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Biomedical subjects

U Saxena

Publications and source records attributed to U Saxena.

At least 55 records · Page 3Linked to original sources

Lipoprotein ApoC-II activation of lipoprotein lipase. Modulation by apolipoprotein A-IV.

Lipoprotein lipase (LPL)-mediated hydrolysis of triglycerides (TG) contained in chylomicrons requires the presence of a cofactor, apolipoprotein (apo) C-II. The physiological mechanism by which chylomicrons gain apoC-II necessary for LPL activation in whole plasma is not known. Using a gum arabic stabilized TG emulsion, activation of LPL by lipoprotein apoC-II was studied. Hydrolysis of TG by LPL was greater in the presence of serum than with addition of either high density lipoproteins (HDL) or very low density lipoproteins (VLDL). LPL activation by either VLDL or HDL increased with addition of the lipoprotein-free fraction of plasma. A similar increase in LPL activity by addition of the lipoprotein-free fraction together with HDL or VLDL was observed when another TG emulsion (Intralipid) or TG-rich lipoproteins from an apoC-II deficient subject were used as a substrate. Human apoA-IV, apoA-I, apoE, and cholesteryl ester transfer protein were assessed for their ability to increase LPL activity in the presence of VLDL. At and below physiological concentrations, only apoA-IV increased LPL activity. One hundred percent of LPL activity measured in the presence of serum was achieved using VLDL plus apoA-IV. In the absence of an apoC-II source, apoA-IV had no effect on LPL activity. Removal of greater than 80% of the apoA-IV from the nonlipoprotein-containing fraction of plasma by incubation with Intralipid markedly reduced its ability to activate LPL in the presence of VLDL or HDL. Gel filtration chromatography demonstrated that incubation of the nonlipoprotein-containing fraction of plasma with HDL and the TG emulsion caused increased transfer of apoC-II to the emulsion and association of apoA-IV with HDL. Our studies demonstrate that apoA-IV increases LPL activation in the presence of lipoproteins. We hypothesize that apoA-IV is required for efficient release of apoC-II from either HDL or VLDL, which then allows for LPL-mediated hydrolysis of TG in nascent chylomicrons.

Apolipoprotein C-II↗

Giant nerve abscesses in leprosy.

Two leprosy patients with neuritis caused by giant abscesses involving almost the entire ulnar nerve are described. One patient, who also had skin lesions, was diagnosed histopathologically as having borderline tuberculoid leprosy both on skin and nerve biopsy, and the other, with only nerve involvement, belonged to the pure neuritic group. The lepromin test was strongly positive (with a vesicular reaction in one patient) and lymphocyte transformation to Mycobacterium leprae antigen was raised. These lesions can be easily mistaken for a peripheral nerve tumour in places where leprosy is uncommon. A brief account of the management of nerve abscess in leprosy is given.

Abscess↗

Nodularity of nerves in treated leprosy.

Ten patients with fully treated paucibacillary leprosy, mainly tuberculoid, had asymptomatic nodules present along the peripheral nerves that persisted even after the skin lesions had completely subsided and treatment was stopped. Histopathology of the nodules revealed no signs of activity of the disease. The evolution, follow-up care, and significance of these nodules are discussed.

Adolescent↗

Removal of apoprotein-B-containing lipoproteins by plasmapheresis using immobilized phosphorylcholine-binding protein affinity adsorbent.

Rat serum phosphorylcholine binding protein was earlier shown to bind lipoproteins containing apoproteins B and E from human very low and low density lipoproteins. The present studies were undertaken to show the effectiveness of rat serum phosphorylcholine-binding protein immobilized on Sepharose affinity column to remove apoprotein-B-containing lipoproteins from normal and hypercholesterolemic rabbit plasma, when used in a plasmapheresis system. The maximum in vitro binding of very low and low density lipoproteins from hypercholesterolemic rabbit plasma to the affinity adsorbent was Ca2+ dependent, and the cholesterol bound to the column at the optimum calcium concentration (2.5 mM) was 21% of the total plasma cholesterol applied. The in vivo binding of total cholesterol from normal and hypercholesterolemic rabbit plasma during plasmapheresis ranged from 0.22 to 7.7%. Total mass of cholesterol bound ranged from 3.86 and 27.52 mg at plasma cholesterol concentrations 13.8 and 282 mg/dL, respectively. Most (greater than 95%) of the bound cholesterol was associated with very low and low density lipoproteins. These studies show the ability of immobilized rat serum phosphorylcholine-binding protein to lower the atherogenic apoprotein-B-containing lipoproteins from plasma of hypercholesterolemic rabbits.

Adsorption↗

Multiple cutaneous nerve abscesses on a healed tuberculoid patch.

A case of healed tuberculoid leprosy (TT) with multiple superficial nerve abscesses involving the whole cutaneous network on the patch is reported. To the best of our knowledge multiple cutaneous nerve abscesses involving the entire subcutaneous plexus on a TT patch is a very uncommon observation.

Abscess↗

Clinical, histopathologic & immunologic features of cutaneous lesions in acute meningococcaemia.

Fifty children with culture proven acute meningococcaemia were studied during the winter outbreak of the disease in 1986-87. Purpuric lesions were seen in 60 per cent, erythematous papules in 32 per cent, faint pink macules in 28 per cent, conjunctival petechiae in 10 per cent and herpes labialis in 20 per cent. Histopathology of skin lesions showed that the primary damage was to the dermal vessels, the extent of damage depending on the type of skin involvement. Diplococci in Gram's stained sections were seen frequently in purpuric as compared to the other skin lesions. They were located in degenerating neutrophils, endothelial cells, fibrin clots or freely in the vascular lumen. Electron microscopic study showed vascular changes accompanied by a perivascular phagocytic response. Both light and electronmicroscopy indicated the involvement of the coagulative mechanism in the pathogenesis of meningococcaemia. However, clinical parameters of clotting were often within normal limits. In the case of a child (who died eventually), a low platelet count and prolonged coagulation indices were observed. Sera from some of the children were tested for the presence of antibodies against meningococci by indirect immunofluorescence. Antibodies were detected in the sera and they may have a role in regulating the severity and course of the illness. The significance of immunoglobulin deposits in the skin lesions is not clear.

Antibodies, Bacterial↗

Release of endothelial cell lipoprotein lipase by plasma lipoproteins and free fatty acids.

Lipoprotein lipase (LPL) bound to the lumenal surface of vascular endothelial cells is responsible for the hydrolysis of triglycerides in plasma lipoproteins. Studies were performed to investigate whether human plasma lipoproteins and/or free fatty acids would release LPL which was bound to endothelial cells. Purified bovine milk LPL was incubated with cultured porcine aortic endothelial cells resulting in the association of enzyme activity with the cells. When the cells were then incubated with media containing chylomicrons or very low density lipoproteins (VLDL), a concentration-dependent decrease in the cell-associated LPL enzymatic activity was observed. In contrast, incubation with media containing low density lipoproteins or high density lipoproteins produced a much smaller decrease in the cell-associated enzymatic activity. The addition of increasing molar ratios of oleic acid:bovine serum albumin to the media also reduced enzyme activity associated with the endothelial cells. To determine whether the decrease in LPL activity was due to release of the enzyme from the cells or inactivation of the enzyme, studies were performed utilizing radioiodinated bovine LPL. Radiolabeled LPL protein was released from endothelial cells by chylomicrons, VLDL, and by free fatty acids (i.e. oleic acid bound to bovine serum albumin). The release of radiolabeled LPL by VLDL correlated with the generation of free fatty acids from the hydrolysis of VLDL triglyceride by LPL bound to the cells. Inhibition of LPL enzymatic activity by use of a specific monoclonal antibody, reduced the extent of release of 125I-LPL from the endothelial cells by the added VLDL. These results demonstrated that LPL enzymatic activity and protein were removed from endothelial cells by triglyceride-rich lipoproteins (chylomicrons and VLDL) and oleic acid. We postulate that similar mechanisms may be important in the regulation of LPL activity at the vascular endothelium.

Animals↗

Hypomelanosis of ito: histochemical and ultrastructural observations.

Skin biopsies were taken from an infant girl with Hypomelanosis of Ito (Incontinentia Pigmenti Achromians) for histopathological, histochemical and electron microscopic studies. Histological observations were similar to those reported previously. Electron microscopy revealed two groups of melanocytes, an effete group and another group with a highly dendritic appearance. The significance of these findings is discussed.

Female↗

Mycosis fungoides with fatal brain involvement.

The clinical course, therapy and investigations in a man with lichenoid mycosis fungoides which resulted in fatal spread to the brain is described. Immunological studies revealed a significant reduction in T cell numbers. Brain lesions were confirmed by CT Scan and drill biopsy. The literature on the subject is discussed.

Brain Neoplasms↗

Clinical, histological and immunological studies in 50 patients with bullous pemphigoid.

Fifty patients with bullous pemphigoid were investigated over periods of up to 7 years. Sequential studies of circulating basement membrane zone (BMZ) antibody titres revealed two groups of patients: 44% had a high initial titre (greater than 1:160) and 56% had a low initial titre (less than 1:160). Subjects with titres greater than 1:160 continued to have high titres, whereas in those with lower titres the BMZ antibodies usually became undetectable after 4 months. The BMZ antibody titres were of no prognostic value. High titres remained high even in patients who were in remission and off treatment, and in these subjects, there was no evidence of a change in the IgG subclass. The initial BMZ IgG antibody titres showed a highly significant correlation with total serum IgE concentrations. A significant correlation also existed between total serum IgE and IgG4 concentrations, although not between the serum IgE and the peripheral blood eosinophil count. No anti-BMZ antibody of IgE class was found, nor specific IgE against inhalants and foods identified, and the significance of the high total serum IgE remains unexplained. The majority of those followed for more than 2 years were able to stop their steroid therapy without further blistering: this confirms that pemphigoid tends to be a self-limiting disease. Nine patients had a recent history of malignant disease, and this is no more than would be expected for this age group of patients: however, 3 patients presented with pemphigoid and figurate erythema and all died of neoplastic disease, suggesting that such patients should be investigated thoroughly for neoplasia.

Adult↗

A study on the selective binding of apoprotein B- and E-containing human plasma lipoproteins to immobilized rat serum phosphorylcholine-binding protein.

Rat serum phosphorylcholine-binding protein (PCBP), a member of the pentraxin family of proteins, was previously shown to bind multilamellar liposomes prepared with egg phosphatidylcholine and lysophosphatidylcholine. The results suggested that the phosphorylcholine groups on the surface of liposomes play an important role in the binding process (Nagpurkar, A., Saxena, U., and Mookerjea, S. (1983) J. Biol Chem. 258, 10518-10523). A study on the binding of human plasma lipoproteins to PCBP immobilized on Sepharose has now been initiated. Very low density lipoproteins were partially bound to a Sepharose-PCBP column, and the bound fraction contained higher concentrations of apoprotein B and E. All the low density lipoproteins applied were bound to the column. In the case of high density lipoproteins, only a small fraction was retained on the column (based on protein analysis), and that bound fraction contained all the apoprotein E and Lp(a) lipoprotein. The binding of very low, low, and high density lipoproteins to Sepharose-PCBP was Ca2+-dependent, and the bound lipoproteins were quantitatively eluted by a phosphorylcholine gradient. Apoprotein B and E were also bound when whole human plasma was applied to Sepharose-PCBP. The effect of selective modification of lysine residues by acetoacetylation and of arginine residues by cyclohexanedione on the binding of low density lipoproteins to Sepharose-PCBP was examined. Modification of arginyl residues resulted in marked reduction of binding, whereas modification of lysine had no effect. Removal of sialic acid from PCBP also had no effect on the binding of low density lipoproteins to immobilized-desialylated PCBP column. The preferential binding of apoprotein B- and E-containing lipoproteins to Sepharose-PCBP indicates a possible physiological role of PCBP and other similar circulating phosphorylcholine-binding proteins of the pentraxin family in lipoprotein metabolism.

Animals↗

The role of the female Syrian hamster protein on the interaction between serum lipoproteins and heparin.

We have previously shown the effect of phosphorylcholine-binding proteins from rat (PCBP) and rabbit (CRP) on the precipitation of serum lipoproteins by heparin in presence of Ca2+. The present paper describes the effect of a phosphorylcholine-binding protein from the female Syrian hamster (FP) on the lipoprotein precipitation reaction. The precipitation of lipoproteins by heparin was lower in assays using female hamster serum in which FP is a prominent protein, compared with assays with male serum in which FP is present in very low concentration. Depletion of FP from female serum resulted in increased lipoprotein precipitation. The addition of purified FP to assays using human very low density lipoprotein (VLDL) inhibited the precipitation reaction. The precipitation of lipoproteins was also examined using serum from male hamsters treated with diethylstilbestrol and female hamsters treated with testosterone, treatments known to modulate the levels of FP. Results indicate an inverse relationship between serum FP levels from normal and hormone-treated hamsters and the precipitation of lipoproteins from their serum. The partially desialylated FP when added to precipitation assays using human VLDL resulted in reduced inhibition of VLDL precipitation.

Animals↗

Inhibition of the binding of low density lipoproteins to liver membrane receptors by rat serum phosphorylcholine binding protein.

Rat serum phosphorylcholine binding protein (PCBP) is characterized by its Ca2+ dependent property to bind phosphorylcholine ligand. PCBP immobilized on sepharose has been shown to selectively bind human plasma apo B and E containing lipoproteins. The present report describes an inhibitory effect of PCBP on the binding of human 125I-LDL to LDL receptors on estradiol treated rat liver membranes. Pre-incubation of liver membranes with PCBP did not affect the binding of 125I-LDL to the membranes. Gel filtration analysis of the incubation products from the LDL-receptor assay showed a concentration dependent binding of 125I-PCBP to LDL. The inhibitory effect of PCBP is likely due to the formation of LDL-PCBP complex and not due to the binding of PCBP to the LDL receptor site.

Animals↗

Physiological stresses in warehouse operations with special reference to lifting technique and gender: a case study.

A field study was conducted to evaluate the effects of lifting technique (free-style vs. straight-back, bent-knee) on male workers' performances and physiological responses. A secondary objective was to study physiological stresses to female order selectors using the free-style lifting technique only. Six male and six female workers performed their routine work of grocery order selection in three different warehouses while their oxygen uptake and heart rates were measured. Workers' performances were determined using the traditional work measurement techniques (time study, methods time measurement and master standard data systems) employed by the warehouses. Total cases, weight, volume, actual and allowed time for each order were also determined. Statistical analysis showed that the performance levels of the male workers (allowed time per order * 100/actual time per order) were significantly lower and oxygen uptake and heart rates were higher for the straight-back, bent-knee method as compared to the free-style lifting technique. Male workers lifted more cases, weight and volume/min with the free-style lifting technique than with the straight-back, bent-knee method. It is concluded that the traditionally recommended straight-back, bent knee method of lifting is slower and physiologically more demanding. It is practically impossible for a substantial number of workers to meet the existing time or performance standards based on traditional work measurement techniques--when using the straight-back, bent-knee method of lifting recommended by the warehouses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Contrasting effect of phosphorylcholine-binding protein from rat and rabbit on heparin-lipoprotein interaction: a role of sialic acid.

The effect of rat phosphorylcholine-binding protein (PCBP) and rabbit C-reactive protein (CRP) on the serum lipoprotein-heparin-Ca2+ precipitation reaction has been examined. Rabbit CRP, a nonglycosylated acute-phase protein, has been isolated from the serum after turpentine-induced inflammation following an isolation procedure similar to that used for rat PCBP. The mobilities of rabbit CRP and rat PCBP on polyacrylamide gel electrophoresis and immunoelectrophoresis have been found to be different. Rabbit CRP, even though a P-choline binding protein, was found to have no inhibitory effect on the serum lipoprotein-heparin-Ca2+ precipitation reaction. Desialylated rat PCBP obtained by enzymatic desialylation of rat PCBP no longer inhibited the precipitation reaction, even though it retained its P-choline binding property and immunochemical identity with rat PCBP. The results suggest that the binding of rat PCBP and rabbit CRP to the P-choline moiety is not a sufficient requirement, and it now appears that the sialic acid moiety must also be present on these proteins to observe the inhibition of lipoprotein precipitation. This requirement is fulfilled by rat PCBP, but not by rabbit CRP which is nonglycosylated.

Animals↗

Synthesis and secretion of serum phosphorylcholine-binding protein by rat hepatocytes.

The incorporation of [1-14C]glucosamine into rat serum phosphorylcholine-binding protein in an isolated rat hepatocyte system was used to demonstrate the synthesis and secretion of this protein by the liver. The hepatocytes after incubating with colchicine resulted in an increased intracellular accumulation of phosphorylcholine-binding protein and less of the synthesized phosphorylcholine-binding protein was secreted into the medium. The synthesis of phosphorylcholine-binding protein was found to be significantly impaired when the hepatocytes were incubated with tunicamycin. The radiolabelled phosphorylcholine-binding protein co-eluted with exogenous phosphorylcholine-binding protein as a homogeneous peak by affinity chromatography. The identity of the radiolabelled phosphorylcholine-binding protein was further established by quantitative immunoprecipitation, polyacrylamide gel electrophoresis and isoelectric focusing.

Animals↗

Interaction of rat serum phosphorylcholine-binding protein with phospholipid-containing liposomes.

Rat serum phosphorylcholine-binding protein (PCBP) has been shown to inhibit the Ca2+-modulated heparin-lipoprotein precipitation reaction. This effect of PCBP on the reaction is prevented by phosphorylcholine (P-choline). A stoichiometric relationship between the serum very low density lipoproteins and PCBP was also evident in the heparin-very low density lipoprotein precipitation reaction (Nagpurkar, A., and Mookerjea, S. (1981) J. Biol. Chem. 256, 7440-7448). A study on the binding of PCBP to artificial liposomes was initiated to understand the mechanism of interaction between PCBP and phospholipids in soluble lipoproteins. Radioiodinated PCBP was incubated with multilamellar liposomes prepared with egg phosphatidylcholine (PC) and lysophosphatidylcholine, and it was found that the binding of PCBP to multilamellar liposomes was Ca2+-dependent and required the incorporation of about 25% lysophosphatidylcholine into the liposomes. Furthermore, the binding could be inhibited by addition of P-choline. The optimum concentrations of Ca2+ and liposomes as well as time and temperature required for binding were established. Analysis of Scatchard binding data yielded an association constant K alpha of 1.8 X 10(6) M-1 and a total binding capacity of 0.96 nmol/mumol of phospholipid. Substitution of P-choline head groups by phosphorylethanolamine and phosphorylserine on the PC of liposomes reduced the binding considerably, whereas the substitution of fatty acyl moieties on the PC of liposomes was without any effect. Bovine serum albumin was required in the assay to prevent artifactual binding of 125I-PCBP to the assay tubes. The results suggest that the P-choline groups on the surface of liposomes play an important role in the binding to PCBP and this may provide a possible explanation of the effect of PCBP on the Ca2+-dependent heparin-lipoprotein precipitation reaction.

Animals↗