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Biomedical subjects

M A Linshaw

Publications and source records attributed to M A Linshaw.

At least 19 recordsLinked to original sources
PubMed2000

Urinary basic fibroblast growth factor: a noninvasive marker of progressive cystic renal disease in a child.

Autosomal recessive polycystic kidney disease (ARPKD) is a hereditary condition with an estimated incidence of 1 in 20,000 live births. Various growth factors have been implicated in the causation of this disease. We describe a child with ARPKD whose levels of urinary basic fibroblast growth factor (bFGF) were markedly elevated. The concentrations of bFGF increased further following right nephrectomy, in response to the compensatory growth of the remaining kidney. We hypothesize that measurement of urinary bFGF may be useful as a noninvasive marker to assess progression of cystic renal development.

Adult↗
PubMed1999

Controversies in childhood urinary tract infections.

Management of childhood urinary tract infections is conceptually straightforward, but controversies persist. Specimens must be collected carefully or culture results can be difficult to interpret. Urine culture remains the diagnostic standard but does not substitute for careful urinalysis. Radiography studies are designed to define abnormalities predisposing patients to pyelonephritis and to assess the extent of renal involvement during infection, but there is no agreement on the most appropriate combination of studies. Circumcision reduces the incidence of urinary infections in male infants. Vaginal reflux may have an impact on recurrent infections, especially after courses of antibiotics. The importance of vesicoureteral reflux remains controversial because renal scarring appears to be related more to infection than to reflux itself. A strong argument can be made for the avoidance of prophylactic antibiotic therapy, even in patients with reflux. Increased attention to early diagnosis and treatment may be responsible for a decreasing incidence in renal failure from reflux nephropathy in children.

Anti-Bacterial Agents↗
PubMed1999

Captopril reduces the proteinuric effect of human growth hormone in adriamycin nephrosis.

Developing male Sprague-Dawley rats (125 g) with adriamycin (doxorubicin hydrochloride) nephrosis (AN) were treated with growth hormone (GH) which may induce hyperfiltration potentiating glomerulosclerosis. Since captopril (CAP) reduces hyperfiltration, we studied its effects in GH-treated rats with AN. After 41, 76, and 90 days of therapy, urine protein excretion was significantly (P<0.05) reduced in GH-treated AN plus CAP compared with AN rats receiving GH alone. After 90 days, urine protein, creatinine ratio was significantly (P<0.05) increased in GH-treated AN (95.2+/-13.9) compared with untreated AN (64.8+/-7.8) and GH-treated AN rats plus CAP (41.8+/-8.8). The mean serum cholesterol level was significantly (P<0.05) reduced in GH-treated AN rats receiving CAP compared with AN rats receiving GH alone and untreated AN controls. Histologically tubular dilation was significantly (P<0.05) reduced in GH-treated AN rats plus CAP compared with AN rats receiving GH alone. Tubular atrophy and scarring were significantly (P<0.05) increased in AN rats treated with GH compared with untreated AN rats, and normalized in GH-treated AN rats plus CAP. We conclude that CAP reduces the proteinuric response of GH in rats with AN and ameliorates tubular injury.

Animals↗
PubMed1997

Immune response to Escherichia coli O157:H7 in hemolytic uremic syndrome following salmonellosis.

Escherichia coli O157:H7, a Shiga-like toxin (SLT)-producing enteric pathogen, has been implicated in most cases of post-diarrheal hemolytic uremic syndrome (D + HUS). Infection with other bacterial pathogens such as Salmonella has also preceded D + HUS episodes, leading to speculation that these organisms may also be etiological. We present two children with unrelated D + HUS following salmonellosis. Both children had negative stool cultures on sorbitol-MacConkey agar soon after the onset of diarrhea. After the diagnosis of HUS, both patients had repeat stool cultures positive for Salmonella alone. Polymerase chain reactions for SLT I and II gene sequences in Salmonella isolates were negative. Enzyme-linked immunosorbent assay for specific humoral response to E. coli O157:H7 lipopolysaccharide in acute and convalescent serum samples revealed evidence of heretofore undetected E. coli O157:H7 infection contemporaneous with each D + HUS episode. These cases demonstrate that isolation of only non-SLT-producing microbes from children with D + HUS should raise suspicion of concurrent undetected infection with SLT-producing organisms. Assaying specific immune response to E. coli O157:H7 can be an important epidemiological adjunct. Bacterial infection with non-SLT-producing Salmonella may represent concomitant enteric pathology rather than D + HUS-instigating infection.

Antibodies, Bacterial↗
PubMed1992

Role of cytoskeleton in volume regulation of rabbit proximal tubule in dilute medium.

When proximal tubules are immersed in hypotonic medium, they quickly swell to a peak volume. In a second, slower phase, termed volume regulatory decrease (VRD), they shrink as K, anion, and water leave the cells. We investigated the role of the cytoskeleton during this biphasic hypotonic volume regulatory response. Isolated, collapsed rabbit proximal convoluted tubules (PCT) were crimped tightly between two pipettes, and their volume was assessed optically. PCT volume increased to a peak 70-80% above baseline on sudden immersion in dilute medium (150 mosmol/kgH2O). After completing VRD, control tubules had regulated their volume 73 +/- 2% back toward baseline. Tubules exposed to the microtubule inhibitor vincristine (5 microM) regulated 75 +/- 2%. Tubules exposed to the microfilament inhibitor cytochalasin B (50 microM) regulated less (57 +/- 5%), and tubules exposed to both inhibitors regulated only 39 +/- 3% (P less than 0.01 vs. control). Hypotonic VRD was unimpaired in PCT loaded with NaCl by prior exposure to ouabain but was significantly reduced by cytochalasin B. We conclude that VRD is not cation specific and that intact microtubules and microfilaments play a synergistic role in the VRD of rabbit PCT in hyposmotic medium.

Animals↗
PubMed1991

Selected aspects of cell volume control in renal cortical and medullary tissue.

Under normal physiological conditions, demands placed on mammalian renal cortical cells are quite different from those in the medulla. Cortical proximal tubule cells exist in an isotonic environment, but must resorb vast amounts of filtered fluid and solute, and also adjust to solute generated from cellular metabolism. In addition, cortical cells must also adjust to occasional pathological derangements in blood osmolality. By contrast, human medullary cells have a smaller solute resorptive load, but exist in a milieu where osmolality varies from 40 to more than 1200 mosmol/kg H2O, depending on water intake. Remarkably, the cells maintain a near normal size despite these stresses. Under isosmotic conditions, the primary regulator of cell volume is Na-K ATPase. In its absence, factors such as external protein, extracellular matrix and basement membrane, cytoskeleton, and perhaps formation of cytoplasmic vesicular-like structures help prevent cells from swelling massively. Under anisosmotic conditions, a variety of transport processes operating across basolateral and apical membranes either remove solute from or add solute (and water) to cells to minimize changes in their size. Medullary cells have the additional ability to accumulate organic, non-toxic, osmolytes that offset external hypertonicity and allow cells to maintain normal size without increasing cellular inorganic ion concentrations.

Cell Membrane↗
PubMed1991

Role of cytoskeleton in isotonic cell volume control of rabbit proximal tubules.

Stability of mammalian cell volume depends primarily on the sodium pump. When active cation transport of rabbit renal proximal tubules is blocked by ouabain, cells swell, but their size is limited by residual volume control mechanisms. This "ouabain-resistant" volume control is not an active process, as it operates in the presence of cyanide and dinitrophenol and in the absence of exogenous energy. Nevertheless, it remains incompletely explained by known transmembrane oncotic and hydrostatic forces. We tested the hypothesis that the cytoskeleton contributes to isotonic cell volume control. Isolated, collapsed rabbit proximal convoluted tubules (PCT) were crimped at both ends with micropipettes and had their volume assessed optically. PCT in ouabain (1 mM) swelled to 1.40 above control with protein, 1.62 without protein, and 1.89 with the cytoskeleton inhibitors vincristine (5 microM) and cytochalasin B (50 microM) and without protein. Tubulozole-C and cytochalasin D gave similar results. A hydrostatic pressure of 50 cmH2O increased tubule volume to 1.93 before the tubule basement membrane (TBM) prevented further volume increase. We conclude that volume of renal tubule cells in ouabain is limited partly by external protein, but primarily by the cytoskeleton. The TBM prevents massive swelling and tubule disaggregation.

Animals↗
PubMed1988

Structural and functional development of outer versus inner cortical proximal tubules.

The concept of centrifugal renal development is based on renal embryogenesis. It implies a relationship between nephron age and nephron position along a cortical to medullary axis. In common usage, however, it often also implies a relationship between nephron age or position and nephron maturity. We consider here whether the ideas of centrifugal development and centrifugal maturation should in fact be considered as separate and distinct concepts. That is, we consider the possibility that nephron maturity does not necessarily correlate with nephron age. Unfortunately, pertinent reported data give no clear answer. We conclude only that further study will be required before definitive conclusions about renal developmental stages can be stated with certainty.

Animals↗
PubMed1988

Importance of anion in hypotonic volume regulation of rabbit proximal straight tubule.

Rabbit proximal straight tubules rapidly swell to a maximum volume when abruptly immersed into hypotonic medium. However, in a second, slower phase, termed volume regulatory decrease (VRD), tubules shrink toward their basal volume due to the efflux of K, accompanying anion and water. In the present study, we investigated the nature of the anion during hypotonic volume regulation. We removed Cl and/or the HCO3 buffer to assess their relative importance in VRD, and we used furosemide, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), and barium to investigate the nature of the transmembrane anion pathway in VRD. Isosmotic replacement of peritubular Cl with gluconate had no effect on either tubule volume in isotonic medium or the initial osmometric swelling response in hypotonic medium. However, the VRD in such Cl-depleted tubules was significantly inhibited. Control tubules regulated 81% below their maximal volume in dilute medium. By contrast, Cl-depleted tubules regulated only 39%. This inhibitory effect could not be attributed to the absence of peritubular Cl or to the presence of gluconate. The absence of the HCO3 buffer or the presence of SITS (0.5 mM) had no inhibitory effect on the rate or extent of VRD. Furosemide alone (1 mM) also had no inhibitory effect on VRD. However, whereas barium alone delays VRD, addition of furosemide to barium-treated tubules further slowed their maximal rate of fluid efflux and delayed VRD even more.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1987

Potassium homeostasis and hypokalemia.

Potassium, largely an intracellular cation, contributes to the regulation of cellular volume, to tissue growth and metabolic synthesis of proteins and nucleic acids, and to the integrity of electrical properties of excitable tissues as well as nonexcitable, transporting epithelia. Potassium balance is closely regulated by a variety of nonrenal and renal mechanisms. When potassium losses are sufficient to induce hypokalemia, either through nonrenal or renal causes, profound adverse effects on neuromuscular, cardiac, vascular, and renal tissues may ensue. The diagnostic approach is straightforward, and therapy must be directed to replenish losses without inducing a rapid, excessive, and potentially fatal increase in the potassium concentration of the serum.

Acid-Base Equilibrium↗
PubMed1987

Hypocomplementemic glomerulonephritis in an infant and mother. Evidence for an abnormal form of C3.

A mother developed hematuria during the fourth month of pregnancy, and her nursing infant son from this otherwise uncomplicated pregnancy developed hematuria at 3.5 months of age. Both had a mild glomerulonephritis characterized by mesangial prominence, focal thickening and mottling of the glomerular basement membrane and electron-dense deposits, predominantly in the intramembranous and subendothelial positions. Immunofluorescence studies revealed striking accumulations of C3 and other complement components associated with alternative complement pathway activation within glomeruli, and the presence of small or equivocal amounts of immunoglobulin. C1q, C4 and factor B were not detectable. The glomerular lesion was accompanied by hypocomplementemia. Sera of both mother and infant displayed half normal levels of C3 and factor B, increased levels of C4, and normal levels of 12 other complement proteins. High normal or slight elevation in nephritic factor-like activity was observed in serial serum samples. Studies suggested that this mother and son represent the second kindred having an abnormal form of C3 which produces an alternative complement pathway C3 convertase, C3b, Bb, resistant to control by factor H. No additional affected family members were identified. The course of the nephritis over 7 years without drug therapy has been mild with resolving hematuria and no abnormal proteinuria or decrease in creatinine clearance.

Adult↗
PubMed1986

Basolateral membrane properties of juxtamedullary proximal tubule in newborn rabbit.

We have evaluated the functional and morphological changes that occur in juxtamedullary proximal convoluted tubules before and after the completion of nephrogenesis at approximately 3 wk of age. Tubules were dissected in connection with glomeruli in the deep juxtamedullary zone, crimped at both ends, and induced to swell in isotonic medium by sequential exposure to ouabain, reduced bath protein concentration, and collagenase. Basolateral membrane surface areas were measured morphometrically in paired tubules if possible. The swelling rates and basolateral areas were the same in tubules from 2-7- and 14-17-day-old rabbits (during nephrogenesis), had increased in 28-42-day-old rabbits (after nephrogenesis), and increased further in adults. Because the surface areas and swelling rates increased proportionally, the nephrons "matured" only after nephrogenesis was complete and then only in basolateral surface area. The intrinsic membrane properties of hydraulic conductivity and ion permeability apparently remained constant.

Animals↗
PubMed1986

Use of trypan blue for identifying early proximal convoluted tubules.

Proximal convoluted renal tubules (PCT) are difficult to dissect for in vitro study, particularly in newborn animals, and are identified with certainty only when obtained in continuity with their parent glomeruli. We show here that the supravital colloidal dye trypan blue preferentially stains early PCT segments of rabbit in vivo and greatly facilitates their isolation. We also show that trypan blue administration does not adversely affect animal growth rate, kidney weight, or several general measures of kidney function. Using isolated PCT from newborn to adult rabbits, control (unstained) and trypan blue-stained tubules also are found not to differ in lateral membrane surface density, in their ability to maintain normal cell volume or to respond to hypotonic osmotic challenge, and in their swelling rate in isotonic medium after ouabain treatment. We conclude that trypan blue has no adverse effects on PCT cell function while greatly facilitating their isolation for physiological studies.

Animals↗
PubMed1985

Effect of barium on cell volume regulation in rabbit proximal straight tubules.

Rabbit proximal straight tubules swell abruptly when exposed to hypotonic medium but then shrink in a few minutes as they approach their base-line volume following loss of solute and water. Potassium, the major intracellular cation, as well as sodium, is lost during this process. In the present experiments, we studied hypotonic cell volume regulation in the presence of barium, an agent reported to decrease potassium permeability. Exposure to BaCl2 significantly prolonged hypotonic volume recovery in a dose-dependent manner. Tubules depleted of potassium and loaded with sodium chloride by exposure to 10(-4) M ouabain for 1 h swelled osmometrically and subsequently volume regulated in dilute medium. Volume regulation in such tubules is a consequence of transbasement membrane hydrostatic forces. By contrast, tubules similarly loaded with sodium, but also exposed to 10(-3) M BaCl2, volume regulated only minimally in dilute medium, suggesting BaCl2 might also affect sodium movement. However, hypotonic volume regulation was restored in sodium-loaded BaCl2-treated tubules when cells were more effectively depleted of potassium by incubation in 0-mM potassium medium. We conclude that barium retards hypotonic volume regulation primarily because of its effect on potassium movement.

Animals↗