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Biomedical subjects

S Higuchi

Publications and source records attributed to S Higuchi.

At least 397 records · Page 22Linked to original sources

Characterization of the human IL-5 receptors on eosinophils.

Interleukin 5 (IL-5) receptors on the cell surface of human eosinophils and other hematopoietic cells were characterized using radiolabeled recombinant IL-5. The binding of 35S-labeled murine IL-5 to eosinophils from normal human peripheral blood was rapid and saturable within a 30-min incubation at both 4 and 37 degrees C. The binding of 35S-labeled murine IL-5 to eosinophils was inhibited by an excess of unlabeled murine and human IL-5 or by an anti-murine IL-5 monoclonal antibody (NC17) but not by other human cytokines. Scatchard plot analysis revealed that human eosinophils have a single class of high affinity receptor (Kd 170-330 pM; number of binding sites: 260-380/cell). IL-5 receptors on eosinophils from four patients with eosinophilia displayed similar characteristics. Affinity cross-linking experiments resulted in the identification of human IL-5 receptor on eosinophils with a molecular mass of 55-60 kDa. Among the various cells besides eosinophils and cell lines that we could test, a subline of HL-60 (YY-1 cells) was found to display a significant number of IL-5 receptor. These results suggest that IL-5 may act on limited types of cells in the human system.

Aged↗

Anti-neutrophil antibodies in patients with nutritional copper deficiency.

Ten patients with nutritional copper deficiency were studied in terms of neutrophil counts and anti-neutrophil antibodies (ANA). In four patients with severe or moderate copper deficiency, the production of ANA was positive and two patients with a severe deficiency had neutropenia. After copper supplementation, ANA titres became negative or were reduced in all patients and neutrophil counts reverted to normal in two patients. It thus appears that copper deficiency is linked to the production of ANA, a condition which partly responsible for neutropenia.

Adolescent↗

Generation of fractal patterns for probing the visual memory.

The effective use of computer-generated pictures as a trial-unique probe for studying the visual memory is described. The shape of the pattern is determined by means of a fractal algorithm with pseudorandom parameters. This method enables us to easily obtain thousands of moderately complex and sufficiently diversified pictures in series from a given number which serves as the seed of a pseudorandom number generator. We can thereby create a new and unique set of pictures if a new seed is given, as well as retrieve exactly the same pictures in the same sequence as when the original seed is given. These properties eliminate the demand for the massive memory space in a computer otherwise needed to store the entire set of stimulus pictures.

Algorithms↗

Alcohol consumption and the risk of developing liver cirrhosis: implications for future research.

Studies of the association of alcohol consumption and liver cirrhosis were reviewed, focusing on possible biases of study design. Daily alcohol consumption (as opposed to intermittent binge drinking), amount of alcohol consumed, longer duration of alcohol abuse, and being female were associated with the increased risk of cirrhosis. Follow-up studies reviewed failed to take full advantage of the study design and added little information to existing literature. Retrospective studies were relatively free of bias and are valuable tools in estimating the risk of cirrhosis. Future research needs to take the following variables into consideration: better ascertainment of alcohol consumption, consumption patterns, changes in alcohol consumption, gender, and body weight.

Alcohol Drinking↗

A method for estimating alcohol-related liver cirrhosis mortality in Japan.

In Japan, per capita alcohol consumption increased sharply during the post World War II period followed by an increase in cirrhosis mortality. The prevalence of alcoholic cirrhosis among hospitalized patients also increased, from 11% in 1969 to 18% in 1985. Despite an increase in the percentage of drinkers among young women, over 80% of women in Japan are still abstainers or light drinkers. Thus, female cirrhosis mortality rates can be used as a proxy measure of non-alcohol-related cirrhosis mortality rates to estimate alcohol-related cirrhosis deaths among Japanese men. Employing this method, we conclude that two-thirds of cirrhosis deaths among men between 24 and 85 years of age and half of all cirrhosis deaths were attributable to alcohol. Two factors are probably responsible for the differences in proportional morbidity and proportional mortality of alcohol-related cirrhosis: differences in survival rates between alcoholic and non-alcoholic cirrhosis patients and detection bias toward post-hepatic cirrhosis. The synergistic effect of alcohol on viral hepatitis may in part explain excess cirrhosis deaths among Japanese men.

Adult↗

Influence of age and concurrent medication on steady-state valproic acid serum level-dose ratios in Japanese paediatric patients.

The effects of age and co-medication on steady-state valproic acid (VPA) level/dose (L/D) ratios were evaluated retrospectively in 382 paediatric patients. The VPA L/D ratio increased significantly with age up to 15 years of age in patients on monotherapy (L/D = 0.149 x AGE + 2.708, n = 192, r = 0.549, P less than 0.001). In patients taking three or more anti-epileptic drugs, including VPA, there was no such effect. Associated anti-epileptic therapy affected the VPA L/D ratio, which was significantly reduced in patients on polytherapy as compared to patients on monotherapy. Therefore, routine monitoring of VPA serum levels would be extremely useful, especially in the paediatric age group, and in patients who require associated anti-epileptic medication.

Adolescent↗

One-point feedback control method for phenytoin dosage adjustment.

Routine clinical pharmacokinetic data collected from patients receiving phenytoin have been analysed to propose a new and simple equation to aid the dosage adjustment of this drug. The data were analysed using NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data. The rate equation for the elimination of phenytoin can be written as Do = kCssn, which fits the steady-state serum concentration (Css) and daily dose data (Do). The parameter n is the kinetic order and the parameter k is an arbitrary rate constant. From the above equation, D2 = D1C1 -nC2n can be derived, which forms the basis of predicting the dosage, D2, to obtain a desired Css, C2, using one initial Css, C1, obtained with an initial dose, D1, and using a population value of n. The value of n for phenytoin was estimated to be 0.312 in this study. The predictive performance of this equation was compared with the Richens and Dunlop nomogram and Bayesian feedback method using two or more steady-state concentration/dose pairs from each of 78 outpatients. This equation allowed the prediction of a dose needed to produce a desired steady-state concentration with errors comparable with the Bayesian feedback method for therapeutic drug monitoring.

Adolescent↗

Effects of temperature and pressure during compression on polymorphic transformation and crushing strength of chlorpropamide tablets.

The effects of temperature on the polymorphic transformation of chlorpropamide during compression and on the physical properties of the tablet have been investigated. A heater and liquid nitrogen pool were mounted on the die of a single punch eccentric tableting machine, and the die temperature was controlled by a thermocontroller. A tableting machine with two load cells (upper and lower punches) and a non-contact displacement transducer were used to measure compression stress, distance and energy. The X-ray diffraction profiles of the deagglomerated compressed sample powder were measured to calculate the polymorphic content. The amount of form C transformed from form A at 45 degrees C was about twice that at 0 degree C with the same compression energy. The amount of form A transformed from form C by compression at 45 degrees C was almost the same as that at 0 degree C. This suggests that the mechanochemical effect of form A depended on the compression temperature, but that of form C was independent of temperature. The crushing strength of tablets of form A was about twice that of form C, even at the same porosity. The plots of log (crushing strength of tablet) against porosity of form A tablets compressed at 0 and 45 degrees C were linear with the same slope; the slope for form C tablets compressed at 45 degrees C was less than that at 0 degree C.

Chemistry, Pharmaceutical↗

Isomerization of lactose in solid-state by mechanical stress during grinding.

Isomerization during grinding of solid-state alpha-monohydrate, alpha-anhydrate and beta-anhydrate of lactose was investigated. Samples were ground in an agate centrifugal ball-mill at 270 rev min-1 at room temperature (20 degrees C). The crystallinity of ground lactose was measured by Hermans' method from the powder X-ray diffraction profiles. The alpha- and beta-lactose content of the ground lactose was obtained from the specific rotation measured by using angular rotation spectrophotometry. The crystalline lactose samples were transformed into non-crystalline solids by mechanical stress during grinding. After grinding, the water content of all ground lactose samples increased, and the samples had about 2 mol water per lactose after 10 h grinding. After 10 h grinding of alpha-monohydrate and alpha-anhydrate, 10 and 15%, respectively, of alpha-lactose was transformed into beta-lactose by the mechanical treatment. After 10 h grinding of beta-lactose, 20% of beta-lactose was transformed into alpha-lactose. The results suggest that crystalline lactose was transformed into a non-crystalline solid, and water was adsorbed on the non-crystalline lactose. The non-crystalline solids of alpha- or beta-lactose were then transformed into their counterparts by the mechanochemical effects of grinding.

Chemical Phenomena↗

Special treatment facilities for alcoholics in Japan.

No comprehensive study on special treatment facilities for alcoholics in Japan has been reported. We conducted a questionnaire survey of alcoholism treatment wards, alcoholism treatment rooms, special outpatient clinics for alcoholics and halfway houses for alcoholics. The survey covered nearly all of such facilities in Japan. The results of the survey revealed the following characteristics: (1) The number of such facilities has increased rapidly in recent years; (2) the facilities are concentrated in cities; (3) the great majority of the facilities are privately operated; (4) many of the facilities are associated with psychiatric departments; and (5) there are very few facilities exclusively for female alcoholics. The most fundamental and important point is that the number of special treatment facilities for alcoholics is insufficient to meet current needs. These facilities have not diversified sufficiently to address adequately the changing needs of Japanese alcoholics.

Alcoholism↗

[A case of lupus erythematosus preceded by right heart failure due to pulmonary hypertension].

A 40-year-old woman was admitted because of increasing exertional dyspnea. Right heart failure was suggested by the presence of hepatomegaly, pretibial edema and also echocardiographic findings. Physical examination and echocardiography showed no evidence of valvular disease or congenital heart disease except for right ventricular dilatation and tricuspid regurgitation. The ventricular septum deviated toward the left ventricle throughout the cardiac cycle, but left ventricular function was preserved. Severe pulmonary hypertension averaging 44 mmHg was revealed by cardiac catheterization. Digital subtraction angiography and pulmonary blood flow scintigraphy showed no evidence of pulmonary artery embolism, and no interstitial pulmonary lesions that might have caused pulmonary hypertension were recognized. Hypergammaglobulinemia suggested an autoimmune disorder, and signs of systemic lupus erythematosus (SLE), such as pleural effusion, proteinuria, lymphocytopenia, LE cell phenomenon and antinuclear antibodies were present. Several autoimmune diseases are known to be causative factors of pulmonary hypertension. However, only ten cases of SLE complicated by pulmonary hypertension have been reported the present one. These cases were characterized by a high incidence of Raynaud's phenomenon and positivity for anti-RNP antibody. In our present case, SLE activity was suppressed using prednisolone, but pulmonary hypertension persisted and the patient eventually died due to right cardiac failure. Judging from the clinical course of the ten reported cases of SLE-pulmonary hypertension, there seems to be no hope of improving the pulmonary hypertension once it has become established. Therefore it is important to detect and cure pulmonary hypertension as early as possible.

Angiography, Digital Subtraction↗

Functional heterogeneity of human eosinophil chemotactic lymphokines.

We have previously isolated two OKT4-positive T lymphocyte-derived eosinophil chemotactic factors (LDECF) with MW of about 45-60 kDa of which production is different in antigen or mitogen dependency (1-4). The production of a LDECF from patients with parasite disease (LDECF-PD) is dependent on antigen or mitogen stimulation, whereas another LDECF from patients with hypereosinophilic syndrome (HES) is independent. Further purification of these LDECF with isoelectric focusing reveals that an isoelectric point of LDECF-HES is about 6.0 and that of LDECF-PD is around 7.0 to 8.0. Little or no activity of partially purified LDECF-HES and LDECF-PD is suppressed by treatment with monoclonal antibodies against GM-CSM, IL-3, and IL-5, which activate eosinophils. LDECF-HES and LDECF-PD attract eosinophils from healthy individuals. In contrast, eosinophils from patients with HES are attracted by LDECF-HES but not LDECF-PD. LDECF-HES enhances the expression of Fc epsilon receptor II (Fc epsilon RII) and Fc gamma receptor III (Fc gamma RIII) but not that of CR1 on eosinophils, whereas LDECF-PD enhances their CR1 and Fc gamma RIII expression but not Fc epsilon RII expression. Moreover, treatment with LDECF-PD suppresses the release of eosinophilic cationic protein (ECP) from eosinophils, whereas that with LDECF-HES fails. Treatment of eosinophils with phorbol myristate acetate enhances ECP release from eosinophils but it fails to enhance the intracellular ECP level. However, the intracellular ECP level is elevated by stimulation with phorbol myristate acetate if eosinophils were previously treated with LDECF-HES but not with LDECF-PD. These results suggest that various kinds of LDECF are produced according to the nature of diseases, and that each LDECF has functional heterogeneity on eosinophils.

Antigens, Surface↗

Development of Babesia ovata in the ovary and eggs of the tick, Haemaphysalis longicornis.

The ovary and eggs of adult tick Haemaphysalis longicornis (H. longicornis) infected with Babesia ovata (B. ovata), were examined at regular intervals of time. As a result kinetes could be detected in the ovary for the first time 6 days after engorgement. The kinetics could be classified into three types on the basis of their morphological characteristics. On the 2nd day after oviposition, round-formed protozoa were found in the ooplasm of the egg. In 5 days after oviposition, these round-formed bodies were transformed into club-forms. On the 9th day after oviposition, the kinetes were observed in the ooplasm. Morphologically, it seemed possible that B. ovata is transmitted by eggs of the tick, H. longicornis.

Animals↗