Association between serotonin type 2 receptor (HTR2) and bronchial asthma in humans.
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Asthma↗
Biomedical subjects
K Morimoto
Publications and source records attributed to K Morimoto.
[Problems related to organ transplantation as an allocation of scarce medical resources: a review].
The criteria for allocation of medical resources at three different stages which lead to organ transplantation are discussed, along with advantages and disadvantages. When each criterion was examined individually, it was difficult to determine the best criterion for selection of recipients of donated organs in the most ethically desirable fashion. However, when we examined the suggested criteria on the basis of an actual case, the efficacy of transplantation or expected length of the survival years was most often used as a criterion to select the recipients of donated organs. To increase more support for organ transplantation in our society, it is necessary to more fully discuss how scarce donated organs should be allocated to recipients in a fair and equitable manner.
Decision Making↗
8-Hydroxydeoxyguanosine in human leukocyte DNA and daily health practice factors: effects of individual alcohol sensitivity.
A typical oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OHdG), was evaluated in human polymorphonuclear leukocytes (PMN) and mononuclear leukocytes (MN) by an anaerobic determination method. The mean 8-OHdG values were the lowest level ever reported [PMN, 3.07 +/- 1.45; MN, 2.37 +/- 1.21 8-OHdG/10(6) deoxyguanosine molecules (dG); n = 92]. According to a self-administered questionnaire to 92 healthy male workers, the relationship was investigated between 8-OHdG in leukocytes and daily health practice factors, that is, the frequency of physical exercise, smoking status, alcohol drinking, nutritional balance, and the degree of mental stress. A significant difference was observed only in alcohol drinking in subjects classified by aldehyde-dehydrogenase 2 isozyme (ALDH2) genotype. Habitual alcohol intake appeared to increase 8-OHdG in PMN from ALDH2-deficient subjects. Neither age, body mass index, nor any other factors examined showed any significant correlation with the 8-OHdG levels in leukocytes.
8-Hydroxy-2'-Deoxyguanosine↗
Low Km aldehyde dehydrogenase (ALDH2) polymorphism, alcohol-drinking behavior, and chromosome alterations in peripheral lymphocytes.
Excessive drinking of alcohol is now widely known to be one of the major lifestyle choices that ca effect health. Among the various effects of alcohol drinking, cytogenetic and other genotoxic effects are of major concern from the viewpoint of prevention of alcohol-related diseases. Alcohol is first metabolized to acetaldehyde, which directly causes various types of chromosomal DNA lesions and alcohol-related diseases, and is then further detoxified to the much less toxic metabolite acetate. About 50% of Oriental people are deficient in the aldehyde-dehydrogenase 2 isozyme (ALDH2) that can most efficiently detoxify acetaldehyde. We have performed a series of experiments to investigate how the genetic deficiency in ALDH2 affects the behavioral pattern for alcohol drinking and the sensitivity of peripheral lymphocytes to the induction of chromosome alterations by exposure to alcohol and alcohol-related chemicals. We found great effects of the ALDH2 genotypes on alcohol sensitivity and alcohol-drinking behavior. We also show that lymphocytes from habitual drinkers with the deficient ALDH2 enzyme had significantly higher frequencies of sister chromatid exchanges than those from ALDH2-proficient individuals.
Adult↗
Health promotion activities in Japan.
In Japan, the spread of immunization and the development of antibiotics and antituberculosis drugs have dramatically decreased the mortality rate from infectious diseases since World War II. Alterations in health practices, such as decreasing the intake of salty foods and strict management of hypertension, have resulted in prominent decreases in the mortality rate from cerebrovascular diseases, especially from cerebral hemorrhage. However, we still have high death rates from malignant neoplasms and circulatory diseases, which may be partly prevented through improvement of health status. We discuss here about various health promotion activities recently reported in Japan, including prevention of smoking, promotion of exercise, improvement of nutrition, improvement of mental health status, and health risk appraisal. Finally we would like to stress the importance of comprehensive assessment of health status in order to encourage health promotion activities further.
Exercise↗
CD44 and hyaluronan binding by human myeloid cells.
The CD44 cell surface molecule has been shown to be the principal cell surface receptor for hyaluronan (or hyaluronic acid), a glycosaminoglycan component of marrow extracellular matrix. However, its affinity for hyaluronan is not constitutive, since it depends on the cell type, the stage of differentiation and on activation by external stimuli including certain anti-CD44 antibodies and phorbol esters. Except for a few lymphoid cell lines, hematopoietic cells do not spontaneously bind hyaluronan and initial studies reported that, contrary to lymphocytes, myeloid cells could not be activated to bind hyaluronan. Because CD44 plays an important role in the initial phases of hematopoiesis, as shown by experiments using blocking anti-CD44 monoclonal antibodies, its capacity to mediate adhesion of primitive myeloid cells has been investigated. It was found that CD44 could mediate spontaneous adhesion to hyaluronan of immature myeloid cell lines KG1, KG1a, and TF1, which serve as a model for hematopoietic progenitors. However, despite expressing high amounts of CD44, no more than 15% of bone marrow progenitors could adhere to hyaluronan. Recent experiments have shown that a very important feature of CD44 is its capacity to be rapidly activated by certain antibodies and cytokines (GM-CSF and KL) from a low affinity to a high affinity state for hyaluronan. These data shed light on striking similarities in the functional regulation of CD44 and of the two integrin receptors VLA-4 (a4b1), and VLA-5 (a5b1), which are also expressed on hematopoietic progenitors. The relevance of these data to the regulation of normal hematopoiesis and mobilization of CD34+ progenitors in the view of cell grafting is analyzed. In addition, we show that in idiopathic myelofibrosis, the amount of hyaluronan is markedly increased in the extracellular matrix from the myeloproliferative spleen. Considering that the production of cytokines is enhanced in this disease, we discuss whether CD44-hyaluronan interaction may have a role in the pathophysiology of this myeloproliferative syndrome.
Antibodies, Monoclonal↗
Effects of long workhours on life-style, stress and quality of life among intermediate Japanese managers.
OBJECTIVES: In accordance with international coordination of labor conditions a Japanese campaign advocating less work finally got under way recently in the form of work-reducing policies of the government to prevent occupational and stress-related diseases. However, long workhours among intermediate managers, who are key persons in most organizations in Japanese industry, are still considered to be prevalent. This study was conducted to examine the workhours of intermediate managers and clarify the effects of long workhours on the life-style, subjective stress, and subjective quality of life among them. METHODS: Questionnaires were administered concerning workhours, life-styles, subjective stress, and subjective quality of life to 3870 heads of a division or a section and 2666 foremen in 110 firms in Japan. RESULTS: The prevalence of > or = 10 workhours was 69.7% for the divisional or sectional heads and 53.2% for the foremen. Long workhours had significant effects on the managers' life-style, such as sleeping pattern and regularity of daily life and meals. The divisional or sectional managers with long workhours perceived higher stress [odds ratio (OR) 2.51, 95% confidence interval (95% CI) 2.17-2.90] and lower quality of life (OR 1.17, 95% CI 1.02-1.36) than those who worked relatively short hours. The foremen with long workhours perceived higher stress (OR 2.35, 95% CI 2.01-2.75) and lower quality of life (OR 1.26, 95% CI 1.08-1.46) than those who worked relatively short hours. CONCLUSIONS: Long workhours may be associated with poorer life-style, higher stress, and lower quality of life among managers at the intermediate level.
Administrative Personnel↗
[Clinical and electroencephalographic studies in children with hemimegalencephaly].
Clinical and electroencephalographic (EEG) studies were performed in two children with hemimegalencephaly. The ages of seizure onset were 44 hours after birth in one infant and 33 days of postnatal life in the other patient. In both children, infantile spasms (IS) associated with hemihypsarrhythmia, developed at 1.5 months and 4 months, respectively. The subsequent clinical courses in these children were notable for frequent, intractable seizures. The seizures consisted of either generalized or partial seizures which originated from not only the hemimegalic hemisphere but also the contralateral one. Later, the clinical and EEG findings in one child indicated the development of Lennox-Gastaut syndrome (LGS). These findings suggested that the lesions of epileptogenesis in patients with hemimegalencephaly involved not only the pathological hemisphere, but also the contralateral hemisphere and subcortical structures. A detailed neurophysiological investigation in hemimegalencephaly could help the elucidation of the pathophysiology of intractable epilepsies, such as IS or LGS.
Brain↗
[A phase 3 clinical trial of 123I-iomazenil, a new central-type benzodiazepine receptor imaging agent (Part 1)--report on clinical usefulness in diagnosis of various brain diseases].
Iomazenil (IMZ) is a partial inverse agonist of central-type benzodiazepine receptors (BZR) which binds specifically to BZR with high affinity. The safety and clinical effectiveness of 123I-IMZ SPECT in the diagnosis of brain diseases were evaluated in 655 patients with various brain diseases, such as epilepsy, cerebrovascular diseases, degenerative diseases and mental disorders relating to BZR. This was a Phase 3 study conducted as a multicenter trial at 52 collaborating institutions. There was no significant adverse reactions in the clinical symptoms or abnormal laboratory test values. The investigators judged 123I-IMZ SPECT to be effective in 95% of 638 analyzed cases. The injected dose did not correlate with the image quality or the clinical effectiveness of 123I-IMZ SPECT, suggesting that these items depend largely on the characteristics of the apparatus used, the disease or pathology of the patients, rather than the dose. We conclude that 123I-IMZ imaging is safe and provides effective information based on BZR binding which is useful in the diagnosis of various brain diseases.
Adolescent↗
[A phase 3 clinical trial of 123I-iomazenil, a new central-type benzodiazepine receptor imaging agent (Part 2)--Report on clinical usefulness in diagnosis of degenerative neurological diseases and mental disorders].
Iomazenil (IMZ) is a partial inverse agonist of central-type benzodiazepine receptors (BZR) which binds specifically to BZR with high affinity. A multi-center Phase 3 clinical study was performed to evaluate the clinical usefulness of 123I-IMZ-SPECT in the diagnosis of brain disorders in 169 patients with degenerative neurological diseases and 37 patients with mental disorders such as neurotic, stress-related and somatoform disorders. In dementia, the decrease in activity in late images, obtained three hours after administration of 123I-IMZ, correlated negatively with the dementia score. In Parkinson's disease and spinocerebellar degeneration. 123I-IMZ showed a more profound decrease in uptake in late images than seen in the cerebral blood flow (CBF) images, and this decrease was in proportion to the duration and severity of the illness. In mental disorders, the ratio of the late to early image counts showed a negative correlation with Hamilton's anxiety scale in all regions in the brain cortices. In panic disorders, the ratio of the cerebral count to the cerebellar count in the late images correlated negatively with the severity of the attack in the frontal, temporal and parietal cortices. These results suggest that 123I-IMZ-SPECT enables us to evaluate the neuronal damage in degenerative diseases and the decrease in the BZR binding potential in mental disorders.
Adult↗
[A phase 3 clinical trial of 123I-iomazenil, a new central-type benzodiazepine receptor imaging agent (Part 3)--Report on clinical usefulness in epilepsy].
A Phase 3 clinical trial of 123I-Iomazenil (IMZ), a tracer which binds specifically to central-type benzodiazepine receptors (BZR), was performed, and the clinical usefulness of IMZ was evaluated in 121 patients with epilepsy (106 cases with partial epilepsy and 15 cases with generalized epilepsy). A regional abnormality in the BZR distribution was detected in late IMZ images in 20 of 24 cases without abnormal MRI and/or X-ray CT findings. Moreover, only 16 of these 20 cases showed abnormal findings in the cerebral blood flow (CBF) images. In partial epilepsy, abnormal regions in late IMZ images agreed or partially agreed with epileptic foci estimated from the clinical symptoms of epileptic seizures, interictal EEG, and MRI and/or X-ray CT findings in 76%, 70% and 96% of the cases detected. These regions also agreed or partially agreed with the estimated epileptic foci in 92% of the cases with foci estimated by combination of those three methods and in 72% of those estimated by ictal EEG. The agreement or partial agreement rates of late IMZ images with each of the other methods were higher than those of CBF images, although the differences were not significant. For surgically-proven epileptic foci without any abnormality in the CBF image, abnormal regions were detected in late IMZ images. These findings suggest that IMZ SPECT is a useful new tool for detecting epileptic foci based on the distribution of BZR in the brain.
Adult↗
[A phase 3 clinical trial of 123I-iomazenil, a new central-type benzodiazepine receptor imaging agent (Part 4)--Report on clinical usefulness in diagnosis of cerebrovascular diseases].
Single photon emission computed tomography (SPECT) using 123I-Iomanzenil (IMZ), a tracer which binds specifically to central-type benzodiazepine receptors, was performed in patients with cerebrovascular diseases (CVD) to determine the clinical signicigance of IMZ SPECT studies in evaluating the pathophysiology of CVD. IMZ SPECT images obtained three hours after administration of the tracer were compared with the images of cerebral blood flow (CBF) studies in 206 cases. In regions with decreased CBF, the uptake of IMZ was relatively preserved in patients with cerebral thrombosis in comparison with cerebral embolism, and in those with perforator branch infarction in comparison with cortical infarction. The uptake of IMZ decreased as a function of both the severity of the decrease in the CBF and the duration of illness in regions with a significantly decreased perfusion reserve. These results suggest that decreased IMZ binding in ischemic stroke reflects the neuronal damage caused by the cerebral ischemia. On the other hand, in patients with intracerebral hemorrhage, the cortical uptake of IMZ was relatively well-preserved in regions with decreased CBF, and the decrease in the uptake of IMZ was more profound as a function of the decrease in the CBF, especially in cases of putaminal hemorrhage. These results also suggest that the decreased cortical CBF is a remote effect caused by a neuronal disconnection, and neuronal damage may occur in regions with severely impaired CBF.
Brain↗
[LY188011 phase I study. Research Group of Gemcitabine (LY188011)].
LY188011 (Gemcitabine hydrochloride) is a new derivative of deoxycytidine. Phase I study was carried out by a cooperative study group. LY188011 was administered weekly for 3 consecutive weeks starting with an initial dose of 60 mg/m2 (1n) and then increasing the dosage to 1,000 mg/m2 (16.7n). Dose limiting factor was found to be myelosuppression (decreases of WBC, neutrophils and platelet), and MTD was considered to be 1,000 mg/m2. The nadir of WBC and platelet were observed after about 1-3 weeks. It took 1-2 weeks for their recovery. Other adverse reactions included fever, fatigue, anorexia, nausea/vomiting, anemia and transient elevations of GOT and GPT. However, those adverse reactions were mild. T1/2 rho of plasma concentration was about 19 min and the C5min was dependent on the dose. Anti-cancer effects were observed in one gastric cancer and two colon cancer patients. It is recommended that the dosing schedule for an early phase II study is 800 mg/m2 weekly for 3 weeks with 1 week of rest as one cycle, in multiple cycles.
Adult↗
[Preparation of F(ab')2 mu fragments of IgM monoclonal antibodies].
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Animals↗
[A study on the maternal plasma C21 steroids concentration during pregnancy].
During pregnancy, C21 steroids such as progesterone (P4), and cortisol (F), have been reported to be closely involved in uterine contraction. To clarify the association between changes in steroid hormones and the onset of delivery, we measured the concentrations of six C21 steroids in maternal blood by high performance liquid chromatography. Changes in each steroid hormone were evaluated by analysis of variance during pregnancy. Pregnenolone, a source of C21 steroids, gradually increased during pregnancy. P4 and 17P4, its metabolite, reached a peak 3 weeks before delivery and noticeably decreased thereafter. Accompanying a decrease in P4 and 17P4, 20P4 and F, its metabolite, were noticeably increased. The association among these steroid hormones was also evaluated. The correlation between P4 and F was reversed after 3 weeks before delivery. These results suggest that steroid hormones in the maternal blood begin to change dynamically about 3 weeks before delivery. In particular, a decrease in P4 and an increase in F seem to be closely related to the onset of delivery.
17-alpha-Hydroxyprogesterone↗
[Phase 2 clinical study of 123I-iomazenil in various cerebral diseases: part 1--examination of injection dose and clinical indications].
A phase 2 study of 123I-Iomazenil (IMZ) was performed to evaluate its clinical usefulness in SPECT imaging of central-type benzodiazepine receptors (BZR). A total of 246 patients with various central nervous system disorders [82 with epilepsy, 94 with cerebrovascular disease (CVD), 47 with degenerative disorders, 14 with mental disorders relating to BZR and 9 with other diseases] were intravenously injected with 111-222 MBq of IMZ. Early and late images were obtained 15 min and 180 min after injection as the mid-scan time, respectively. In comparison with regional cerebral blood flow (rCBF) images, the uptake of IMZ in the late images, which reflect the regional distribution of BZR, was relatively preserved compared to the uptake of CBF tracers in most of the patients with CVD. In the area of hyperperfusion in the subacute phase of cerebral infarction, however, the defects of IMZ uptake were accompanied by increased uptake of the CBF tracers. On the other hand, late IMZ uptake in most of the patients with the other diseases was decreased more significantly than the uptake of the CBF tracers, suggesting that cortical neuronal damage is more prominent than rCBF in these diseases compared to the vascular perfusional state. No adverse reactions were recognized relating to the IMZ administration. These results suggest that IMZ may provide us with valuable information for assessing pathophysiological state in the brain, which are difficult to achieve with other imaging modalities.
Adult↗
[Phase 2 clinical study of 123I-iomazenil in various cerebral diseases: part 2--clinical evaluation of central-type benzodiazepine receptor imaging with 123I-iomazenil SPECT].
A phase 2 clinical study of 123I-iomazenil (IMZ) was performed to evaluate its clinical usefulness as central-type benzodiazepine receptor imaging agent in 81 cases with epilepsy, 82 cases with cerebrovascular diseases (CVD), 35 cases with degenerative disorders and 14 cases with mental disorders. In epilepsy, IMZ SPECT images for detection of epileptic foci showed relatively high specificity compared with EEG recording in not only interictal but also ictal state, in spite of the fact that IMZ SPECT images was performed during interictally. It was surmised that IMZ SPECT provides valuable clinical information for detection of epileptic foci which are hard to be diagnosed by EEG. The frequency of abnormal findings by IMZ late images was higher than that by interictal blood flow images and comparable to that by ictal blood flow images. In patients with CVD, different observations were obtained between IMZ late images and blood flow images; for example, in regions of hemodynamic cerebral ischemia, postischemic reperfusion and other pathological perfusion, IMZ late images seemed to reflect the degree of cortical neuronal loss. In patients with degenerative disorders, the binding potential (calculated by a simple quantitative method for IMZ) and other parameters correlated with the dementia score. While the number of examined cases with mental disorders was limited, the frequency of abnormal findings with IMZ imaging was higher than that with morphological imaging.
Adult↗
[Isolation rate of E. coli from surgical infections and their susceptibilities].
Escherichia coli isolated from surgical infections during the period from July 1983 to June 1995 were investigated in a multicenter study involving 19 hospitals in Japan, and the following results were obtained. 1. Although the isolation rate of E. coli was not high from postoperative infections, it was most frequently isolated from primary infections throughout the study period. E. coli, Klebsiella spp. and anaerobic bacteria were predominant from fresh infections. From the cases that had previous antibiotics treatment, Enterococcus spp. were the most predominant isolates followed by MRSA and Pseudomonas spp. in this order. 2. Against E. coli, cefozopran, carumonam and aztreonam had the strongest activity, followed by cefmenoxime, imipenem, latamoxef, gentamicin and ofloxacin. Recently, we have noticed that antibiotic resistant E. coli strains particularly against cefazolin are increasing year by year.
Anti-Bacterial Agents↗