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Biomedical subjects

F Kobayashi

Publications and source records attributed to F Kobayashi.

At least 91 records · Page 5Linked to original sources
PubMed1994

Pharmacological profiles of a novel aldose reductase inhibitor, SPR-210, and its effects on streptozotocin-induced diabetic rats.

SPR-210 (2-[4-(4,5,7-trifluorobenzothiazol-2-yl)methyl-3-oxo-3,4-dihydro- 2H-1,4-benzothiazin-2-yl] acetic acid), a novel aldose reductase (AR) inhibitor, exhibited highly potent inhibition of partially purified AR from porcine lens (IC50 = 9.5 x 10(-9) M) and human placenta (IC50 = 1.0 x 10(-8) M). On the other hand, very weak inhibition by SPR-210 was observed against human placenta aldehyde reductase, which is the most closely related enzyme to AR, and against several adeninenucleotide-requiring enzymes. SPR-210 showed a noncompetitive mechanism with respect to DL-glyceraldehyde against porcine lens AR. Sorbitol accumulation in isolated human erythrocytes was effectively inhibited by SPR-210 during incubation with 50 mM glucose (IC50 = 1.6 x 10(-8) M). Oral administration of SPR-210 (1-30 mg/kg/day for 5 days) to streptozotocin-induced diabetic rats decreased the sorbitol contents in the sciatic nerve and lens (ED50 = 1.9 and 6.8 mg/kg/day, respectively). SPR-210 had higher potency in the lens than other AR inhibitors. Moreover, the deterioration in motor nerve conduction velocity in diabetic rats was ameliorated by treatment with SPR-210 (1-30 mg/kg/day) accompanying the reduction in sorbitol content in the sciatic nerve. SPR-210 induced the recovery of the delayed peak latency of oscillatory potentials (O1-O4) in the electroretinogram in diabetic rats (10 mg/kg/day). These results suggest that the specific AR inhibitor SPR-210 will be a useful therapeutic agent for preventing and improving some diabetic complications, especially diabetic neuropathy and retinopathy, and therefore, can be discriminated from other AR inhibitors.

Aldehyde Reductase↗
PubMed1994

[Thyroid disorders and sarcoidosis].

Thyroid disorders were detected in 3.7% of our 269 cases of sarcoidosis histologically confirmed. This is close to the rate in the literature. As a probability of this complication that some of closely allied autoimmune disorder may relate both disease, except by chance. In 2 of our cases, these diseases appeared alternately as follows. A 49 years old woman suffered from granular-hard struma with hypothyroid from 4 years ago when sarcoidosis had completely healed. On the other side, a 55 years old woman had the apparent struma for about 16 years from her 6 years of age and gradually disappeared after the signs of sarcoidosis became apparent. She also had a Basedow's patient in her family.

Adult↗
PubMed1994

Platelet-activating factor-acetylhydrolase activity in maternal and umbilical venous plasma obtained from normotensive and hypertensive pregnancies.

OBJECTIVE: To elucidate whether plasma platelet-activating factor-acetylhydrolase activities in women with pregnancy-induced hypertension and in their fetuses are different from those in normotensive mothers and fetuses. METHODS: We measured platelet-activating factor-acetylhydrolase activity in the plasma of 11 normotensive nonpregnant women, 39 normotensive pregnant women, 30 pregnant women with pregnancy-induced hypertension, 31 fetuses delivered from normotensive pregnant women, and 12 fetuses delivered from women with pregnancy-induced hypertension. RESULTS: Plasma platelet-activating factor-acetylhydrolase activity in normotensive pregnant women at 28-31 weeks' gestation was significantly lower than that in normotensive nonpregnant women (P < .001). In contrast, in women with pregnancy-induced hypertension at 28-31 weeks' gestation, the activity of this enzyme was significantly higher than that in gestational age-matched, normotensive pregnant women (P < .01). Platelet-activating factor-acetylhydrolase activity in the umbilical venous plasma of fetuses delivered from women with pregnancy-induced hypertension at 37-40 weeks' gestation was significantly higher than that in the gestational age-matched term fetuses of normotensive mothers (P < .001). CONCLUSION: These findings indicate that the hydrolysis of platelet-activating factor is decreased during a normal pregnancy and that such modulation does not occur in pregnant women with pregnancy-induced hypertension or in their fetuses.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1993

Identification and partial characterization of phospholipase D in the human amniotic membrane.

The enzymatic activity of phospholipase D and its characteristics have been examined in human amnion tissue. The phospholipase D activity was not Ca(2+)- or Mg(2+)-dependent and was activated by unsaturated fatty acids. The optimal pH of phospholipase D was 5.5. The phospholipase D activity in amnion tissue was highest in the microsomal fraction, and preferentially utilized phosphatidylcholine as a substrate. The phospholipase D activity of the microsomal fraction of amnion tissue obtained at term before labor onset (34.0 +/- 16.3 nmol/hour/mg protein, mean +/- SD, n = 11) was significantly (p < 0.05) higher than the activity in this tissue obtained from women in the mid-trimester (15.0 +/- 7.5 nmol/hour/mg protein, n = 9).

Amnion↗
PubMed1993

Assessment of sympathetic nerve activity controlling blood pressure in the elderly using head-up tilt.

In order to assess age-related changes in sympathetic nerve activity controlling blood pressure, we recorded muscle sympathetic nerve activity, blood pressure, and heart rate during head-up tilt in 10 healthy elderly (69-75 years) and 16 healthy young (19-23 years) subjects. The elderly had significantly lower responsiveness of muscle sympathetic nerve activity to postural change than did the young subjects. In the elderly, marked rise in blood pressure without increase in muscle sympathetic nerve activity was observed in nearly upright position during head-up tilt, whereas this phenomenon was not observed in the young. We conclude that neural control function of blood pressure during head-up tilt in the elderly differs from that in the young, which may be due to age-related change in baroreflex function.

Adrenergic Fibers↗
PubMed1993

Effects of aerobic exercise conditioning at intensities corresponding to lactate threshold in the elderly.

In this study we attempted to determine the effects of exercise training at the intensity corresponding to lactate threshold (Thla-) on various health-related variables in sedentary but apparently healthy elderly subjects. Six men and five women volunteers [mean age 68.9 (SD 3.4) years] performed supervised endurance-type training on stationary cycle ergometers for 30 min and recreational activities for 30 min, 3 days a week for 12 weeks. Four men and four women served as the control group [68.8 (SD 4.4) years]. As a result of the training programme, statistically significant increases in maximal oxygen consumption (10%), oxygen consumption at Thla- (18%), distance covered in 12-min walk, side step, and leg extensor power were found in the training group, while no changes occurred in the control group. The changes in serum cholesterol and triglyceride concentrations from the pre- to post-training period were statistically significant. High-density lipoprotein cholesterol remained unchanged, and low-density lipoprotein cholesterol tended to decrease following the training programme. These data would indicate that exercise training at the intensity corresponding to Thla- may have favourable effects on overall physical fitness and some serum lipid variables in older individuals.

Aged↗
PubMed1993

Maternal serum CA125 levels in early intrauterine and tubal pregnancies.

Using an immunoradiometric assay, serum CA125 levels were measured in 13 women with a normal pregnancy, 9 with a spontaneous abortion, 3 with a hydatidiform mole, and 15 with a tubal pregnancy. Serum CA125 levels were high in patients with a normal pregnancy (154 +/- 169 U/ml; mean +/- S.D.), a spontaneous abortion (244 +/- 258 U/ml), or a hydatidiform mole (54 +/- 16 U/ml). In contrast, CA125 levels in patients with a tubal pregnancy (33 +/- 25 U/ml) were low, and almost all of those without uterine bleeding (25 +/- 9 U/ml) were within the normal range for non-pregnant women (< 35 U/ml). The difference between serum CA125 levels with intrauterine pregnancy and with tubal pregnancy may be ascribed to the difference of the amount of decidual tissues at the site of trophoblastic invasion.

Abortion, Spontaneous↗
PubMed1993

Comparison of haemoconcentration induced by big endothelin-1 and endothelin-1 in mice.

1. The profile of haemoconcentration induced by big endothelin-1(big ET-1), a precursor of endothelin-1 (ET-1), was compared with that induced by endothelin-1 in mice. 2. ET-1(1.5 nmol kg-1, i.v.) increased haematocrit in mice, which reached a maximum at 5 min and then returned to the control value within 30 min after the administration, this occurred at the same time as changes in the plasma immunoreactive endothelin-1 and rat atrial natriuretic peptide (rANP)-like activities (IR-ET-1 and IR-rANP, respectively). 3. Big ET-1(2.5-15 nmol kg-1, i.v.) also caused a significant and dose-dependent increase in haematocrit, that lasted over 3 h although elevated plasma IR-ET-1 and IR-rANP had almost been restored to the initial levels within 10 min after big ET-1 injection. 4. A metalloproteinase inhibitor, phosphoramidon (10 mg kg-1, i.v.), which inhibits the activity of endothelin converting enzyme (ECE), delayed the onset of big ET-1-induced haemoconcentration, but failed to alter the maximal value and the duration of the haemoconcentration. 5. Pretreatment with phosphoramidon (10 mg kg-1, i.v.) did not affect the big ET-1-induced change in plasma IR-ET-1, while significant delay of the disappearance of plasma IR-rANP and significant suppression of a sustained increase in tissue IR-ET-1 were observed. 6. These results suggest that ET-1, not in plasma but in tissue, plays an important role in the pathogenesis of big ET-1-induced long-lasting haemoconcentration, in which unknown factors besides rANP are involved.

Animals↗
PubMed1993

Pharmacological profiles of aspergillomarasmines as endothelin converting enzyme inhibitors.

Aspergillomarasmine-A and -B (AM-A and -B), which were isolated from the cultured broth of an unidentified fungus N877, showed apparent inhibition against endothelin-converting enzyme (ECE) from bovine endothelial cells as measured by the formation of endothelin-1 (ET-1) converted from big endothelin-1 (bET-1), with IC50 values of 3.4 and 2.5 microM for AM-A and -B, respectively. EDTA also inhibited ECE (IC50 = 1.1 microM), but the inhibitions by AM-A, AM-B and EDTA were each abolished by the addition of 10 microM Zn2+ to the reaction mixture. In mice, AM-A and -B dose-dependently (10-50 mg/kg, i.v.) caused significant prolongation of the latency to sudden death induced by i.v. bET-1 (25 nmol/kg), but not that by ET-1 (5 nmol/kg), accompanied by a decrease in plasma immunoreactive ET-1 formation, while EDTA (24 mg/kg) failed to do so. In mice, the LD50 value of AM-A was calculated to be 159.8 mg/kg, i.v., which was much larger than that of EDTA (28.5 mg/kg, i.v.), indicating the low toxicity of AM-A. AM-A (30 mg/kg, i.v.) also suppressed bET-1-induced hemoconcentration and hypertension in mice and rats, respectively. These findings suggest that although ECE inhibition by AM-A was mainly attributable to its chelating activity, it showed apparent in vivo activities due to ECE inhibition with low toxicity.

Animals↗
PubMed1993

The relationship between the ambulatory variability and the laboratory reactivity of blood pressure and heart rate.

We examined the relationship between the ambulatory variability and the laboratory reactivity of systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) in 21 male college students. The mean increase during the waking period from that during sleep was defined as variability 1, and the standard deviation of the ambulatory measurements during waking was defined as variability 2. The reactivity to laboratory tests was measured by the pretask-to-task increase in variables. The high SBP variability 1 group showed a significantly higher reactivity of SBP and noradrenaline in the bicycle exercise test (70w). This suggests the possibility that SBP variability 1, can be predicted by increased reactivity to a mild limb exercise test. The high HR variability 1 group, and the high SBP variability 2 group showed significantly lower reactivity of stroke volume (SV) and cardiac output (CO) in the cold face test. Thus, parasympathetic responses such as trigeminal-brainstem-vagal pathway function or baroreflex sensitivity seemed to be reduced in these groups. The high DBP variability 2 group showed significantly lower DBP reactivity in the cold face test, and low noradrenaline reactivity in the mental arithmetic test, which indicated a reduced alpha-adrenergic response in this group. No other significant differences in reactivity to the laboratory mental stress tests were found between the variability 1 and variability 2 groups.

Adult↗
PubMed1993

Cardiovascular function in the elderly during water immersion.

In attempting to clarify the effects of aging on the regulatory functions of the cardiovascular system, we measured blood pressure, heart rate and stroke volume during thermoneutral head-out water immersion in seven healthy elderly and eight healthy young subjects. In the young subjects water immersion resulted in a marked increase in stroke volume, a deceleration of the heart rate and stable blood pressure values. In the elderly group the blood pressure increased significantly during shoulder-level water immersion. Compared to the young subjects, the elderly presented a less pronounced elevation of the stroke volume, and no change in the heart rate. These results indicate that the vasodepressive mechanisms regulated by baroreflexes diminish with aging, resulting in an elevation of blood pressure.

Adult↗
PubMed1993

Pharmacological profiles of the new histamine H2-receptor antagonist N-ethyl-N'-[3-[3-(piperidinomethyl)phenoxy] propyl] urea.

The histamine H2-receptor antagonistic activity and antisecretory effects of KU-1257 (N-ethyl-N'-[3-[3-(piperidinomethyl) phenoxy]propyl]urea, CAS 120958-90-9) were studied. The Ki values of KU-1257, roxatidine acetate, famotidine and cimetidine for the inhibition of [3H]-tiotidine binding to guinea-pig cerebral cortex were 0.040, 0.13, 0.016 and 0.40 mumol/l, respectively. The KB values of KU-1257, roxatidine acetate, famotidine and cimetidine for the antagonism against histamine-induced positive chronotropic response of isolated guinea-pig right atrium were 0.041, 0.14, 0.031 and 0.51 mumol/l, respectively. In pylorus-ligated rats, KU-1257, roxatidine acetate and famotidine inhibited gastric acid secretion with respective intraduodenal ID50 values of 12.3, 18.5 and 0.45 mg/kg. In dogs with Heidenhain pouch, the ID50 values of KU-1257 for the inhibition of acid output stimulated by histamine, tetragastrin and meat meal were 0.08, 0.39 and 0.15 mg/kg p.o., respectively. KU-1257 was 2-3 times more potent than roxatidine acetate regardless of secretagogues and twice less than famotidine in meat meal stimulation. These results indicate that KU-1257 is a potent and competitive histamine H2-receptor antagonist.

Animals↗
PubMed1993

A new treatment for dialysis-related amyloidosis with beta 2-microglobulin adsorbent column.

Dialysis-related amyloidosis (DRA) is characterized by the presence of beta 2-microglobulin (beta 2-m) in the plasma. In order to eliminate beta 2-m from the circulating blood, the beta 2-m selective adsorbent for direct hemoperfusion (DHP) was developed. A DHP column (BM-01), containing 350 ml of the adsorbent, was subjected to clinical trials. The column was connected with a PAN (AN69) membrane dialyzer in series and used 3 times a week for 1 week (11 patients), 4 weeks (5 patients), 6 months (1 patient) and 12 months (2 patients). The percent reduction (%) of beta 2-m was for 16 patients (for 1 or 4 weeks), more than 65, and for 3 patients (for more than 6 months), 76.5 +/- 4.9, 73.5 +/- 5.7, 72.2 +/- 6.2. At the end of each session, beta 2-m plasma levels were found to be below 10 mg/L, with 3.4 mg/L being the lowest. The total amounts of beta 2-m removed were 172.5 +/- 22.3, 257.0 +/- 75.6, 157.6 +/- 32.2 and 429.8 mg/session at max. Two out of these three patients had a favorable effect on joint symptoms and ocular fundus. It can be concluded that this selective adsorption therapy may delay the progression of DRA, and is worth considering for wide application.

Adsorption↗
PubMed1993

Adenosine deaminase isoenzymes in liver disease.

To clarify the clinical significance of increased serum adenosine deaminase (ADA) activity, and its mechanisms in various liver diseases, ADA isoenzyme activities (ADA1 and ADA2) in serum and the peripheral blood mononuclear cells were studied. High serum ADA activities were found in patients with acute hepatitis, alcoholic hepatic fibrosis, chronic active hepatitis, liver cirrhosis, and hepatoma. The ADA2:ADA ratio was decreased in acute hepatitis, but was increased in chronic active hepatitis and liver cirrhosis. Clinically, ADA2 activity was correlated with serum gamma-globulin levels. In chronic active hepatitis, total ADA activities in the peripheral blood mononuclear cells were similar to those in controls. Furthermore, ADA2 activities after phytohemagglutinin (PHA) stimulation were significantly lower than those without PHA stimulation, although total ADA activities were increased after PHA stimulation. These findings suggest that serum ADA isoenzyme activities may be a new marker for liver disease, and that the increased serum ADA2 in chronic active hepatitis is unlikely to be the result of an increase in ADA2 production by activated peripheral blood mononuclear cells.

Adenosine Deaminase↗
PubMed1992

Woodfruticosin (woodfordin C), a new inhibitor of DNA topoisomerase II. Experimental antitumor activity.

Woodfruticosin (woodfordin C) (WFC), a new inhibitor of DNA topoisomerase II (topo-II), was isolated from methanol extract of Woodfordia fruticosa Kurz (Lythraceae) and studied for in vitro and in vivo antitumor activities in comparison with Adriamycin (ADR) and etoposide (ETP), well known inhibitors of topo-II. The inhibitory activity against DNA topo-II shown by WFC was much stronger than that shown by ETP or ADR. WFC inhibited strongly intracellular DNA synthesis but not RNA and protein synthesis. On the other hand, WFC had a weaker growth inhibitory activity against various human tumor cells than ETP or ADR, but it showed remarkable activity against PC-1 cells and moderate activity against MKN45 and KB cells. Furthermore, WFC had in vivo growth inhibitory activity against s.c. inoculated colon38. These results indicate that the mechanism by which WFC exhibits antitumor activity may be through inhibition of topo-II.

Animals↗
PubMed1992

Big endothelin-1-induced sudden death is inhibited by phosphoramidon in mice.

The lethal activity of big endothelin-1 (bET-1) was examined in mice and compared with endothelin-1 (ET-1). Like ET-1, intravenous administration of bET-1 produced sudden death with an approximate LD50 value at 21.0 nmol/kg, higher than that of ET-1 (3.8 nmol/kg). At doses above the respective LD90 value, the latency to death was much longer in bET-1-treated mice with sustained elevation of plasma immunoreactive ET-1 (IR-ET-1). A metalloproteinase inhibitor, phosphoramidon, although failing to inhibit sudden death induced by ET-1, suppressed bET-1-induced lethality and elevation of plasma IR-ET-1 probably due to an inhibition of the enzymatic conversion of bET-1 to ET-1.

Animals↗