Search PubMed⌕ Search

Biomedical subjects

V Shah

Publications and source records attributed to V Shah.

At least 109 records · Page 6Linked to original sources
PubMed1996

Abnormalities of erythrocyte sodium transport in reflux nephropathy.

Hypertension is a complication of reflux nephropathy commonly occurring during adolescence and young adult life. We studied cellular sodium transport in an adolescent cohort with this condition as abnormal sodium transport is a feature of human hypertension. Thirty males and 52 females with reflux nephropathy, (median age 20.3 years) had erythrocyte ouabain sensitive sodium-potassium ATPase (Na/K ATPase) pump site number (Bmax) and red cell sodium concentration (RBC Na+) measured in 1988. Six years later, 55 of those had red cell sodium-lithium counter transport (LCT) measured. On both occasions, their renal function and blood pressure (BP) were determined. Bmax in the study group (median 10.3 nmol/l) was significantly less than that of controls (median 11.45 nmol/l). Nine patients who were diagnosed as having hypertension during the 6 year study period appeared to have a lower Bmax compared with that of normotensives in the group. RBC Na+ and LCT of the study group were not significantly different from that of controls. The Na/K ATPase activity is diminished, and sodium-lithium counter transport is unchanged in reflux nephropathy. Further study is needed to ascertain the link between these observations and the onset of high BP.

Adolescent↗
PubMed1995

Glomerular and tubular function in glycogen storage disease.

Urinary protein and calcium excretion were assessed in 77 patients with the hepatic glycogen storage diseases (GSD): 30 with GSD-I (median age 12.4 years, range 3.2-32.9 years), 25 with GSD-III (median age 10.5 years, range 4.2-31.3 years) and 22 with GSD-IX (median age 11.8 years, range 1.2-35.4 years). Inulin (Cinulin) and para-aminohippuric acid (CPAH) clearances were also measured in 33 of these patients. Those with GSD-I had significantly greater albumin (F = 15.07, P < 0.001), retinol-binding protein (RBP) (F = 14.66, P < 0.001), N-acetyl-beta-D-glucosaminidase (NAG) (F = 9.41, P < 0.001) and calcium (F = 7.41, P = 0.001) excretion than those with GSD-III and GSD-IX. GSD-I patients (n = 18) also had significantly higher Cinulin (F = 5.57, P = 0.009), but CPAH did not differ (F = 0.77, NS). Renal function was normal in GSD-III and GSD-IX patients. In GSD-I, Cinulin (r = -0.51, P = 0.03) and NAG excretion (r = -0.40, P = 0.03) were inversely correlated with age, whereas albumin excretion was positively correlated with age (r = +0.41, P = 0.03). RBP and calcium excretion were generally high throughout all age groups. Hyperfiltration in GSD-I is associated with renal tubular proteinuria that occurs before the onset of significant albuminuria. Deficiency of glucose-6-phosphatase within the proximal renal tubule may primarily cause tubular dysfunction, glomerular hyperfiltration being a secondary phenomenon.

Adolescent↗
PubMed1995

Anti-neutrophil cytoplasmic antibodies in childhood systemic lupus erythematosus.

The prevalence and antigen specificity of anti-neutrophil cytoplasmic antibodies (ANCA) in sera from 23 children with active systemic lupus erythematosus (SLE) were studied utilizing indirect immunofluorescence and IgG and IgM ELISA using crude neutrophil extract and purified proteinase 3, myeloperoxidase, lactoferrin, cathepsin G and elastase. ANCA were present in 69% of SLE children and consisted of IgM and IgG antibodies of variable specificities, but did not correlate with organ involvement or disease activity. It remains unclear whether they have pathogenic significance or are epiphenomena in the category of polyclonal B-cell activation. However, their presence is entirely compatible with SLE even though they have hitherto been commonly associated with other systemic vasculitides.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1995

Anti-neutrophil cytoplasmic antibodies and anti-endothelial cell antibodies are not increased in Kawasaki disease.

We studied anti-neutrophil cytoplasmic antibodies (ANCA) and anti-endothelial cell antibodies (AECA) in 58 children with acute Kawasaki disease (KD) before i.v. gamma globulin treatment, 35 children with infection and fever > 38.5 degrees C, and 48 healthy afebrile children. ANCA were studied by indirect immunofluorescence (IIF) on ethanol-fixed neutrophils and by ELISA with crude neutrophil extract as antigen. AECA were studied using ELISA on resting and activated endothelial cells. ANCA IIF was weakly positive, cytoplasmic, diffuse and homogeneous in all three groups. ANCA IIF, ANCA ELISA and AECA ELISA were no higher in KD than in febrile children. There was no difference between KD with and KD without coronary artery aneurysms. AECA differences between the KD and afebrile group were not significant after correction for total IgM. In contrast with our previous findings, we conclude that ANCA and AECA are not raised in KD compared with febrile controls. It therefore seems unlikely that they are important in the pathogenesis of vasculitis in KD.

Adolescent↗
PubMed1995

Soluble cell adhesion molecules and von Willebrand factor in children with Kawasaki disease.

Fifty-nine children with acute Kawasaki disease (KD), a childhood vasculitis, were compared with 35 children with fever due to infection and 48 healthy children. Levels of soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) in the healthy children were double those found in adults. All three soluble cell adhesion molecules and von Willebrand factor (vWF) were higher in the children with KD than in the healthy children, but only sE-selectin, a marker for activated endothelial cells, and sICAM-1 were higher than in the febrile children. The high levels of vWF in KD appear to reflect the prominent acute-phase reaction. This information can help us to understand further the complex interactions between cytokines, circulating inflammatory cells and the vascular endothelium, and may lead to new therapeutic avenues in KD and other inflammatory diseases and vasculitides.

Adolescent↗
PubMed1995

Sodium-lithium countertransport in children with diabetes and their families.

Abnormalities of sodium-lithium countertransport have been extensively implicated in adult primary hypertension and a relationship between sodium-lithium countertransport and family history of hypertension in children has been previously found. More recently it has been suggested that increased sodium-lithium countertransport may play a part in the pathogenesis of nephropathy in insulin dependent diabetes mellitus (IDDM). Children and adolescents with IDDM and their family members were studied. In those with IDDM (n = 36, median age 14.6 years, range 9.5-19.2 years) there was no relationship between sodium-lithium countertransport (range 0.098-0.585 mmol/l red blood cells/hour) and age, blood pressure as expressed by systolic or diastolic SD scores, glycated haemoglobin, serum lipids, or intracellular sodium concentration. A positive relationship (rs = 0.44) was found between sodium-lithium countertransport and early morning urinary albumin to urinary creatinine ratio (UA/UC), expressed as the logarithm of the geometric mean of two consecutive samples, for each individual (range 0.4-22 mg/mmol). Sodium-lithium countertransport was increased in those with IDDM compared with their non-diabetic siblings, in a paired analysis (n = 26). There was no relationship between UA/UC in the children with diabetes and sodium-lithium countertransport in their parents. These studies in this population of diabetic children indicate that increased sodium-lithium countertransport may play a part in the early stages of the development of nephropathy in IDDM.

Adolescent↗
PubMed1995

T-lymphocyte activation in steroid-sensitive nephrotic syndrome in childhood.

We undertook a sequential study in 29 children with steroid-sensitive nephrotic syndrome (SSNS) off treatment to seek evidence for T-cell activation in relapse. T-cell subsets and activation markers were analysed using two-colour flow cytometry. Soluble IL2 receptor (sIL2R) was measured in serum and urine by enzyme-linked immunosorbent assay (ELISA). Fifteen children were examined in remission and subsequent relapse (group A) and fourteen remained in remission (group B). In group A the proportion of CD4+ cells expressing the activation marker CD25 (alpha-chain of the IL2 receptor) increased significantly from remission to relapse: CD4+25+ cells rose from 5.6 to 7.0% of total lymphocytes, and from 15.8 to 19.1% of CD4+ lymphocytes (paired t test: P < 0.0005 and < 0.001 respectively). No correlations were found between CD4+25+ cells and plasma albumin or cholesterol concentrations. SIL2R concentration in serum did not change in relapse, but increased significantly in urine from 272 to 592 U/mg creatinine (P < 0.01). No significant difference was found in remission between groups A and B. We conclude that early relapse in SSNS is associated with activation of CD4+ (T-helper) cells which is not secondary due to the nephrotic state itself.

Adolescent↗
PubMed1994

Effect of cyclosporin A on glomerular filtration rate in children with minimal change nephrotic syndrome.

Cyclosporin A (CyA) is now commonly used in the management of children with steroid-dependent nephrotic syndrome. In order to assess nephrotoxicity related to CyA therapy, we measured glomerular filtration rate (GFR) on 123 occasions in 24 children with minimal change nephrotic syndrome receiving CyA. GFR was estimated from the plasma clearance of 51chromium-EDTA every 3 months during CyA therapy of up to 27 months duration. There was a significant reduction in GFR after 3 months of CyA therapy [118 +/- 33 (SD) to 93 +/- 24 ml/min per 1.73 m2] but no further fall thereafter, although the reduction in GFR was sustained for the duration of CyA therapy. This reduction in GFR appeared to be reversible upon cessation of CyA, but careful monitoring of renal function is necessary in such patients to prevent the development of longer term nephrotoxic sequelae.

Adolescent↗
PubMed1994

Lymphocyte subpopulations, interleukin-2 and interleukin-2 receptor expression in childhood nephrotic syndrome.

Abnormal T lymphocyte function and reduced interleukin-2 (IL-2) production have been implicated in the pathogenesis of the nephrotic syndrome (NS). We investigated: (1) lymphocyte subpopulations and expression of IL-2 receptor (IL-2R) on T cells using two-colour flow cytometry, (2) serum IL-2 and (3) the soluble component of IL-2R (sIL-2R) in serum, using enzyme-linked immunosorbent assay, in 38 children with NS. All children, except those in remission, had marked proteinuria. They were divided into groups according to renal pathology: (1) steroid-sensitive NS (SSNS) not receiving prednisolone therapy, (2) SSNS on prednisolone, (3) focal segmental glomerulosclerosis (FSGS), (4) SSNS in remission and not receiving prednisolone therapy, (5) congenital NS (CNS). Results were compared with 26 age-matched controls. Total T lymphocytes (CD3) were reduced in groups 1 and 2; CD4 count was reduced in groups 1-4; CD8 count increased in groups 2 and 3; CD8 and CD19 (B lymphocytes) were significantly reduced in group 5. Increased IL-2R expression (CD25) on CD4 lymphocytes was noted in groups 1, 2 and 3 implying activation of these cells. In patients with SSNS, increased serum sIL-2R was recorded during relapse (1,273 +/- 497 U/l vs. 913 +/- 401 U/l in remission, P < 0.005) but free serum IL-2 was not detectable at any stage. The specific alterations in lymphocyte subpopulations in SSNS and FSGS would imply an involvement of the immune system distinct from that in CNS.

Acute Disease↗
PubMed1994

Terminal differentiation and senescence in the human melanocyte: repression of tyrosine-phosphorylation of the extracellular signal-regulated kinase 2 selectively defines the two phenotypes.

Melanocytes are pigmented cells distributed in humans in several organs like the epidermis, the leptomeninges, the eye, and the inner ear. Epidermal melanocytes, whether derived from adult or neonatal skin, proliferate well in a medium supplemented with phorbol esters and other mitogens before they undergo senescence. Potent cAMP inducers like cholera toxin are also growth promoters for neonatal melanocytes but only transient growth stimulators for cells derived from adults. We used this cellular system to delineate biochemical pathways involved in proliferation and in terminal differentiation. Here we show that after a period of 4-8 wk of sustained proliferation in the presence of cholera toxin, the adult melanocytes became round, flat, and enlarged. These changes were associated with terminal growth and preceded by a five- to sixfold increase in cAMP levels and an 8- to 10-fold increase in melanin content. The simultaneous addition of phorbol esters and cholera toxin did not prevent cells from reaching terminal differentiation. Identified targets for phorbol esters are protein kinase C (PKC) and the mitogen-activated kinases (MAPKs), also called extracellular signal-regulated kinases (ERKs). PKC was found to be similarly regulated in proliferating and in terminally differentiated melanocytes. Proliferating melanocytes in early or late passage showed identical activation of the kinase ERK2. This kinase was rapidly phosphorylated upon phorbol 12-myristate 13-acetate (PMA) addition and specifically accumulated in the nucleus of the cells, whereas in unstimulated cells it had a perinuclear distribution. In contrast, senescent and terminally differentiated cells were unable to phosphorylate tyrosine residues of the ERK2 gene product in spite of presenting normal amounts of ERK2 protein. In addition, ERK2 did not show the nuclear accumulation observed in proliferating melanocytes after PMA activation and remained localized in the perinuclear area. These results demonstrate that senescent and terminally differentiated melanocytes share a common block in a critical pathway thought to integrate multiple intracellular signals transmitted by various second messengers and specifically prevent the continuation of the signal transduction cascade initiated by PMA activation of PKC.

Adult↗
PubMed1994

Antiendothelial cell antibodies can be cytotoxic to endothelial cells without cytokine pre-stimulation and correlate with ELISA antibody measurement in Kawasaki disease.

To confirm the presence of antiendothelial cell antibodies (AECA) and study the clinical value of their measurement in Kawasaki disease (KD), sera from patients with KD were assessed for binding to human umbilical vein endothelial cells (HUVEC) using a cellular based ELISA, and for complement-mediated cytotoxicity using 111In-labelled HUVEC. In the ELISA assay, IgM AECA were detected in 16/22 sera, whereas IgG AECA were only present in one out of 19 sera. There was a significant difference in IgM AECA titres when comparing patients with controls. Eight out of 16 sera showed cytotoxicity against HUVEC, and this was significantly enhanced when HUVEC were pretreated with tumour necrosis factor (TNF). IgM AECA titres measured by ELISA were positively correlated with their cytotoxicity. The findings suggest that IgM class AECA in sera from patients with KD are detectable by ELISA method, and that some of these antibodies, 50% in this study, can mediate complement-dependent cytotoxicity against endothelial cells.

Adolescent↗
PubMed1994

Evaluation of effects of altered gastric pH on absorption of dapsone in healthy volunteers.

A prospective, randomized, crossover study was performed with seven healthy volunteers to address the effect of increased gastric pH on dapsone absorption. Subjects were randomized to receive a single 100-mg dose of dapsone or a single 100-mg dose of dapsone in addition to 30 ml of a high potency antacid 1 h before dapsone administration and hourly thereafter for a total of 10 doses. Dapsone concentrations in serum were measured periodically for 48 h. No statistical differences between the two regimens were noted when mean dapsone maximal initial concentrations, times to peak, and areas under the curve were compared. These data suggest that an increase in gastric pH has little or no effect on the absorption of dapsone in healthy subjects.

Adult↗
PubMed1994

Circulating insulin-like growth factor binding proteins (IGFBPs) 1 and 2 induced in vitamin C-deficient or fasted guinea pigs inhibit IGF-I action in cultured cells.

Collagen gene expression and proteoglycan synthesis are decreased in vitamin C-deficient guinea pigs losing weight and in fasted guinea pigs receiving ascorbate. Sera from such guinea pigs contain an insulin-like growth factor (IGF)-I-reversible inhibitor of collagen, proteoglycan and DNA synthesis and elevated levels of 29 and 35-kDa IGF binding proteins (IGFBPs). We now have identified the induced proteins as IGFBPs 1 and 2 and investigated their role as inhibitors. Guinea pig sera were treated with antibodies to IGFBPs 1 and 2 and antibody-IGFBP complexes were removed by passage through a Protein A-Sepharose column. Inhibitor content of fasted and scorbutic sera, and Protein A pass-through fractions derived from them, was assessed by their level of stimulation of DNA and collagen synthesis in 3T3 cells, compared to analogously treated normal guinea pig serum. Removal of IGFBP-1 from scorbutic serum reversed inhibition of collagen and DNA synthesis by more than half but removal of IGFBP-2 was less effective. Removal of both IGFBPs reversed inhibition almost completely. Similar results were obtained with fasted guinea pig serum. Conversely, purified rat IGFBPs 1 and 2 inhibited DNA and collagen synthesis in cells cultured in normal guinea pig serum or IGF-I-stimulated DNA synthesis, with IGFBP-1 being more potent. Thus, IGFBP-1 and, to a lesser extent IGFBP-2, cause inhibition of IGF-I action by sera from fasted and scorbutic guinea pigs and may inhibit collagen gene expression in vivo.

3T3 Cells↗
PubMed1993

Transformation of immortal, non-tumorigenic osteoblast-like human osteosarcoma cells to the tumorigenic phenotype by nickel sulfate.

Epidemiological studies have indirectly linked compounds of chromium, nickel and arsenic to human carcinogenesis. However, there is no evidence that metal compounds can transform human cells to the tumorigenic phenotype in culture. We show here that exposure to 36 microM NiSO4 for 48-96 h results in transformation of an immortal, nontumorigenic, osteoblast-like cell line, HOS TE85, to the tumorigenic phenotype. Continuous passaging following treatment leads to the formation of a few dense foci. The cells isolated and expanded from the foci are morphologically transformed, and form anchorage-independent colonies of the size and abundance comparable to that formed by Kirsten murine sarcoma virus transformed HOS TE85 cells. The transformed cells from tumors in nude mice, have enhanced levels of plasminogen activators and have lost the ability to form model bone matrix on extended culture in the presence of ascorbic acid and beta-glycerophosphate. A number of cell lines have been established from nude mouse tumors. Cytogenetic analysis reveals 16 marker chromosomes and an aberrant chromosome 16. This is the first report of the transformation of a human cell line to tumorigenic phenotype by a metal carcinogen.

Animals↗