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Biomedical subjects

S Lawrence

Publications and source records attributed to S Lawrence.

At least 91 records · Page 5Linked to original sources

Delayed lung maturation in the macrosomic offspring of genetically determined diabetic (db/+) mice.

We studied a genetically determined diabetes in pregnancy, the heterozygous diabetes (db/+) mouse. We found that fetal mice from these pregnancies are macrosomic with increased body, lung, and placenta wt, have altered organ protein, DNA and phospholipid content, and exhibit abnormal carbohydrate metabolism with increased liver and glycogen content. We further studied the effect of increased substrate availability and utilization on lung growth and maturation in (db/+) fetal mice, by measuring lung phospholipid synthesis as represented by the incorporation of the radiolabeled precursors, [3H]choline and [14C]glycerol, in fetal lung at 18 days' gestation (term = 19). Diabetic fetuses incorporated significantly more [3H]choline into disaturated phosphatidylcholine than controls (1.32 +/- 0.10 X 10(-2) versus 0.78 +/- 0.05 X 10(-2) nmol/g protein/min, mean +/- SE; p less than 0.001), but significantly less [14C]glycerol into phosphatidylglycerol than controls (3.18 +/- 0.38 versus 4.91 +/- 0.53 nmol/g protein/min, mean +/- SE; p less than 0.002), and their phosphatidylglycerol/phosphatidylinositol synthesis ratios were decreased (1.81 +/- 0.18 versus 3.17 +/- 0.14; mean +/- SE; p less than 0.001). Diabetic fetal lungs appeared morphologically less mature than controls at 18 days' gestation, as shown by a significantly decreased air space density (0.27 +/- 0.01 versus 0.43 +/- 0.02, mean +/- SE; p less than 0.001) and alveolar epithelial cell/total tissue ratio (0.54 +/- 0.02 versus 0.66 +/- 0.03, mean +/- SE; p less than 0.01). The increased synthesis of lung disaturated phosphatidylcholine in diabetic fetal mice may reflect the enhancement of body and lung growth in these macrosomic fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Increased binding of epidermal growth factor to placental membranes of intrauterine growth restricted fetal rats.

To examine the relationship between nutrient supply and fetal and placental growth, we examined epidermal growth factor (EGF) binding to membranes prepared from placentas of growth-restricted fetal rats. Intrauterine growth retardation was accomplished by unilateral ligation of the uterine artery; fetal rats on the contralateral uterine horn served as controls. Fetal growth restriction was accompanied by decreased placental wt at 19 and 20 day's gestation and significantly decreased placental glycogen content at 20 and 21 days, 30% and 15%, respectively. Placental DNA content and protein/DNA ratios were similar in the growth-restricted and control groups. Specific binding of 125I-EGF was increased in growth-restricted placentas at 19 and 20 days' gestation by 32% and 16%, respectively. 125I-EGF binding at 20-21 days increased linearly with the extent of placental growth restriction. Competitive binding experiments yielded linear Scatchard plots with an increased receptor density in growth-restricted placenta at 19 and 20 days' gestation, 74% and 60%, respectively. Binding affinities for the EGF receptor were similar in the two groups. The increased binding of EGF to membranes prepared from growth-restricted fetal rats may serve to enhance nutrient uptake under conditions of decreased uterine blood flow.

Animals↗

[14C]-triolein absorption: a useful test in the diagnosis of malabsorption.

The [14C]-triolein absorption test has been assessed using a preprepared fat meal in a procedure that can be completed within a working day on an inpatient or outpatient basis. An initial study showed complete discrimination between 30 control subjects and 13 patients with raised faecal fat excretion. A prospective evaluation in 57 patients under investigation for gastrointestinal disease showed a sensitivity of 85% and specificity of 93% (100% if two obese subjects are excluded). The test discriminates satisfactorily between patients with and without fat malabsorption and makes the measurement of faecal fat unnecessary in most circumstances.

Adult↗

Feasibility of extended wear lens use in chlorinated swimming pools.

A group of 14 active swimmers was studied to evaluate corneal and conjunctival health immediately after extended wear contact lenses were worn in a chlorinated swimming pool. Two different lenses, a high (70%) and a low (38%) water content, were used for each subject in order to compare the corneal response to the high and low water content lenses. No significant difference in corneal and conjunctival response was found between the two lenses. Statistically significant differences were seen in corneal thickness and halo size between swimming with and without contact lenses. Corneal superficial erosion was of greater concern under both the control and test conditions, but this is believed to be due to unforeseen experimental design errors. The frequency of contact lens loss in this study was 3.57%. Hence, the conclusion that the rate of loss of hydrophilic lenses in a swimming situation is not the only concern in regard to lens wear during swimming, but there are other important factors such as lens adherence to the cornea and bacterial contamination of the lenses that need to be studied further.

Chlorine↗

Factors influencing reticulophagocytic function in insulin-treated diabetes.

The splenic component of reticulophagocytic function (RPF) was examined in 29 insulin-treated diabetic subjects (13 type I and 16 type II) by measurement of clearance of altered, radiolabeled, autologous erythrocytes. Double-isotope studies were performed with cells altered by: (1) preincubation with N-ethylmaleimide (NEM) and (2) coating with IgG antibody to the Rhesus (Rh) D antigen, labeled with 99mTc and 51Cr, respectively. HLA typing for the A, B, and DR loci was performed in those patients showing a defect in the clearance of IgG-coated cells. Values for half-life (t1/2) were correlated with the incidence of diabetic complications, levels of HbA1, and circulating immune complexes (CIC). Two patterns of abnormal clearance were observed: first, an isolated defect of IgG-coated cell clearance in 7 patients (3 had the HLA B8/DR3 haplotype) and second, abnormal removal of both types of cell in a further 7 patients (3 had B8/DR3). There was no correlation between half-lives as measured by the two methods, although exclusion of the patients with a defect of IgG-coated cell clearance alone yielded a highly significant correlation for the remaining 15 Rh-positive patients (P less than 0.01). Abnormalities of IgG-coated cell clearance were more frequent in patients with HbA1 greater than 9% (P less than 0.02), while t1/2 of NEM-altered cells was significantly greater in patients with CIC (P less than 0.05). There was no correlation between t1/2 and the incidence of peripheral complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Mesangial IgA nephropathy: detection of defective reticulophagocytic function in vivo.

The splenic component of the reticulophagocytic system (RPS) was studied in 20 patients with primary mesangial IgA nephropathy and 15 healthy controls. Eight patients were hypertensive, seven had renal failure and six had significant proteinuria. RPS function was assessed by the measurement of T1/2 clearance of altered, radio-labelled autologous erythrocytes. Three different methods were used to alter the red cells - thermal stress, sulfhydryl inhibition with N-ethylmaleimide (NEM) and antibody-coating - and in 12 patients two of these methods were used simultaneously in double-isotope-labelled studies. Impaired clearance was demonstrated in 16 of the 20 patients. T1/2 of NEM-altered cells was abnormal in 12 of 19 studies in 17 patients (i.e. T1/2 greater than 22.5 mins) while T1/2 of IgG-coated cells was abnormal in 8 of 10 patients (i.e. T1/2 greater than 62 mins). The clearance of thermally-damaged cells was not significantly different from that observed in controls (normal range: 10.5-17 mins). In the double-isotope studies, the clearance of NEM-altered cells correlated with the clearance of IgG-coated cells (P less than 0.05). There was no correlation between T1/2 clearance times and circulating immune complexes. These abnormalities of splenic function suggest there is a primary reticulophagocytic defect in patients with mesangial IgA nephropathy. This finding could bear relevance to the pathogenesis of the disease.

Adolescent↗

Association of Sjögren's syndrome with C4 deficiency, defective reticuloendothelial function and circulating immune complexes.

A case of Sjögren's syndrome with the sicca complex is presented which was associated with persistently low or absent C4 levels, high levels of circulating immune complexes and abnormal reticuloendothelial clearance of damaged or IgG antibody sensitized autologous red blood cells (RBCs). Investigation of normal relatives of the patient revealed low C4 levels and abnormal reticuloendothelial clearance of damaged or sensitized RBCs. HLA, A, B, DR typing revealed a high incidence of the HLA B8, DR3 haplotype and of homozygous null alleles at the C4A locus in the family members. These results suggest that the C4 deficiency and the abnormal reticuloendothelial function in the patient was in part genetically determined and may have predisposed to the development of Sjögren's syndrome. These findings serve to emphasize the possible importance of abnormal macrophage function in the pathogenesis of Sjögren's syndrome and suggest that further investigation of these aspects may increase understanding of this disease.

Antigen-Antibody Complex↗