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Biomedical subjects

H Wada

Publications and source records attributed to H Wada.

At least 757 records · Page 42Linked to original sources

Hypothalamic histamine modulates adaptive behavior of rats at high environmental temperature.

Histamine content in the rat hypothalamus was lower at 4 degrees C and higher at 31 degrees C compared to that at 21 degrees C. Pretreatment with alpha-fluoromethylhistidine, a 'suicide' inhibitor of histamine decarboxylase, attenuated both the increased level of hypothalamic histamine and rat adaptive behavior at 31 degrees C. Increase of histamine content in the hypothalamus appears to be an important factor contributing to rat adaptive behavior to high environmental temperature.

Adaptation, Physiological↗

Expression of major blood group antigens on human erythroid cells in a two phase liquid culture system.

In order to examine the sequential expression of major blood group antigens on human erythroblasts, a selective two phase liquid culture system for erythroid progenitors was established. After mononuclear cells obtained from peripheral blood were cultured in the presence of phytohemagglutinin stimulated-leukocyte conditioned medium (PHA-LCM) for 7 days (the first phase), nonphagocytic cells were recultured under hypoxic culture conditions containing 30% fetal calf serum, 1% bovine serum albumin, 300 micrograms/mL transferrin and 2 U/mL recombinant erythropoietin (the second phase). Mature (orthochromatic) erythroblasts were observed on day 4 of the second phase, and reached 57.1 +/- 3.1% of total cells on day 8, followed by the appearance of denucleated red cells, equivalent to mature red cells in peripheral blood. Hemoglobin contents reached the level of 16.8 +/- 0.7 micrograms/10(6) cells on day 8. Flow cytometric analyses revealed that, on day 3 of the second phase, cells became blood type M-positive, corresponding to the maturation of erythroid cells. Regarding the expression of ABH blood group antigens, a small number of blood type H-positive cells were initially detected on day 0 of the second phase, while blood type A-positive cells, which essentially were not observed on day 0, increased gradually corresponding to the extent of erythroid maturation. In the present system, Lewis and P1 blood group antigens were expressed at day 5 of the second phase, although autologous plasma was required to determine the expression of Lewis blood group antigens. This culture system is beneficial for studies on normal and abnormal human red cell membranes, because the erythroid progenitors in human peripheral blood were used, and a reasonable number of erythroid cells (0.5 to 1.5 x 10(7] was obtained with good maturation.

ABO Blood-Group System↗

Eradication of oesophageal varices recurring after portal non-decompressive surgery by injection sclerotherapy.

The results of injection sclerotherapy for oesophageal varices which recurred after portal non-decompressive surgery were analysed retrospectively to evaluate its efficacy. We treated 60 consecutive patients with portal hypertension; 19 were treated on an emergency basis, seven electively and 34 on a prophylactic basis. All acute bleeding was controlled with one session of sclerotherapy using a transparent overtube. After eradication by sclerotherapy, no bleeding episodes occurred and there was no recurrence of the varices, except in three uncompliant patients, during a mean follow-up period of 33.1 months. Bleeding from a gastric ulcer and gastritis occurred in one patient each. Oesophageal stenosis occurred in nine (15 per cent) patients and gastric varices developed in two (3 per cent) patients. Twelve patients died, five from liver failure and six with hepatoma, but there was no bleeding from the gastrointestinal tract. The overall 4-year survival rate was 80 per cent. We recommend the use of sclerotherapy as the primary treatment for recurrent oesophageal varices.

Adult↗

An analysis of histaminergic efferents of the tuberomammillary nucleus to the medial preoptic area and inferior colliculus of the rat.

The efferent projections of the five histaminergic neuronal subgroups in the tuberomammillary nucleus to the medial preoptic area (MPO) and inferior colliculus (IC) were examined by immunocytochemistry with antihistidine decarboxylase (HDC) antibodies combined with retrograde axonal tracing with Fast Blue (FB). The term "E groups" were used for the histaminergic neuronal subgroups. About 10% of the HDC-immunoreactive (HDCI) neurons were retrogradely labeled after FB injection into the MPO. The labeled neurons were not concentrated in any particular area, but were diffusely distributed bilaterally in all the subgroups. About two-thirds of the labeled neurons were observed on the side ipsilateral to the injection site and one-third on the contralateral side. The percentages of labeled neurons (double-labeled neurons/HDCI neurons) in the five subgroups were not significantly different with each other. The percentages in group E1 and E2 were particularly close, while that in group E4 resembled that in group E5. About 4% of the HDCI neurons were retrogradely labeled after the dye injections into the IC, and about half of the labeled neurons were detected on the ipsilateral side. The percentage of the double-labeled neurons in the five groups were not significantly different. Furthermore, those in E1 and E2, and in E4 and E5 were almost identical, respectively, to the situation following injection of FB into the MPO. These results indicate that each subgroup of histaminergic neurons in the tuberomammillary nucleus has similar efferent projections to the MPO and IC.

Animals↗

Results of newborn screening for galactose metabolic disorders.

A screening strategy has been used which uses the Paigen and Beutler methods for the determination of galactose and galactose-1-phosphate. A blood spot test for epimerase has also been developed. In the last 10 years, 265,019 samples from newborns have been tested by these methods. Among the 154 screening positives, we have detected seven cases of epimerase-deficient galactosaemia (Type III), seven cases of Duarte/galactosaemia heterozygotes, 48 cases of other various types of heterozygotes, four cases of persistent hypergalactosaemia, three cases of hepatitis and one case of congenital atresia of the bile duct. These results indicate that our screening system has effectively detected the infants with galactose metabolic disorders.

Carbohydrate Metabolism, Inborn Errors↗

Effects of histamine and alpha-fluoromethylhistidine injections on circadian phase of free-running rhythms.

Sequential IP injections of alpha-fluoromethylhistidine at CT-6 and CT-18 elicited transient delay during the injection period in the onset of activity in the free-running circadian rhythms of locomotor and drinking activities. Histamine injection ICV resulted in various changes, permanent or transient, in the circadian phase of the free-running rhythms depending on the subjective time of the injection: it caused transient advance in onset of activity when injected at CT-0, 3, 6, 9, 18 or 21, whereas it caused permanent phase-delay when injected at CT-12 or 15. These permanent effects were plotted in a phase-response curve. Histamine administration at CT-6 and CT-18 resulted in transient, reciprocal changes of almost equivalent amplitude changes to those of histamine depletion at the corresponding subjective times. Although this transient shift may represent a masking effect of the drug, HA may modulate the circadian synchronization mechanism(s) during the advance sensitive phase. Moreover, HA seems to elicit phase-delay by affecting the light-relaying tract.

Animals↗

Development of a computer program classifying rat sleep stages.

We developed a simple and precise program for the on-line judgement of the sleep stages of four rats simultaneously for an unlimited period, using a commercially available general purpose signal processor (NEC-Sanei 7T17; 32-bit, 5 MHz, 4 Mbyte, 1 Mbyte 1 floppy disc drive). EEG and EMG were recorded with an 8-channel polygraph (NEC-Sanei, System 380) through electrodes chronically implanted into the brain. The signals were A/D converted every ms and integrated for 2760 ms after full-wave rectification, and the subsequent 2240 ms was used for calculation and further analysis. All data were handled with this 5000 ms as the minimum unit. Then 3 sleep stages, i.e., waking, slow-wave sleep, and REM sleep, were determined by a template matching method from the relative amplitudes and durations of the integrated EEG, EMG and EMG surge data based on algorithms of standard visual amplitude analysis criteria for the sleep-stage classification. An agreement matrix was constructed between the data scored by the visual and by the automatic analysis, and the agreement value was satisfactory, although slight variability was seen in the REM sleep-stage determination. This result indicated that EEG and EMG data analysis is appropriate for researching the circadian rhythmic mechanism of the sleep-wake cycle.

Animals↗

Pharmacology of alpha-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase.

alpha-Fluoromethyl-[S]-histidine (FMH) is a specific and potent inhibitor of histidine decarboxylase, which forms histamine from histidine. It acts selectively and irreversibly by formation of a covalent linkage, possibly with the serine residue in the active site of the enzyme. A single administration of FMH decreases the histamine content only of non-mast cells in the brain and stomach of rodents, but repeated administration gradually decreases the histamine content of mast cells in all tissues. Thus, FMH can be used to deplete histamine in pharmacological studies. As no marked side-effects have been observed during administration of FMH, it may be useful in pathological conditions, such as some allergic diseases, peptic ulcers and mastocytosis, in which excess production of histamine is involved.

Animals↗

Glucose, free fatty acid and ketone body metabolism in Duchenne muscular dystrophy.

We examined how the substances, especially glucose, free fatty acids (FFA) and ketone bodies, and hormones associated with energy metabolism change with the disease progress in Duchenne muscular dystrophy (DMD). Serum creatine kinase (CK) activity was used as an index of the stage of DMD, because this activity is exponentially decreases with the progress of the disease. The glucose concentration in DMD patients with CK activity of less than 1,000 U/l (low CK) was significantly lower than that in controls, although there was no significant difference between that in DMD patients with CK activity of more than 1,00 U/l (high CK) and that in controls. The FFA concentration in both high CK and low CK patients was significantly higher than that in controls. The FFA concentration in low CK patients tended to be higher than that in high CK patients. The ketone body concentration in low CK patients was significantly higher than that in controls and that in high CK patients. The [glucagon]:[insulin] ratio in low CK patients was significantly higher than that in controls and that in high CK patients. It was also observed in a correlational study that the glucose concentration decreased with the age and the decrease in CK activity, i.e., with the progress of DMD. The FFA and ketone body concentrations increased with the decrease in the glucose concentration. The decrease in the glucose concentration may be due to a caloric shortage and/or degenerated muscle, which cannot supply enough gluconeogenic substrates, such as alanine. The kinetics of insulin and glucagon in DMD may help to maintain the glucose metabolism. Increased concentrations of FFA and ketone bodies may be helpful in the advanced stage of DMD, as energy sources and as substrates, sparing muscle protein.

Adolescent↗

Plasma membrane fatty acid-binding protein and mitochondrial glutamic-oxaloacetic transaminase of rat liver are related.

The hepatic plasma membrane fatty acid-binding protein (h-FABPPM) and the mitochondrial isoenzyme of glutamic-oxaloacetic transaminase (mGOT) of rat liver have similar amino acid compositions and identical amino acid sequences for residues 3-24. Both proteins migrate with an apparent molecular mass of 43 kDa on SDS/polyacrylamide gel electrophoresis, have a similar pattern of basic charge isomers on isoelectric focusing, are eluted similarly from four different high-performance liquid chromatographic columns, have absorption maxima at 435 nm under acid conditions and 354 nm at pH 8.3, and bind oleate with a Ka approximately 1.2-1.4 x 10(7) M-1. Sinusoidally enriched liver plasma membranes and purified h-FABPPM have GOT enzymatic activity; the relative specific activities (units/mg) of the membranes and purified protein suggest that h-FABPPM constitutes 1-2% of plasma membrane protein in the rat hepatocyte. Monospecific rabbit antiserum against h-FABPPM reacts on Western blotting with mGOT, and vice versa. Antisera against both proteins produce plasma membrane immunofluorescence in rat hepatocytes and selectively inhibit the hepatocellular uptake of [3H]oleate but not that of [35S]sulfobromophthalein or [14C]taurocholate. The inhibition of oleate uptake produced by anti-h-FABPPM can be eliminated by preincubation of the antiserum with mGOT; similarly, the plasma membrane immunofluorescence produced by either antiserum can be eliminated by preincubation with the other antigen. These data suggest that h-FABPPM and mGOT are closely related.

Amino Acid Sequence↗

Temperature-Induced Changes in the Fatty Acid Composition of the Cyanobacterium, Synechocystis PCC6803.

Changes in glycerolipid and fatty acid composition with a change in growth temperature were studied in the cyanobacterium, Synechocystis PCC6803. Under isothermal growth conditions, temperature did not significantly affect the composition of the various classes of lipids, but a decrease in temperature altered the degree of unsaturation of C(18) acids at the sn-1 position, but not that of C(16) acids at the sn-2 position of the glycerol moiety in each class of lipids. When the growth temperature was shifted from 38 degrees C to 22 degrees C, the desaturation of C(18) acids, but not that of C(16) acids, was stimulated. The desaturation of fatty acids occurred only in the light and was inhibited by chloramphenicol, rifampicin and 3-(3,4-dichlorophenyl)-1, 1-dimethylurea, but not by cerulenin, an inhibitor for fatty acid synthesis. These findings suggest that desaturase activities are induced after a shift from a higher to a lower temperature, and that the desaturation of fatty acids is connected with the reactions involved in photosynthetic electron transport.

Journal Article↗

Extramammary Paget's disease: comparative histopathologic studies of intraductal carcinoma of the breast and apocrine adenocarcinoma.

We examined 32 cases (38 lesions) of extramammary Paget's disease (EMPD) in relation to comparative studies on intraductal carcinoma of the breast (ductal carcinoma in situ, DCIS) and apocrine adenocarcinoma (AAC). Lesions included scrotum (18 lesions), vulva (8), axilla (6), groin (3), penis (2) and chest wall (1), and the distribution was compatible with that of apocrine or supernumerary mammary glands. Histologically, extra-mammary Paget's and DCIS cells exhibited a large amount of a pale-stained cytoplasm. The cytoplasm of AAC cells frequently contained granules, was eosinophilic and differed from that of Paget's or DCIS cells. Immunohistochemical studies revealed positive reactions for polyclonal and monoclonal antibodies to carcinoembryonic antigen in all EMPD and most DCIS, but not in AAC. Recent studies have shown that extramammary Paget's cells exhibit characteristics of glandular epithelial cells and that most cases of EMPD are not accompanied by an underlying carcinoma. The results obtained in this study, coupled with data on the frequency of the supernumerary breasts, lead to the speculation that extramammary Paget's cells originate from ectopic mammary glands or from pluripotential germinative cells in the epidermis, capable of differentiating toward the mammary glands.

Adenocarcinoma↗

Dynamical behavior of middle ear: theoretical study corresponding to measurement results obtained by a newly developed measuring apparatus.

An attempt is made to develop a new measuring apparatus, and the dynamical characteristics of the middle ear of normal subjects and patients are measured with this apparatus. Applying the impedance theory of the tube to the external auditory canal, the aditus, and the tympanic and mastoid cavities, and applying the energy method to the eardrum and the ossicular chain, the equation of the middle ear, corresponding to the output of the apparatus and including the pressure difference effect upon the eardrum, is obtained. The numerical results are compared with the measurement results, and the effects of each part of the middle ear upon its dynamical characteristics are clarified. The great dependence of the dynamical characteristics of the middle ear upon the external auditory canal pressure is mainly caused by the pressure-dependent ossicular chain angular stiffness. The clearly different measurement results of the ossicular chain disorder patients from those of the normal subjects are obtainable by this apparatus, and these characteristics can be explained theoretically.

Acoustic Impedance Tests↗

Hemodynamic and morphological changes in the dog kidney after injection of 5% ethanolamine oleate into the superior vena cava.

The effect of the sclerosant 5% ethanolamine oleate (EO) on renal circulation was evaluated in 20 mongrel dogs into which we injected 5% EO (0.5 ml/kg) into the superior vena cava. There was a marked hemolysis and a significant decrease in creatinine clearance from 104.4 +/- 17.1 (mean +/- SD) to 40.7 +/- 5.0 ml/min (p less than 0.01) at 120 min. The renal arterial blood flow (RAF) decreased biphasically; from 75.3 +/- 13.1 to 9.8 +/- 9.3 ml/min during an average of 2.3 min, immediately after the injection (p less than 0.01) and gradually decreased after reaching the pretreatment level to 43.2 +/- 8.6 ml/min at 120 min (p less than 0.01). Cardiac output significantly decreased from 1.86 +/- 0.08 to 1.54 +/- 0.08 l/min (p less than 0.01). Tubular necrosis was histologically evidenced in the tissues examined at 6 h after the injection of EO. Biphasic decrease in renal arterial blood flow can be explained by the possible occurrence of spasm of the peripheral renal arteries in the acute phase and tubular necrosis in the late phase. This study suggests to us that the tubular necrosis induced by decreases in RAF as well as hemolytic nephropathy play a significant role in cases of renal dysfunction following the endoscopic injection of 5% EO to sclerose esophageal varices.

Animals↗