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Biomedical subjects

N Kase

Publications and source records attributed to N Kase.

At least 19 recordsLinked to original sources

Role of decidual natural killer (NK) cells in patients with missed abortion: differences between cases with normal and abnormal chromosome.

In order to study the mechanism of abortion, the proportions of NK cells in the peripheral blood and decidual lymphocytes were evaluated in both chromosomally normal and abnormal missed abortions. In normal pregnancy, CD56+16-3- NK cells are a major element of decidual lymphocytes. The percentages of CD56+16-3-NK cells of peripheral lymphocytes in normal pregnancies were not statistically significantly different from those of chromosomally normal and abnormal abortions. In the decidua, the percentages of CD56+16-3- NK cells of decidual lymphocytes showed no statistically significant differences between normal pregnancies and chromosomally abnormal abortions. However, the percentages of CD56+16-3-NK cells of chromosomally normal abortions were lower than those of chromosomally abnormal (P = 0.0025). Moreover, the percentages of CD56+16- NK cells in abortions with normal chromosomes were lower than those in normal pregnancies or abortions with abnormal chromosomes (P = 0.0037, P = 0.0025). However, when the proportion of CD56+ NK cells expressing CD16 was evaluated, there were no statistically significant differences in the percentages of CD56+16+ NK cells in normal pregnancies and missed abortions with normal chromosomes and abnormal chromosomes. We conclude that the expression of decidual CD56+16-3- NK cells in missed abortions with normal chromosomes is different from abortions with abnormal chromosomes and that this phenomenon may depend on an abnormal immune response of the maternal side.

Abortion, Missed↗

Proportion of CD56+3+ T cells in decidual and peripheral lymphocytes of normal pregnancy and spontaneous abortion with and without history of recurrent abortion.

PROBLEM: The present study investigated the proportion of CD56+3+ T cells in maternal peripheral and decidual lymphocytes in normal pregnancy and spontaneous abortion with and without history of recurrent spontaneous abortion (RSA). METHOD OF STUDY: Maternal peripheral blood and decidua were taken from normal pregnancies and missed abortions with and without RSA. Decidual lymphocytes were prepared from decidual tissue and analyzed by flow cytometry. RESULTS: In normal pregnancy, the percentages of CD56+3+ T cells in decidual lymphocytes did not differ from those in the peripheral blood. However, the proportion of CD56+3+ T cells in decidual CD3+ T cells increased higher than that in the peripheral CD3+ T cells. The percentages of decidual CD56+3+ T cells in missed abortions with and without RSA were lower than those in normal pregnancies. CONCLUSION: CD56+3+ T cells may play a role in the maintenance of pregnancy. The phenomenon, where the proportion of CD56+3+ T cells in decidual lymphocytes decreases, may be due to an immunologic event leading to missed abortion.

Abortion, Habitual↗

Decidual natural killer cells in recurrent spontaneous abortion with normal chromosomal content.

PROBLEM: The maternal local immune responses in unexplained recurrent spontaneous abortion (RSA) are not yet well known. Maternal peripheral and decidual natural killer (NK) cells were evaluated in RSA with normal chromosomal content. METHOD OF STUDY: Maternal peripheral blood, villous trophoblast, and decidua were taken from 15 normal pregnancies and 9 RSA patients with normal chromosomes. The NK cells in decidual lymphocytes were evaluated by flow cytometry using monoclonal antibodies for CD56, CD16, and CD3. RESULTS: The percentages of CD56+ CD16- CD3- cells in decidual lymphocytes in RSA were lower than in normal pregnancies (P < 0.002). The CD56+CD16+/CD56+CD16- cells ratio in RSA was higher than in normal pregnancies (P < 0.02). CONCLUSION: The lower percentages of CD56+CD16-CD3- cells in RSA cases may show an inappropriate accumulation of NK cells in the decidua, and this finding may be a factor involved in RSA.

Abortion, Habitual↗

Capsaicin-induced calcitonin gene-related peptide release from isolated rat stomach measured with a new chemiluminescent enzyme immunoassay.

The peripheral capsaicin-sensitive afferent nerve has been reported to play an important role in gastroprotection and to release a calcitonin gene-related peptide (CGRP). We developed a new chemiluminescent enzyme immunoassay (CLEIA) for CGRP and measured capsaicin-induced CGRP release from the isolated and inverted rat stomach. The basal CGRP release from the stomach was 0.40 +/- 0.02 pg/mg wet weight in a 30-min incubation. Capsaicin (1 x 10(-8)-1 x 10(-5) M) stimulated CGRP release in a concentration-dependent manner. In the stomach from rats with defunctionalization of afferent neurons, the levels of the basal and capsaicin-induced CGRP release were below the limit of detection. On the other hand, the capsaicin-induced CGRP release was not blocked by tetrodotoxin treatment. The gangliosym-pathectomy abolished the increase in the CGRP levels. However, the capsaicin-induced CGRP release was not affected by pretreatment with 6-hydroxydopamine, a neurotoxin that causes a complete degeneration of adrenergic nerve terminals. In conclusion, the CLEIA system may be useful for detecting the released CGRP and studying the activity of capsaicin-sensitive nerves, particularly the CGRP-containing nerves. Our results also confirmed that although the CGRP-containing nerve runs in the sympathetic nerve trunk, the activity of the nerve is not affected by adrenergic nerves, and the capsaicin-induced CGRP release may be attributable to the tetrodotoxin-resistant component.

Adrenergic Agents↗

[Pharmacological profile of F-0401, a novel dihydropyridine derivative. III. The anti-aggregatory action of F-0401 on rabbit platelets].

F-0401 is a newly synthesized dihydropyridine derivative with both antagonistic activity on platelet-activating factor (PAF) and inhibitory action on thromboxane A2(TXA2) synthetase activity. In the present study, we examined the effects of F-0401 on platelet aggregations in vitro and ex vivo in rabbits. F-0401 prevented PAF-, arachidonic acid (AA)- and collagen-induced platelet aggregations in vitro, but did not prevent the aggregation by ADP. The inhibitory effect of F-0401 on the aggregation by PAF (IC50 value: 3.4 x 10(-6) M) or by the threshold amount of AA (IC50 value: 4.3 x 10(-6) M) had the same potency as that of CV-3988 (a PAF antagonist) and ozagrel a (TXA2 synthetase inhibitor). Ex vivo studies also revealed that the anti-aggregatory effect occurred 1 h after the treatment of F-0401 (> 10 mg/kg, p.o.) and this effect had a tendency to last for 6 h. Nicardipine prevented the platelet aggregation only by PAF (IC50 value: 6.6 x 10(-5) M) in vitro. However, the preventive effect was not seen ex vivo. On the other hand, neither nifedipine nor flunarizine showed any effect on the stimulant-induced platelet aggregation in rabbits. These results suggest that F-0401 has anti-aggregatory action, which is attributable to both PAF antagonistic action and TXA2 synthetase inhibition in vitro and ex vivo.

Animals↗

Hypocholesterolemic action and prevention of cholesterol absorption via the gut by F-1394, a potent acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, in cholesterol diet-fed rats.

In the present study, we investigated the hypocholesterolemic effect of F-1394 ((1s,2s)-2-[3-(2,2-dimethylpropyl)-3-nonylureido]aminocycloh exane-1-yl 3-[N-(2,2,5,5-tetramethyl-1,3-dioxane-4-carbonyl)amino] propionate), a potent and selective inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), and the effect on cholesterol absorption via the gut in rats fed a 1% cholesterol diet. Single administration of F-1394 to the cholesterol diet-fed rats at the doses of 3-30 mg/kg, p.o. decreased the serum cholesterol levels by 16-54% 3 hr after the administration. The ACAT activity in the small intestinal mucosa of the rats given orally F-1394 (30 mg/kg) was significantly inhibited 3 hr after the administration. The hypocholesterolemic action of F-1394 had a faster onset than that of DL-melinamide or CL-277,083. The study by the dual isotope ratio method showed that F-1394 (30 mg/kg, p.o.) significantly suppressed the dietary cholesterol absorption. Furthermore, in the determination of cholesterol absorption by using 14C-cholesterol as the oral tracer, the administration of F-1394 (30 mg/kg, p.o.) 1 or 2 hr before or immediately after the application of the oral tracer significantly prevented the appearance of the radioactivity in the circulation by around 90%. These results indicate that oral administration of F-1394 inhibits the ACAT activity in the small intestinal mucosa and subsequently contributes much to the prevention of cholesterol absorption via the gut, resulting in the decrease in serum cholesterol levels in the cholesterol diet-fed rats. Furthermore, the effect of F-1394 appears immediately after its administration in contrast to that of DL-melinamide or CL-277,082.

Administration, Oral↗

[Pharmacological profile of F-0401, a novel dihydropyridine derivative. (1) Mechanisms of action].

F-0401 is a novel dihydropyridine (DHP) derivative with potent vasodilative and anti-aggregatory actions. In the present study, we examined the mechanisms of the actions of F-0401 and obtained the following findings: F-0401 suppressed [3H]nitrendipine binding to rat heart membrane (Ki value: 2.2 x 10(-7) M). CaCl2-induced contractions of rabbit aorta and guinea pig taenia coli were inhibited by F-0401 (pA2 values: 7.7 and 6.6). These results indicated that F-0401 had calcium antagonistic activity slightly less potent than that of the other DHP derivatives. In addition, F-0401 significantly inhibited the activity of thromboxane (TX) A2 synthetase (IC50 value: 2.5 x 10(-7) M) and [3H]PAF binding to rabbit platelets (Ki value: 1.4 x 10(-8) M). The other DHP derivatives tested did not affect TXA2 synthetic activity, and the PAF antagonism of the other derivatives were less than that of F-0401. Neither F-0401 nor the other DHP derivatives inhibited cAMP- or cGMP-dependent phosphodiesterase activity. These results revealed that F-0401 has calcium antagonistic, anti-PAF and TXA2 synthetase inhibitory actions in the same dose ranges.

Animals↗

[Pharmacological profile of F-0401, a novel dihydropyridine derivative. (2). The vasodilator action of F-0401 in isolated canine arteries].

F-0401 ((+/-)-(E)-3-[4-(1-imidazolyl)methylphenyl]-2-propen-1-yl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate) is a newly synthesized dihydropyridine derivative. We investigated the vasodilator action of F-0401 in isolated canine cerebral and peripheral arteries. F-0401 reduced KCl-induced contraction of the arteries in a concentration-dependent manner. The inhibitory action on cerebral arteries was greater than that on the peripheral ones. Its pD'2 values were as follows: Middle cerebral(8.3), basilar(8.1) > coronary(6.9) > femoral, renal, internal carotid, vertebral, mesenteric(6.0-5.5) arteries. The cerebrovascular-selectivity (the ratio of the pD'2 of the basilar artery to that of the femoral one) of F-0401 was 4, 25 and 40 times as large as that of flunarizine, nicardipine and nimodipine, respectively. F-0401 shifted to the right the concentration-response curve for CaCl2 in the depolarized basilar artery (pA2 value: 8.9). However, the reductions of 5-HT and PGF2 alpha-induced contractions by F-0401 in this artery were very weak (pD'2 value:5.9 and < 4.5). These results suggest that F-0401 is a potent cerebrovascular-selective vasodilator and its effects were attributed to the inhibitory effect on the voltage-dependent Ca2+ channels.

Animals↗

Donor-HLA-incompatible marrow transplantation with an anti-donor cytotoxic antibody in the serum of the patient.

A 42-year-old female with acute mixed lineage leukemia received a marrow transplantation from an HLA non-identical sibling. The serum of the patient showed a positive crossmatch for anti-donor lymphocytotoxic antibody and exhibited a complement-mediated cytotoxicity to donor hematopoietic progenitor cells. In an attempt to reduce the risk of graft rejection, a large volume plasma exchange was performed, which was followed by an infusion of irradiated donor lymphocytes to eliminate remaining antibodies from her serum. The level of anti-donor antibody fell below the sensitivity of the anti-human immunoglobulin lymphocytotoxicity test after the infusion of donor lymphocytes. The cytotoxic activity against donor progenitor cells also disappeared from the serum. Cyclosporin had been administered for 2 weeks before marrow infusion, and methylprednisolone and prednisolone for 1 week before the initiation of conditioning chemoradiotherapy. Conditioning comprised cytosine arabinoside 5.6 g/m2, cyclophosphamide 4500 mg/m2 and fractionated total body irradiation with 15 Gy followed by an infusion of 4.0 x 10(8) cells/kg of unmodified marrow cells. Engraftment of donor cells was documented by HLA typing of peripheral lymphocytes. A sustained engraftment may be obtained in a donor-incompatible HLA non-identical marrow transplantation with anti-donor antibody by elimination of the antibody and achieving an intensive immunosuppression in the recipient before marrow infusion.

Adult↗

[The antiinflammatory effect of EB-382].

This study was conducted to clarify the antiinflammatory profile of EB-382, comparing it with those of ibuprofen and other antiinflammatory agents. EB-382 had a more potent inhibition on the acetic acid-induced intensive mouse intraperitoneal vascular permeability and carrageenin-induced rat hind paw edema, but a less potent inhibition on the ultraviolet-induced guinea-pig erythema and the prostaglandin biosynthesis in vitro than ibuprofen. The inhibition by EB-382 was equipotent to that of indomethacin on carrageenin-induced rat pleurisy and the zymosan air pouch, and it demonstrated a strong inhibition on the kallikrein and zymosan-induced intensive guinea-pig skin vascular permeability. EB-382 had a more effective activity on paper disk-induced granuloma and adjuvant arthritis, and it had a less potent action on the gastric mucosal membrane than ibuprofen. EB-382 had a weak action on histamine-induced rat back skin vascular permeability and heat-induced protein denaturation and hemolysis in vitro, as also shown by other test agents. The above results indicate that EB-382 will be useful as an antiinflammatory agent with a new pharmacological effectiveness besides possessing properties common to other acidic non-steroidal antiinflammatory agents in clinical studies.

Animals↗

Antihypertensive and cardiovascular effects of the new dihydropyridine derivative methyl (E)-3-phenyl-2-propen-1-yl-1,4-dihydro-2,6-dimethyl- 4-(3-nitrophenyl)pyridine-3,5-dicarboxylate.

The hypotensive and cardiovascular effects of a newly synthetized dihydropyridine derivative, methyl (E)-3-phenyl-2-propen-1-yl-1,4-dihydro-2,6-dimethyl-4-(3- nitrophenyl)pyridine-3,5-dicarboxylate (FRC-8411) were investigated in rats, guinea pigs, and rabbits, in comparison with nifedipine, nicardipine, and diltiazem. In conscious hypertensive rats, FRC-8411 (0.3-3 mg/kg p.o.) was found to be an orally effective antihypertensive agent and its effect lasted for more than 7 h. This effect was gradual and yet much more potent and longer than those of other reference drugs. An accompanied tachycardia was observed after oral administration of FRC-8411 and other dihydropyridine derivatives. In anesthetized rats, FRC-8411 (3-30 micrograms/kg i.v.) also showed a gradual, potent and long-lasting hypotension with a tachycardia. FRC-8411 (up to 3 mg/kg i.v.) had no effect on the PQ interval of the ECG in anesthetized rats. In isolated guinea pig atria, FRC-8411 (10(-9) - 3 X 10(-8) mol/l) showed a negative chronotropic effect, but a higher dose of the drug was needed for induction of the negative inotropic effect. In K+-depolarized rabbit aorta and guinea pig taenia coli, FRC-8411 (3 X 10(-9) - 3 X 10(-7) and 10(-7) - 3 X 10(-7) mol/l) showed a dose-dependent inhibition of the calcium-induced contraction, and its pA2 value was 8.4 and 7.1, respectively. FRC-8411 had a much higher sensitivity to the aorta than the taenia coli, though it was less potent than nifedipine and nicardipine in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

Long-term culture and passage of human fetal liver cells that synthesize albumin.

Long-term cultures of hepatocytes were established from livers of human fetuses obtained by abortion at 18 to 23 wk of gestation. Cells obtained by collagenase dissociation of liver were maintained in defined serum-free medium on a substratum of positively charged plastic. Under these conditions, the cells divide and form a confluent monolayer. After multiple passages over a period of 3 mo., the cells retained an epithelioid morphology and continued to synthesize and secrete albumin.

Albumins↗

Increased glycosylation of proteins from cataractous lenses in diabetes.

The rates of glycosylation of lens proteins were determined in extracts of human 'diabetic' and 'senile' cataractous lenses by a method employing thiobarbituric acid. Incubation of soluble lens proteins (6,500 X g supernatant of homogenates) in vitro with various concentrations of D-glucose in sodium phosphate buffer (50 mmol/l, pH 7.2) resulted in a gradual glycosylation which was time and concentration dependent. Glycosylated proteins from the cataractous lenses of 21 senile and 12 diabetic subjects afforded 0.72 +/- 0.22 and 1.84 +/- 0.44 nmol 5-hydroxymethylfurfural/mg protein (mean +/- SD), respectively. The value is significantly higher in the diabetic than in the senile group (p less than 0.001), although the mean age of the diabetic patients (67 years) was significantly younger than that of senile subjects (75 years; p less than 0.01). These results indicate that human lens proteins can be glycosylated both in vitro and in vivo, and that hyperglycaemia can accelerate the non-enzymatic glycosylation of lens proteins in diabetic patients.

Aged↗

[Effects of gamma-oryzanol on the hypothalamo-pituitary axis in the rat].

The effects of gamma oryzanol (gamma-OZ), a ferulic acid of triterpene alcohol, on the synthesis and release of the growth hormone (GH) and prolactin (PRL) in vitro and turnover rates of hypothalamic catecholamines were investigated. A single subcutaneous injection of 20 mg/kg of gamma-OZ suppressed GH synthesis and PRL release 1 hour after the injection. gamma-OZ increased medial basal hypothalamic (MBH) dopamine (DA) content, and the DA content was decreased by a treatment of alpha-methyl-p-tyrosine (alpha MpT), a tyrosine hydroxylase inhibitor, indicating increased synthesis and release of DA in MBH by gamma-OZ. gamma-OZ did not alter norepinephrine (NE) content in MBH, while the NE content was significantly decreased, indicating unchanged synthesis and increased release of NE in MBH by gamma-OZ. These results may explain the previous data concerning the changes in serum levels of GH and PRL by gamma-OZ and also suggest that gamma-OZ can affect the synthesis and/or release of at least two hypothalamic neurotransmitters, DA and NE, resulting in the alterations of anterior pituitary hormone synthesis and/or release.

Animals↗

Abnormal ovarian cycles as diagnosed by ultrasound and serum estradiol levels.

A significant portion of human infertility is presumably due to defective ovulation, including patients who fail to conceive despite medical induction of ovulation, those who fail despite repeated timely donor inseminations, and those with "infertility of unknown etiology". All point out the inadequacy of standard criteria for normal ovulation. This investigation correlates preovulatory serum estradiol and gonadotropin concentrations with dominant follicle growth measured ultrasonographically and serum progesterone levels. The data indicate a 35% incidence of cycles with significantly abnormal serum estradiol levels, decreased dominant follicle size, and abnormal progesterone levels despite biphasic basal body temperature curves and normal cycle length. If these cycles represent inadequate or abnormal ovulation, they can be distinguished from adequate cycles prior to follicle rupture and may benefit the treatment of human infertility.

Adult↗