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Biomedical subjects

L Low

Publications and source records attributed to L Low.

11 recordsLinked to original sources

Sulfated polyanions prevent HIV infection of lymphocytes by disruption of the CD4-gp120 interaction, but do not inhibit monocyte infection.

Sulfated polyanions (SPs) bind variably to lymphocyte-expressed CD4 and inhibit binding of monoclonal antibodies to the first two domains of CD4. To further define this interaction, soluble recombinant CD4 (sCD4; four extracellular domains), its truncated amino-terminal two-domain derivative, and three linear peptide analogues spanning residues 6-60 (6-24, 20-40, 41-60) in the first domain were investigated for SP binding. Dextran sulfate (DXS) (500 kDa), polyvinyl sulfate, fucoidan, and carrageenan-kappa, each immobilized on carboxymethyl cellulose fibers, bound strongly to both the two-domain and four-domain recombinant CD4 molecules (similar to that observed with native CD4), whereas dextran sulfate (5 kDa), chondroitin 6-sulfate, and pentosan sulfate bound relatively poorly. No peptide binding to SPs was observed. Recombinant gp120 bound poorly (< 10%) to all of the immobilized polyanions, except pentosan sulfate (17%), for which some binding was noted. Binding of radiolabeled V3 loop peptide to SPs was slightly greater, with 20-30% binding to polyvinyl sulfate, dextran sulfate (500 kDa), and pentosan sulfate. Competitive binding studies demonstrated the predominance of sCD4 rather than rgp120 binding to SPs and supported previous data demonstrating a binding site for DXS (500 kDa) on the first domain of CD4 adjacent to the gp120 binding site and recognized by OKT4C and E monoclonal antibodies. Hence disruption of the CD4-gp120 interaction is probably responsible for most of the observed antiviral activity of SPs toward HIV infection of lymphocytes. However, HIV infection and gp120 binding to monocytes was unaffected by SPs, probably because SPs were unable to block the CD4-gp 120 interaction in monocytes.

Amino Acid Sequence

On the dynamics of the growth process.

Recent publications have provided evidence that the short-term growth process may be regarded as pulsatile rather than constant over time. The possible influence of changes in soft tissue thickness is one reason why it is not possible to draw any final conclusion about the existence or not of such a pulsatile short-term growth pattern. An answer can probably not be reached until a method has been developed that measures longitudinal bone growth without any soft tissue involvement, especially since such a method has recently been used in the rabbit showing that the day-to-day growth rate was linear or continuous.

Age Determination by Skeleton

A polyanion binding site on the CD4 molecule. Proximity to the HIV-gp120 binding region.

Recent studies have demonstrated that sulfated polyanions (SP) are potent inhibitors of HIV infection in vitro, appearing to inhibit virus attachment. To understand the mode of action of these compounds a large panel of SP were examined for their ability to inhibit HIV infection, block anti-CD4 mAb binding and, when immobilized, bind soluble CD4 and virion gp120. Based on anti-CD4 mAb binding-inhibition studies a SP binding site was identified on the CD4 molecule. Dextran sulfate (DXS)-500 kDa, polyvinylsulfate (PVS), and polyanethole sulfonate were particularly potent SP inhibitors, blocking the binding of 11 of the 12 anti-CD4 mAb tested. These 11 mAb are known to interact with the two amino-terminal Ig-like domains of CD4. In fact, DXS-500 kDa exhibited an hierarchy of inhibition of anti-CD4 mAb which suggests that SP bind to a conformational site incorporating the first two Ig-like domains of CD4. This SP binding site is clearly distinct but closely associated with the gp120 binding region of CD4. In terms of anti-HIV activity there was no evidence that SP act at the virion level as rgp120 did not bind to immobilized SP and preincubation of virions with SP did not affect infectivity. In contrast, many of the SP tested showed some affinity for CD4 based on anti-CD4 mAb blocking studies and binding of soluble CD4 to immobilized SP. The most active in this regard were DXS-500 kDa and PVS, whose anti-HIV activity could be entirely due to disruption of the CD4-gp120 interaction. However, with SP such as heparin, fucoidan, the carrageenans, and polyanethole sulfonate, although CD4 blocking may contribute to anti-HIV activity, some other anti-viral mechanism is also operating. Finally, pentosan sulfate, a SP with anti-HIV activity comparable to DXS-500 kDa and PVS, showed little or no reactivity with CD4 and must inhibit HIV infection by a totally CD4-independent mechanism.

Antibodies, Monoclonal

Self-concepts of disabled youth athletes.

A self-concept inventory was administered to 158 youth athletes, ages 9 to 18 yr. (M = 13.94 yr., SD = 2.63) who competed in the first Pan American Victory Games for Physically Disabled Youth. Disabilities represented were blind (n = 57), cerebral palsy (n = 52), dwarfs (n = 18), spinal cord injured (n = 12), amputation (n = 10), and les autres (n = 9). The purpose was to examine the self-concepts of disabled youth athletes and begin a data base. Analysis indicated that mean self-concept scores fell within or were close to ranges of means for able-bodied youth, as given in the test manual.

Adaptation, Psychological

Acromegaloid patients with type A insulin resistance: parallel defects in insulin and insulin-like growth factor-I receptors and biological responses in cultured fibroblasts.

A subset of patients with the syndrome of acanthosis nigricans and insulin resistance type A is characterized by acromegaloid features in addition to hyperinsulinemia, hyperandrogenemia, and an inherent defect in insulin receptor function. It has been proposed that the acromegaloid features result from the interaction of insulin at concentrations encountered in vivo, with a functionally intact insulin-like growth factor-I (IGF-I) receptor closely related to the insulin receptor. We investigated this possibility by examining binding and hormone-stimulated [14C]glucose uptake, [3H]thymidine uptake, and receptor autophosphorylation by both insulin and IGF-I in cultured fibroblasts from two affected patients. In comparison to normal fibroblasts, [125I]insulin binding, insulin-stimulated [14C]glucose, and [3H]thymidine uptake, and insulin-stimulated autophosphorylation were each reduced by approximately 50-60% of the absolute values in controls. In contrast to expectation, each of these apparent defects in insulin binding and action were mirrored by a parallel decrease in IGF-I binding and action. Thus, [125I]IGF binding was approximately 50%, IGF-I stimulated [3H]thymidine uptake was approximately 40% and 60% of the control value, and IGF-I-stimulated receptor autophosphorylation was reduced by 40%. Incubation of fibroblasts with insulin at 25 ng/mL reduced subsequent binding of [125I]IGF-I by approximately 20% and did not enhance maximal stimulation of [3H]thymidine incorporation. We conclude that in some patients with acanthosis nigricans and acromegaloid features, IGF-I receptors of cultured fibroblasts may share the inherent defects of insulin receptor function. These in vitro data do not explain the acromegaloid features observed in vivo, suggesting that acromegaloid features are mediated by other mechanisms.

Acanthosis Nigricans

Chloride transport inhibition by piretanide and MK-196 in bullfrog corneal epithelium.

Two new diuretic agents, piretanide and MK-196, inhibited short-circuit current (SCC) across the isolated frog corneal epithelium. The effect is explained as an inhibition of active Cl transport. A definite decrease in SCC and an increase in electrical resistance was observed with both diuretics in concentrations as low as 10(-6) M. Piretanide, at 10(-4) M, reduced the SCC by 90%, reduced th unidirectional forward Cl flux from 0.60 to 0.28 mueq x h-1 x cm-2, and increased the resistance by 60%. There was no effect on the Cl backflux. At 10(-4) M, MK-196 reduced the SCC by 83% and increased the resistance by 72%, from 1.68 to 2.91 k omega x cm2. Replacement of Cl by SO4 in the bathing solutions resulted in a larger increase in resistance, from 1.68 to 3.80 k omega x cm2. The diuretics had no effect on active Na transport across the corneal epithelium. After the permeability of the apical side was increased by amphotericin B, the drugs could not inhibit the Cl-originated SCC. These results suggest that piretanide and MK-196 selectively inhibit active Cl transport in the cornea by blocking Cl permeability of the apical side of the epithelial cells.

Animals

Intramural cysts of the ileum.

A case of intramural cysts of the ileum is described for the first time. The clinical presentation and pathological findings are presented and the possible aetiology is discussed.

Adult