PubMed Health⌕ Search

Biomedical subjects

J I Thorell

Publications and source records attributed to J I Thorell.

At least 37 records · Page 2Linked to original sources

Radioimmunoassay of pro-gamma-melanotropin, the amino-terminal fragment of proopiolipomelanocortin.

A RIA has been developed for natural porcine pro-gamma MSH, the 103-amino acid peptide that represents the amino-terminal part of proopiolipomelanocortin. Rabbits were immunized with the purified peptide polymerized with glutaraldehyde. The antiserum is directed against the amino-terminal end of the antigen and does not cross-react with corticotropin, beta-lipotropin, beta-endorphin, gamma 3MSH, or gamma 2MSH. The minimum detectable concentration is 0.15 ng/ml standard pro-gamma MSH (15 pg/tube). Pro-gamma MSH-like immunoreactivity was detected in plasma and extracts of the hypothalamus and pituitary of pigs. Gel chromatography of these extracts revealed at least three immunoreactive peaks in the anterior and neurointermediate lobes of the pituitary, whereas two immunoreactive peaks were found in extracts of the hypothalamus.

Amino Acid Sequence↗

Use of an internal sample attenuator in radioimmunoassay. Assay of triiodothyronine (T3) using starch particles containing entrapped charcoal and bismuth oxide in combination with free antibodies.

A radioimmunoassay for triiodothyronine involving no separate washing or separation steps is described. By using an internal sample attenuator, bismuth oxide, co-immobilized with the sorbent, charcoal, for the non-bound fraction of T3, a system was designed in which a suspension of starch spheres containing the sorbent and the attenuator was added after the immunological reaction had taken place. The particles sedimented and the whole test tube was counted in a gamma-counter. The coefficient of correlation between the results obtained with the present method and those from conventional procedures was 0.993.

Adsorption↗

Decreased radioiodine uptake values without increase in urinary iodine excretion.

A total of 12842 radioiodine uptake measurements (RIU), performed for diagnostic purposes at Malmö General Hospital 1955-75, have been reviewed. In agreement with the general trend in Europe and the USA, there was a significant decrease in uptake during this period. The 24-hour RIU (mean +/- S.D.) was 51 +/- 18% in 1955, 41 +/- 17% in 1965 and 37 +/- 18% in 1975. The 3- and 48-hour uptake values, as well as the protein-bound radioiodine, fell in a parallel fashion. The fall can not be explained by an increased dietary supply of iodine, because the mean urinary excretion did not show any consistent change from 1965 to 1975, apart from a falling trend from 1967 to 1971. The cause of the decrease in thyroid iodine uptake is not elucidated by this study.

Diet↗

Reticulocytes and insulin binding to erythrocytes.

The relationship between erythrocyte insulin receptors and the reticulocytes were studied in a group with a varying degree of reticulocytosis. The maximal I-insulin binding to erythrocytes varied between 6% and 37% and it showed a highly significant positive correlation with the reticulocyte count (r=0.85). The highest binding was found in a patient with hereditary spherocytosis and very active hematopoiesis (312 x 10(9) reticulocytes per litre). The results suggest that insulin receptors are predominantly localized to the young erythrocytes, and that further studies are needed to characterize the dependence of the receptor on erythrocyte maturation.

Adult↗

Internal sample attenuator counting (ISAC). A new technique for separating and measuring bound and free activity in radioimmunoassays.

I describe a new method for the separation and counting of bound and free activity in radioimmunoassays. Particles containing a radiation-absorbing (attenuating) material are added to the assay. They shield the radiation from either the antibody-bound or the free radioligand. This obviates such manipulations conventionally involved in the separation and counting steps of radioimmunoassays as centrifugation and decanting. Bismuth oxide is used as the attenuator. Particles with different properties are described. In one type, bismuth oxide is combined with active charcoal in an agarose matrix and serves as an adsorbant for the free radioligand. In another type bismuth oxide is trapped within a polyacrylamide matrix to which antibodies are coupled. This particle can be used with a first- or a second-antibody bound activity. Application of the technique is illustrated with radioimmunoassays for thyroxin, triiodothyronine, human choriogonadotropin, and lutropin (luteinizing hormone).

Adsorption↗

The production of antibodies to vitamin B-12.

The conjugation of vitamin B-12 to HSA by means of a combined ethylcarbodiimide N-hydroxysuccinimide conjugation method at pH 5.5 is described. It gave a ratio of 2.7 mol vitamin B-12/mol HSA. Five rabbits were immunized with this conjugate emulsified in Freund's complete adjuvant. After one booster injection high titre antisera (1 : 450 000--1 : 1 500 00) to vitamin B-12 were collected.

Animals↗

Metabolic studies and glucagon gel filtration pattern before and after surgery in a case of glucagonoma syndrome.

A case of glucagonoma syndrome with necrolytic migratory erythema, glossitis, anemia, hyperglucagonemia and a malignant, pancreatic A-cell tumour in a 68-year-old male is described. Gel filtration of the highly elevated circulating glucagon immunoreactivity (2200 pg/ml) demonstrated 60% pancreatic glucagon and 30% "proglucagon". Metabolic studies before operation demonstrated suppression of the total plasma glucagon concentration on oral glucose tolerance test, unchanged total plasma glucagon concentration during intravenous glucose tolerance test and insulin-induced hypoglycemia. Administration of arginine was followed by a rise in both the pancreatic glucagon and the "proglucagon", whereas alanine increased only the pancreatic glucagon. The plasma somatostatin level was immeasurable preoperatively. Somatostatin infusion completely suppressed the release of the pancreatic glucagon but did not significantly affect the "proglucagon". After removal of the tumour the skin lesions disappeared and the total plasma glucagon values fell to normal levels (120 pg/ml). Also, other abnormal laboratory findings returned to normal, including the preoperatively observed renal glucosuria.

Adenoma, Islet Cell↗

Direct radioiodination of estradiol for a sensitive radioimmunoassay.

17 beta-estradiol (E2) was iodinated with the chloramine-T method. The 125I-labelled material was purified with thin-layer chromatography. The major fraction was applied to a radioimmunoassay with an antiserum against estradiol-6-(0-carboxymethyl)oxime-BSA. The sensitivity of the assay was comparable to assays with 3H-E2 or 125I-histamine-E2 as tracers. The working antiserum dilution (1:1 000 000) was the same with 125I-E2 and 3H-E2 but lower than that with 125I-histamine-E2. The results indicate that iodination of the A-ring of estrogens will not cause significant reduction of the immunoreactivity when combined with an antiserum to a B-ring conjugate.

Estradiol↗

Characterization of specific antisera to native human luteinizing hormone.

Antisera against highly purified native hLH (10 000 IU/mg = 0.5 mg hLH/mg protein) were raised in 4 rabbits. The antisera were invariably of high titre and high avidity. They were purified by affinity chromatography on a column with hCG-Sepharose 4 B. Before and after adsorption the antisera were tested in a double antibody radioimmunoassay. Before adsorption hCG cross-reacted in all antisera, but in none were the inhibition curves identical. No such cross-reaction remained after the affinity chromatography. These purified antisera made it possible to develop highly specific and sensitive assays for measuring native hLH. We conclude from studies of the effect of native glycoprotein hormones and their subunits that there are probably differences in the antigenic sites of the complete hLH molecule and in the isolated beta-subunit of hLH. The investigation also indicates that even highly purified preparations of hTSH may be contaminated with hLH and that the preparations of hLH-subunits may contain a certain amount of the native hormone.

Adsorption↗

Effect of danazol on thyroid function in women.

A longitudinal study of thyroid function during danazol treatment was performed in 18 women. Serum concentrations of thyroid stimulating hormone (TSH), thyroxine (T4), tri-iodothyronine (T3), free T4-and free T3 index as well as thyroid hormone binding globulin (TBG) were measured before and during 6 months therapy. Thyroxine binding globulin showed a marked decrease to one third of the pretreatment level. All the hormones showed significant alterations within the normal ranges for this group. T3 and T4 decreased slightly and the free T4 and free T3 index showed an increase. TSH decreased from 2.4 +/- 0.6 to 1.7 +/- 0.3 mIU/l. The observed hormonal changes were most likely induced by the decreased TBG concentrations and were probably without pathological significance. However these changes must be kept in mind when thyroid function tests from patients with danazol are evaluated.

Adult↗

Insulin secretion and peripheral insulin sensitivity in obese children. Evidence of deficient glucose-stimulated early insulin release despite hyperinsulinemia.

Insulin secretion and peripheral insulin sensitivity were studied in 19 grossly-obese girls and 17 age-matched non-obese girls by means of the intravenous glucose tolerance test (IVGTT) and the simulated early insulin response test (SERT) respectively. SERT measures the fall in fasting blood glucose after a short infusion of insulin, performed so as to simulate the early phase of insulin release to the acute stimulus of an intravenous glucose load (ERex). In the IVGTT, the obese girls showed significantly increased early insulin response (ERend) in comparison with the non-obese girls. The glucose disappearance rate (KG) was similar in the two groups, although four obese girls had borderline low values. In the SERT, the rise in plasma insulin caused a much smaller decrease in blood glucose in the obese girls, than in the reference girls over the whole range of insulin levels studied. The relationship between insulin sensitivity and insulin secretion of each subject was evaluated from the plot of the ERex/ERend ratio vs blood glucose decrement. This showed that the hyperinsulinemia of the obese girls did not match the degree of peripheral resistance.

Blood Glucose↗

Basal and LRH-stimulated secretion of FSH during early pregnancy.

The gonadotropin response to 25 mug of LH/FSH releasing hormone (LRH) intravenously was investigated during the very first weeks of pregnancy. It was found progressively to decrease, and no response in FSH was found for more than 5 weeks. The basal levels of FSH showed the same decreasing tendency, and a few weeks after conception they were often close to the sensitivity limit of the assay. With this report we have continued our description of the changing pituitary responsiveness to LRH from conception to the puerperium. During later stages of pregnancy the plasma levels of FSH were markedly reduced, and the response was inhibited even after 500 mug of LRH intervenously. The return of the response during the puerperium showed a specific pattern with a dissociation of the response in FSH and LH. No such dissociation was found during the period of progressive inhibition during the very first weeks of pregnancy.

Adult↗

Lactoferrin and lysozyme in arthritic exudates.

Lactoferrin (LF) has been assayed by radioimmunoassay in plasma and arthritic exudates and compared with lysozyme (LZ) levels and leukocyte counts. The mean LF concentration in 38 rheumatoid arthritis (RA) exudates was 9.1 mg/l (range 0.02-39.2). In 30 non-RA exudates LF was 3.3 mg/l (range 0.01-14.6). The corresponding LZ levels were 7.4 mg/l (range 2.5-18.5) in RA and 4.7 (range 1.0-12.5) in non-RA fluids. Exudate/plasma ratios were much higher for LF than for LZ and higher in RA than in non-RA exudates, whereas leukocyte counts did not differ. The LF/leukocyte count ratio was significantly higher in RA than in the non-RA group. The data suggest a more prominent release of neutrophilic granulocyte components in RA than in non-RA arthritis.

Animals↗

The effects of digoxin and beta-methyldigoxin on the heart rate of decompensated patients with atrial fibrillation.

Eighteen patients with atrial fibrillation were given digoxin 0.13 mg twice daily for 3 weeks and beta-methyldigoxin 0.10 mg twice daily for another 3 weeks. At the end of each 3 week period an exercise test was performed and the effects on the heart rate of the two drugs were compared. No difference in heart rate was obtained at rest, whereas the heart rate after 6 min of exercise was higher during treatment with digoxin (131 beats/min) than when the patients were taking beta-methyldigoxin (124 beats/min). There were no significant differences between digoxin and beta-methyldigoxin in their effects on the ECG (R-R intervals, T-wave, Q-T duration). The plasma concentrations of the two glycosides were determined by radioimmunoassay and by 86Rb-uptake inhibition assay. Comparable plasma concentration values (1.0 ng/ml for digoxin, 1.1 ng/ml for beta-methyldigoxin, mean values) were obtained by radioimmunoassay, but the 86Rb-technique gave significantly higher values (mean 1.5 ng/ml) for beta-methyldigoxin. It is concluded that beta-methyldigoxin is equal to digoxin for producing slowing of the heart rate in patients with atrial fibrillation.

Aged↗

Influence of LH/FSH releasing hormone (LRH) on the basal secretion of gonadotrophins in relation to plasma levels of oestradiol, progesterone and prolactin during the post-partum period in lactating and in non-lactating women.

The pituitary responsiveness to LH/FSH releasing hormone (LRH) was studied in the puerperium in lactating and in non-lactating women. The response of both groups of patients to 25 mug LRH iv was tested 8-10 days, 15-17 days, and 29-32 days after a normal delivery at full term. The basal levels of FSH were low during the first 10 days after delivery. A rise was then observed, and about 4 weeks after delivery levels above or in the upper normal range of a normal follicular phase were recorded. The levels were significantly higher in the lactating group. When compared with the normal follicular phase, the relative increase in FSH basal levels was higher than the increase in LH basal levels in both groups of patients. The period of non-responsiveness of the pituitary to LRH was found to be of equal length in the two groups. In both groups the FSH response returned more rapidly than the LH response. About 2 weeks after delivery a reverse pattern of gonadotrophin response to LRH was seen with a FSH response that was greater than the LH response compared with what is generally observed in the various phases of the menstrual cycle in eumenorrhoeic women. This pattern was more pronounced in the lactating group about 4 weeks after delivery. Oestradiol levels were low and roughly equal on the three test occasions in each group, but in the non-lactating group there was a tendency to higher concentrations. Prolactin levels were highest about one week after delivery and then showed a tendency to decrease, and this was more pronounced in the non-lactating group. Progesterone levels were invariably low in both groups.

Adult↗

Pituitary gonadotrophin secretion during the first weeks of pregnancy.

A longitudinal study of basal plasma LH and FSH and their responses to 25 microng LRH iv as well as basal levels of oestradiol, progesterone, prolatin and HCG was performed every week in 3 women, pregnant after heterologous insemination, from conception until the 6th week of gestation. A comparative study was carried out in 7 women in cycles in which no conception occurred after insemination. All hormones were assayed with radioimmunoassay. LH was measured with a specific assay for native HL, which did not cross-react with HCG. A decrease in basal levels of LH and FSH as well as decreasing responses to LRH was found during the first 2 weeks of gestation. These changes did not differ from what was observed during the luteal phase in the non-conception cycles. One week later the basal FSH levels and the FSH response in the pregnant women showed a further decrease, while in the non-pregnant women, now reaching the early follicular phase, a rise in FSH basal levels occurred. The basal levels of LH and the LH response, however, did not differ from that found in the non-pregnant woment at this time. FSH basal levels remained below the lower normal limit in eumenorrhoic women from the 3rd week of gestation. By this time the FSH response was almost completely inhibited. The LH basal levels, however, remained above the lower normal limit in eumenorrhoic women, but the LH response to LRH progressively decrease and was completely inhibited by the 5th week of gestation. In the non-conception cycles the LH response varied with the levels of oestradiol in plasma. This was not found in the pregnant women as the decrease in gonadotrophin response occurred while oestradiol remained at mid-cycle levels during the first 4 weeks of gestation. Rather it seems that the increasing and continuously elevated level of progesterone, in the presence of appropriate levels of oestradiol, might be the main go nadal steroid responsible for the diminishing pituitary secretion. The contribution of HCG to the further decrease in gonadotrophin secretion after the 2nd week of pregnancy cannot be answered by the present studies. Prolactin remained at non-pregnant levels until the 6th week of gestation, and appeared to have no influence on the secretion of gonadotrophins during early pregnancy.

Adult↗

Screening for detecting twin pregnancy.

Estimation of HPL during the twenty-ninths to the thirtieth week of pregnancy is a simple and safe method for detecting twins. Nine out of 10 pregnant women have a value below 5.0 mug per milliliter, which excludes the suspicion of twins. In the remaining women with higher values the diagnosis can be confirmed or excluded by ultrasound or x-ray.

Female↗