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Biomedical subjects

H Lovell

Publications and source records attributed to H Lovell.

10 recordsLinked to original sources

Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis.

BACKGROUND: Heavy proteinuria and progressive renal injury recur after transplantation in up to 40 percent of patients with renal failure caused by idiopathic focal segmental glomerulosclerosis. A circulating factor may be responsible for this recurrence. METHODS: To determine whether patients with focal segmental glomerulosclerosis have a circulating factor capable of causing glomerular injury, we tested serum samples from 100 patients with the disorder in an in vitro assay of glomerular permeability to albumin. Of the 56 patients who had undergone renal transplantation, 33 had recurrences. Sixty-four patients, many of whom had undergone transplantation, were being treated with dialysis. Thirty-one patients with other renal diseases and nine normal subjects were also studied. RESULTS: The 33 patients with recurrent focal segmental glomerulosclerosis after transplantation had a higher mean (+/-SE) value for permeability to albumin (0.47+/-0.06) than the normal subjects (0.06+/-0.07) or the patients who did not have recurrences (0.14+/-0.06). After plasmapheresis in six patients with recurrences, the permeability was reduced (from 0.79+/-0.06 to 0.10+/-0.05, P = 0.008), and proteinuria was significantly decreased. Patients with corticosteroid-sensitive nephrotic syndrome or with membranous nephropathy after transplantation had low levels of serum activity. The circulating factor bound to protein A and hydrophobic-interaction columns and had an apparent molecular mass of about 50 kd. CONCLUSIONS: A circulating factor found in some patients with focal segmental glomerulosclerosis is associated with recurrent disease after renal transplantation and may be responsible for initiating the renal injury.

Adult↗

Brain-reactive autoantibodies in BB/d rats do not recognize glutamic acid decarboxylase.

The BB rat spontaneously develops insulin-dependent diabetes mellitus (IDDM) similar to that in humans. The most practical markers of beta cell autoimmunity are circulating antibodies to islet cell components. In particular autoantibodies to the enzyme glutamic acid decarboxylase (GAD) are a common feature of IDDM development in humans. This study aims at investigating the prevalence and levels of autoantibodies in BB rats to antigens in a semipurified, GAD-enriched preparation from rat brain. Eighteen diabetes-prone BB/d rats (10 male and eight female) were tail bled weekly from age 28 days to 113 days and antibodies detected on the rat brain preparation by ELISA. Antibody levels were expressed as arbitrary units relative to a standard positive serum. Individual rats varied in the time and order of antibody appearance and IDDM onset, with the earliest occurrence being 42 days and 69 days, respectively. In some rats antibody production was maintained but declined in others. By 113 days 85% of diabetic rats had at some time been positive for autoantibodies to brain components, compared with 25% of non-diabetics (P = 0.09 by Fisher's exact test). Immunoabsorption studies using recombinant rat GAD-65 or recombinant human GAD-67 failed to inhibit the binding of BB rat sera to the original rat brain preparation. A capture ELISA using GAD-6 MoAb to capture GAD-65 from rat brain preparation or from a preparation of recombinant rat GAD-65, failed to detect anti-GAD antibodies in BB rats. Immunofluorescent staining of tissue sections showed the autoantibodies to be brain-specific, but having distinct staining patterns to the anti-GAD antibodies of Stiff Man Syndrome serum. In conclusion, BB rats possess autoantibodies reactive with rat brain antigens which may be associated with IDDM. However, these are not directed against GAD.

Animals↗

Sexual development of malaria parasites is inhibited in vitro by the neem extract azadirachtin, and its semi-synthetic analogues.

We have shown that azadirachtin, a compound from the neem tree, Azadirachta indica, and selected semi-synthetic derivatives, block the development of the motile male malarial gamete in vitro. Changes in the hemiacetal group at position C11 in the molecule result in a loss of activity in this assay. The motility of fully formed male gametes, and other selected flagellated cells, is unaffected by azadirachtin in vitro. These findings raise the possibility of developing azadirachtin-based compounds as antimalarials with transmission-blocking potential, as well as permitting the further study of structure-activity relationships in these compounds.

Animals↗

Growth and development of infants with end-stage renal disease receiving long-term peritoneal dialysis.

The growth and development of four infants with end-stage renal disease receiving long-term peritoneal dialysis was studied during the first year of life. In each patient, dialysis was begun before 4 weeks of age. A nutritional regimen was designed to attain a daily weight gain appropriate for height age while minimizing the blood urea nitrogen level. A neurodevelopmental evaluation of gross and fine motor, cognitive, language, and psychosocial skills was performed at least every 3 months. At age 1 year, the mean height standard deviation score (SDS) was -1.33 +/- 0.2. Weight for height was greater than 95th percentile in one patient and normal in three. Mean caloric and protein intake were 105 +/- 20 kcal/kg/d (11.4 +/- 2.7 kcal/cm/d) and 2.7 g/kg/d (0.30 +/- 0.11 g/cm/d), respectively. Mean blood urea nitrogen was 53.6 +/- 17.8 mg/dL. Developmentally, three of the patients were functioning in the normal range and one was mildly retarded. However, gross motor skills were delayed in all patients. Although infants with end-stage renal disease are usually severely growth retarded and developmentally delayed, our observations suggest that early nutritional intervention and dialysis can yield improved results.

Blood Urea Nitrogen↗