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Biomedical subjects

M Nishida

Publications and source records attributed to M Nishida.

At least 379 records · Page 21Linked to original sources

Transcardiac alteration of neutrophil function before and after coronary thrombolysis in human myocardial infarction.

We examined function of isolated neutrophils taken from aorta and coronary sinus before and after thrombolytic reperfusion in 17 patients whose infarct-related coronary arteries were totally occluded. Before reperfusion in left coronary artery disease, free radical generation by activated neutrophils in coronary sinus, assessed by ferricytochrome c reduction (phorbol myristate acetate, 10 ng/ml) and luminol-enhanced chemiluminescence (A23187, 2 microM), was reduced by 20% (P less than 0.05) and 30% (P less than 0.05), respectively, compared with those in aorta. Neutrophil aggregation (A23187, 10 microM) and chemotactic activity (formyl-methionyl-leucyl-phenylalanine, 5 microM) were also reduced in coronary sinus by 21% and 20%. After reperfusion the extent of such neutrophil function in coronary sinus recovered and was similar to that in aorta. There were no significant differences between neutrophil counts in aorta and coronary sinus before and after reperfusion. In right coronary artery disease, no significant changes were seen in these functions of neutrophils of aorta and coronary sinus before and after reperfusion. These results indicate that function of neutrophils passing through coronary circulation fluctuated significantly in association with reperfusion, suggesting (1) factor(s) that depress neutrophil function are produced in coronary circulation during myocardial ischemia and their effects are overcome after reperfusion or (2) activated neutrophils, trapped in the ischemic coronary bed, are washed out to coronary sinus after reperfusion.

Chemotaxis, Leukocyte↗

In vitro antibacterial activity of ME1207, a new oral cephalosporin.

ME1207 is the prodrug of ME1206. Its in vitro antibacterial activity was compared with that of cefteram, cefpodoxime, cefixime, and cefaclor against various clinical isolates. ME1206 was more active than the other cephems tested against staphylococci, streptococci, Morganella morganii, Pseudomonas cepacia, and Flavobacterium meningosepticum and had the most potent activity against Haemophilus influenzae and Neiserria gonorrhoeae. The drug also showed a wide spectrum of activity against other gram-positive and gram-negative bacteria, except methicillin-resistant Staphylococcus aureus, Enterococcus faecalis, Citrobacter freundii, Pseudomonas aeruginosa, Xanthomonas maltophilia, and Alcaligenes xylosoxydans.

Administration, Oral↗

NADH measurements in adult rat myocytes during simulated ischemia.

In isolated adult rat myocytes, we tested the hypothesis that metabolic inhibition and simulated ischemia regulate the NADH/NAD+ redox couple with concomitant impairment of energy-dependent process, including contraction and maintenance of high-energy phosphate stores. We developed a method to examine the relationship among the redox couple, ATP content, and contractile performance in single cells under several conditions analogous to myocardial ischemia, with and without reperfusion. Myocytes were paced at 1 Hz while cell contraction and NADH fluorescence were determined simultaneously for single cells at 37 degrees C. Cells were exposed to cyanide and 2-deoxy-D-glucose (metabolic inhibition) or to metabolic inhibition plus 12 mM KCl and 20 mM lactate at pH 6.5 (simulated ischemia). Pyridine nucleotide fluorescence signals from single cells studied in this fashion could be modulated by metabolic inhibitors in a manner similar to that classically described for isolated mitochondria. Metabolic inhibition or simulated ischemia quickly produced maximal reduction of NAD+ to NADH. When cells were exposed to simulated ischemia for 10 min, then superfused with glucose-containing control buffer, 28% of cells exposed to conditions of simulated ischemia developed hypercontracture on reperfusion. Hypercontracture developed despite mitochondrial electron transport being reestablished. When myocyte suspensions in a cuvette were studied spectrofluorimetrically, the pyridine nucleotide fluorescence response to metabolic inhibitors was similar to that for a single cell. This permitted correlation of ATP determinations on cells in suspension with contractile and fluorescence measurements from single myocytes. In the absence of glycolysis there is correspondence among loss of electron transport, decline in high-energy phosphate concentration, and decline in contraction. Irreversible disruption of the electron transport process does not appear to be an early event in ischemic injury.

Adenine Nucleotides↗

Differential effects on fatty acid compositions in the liver microsomes of thyroidectomized or streptozocin induced diabetic rats.

The purpose of the present study was to locate a controversial site and to make generalizations about the effects of thyroidectomy (Tx) and streptozocin (STZ) on the distribution pattern of an individual fatty acid in microsomal fractions of the animals thus treated. The results obtained were compared with the reported data. The effects of Tx on C18:1, C18:2, and all detectable C20 and C22 species harmonized well within each species; however the effects of Tx on C16 species and C18:0 varied within each species. Meanwhile, all the effects of STZ were identical within the species, but were often in opposite directions between two adjacent species; e.g. C18:0 and C18:1. These findings strongly indicate that desaturation and elongation sites were independently affected by either Tx or STZ. The comparison suggested that controversial effects appeared in the distribution proper to species C18. Therefore, delta 9-desaturase activity in the microsomal fractions was measured, using stearoyl coenzyme A (CoA) as substrate, resulting in some partial reduction in Tx, but complete suppression in STZ-treated animals. The total contents of phospholipid and cholesterol in the microsomes were also measured. Results showed a significant increase in microsomes within the STZ-group, but almost no change in the Tx-group, indicating that the changes in an individual fatty acid component and in the total fatty acids do not always take place in parallel.

Animals↗

Uptake of nicotinamide by rat pancreatic beta cells with regard to streptozotocin action.

Exposure of rat pancreatic beta cells in monolayer culture to 2 mmol streptozotocin (STZ)/l for 1 h followed by thorough washing inhibited their uptake of [14C]nicotinamide and [3H]2-deoxyglucose [( 3H]2-DG) to about 50% and also reduced the intracellular ATP concentration to 50% of that in control cells. These changes were not due to a lethal cytotoxic effect of STZ, because cell viability, as estimated by succinic dehydrogenase activity, was 90% of that of control cells. Oligomycin and carbonylcyanide-m-chlorophenylhydrazone (CCCP), an uncoupler of oxidative phosphorylation, caused a dose-dependent decrease in intracellular ATP concentration while maintaining high cell viability. These ATP-depleted cells showed a decrease in insulin release and an inhibition of the uptake of [14C]nicotinamide and [3H]2-DG in a dose-dependent manner. Therefore oligomycin and CCCP reproduced the same effects as those found in beta cells treated with STZ. These results suggest that the uptake of nicotinamide and 2-DG by beta cells might be regulated by their intracellular ATP concentration. The decreased uptake of nicotinamide in ATP-depleted beta cells caused by STZ might explain the lack of protective effect of nicotinamide against STZ cytotoxicity when administered after the latter. Furthermore, the radiotracer experiments demonstrated that the transport of nicotinamide by intact beta cells was inhibited in a dose-dependent manner by 2-DG and vice versa, i.e. the transport of 2-DG was inhibited by nicotinamide. These findings suggest the existence of a common transport mechanism in beta cells responsible for the uptake of nicotinamide and 2-DG, the transport of which is known to occur by facilitated diffusion.

Adenosine Triphosphate↗

[Establishment and characterization of a human scirrhus type gastric cancer cell line, GCIY, producing CA19-9].

A human gastric cancer cell line, designated GCIY, was established from ascites of a patient with scirrhus type gastric cancer. Doubling time of this cell line was 55 hours. The karyotype indicated that these cells were human cells and the chromosome number varied widely, the mode being 57. GCIY cells were of moderate size and showed monolayer arrangement. They had a large nucleus and a clear nucleolus. Papanicolaou staining showed that they had the characteristics of adenomatous epithelia. They could be subcutaneously transplanted into nude mice, and they histologically resembled the original tumor. They were immunohistochemically recognized by anti-CA19-9 antibody and weakly by anti-CA125, CEA and alpha FP antibodies. Cultured medium also contained CA19-9, CA125, CEA and alpha FP.

Adenocarcinoma, Mucinous↗

Changes in stainability observed by light microscopy in the brains of ataxial mice subjected to three generations of manganese administration.

Two neonates of mice which manifested abnormal motions in their gait in the third generation litter, following the start of manganese (Mn) administration, were selected. One was severely affected by Mn and the other was only moderately affected. Various regions in the brains of the neonates were subjected to histochemical examination under a light microscopy. The losses of stainability in granular cells in the external layer of the cerebral cortex, and Purkinje cells in the cerebellar cortex, and the increase in stainability of the nerve fibers in the cerebellar medulla were in parallel to the degree of abnormal movement in the gait; the greater loss or gain in stainability, varying according to the regions, was associated with the more severe damages to motion. Meanwhile, the changes in the stainabilities of nerve cell nuclei in the lamellar structure of cerebral motor areas and the Nissl bodies in the cerebral medulla were already maximal in the moderately affected neonate. These results indicate that the Mn effect covers a broad area of the extrapyramidal tract even though there are some differences in the sensitivity to Mn in different regions.

Animals↗

Synergistic and antagonistic effects on fatty acid composition in the liver mitochondria of rats by thyroidectomy and streptozotocin-administration.

The content of individual fatty acid component in mitochondria of livers from thyroidectomized (Tx) and streptozotocin (STZ)-induced diabetic rats was measured to investigate how different hormones are interrelated to control the amount of a particular fatty acid in mitochondria. The results showed (1) diabetes, in general, affected fatty acid contents more severely than hypothyroidism, regardless of the direction of the changes; (2) Hypothyroidism and diabetes affected antagonistically the contents of C16 species and C18:1, which belong to a de novo synthesis (oleate series). However, the two pathological conditions affected synergistically those of higher unsaturated species, eg. C18:2, C20:3 and C20:4, which belong to a dietary-dependent synthesis (linoleate series). These results strongly indicated that each desaturation site and elongation site is affected in a preferential order by either thyroid hormone or insulin, and that hypothyroidism and diabetes have their effects differently on the process of de novo synthesis and the pathways initiated from an essential fatty acid in mitochondria.

Animals↗

Changes in mouse brain monoamine oxidase activity in the first, second and fourth generations after manganese administration.

The present study was conducted to explore whether or not manganese effect on brain monoamine oxidase (EC 1.4.3.4) is subject to hereditary genetic amplification. Mice of both sexes were given manganese through four generations, and the enzyme activity was measured in the cerebral cortex, cerebellum, hypothalamus and hippocampus of each of the generations except for the third, whose activity we were not in a position to measure. Intrinsic enzyme activity was highest in the cerebellum, and was followed by those in the cerebral cortex and hypothalamus. The activity in the hippocampus was the lowest. Manganese administration greatly stimulated the activity in the cerebellum. However, as generation succeeded, the level of susceptibility to manganese gradually declined. Manganese concentration in pooled suborgan fractions proved to be, in every case, higher in the cerebral cortex, cerebellum and hippocampus and lower in the hypothalamus. No indication was found that the manganese effect is genetically inherited.

Activation Analysis↗

[A study of forearm muscle metabolism in patients with chronic heart disease].

To assess forearm exercise capacity and exercise energy metabolism in relationship to forearm muscle mass and blood flow in patients with chronic heart disease, 22 patients (NYHA class I (C1) 8, class II(C2) 10, class III (C3) 4) and 10 normal subjects were studied using Phosphorus-31 magnetic resonance spectroscopy (31P-MRS). First, the maximal cross sectional area (MCA) of the forearm flexor muscles was estimated in each individual using magnetic resonance imaging. Then, during multistage forearm flexor exercise, 31P-MRS was performed to estimate phosphocreatine (PCr), inorganic P (Pi), and intracellular pH. Forearm blood flow was measured by plethysmography. An initial work load of forearm exercise was decided by MCA as 1 J/cm2, and multistage exercise was done with an increment of 1 J/min/cm2 to the point of maximal muscle exhaustion. The maximal load (J/min) was decreased in cardiac groups as NYHA class advanced. However, the difference among all groups except group C3 was not significant when the max load was adjusted for muscle MCA. As the work load was increased during forearm exercise, PCr and intracellular pH decreased, and Pi increased in every group. Standardized PCr [PCr/(PCr + Pi)] was lower in group C2 and C3 than in group N at each work load. At high work loads, intracellular pH tended to be lower in group C2 and C3 than in group N and C1. Forearm blood flow during forearm exercise was not different among the four groups. In the maximal exercise test using upright ergometer, peak oxygen uptake and anaerobic threshold were lower in group C1, C2 and C3 than in group N.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Identification of a chromosome carrying a putative tumor suppressor gene in human choriocarcinoma by microcell-mediated chromosome transfer].

There are two main mechanisms of origin for complete hydatidiform mole; a) fertilization of an empty egg by a haploid sperm followed by duplication, and b) fertilization of such an egg by two haploid spermatozoa. It is widely accepted that, of all forms of pregnancy that had to choriocarcinoma, the risk associated with moles is by far the highest. Homozygous expression of a recessive mutation of moles has been assumed to associate with this propensity to malignancies. Alterations of several tumor suppressor genes together with activation of oncogenes are assumed to be necessary for choriocarcinogenesis. Genetic characteristics shown in the moles suggest that the former alterations are especially important to explore the multistep conversions to malignancies. Thus, individual chromosomes derived from normal cells were introduced into choriocarcinoma cells via microcell fusion. Evaluation of tumorigenicity in microcell hybrids suggested that chromosome #7 carried a putative tumor suppressor gene for choriocarcinoma. The gene imprinting or recessive mutation may be responsible for the inactivation of such a gene, being able to correspond with the high propensity to malignancy of moles.

Animals↗

[Alprazolam for patients with psychotic symptoms or autonomic imbalance symptoms after breast cancer surgery].

Effectiveness of alprazolam in daily dosages of 0.8-1.2 mg was studied in 28 patients who showed psychotic symptoms or autonomic imbalance symptoms after operation for breast cancer. Psychotic symptoms included depression, anxiety, tension, and restlessness, and symptoms of autonomic imbalance included sleep disorder, anorexia, and pains. All of these symptoms were improved at high ratios by alprazolam. The drug was very useful in 16 cases (57.1%), useful in 11 cases (39.3%), and slightly useful in one case (3.6%). The only adverse reaction reported was unsteady gait in one case.

Adult↗

Glucose-evoked recovery of hepatic thyroxine 5'-deiodinase independent of de novo protein synthesis in fasted rat.

The glucose-evoked recovery of Type I thyroxine 5'-deiodinase activity in the hepatic microsomes of fasted rat was not inhibited by either cycloheximide, puromycin or actinomycin D during 3 h after glucose feeding; however, [3H]-leucine uptake by the liver or the hepatic microsomal fraction was significantly inhibited by cycloheximide and puromycin but not by actinomycin D. These results indicate that the glucose-evoked recovery of deiodinase activity may be independent of de novo protein synthesis.

Animals↗

Effect of human macrophage colony-stimulating factor on granulopoiesis and survival in bone-marrow-transplanted mice.

Human macrophage colony-stimulating factor (hM-CSF) has been isolated from normal human urine and purified to a homogeneous protein. The effect of hM-CSF on granulopoiesis was investigated in BALB/c mice transplanted with a suboptimal number of bone marrow cells. Lethally irradiated (7.8 Gy) mice were transplanted with 1 x 10(6) syngeneic mouse bone marrow cells and treated with a daily intraperitoneal dose of 64 micrograms/kg of hM-CSF for 5 days following the transplant. The hM-CSF injection resulted in stimulation of the recovery of blood neutrophils as well as an increase in the number of granulocyte-macrophage progenitor cells (CFU-GM) in the femur and spleen. The survival of lethally irradiated mice was dependent on the cell number transplanted; most mice transplanted with 2 x 10(4) cells died within 2 weeks. The recovery of hematopoiesis in mice transplanted with 2 x 10(4) cells was modestly but significantly stimulated by hM-CSF administration initiated from 5 days before or 1 day after transplantation for a 5-day period. Furthermore, the hM-CSF administrations markedly reduced the mortality in these mice during the early period after the transplantation. Since anaerobic bacteria were frequently detected in arterial blood immediately before the deaths but were not found in the surviving mice, it is speculated that early deaths occurring within 2 weeks after the transplant may be caused by opportunistic infections, and hM-CSF injection may prevent these mortal infections through its stimulating effect on monocyte-macrophage functions that are responsible for the production of hematopoietic regulators.

Animals↗

Polymorphonuclear leukocytes induced vasoconstriction in isolated canine coronary arteries.

To assess how polymorphonuclear leukocytes (PMNs) act on coronary vasoactivity, we measured the changes in isometric tension of isolated rings of canine coronary arteries upon addition of autologous PMNs to organ chambers in which the rings were suspended. When PMNs isolated by the colloidal polyvinylpyrrolidone-coated silica (Percoll) gradient method were added to the chambers, ring preparations of left circumflex coronary arteries developed isometric tension. The increase in tension was dependent on the amount of PMNs (1 X 10(4) to 5 X 10(6) cells/ml). Maximal tension obtained by an optimal amount of PMNs (5 X 10(5) cells/ml) was almost comparable to that produced by prostaglandin F2 alpha (5 microM). Integrity of endothelial cells was not disrupted after the addition of PMNs because the developed tension could be reversed by the addition of acetylcholine in an endothelium-dependent manner. Mechanical rubbing of endothelium abolished the PMN-induced vasoconstriction, which was regained by placing an endothelium-unrubbed ring inside a rubbed ring ("sandwich preparation"). When PMN suspensions were pretreated with 5-lipoxygenase inhibitors of arachidonate, PMN-induced vasoconstriction was greatly suppressed, although the pretreatment of vascular preparations did not alter the development of isometric tension. These findings indicate that PMNs induce the contraction of coronary arterial rings in the presence of intact endothelial cells. The mechanism by which PMNs induce the contraction is the release of vasoconstrictive substances by metabolic interaction between PMNs and endothelial cells. Vasoconstrictive substances produced by the PMN-endothelial system, such as 5-lipoxygenase metabolites through a "leukotriene A4 steal" mechanism, may contribute to the contraction of vascular smooth muscle.

Animals↗