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Biomedical subjects

A Lambert

Publications and source records attributed to A Lambert.

At least 19 recordsLinked to original sources
PubMed1992

Human chorionic gonadotrophin contributes to the bioactivity of Pergonal.

OBJECTIVE: We examined batch variation in the LH-like bioactive content of Pergonal and determined whether hCG contributes to this. DESIGN: Random selection of three batches of Pergonal, consisting of three ampoules in each batch. MEASUREMENTS: The LH content in each ampoule was determined by radioimmunoassay (R-LH), immunoradiometric assay (I-LH) and in vitro Leydig cell bioassay (B-LH) using the urinary hMG International Standard 70/45. Human chorionic gonadotrophin was determined by immunoradiometric assay (I-hCG) using the hCG IRP 75/537. The isohormone content of each batch was examined by chromatofocussing over the range pH 4.5-7.0 and the fractions collected were assayed for LH and hCG content. The variability in potency between batches was assessed by single factor analysis of variance. RESULTS: The gonadotrophin content of each batch (IU/ampoule, mean +/- SEM, n = 3 ampoules) was R-LH (40.9 +/- 0.5, 40.8 +/- 0.2, 39.3 +/- 0.7, P > 0.15), I-LH (39.0 +/- 1.5, 28.3 +/- 0.8, 36.9 +/- 3.3, P < 0.001), B-LH (27.3 +/- 0.3, 12.0 +/- 0.9, 19.3 +/- 0.9, P < 0.001) and I-hCG (16.4 +/- 0.7, 11.7 +/- 0.2, 10.5 +/- 0.5, P < 0.001). The chromatofocussing recoveries below pH 5.5 expressed as a percentage of the total amount of analyte eluted from the column and collated for all three batches of Pergonal were (mean % +/- SD, n = 3 batches) R-LH (58.4 +/- 4.0), I-LH (41.3 +/- 7.5), B-LH (81.4 +/- 2.8) and I-hCG (87.8 +/- 3.7). CONCLUSIONS: There was significant batch variation in the I-LH, B-LH and I-hCG (P < 0.001) but not the R-LH (P > 0.15) content of Pergonal. More than 80% of the total B-LH recovery chromatofocussed below pH 5.5 and corresponded to the region of highest I-hCG (> 87%) and lowest I-LH (< 42%) recovery. This was highly suggestive of hCG contributing to the LH-like bioactivity of Pergonal.

Chorionic Gonadotropin↗
PubMed1992

Variations of magnesium, iron, copper and zinc during the colonic wound healing process: experimental study on rabbits.

The role of trace elements in the wound-healing process is still controversial. Their variations within a normal colonic wound healing have never been studied. An experimental study on rabbits was designed to study magnesium, iron, copper and zinc variations in blood, normal colonic walls and colonic anastomoses on each of the first 7 postoperative days. No major variations of Mg could be observed. Fe decreased in blood as well as in colonic walls and anastomoses. Cu increased in blood, whereas it decreased in colonic walls and anastomoses. Zn decreased in blood, whereas it increased in colonic walls without significant changes in anastomoses. The role of Fe seemed to be rather difficult to understand. Plasma mobilization seems to explain the local use of Zn, while early tissue release with further return in blood occurred for Cu. The importance of a well-balanced nutritional status is underlined to prevent and correct the variations of trace elements in the postoperative course.

Anastomosis, Surgical↗
PubMed1992

Microheterogeneity of thyroid-stimulating hormone from the pituitaries of euthyroid, hypothyroid and hyperthyroid rats.

The microheterogeneity of pituitary thyroid-stimulating hormone (TSH) is dependent on variations in the hormone's carbohydrate moieties. In this study, changes in the pattern of heterogeneity have been assessed by chromatofocusing, which separates the isospecies on the basis of their isoelectric points (pI). Rats (n = 6 per group) were either untreated or rendered hypo- or hyperthyroid by including in the drinking water either propylthiouracil (0.05% for 8 weeks) or thyroxine (T4; 4 mg/l for 6 weeks) before they were killed at 16 weeks. On autopsy, serum TSH and total T4 were (means +/- S.E.M.): 2 +/- 0.3 micrograms TSH/l and 64 +/- 5 nmol T4/l (control); < 1 microgram TSH/l and 133 +/- 6 nmol T4/l (hyperthyroid); 58 +/- 6 micrograms TSH/l and 32 +/- 6 nmol T4/l (hypothyroid). The pituitaries were individually homogenized and the TSH isoforms separated by chromatofocusing over a pH range of 7-4. Fractions were assayed for TSH by radioimmunoassay. TSH from the control group was distributed into seven major peaks with pI values of (means +/- S.E.M., n = 6) 6.9 +/- 0.1, 6.6 +/- 0.1, 6.2 +/- 0.1, 5.8 +/- 0.1, 5.5 +/- 0.1, 5.2 +/- 0.1 and 4.8 +/- 0.1; 7 +/- 3% of the TSH had a pI of < 4.0. Six peaks of TSH were conserved in the hypothyroid group (with pI values of 6.8 +/- 0.1, 6.5 +/- 0.1, 6.2 +/- 0.1, 5.8 +/- 0.1, 5.4 +/- 0.1 and 5.2 +/- 0.1), and 11 +/- 4% of the hormone had a pI of < 4.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Different isoforms of human pituitary thyroid-stimulating hormone have different relative biological activities.

The relationship between the immunological and biological activities of thyroid-stimulating hormone (TSH) isoforms present in the three human pituitary preparations 68/38 (1st IRP), 80/558 (2nd IRP) and 63/14 (MRC Research Standard A) was investigated. The isoforms were separated by chromatofocusing. Six peaks of immunoactivity were detected in 80/558, with pI values (means +/- S.E.M.) of 6.6 +/- 0.1, 6.2 +/- 0.1, 5.9 +/- 0.1, 5.5 +/- 0.1, 5.2 +/- 0.1 and 4.9 +/- 0.1. Four peaks, with pI values of 6.8 +/- 0.1, 5.9 +/- 0.1, 5.5 +/- 0.1 and 5.2 +/- 0.1, were observed for 68/38. Standard 63/14 had five peaks, with pI values of 6.9 +/- 0.1, 6.4 +/- 0.1, 5.9 +/- 0.1, 5.4 +/- 0.1 and 4.9 +/- 0.1. For each standard, six fractions around the peak areas and at the top and bottom of the gradient were pooled and microconcentrated to < 1.0 ml. Microconcentrated TSH samples were assayed in three TSH bioassays based upon FRTL-5 thyroid cells, utilizing cyclic AMP accumulation, iodide and thymidine uptake as end-points and standard 80/558 as reference preparation. The more acidic forms of TSH showed a higher biological:immunological (B:I) ratio for cyclic AMP accumulation with, for example, 63/14 having a maximum of 3.7 (pI 4.9) and a minimum of < 0.7 (pI 6.9). In contrast, the maximum and minimum B:I ratios for iodide uptake for 63/14 were 3.8 (pI 6.9) and < 0.8 (pI 4.6), and for thymidine uptake, maximum and minimum ratios were 7.2 (pI 6.9) and 1.1 (pI 4.6) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Assay↗
PubMed1991

Determination by latex immunoassay of protein 1 in normal and pathological urine.

A sensitive latex particle assay has been developed to study the occurrence of protein 1 in human urine. The coefficients of variation (CVs) of the method which is fully automated vary between 3 and 11.5%. The assayable concentration range is 0.3 to 40 micrograms/l. Protein 1 is clearly a sex-dependent protein. In contrast to urinary retinol-binding protein (RBP) which shows no variation with age or sex, protein 1 is excreted in greater amounts in males from the puberty. In adults, the mean concentration of protein 1 in urine of men is approximately 5 times that of women. In the urine from both sexes, protein 1 occurs as a single component with a Mr around 21,000 and an pI of about 4.8. Protein 1 is correlated with RBP in the urine from female or male patients with impaired proximal tubular function, which suggests that it is handled by the kidney in a similar manner as RBP. Diabetics, however, show elevations of urinary protein 1 which do not correlate with the RBP excretion but with the albuminuria. A competition between albumin and protein 1 for renal tubular uptake might explain this paradoxical behaviour of protein 1 in the course of diabetic nephropathy.

Adolescent↗
PubMed1991

Autonomous telemetric capsule to explore the small bowel.

An intestinal telemetric capsule has been developed to study the small bowel in man. It consists of a cylinder (11 mm in diameter and 39 mm in length) containing a location detector, a radiotransmitter, a lithium battery and an interchangeable tip. After having been swallowed by the patient, the capsule passes through the whole gut and is recovered in the stools. During the transit through the small bowel, the information provided by the radiotransmitter allows continuous monitoring of the distance covered from the pylorus, the direction and the velocity of progression. Moreover, according to the type of interchangeable tip, it is possible, by remote control, to sample 0.5 ml of intraluminal fluid for subsequent analysis or to release 1 ml of any liquid substance in a precisely determined place for pharmacological studies. The main originality of the capsule is its ability to transmit its precise location inside the small bowel.

Gastrointestinal Motility↗
PubMed1991

Peripheral visual changes and spatial attention.

Three experiments are reported investigating the attentional effects of peripheral visual changes. In agreement with previous work, experiment 1 demonstrated facilitatory and inhibitory effects of a peripheral visual change on the latency of peripheral target detection. However, after a few minutes practice the facilitatory effect disappeared entirely. The inhibitory effect, though slightly reduced in later blocks, remained significant. Hence, the two effects are dissociable and not inter-dependent as argued by Maylor (1985). In experiments 2 and 3 the perceptual salience of the peripheral cue was manipulated. With a low energy, barely noticeable cue there was no reduction in either facilitation or inhibition as a function of practice. In contrast, the attentional effects of cues higher in energy tended to diminish with practice. Theoretical implications of these data are discussed.

Adult↗
PubMed1991

Follicle-stimulating hormone-dependent estrogen secretion by rat Sertoli cells in vitro: modulation by calcium.

We have investigated the role of Ca2+ in the control of FSH-induced estradiol secretion by Sertoli cells isolated from 8-10 days old rats. Exogenous Ca2+ (4-8 mmol/l) inhibited FSH-stimulated E2 secretion such that, with 8 mmol/l Ca2+ and FSH (8 IU/l) E2 secretion decreased from 2091 +/- 322 to 1480 +/- 84 pmol/l (p less than 0.002), whilst chelation of Ca2+ in the culture medium with EGTA (3 mmol/l) increased E2 secretion from 360 +/- 45 to 1242 +/- 133 pmol/l) in the absence of FSH. Further, EGTA (3 mmol/l) markedly potentiated FSH (8 IU/l), forskolin (1 mumol/l) and dibutyryl cAMP (1 mmol/l)-stimulated E2 secretion. Addition of the Ca2+ ionophores, ionomycin (2-5 mumol/l) and A23187 (2 mumol/l), inhibited FSH (8 IU/l)-stimulated E2 secretion by greater than 80%. The effect of ionomycin was totally reversible, whereas that of A23187 was irreversible. Ionomycin (5 mumol/l) had no effect on EGTA-induced E2 secretion in the absence of FSH, but reduced EGTA-provoked E2 secretion by 59% in the presence of FSH (8 IU/l). Similarly, forskolin- and dibutyryl cAMP-provoked E2 production was inhibited 46-50% by ionomycin (5 mumol/l). We conclude that FSH-induced E2 secretion from immature rat Sertoli cells is modulated by intra- and extracellular Ca2+.

Animals↗
PubMed1991

Inhibition of protein kinase C by staurosporine increases estrogen secretion by rat Sertoli cells.

We have examined the effect of inhibition of protein kinase C activity by staurosporine on estradiol secretion by Sertoli cells isolated from 8-10 days old rats. Staurosporine lead to a dose-related increase in estradiol secretion independent of FSH, such that with 100 nmol/l staurosporine basal estradiol levels increased 10-fold. The maximal response seen with staurosporine alone (100 nmol/l) or in combination with FSH (0.4-8 IU/l) was similar to that seen with a saturating dose of FSH (8 IU/l). There was no evidence of synergy between FSH and staurosporine. Activation of protein kinase C by phorbol 12,13 dibutyrate (10(-7) mol/l) resulted in a 53-74% inhibition of estradiol production provoked by FSH (8 IU/l), staurosporine (5-100 nmol/l) or staurosporine in combination with FSH. Staurosporine (5-100 nmol/l), in the absence or presence of FSH, was unable to overcome inhibition of estradiol secretion by phorbol ester, indicating the presence of at least two independent binding sites on protein kinase C for these molecules. Forskolin (1 mumol/l)- and dibutyryl cAMP (1 mmol/l)-stimulated estradiol secretion was inhibited by 31 +/- 5% and 64 +/- 5% respectively, by phorbol 12,13 dibutyrate (10(-7) mol/l). We conclude that FSH-induced estradiol secretion in immature rat Sertoli cells is affected by protein kinase C activity.

Alkaloids↗
PubMed1991

[Intestinal absorption of insulin with a new telemetric shuttle in dogs].

Telemetric shuttles for the in vivo investigation of the gastrointestinal tract have been available for sometime. We describe herein the use of a new shuttle model whose original features include: a) continuous, real time transmission of its location in the small bowel and accurate measurement of the gut length, b) controlled release of 1 ml of a given substance at any chosen site, allowing detailed investigation of intestinal absorption at different levels of the small bowel under physiological conditions. Small bowel length was measured in dogs using the shuttle and was later compared to the actual small gut length measured in the same animals at laparotomy. The telemetric measurements appeared to closely match the direct operative measurements. Insulin absorption from the canine small bowel was then investigated releasing different dosages of insulin together with the pancreatic enzyme inhibitors Soybean and Aprotinine and a surfactant (5-methoxysalicylate). By adjusting the dose of insulin released, the type of adjuvant substance delivered with it and the site of release in the small bowel, we have been able to precisely define the conditions of insulin absorption. Insulin as such is exclusively absorbed in the ileum when released in doses of 500 IU or higher and mixed with aprotinine. For absorption to take place the solution delivered by the shuttle needs to have the correct pH and natremic concentration.

Animals↗
PubMed1990

Urinary proteins and red blood cell membrane negative charges in diabetes mellitus.

The nature and origin of proteinuria in diabetes mellitus have been investigated by measuring the urinary excretion of seven specific proteins of low (beta 2-microglobin, retinol-binding protein) or high molecular weight (albumin, transferrin, hemopexin and IgG). Using the Alcian Blue binding test, we also measured negative charges on red blood cell (RBC) membrane which according to recent studies might mirror the glomerular polyanion charge. A group of 190 diabetics was examined, including 90 patients with type I diabetes, 23 type II diabetics treated with diet and/or hypoglycaemic agents and 77 longstanding type II diabetics requiring insulin therapy. With the exception of beta 2-microglobulin all proteins measured were excreted in the urine of diabetics in significantly higher amounts than in controls. The assay of transferrin proved the most sensitive (58% positive) followed by albumin (49%), IgG (34%), hemopexin (28%) and retinol-binding protein (26%). Practically the same ranking was obtained when only type I diabetics were considered. RBC membrane negative charges were diminished in diabetics and negatively correlated with the urinary excretion of albumin (r = -0.61, n = 190). RBC charges were also negatively correlated with other urinary proteins of high molecular mass (r between - 0.5 and - 0.2) but presented no relation with urinary beta 2-microglobulin or retinol-binding protein. The loss of RBC charges in diabetics most likely reflects the concomitant depletion of the glomerular polyanion responsible for the increased glomerular leakage of high molecular mass plasma proteins. The preferential increase in transferrin excretion together with the progressive rise in the urinary excretion of IgG lead us to postulate that the loss of glomerular polyanion in diabetes is accompanied, from the early stage, by a progressive decrease in the size-selectivity of the glomerular filter. The urinary excretion of retinol-binding protein was weakly correlated with albuminuria (r = 0.26, n = 186). Eight % of diabetics showed an elevation of urinary retinol-binding protein without evidence of microalbuminuria, which clearly demonstrates that a proximal tubular impairment can occur independently of the glomerular alterations in the course of diabetic nephropathy.

Adult↗
PubMed1990

ACTH adrenal cell bioassay: improved sensitivity (12 ng/L) achieved by immunoextraction of ACTH from human plasma by a monoclonal antibody.

We have previously reported a bioassay for human plasma ACTH based upon trypsin dispersed guinea-pig adrenal cells which was sensitive to 100 ng/L ACTH in unextracted human plasma when measured against human pituitary ACTH (1-39) standard 74/555. We now present a bioassay of increased sensitivity (12 ng/L) which incorporates three major changes. The trypsin/trypsin inhibitor step in the cell dispersion protocol has been replaced with collagenase, donor calf serum (3%) has been incorporated into the standard curve and ACTH has been extracted from human plasma and dilutions of standard hormone by a sephacryl bound monoclonal antibody (2A3) directed towards the 25-39 sequence. The extracted standard curve has a detection limit of 6 ng/L and the cells can tolerate up to 50% plasma equivalent concentration. Thus, the improved assay has a detection limit of 12 ng/L ACTH in plasma. The assay can now measure bioactive plasma ACTH levels reliably in the normal range.

Adrenal Glands↗
PubMed1990

Environment and host-parasite relationships in Monogenea.

The interest of a new approach in taking up the problems of host-parasite relationships with environment is proposed in terms of population biology. Two different integrating levels are considered: a microenvironment that corresponds particularly to the host and a macroenvironment corresponding to the whole host-parasite system. Some examples are given that provide significant reasons in perceiving the biology of Monogenea under these aspects. To conclude we emphasize the importance of developing this new way for the study of hybrids models in relation to parental host systems.

Amphibians↗
PubMed1990

[Difference in the action of prostaglandin E2 (PGE2) on longitudinal circular muscle contractions of the colon. Experimental study in dogs].

The effect of prostaglandin E2 (PgE2) on the circular and longitudinal contractions of the canine colon was studied in chronic conditions. A mechanical transducer developed in our laboratory and implanted on the canine colon collected simultaneously and separately the variations of length in two perpendicular directions. The recordings started at the 6 postoperative day. The colonic motility was recorded two hours before (as control period) and two hours after the intravenous injection of PgE2 at three different doses: 0.1-1.0 and 10 micrograms/kg. PgE2, at the three doses, induced, progressively over time, a significant decrease in duration and amplitude of the circular contractions, while the amplitude of longitudinal contractions remained unchanged. 10 micrograms/kg of PgE2 immediately induced a significant increase in the duration of longitudinal contractions followed by a decrease in this value during the 2nd hour after PgE2 administration. Each dose of PgE2 shortened the period of recurrence of longitudinal contractions, inducing rapid or immediate bursts of contractions. This effect was moderate or absent for the circular contractions. It is concluded, that PgE2 has different actions on circular and longitudinal contractions of the colon. According to the dose used, it induces hypokinesia (relaxation) in the circular muscle and premature strong contractions in the longitudinal motor activity.

Animals↗
PubMed1989

The effect of some antiprostatic steroids upon cortisol production by guinea-pig adrenal cells stimulated by ACTH.

The antiprostatic steroids 6-methylene-4-pregnene-3,20-dione (6-MP) (I), 17-alpha-acetoxy-6, 16-dimethylene-4-pregnene-3,20-dione (II), and melengestrol acetate (MGA) (III) were incubated with guinea-pig adrenal cells, both alone and maximally stimulated with ACTH. Cortisol output was then measured by RIA. Increased cortisol-like secretion was obtained with 6-MP in the absence of ACTH. In the presence of ACTH, cortisol-like steroid secretion was the sum of that seen with ACTH and 6-MP alone. It follows that 6-MP stimulates in vitro a cortisol-like steroid cross reacting with the cortisol antibody by a mechanism that by-passes ACTH. Steroid (II) weakly inhibited cortisol output. MGA, in contrast, proved to be a strong inhibitor of cortisol output (ID50 of 2.3 mumol/l). Its site of action was established by adding it to adrenal cells incubated with precursor steroids on the cortisol pathway. Conversion of 3 beta-hydroxysteroids to cortisol was inhibited whereas conversion of 3-keto steroids was not affected. It follows that MGA inhibits 3 beta-hydroxysteroid dehydrogenase.

3-Hydroxysteroid Dehydrogenases↗
PubMed1989

Assessment of the bioactivity of human and bovine thyrotrophin preparations using a porcine thyroid cell bioassay.

The biopotency of six preparations of thyrotrophin (TSH) has been compared in a highly sensitive in vitro porcine thyroid cell bioassay using iodide uptake as an endpoint. Three of these preparations were of human origin and three derived from bovine pituitary tissue. One human TSH preparation, the 2nd International Reference Preparation, 80/558, was used to calibrate the other five. The log dose-log response curves for all preparations were sigmoidal in shape. For the purpose of evaluation the central linear portions of the curves were compared. With all preparations the slopes in this region were very similar. The relative biopotencies of the bovine preparations (unit:unit) were at least five times those of the human standards when measured using the porcine thyroid cell bioassay. These findings emphasise the need to control the TSH standards employed in a variety of bioassays, particularly those used for between-laboratory comparison.

Animals↗