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Biomedical subjects

D M Ford

Publications and source records attributed to D M Ford.

At least 19 recordsLinked to original sources
PubMed2000

Cystic renal lymphangiectasia presenting as renal insufficiency in childhood.

Cystic renal lymphangiectasia is an unusual cause of cystic renal disease in childhood. We present a case of bilateral cystic renal lymphangiectasia in a 7-year-old boy who presented with asymptomatic renal insufficiency and anemia with decreased erythropoietin production. The clinical features of this condition and the diagnostic approach are reviewed. Although rare, this disorder should be considered in the differential diagnosis of cystic renal disease.

Anemia↗
PubMed1998

The effects of salinity, pH and temperature on the half-life and longevity of Echinostoma caproni miracidia.

Miracidia of Echinostoma caproni were exposed to solutions varying in salinity, pH, and temperature in 1 ml concavity slides. Half-lives of the miracidial populations were determined and longevity curves constructed to find maximum life spans of the miracidia in the different conditions. Control miracidia in aquarium water at pH 7.2 and 22 degrees C. had a half-life of 3.6 h and a maximum life span of 9 h. Miracidia of E. caproni were not very tolerant of saline solutions from 0.1% to 0.4%, the latter being lethal within an hour. A bimodal effect was found with exposure to aquarium water of varying pH, with a peak at pH 5 in acid solutions and pH 9 in alkaline solutions. Miracidia tolerated pH ranges from 3 to 11 exhibiting half-lives of 2.4 h or greater in these solutions. At lower than ambient temperatures, E. caproni miracidia lived longer, the greatest being a half-life of 5.0 h and a maximum life span of 15 h at 5 degrees C. At warmer temperatures, the half-life was reduced until lethality was reached at 40 degrees C. ANCOVA analysis of log transformed longevity curves supported the observation that in pH trials many miracidia survived initially with a major die-off after 3.3 h. The opposite trend of early die-off and gradual mortality of the survivors was supported in the temperature trials.

Animals↗
PubMed1995

HWA-448 reduces gentamicin toxicity in LLC-PK1 cells.

An LLC-PK1 cell culture model was used to evaluate for a direct protective effect of the pentoxifylline analogue HWA-448 in gentamicin nephrotoxicity at the cellular level. Cells exposed to 2 mM gentamicin for 6 days displayed a significant decrease in specific activities of leucine aminopeptidase, NaK ATPase, and N-acetyl glucosaminidase, and an increase in total cellular phospholipids (P < .05). Concomitant exposure to 0.125 mM HWA-448, a dose that did not alter cellular enzymes or total phospholipids under physiologic conditions, prevented the alterations in marker enzymes and total phospholipids induced by gentamicin (P < .05). Gentamicin binding and uptake studies revealed 0.125 mM HWA-448 had no effect on LLC-PK1 cell plasma membrane binding or cellular gentamicin uptake. We conclude that HWA-448 ameliorates gentamicin-induced alterations in LLC-PK1 cell enzymes and phospholipids by a mechanism independent of plasma membrane binding or cellular uptake.

Animals↗
PubMed1994

Apically and basolaterally internalized aminoglycosides colocalize in LLC-PK1 lysosomes and alter cell function.

Aminoglycosides bind to apical and basolateral (BL) membranes of renal epithelial cells. However, little is known regarding differential uptake and intracellular processing after internalization across these distinct surface membrane domains. To examine these processes independently, LLC-PK1 cells were grown on porous filters, which allow selective access to both domains. Apical and BL membrane uptakes of gentamicin (0.5 mM), quantified using [3H]gentamicin, were linear from 2 to 24 h (r = 0.99). The 4-h apical gentamicin uptake was 667 +/- 59 pmol/mg protein, the BL 748 +/- 26 pmol/mg protein, and concurrent apical and BL uptake 1,389 +/- 22 pmol/mg protein. Aminoglycoside uptake, documented using indirect immunogold techniques, occurred via the apical and BL endocytic systems and colocalized with cationic ferritin. Aminoglycosides internalized via the apical (gentamicin) and BL (tobramycin) membrane converged at the lysosomal level. Gentamicin incorporated via either domain significantly decreased lysosomal N-acetylglucosaminidase below control values (P < 0.05). We conclude that, after binding, aminoglycosides are internalized equally across apical and BL membranes of LLC-PK1 cells via receptor-mediated endocytosis, colocalize within the lysosomal compartment, and alter cellular function similarly.

Aminoglycosides↗
PubMed1992

Childhood membranoproliferative glomerulonephritis type I: limited steroid therapy.

Nineteen patients with biopsy proven membranoproliferative glomerulonephritis type I (MPGN I) and a minimum of three years of follow-up (mean 6.5 +/- 0.7 years) have been treated with an uncontrolled regimen of limited corticosteroids. Initial therapy ranged from 20 mg per os (po) every other day to 30 mg/kg/day i.v. for three consecutive days, depending on clinical disease severity. Therapy was then decreased based on each patient's improving clinical status. At diagnosis creatinine clearance (CCr) was less than 80 ml/min/1.73 m2 in 12 patients and less than 50 in 2. All patients had hematuria and proteinuria, with 15 in the nephrotic range. Hypertension, present at diagnosis in 13, developed in five others following institution of prednisone, and was controlled medically. Renal biopsy was repeated after two years of therapy prior to cessation of treatment (mean total treatment duration 38 +/- 3 months). Follow-up biopsy revealed decreased glomerular inflammatory activity in 88% of patients. All patients have now been off prednisone for 40 +/- 9 months. The mean CCr is 126 +/- 5 ml/min/1.73 m2. Eight patients have normal urinalyses. These data suggest that early therapy with a limited course of corticosteroids, and control of associated hypertension, may forestall progressive renal insufficiency in children with MPGN type I.

Adolescent↗
PubMed1991

Hemolytic uremic syndrome complicated by vitamin K deficiency.

A 5-year-old child with hemolytic uremic syndrome developed bleeding due to vitamin K deficiency 9 days after the onset of a diarrheal prodrome. Vitamin K deficiency was documented by rapid correction of the PT and PTT and cessation of bleeding following administration of vitamin K, as well as by the detection of noncarboxylated prothrombin in plasma. The case is instructive because it suggests that previously healthy older children who become acutely ill may develop vitamin K deficiency more rapidly than heretofore has been appreciated.

Child, Preschool↗
PubMed1991

Abnormal proximal tubule apical membrane protein composition in X-linked hypophosphatemic mice.

The hypophosphatemic (Hyp) mouse is characterized by an isolated X-linked defect in proximal tubular phosphate (Pi) reabsorption associated with a decreased maximum velocity (Vmax) and a normal affinity (Km). To directly investigate the underlying cellular defect proximal tubular brush-border membranes (BBM) from normal control (Con) and Hyp male littermates were examined for differences in cholesterol content, total and individual phospholipid composition, phospholipid incorporation rates, membrane fluidity, and by two-dimensional sodium dodecyl sulfate (SDS)-polyacrylamide protein electrophoresis. The cholesterol content, total and individual phospholipid profiles, phospholipid incorporation rates, and membrane fluidity of Con and Hyp BBM samples were comparable. However, the two-dimensional gel electrophoreses of Con and Hyp BBM proteins, run simultaneously under identical conditions, revealed a protein with an apparent abnormal isoelectric migration pattern in Hyp BBM samples. This protein had an apparent molecular weight 56,000 and an apparent pI of 7.2 and was consistently evident on Hyp gels (n = 3) but not on Con gels (n = 3). The appearance of this protein band was associated with a diminution in staining of a control protein of comparable apparent molecular weight but markedly lower apparent pI.

Animals↗
PubMed1990

Pancreatitis in children on chronic dialysis treated with valproic acid.

Four children treated with maintenance dialysis, three peritoneal and one hemodialysis, developed pancreatitis while receiving valproic acid (VPA) for chronic seizure disorders. Two patients recovered, eventually resuming VPA therapy after successful cadaveric renal transplantation. Two children died after complications of pancreatitis. No episodes of pancreatitis occurred in the other 74 children in this maintenance dialysis population; none of whom received VPA. Although pancreatitis is a known complication of VPA treatment or end-stage renal disease (ESRD), this is the first reported series specifically relating pancreatitis to VPA administration in children treated with maintenance dialysis. The literature related to the association of pancreatitis with VPA administration and ESRD therapy is briefly reviewed and the clinical implications are discussed.

Child↗
PubMed1988

Muscle spindles in the paraspinal musculature of patients with adolescent idiopathic scoliosis.

Electromyographic studies have determined that muscle imbalance and asymmetry of stretch receptors in the paraspinal muscle of patients with idiopathic scoliosis may have a large role to play in the development and production of the deformity. This project consisted of a detailed histologic and histochemical analysis of the distribution of muscle spindles in paraspinal musculature of patients suffering from idiopathic scoliosis, using the reduced form of nicotinamide-adenine dinucleotide (NADH), adenosine triphosphatase (ATPase), and Tri-chrome stain techniques. Muscle biopsy samples were taken at operation for spinal instrumentation from each of 13 patients (mean age: 16.2 years; 3 males, 10 females) with all but one female exhibiting right thoracic curves. The samples were collected from two specific sites (superficial and deep) on both sides of the vertebral column at the level of the apex of the primary curve and two vertebral levels above and below the apex. From the results there appear to be few muscle spindles in the scoliotic muscle of this region. All of the patients from whom muscle samples were taken possessed at least one sample with a muscle spindle. However, each patient had very few samples which contained a minimum of one muscle spindle (mean: 20.3%; SD: 12.6). It is clear that further examination is necessary, particularly in the area of comparison with 'normal' standards when these standards become available.

Adolescent↗
PubMed1988

Photosynthesis and Other Traits in Relation to Chloroplast Number during Soybean Leaf Senescence.

Soon after attaining full expansion, soybean (Glycine max [L.] Merr.) leaves enter a senescence phase marked by decline in photosynthetic rate and the progressive loss of chloroplast activity and composition. Our primary goal was to determine if this loss could be accounted for by sequential degradation of whole chloroplasts or by simultaneous degeneration of all chloroplasts. Total photosynthesis (TPs) measured as (14)CO(2) uptake, chloroplast number, ribulose 1,5-bisphosphate carboxylase activity, uncoupled photosynthetic electron transport activity, soluble protein content, and chlorophyll content declined progressively during the 37 days after full leaf expansion. During this period, chloroplast number per unit leaf area was constant for all genotypes studied. We conclude that leaf senescence may be a two-stage process wherein the first stage chloroplast activity and composition declines, but chloroplast numbers do not change. During a brief terminal stage (11 days in our experiment), whole chloroplasts may be lost as well. As a second objective we wished to determine if variation in single-leaf total photosynthetic rate among soybean cultivars is related to corresponding variation in chloroplast number and/or chloroplast activity/composition. By comparing the means for three cultivars known to have rapid leaf TPs and for the three known to have slow TPs, we found the former group to be superior to the latter for all the previously mentioned leaf physiological traits. This superiority was related primarily to differences in chloroplast number and only secondarily to differences in activity and composition per chloroplast.

Journal Article↗
PubMed1987

Photosynthetic carbon metabolism in isolated pea chloroplasts: metabolite levels and enzyme activities.

We report here that enzyme activation precedes the rise in metabolite levels, which appear to limit photosynthetic CO2 fixation during induction in pea leaf chloroplasts. Therefore light activation may be required for the build-up of photosynthetic intermediates and hence for photosynthesis in isolated chloroplasts. Analysis of metabolite levels and the known kinetic properties of the chloroplast enzymes indicates that the reductive pentose phosphate cycle is subject to control which fluctuates between several points during induction and when CO2 fixation is maximal. The transketolase-aldolase-catalyzed reactions around sedoheptulose-biphosphatase appear to provide a simple and effective primary control for photosynthetic CO2 fixation. When substrate levels and enzyme active site concentrations are taken into account, there is insufficient glyceraldehyde 3-phosphate dehydrogenase, aldolase, and transketolase activity to support photosynthetic CO2 fixation at observed rates. These results suggest that there may be direct transfer of glyceraldehyde 3-phosphate among these enzymes in the pea chloroplast.

Carbon↗
PubMed1987

Unexpected seizures during hemodialysis. Effect of dialysate prescription.

To assess the effects of the dialysate prescription on the intradialytic neurological stability of children requiring chronic hemodialysis (HD), continuous EEG monitoring (CEM) was performed on five children before, during and after HD against: (1) low sodium acetate (LAc: Na 132 mEq/l, acetate 38 mEq/l); (2) high sodium acetate (HAc: Na 144 mEq/l, acetate 41 mEq/l), and (3) low sodium bicarbonate (LBi: Na 133 mEq/l, bicarbonate 35 mEq/l) dialysate. Three children, two with clinically well-controlled seizure disorders and one with no seizure history, exhibited subclinical seizures on LAc and HAc but improved neurological stability on LBi. Two children had essentially unchanged CEM studies on any HD regimen. Symptoms of disequilibrium were noted in four of the five children on LAc, two of the five on HAc and only one of the five on LBi. The data suggest that bicarbonate HD may enhance intradialytic neurological stability, particularly in children with known seizure disorders. Furthermore, CEM was found to be a useful tool for evaluating the neurological stability of children during HD.

Adolescent↗
PubMed1987

Protein modulase appears to be a complex of ferredoxin, ferredoxin/thioredoxin reductase, and thioredoxin.

Protein modulase and ferredoxin/thioredoxin reductase are soluble proteins that have been suggested to catalyze the light-dependent modulation of enzyme activity in the stromal compartment of the chloroplast. Protein modulase is active in vitro without additional ferredoxin and thioredoxin, whereas ferredoxin/thioredoxin reductase requires additional ferredoxin and thioredoxin. We hypothesize that protein modulase is a complex protein composed of ferredoxin/thioredoxin reductase, ferredoxin, and thioredoxin. In reconstituted chloroplast systems, antiserum directed against ferredoxin, at concentrations sufficient to inhibit the photoreduction of NADP, had no effect on light modulation. Antiserum directed against thioredoxin gave variable results: one batch of polyclonal antibodies inhibited light modulation, another was stimulatory, and another was without effect. These results suggest that the ferredoxin and thioredoxin active in light modulation are not free in solution. Furthermore, molecular sieve chromatography of stromal proteins results in the elution of four species that catalyze light modulation. Based on whether or not ferredoxin and/or thioredoxin must be added for activity, these four species have been tentatively identified as protein modulase, a complex of ferredoxin/thioredoxin reductase and ferredoxin, a complex of ferredoxin/thioredoxin reductase and thioredoxin, and ferredoxin/thioredoxin reductase. That is, the four correspond to all the possible combinations of ferredoxin, ferredoxin/thioredoxin reductase, and thioredoxin. We suggest that buffer ionic strength affects the interactions among these proteins and in part determines the fate of the protein modulase complex in vitro.

Journal Article↗
PubMed1986

A comparison of muscle fiber characteristics at different levels of the vertebral column in the rhesus monkey.

The vertebral muscle fiber characteristics of adult female rhesus monkeys have been examined. Muscle samples were obtained from precisely defined superficial and deep sites on both sides of the vertebral column. In particular, samples were collected from three different levels of the column and the muscle fiber characteristics from all these different sites were compared. It is clear that in the rhesus monkey at least, muscle fiber characteristics are dependent on the vertebral level although not necessarily on the side of the vertebral column.

Animals↗
PubMed1986

Aluminum intoxication in a child: treatment with intraperitoneal desferrioxamine.

We report the successful chelation of aluminum and the clinical resolution of severe aluminum intoxication in an infant receiving chronic peritoneal dialysis through the use of intraperitoneal desferrioxamine. Following the introduction of desferrioxamine, urine and dialysate fluid aluminum levels exceeded those noted without the chelating agent, thus demonstrating enhanced removal of aluminum. As a result of therapy, plasma and bone aluminum levels decreased markedly, and previously noted histomorphometric abnormalities on bone biopsy resolved. Clinically, the aluminum-associated osteomalacia and microcytic hypochromic anemia completely reversed. Moderate developmental delay has also improved slightly but persists. Our experience suggests that intraperitoneal chelation therapy with desferrioxamine may be helpful to reverse aluminum intoxication in children with chronic renal failure. However, limited exposure to aluminum should remain a primary goal.

Aluminum↗