A plan to ensure standards in residential homes.
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Biomedical subjects
Publications and source records attributed to A Lambert.
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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.
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.
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.
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.
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.
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.
Gastric bezoars were observed after esophageal variceal injection of polidocanol in 5 of 56 patients with alcoholic cirrhosis treated by endoscopic sclerosis. We suggest that endoscopic sclerotherapy could have induced a transient vagal injury resulting in delayed gastric emptying and subsequent bezoar formation. Although the volume of sclerosant (25-35 ml per session) and the length of the injector needle (4 mm) were the same in all patients, two reasons could explain the occurrence of bezoars in these five patients: a deeper injection of sclerosant, and a worsening of a preexistent vagal neuropathy due to diabetes mellitus and/or alcoholism.
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To investigate whether Addison's disease may in some cases be due to the blocking of adrenocorticotrophic hormone's action at the adrenal cortex by antibodies IgG isolated from a woman with Addison's disease associated with the autoimmune polyglandular syndrome type I was studied. Its effects on guinea pig adrenal cells in vitro were investigated and compared with those of IgG from three normal subjects and IgG obtained commercially. IgG from the patient inhibited the stimulation of cortisol secretion by adrenocorticotrophic hormone by 77 (SD 2)% and 57 (12)% at concentrations of 0.5 and 0.05 g/l, respectively; IgG prepared five months after she had started treatment with replacement steroids inhibited cortisol secretion by 74 (1)% (0.5 g/l) and 51 (15)% (0.05 g/l). The other IgGs had no inhibitory effects. The IgG from the patient and that obtained commercially did not inhibit the stimulation of cortisol secretion by dibutyryl cyclic adenosine monophosphate or precursors of cortisol. None of the IgGs bound to adrenocorticotrophic hormone. These results suggest that the IgG from the patient acted against the receptor for adrenocorticotrophic hormone, and its presence may explain the patient's raised concentrations of adrenocorticotrophic hormone, failure to respond to exogenous adrenocorticotrophic hormone, and normal basal cortisol concentrations. Addison's disease may thus in some instances be a receptor antibody disease.
The evolutionary geographic origin of Diplozoon and Octomacrum (Monogenea, Polyopisthocotylea) is discussed. Diplozoon occurs in Eurasia and Africa, whereas the distribution of Octomacrum is limited to North-America. These two monogeneans likely had a common progenitor originating from the Pacific. This hypothesis is suggested by the morpho-anatomical resemblances between Diplozoon and Octomacrum and by the analysis of their geographic distribution.
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The degree of stability in vitro of bioactive and immunoreactive LH in human blood, plasma and serum was examined. Bioactivity and immunoreactivity of LH were assayed by the dispersed mouse Leydig cell assay and by standard radioimmunoassay respectively, using the same reference preparation (first international reference preparation for human pituitary LH 68/40 for immunoassay). Bioactive and immunoreactive LH were stable in blood and plasma at 22 degrees C for up to 4 and 24 h respectively, and in blood at 4 degrees C for up to 24 h. There was no loss of biological or immunological LH activity in plasma which had been either snap-frozen and stored at -70 degrees C, allowed to freeze at -20 degrees C and stored at that temperature or kept at 4 degrees C for 24 h and then stored at -70 degrees C. Likewise, the levels of LH in plasma and serum which had been stored at either -20 or -70 degrees C and then thawed and refrozen up to four times remained unchanged. In addition, the biological and immunological activity of LH was not affected after vortexing samples of plasma or serum for up to 60 s. Bioactive LH was also stable in plasma samples after prolonged storage (up to 9 months) at either -70 or -20 degrees C. We conclude that LH bioactivity and immunoreactivity are stable in blood and plasma following a variety of treatments commonly experienced during normal handling of a blood sample after venepuncture.
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The effect of six drugs on the uptake and organification of iodide by porcine thyroid cells stimulated with bovine TSH (10 miU/L) has been investigated. The drugs fall into two categories: the peroxidase inhibitors, methimazole (MMI), 2-thiouracil (2-TU) and 3-amino 1,2,4 triazole (3-ATA) and the ionic inhibitors, lithium chloride (LiCl), potassium perchlorate (KC10(4], and sodium iodide (NaI). All the drugs led to a dose-related inhibition of iodide metabolism. The most potent effect on iodide uptake was seen with NaI which inhibited this function by 20% even at 10(-8) mol/l. In contrast, the most potent effect on iodide organification was observed with methimazole which led to a 25% inhibition at 10(-8) mol/l. The concentrations of drug which gave rise to a 50% inhibition of iodide uptake were (mumol/l) 0.26 (NaI), 3.5 (KClO4), 9.7 (2-TU), 15 (MMI), 26 (3-ATA), and 1500 (LiCl). The comparable figures for organification were 0.13 (MMI), 0.18 (2-TU), 0.23 (NaI), 1.2 (3-ATA), 15 (KClO4) and 1300 (LiCl). We conclude that this in vitro system has considerable potential for the assessment of potency and possible bioassay of anti-thyroid drugs of varying structures and sites of action.
A fibrinogen derivative generated by thrombin was reacted with elastin to yield a new addition product or adduct between the two proteins. Addition of fibronectin, and then of collagen, did not interfere with the basic elastin-fibrinogen reaction and conferred the qualities of an artificial connective tissue to the product. Biochemical, structural and biomechanical aspects of the new matrix were studied. Aprotinin, heparin, thiomersal, and thiourea did not inhibit the main reaction; indeed, some of these ingredients improved the matrix cohesion. Scanning electron microscopy showed the genesis of a true network whose meshes were more reticulated by the addition of thiourea. Biomechanical studies, i.e., strength and elasticity showed the thiourea matrix to be the strongest. These intrinsic properties suggest the product could have biological and clinical applications.