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Biomedical subjects

H Nomura

Publications and source records attributed to H Nomura.

At least 19 recordsLinked to original sources
PubMed1992

Selective removal of cholesterol by plasmapheresis and the progression of atherosclerosis.

There is a strong correlation of plasma cholesterol levels with the risk of coronary heart diseases as shown by epidemiologic studies. This study was undertaken to evaluate the effect of plasma cholesterol lowering on the progression of atherosclerosis in the homozygous Watanabe heritable hyperlipidemic (WHHL) rabbit. The effect of cholesterol lowering, which was accomplished by thermofiltration (on-line plasma separation with plasma filtration at 39 degrees C) was evaluated by comparison between treated and untreated control groups. Thermofiltration reduced significantly the mean plasma level of total cholesterol (284 vs. 655 mg/dl, P = 0.0005) and the percent aortic area occupied by atherosclerotic plaque (15.0 vs. 44.2%, P = 0.0003). The total lipid and cholesterol contents in the aortas in the treated group were also significantly lower than those in the control group. Microscopically, thickness measurements of the lesions showed that the mean thickness of the fibrous cap and the ratio of the thickness of the intima to that of the media were smaller for the treated group than the control group. This study demonstrated the slowing or stopping of the progression of atherosclerosis by lowering the plasma total cholesterol level in WHHL rabbits.

Animals↗
PubMed1992

Determinants of left ventricular filling dynamics: alteration in the Doppler-derived transmitral filling profile with progressive impairment of cardiac function in a dog preparation.

To clarify the factors determining transmitral filling, left ventricular and atrial pressures (LVP and LAP) and Doppler-derived diastolic indices were analysed in six anaesthetized dogs at various right atrial pacing rates during dextran infusion. The relationship of the late to early diastolic peak velocity ratio (A/E ratio) to end-diastolic LVP (LVEDP) showed a quadratic curve concave to the LVEDP axis in five animals (r2 = 0.320-0.588). An elevation in LVEDP up to 25 mmHg accompanied an increase in A/E ratio (ascending limb), and further LVEDP elevation caused its inverse decline (descending limb). Multiple regression analysis indicated that A/E ratio correlated positively with maximal LVP, a-wave LAP and heart rate, and negatively with v-wave LAP in both limbs. The time constant of isovolumic LVP decline, which was prolonged as LVEDP was elevated, was a positive correlate of A/E ratio in the ascending limb, but lost its influence on A/E ratio in the descending limb. An elevation in v-wave LAP must have masked the expected effect of left ventricular relaxation abnormality on A/E ratio in this limb. Thus, the transmitral filling profile did not alter unidirectionally, but returned to that seen before volume loading, with a simultaneous progressive impairment of cardiac function.

Animals↗
PubMed1992

Effects of recombinant human granulocyte colony-stimulating factor on neutrophil functions in aged animals.

We have studied the effects of recombinant human granulocyte colony-stimulating factor (rG-CSF) on granulopoiesis and neutrophil functions in aged rats and aged mice. We subcutaneously injected rG-CSF or control vehicle into aged rats (22 months old and 25 months old) for 7 consecutive days, counted the peripheral neutrophils and evaluated the functions of neutrophils isolated from venous blood. The peripheral neutrophil count in aged rats tended to be increased as compared with that in young rats (11 weeks old). However, the neutrophils in aged rats exhibited a decline of superoxide anion (O2-) release and phagocytic activity as compared with young rats. The peripheral neutrophil count in aged rats was significantly increased 5-6-fold as many as the control value by rG-CSF treatment, which was accompanied by a significant enhancement of O2- release and of phagocytic activity being restored to normal levels or better. In another series of experiments, we subcutaneously injected rG-CSF or control vehicle into aged mice (24-28 months old) or young mice (8 weeks old) for 7 consecutive days, and evaluated the functions of neutrophils isolated from peritoneal cavity. The peritoneal exudate neutrophils from the aged mice exhibited a decline of phagocytic and chemotactic activity as compared with the young mice. These functions in both young and aged mice were significantly enhanced by rG-CSF-treatment, and these functions in rG-CSF-treated aged mice were restored to a level higher than the level in control young mice. These findings demonstrate that rG-CSF is capable of enhancing granulopoiesis and restoring the age-related decline of neutrophil functions.

Aging↗
PubMed1992

An index for proportion of head size to body mass during infancy.

The index "head circumference (cm)3/body weight (g)" gave an almost constant average (about 10) and standard deviation (about 1) in more than 2000 children at birth and at 4, 10, and 18 months. Application of this index to the data previously published confirms that the average is almost constant throughout the period from birth to 18 months, irrespective of sex or race. Head circumference cubed and body weight correlate significantly. This index seems to be useful to assess the proportion of head size to body mass during infancy, and to contribute to early diagnosis of diseases such as hydrocephalus or microcephaly.

Body Mass Index↗
PubMed1992

Direct modulation of secretin binding sites by gastrin in the rat stomach.

The effect of gastrin on secretin binding sites in the stomach was studied using the plasma membranes from rat gastric mucosa and vascularly perfused rat stomach. Tetragastrin transiently increased secretin binding to the mucosal plasma membranes. In the perfused stomach secretin binding was also modulated by the inclusion of tetragastrin or human [Leu15] gastrin I in the perfusate. However, histamine did not show such a modulatory effect. Tetragastrin had an insignificant effect on secretin binding sites in rat pancreas. These results suggest that the direct modulation of secretin binding by gastrin to its receptors may be involved in the inhibitory action of secretin on acid secretion induced by gastrin.

Animals↗
PubMed1992

Effects of long-term beta-blockade therapy in patients with dilated cardiomyopathy--serial clinical and echocardiographic observations.

Twenty-three patients with dilated cardiomyopathy (DCM) were treated with metoprolol and their clinical courses compared with those of 26 patients untreated with beta-blocking agents (non beta group). Of the 23 patients treated with metoprolol, 20 (beta group) were treated for 6 months or longer, while the remaining 3 patients were intolerant of the drug and suffered aggravation of heart failure. In the beta group, 2 deaths occurred, while of the remaining 18 patients 4 were considered clinically improved in NYHA class 6 or 12 months later, and none suffered clinical deterioration during the follow-up period. In the non-beta group, clinical improvement was found in 2 patients and deterioration of functional class in 10. Heart rate and pressure rate product were significantly decreased by 1 month after the treatment with metoprolol. At that time, blood pressures, systolic and diastolic left ventricular dimensions, indices of systolic function (% FS, mVcf) and exercise capacity had not changed, while cardiac output was decreased and systemic peripheral vascular resistance was significantly increased. In the beta group, significant improvements in left ventricular dimensions, systolic function and exercise tolerance were delayed and observed within 3 to 6 months during the follow-up period, while no such improvements occurred in patients of the non-beta group. During the follow-up period, 2 patients of the beta group and 10 patients of the non-beta group died. The survival curve for patients of the beta group, prepared using the Kaplan Meier's Method, was better than that for patients of the non-beta group. Metoprolol was therefore found to be useful for treatment of DCM.

Adult↗
PubMed1992

Hereditary angioedema complicated with chronic renal failure: report of sibling cases.

Hereditary angioedema (HAE) is known as a deficiency state of C1 inhibitor (C1 INH), an important protease inhibitor protein involved in the complement system. As with other components of the classical pathway of the complement system, a state of its deficiency often causes clinical immunoregulatory disorders. A 45-yr-old brother and a 63-yr-old sister with HAE both developed chronic renal failure, probably due to chronic glomerulonephritis, and required regular hemodialysis. This is, to our knowledge, the first report of sibling cases of HAE associated with chronic renal failure.

Angioedema↗
PubMed1992

[Function, molecular structure and gene expression of IL-8].

Interleukin-8 (IL-8) is a potent chemotactic factor for neutrophils and T lymphocytes. Various reagents such as lectins, mitogens, IL-1, TNF, induce IL-8 production in a wide range of cells and tissues. The IL-8 gene is known to be activated by AP-1, NF-kB like factor and C/EBP like factor, but the relative importance of these transcriptional factors varies from cell to cell. Two types of human IL-8 receptor cDNA have recently been cloned. Both are G-protein coupled receptors and the amino acid sequences are highly homologous. Other members of the IL-8 family, such as GRO/MGSA and MIP2, bind to IL-8 receptors, and the receptors of other chemoattractants such as fMLP and C5a, show high homology to the IL-8 receptors.

Amino Acid Sequence↗
PubMed1992

[Augmentation of left ventricular slow filling in hypertrophic cardiomyopathy].

To investigate the significance of augmentation of left ventricular slow filling, trans-mitral flow (TMF) was echocardiographically observed through pulsed Doppler method in 116 patients with hypertrophic cardiomyopathy (HCM), 74 with dilated cardiomyopathy (DCM), 27 with mitral regurgitation (MR), 86 with old myocardial infarction (OMI) and 80 normal controls (C). The slow filling-wave (SFW) in TMF was defined as the filling wave with obvious peak velocity during slow filling phase. The peak velocities (E, A, S) of the early filling, the atrial contraction and the slow filling waves were measured. The SFW was divided into two patterns according to the S and E ratio: large SFW (S/E greater than or equal to 1/2) and small SFW (S/E less than 1/2). 1) The small SFW was more frequently, but not significantly, observed patients with MR (37%) than in normal subjects (18%), patients with HCM (10%), DCM (4%) and OMI (7%). However large SFW was observed in 16 patients (14%) with HCM, but not in normal subjects and patients with other cardiac diseases excluding one patient with DCM. 2) In normal subjects and patients with DCM, OMI and MR, those with small SFW had larger E and smaller A/E than those without small SFW. However in patients with HCM, there was no difference in these indices (E and A/E) according to whether the patients were with or without SFW. 3) In HCM, patients with large SFW had significantly smaller E and significantly larger isovolumic relaxation time than those without SFW. Thus, appearance of the large slow filling wave, which might be caused by abnormal relaxation of the left ventricle, was frequently observed in patients with HCM.

Adult↗
PubMed1992

Two cases of acquired syphilis with acute central chorioretinitis as initial manifestation.

Acquired syphilis has become an overlooked cause of posterior uveitis including chorioretinitis. Two male cases of bilateral acute acquired syphilitic chorioretinitis were observed, one of whom demonstrated an early delay of choroidal circulation during fluorescein angiography, possibly indicating the choroidal or subretinal neovascular proliferation which occurred later. Although both patients had been treated with oral prednisone for approximately one month before their initial visit to our clinic, good visual recovery had not been achieved. Diagnosis was first confirmed by the positive results of serologic Treponema pallidum hemagglutination and Venereal Disease Research Laboratory tests. The patients were successfully treated with orally administered bacampicillin, which resulted in the complete recovery of visual acuity and normal fundus appearance except for slight pigmentary changes of the retina in the macular area.

Acute Disease↗
PubMed1991

Simple isocratic high-performance liquid chromatographic method for measurement of iodixanol in human plasma.

A simple isocratic high-performance liquid chromatographic method was developed for the determination of iodixanol in human plasma. Samples containing an internal standard were prepared for analysis using a simple clean-up procedure based on Sep-Pak C18 solid-phase extraction and chromatographed using a size-exclusion column with purified water as a mobile phase. The iodixanol peak was completely separated from the peaks of an internal standard and endogenous substances on this column. Three geometric isomers (exo-exo, endo-exo and endo-endo forms) of iodixanol could be eluted as a single peak. The method was found to be applicable to pharmacokinetic studies of iodixanol in human plasma.

Chromatography, High Pressure Liquid↗
PubMed1991

Alpha 1-adrenergic regulation of ketogenesis in isolated rat hepatocytes.

Studies were conducted to clarify the effects of noradrenaline on oleate metabolism in isolated hepatocytes from fed rats. Noradrenaline caused an inhibition of ketogenesis from oleate along with a stimulation of glucose release through alpha 1-adrenergic receptors. Anti-ketogenic action of noradrenaline was confirmed by the suppression of the formation of radioactive acid-soluble products from [1-14C]oleate in response to this agent. Noradrenaline increased the conversion of [1-14C]oleate into 14CO2 but failed to affect [1-14C]oleate esterification. When hepatocytes were incubated in a medium containing 1 mM EGTA but no Ca2+, the effects of noradrenaline on oleate oxidation were negated. On the other hand, noradrenaline-induced increase in glucose release remained unchanged even in the absence of Ca2+ in the incubation medium. Decrease in ketogenesis and increase in glucose release produced by vasopressin was completely abolished by calcium depletion. Noradrenaline caused a significant increase in cAMP levels in both the presence and absence of Ca2+, although the effect was more marked in the latter. Vasopressin did not affect it. The noradrenaline-induced increase in cAMP and glucose release in the absence of Ca2+ was also mediated by alpha 1-adrenergic receptors. These data are discussed and it is suggested that alpha 1-adrenergic agonists may control hepatic ketogenesis and glycogenolysis through two separate signal transduction mechanisms, i.e., a calcium-mobilizing system which is common with vasopressin, and a cAMP generation system which vasopressin lacks.

Animals↗
PubMed1991

Cytochemical localization of adenylate cyclase activity in rat olfactory cells.

Adenylate cyclase activity was demonstrated in the cilia, dendritic knob and axon of rat olfactory cells by using a strontium-based cytochemical method. The activity in the cilia and the dendritic knob was enhanced by non-hydrolyzable GTP (guanosine triphosphate) analogues and forskolin, and inhibited by Ca2+, all in agreement with biochemical reports of the odorant-sensitive adenylate cyclase. The results support the hypothesis of cyclic AMP working as a second messenger in olfactory transduction and imply that the transduction sites exist not only in the olfactory cilia but also in the dendritic knob. Enzymatic activity was also observed in the olfactory dendritic shaft by treating the tissue with 0.0002% Triton X-100, although the properties and role of the enzyme in this region are uncertain. The detergent inhibited the enzymatic activity in the cilia and the dendritic knob.

Adenylyl Cyclases↗
PubMed1991

Comparison of selective cytotoxicity of alkyl lysophospholipids.

Alkyl lysophospholipids have been shown to be cytooxic to a number of neoplastic tissues. One, ET-18-OCH3, has been used to selectively purge leukemic cells from mixtures with normal marrow progenitor cells, in vitro and in vivo. We have measured the 50% inhibitory (IC50) effect of a series of ether lipids (EL) on leukemic cells (HL60, K562, Daudi, KG-1, KG-1a) and normal marrow progenitor cells. Cells were incubated with varying concentrations of EL for 4 hr and assayed for viability, [3H]thymidine incorporation and clonogenicity in semi-solid media. The effect on protein kinase C (PKC) activity was assayed for each compound. Compounds tested included three glycerophosphocholine analogs--ET-18-OCH3, ET-16-NHCOCH3, and BM 41.440. In addition, a lipoidal amine, CP 46665, an ethyleneglycolphospholipid, AEPL, and four single chain alkylphosphocholine analogs, HePC2, HePC3, HePC4 and HePC6 were also tested. During the period of incubation, the cells remained viable (greater than 70%) as judged by trypan blue dye exclusion. The glycerophosphocholines were the most active and showed the highest therapeutic index. The lipoidal amine was active, but toxic to normal marrow progenitor cells. The ethyleneglycolphospholipid was active against HL60, but not against the other cell lines. The single chain alkylphosphocholine analogs were less active. All of the compounds inhibited PKC activity; however, the glycerophosphocholines were the most inhibitory.

Antineoplastic Agents↗
PubMed1991

Induction of differentiation of human myeloid leukemia HL-60 cells by novel nonphosphorus alkyl ether lipids.

We synthesized a new series of nonphosphorus alkyl ether glycerolipids, in which the 2-acetyl group of platelet-activating factor was replaced by a pyrimidin-2-yl group and the 3-phosphocholine portion by an omega-(substituted ammonio)ethoxyethyl side-chain including omega-thiazolio-, imidazolio- and pyridinio groups with or without a carboxyl substituent, respectively (compound I-XI). Their effects on cell proliferation and differentiation of human myeloid leukemia HL-60 cells were examined. Incubation of HL-60 cells with these cationic and zwitterionic alkyl ether lipids inhibited proliferation of HL-60 cells with IC50 values ranging from 10 to 500 ng/mL. The cells were induced by the lipids to differentiate into morphologically and functionally mature granulocytes. Among the compounds we tested, 1-octadecyl-2-pyrimidinyl-3-[3-(5- carboxylatepentyl)imidazolioethoxyethyl]glycerol (compound I) was the most effective in inducing differentiation of HL-60 cells. Compound I showed on a molar basis, an inhibitory effect on the leukemic cells over 50 times greater than did 2-(2-dodecyloxyethoxy)ethyl 2-pyridinio-ethyl phosphate, the antileukemic alkyl ether phospholipid.

Antineoplastic Agents↗