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Biomedical subjects

M Kohno

Publications and source records attributed to M Kohno.

At least 361 records · Page 20Linked to original sources
PubMed1991

Effect of hypoxia on plasma immunoreactive endothelin-1 concentration in anesthetized rats.

The present study was designed to examine the possible influence of hypoxia on plasma immunoreactive (ir) endothelin-1 concentrations in anesthetized rats. Plasma ir-endothelin-1 concentration, blood pressure, heart rate, and arterial gas levels were measured 1 and 2 hours after exposure to normoxic (20% O2), mildly hypoxic (16% O2), and severely hypoxic (12% O2) gas. Mean blood pressure and heart rate were significantly decreased and the plasma ir-endothelin-1 concentration was significantly increased in severely hypoxic rats after both 1 and 2 hours. In mildly hypoxic rats, the plasma ir-endothelin-1 concentration was also increased, but this value was not statistically significant. The plasma ir-endothelin-1 concentration was inversely correlated with arterial blood PO2 in the three study groups (normoxic, mildly hypoxic, and severely hypoxic rats) after 1 hour (n = 18, r = -.74, P less than .01), and after 2 hours (n = 18, r = .71, P less than .01). Our results indicate that severe hypoxia increased the plasma ir-endothelin-1 level in anesthetized rats. The observed increase in plasma ir-endothelin-1 level may represent a compensatory mechanism against the blood pressure reduction associated with severe hypoxia.

Anesthesia↗
PubMed1991

Endothelin-secreting tumor.

Recently, we have reported two cases with endothelin (ET)-secreting tumor presenting with hypertension and elevated plasma endothelin-1 (ET-1) levels. The present study examines the histopathology of the ET-secreting tumor in one of these cases. The neoplasm was located in the skin and microscopically characterized as a malignant hemangioendothelioma by remarkable intravascular proliferations of atypical endothelium with the expression of Factor VIII-related antigen in the tumor cells. The tumor enlarged rapidly with rising ET-1 and blood pressure levels. The ET-1 content and its messenger RNA expression in the tumor extract were higher than those from normal parts of skin. ET-1 may play a pathophysiological role in patients with ET-secreting malignant hemangioendothelioma.

Aged↗
PubMed1991

Involvement of active oxygen in lipid peroxide radical reaction of epidermal homogenate following ultraviolet light exposure.

To elucidate the radical mechanism of lipid peroxidation induced by ultraviolet light (UV) irradiation, an electron spin resonance (ESR) study was made on epidermal homogenate prepared from albino rat skin. The exposure of the homogenate to UV light resulted in an increase in lipid peroxide content, which was proportional to the time of UV exposure. Using ESR spin trapping (dimethyl-1-pyrroline-N-oxide, DMPO), the DMPO spin adduct spectrum of lipid radicals (L.) was measured following UV exposure (DMPO-L.:aN = 15.5 G, aH = 22.7 G), as was the spectrum of DMPO-hydroxyl radical (DMPO-OH, aN = aH = 15.5 G). In the presence of superoxide dismutase, the DMPO spin adduct spectrum of lipid radicals was found to be reduced remarkably. Therefore, it was shown that the generation of the lipid radicals partially involves superoxide anion radicals, in addition to hydroxyl radicals. In the ESR free-radical experiment, an ESR signal appeared at g = 2.0064 when the ESR tube filled with homogenate was exposed to UV light at -150 degrees C. The temperature-dependent change in the ESR free radical signal of homogenate exposed to UV light was observed at temperatures varying from -150 degrees C to room temperature. By using degassed samples, it was confirmed that oxygen is involved in the formation of the lipid peroxide radicals (LOO.) from the lipid radicals (L.).

Animals↗
PubMed1991

Development of a radioimmunoassay for human group-II phospholipase A2 and demonstration of postoperative elevation.

A radioimmunoassay (RIA) for the determination of human group-II phospholipase A2 (M-PLA2) has been developed. M-PLA2 was purified from human spleen. Monoclonal antibody (IgG) was prepared by fusion of splenic cells from immunized mice with M-PLA2 and the mouse myeloma cell line NS-1. The RIA was carried out by a single antibody method. The assay is sensitive (0.78 micrograms/l), reproducible and specific. In healthy individuals, the serum M-PLA2 concentration ranges from 1.4 to 4.2 micrograms/l, the average being 2.2 +/- 0.1 micrograms/l (mean +/- SE). Using the RIA, we found increased serum M-PLA2 in patients with various infections and malignant tumors. We also showed the postoperative transient elevation of serum M-PLA2 in cases without any infectious complications. The elevation was independent of the surgical procedure or site. The maximum serum M-PLA2 level was seen on the 2nd to 4th postoperative day. In these patients, the serum M-PLA2 and C-reactive protein levels were significantly correlated. The present study indicated that serum M-PLA2 is an acute phase reactant.

Acute-Phase Proteins↗
PubMed1991

Plasma immunoreactive endothelin-1 in experimental malignant hypertension.

We measured plasma concentrations of immunoreactive endothelin-1 (irET-1) in the prehypertensive and hypertensive phases in spontaneously hypertensive rats (SHR) and in malignant hypertension caused by deoxycorticosterone acetate (DOCA)-salt administration in SHR. We also measured concentrations of this peptide in another model of malignant hypertension, the two-kidney, one clip (2K1C) renovascular hypertensive rats chronically given caffeine. Plasma irET-1 concentrations in young (6-week-old) and mature (18-week-old) SHR did not differ from those of age-matched Wistar-Kyoto (WKY) rats. Four weeks of treatment with DOCA-salt increased blood pressure, blood urea nitrogen, serum creatinine, and plasma irET-1 in SHR but not in WKY rats. Eight weeks of DOCA-salt treatment further increased these values in SHR. Plasma irET-1 concentrations were not increased in the 2K1C rats. Six weeks of caffeine administration increased blood pressure, blood urea nitrogen, serum creatinine, plasma renin activity, and plasma irET-1 in the 2K1C rats but not in the sham-operated rats. High-performance liquid chromatographic profiles of plasma extracts pooled from these rats with malignant hypertension showed that a major component of irET-1 eluted in the position of synthetic ET-1 (1-21). Furthermore, acute hypertension induced by angiotensin II or phenylephrine did not affect the plasma irET-1 concentration in rats. The results suggested that the plasma ET-1 concentration is increased in rat models of malignant hypertension and that the high blood pressure itself is not the main factor involved in the increase of plasma ET-1.

Aging↗
PubMed1991

Endothelin-3 regulates endothelin-1 production in cultured human endothelial cells.

Effects of endothelin-3 on the secretion of endothelin-1 and other endothelium-derived substances were investigated in cultured human umbilical vein endothelial cells. The present binding study showed two distinct subpopulations of binding sites for endothelin-3 with higher and lower affinities in cultured human endothelial cells. Endothelin-3 caused an increase in intracellular Ca2+ and inositol 1,4,5-trisphosphate levels and activated protein kinase C in a dose-dependent manner. Endothelin-3 also caused an increase in [3H]thymidine incorporation into cellular DNA and stimulated the production of cyclic guanosine 3',5'-monophosphate, 6-ketoprostaglandin F1 alpha, and immunoreactive endothelin-1 in cultured human endothelial cells. NG-Monomethyl L-arginine (3 x 10(-4) mol/l) and indomethacin (10(-5) mol/l) enhanced endothelin-3-induced endothelin-1 production. These results suggest that endothelin-3 bound to its specific receptors and then caused phosphoinositide breakdown, subsequently mobilizing intracellular Ca2+ and leading to protein kinase C activation and the initiation of DNA synthesis, resulting in the stimulation of endothelin-1 production by human endothelial cells. Furthermore, this endothelin-1 production may be suppressed by endothelium-derived relaxing factor and prostacyclin produced in response to endothelin-3 in cultured human endothelial cells.

Calcium↗
PubMed1991

Inhibition by atrial and brain natriuretic peptides of endothelin-1 secretion after stimulation with angiotensin II and thrombin of cultured human endothelial cells.

We examined the inhibition by atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) of endothelin-1 secretion stimulated by angiotensin II (ANGII) and thrombin using cultured human umbilical-vein endothelial cells. ANGII and thrombin dose-dependently stimulated immunoreactive (ir) endothelin-1 secretion. Human ANP(1-28) and human BNP-32 both inhibited such secretion in a dose-dependent way. Inhibition of this secretion by ANP and BNP was paralleled by an increase in the level of cyclic guanosine 5'-monophosphate (GMP). The addition of a cyclic GMP analogue, 8-bromo cyclic GMP, reduced this stimulated secretion. Rat ANP(5-25) was weaker than human ANP(1-28) at inhibiting ir-endothelin-1 secretion and increasing cyclic GMP in the cells. ir-Endothelin-1 in the medium consisted of two components separated by high pressure liquid chromatography; the major one corresponded to endothelin-1(1-21) and the minor one corresponded to big endothelin-1(1-38). Treatment with ANP and BNP did not affect this profile. These findings suggest that human ANP and BNP inhibit endothelin-1 secretion stimulated by ANGII and thrombin in these cells through a cyclic GMP-dependent process. Taken together with endothelin stimulation of ANP and BNP secretion from the heart, our results suggest the existence of a cardiac-endothelium feedback.

Angiotensin II↗
PubMed1991

Acute effects of alpha- and beta-adrenoceptor blockade on plasma atrial natriuretic peptides during exercise in elderly patients with mild hypertension.

In a randomized study in 26 elderly patients with mild essential hypertension, acute effects of alpha- and beta-adrenoceptor blockade on plasma ANP levels were examined at rest and during ergometric exercise. Plasma ANP level and LVEF were measured before and after administration of prazosin (an alpha 1-adrenergic blocker), atenolol (a cardioselective beta-adrenergic blocker), or carteolol (a nonselective beta-adrenergic blocker). Plasma ANP level was increased by exercise. Carteolol and atenolol increased plasma ANP levels at rest and during exercise, but the effect of atenolol was not statistically significant. Prazosin significantly suppressed the ANP values at rest and during exercise. The LVEF was increased by prazosin and decreased by beta-blockers, especially by carteolol. Multivariate regression analysis showed that LVEF was the most significant predictor of the plasma ANP level at maximal exercise; the resting blood pressure and heart rate were not predictors of this value. The results showed that single administrations of an alpha-blocker and a nonselective beta-blocker had opposite effects on the plasma ANP level both at rest and during exercise in elderly patients with mild essential hypertension. The observed difference in the ANP response seems to be related to changes in left ventricular function rather than changes in blood pressure or heart rate.

Aged↗
PubMed1991

Difficulties encountered in the detection of nitric oxide (NO) by spin trapping techniques. A cautionary note.

The spin trapping technique was used in an attempt to detect the free radical nitric oxide (NO) in solution. Five different spin traps were examined, alpha-phenyl-N-tert butyl nitrone (PBN), alpha-(4-pyridyl-N-oxide) N-tert-butylnitrone (POBN), 5,5-dimethyl-pyrroline-N-oxide (DMPO), 2-methyl-2-nitrosopropane (MNP) and 3,5-dibromo-4-nitrosobenzene sulfonate (DBNBS). Our results suggest that the nitroso spin traps (MNP, DBNBS) are better suited for the identification of NO-related signals, than the nitrones, DMPO, PBN and POBN. In addition, it is shown that spin trapping of NO-related signals with nitroso and nitrone spin traps is subject to many artifacts.

Cyclic N-Oxides↗
PubMed1991

[Temporal profile of the superoxide dismutase and the ascorbic acid in focal cerebral ischemia].

It has been proposed that free radical reactions are involved in ischemic brain damage. Since irreversible pathological changes occurs very early phase of the focal ischemia and the ischemic brain edema reaches its peak at about 2 days of ischemia, the free radical reactions must take place before these changes. Superoxide dismutase is a famous enzyme that dismutase superoxide anion, which is believed to be one of the initiator of the free radical reactions. If superoxide anion plays a pivotal role in the genesis of pathological ischemic brain damage and edema, the activity of the enzyme may decrease in the early phase of ischemia. Ascorbic acid is also known to be a scavenger of superoxide anion, and brain tissue contains it in a high concentration. We investigated the changes in superoxide dismutase activity and concentration of reduced ascorbate in focal ischemia. Focal ischemia was produced in rats by permanent occlusion of the left middle cerebral artery. The animals were decapitated 30 minutes, 4, 24, and 48 hours after the operation. Middle cerebral artery territory of each cerebral hemisphere was homogenized and centrifuged with phosphate buffer. The supernatant was divided into two aliquots; one was dialyzed to remove ascorbate and the other was not. The SOD activity was measured by electron-spin-resonance (ESR) spin trapping method, and the ascorbic acid concentration was measured by high performance liquid chromatography with electrochemical detection (HPLC-ECD). Protein concentration was measured by Lowry's method. The enzyme activity was expressed as unit/mg protein, and the ascorbic acid concentration was expressed as microgram/g tissue. The SOD activity decreased markedly by dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

65-kilodalton protein phosphorylated by interleukin 2 stimulation bears two putative actin-binding sites and two calcium-binding sites.

We have previously characterized a 65-kilodalton protein (p65) as an interleukin 2 stimulated phosphoprotein in human T cells and showed that three endopeptide sequences of p65 are present in the sequence of l-plastin [Zu et al. (1990) Biochemistry 29, 1055-1062]. In this paper, we present the complete primary structure of p65 based on the cDNA isolated from a human T lymphocyte (KUT-2) cDNA library. Analysis of p65 sequences and the amino acid composition of cleaved p65 N-terminal peptide indicated that the deduced p65 amino acid sequence exactly coincides with that of l-plastin over the C-terminal 580 residues [Lin et al. (1988) Mol. Cell. Biol. 8, 4659-4668] and has a 57-residue extension at the N-terminus to l-plastin. Computer-assisted structural analysis revealed that p65 is a multidomain molecule involving at least three intriguing functional domains: two putative calcium-binding sites along the N-terminal 80 amino acid residues; a putative calmodulin-binding site following the calcium-binding region; and two tandem repeats of putative actin-binding domains in its middle and C-terminal parts, each containing approximately 240 amino acid residues. These results suggest that p65 belongs to actin-binding proteins.

Actins↗
PubMed1990

Mitogenic signalling pathway of tumour necrosis factor involves the rapid tyrosine phosphorylation of 41,000-Mr and 43,000-Mr cytosol proteins.

Tumour necrosis factor (TNF) is a potent mitogen for some fibroblast cell lines. Here we have examined the TNF-mediated changes in protein phosphorylation in Swiss 3T3 and human FS-4 fibroblasts, and compared them with changes observed after the treatment of cells with other mitogens, such as platelet-derived growth factor (PDGF) and bombesin. TNF stimulated the rapid phosphorylation of two 41,000-Mr and two 43,000-Mr cytosol proteins on tyrosine, threonine and/or serine, as did PDGF, epidermal growth factor and fibroblast growth factor; the increased levels of this mitogen-induced protein-tyrosine phosphorylation correlated well with the extent of mitogen-induced DNA synthesis as determined by the percentage of labelled nuclei. In contrast, bombesin, which is an even better mitogen for Swiss 3T3 cells than TNF, stimulated the tyrosine phosphorylation of 41,000-Mr and 43,000-Mr proteins only to a limited extent. On the other hand, bombesin and PDGF stimulated the rapid serine phosphorylation of an 80,000-Mr acidic protein, a major substrate for protein kinase C; increased phosphorylation of the 80,000-Mr protein was not observed at all when cells were stimulated with TNF. These results suggest significant differences among the mitogenic signalling pathways of TNF, PDGF and bombesin as regards the involvement of protein kinases; the mitogenic signalling pathway of TNF involves the activation of tyrosine kinase, but not of protein kinase C, whereas bombesin seems to transduce its mitogenic signal mainly through the activation of protein kinase C, and the activation of both kinases seems to be involved in the mitogenic signalling pathway of PDGF.

Animals↗
PubMed1990

Characterization of interleukin 2 stimulated 65-kilodalton phosphoprotein in human T cells.

We have characterized the cellular proteins which are rapidly phosphorylated by interleukin 2 (IL 2) in a human IL 2 dependent cell line. When treated with IL 2, the phosphorylation of five proteins, 65, 50, 37, 24, and 21 kDa, was found in IL 2 dependent cell lines by two-dimensional gel electrophoretic analysis. After cell conversion from an IL 2 dependent state to an IL 2 independent state, one of the five phosphoproteins, the 65-kDa protein, became constitutively phosphorylated even without addition of IL 2. Also, in other IL 2 independent cell lines, such as KUT-2 and HUT-102, constitutive phosphorylation of the 65-kDa protein occurred without IL 2-stimulation. So our researchers were focused on biochemical characterization of the 65-kDa protein. It was found that the 65-kDa protein was one of the major cellular proteins by comparing the results of two-dimensional gel electrophoretic analysis of [32P]Pi-labeled and [3H]leucine-labeled cellular proteins and peptide mapping analysis. Subcellular fractionation studies indicated that the 65-kDa protein is a cytosol protein. The 65-kDa protein was purified from cytosol of a human T cell line, and its amino acid composition and amino acid sequences of its three oligopeptides were determined. It was found that the 65-kDa protein is identical with 1-plastin.

Amino Acid Sequence↗
PubMed1990

Efficacy and safety of carvedilol in renal hypertension. A multicenter open trial.

Carvedilol, a novel beta-blocker with a vasodilating action, was given either alone (monotherapy) or with diuretics (combination therapy) to 42 patients with renal hypertension. The hypotensive effect, safety, and optimal dose were investigated. In all, 23 untreated patients (16 men and 7 women; average age, 56.4 +/- 2.5 years) made up the monotherapy group and 19 diuretic-treated patients (11 men and 8 women; average age, 56.4 +/- 2.5 years) comprised the combined therapy group. All subjects had an initial blood pressure (BP) of greater than 160/95 mmHg and were started on 5 mg/day oral carvedilol. The dose was gradually increased to a maximum of 20 mg/day, or until either the BP was reduced to less than 149/89 mmHg or the reduction in mean BP was greater than 13 mmHg compared with baseline levels. The total study period was 8 weeks. With monotherapy, the BP and heart rate decreased significantly from 167/102 to 150/94 mmHg and from 81 to 74 beats/min, respectively. With combined therapy, the BP and heart rate fell significantly from 176/103 to 142/85 mmHg and from 81 to 70 beats/min, respectively. Responders were defined as subjects with a BP of less than or equal to 149/89 mmHg or those showing a fall of greater than or equal to 13 mmHg in mean BP. Responders accounted for 52.2% of the monotherapy group and 73.6% of the combination therapy group. Orthostatic hypotension was not seen in either group. Serum creatinine and blood urea nitrogen (BUN) levels were not altered by administration of carvedilol. Dizziness was noted by 1 of the 23 subjects in the monotherapy group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1990

A clinicopathological study of asymptomatic primary biliary cirrhosis in three aged patients.

The 3 cases suffering from asymptomatic primary biliary cirrhosis (aPBC) were all older than 70 and female. Case 1, 2 and 3 were respectively 77, 72 and 70 years old. The final diagnosis was made on the basis of clinical observation and liver biopsy. Case 1 was diagnosed as CAH-PBC mixed type from histological findings and classified as stage II-III according to Scheuer's classification. Case 2 was stage I and exhibited morphological features of PBC with arteriosclerotic change. Case 3 was stage I and had dysplasia-like large nuclei in some hepatic cells. Clinically, all cases were AMA positive. Elevation of serum ALP and IgM values was recognized in 2 cases, but serum transaminase and ALP values were not elevated in Case 2 for 1 year. In the follow-up observation during 5 years. Case 1 remained asymptomatic except for gradual elevation of serum ALP value. AMA, which was positive at the time of diagnosis, is now negative after 5 years, but now produces high potency ANA. The incidence of PBC in those aged older than 70 in Japan accounts for only 2-3% of all PBC cases. According to some reports, the prognosis of PBC deteriorates with age. In 3 cases reported here, however, the clinical course did not deteriorate even in untreated cases. This suggests the possibility that some aPBC cases diagnosed at an age older than 70 may have a favorable prognosis.

Aged↗