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Biomedical subjects

K Kurachi

Publications and source records attributed to K Kurachi.

At least 145 records · Page 8Linked to original sources
PubMed1982

Abortifacient effect and uterine cervix-dilating action of 16, 16-dimethyl trans delta 2 PGE1 methyl ester (ONO 802) in the form of a vaginal suppository (a randomized, double-blind, controlled study in the second trimester of pregnancy).

A newly synthesized 16, 16-dimethyl trans delta 2 PGE1 methyl ester (ONO 802) was clinically applied in the form of a vaginal suppository for therapeutic abortion of second trimester pregnancies. Its effects were studied in a double-blind test comparing it with an inactive placebo suppository. The study was conducted at 12 Japanese university hospitals. The number of patients was 125 in total, i.e. 63 receiving ONO 802 vaginal suppository (containing 1.0 mg ONO 802) and 62 receiving inactive placebo suppository. ONO 802 was more effective than placebo with a success rate of 87% (complete (71%) and incomplete (16%) abortions). The onset of uterine contractions was observed in 154.3+/-18.1 min. and the onset of uterine bleeding in 323.6+/-41.0 min. The expulsion of the fetus and placenta was observed in 955.4+/-97.0 and 961.6+/-97.0 min., respectively. The cervix dilating effect of ONO 802 was observed in 63.5% of the patients at 3 hours after the start of administration. Nausea, vomiting, abdominal cramps, diarrhea and pyrexia were noticed. However, all these side effects were transient and mild, requiring no treatment. No abnormality was observed in the puerperal course, duration of uterine bleeding or onset of subsequent menstruation following the therapeutic abortion. Therefore, the present study demonstrated that ONO 802 vaginal suppository was an effective and valuable drug for therapeutic abortion of second trimester pregnancies.

Abortifacient Agents↗
PubMed1982

Isolation and characterization of a cDNA coding for human factor IX.

A cDNA library prepared from human liver has been screened for factor IX (Christmas factor), a clotting factor that participates in the middle phase of blood coagulation. The library was screened with a single-stranded DNA prepared from enriched mRNA for baboon factor IX and a synthetic oligonucleotide mixture. A plasmid was identified that contained a cDNA insert of 1,466 base pairs coding for human factor IX. The insert is flanked by G-C tails of 11 and 18 base pairs at the 5' and 3' ends, respectively. It also included 138 base pairs that code for an amino-terminal leader sequence, 1,248 base pairs that code for the mature protein, a stop codon, and 48 base pairs of noncoding sequence at the 3' end. The leader sequence contains 46 amino acid residues, and it is proposed that this sequence includes both a signal sequence and a pro sequence for the mature protein that circulates in plasma. The 1,248 base pairs code for a polypeptide chain composed of 416 amino acids. The amino-terminal region for this protein contains 12 glutamic acid residues that are converted to gamma-carboxyglutamic acid in the mature protein. These glutamic acid residues are coded for by both GAA and GAG. The arginyl peptide bonds that are cleaved in the conversion of human factor IX to factor IXa by factor XIa were identified as Arg145-Ala146 and Arg180-Val181. The cleavage of these two internal peptide bonds results in the formation of an activation peptide (35 amino acids) and factor IXa, a serine protease composed of a light chain (145 amino acids) and a heavy chain (236 amino acids), and these two chains are held together by a disulfide bond(s). The active site residues including histidine, aspartate, and serine are located in the heavy chain at positions 221, 270, and 366, respectively. These amino acids are homologous with His57, Asp102, and Ser195 in the active site of chymotrypsin. Two potential carbohydrate binding sites (Asn-X-Thr) were identified in the activation peptide, and these were located at Asn157 and Asn167. The homology in the amino acid sequence between human and bovine factor IX was found to be 83%.

Amino Acid Sequence↗
PubMed1982

Immunohistological study of mucous antigens in gynecologic tumors with special reference to argyrophil cells.

Mucinous tumors of the ovary and adenocarcinomas of the female genital tract with or without argyrophil cells were studied by immunohistology for mucous antigens. These were isolated from intestinal mucosa and ovarian mucinous cyst fluid. Mucous antigen, M1 which is primarily associated with ovarian mucinous cystadenoma, was found in all mucinous tumors of the ovary, adenocarcinoma of the cervix, and endometrium. Intestinal mucous antigen (IMA), which is specific for goblet cells of the normal intestinal mucosa, was detected only in a few mucinous tumors of the ovary, with or without argyrophil cells. It was concluded that, while M1 was common to glandular gynecologic neoplasms, no special relationship existed between IMA and argyrophil cells in tumors of the ovary, endometrium, and endocervix.

Adenocarcinoma↗
PubMed1982

Endometrial argyrophil cell adenocarcinoma with indole- or catecholamine precursor uptake and decarboxylation.

The capacity for indole- or catecholamine precursor uptake and decarboxylation of the argyrophil cell adenocarcinoma of the endometrium was examined by fluorescence microscopy, microspectrofluorometry, and biochemical analyses. Both argyrophil and nonargyrophil cell adenocarcinomas of the human endometrium have been grown serially in nude mice. With the use of the formaldehyde-induced wet-histofluorescence method, yellowish green fluorescence was demonstrated in the cytoplasm of some cells of the argyrophil cell adenocarcinomas after exposure in vitro and in vivo to L-dopa. When 5-hydroxytrytophan was administered in vitro and in vivo to these tumors, an intense yellow fluorescence was also obtained in the cytoplasm. These fluorescent products were located in the argyrophil cells and corresponded to argyrophil granules. Microspectrofluorometrical and biochemical analyses strongly suggested that the yellowish green fluorescent products were dopamine and the yellow ones were serotonin, produced by decarboxylation of each amine precursor.

APUD Cells↗
PubMed1982

Aggravation of thyrotoxicosis in early pregnancy and after delivery in Graves' disease.

The effect of pregnancy on the clinical course of Graves' disease was examined by studies on 41 pregnancies in 35 patients with Graves' disease, who were considered to be in a state of remission or near remission and were not receiving antithyroid drugs, during and after delivery. Eighteen of the 41 cases (44%) showed transient increases in the serum free T4 index (FT4 index) during weeks 10--15 of pregnancy, but normal thyroid function in the second and third trimesters. Similar transient increases in the serum free T3 index (FT3 index) were observed in early pregnancy in these patients. These early increases in the FT4 and FT3 indexes were specific to Graves' disease and were not observed in Hashimoto's disease. Two to 4 months postpartum, 32 cases (78%) developed various degrees of thyrotoxicosis, which was divided into 3 types: 1) persistent thyrotoxicosis with high radioactive iodine (RAIU) (10 cases), 2) transient thyrotoxicosis with normal or high RAIU) (10 cases), and 3) destruction-induced thyrotoxicosis with low RAIU (12 cases). An increase in the FT4 index in early pregnancy was significantly (P less than 0.001) associated with relapse of stimulation-induced thyrotoxicosis of either the persistent or transient type. Patients who developed destruction-induced thyrotoxicosis after delivery had significantly higher titers of antithyroid microsomal antibodies (P less than 0.001) and a longer euthyroid period before pregnancy (P less than 0.01) than patients who had recurrent persistent thyrotoxicosis. These data indicate that Graves' disease is aggravated in early pregnancy and after delivery and ameliorates in the latter half of pregnancy. Postpartum relapse of persistent hyperthyroidism could be predicted from an early increase in the FT4 index during pregnancy.

Adult↗
PubMed1982

Restoration of oestrogen-positive feedback effect on LH release in women with prolactinoma by transsphenoidal surgery.

The effects of hyperprolactinaemia on the hypothalamo-pituitary axis by iv injection of 100 micrograms luteinizing hormone releasing hormone (LRH) in 7 women with prolactinoma before and 3 months after normalization of the Prl level by transsphenoidal surgery. A dose of 20 mg of conjugated oestrogen (Premarin) was also infected iv into patients with prolactinoma before and 4 months after surgery, and the serum LH levels were determined serially for 120 h after the injection. Surgical treatment caused significant reduction of the mean (+/- SE) serum prolactin (Prl) level from 123.3 +/- 7.8 to 19.4 +/- 5.6 ng/ml. But the differences in the basal levels of HL (11.3 +/- 2.2 to 8.6 +/- 1.5 mIU/ml), FSH (8.3 +/- 2.4 to 10.6 +/- 3.7 mIU/ml) and oestradiol (26.6 +/- 8.6 to 37.5 +/- 5.5 pg/ml) before and 4 months after surgery were not significant. An exaggerated LH response to LRH in untreated prolactinoma patients was also observed after surgical treatment. After surgical treatment, patients showed LH release with a peak between 48 and 72 h after the injection of Premarin, whereas before treatment they did not show any LH discharge. The mean percent increase in LH between 48 and 72 h was also significantly higher after operation than before operation. These results suggest that the hyperprolactinaemia in prolactinoma patients may cause an impaired positive feedback effect of oestrogen on LH release and that this derangement can be reversed by reduction of the Prl level by adenomectomy.

Adenoma, Chromophobe↗
PubMed1982

Effects of amine precursor administration on the morphological findings of transplanted argyrophil cell adenocarcinoma of the endometrium.

Argyrophil cell adenocarcinoma of the endometrium has been kept serially in nude mice. Histological appearances of the tumor were not much changed by transplantations. Argyrophil granules were located mainly in the apical portion of glandular tumor cells in the transplanted tumors as in the original one. However, the cells with argyrophil granules in the entire cytoplasm were made conspicuous after the administration of L-DOPA. These results may suggest the existence of latent APUD cells in the argyrophil cell adenocarcinoma of the endometrium which are activated by the treatment of amine-precursor.

Adenocarcinoma↗
PubMed1982

Changes in luteinizing hormone-releasing hormone in human placenta throughout pregnancy.

The distribution and content of luteinizing hormone-releasing hormone (LH-RH) in human placental tissues were detected by enzymatic antibody and immunofluorescence techniques. Anti-LH-RH was taken up strongly by cytotrophoblasts and the villous stroma at 8 weeks of pregnancy; the uptake decreased with the progress of pregnancy. Anti-LH-RH was not taken up at all by syncytiotrophoblasts throughout pregnancy. These findings suggest that LH-RH is synthesized in the cytotrophoblast and villous stroma. The role of placental LH-RH in the synthesis of human chorionic gonadotropin is discussed.

Female↗
PubMed1982

[Clinicopathological study of ovarian embryonal carcinoma (Higuchi-Kato)].

Prognoses of embryonal carcinoma (Higuchi-Kato) of the ovary are extremely poor, and new modalities of the treatment are desired. In the present paper, we describe a clinicopathological study of ovarian embryonal carcinoma (Higuchi-Kato) with special references to the treatment and prognosis. 1) The patients examined were 20 in all, 8 belonging to embryonal carcinoma (Higuchi-Kato) Group A, 6 to the Group B, and 6 to the Group C. 2) The median age of patients was 20 years old. 3) The development of tumor was unilateral in all patients but one unsettled. 4) One patient was pregnant when the tumor was discovered. 5) The prognoses of patients in Group C were better than those of others. 6) Serum AFP is a good tumor marker, correlating well with the clinical courses of the patients. 7) To maintain ovarian function of young patients in stage Ia, unilateral adnexectomy with contralateral wedge resection and postoperative intensive chemotherapy are considered to be a choice of treatment method.

Adolescent↗
PubMed1981

Mapping the active sites of bovine thrombin, factor IXa, factor Xa, factor XIa, factor XIIa, plasma kallikrein, and trypsin with amino acid and peptide thioesters: development of new sensitive substrates.

The subsite specificities of bovine factor IXa, factor Xa, factor XIa, factor XIIa, thrombin, plasma kallikrein, and trypsin were mapped with amino acid, dipeptide, and longer peptide thioester substrates. Each substrate contained a P1 Arg residue. The P1' residues included thiol residues which are analogues of valine, leucine, and isoleucine, respectively, and the P2 residue included 12 representative amino acid residues. Longer substrates with the sequence at the antithrombin III reactive site and at the zymogen activation site of various coagulation factors were also studied. The enzymatic hydrolysis of the thioesters was measured in the presence of 4,4'-dithiodipyridine which provides a very sensitive assay for the free thiol. The thioesters were excellent substrates for the coagulation factors studied, and the kcat/Km values for the best thioester substrates were higher than those previously reported for most of these enzymes. Thrombin and plasma kallikrein were the most active of the coagulation factors toward the thioester substrates. The best substrate for thrombin was Z-Gly-Arg-SCH2C6H5, although substrates containing proline in the P2 position were also quite effective. Some of the better substrates for plasma kallikrein had a P2 Phe or Trp residue. Factor IXa was the least reactive of the coagulation factors and hydrolyzed only four of the dipeptide thioesters. Substrates with bulky hydrophobic groups such as Phe or Trp in the P2 position were the most reactive with factor IXa. Factor Xa hydrolyzed all the thioester substrates tested, the most reactive being Z-Gly-Arg-SCH2C6H5. This is consistent with the fact that glycine and arginine are present in the P2 and P1 positions, respectively, of the factor Xa sensitive bonds in prothrombin which is the physiological substrate for factor Xa. Bovine factor XIa showed the least amount of specificity of the various coagulation factors and was quite reactive toward all of the thioester substrates. The most sensitive substrate for this enzyme was also Z-Gly-Arg-SCH2C6H5. Factor XIIa preferred the dipeptide with a P2 Phe, although the simpler thioester Z-Arg-SCH2CH(CH3)2 was more reactive. Trypsin hydrolyzed all of the thioester substrates at a high rate and showed little substrate specificity. With all enzymes studied, extension of the thioester substrate beyond P2 or the P1' thiol leaving group did not lead to an improvement in hydrolysis. Due to their high kcat/Km values and the ease of detecting the thiol leaving group, thioester substrates should be extremely useful for future studies of coagulation proteases.

Amino Acids, Sulfur↗
PubMed1981

The molecular-weight dependence of the rate-enhancing effect of heparin on the inhibition of thrombin, factor Xa, factor IXa, factor XIa, factor XIIa and kallikrein by antithrombin.

Heparin fractions of different molecular weight and with high affinity for antithrombin were studied with respect to their ability to potentiate the inhibition of activated clotting factors by antithrombin. Inhibition of thrombin, Factor IXa and Factor XIa showed similarities in the dependence on the molecular weight of heparin and was found to decrease with decreasing molecular weight. Inactivation of Factor Xa, Factor XIIa and kallikrein was, however, less dependent on the size of the polysaccharide and, to a great extent, was potentiated even by low-molecular-weight heparin fractions that had virtually no effect on the inhibition of thrombin, Factor IXa and Factor XIa.

Antithrombin III↗
PubMed1981

Induction of ovulation in patients with normoprolactinemic amenorrhea by combined therapy with bromocriptine and clomiphene.

Bromocriptine is known to be effective in the treatment of women with hyperprolactinemic anovulation or amenorrhea-galactorrhea. A new schedule of combined treatment with bromocriptine and clomiphene citrate was applied to 23 patients with normoprolactinemic amenorrhea who failed to respond to clomiphene alone. Ovulation was restored by treatment in 14 of these patients (60.9%), resulting in pregnancy in 3 women. Treatment resulted in immediate suppression of serum prolactin levels and a gradual increase in serum luteinizing hormone levels and estradiol levels followed by a luteinizing hormone surge. The present results indicate that bromocriptine/clomiphene combination therapy is effective in the treatment of amenorrheic patients with normoprolactinemia who do not respond to clomiphene alone, and suggest that bromocriptine restores the responsiveness of the hypothalamic-pituitary-ovarian system to clomiphene.

Adult↗