Search PubMed⌕ Search

Biomedical subjects

H Takikawa

Publications and source records attributed to H Takikawa.

At least 127 records · Page 7Linked to original sources

Determination of 3 beta-hydroxy-5-cholenoic acid in serum of hepatobiliary diseases--its glucuronidated and sulfated conjugates.

3 beta-Hydroxy-5-cholenoic acid in the serum of control subjects and 62 patients with various hepatobiliary diseases was quantitated by mass fragmentography after separation into nonglucuronidated-nonsulfated, glucuronidated, and sulfated fractions. Deuterium-labeled deoxycholic acid and its glucuronide and sulfate were used as internal standards. Mean concentrations of total 3 beta-hydroxy-5-cholenoic acid in serum (mumole/liter) were as follows: Control subjects (14), 0.184; obstructive jaundice (15), 6.783; liver cirrhosis, compensated (12), 0.433, and decompensated (12), 1.636; chronic hepatitis (12), 0.241; and acute hepatitis (11), 2.364. Most of the 3 beta-hydroxy-5-cholenoic acid was glucuronidated or sulfated. Only in patients with obstructive jaundice did glucuronidation (60 +/- 14%) exceed sulfation (31 +/- 14%), sulfation exceeding glucuronidation in the others. The UDP-glucuronyltransferase might have different substrate specificities for 3 beta-hydroxy-5-cholenoic acid and other common bile acids, especially in the cholestatic state.

Adult↗

Comparative studies on the electric nature of amphibian gonadotropin.

The isoelectric focusing (IEF) profiles of pituitary gonadotropic (GTH) activity in six species of adult male amphibians were examined in addition to the newt and bullfrog. The GTH activity was measured by two radioreceptor assay (RRA) systems; one with Xenopus laevis testicular homogenate as the receptor preparation, and the other with Anolis carolinensis testicular homogenate, both employing 125I-labeled rat FSH as the radioligand, or by a radioimmunoassay (RIA) system for bullfrog basic GTH (LH). The IEF profiles were classified into four groups: (1) Cynops pyrrhogaster pyrrhogaster, Onychodactylus japonicus, (2) X. laevis, (3) Rana japonica, Bufo japonicus formosus, (4) Rana nigromaculata, Hyla arborea japonica, Rana catesbeiana. In Onychodactylus japonicus (Group 1), Anolis RRA-positive peaks and Xenopus RRA-positive peaks were found in almost the same fractions. They were in the alkaline to neutral pH region. This IEF profile was very similar to that of newt pituitary GTH in July when spermatogenesis was active. In X. laevis (Group 2), the IEF profile was similar to that of urodeles. However, the most alkaline peak was found at pH 9.02, which was lower than those of urodeles. These peaks showed some differences in the reactivity to the RRA systems. In R. japonica (Group 3), the major peak obtained by Xenopus RRA was found at pH 10.27, which corresponded to the only positive peak obtained by the RIA system for bullfrog basic GTH. Furthermore, this peak was also recognized by Anolis RRA as one of the eight peaks, which appeared in the alkaline to acidic region. In B. japonicus formosus (Group 3), similar results were observed. In H. arborea japonica, R. nigromaculata and R. catesbeiana (Group 4), Anolis RRA-positive and Xenopus RRA-positive peaks were quite independent, indicating distinct separation of LH and FSH, though pIs of FSH-like GTH in the frogs were not so acidic as those of mammalian and avian FSH.

Amphibians↗

Bile acid profiles in analbuminemia rats.

Bile acid profiles in serum, urine and bile of Nagase analbuminemia rats (NAR) and Sprague-Dawley rats (SDR) were examined. Serum bile acid levels in NAR (2.02 + 0.51 micrograms/ml, n = 15, M +/- S.E.) were markedly decreased as compared with those in SDR (20.86 +/- 3.72 micrograms/ml, n = 10). The unbound fraction of acids in serum examined by equilibrium dialysis was about ten times higher in NAR than in SDR. In the profiles of urinary and biliary bile acids in NAR and SDR, as big differences as seen for serum bile acids were not observed. Low bile acid levels in serum of NAR may reflect low bile acid binding capacity of NAR serum because the absence of albumin was thought to be one of the major causes of low bile acid levels in serum of NAR.

Aging↗

Profiles of bile acids and their glucuronide and sulphate conjugates in the serum, urine and bile from patients undergoing bile drainage.

Bile acid profiles in serum, urine, and bile from patients undergoing bile drainage and the changes of serum bile acids after bile drainage were studied. Bile acids were separated into non-glucuronidate-non-sulphate, glucuronidated, and sulphated fractions and were measured by mass fragmentography using conjugates of deuterium labelled bile acids as internal standards. Glucuronidated and sulphated bile acids contribute 14-32% and 16-44% of serum bile acids, 4-11% and 61-82% of urine bile acids and 0.2-1% and 0.3-2% of biliary bile acids respectively. After bile drainage the concentration of serum non-glucuronidated-non-sulphated bile acids decreased more rapidly than glucuronidated and sulphated bile acids. There was little biliary excretion of the glucuronidated and sulphated bile acids. Such conjugation appears to have a role in facilitating bile acid excretion by the urinary route.

Aged↗

Hormone dependency of a serially transplantable human prostatic cancer (HONDA) in nude mice.

Human prostatic cancer (HONDA) serially transplanted in nude mice grew well in male mice but not at all in untreated female mice or in castrated male mice. Progressive growth in female mice was obtained by i.m. administration of 1 mg of testosterone twice a week. Estradiol inhibited the growth of the tumor in male mice to some extent; however, some growth was observed. The tumor in untreated male mice retained the histological features of poorly differentiated adenocarcinoma. Tumors in castrated male mice showed reduction in size of tumor cell nests with relative overgrowth of stroma. The tumor in androgenized female mice consisted of columnar epithelial cells with large nuclei and more abundant cytoplasms and a large glandular lumen, showing histology of moderately differentiated adenocarcinoma. High levels of human prostatic acid phosphatase (PAP) were detected in sera from untreated male mice. Testosterone markedly increased the content of serum PAP of androgenized female mice. Estradiol reduced the levels of PAP in sera from untreated male mice regardless of the tumor weight. High-affinity androgen receptors were present in cytosol and in nuclear extract of the tumor in untreated male mice. No measurable amount of progesterone or estrogen receptors was present in cytosol from untreated male mice.

Acid Phosphatase↗

Urinary concentrations of bile acid glucuronides and sulfates in hepatobiliary diseases.

Urinary bile acids in normal subjects and patients with obstructive jaundice and liver cirrhosis were quantitated by mass fragmentography after separation into nonglucuronidated-nonsulfated, glucuronidated and sulfated fractions. Mean values of total bile acids in urine were as follows: Control subjects (n = 7), 1.90 +/- 0.67; obstructive jaundice (n = 9), 77.90 +/- 40.39; liver cirrhosis, compensated (n = 6), 15.14 +/- 8.97, and decompensated (n = 6), 11.84 +/- 9.32 (mean +/- SD, mg/day). The percentages of each conjugate was 19-29% in the non-glucuronidated-nonsulfated fraction, 6-14% in the glucuronidated fraction and 60-74% in the sulfated fraction. Bile acids in urine and serum correlated well in each fraction (r = 0.82-0.84, p less than 0.001). The clearance of the three conjugates was the highest in the sulfates, and the clearance of glucuronides was higher than that of non-esterified bile acids. The glucuronidation and sulfation of bile acids play an important role in the detoxication of bile acids by excreting them into urine, especially in patients with elevated serum bile acids.

Bile Acids and Salts↗

Conjugated hyperbilirubinemia in an autopsy case with myocardial infarction and sepsis.

The marked conjugated hyperbilirubinemia in a 72-year-old patient with myocardial infarction and sepsis is reported. The serum bilirubin, which was predominantly composed of conjugated bilirubin, was elevated to 21 mg/100 ml, while serum bile acid and alkaline phosphatase levels were normal or slightly elevated. Postmortem examination of the liver revealed slightly proliferated bile ductules and some bile thrombi with little liver cell necrosis.

Aged↗

Quantitative determination of non-sulfated bile acids in the serum of patients with hepatobiliary diseases by mass fragmentography.

Individual non-sulfated bile acids in the serum of 65 patients with hepatobiliary diseases were quantitated by mass fragmentography. Serum with deuterium labeled deoxycholic acid as an internal standard was hydrolyzed with strong alkali, extracted with ether after acidification under cooling, and quantitated by mass fragmentography as the hexafluoroisopropyl-trifluoracetyl derivatives. In obstructive jaundice, the ratio of cholic to chenodeoxycholic acid was significantly higher than others. Cholic or chenodeoxycholic acid levels were correlated with total bilirubin levels in obstructive jaundice and acute hepatitis. Lithocholic acid value was independent of the degree of liver injury. Total bile acid value was helpful in estimating the extent of liver cell injury and cholestasis, and these two pathological conditions can be distinguished to some extent by cholic to chenodeoxychoic acid ratio.

Bile Acids and Salts↗

Determination of sulfated and nonsulfated bile acids in serum by mass fragmentography.

A Sep-Pak C18 cartridge was used for purification of bile acids from serum. Three kinds of deuterium labeled internal standards were required for accurate measurement of individual sulfated and nonsulfated bile acids. These internal standards were added to the serum before its application to the cartridge. Separation of sulfated and nonsulfated bile acids was performed on piperidinohydroxypropyl Sephadex LH-20 column chromatography. The nonsulfate fraction was submitted to alkaline hydrolysis, and the sulfate fraction to solvolysis followed by alkaline hydrolysis. Each fraction was converted to the hexafluoroisopropyl-trifluoroacetyl derivatives and quantitated by mass fragmentography. The recovery of each bile acid sulfate was quite satisfactory. In fasting healthy subjects the mean of total nonsulfated bile acids in serum was 1.324 micrograms/ml, and that of total sulfated bile acids was 0.450 micrograms/ml. Sulfated lithocholic acid comprised a large part of sulfated bile acids in healthy subjects.

Bile Acids and Salts↗

Serum concentrations of bile acid glucuronides in hepatobiliary diseases.

Bile acid glucuronides in the serum in various hepatobiliary diseases (36 cases) were quantitated by mass fragmentography and their clinical significance was discussed. Serum was added to defined amounts of deuterium-labeled bile acids and their glucuronide and sulfate derivatives, and the bile acids were separated into unconjugated, glucuronidated and sulfated groups after enzymatic cleavage of amide bonds. The liberated bile acids were quantitated by mass fragmentography. Bile acid glucuronides comprised about 7-8% of the total bile acids in the serum of various patients. Chenodeoxycholic acid was the major glucuronidated bile acid while cholic acid was mostly unconjugated. Lithocholic acid was almost all either sulfated or glucuronidated. In patients with obstructive jaundice, glucuronidated bile acids also comprised about 5%, although their absolute amounts were increased. In patients with liver cirrhosis, bile acid glucuronides were decreased, especially in decompensated cases, possibly as a result of hepatocellular dysfunction.

Adult↗

Seasonal changes in plasma testosterone and 5 alpha-dihydrotestosterone levels in the adult male newt, Cynops pyrrhogaster pyrrhogaster.

Seasonal changes in plasma levels of testosterone (T) and 5 alpha-dihydrotestosterone (DTH) were examined in the adult male Japanese red-bellied newt. The concentration of plasma T increased significantly (p less than 0.05) from January to February and decreased drastically from April to July when it reached its minimum. After the summer decline, plasma T increase rapidly from July to October (P less than 0.05) and reached its maximum in October. Concerning the seasonal fluctuation of plasma DHT levels, three peaks were observed; one, the highest peak, appeared in the middle of May, and two lower peaks in early spring (Feb.-March) and autumn (Sept.-Oct.). In this report, the role of plasma T and DHT in the reproductive cycle is discussed.

Animals↗

[Effect of medroxyprogesterone acetate (MAP) and vitamin C on DMBA induced rat mammary cancer in relation to estrogen receptor(ER)].

In mature male and female SD rats, the anti-weight gain effect of durabolin plus vitamin C or vitamin C alone was statistically significant compared to durabolin-treated and control rats. The anti-tumor and anti-weight gain effects of MAP plus vitamin C on DMBA-induced rat mammary cancer were compared with those of MAP and vitamin C in relation to ER. An anti-tumor effect was noted in the MAP treated groups, irrespective of the ER status; it was more pronounced in the MAP (100 mg/kg) plus vitamin C treated group with ER+tumors. Among the ER+tumor groups, weight gain was remarkable in the MAP-treated (20 mg/kg) animals; an anti-weight gain effect was seen in the MAP (20 mg/kg) plus vitamin C group.

9,10-Dimethyl-1,2-benzanthracene↗

Quantitative determination of bile acid glucuronides in serum by mass fragmentography.

Individual non-glucuronidated . non-sulfated, glucuronidated and sulfated bile acids in serum were determined, i.e. lithocholic acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, and cholic acid, by mass fragmentography. Glucuronic acid conjugates of lithocholic acid, deoxycholic acid, chenodeoxycholic acid, and cholic acid were synthesized via the Koenigs-Knorr condensation reaction. Deuterium labeled deoxycholic acid, lithocholic acid glucuronide, deoxycholic acid glucuronide, and deoxycholic acid sulfate were synthesized and used as internal standards. A serum sample of 1 ml including internal standards was purified with a Sep-Pak C18 cartridge. After the enzymatic cleavage of amino acid conjugates, bile acids were separated into three fractions, free, glucuronidated, and sulfated bile acids, using piperidinohydroxypropyl Sephadex LH-20 (Goto et al. (1978) Clin. Chim. Acta 87). Glucuronidated and sulfated bile acids were deconjugated by beta-glucuronidase treatment and solvolysis. Each fraction was converted to the hexafluoroisopropyl-trifluoroacetyl derivative and quantitated by mass fragmentography. The average concentrations of individual bile acid glucuronides from healthy fasting subjects (n = 9) were as follows; lithocholic acid 0.013 microgram/ml, deoxycholic acid 0.083 microgram/ml, chenodeoxycholic acid 0.078 microgram/ml, ursodeoxycholic acid 0.013 microgram/ml, and cholic acid 0.007 microgram/ml. Bile acid glucuronides occupied 7.8% of the total bile acids.

Bile Acids and Salts↗

Seasonal variation in pituitary gonadotropin in the adult male newt, Cynops pyrrhogaster pyrrhogaster, revealed by isoelectric focusing technique and radioreceptor assay.

The seasonal variation in pituitary gonadotropin in the adult male newt, Cynops pyrrhogaster pyrrhogaster was investigated by means of isoelectric focusing (IEF) coupled with radioreceptor assay (RRA), which employed Anolis or Xenopus testicular homogenates as receptors and 125I-rat FSH as radioligand. In the Anolis RRA system, the standard curve was obtained with 0.125-16 ng/tube of NIAMDD rat FSH I-3. Purified preparations, chicken LH IEF-1, chicken FSH AGCHD11113A and bullfrog basic gonadotropin-IV competitively inhibited the binding of the radioligand, but NIAMDD rat LH I-4 and human chorionic gonadotropin did not crossreact. The autoradiographic study revealed that 125I-rat FSH bound to the constituent cells of the seminiferous tubules in the Anolis testis, but scarcely to Leydig cells. In the IEF pattern of gonadotropin in February obtained by Anolis RRA, distinct peaks were observed at pH 9.05 (component B) and 8.55 (component C), and less distinct peaks were observed at pH 9.80 (component A), 7.55 (component D) and 7.05 (component E). When the same fractions were assayed by Xenopus RRA, five components were found in the alkaline region, which corresponded to those observed with Anolis RRA. Similar results were obtained with pituitary extracts in May. In July, the IEF pattern obtained by Anolis RRA indicated two additional components at pH 6.30 (component F) and 5.27 (component G) in the acidic region, which were not found by Xenopus RRA. The relationship between the testicular function and the nature of pituitary gonadotropin in the reproductive cycle was discussed.

Animals↗

Comparative histochemical and biochemical assays of estrogen receptors in breast cancer patients.

Estrogen receptors (ER) in breast cancer tissue were determined in 51 patients by a histochemical method with estradiol-17 beta-bovine serum albumin-fluorescein isothiocyanate conjugate and were compared with those in the adjacent tissue determined by biochemical method, i.e., the sucrose density gradient (SDG) and dextran-coated charcoal (DCC) methods. Excluding one non-evaluable case, 26 specimens were ER(+) and 24 were ER(-) in histochemical assay. The presence of ER(+) cells in histochemical assay was not related to menopause or to the molecular pattern of ER determined by the ASG method, or to the histological type of cancer. The percentage of fluorescent cells to all cancer cells was not related to the number of binding sites of ER determined by the DCC method. As determined by the histochemical assay, breast cancer cells having ER accounted for 20 to 100% of all cancer cells examined and ER(+) cells were in clumps or intermixed with ER(-) cells in cancer tissue. The co-existence of Er(+) and Er(-) cells may be one reason for the fact that surgical ablation of breast cancer rarely results in complete tumor regression.

Adult↗