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Biomedical subjects

O Jänne

Publications and source records attributed to O Jänne.

At least 19 recordsLinked to original sources
PubMed1996

Polymorphism of the beta 3-adrenergic receptor gene in morbid obesity.

OBJECTIVE: The Trp64-->Arg allele of the beta 3-adrenergic receptor gene was recently proposed to be associated with an earlier onset of non-insulin-dependent diabetes mellitus (NIDDM), features of insulin resistance and a tendency to gain weight. We investigated whether the Arg64 allele predisposes to severe obesity. DESIGN AND SUBJECTS: A genetic association study of 254 subjects with morbid obesity [body-mass index (BMI) > or = 40; mean 42.8 +/- 7.0] and 151 lean healthy control subjects [BMI < or = 25; mean BMI 22.3 +/- 1.9]. MEASUREMENTS: beta 3-adrenergic receptor genotyping was carried out with a solid-phase minisequencing technique. Serum lipids, glucose and insulin levels in the obese subjects were also determined. RESULTS: The frequency of the Arg64 did not significantly differ in the morbidly obese patients (9.1%) and lean controls (8.9%), nor was there any statistically significant association between the mean BMI values and the beta 3-adrenergic receptor genotype. However, obese subjects carrying the Arg64 allele developed obesity more often before the age of 15 y than those without it (P < 0.05, adjusted for multiple comparisons). The frequency of the Arg64 allele was similar in nondiabetic and diabetic patients; the mean age at the onset of NIDDM did not differ according to the beta 3-adrenergic receptor genotype. There was no significant association between the receptor genotype and the level of the serum cholesterol, HDL-cholesterol, triglyceride, glucose or insulin, nor was this polymorphism associated with the behavioural or psychopathological characteristics of the morbidly obese subjects. Response to a 16 w treatment program including a very-low calorie diet (VLCD) regimen, dietary and exercise counseling, as well as behavioural modifications, did not differ according to the genotype. CONCLUSION: Our data do not support a significant role for the codon 64 polymorphism of the beta 3-adrenergic receptor as a genetic marker of morbid obesity. Although there was an association between the Arg64 allele and an earlier onset of obesity in individuals subsequently developing morbid obesity, this allele was not associated with the actual BMI gained or response to weight-loss therapy on a hypocaloric diet.

Adult↗
PubMed1982

Serum sex steroid and peptide hormone concentrations, and endometrial estrogen and progestin receptor levels during administration of human leukocyte interferon.

Five normally cycling healthy women were given daily subcutaneous injections of human leukocyte interferon (3 X 10(6) units/day) from the 3rd through 23rd day of the menstrual cycle, and serum steroid and peptide hormone concentrations monitored at 3-day intervals during the treatment and the preceding control cycle. Concentrations of cytosol and nuclear estrogen receptors (ERC and ERN, respectively) and progestin receptors (PRC and PRN) were also measured from endometrial biopsies taken on the 24th day of the control and treatment cycle. In addition, an extensive monitoring of clinical chemical and hematological tests from the blood samples were performed. Serum estradiol and progesterone concentrations were significantly decreased during the treatment cycle, suggesting that interferon interacts in vivo with the function of both FSH and LH. No significant changes were observed in the serum peptide hormone concentrations measured (FSH, LH, prolactin, insulin, growth hormone and TSH); neither were the levels of endometrial ERC, ERN, PRC and PRN affected by interferon administration. As expected, interferon administration resulted in decreased leukocyte counts. Moreover, an increasing tendency in the activities of serum alkaline phosphatase and gamma-glutamyltransferase during the interferon therapy shows that interferon may slightly interfere with the liver function. These results suggest that one of the mechanisms by which interferon treatment may affect the growth of hormone-dependent neoplasms could be the interaction with production and/or function of circulating hormonal compounds.

Adult↗
PubMed1982

Serum bile acids during biphasic contraceptive treatment with ethinyl estradiol and norgestrel.

Twenty-nine women were treated with biphasic combined oral contraceptive pills containing ethinyl estradiol 0.05 mg and levonorgestrel 0.050-0.125 mg. Serum primary bile acids (cholic acid and chenodeoxycholic acid) and one secondary bile acid (deoxycholic acid) were measured by radioimmunoassay. The serum samples were collected before the treatment and at one, three and twelve months during the treatment. No significant changes were found in these bile acid levels during the treatment. The ratio of cholic/chenodeoxycholic acid did not change either. No pathological values were found in the conventional liver function tests although serum alanine aminotransferase activity was significantly increased after twelve months' treatment. It can therefore be concluded that the present contraceptive pill does not cause any liver dysfunction detectable by bile acid measurements of other "classical" liver function tests.

Adolescent↗
PubMed1982

Serum bile acid levels in intrahepatic cholestasis of pregnancy during treatment with phenobarbital or cholestyramine.

Nineteen patients suffering from the intrahepatic cholestasis (IHC) of pregnancy were studied. Twelve of them were treated with phenobarbital (100 mg/day) and seven with cholestyramine (18 g/day). The overnight fasting levels of serum cholic acid (CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) were measured by radioimmunoassay. The activities of serum transaminases, gamma-glutamyltranspeptidase, alkaline phosphatase and total and conjugated bilirubins were also analyzed. It was found that there was no correlation between the itching symptom and the serum bile acid levels. During phenobarbital treatment serum bile acid concentrations did not change. Also, the other measured parameters as well as the CA/CDCA ratio did not change significantly. Transaminases had, however, a slight tendency to decrease. The therapy successfully relieved itching in half of the cases. There was no relationship between the relief of the itching and the change in the bile acid concentrations. Cholestyramine treatment did not decrease the CA level significantly, but that of the CDCA decreased (P less than 0.05) and the ratio of CA/CDCA increased (P less than 0.05). In the other analyzed liver function test results, an increase (P less than 0.05) occurred only in the concentrations of conjugated bilirubin. The itching was relieved in five of the seven cases during the first week of treatment, but after that the symptom tended to reappear. There was a slight correlation between the decrease in the CDCA level and in the relief of the itching. The two drugs did not cause any particular side effects.

Bile Acids and Salts↗
PubMed1982

The desmoid tumor. III. A biochemical and genetic analysis.

We have carefully examined four patients with desmoid tumor (DT) and their 31 relatives. In three of four cases, biopsies of the DT demonstrated low yet significant amounts of estrogen but not progesterone receptors in the tumor cytosol. In the fourth case, where the receptors were not demonstrable, the affected patient was a menopausal woman and the receptors may have been blocked by endogenous estrogen. Fourteen of their 31 relatives demonstrated multiple minor bone malformations in x-ray screening of the skeleton. The inheritance of these malformations was compatible with an autosomal dominant trait with variable penetrance. These findings are compatible with our suggestion that the basic underlying cause for DT is an inherited defect in growth regulation of the connective tissue. When a trauma is superimposed on such an individual, a DT may result. The growth of the tumor is, however, controlled primarily by sex hormones, estrogen predominance over progesterone being inducive to tumor growth.

Abnormalities, Multiple↗
PubMed1982

Danazol has progestin-like actions on the human endometrium.

The administration of danazol, 200 mg three times daily, from the 3rd to the 23rd day of the cycle to normally menstruating women exhibited the following actions on the human endometrium: significantly reduced cytosol oestrogen and progestin receptor concentrations, and declined 17 beta-hydroxysteroid dehydrogenase activity. Very similar results were obtained during medroxyprogesterone acetate (100 mg daily) treatment for the same period of time. Danazol administration did not decrease circulating gonadotrophin levels but clearly suppressed luteal serum oestradiol and progesterone concentrations. Danazol was found to bind in vitro to endometrial progestin receptor with an affinity approximately 3% of that of progesterone. These findings are compatible with the notion that a local progestin-like rather than a systemic action of danazol is the way by which its therapeutic effect is exerted. This may be potentiated by the suppression of circulating oestradiol levels.

17-Hydroxysteroid Dehydrogenases↗
PubMed1982

Bromocriptine and norethisterone in the treatment of premenstrual syndrome.

Thirty-six women suffering from premenstrual syndrome were treated with bromocriptine or norethisterone in a randomized placebo-controlled double-blind study. Bromocriptine decreased breast engorgement and irritability (P less than .01) and also decreased the total score of all symptoms (P less than .05). Weight gain during the luteal phase was smaller (P less than .05) during bromocriptine than during placebo treatment. Norethisterone treatment alleviated (P less than .05) breast tenderness. Changes in hormonal parameters and liver function tests during bromocriptine treatment were minimal, whereas norethisterone decreased serum levels of luteinizing hormone (P less than .01), follicle-stimulating hormone (P less than .001), and progesterone (P less than .05), while increasing the serum level of prolactin (P less than .01) and gamma-glutamyltranspeptidase activity (P less than .05). Serum levels of cholic acid and chenodeoxycholic acid remained unchanged during both therapies. Bromocriptine treatment brought about side effects in 6 and norethisterone in 3 women. At the doses used, bromocriptine appears more efficient than norethisterone with regard to premenstrual symptoms, although norethisterone is better tolerated.

Adult↗
PubMed1981

Estrogen and progestin receptors in endometriosis lesions: comparison with endometrial tissue.

Cytosol estrogen (ER) and progestin (PR) receptors were quantified in 47 endometriosis lesions from 41 patients and compared with receptor measurements in the endometrial tissue of nine of these patients. Half of the specimens of endometriosis tissue contained PR only, in concentrations that were significantly lower than in the endometrium. Only 30% of the specimens of endometriosis tissue contained the two receptors simultaneously, and levels of ER were very low compared with those in the endometrium. Levels of PR in the specimens of endometriosis tissue were highest at the periovulatory period, whereas concentrations of ER tended to be highest at the beginning and close to the end of the cycle. These results suggest that regulation of these receptors is dissimilar in endometriosis lesions and endometrium. It remains to be seen whether differences in receptor distribution in the lesions of individual patients could explain differences in the course of this disease, and have therapeutic implications. The presence of PR in the majority of the endometriosis lesions is in accord with the favorable therapeutic response often obtained with progestin treatment of this disease.

Adult↗
PubMed1981

Postmenopausal hormone replacement therapy with estrogen periodically supplemented with antiestrogen.

To inhibit endometrial stimulation during postmenopausal estrogen therapy, 25 women with climacteric symptoms were treated with a daily dose of 1.25 mg of conjugated estrogens for 7 weeks followed by a period of 10 days with clomiphene citrate administration (50 mg per day). This combination was repeated three times during the 6-month trial. The marked relief of climacteric symptoms with estrogen was slightly less during clomiphene treatment. Uterine bleeding occurred five times during estrogen treatment periods but never during or after clomiphene supplementation. Histologic examination revealed endometrial atrophy in 41% of the samples after the first estrogen treatment, whereas after the first and third clomiphene periods this was increased to 77% and 73%, respectively. The first clomiphene treatment significantly decreased the concentrations of cytosol estrogen and progestin receptors in endometrium, as compared with the levels recorded at the end of the preceding estrogen therapy. The depression in the cytosol estrogen receptor concentration was persistent, whereas cytosol progestin receptor concentration tended to increase during the subsequent estrogen-plus-clomiphene treatment. Estrogen declined serum concentration of follicle-stimulating hormone (FSH), whereas the concentration of luteinizing hormone (LH) and prolactin remained unchanged. Clomiphene did not change the levels of these hormones from those observed during the estrogen treatment. The concentration of free fatty acids in serum was increased during the estrogen and clomiphene treatments, whereas the levels of cholesterol and high-density lipoprotein--cholesterol did not change. Our results suggest that this treatment regimen relieves climacteric symptoms without endometrial stimulation or other adverse effects. Thus, clomiphene appears to be a practical alternative to progestin for interruption of the postmenopausal endometrial effect of estrogen.

Clomiphene↗
PubMed1981

Serum bile acids and lipids during treatment of climacteric symptoms with natural oestrogen--progestin combinations.

Climacteric symptoms of 21 women were treated for 6 mth with sequential combination preparations containing natural oestrogen (oestradiol and oestriol) and norethisterone acetate as progestin. There were no significant changes during the treatment period in the serum alanine aminotransferase activity or concentrations of cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, cholic acid and deoxycholic acid. The concentration of chenodeoxycholic acid was, however, significantly decreased after 6 mth treatment. It thus appears that the above natural oestrogen--progestin combinations do not have adverse effects on hepatic function and lipid metabolism.

Adult↗
PubMed1981

Serum cholic acid and chenodeoxycholic acid concentrations in neonatal hyperbilirubinemia.

Primary bile acid concentrations were measured in serum of 332 newborns with neonatal hyperbilirubinemia (serum total bilirubin level greater than 200 mumol/l) and compared with those of 95 nonhyperbilirubinemic neonates (serum total bilirubin level less than 200 mumol/l). The serum concentrations (mumol/l; mean +/- SEM) for cholic acid (8.78 +/- 0.44) and chenodeoxycholic acid (10.5 +/- 0.68) were significantly higher (p less than 0.001) in the hyperbilirubinemic group than in the controls (7.16 +/- 0.48 and 6.67 +/- 0.48, respectively). 80 (24%) of the hyperbilirubinemic newborns had true cholestasis (serum levels of cholic and/or chenodeoxycholic acid higher than mean +/- 2 SD in the reference group). The ratio of cholic to chenodeoxycholic acid was significantly higher (p less than 0.05) in the cholestatic group than in the hyperbilirubinemic newborns without cholestasis. There was no significant differences in the serum concentrations of alkaline phosphatase or lactate dehydrogenase between the cholestatic and noncholestatic groups. In the hyperbilirubinemic newborns, the primary bile acids were indiscriminately raised. Only 8 infants from the 332 newborns had jaundice at the age of 1 month. Of these 8 infants only 2 had neonatal cholestatic hyperbilirubinemia. It thus appears that measurement of serum primary bile acid concentrations has only limited diagnostic value in assessing the severity or prognosis of neonatal hyperbilirubinemia.

Chenodeoxycholic Acid↗
PubMed1981

Cyclic clomiphene citrate treatment lowers cytosol estrogen and progestin receptor concentrations in the endometrium of postmenopausal women on estrogen replacement therapy.

Clinical and experimental studies have indicated that a nonsteroidal antiestrogen, clomiphene citrate, might prevent the stimulatory action of estrogens on the human endometrium. To investigate the mechanisms of this effect, the treatment of 19 postmenopausal patients with conjugated estrogens for 6 months was supplemented cyclically for 10 days with clomiphene citrate after every 7 weeks. Ten patients ingested clomiphene citrate alone, whereas 9 patients continued estrogen treatment during clomiphene supplementation. Estrogen and progestin receptors were measured from the cytosol of the endometrium after the first estrogen period and after the first and third clomiphene treatment. The estrogen receptor concentration was significantly lower after both clomiphene supplementation periods than after the initial estrogen administration. The progestin receptor concentration was significantly lower only after the first clomiphene citrate period. The effect of clomiphene citrate was independent of the initial histological appearance of the endometrium and led to atrophy of the endometrium in most of the patients. Because the effect of clomiphene citrate was independent of simultaneous estrogen administration, it acted as a pure antiestrogen in this treatment modality. The relative decreases in estrogen and progestin receptor concentrations on the present treatment regimen were different from those previously found on progestin treatment and most likely occur via different mechanisms. It is not known whether these two treatment types will have additive effects.

Clomiphene↗
PubMed1981

Changes in serum bile acid concentrations during normal pregnancy, in patients with intrahepatic cholestasis of pregnancy and in pregnant women with itching.

Two primary bile acids, cholic acid (CA) and chenodeoxycholic acid (CDCA), and one secondary bile acid, deoxycholic acid (DCA), were measured by radioimmunoassay in pregnancy serum from 30 healthy women, 49 women with itching and 45 with intrahepatic cholestasis of pregnancy. All subjects were studied serially from between 16 and 20 weeks gestation until 35-60 days post partum. In healthy pregnant women, serum CA and DCA levels did not change significantly at any time. The mean CDCA level rose significantly towards term. In women with intrahepatic cholestasis, serum levels of CA and CDC were increased ten- and five-fold, respectively, at the time of appearance of clinical symptoms and the CA/CDCA ratio rose from 1/1 to 2/1; there was also a moderate increase in the serum concentration of DCA. In 4 of 8 women studied prospectively an increase in serum bile acid levels preceded the appearance of symptoms or other laboratory evidence of intrahepatic cholestasis. Nine of the women with itching with normal routine liver function test results had increases in serum CA and CDCA concentrations suggesting mild cholestasis.

Bile Acids and Salts↗
PubMed1980

Treatment of advanced endometrial adenocarcinoma with a combined cytotoxic therapy. Predictive value of cytosol estrogen and progestin receptor levels.

Twenty patients with advanced or recurrent endometrial adenocarcinoma were treated with combination chemotherapy consisting of Adriamycin, cyclophosphamide, 5-fluorouracil, and vincristine at three-week intervals. A minimum of four treatment courses was given in each case. There were five total and five partial responses (50% favorable response rate); progression of the disease was evident in seven cases (35%). Lung metastases responded significantly better (P < 0.01) than other lesions: seven out of nine lung metastases showed an objective remission, whereas only two out of 11 tumors in pelvic, abdominal, or retroperitoneal space responded. The response rate did not correlate with histologic grade of tumor differentiation, or the performance state and age of the patient. Cytosol estrogen and progestin receptor levels were measured in 15 cases from the carcinomatous endometrial tissue prior to therapy. Ten patients with low receptor values (estrogen and/or progestin receptors below 30 fmol/mg cytosol protein) had a significantly (P < 0.025) greater response rate (70%) than did patients with higher receptor values (both receptors above 30 fmol/mg protein, response rate 20%). Determination of only one of the two receptors did not differentiate the patients equally well, although the response rate tended to be better (0.05 < P < 0.1) in patients with a low level of either estrogen or progestin receptor (67% response rate) when compared with a 33% response rate in patients with a high level of the corresponding receptor. Our results suggest that the measurement of cytosol steroid hormone receptors has the potential to serve as a suitable indicator for selection of endocrine or nonhormonal chemotherapy for patients with advanced endometrial adenocarcinoma.

Adenocarcinoma↗