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Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 1,153 records · Page 64Linked to original sources

A 1H NMR method for the analysis of antigen-antibody interactions: binding of a peptide fragment of lysozyme to anti-lysozyme monoclonal antibody.

A proton nuclear magnetic resonance (NMR) study is reported of the molecular structural basis of antigen-antibody interactions. An immunologically reactive proteolytic fragment corresponding to one of the antigenic regions on hen egg-white lysozyme (HEL) was used in combination with a monoclonal antibody that recognizes this site. Using spin diffusion, we prepared an antibody in which the magnetization of the antigen binding site was saturated by non-specific nuclear Overhauser effect. Under these conditions the effect of the saturation of the antibody was observed to spread over the peptide fragment through the antigen binding site. On the basis of the results obtained for the intermolecular nuclear Overhauser effect, we discuss how the peptide fragment interacts with the antibody. The side chains of aromatic residues, Trp, Tyr, and His, and of ionic residues, especially Arg, Lys, and Glu, are suggested to be important in the antigen-antibody interaction.

Animals↗

Prostaglandin E1 in pulmonary hypertension of collagen disease.

A 47-yr-old woman with low cardiac output and dyspnea due to pulmonary hypertension associated with rheumatoid arthritis was treated with two vasodilators. Although nicardipine, a Ca-channel blocking agent, reduced the pulmonary artery pressure (PAP), it reduced simultaneously the arterial BP, resulting in fluid retention with a low urine output and persistent high CVP. In contrast, prostaglandin E1 (PGE1) reduced successfully both the PAP and CVP. Although the BP decreased, a satisfactory urine output was maintained. The cardiac output increased from 3 to 4.5 L/min. PGE1 may help reduce reversible pulmonary hypertension of collagen disease.

Alprostadil↗

Characterization of a cytosolic aconitase in higher plant cells.

Protoplasts obtained from sycamore (Acer pseudoplatanus) cell suspensions were found to be highly intact. If the protoplasts were taken up and expelled through a fine nylon mesh, all the protoplasts were ruptured leaving the fragile amyloplasts largely intact. Aconitase hydratase (citrate [isocitrate] hydro-lyase, EC 4.2.1.3) activity of sycamore cells was associated with two protein fractions, one present in the cytosol while the second is of mitochondrial origin. Chromatography on DEAE-trisacryl did not separate the aconitase hydratase isoenzymes. EPR studies established that both isoenzymes exhibited an EPR signal at g = 2.03 once oxidized.

Journal Article↗

Proglobulin processing enzyme in vacuoles isolated from developing pumpkin cotyledons.

The enzymic conversion of proglobulin to globulin catalyzed by the extracts of vacuoles isolated from developing pumpkin (Cucurbita sp. cv Kurokawa Amakuri Nankin) cotyledons was investigated. The endoplasmic reticulum fraction isolated from the developing cotyledons pulselabeled with [(35)S]methionine was shown to contain mainly the radiolabeled proglobulin, which was used as a substrate for assaying the proteolytic processing in vitro. The vacuolar extracts catalyzed the proteolytic processing of the proglobulin molecule to produce globulin containing two kinds of polypeptide chains, gamma and delta. The pH optimum for the vacuole-mediated conversion was at pH 5.0. The proteolytic processing of proglobulin by the vacuolar extracts was inhibited in the presence of various thiol reagents, e.g. p-chloromercuribenzoate, N-ethylmaleimide, iodoacetic acid, Hg(2+), and Cu(2+), but not phenylmethylsulfonyl fluoride, EDTA, o-phenanthroline, leupeptin, antipain, pepstatin, chymostatin, or pumpkin trypsin inhibitor, and was activated in the presence of dithiothreitol and cysteine, indicating that the processing enzyme is a thiol protease. The suborganellar fractionation of the vacuoles showed that the processing activity was localized in the matrix fraction, but not in the membrane or crystalloid fractions. During the seed development, the enzyme was shown to increase, exhibiting the maximal activity at the late developmental stage. The matrix fraction of the protein bodies isolated from the dry castor bean (Ricinus communis) exhibited the processing activity toward the pumpkin proglobulin molecules in the same manner as that by the matrix fraction of pumpkin vacuoles.

Journal Article↗

Enhanced biliary gamma-glutamyltransferase excretion following prolonged alcohol consumption in rats.

In order to study the question of whether chronic ethanol consumption may alter the biliary excretion of gamma-glutamyltransferase (gamma-GT), female rats were pair-fed nutritionally adequate liquid diets containing either ethanol (36% of total calories) or isocaloric carbohydrates for 24 days. Compared to pair-fed controls, the administration of the alcohol-containing diet resulted in an increased biliary excretion of gamma-GT (5.84 +/- 0.73 mU 6 h-1 100 g-1 b.w. vs. 8.82 +/- 0.79, P less than 0.001). This was associated with a corresponding enhanced biliary output of total bile acids. An apparent linear relation between the biliary output rates of gamma-GT and those of total bile acids was observed both in alcohol-fed animals (r = 0.83) and in their pair-fed controls (r = 0.95). In addition, there was a significant increase of gamma-glutamyltransferase activities in the liver homogenate and in liver plasma membranes, both in fractions rich in bile canalicular and basolateral membranes and in those rich in blood sinusoidal site. Serum gamma-glutamyltransferase activities as well as serum bile acid concentrations were also enhanced by 96.8% (P less than 0.001) and 233% (P less than 0.001), respectively. These data show that chronic alcohol consumption enhances hepatic gamma-GT activities, leading to an increased efflux of gamma-GT into the bile and possibly into the blood out of the liver cell. Furthermore, these data suggest the involvement of bile acids with their solubilizing properties for the biliary excretion of gamma-GT.

Alcoholism↗

Effect of brain blood flow on hypoxic ventilatory response in humans.

To assess the effect of brain blood flow on hypoxic ventilatory response, we measured arterial and internal jugular venous blood gases and ventilation simultaneously and repeatedly in eight healthy male humans in two settings: 1) progressive and subsequent sustained hypoxia, and 2) stepwise and progressive hypercapnia. Ventilatory response to progressive isocapnic hypoxia [arterial O2 partial pressure 155.9 +/- 4.0 (SE) to 46.7 +/- 1.5 Torr] was expressed as change in minute ventilation per change in arterial O2 saturation and varied from -0.16 to -1.88 [0.67 +/- 0.19 (SE)] l/min per % among subjects. In the meanwhile, jugular venous PCO2 (PjCO2) decreased significantly from 51.0 +/- 1.1 to 47.3 +/- 1.0 Torr (P less than 0.01), probably due to the increase in brain blood flow, and stayed at the same level during 15 min of sustained hypoxia. Based on the assumption that PjCO2 reflects the brain tissue PCO2, we evaluated the depressant effect of fall in PjCO2 on hypoxic ventilatory response, using a slope for ventilation-PjCO2 line which was determined in the second set of experiments. Hypoxic ventilatory response corrected with this factor was -1.31 +/- 0.33 l/min per %, indicating that this factor modulated hypoxic ventilatory response in humans. The ventilatory response to progressive isocapnic hypoxia did not correlate with this factor but significantly correlated with the withdrawal test (modified transient O2 test), which was performed on a separate day. Accordingly we conclude that an increase in brain blood flow during exposure to moderate hypoxia may substantially attenuate the ventilatory response but that it is unlikely to be the major factor of the interindividual variation of progressive isocapnic hypoxic ventilatory response in humans.

Carbon Dioxide↗

Relationship between the ability to detect added resistance at rest and breathlessness during bronchoconstriction in asthmatics.

The ability to detect added resistance at rest was compared to the magnitude of breathlessness (evaluated by a modified Borg scale) during bronchoconstriction in 27 stable asthmatics. Threshold for resistive load detection was analyzed in terms of the Weber fraction (delta R/R0) and mouth pressure (P) at the threshold. Bronchoconstriction was induced by inhalation of aerosolized acetylcholine. Both delta R/R0 and P correlated inversely with the Borg score during bronchoconstriction (r = -0.537 and r = -0.689, respectively; p less than 0.01). On the other hand, during bronchoconstriction the Borg score did not correlate with increased lung volume, acute changes in arterial blood gas composition and drive and timing component of ventilation during bronchoconstriction, although bronchoconstriction caused significant changes in these variables. These results indicate that central processing of afferent stimuli rather than peripheral sensor contribute both to the ability to detect added resistance at rest and to the magnitude of breathlessness during bronchoconstriction in asthmatics.

Acetylcholine↗

The pathophysiological role of renal dopaminergic activity in patients with essential hypertension.

To evaluate the role of the renal dopaminergic system on renal water-sodium metabolism patients with essential hypertension (EHT), urinary excretion of dopamine, urinary excretion of sodium (UNaV) and fractional excretion of sodium (FENa) were all investigated before and after the administration of dopamine (3 micrograms/kg/min, intravenous infusion for 60 minutes), dopamine antagonist, metoclopramide (8 mg/m2 BSA, intravenous injection) or mild sodium loading in both normotensive subjects and benign EHT. In the basal values, no significant difference in urinary excretion of free (u-fDA), conjugated (u-cDA) or total dopamine (u-tDA) was found between normotensives and hypertensives. However, low renin EHT showed a pronounced reduction in u-fDA compared with normotensis subject and (NT) normal renin EHT. In this study, a significant reduction of u-cDA and of u-tDA was also found in those patients with low renin essential hypertension. In the normotensive and essential hypertensive groups UNaV or FENa showed a positive correlation with u-fDA (measured simultaneously), but not with u-tDA or u-cDA. The regression line between u-fDA and UNaV or FENa in EHT was shifted towards a lower u-fDA level than in NT. UNaV and FENa were increased by dopamine infusion and were decreased by metoclopramide injection in both NT and EHT. Changes of UNaV and FENa following dopamine or metoclopramide, showed a negative correlation with u-fDA measured immediately before the administration of these drugs. The enhanced natriuretic response to infused dopamine and the attenuated antinatriuretic response to injected metoclopramide were significant in low renin EHT, when compared with NT or normal renin EHT patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of hypoxia, 2,4-dinitrophenol and ouabain on twitch potentiation elicited following conditioning pulses in the mouse phrenic nerve-diaphragm preparation.

Hypoxia is suggested to increase intracellular Ca2+, thereby affecting cellular functions. If this is the case, the effect would be modified by other treatments which also elevate intracellular levels of Ca2+. To test this possibility, in mouse diaphragm preparations, the effects of hypoxia were examined on twitch potentiations after application of neural conditioning pulses which are considered to elevate intracellular Ca2+. The effects were compared with those of 2,4-dinitrophenol (DNP) and ouabain. Hypoxia increased the tension of twitches elicited directly or neurally with 0.1 or 0.5 Hz pulses at 36 degrees C but not at 24 degrees C. Paired pulses to the nerve induced a complex response profile in which the amplitude of the second twitch was enhanced (twitch facilitation). Tetanic pulses (50 Hz) to the nerve were followed by post-tetanic twitches of increased amplitude (post-tetanic twitch potentiation, PTP). Hypoxia little affected the twitch facilitation but abolished PTP at both temperatures. These effects differed from those of DNP and ouabain in some ways. Thus, present experiments indicate that hypoxia selectively influences the process which is responsible for the PTP phenomenon rather than for the twitch facilitation. It is possible that the mechanism by which hypoxia would accumulate intracellular Ca2+ may be included in the process through which PTP occurs.

2,4-Dinitrophenol↗

Doxapram on blunted respiratory chemosensitivity to hypoxia in hypoxemic, chronic obstructive pulmonary disease.

We investigated a possible effect of doxapram (a respiratory stimulant) on the peripheral chemoreceptors in man (8 control subjects, 11 bronchitics, and 4 emphysematous). In addition, we determined whether infusion of doxapram could augment blunted chemosensitivity to hypoxia or hypercapnia seen in both chronic obstructive pulmonary disease (COPD) patients and normal subjects. Doxapram infusion caused a significant increase in delta VE/delta SaO2 (p less than 0.05), as well as delta Po.1/delta SaO2 (p less than 0.05) in control subjects, although the changes in both delta VE/delta PeAco2 (where, PeAco2 = end-tidal Pco2) and delta Po.1/delta PeAco2 did not attain significant level. Control subjects with low baseline delta Po.1/delta SaO2 showed significantly larger changes in both delta Po.1/delta SaO2 and delta VE/SaO2 during doxapram infusion than the patients with chronic bronchitis (0.02 less than p less than 0.05). We conclude that doxapram increases chemosensitivity to hypoxia and slightly increase chemosensitivity to hypercapnia, indicating its primary action being stimulation of peripheral chemoreceptors, and doxapram stimulates chemoreceptors little in patients with chronic bronchitis, whereas blunted hypoxic response in normal subjects could be increased markedly.

Adolescent↗

Diffuse pulmonary ossification associated with chronic bronchitis.

A thirty-three-year-old man with diffuse pulmonary ossification associated with chronic bronchitis is described. Chest roentgenograms of the patient showed diffuse reticulo-nodular shadows partially super-imposed by calcified reticular opacities. Marked declines in forced vital capacity and air-flow limitation were associated with decreased diffusing capacity of the lung for CO, hypoxemia, and hypercapnia. In the postmortem examination, diffuse dendriform ossification was found mainly in the alveolar space. Neither interstitial fibrosis nor capillary congestion was found histopathologically in the lung.

Adult↗

[Adult Wilms tumor: a case of prolonged survival achieved by multimodal treatment].

Wilms tumor is one of the most common malignant neoplasms in children. In the last 2 decades the survival rate of children with this disease has dramatically increased. However, in adults, the guideline for its management is less clear. We herein report the prolonged survival of a patient with advanced adult Wilms tumor after treatment with chemotherapy, irradiation and operations. Adult Wilms tumor should be treated aggressively with a well-timed combination of surgery, chemotherapy and radiotherapy (i.e., multimodal treatment), even if the stage of the disease was advanced. Thereby, we suspect that the prognosis of adult Wilms tumor would be markedly improved.

Adult↗