TOF stimulation and D2/D1 ratios determined by supramaximal DBS3.3 and submaximal DBS3.3 were Y = 0.99X + 0.08 and Y = 1.01X + 0.04, respectively, and there was no statistical difference between the two regression lines. The same relation between T4/T1 ratios and D2/D1 ratios by DBS3.2 were Y = 0.69X + 0.05 and Y = 0.72X + 0.02, respectively, and there was no significant difference. It is concluded that evaluation of the response to DBS at 30 mA has the same reliability as evaluation with supramaximal current.

Adult↗

[Megaloblastic anemia due to folate deficiency associated with hereditary spherocytosis].

A 19 years old male admitted to our hospital with fever, abdominal pain in May 1991. Physical examination revealed anemia, jaundice and marked splenomegaly. Severe pancytopenia with macrocytic hyperchronic anemia was noted along with elevated LDH and reduced serum folate. Blood smear showed nucleated RBCs, but only few microspherocytes. Bone marrow showed erythroid hyperplasia with remarkable megaloblastic changes. Megaloblasts were negative for PAS stain. Chromosome analysis revealed normal karyotype. Erythroleukemia was suspected initially, but his general condition as well as hematological data improved following 10 units of RBC transfusion. Following brief folic acid supplements, numerous microspherocytes became evident, typical osmotic fragility test revealed a pattern for hereditary spherocytosis. These observations led us to the diagnosis of hereditary spherocytosis complicated by megaloblastic anemia due to folate deficiency. As he developed folate deficiency again 10 months later, splenectomy were performed. The anemia improved after splenectomy.

Adult↗

[Cytological features and prognosis of megakaryoblastic leukemia].

Nine patients with acute leukemia showing 10% or more positive blast cells with platelet peroxidase (PPO) or CD41b were diagnosed as megakaryoblastic leukemia. Three patients transformed from myelodysplastic syndromes or myeloproliferative disorders. The PPO positivity ranged from 7 to 55% (median 45%), and that for CD41b was 1.6 to 67.0% (median 16.4%). Because electron microscopic myeloperoxidase or glycophorin A were also positive in some patients, and also because CD41b positivity was often discordantly lower than PPO positivity, a possibility of mixed leukemia demonstrating myeloid or erythroid differentiation was suggested in 6 of these cases. As for the treatment results, all 3 pediatric cases who received combination chemotherapy achieved complete remission (CR). Among 6 adult cases CR was obtained in only one patient to whom low-dose cytosine arabinoside was administered. The remaining adult patients who received combination chemotherapy died relatively early.

Adult↗

The oncogenic transcription factor IRF-2 possesses a transcriptional repression and a latent activation domain.

IRF-1 and IRF-2 are two structurally related transcription factors originally identified as regulators of the type I interferon (IFN) system. IRF-1 functions as an activator whereas IRF-2 binds to the same cis-elements and can repress IRF-1 action. More recently these two factors have been shown to act in a mutually antagonistic manner to regulate cell growth; overexpression of the repressor IRF-2 leads to cell transformation, whereas concomitant overexpression of IRF-1 leads to reversion. Previous studies have identified DNA-binding domains in IRF-1 and IRF-2 and an activation domain in IRF-1. In the present study we show that IRF-2 also possesses a transcriptional repression domain in its carboxyl terminal region. We further observe that a LexA-IRF2 fusion can inhibit the function of an activator positioned nearby in the promoter. Thus, repression by IRF-2 may involve both competition with IRF-1 for binding to the promoter as well as the 'silencing' of nearby activators. Furthermore, we demonstrate the presence of a latent activation domain in the central region of IRF-2 and speculate that IRF-2 may contribute to gene activation under certain conditions.

Animals↗