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M Ahuja

Publications and source records attributed to M Ahuja.

12 recordsLinked to original sources
PubMed1995

Can immunosuppressive drugs slow the progression of IgA nephropathy?

The role of immunosuppressive drugs in the treatment of IgA nephropathy (IgAN) remains controversial. The effect of treatment with prednisolone and azathioprine on the clinical course of patients with IgA nephropathy is described in this retrospective study. One hundred and fourteen patients, 66 treated (age 13-77 years) and 48 untreated (age 15-64 years), were evaluated. The two groups of patients differed significantly with respect to heavier proteinuria (median 3.6 g/day, range 0.2-18 g/day), lower serum albumin level (< 40 g/l) and more severe renal histopathological involvement in the treated group (P < 0.01). Oral prednisolone 40 mg/day and azathioprine 2 mg/kg BW/day was commenced initially and after gradual tapering was continued at low dose (5 mg/day) for a median duration of 24 months (range 12-98). The median duration of follow-up was 46 months (range 12-180). The clinical course was defined as progressive or non-progressive on the basis of serial serum creatinine (Scr). Of the patients who presented with renal impairment (Scr > 110 mumol/l), a non-progressive course was observed in 79.5% patients of the treated group (n = 39), while only in 36% of the untreated group (n = 22), the difference was statistically significant (P < 0.001). Slopes of reciprocal of Scr versus time were also calculated by linear regression analysis to represent the trend of renal function for patients who had had 3 or more years follow-up (n = 101). An analysis of variance of these trends in patients with renal impairment at presentation (n = 51) showed significant recovery of renal function in the treated group (n = 33) and a decline of renal function in the untreated group (n = 18, P = 0.004). There was no significant effect of the treatment on proteinuria. The histopathological features that favoured response to the treatment were mesangial proliferation, capsular adhesions and interstitial infiltration on light-microscopy, C3 and fibrin deposits on immunofluorescence (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Changes in the structure and function of the human thrombin receptor during receptor activation, internalization, and recycling.

According to current models, human thrombin receptors are activated when thrombin cleaves the receptor's N terminus, exposing the tethered ligand domain, SFLLRN. In the megakaryoblastic CHRF-288 cell line, thrombin receptor activation is followed by the rapid internalization of > 90% of the receptors. In the present studies, antibodies directed at the site of cleavage by thrombin were used to examine changes in receptor structure during activation, internalization, and recovery. As would be expected, the initial rate of receptor cleavage was directly related to the thrombin concentration. However, even after prolonged incubation, receptor cleavage was incomplete until the thrombin concentration exceeded the receptor concentration. Only cleaved receptors were internalized in response to thrombin and only catalytically active thrombin and active variants of SFLLRN-containing peptides caused receptor internalization. Over a 3-h period following receptor activation by thrombin, there was a gradual recovery of approximately one-quarter of the receptors on the cell surface. These receptors were detectable with antibodies directed at retained portions of the receptor N terminus, but not with antibodies directed at the proposed site of cleavage, confirming that they are recycled, rather than new, receptors. At 4 degrees C two-thirds of the receptors cleaved by thrombin were retained on the cell surface. Like recycled receptors these "cold-cleaved" receptors failed to self-activate when warmed to 37 degrees C, but could be activated by SFLLRN. Unlike recycled receptors, however, the cold-cleaved receptors were also internalized and appeared to be activated by a second addition of thrombin. These results 1) provide strong evidence at the protein level that thrombin cleaves its receptors at the predicted site, 2) show that receptor activation is necessary for internalization, 3) suggest that each thrombin molecule may not activate large numbers of receptors, 4) demonstrate that a substantial fraction of internalized thrombin receptors can be recycled, and 5) suggest that the failure of recycled receptors to be reactivated by thrombin may involve a change in the receptor that does not occur at 4 degrees C. Finally, the inability of cold-cleaved receptors to self activate in the absence of thrombin, suggests that in addition to cleaving the receptor, thrombin may also play an important role in guiding the tethered ligand domain to regions on the remainder of the receptor that mediate activation.

Amino Acid Sequence↗
PubMed1994

Sarcomatoid renal cell carcinoma arising in hemodialysis-associated acquired cystic kidney disease presenting with disseminated bone marrow infiltration.

A 51-year-old man with a 23-year history of hemodialysis-dependant end-stage renal failure presented with pyrexia, malaise, and progressive pancytopenia. Investigations revealed acquired cystic kidney disease, with one cyst being interpreted as showing evidence of recent hemorrhage, and a malignant sarcomatoid bone marrow infiltrate. The patient rapidly deteriorated and died. At autopsy a seminecrotic and cystic sarcomatoid renal cell carcinoma was identified, with metastases in the adrenals, bone marrow, liver, lungs, and abdominal lymph nodes. The case is reviewed with regard to epithelial membrane antigen- and cytokeratin-negative bone marrow immunohistology as well as the immunophenotype of acquired cystic kidney disease and that expected in renal carcinoma, with reference to the literature on acquired cystic kidney disease.

Bone Marrow↗
PubMed1994

Thrombin receptors: turning them off after turning them on.

Recent studies have helped to define the mechanisms by which thrombin activates platelets and other cells. Those studies show that the human thrombin receptor has a structure similar to other G protein-coupled receptors, but is activated by a novel mechanism in which thrombin cleaves its receptor, creating a new N-terminus that can serve as a tethered ligand. Shortly after activation, thrombin receptors become temporarily resistant to re-activation. Present evidence suggests that this loss of function is due to a combination of receptor desensitization, phosphorylation and internalization, and that recovery may involve dephosphorylation, as well as receptor recycling and the expression of newly-synthesized receptors. Together these processes provide a potent mechanism for limiting the duration of thrombin-initiated events in platelets and other thrombin-responsive vascular cells.

Amino Acid Sequence↗
PubMed1993

Regulation of the endothelial cell urokinase-type plasminogen activator receptor. Evidence for cyclic AMP-dependent and protein kinase C-dependent pathways.

Binding of urokinase-type plasminogen activator (u-PA) to specific receptors (u-PAR) on the surface of endothelial cells contributes to the regulation of plasmin-dependent processes such as fibrinolysis and angiogenesis. We studied the effect of raising intracellular levels of cyclic AMP (cAMP) and/or activating protein kinase C on the expression of u-PAR in cultured human umbilical vein endothelial cells (HUVEC). Incubation of HUVEC with forskolin stimulated a time- and concentration-dependent increase in the expression of u-PAR, measured both by an increase in the specific binding of radiolabeled single-chain u-PA (scu-PA) and by increased binding of anti-u-PAR antibodies. Maximal increase in u-PAR expression (81 +/- 11% above control, n = 11) was not associated with a change in receptor affinity for scu-PA when HUVEC were incubated for 20 hours at 37 degrees C with 50 microM forskolin. Receptor induction by forskolin was inhibited when HUVEC were preincubated with deoxyadenosine monophosphate (DAM), an inhibitor of adenylyl cyclase. A similar increase in receptor expression (128 +/- 27% above control, n = 3) was induced by the cAMP analogue 8-bromoadenosine 3':5'-cyclic monophosphate (50 mM). Forskolin induced an approximately twofold increase in the expression of a single approximately 1.4-kb u-PAR messenger RNA (mRNA) transcript within 2 hours. Phorbol myristate acetate (PMA) also stimulated a time- and concentration-dependent increase in specific scu-PA binding. The maximal increase in u-PAR expression (254 +/- 27% above control, n = 11) was observed when HUVEC were preincubated with 10 nM PMA for 20 hours. Induction of u-PAR by PMA was inhibited when HUVEC were preincubated with either cycloheximide or H7 but was unaffected by DAM. u-PAR induced by PMA showed a reduced affinity for scu-PA (Kd, 14 +/- 2 nM versus 3.6 +/- 0.6 nM, p < 0.001; n = 8). PMA stimulation for 20 hours resulted in a sixfold increase in a single approximately 1.4-kb u-PAR mRNA transcript, with increased levels detectable within 30 minutes. Coincubation of HUVEC with optimal concentrations of forskolin and PMA for 20 hours produced a fully additive increase in u-PAR expression at both the mRNA and protein levels. These data suggest that both cAMP-dependent and protein kinase C-dependent protein kinase pathways may independently regulate u-PAR expression in human endothelial cells.

Blotting, Northern↗
PubMed1992

Structure and function of the human platelet thrombin receptor. Studies using monoclonal antibodies directed against a defined domain within the receptor N terminus.

Based upon its recently cloned nucleotide sequence, the human platelet thrombin receptor is thought to be formed by a single polypeptide chain with seven transmembrane domains and an extracellular N terminus that can be cleaved by thrombin. As yet, however, little is known from studies of the receptor protein itself. To obtain such information, we have prepared monoclonal antibodies against a peptide corresponding to receptor residues Ser42 through Phe55, the domain immediately distal to the site of cleavage by thrombin. By flow cytometry, all of the antibodies reacted with the thrombin-responsive megakaryoblastic CHRF-288 and HEL cell lines, but not with the T-lymphoid Sup-T1 cell line. Functionally, the antibodies inhibited platelet responses to alpha-thrombin, gamma-thrombin, and trypsin, but had no effect on platelet activation by ADP, epinephrine, or the thromboxane analog U46619. Radioiodinated antibody bound to approximately 1,800 sites/platelet, a value similar to the reported number of moderate affinity thrombin binding sites per platelet. On Western blots, the antibodies recognized a 66-kDa protein in platelet, HEL, and CHRF-288 membranes. The discrepancy between this apparent size and the predicted mass of the receptor suggests that, as with other G protein-coupled receptors, one or more of the potential sites for N-linked glycosylation have been utilized. Therefore, these results suggest that: 1) the cloned thrombin receptor is involved in a broad range of platelet responses to thrombin, as well as gamma-thrombin and trypsin; 2) as predicted, the N terminus of the receptor is accessible on the platelet surface; 3) the moderate affinity thrombin binding site noted in earlier studies may be the receptor; 4) potentially as much as one third of the mass of the receptor is carbohydrate.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Macronodular adrenal hyperplasia causing Cushing's syndrome: report of two cases and an overview.

Of the various entities producing adrenal hyperfunction, nodular adrenal hyperplasia is rarely described, however, recent reports have established it as a distinct cause of Cushing's syndrome. Although the etiology of this disease remains uncertain, two distinct forms are recognised, namely: macronodular hyperplasia and micronodular dysplasia. Establishing the diagnosis preoperatively is difficult but essential to ensure the correct treatment is performed. Two cases of macronodular hyperplasia are reported herein followed by a review of the available literature on this subject.

Adrenal Glands↗
PubMed1990

Rehabilitation in chronic back pain: employment status after four years.

Of 129 chronic back pain patients treated consecutively at the Palmerston North hospital rehabilitation unit in 1982-3, 102 responded to a questionnaire in 1987. The 27 nonresponders had had pain for a shorter time and were considered to have a better prognosis. Of the 102 responders, 31 no longer had back pain; 51 (six women) were employed full or part time and 17 (two women) were looking for work. Two men had reversed roles and 17 had retired. Women who no longer had a job outside the home classed themselves as housewives rather than as retired or unemployed. This study provides data for future planning but without controls, confident conclusions cannot be drawn on the efficacy of the rehabilitation programme. There is a need for further controlled studies.

Adolescent↗
PubMed1982

Elevation board.

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Edema↗