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Biomedical subjects

A Lambert

Publications and source records attributed to A Lambert.

At least 37 records · Page 2Linked to original sources

Exogenous steroids and the control of oestradiol secretion by human granulosa-lutein cells by follicle stimulating hormone and insulin-like growth factor-I.

This study first examined the relative activities of 17 alpha-hydroxylase, 17,20-lyase and aromatase in human granulosa-lutein cells by challenging the cells with steroid precursors in the oestradiol biosynthetic pathway. When cells from four patients were challenged with precursor steroids on the pathway to oestrogen synthesis (pregnenolone, 17 alpha-hydroxypregnenolone, progesterone, 17 alpha-hydroxyprogesterone and androstenedione at 5 x 10(-6) M), oestradiol (nmol/l) outputs after 1 day of culture were (median, interquartile range) as follows: 4.1 (2.1-8.8; pregnenolone), 3.1 (1.7-6.0; progesterone), 12.5 (6.9-18.1; 17 alpha-hydroxypregnenolone), 8.2 (4.1-16.7; 17 alpha-hydroxyprogesterone) and 251 (140-819; androstenedione). No further increases were seen when the steroid concentration was increased to 1 x 10(-5) M. Basal oestradiol secretion was 3.5 (1.6-8.2) nmol/l. We conclude that the conversion of pregnenolone/progesterone to oestradiol by granulosa-lutein cells is rate limited by 17 alpha-hydroxylase activity but that these cells are capable of oestradiol secretion (in the nmol/l range) in the absence of androstenedione. In the second part of this study we examined the control of granulosa-lutein oestradiol secretion by follicle stimulating hormone (FSH) and insulin-like growth factor-I (IGF-I) in the presence and absence of exogenous androstenedione (10(-6) M). Cells were cultured for up to 6 days and basal oestradiol (nmol/l) fell dramatically over this period both in the presence and absence of androtenedione, e.g. from 339 (223-419) (median and interquartile range, cells from five patients cultured in the presence of androstenedion) after 2 days to 14 (7-59) after 6 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde-Lyases

[Subcapsular liver hematoma, a HELLP syndrome complication].

The authors report a case of unruptured subcapsular haematoma of the liver in a 31-year-old woman, para 2, in the 34th week of pregnancy, complicated by preeclampsia. Clinical signs of preeclampsia were associated with pain in the right hypocondrium and laboratory findings consistent with a true HELLP syndrome. The diagnosis of subcapsular haematoma was confirmed by tomodensimetry. A cesarean section was carried out but a conservative treatment of the hepatic haematoma was decided. Regular X-ray follow-ups showed the regression of the hepatic lesion. This case confirms recent reports that patients with unruptured capsular haematoma should be treated conservatively but should receive careful monitoring.

Adult

[Aneurysmal malformation of the extrahepatic portal vein].

Malformations of extrahepatic portal vein are rare. We report a case of extrahepatic portal vein aneurysm which was incidentally found in a female patient, aged 67, suffering from alcoholic cirrhosis. This malformation was located at the portal bifurcation and presented ultrasonically as an oval, non-echogenic, parahilar mass, 38 mm in diameter, and in continuity with the portal trunk. On CT-scan and angiography, diagnosis of portal vein aneurysm located at its extrahepatic segment was confirmed. The cause of extrahepatic portal vein aneurysm remains controversial. A congenital and/or acquired origin induced by portal hypertension explains their development.

Aged

A left visual field bias for semantic encoding of unattended words.

Previous studies have shown that verbal processing in both normal individuals and a split-brain patient can be strongly affected by the semantic category of an unattended word presented to the left visual field (LVF). The effect was interpreted in terms of inhibition, since responses were slower when the unattended LVF word belonged to the same category as the target word. The present experiment discriminated between two alternative explanations for this finding. Subjects were presented with two letter strings, one in central vision and one to the left or right of centre. Subjects made a speeded lexical decision to the central string, and were instructed to ignore the lateral string. When a word was presented to the LVF subjects responded more slowly when it was semantically related to the central word. When an unattended word was presented to the RVF, its semantic relationship to the central word had no effect on decision latency. This finding is discussed in relation to views of performance laterality and selective attention.

Analysis of Variance

Insulin-like growth factor-I stimulated growth and progesterone production by granulosa-lutein cells. Lack of interaction with physiological concentrations of luteinizing hormone and follicle stimulating hormone.

This study examined the effect of physiological concentrations of insulin-like growth factor-I (IGF-I), follicle stimulating hormone (FSH) and luteinizing hormone (LH) alone and in combination on growth and progesterone production by human granulosa-lutein cells. Granulosa-lutein cells were obtained from patients (n > 5) undergoing in-vitro fertilization (IVF) or gamete intra-Fallopian transfer (GIFT) treatment. Cells were cultured for 2 and 4 days in the presence of physiological concentrations of human LH (code 68/40, 5 IU/l), FSH (code 83/575, 20 IU/l), or IGF-I (30 ng/ml) alone and in combination. Medium was changed every 2 days. No change in cell number (relative to each patient's own control) was observed after treatment with FSH or LH alone or in combination at any time. IGF-I alone produced a 117 +/- 8% and 176 +/- 15% (mean +/- SEM, n = 5) increase in cell number after 2 and 4 days respectively. This increase was unaffected by the addition of LH or FSH at any time. Basal progesterone secretion was variable (1633, 975-2409 nmol/l, median and interquartile range, day 2) and decreased with time in culture (564, 375-1089 nmol/l, day 4). After 2 days culture progesterone output increased by 116 +/- 5% of control in response to LH and 153 +/- 13% (mean +/- SEM, n = 5) of control in response to IGF-I. After 4 days, LH and IGF-I stimulated progesterone levels by 279 +/- 52% and 264 +/- 37% (mean +/- SEM, n = 5) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstenedione

[Neonatal thrombosis of the aortic arch].

The authors report a case of aortic arch thrombosis in a neonate probably related to perinatal placental emboli. However the finding of a fibroblastic endarteritis raised the possibility of a primitive lesion of the aortic wall. The evolution was complicated by cerebral ischemia. A surgical thrombectomy was performed. The outcome was favourable with persistence of a moderate right motor deficiency at 9 months. The authors advise the addition of an enlargement patch and the use of anticoagulation therapy in case of intimal lesion or very adherent thrombus.

Aorta, Thoracic

[Diffuse neonatal hemangiomatosis. A case with tetralogy of Fallot].

In neonatal disseminated hemangiomatosis, multiple immature capillary hemangiomas are widely distributed in the skin, mucous membranes, and internal organs including the liver, lungs, and larynx. In patients with life-threatening visceral involvement, corticosteroids or interferon may be required. A case in a female infant with tetralogy of Fallot is reported.

Adrenal Cortex Hormones

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

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

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

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

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

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

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

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

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

[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