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V Cattell

Publications and source records attributed to V Cattell.

At least 19 recordsLinked to original sources
PubMed2003

Social inequalities in depressive symptoms and physical functioning in the Whitehall II study: exploring a common cause explanation.

STUDY OBJECTIVE: This study investigated which risk factors might explain social inequalities in both depressive symptoms and physical functioning and whether a common set of risk factors might account for the association between depressive symptoms and physical functioning. DESIGN: A longitudinal prospective occupational cohort study of female and male civil servants relating risk factors at baseline (phase 1: 1985-8) to employment grade gradients in depressive symptoms and physical functioning at follow up (phase 5: 1997-9). Analyses include the 7270 men and women who participated at phase 5. SETTING: Whitehall II Study: 20 London based white collar civil service departments. PARTICIPANTS: Male and female civil servants, 35-55 years at baseline. MAIN RESULTS: Depressive symptoms were measured by a subscale of items from the 30 item General Health Questionnaire. Physical functioning was measured by a subscale of the SF-36. Employment grade was used as a measure of socioeconomic position as it reflects both income and status. The grade gradient in depressive symptoms was entirely explained by risk factors including work characteristics, material disadvantage, social supports, and health behaviours. These risk factors only partially explained the gradient in physical functioning. The correlation between depressive symptoms and physical functioning was reduced by adjustment for risk factors and baseline health status but not much of the association was explained by adjustment for risk factors. Among women, the association between depression and physical functioning was significantly stronger in the lower grades both before and after adjustment for risk factors and baseline health. For women, there was only a significant grade gradient in depressive symptoms among those reporting physical ill health. CONCLUSIONS: Some risk factors contribute jointly to the explanation of social inequalities in mental and physical health although their relative importance differs. Work is most important for inequalities in depressive symptoms in men, and work and material disadvantage are equally important in explaining inequalities in depressive symptoms in women while health behaviours are more important for explaining inequalities in physical functioning. These risk factors did not account for the association between mental health and physical health or the greater comorbidity seen in women of lower socioeconomic status. The risk of secondary psychological distress among those with physical ill health is greater in the low employment grades.

Adult↗
PubMed2001

Cutting edge: amelioration of kidney disease in a transgenic mouse model of lupus nephritis by administration of the caspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-(beta-o-methyl)-fluoromethylketone.

Systemic lupus erythematosus (SLE) is a common, potentially fatal, non-organ-specific autoimmune disorder. Immune complex-mediated kidney disease is the major cause of mortality. Apoptotic cells in the epidermis are a possible source of self Ags, and apoptosis of endothelial cells and lymphocytes is thought to contribute to end-organ damage. We have previously shown that female transgenic mice expressing IFN-gamma in the epidermis develop inflammatory skin disease and features of SLE that have striking parallels with the human condition. We have now tested the effects of a pan-caspase inhibitor, carbobenzoxy-valyl-alanyl-aspartyl-(beta-o-methyl)-fluoromethylketone, on disease progression. Daily s.c. administration of carbobenzoxy-valyl-alanyl-aspartyl-(beta-o-methyl)-fluoromethylketone to female transgenic mice over a 3-wk period resulted in significant amelioration of both glomerular and interstitial renal damage, independent of the effects on autoantibody levels or skin inflammation. We propose that apoptosis inhibitors could be beneficial in the treatment of human SLE.

Amino Acid Chloromethyl Ketones↗
PubMed2001

Poor people, poor places, and poor health: the mediating role of social networks and social capital.

This paper explores the dynamics between poverty and exclusion; neighbourhood, and health and well being by considering the role of social networks and social capital in the social processes involved. It is based on qualitative research taking two deprived areas as exemplary case studies, and involving depth interviews with residents. Neighbourhood influences on networks and social capital were explored, network typologies developed reflecting structural and cultural aspects of individual's networks, and pathways implicated in health effects considered. The complexity of social capital is addressed. The role of three factors in influencing social networks and social capital are demonstrated: neighbourhood characteristics and perceptions; poverty and social exclusion, and social consciousness. Perceptions of inequality could be a source of social capital as well as demoralisation. Different network structures-dense and weak, homogeneous and heterogeneous- were involved in the creation of social capital and had implications for well being. Coping, enjoyment of life and hope are identified as benefits. Although participation in organisations was confirmed as beneficial, it is suggested that today's heterogeneous neighbourhoods also require regenerated local work opportunities to develop bridging ties necessary for the genesis of inclusive social capital and better health. Despite the capacity of social capital to buffer its harsher effects, the concept is not wholly adequate for explaining the deleterious effects of poverty on health and well being.

Adaptation, Psychological↗
PubMed2001

Red cell traverse through thin glomerular basement membranes.

BACKGROUND: How red cells enter the urinary filtrate in most cases of hematuria of glomerular origin has remained a mystery despite the frequent ultrastructural examination of renal biopsy material. METHODS: Serial sections of glutaraldehyde-fixed, resin-embedded material from a case of sporadic microhematuria were examined by transmission electron microscopy when the site of a red cell traversing the glomerular capillary wall was fortuitously discovered on routine examination. RESULTS: The red cell assumed a dumbbell shape and traversed a localized gap 2.25 microm in diameter in the glomerular endothelium and basement membrane. Serial sections suggested a transcellular route. Apart from the thinning of the basement membrane (167 nm), there were no other generalized abnormalities. CONCLUSION: Red cells can traverse through gaps in the glomerular capillary walls to gain access to Bowman's space. This may be the origin of glomerular hematuria in common noninflammatory forms of glomerular disease, including thin basement membrane nephropathy.

Adult↗
PubMed2001

Why is there so much end-stage renal failure of undetermined cause in UK Indo-Asians?

There is a high incidence of end-stage renal failure (ESRF) of undetermined cause in the Indo-Asian population of the UK. We studied patients presenting from the district of Brent and Harrow, which has a large Indo-Asian community, and whose renal services are largely provided by our centre. The diagnosis and ethnicity of patients starting renal replacement therapy and/or undergoing renal biopsy were collated. The incidences of ESRF, rates of renal biopsy and underlying diagnoses were calculated for Indo-Asians and Caucasians. Requirement for renal replacement therapy in Indo-Asians presenting to our centre from Brent and Harrow was 221/10(6)/year; no underlying diagnosis was identified in 77/10(6)/year. Renal biopsy rate in these patients was 456/10(6)/year, and the diagnostic categories significantly over-represented compared to Caucasians were: hypertension and ischaemia, focal segmental glomerulosclerosis (FSGS), idiopathic interstitial nephritis (IIN), diabetic nephropathy, minor glomerular abnormality, lupus nephritis and non-specific advanced chronic renal disease (p<0.001). The first three of these had a combined incidence of 135/10(6)/year in Indo-Asians and 31/10(6)/year in Caucasians. ESRF of undetermined cause is common in UK Indo-Asians, as is requirement for renal biopsy. Hypertension with ischaemia, FSGS and IIN are over-represented in the Indo-Asian population, and should be targeted for early diagnosis and treatment in this group.

Adult↗
PubMed2000

Mesangial cell necrosis in Thy 1 glomerulonephritis--an ultrastructural study.

Cell death is central to many physiological and pathological processes. As tissue reactions to the two forms of cell death, necrosis and apoptosis, differ, it is critical to distinguish between them. Although ultrastructure is still the definitive means of assessing this, there are very few in vivo studies. Administration of anti-Thy 1 antibody in rats is a model of acute glomerular mesangial cell death due to their expression of the Thy 1.1 epitope. The nature of this process is unclear; apoptosis was suggested from early morphological studies and recent in vitro effects of anti-Thy 1.1 antibody. We have re-examined the changes by electron microscopy, and identified a process of cell necrosis starting within 30 min of anti-Thy 1.1 antibody administration. Although there was chromatin condensation, the necrotic features distinctive from apoptosis were: loss of nuclear membranes, cell swelling and degeneration of cytoplasmic organelles, with liberation of chromatin and organelles into the interstitium causing acute inflammation without phagocytic uptake of apoptotic bodies. These findings accord with the known complement dependence of this model. Ultrastructure is a valuable means of differentiating between in vivo necrosis and apoptosis and this is important for understanding the pathogenesis of injury and subsequent tissue responses.

Animals↗
PubMed1999

A central role for alpha beta T cells in the pathogenesis of murine lupus.

We have previously shown that female transgenic mice expressing IFN-gamma in the epidermis, under the control of the involucrin promoter, develop inflammatory skin disease and a form of murine lupus. To investigate the pathogenesis of this syndrome, we generated female IFN-gamma transgenic mice congenitally deficient in either alpha beta or gamma delta T cells. TCR delta-/- transgenics continued to produce antinuclear autoantibodies and to develop severe kidney lesions. In contrast, TCR beta-/- IFN-gamma transgenic mice failed to produce antinucleosome, anti-dsDNA, or antihistone autoantibodies, and kidney disease was abolished. Both alpha beta- and gamma delta-deficient transgenics continued to develop IFN-gamma-associated skin disease, lymphadenopathy, and splenomegaly. The data show that the autoantibody-mediated pathology of murine lupus in IFN-gamma transgenic mice is completely alpha beta T cell dependent and that gamma delta T cells cannot drive autoantibody production. These results imply that production of antinuclear autoantibodies in IFN-gamma transgenic animals is Ag driven, and we identified clusters of apoptotic cells in the epidermis of the mice as a possible source of self Ags. Our findings emphasize the relevance of this murine lupus model to the human disease.

Animals↗
PubMed1999

Induced nitric oxide (NO) synthesis in heterologous nephrotoxic nephritis; effects of selective inhibition in neutrophil-dependent glomerulonephritis.

Increased NO synthesis, due to inducible NO synthase (iNOS) activity, is found in macrophage-associated glomerulonephritis. Little is known about NO in neutrophil-dependent immune complex inflammation, and its role remains controversial. We therefore studied early phase heterologous nephrotoxic nephritis (HNTN) induced in rats by nephrotoxic globulin and the effects of selective iNOS inhibition of this model. At 2 h of the model iNOS mRNA was induced and nitrite (NO-2) was generated in glomeruli incubated ex vivo (5.2 +/- 1.0 nmol/2000 glomeruli per 24 h). There were 14.7 +/- 2.2 polymorphonuclear neutrophils (PMN)/glomerulus (normal controls 0.1 +/- 0.1). At 8 h urinary protein was 69 +/- 15.3 (normal controls 0. 6 +/- 0.2 mg/24 h). Peritoneal PMN expressed iNOS and produced significant NO-2 (basal 11.2 +/- 0.3 nmol/106 cells per 24 h). Selective iNOS inhibition with L-N6-(1-iminoethyl)-lysine (L-NIL) in vitro inhibited nephritic glomerular and PMN NO-2 synthesis. In HNTN L-NIL in vivo significantly suppressed elevated plasma NO-2/NO-3 levels (representative experiment: 17 +/- 2 microM, untreated 40 +/- 4 microM, P = < 0.01, normal control 18 +/- 2 microM). This inhibition did not affect leucocyte infiltration into glomeruli or induce thrombosis. There was no consistent effect on proteinuria. This is the first demonstration of glomerular iNOS induction and high output NO production in the acute phase of PMN-dependent acute immune complex glomerulonephritis. Selective iNOS inhibition does not affect the primary mechanism of injury (leucocyte infiltration) in this model.

Animals↗
PubMed1999

Nitric oxide and glomerulonephritis.

The normal glomerulus expresses constitutive nitric oxide (NO) synthesis. Increased NO from inducible nitric oxide synthase (iNOS) occurs in acute immune glomerulonephritis (GN), in which rapid induction probably depends on local cytokines and/or oxygen radical production. Although intrinsic glomerular cells possess iNOS, in acute GN, a leukocyte origin for iNOS activity is most evident. Although NO potentially could be toxic or protective, there is as yet no clear understanding of how it affects the pathogenesis of GN. This may depend on the amount present, which in turn depends on NOS gene regulation, simultaneous production of other radicals, and the activity of arginase. High-output NO has been implicated in injury in only one model of GN, and no effect of iNOS knockout found in another. The concept is emerging that constitutive NO is critical for offsetting increased vasoconstriction in the injured glomerulus.

Animals↗
PubMed1998

Arginase AI is upregulated in acute immune complex-induced inflammation.

Previous studies have shown high arginase activity at inflammatory sites. Arginase converts L-arginine to L-ornithine, sharing a common substrate with nitric oxide synthase. It exists as two isoforms, AI and AII. While the function of liver arginase (AI) in ureagenesis has been defined, the role and isoform of arginase in cells without a complete urea cycle are unknown. We therefore determined arginase isoform mRNA expression in glomerular acute immune complex inflammation, and its cultured constituent cells. AI was induced in nephritic glomeruli, and in mesangial cells stimulated with IL-4 and cAMP, and was present in elicited neutrophils and macrophages. AII was constitutively expressed. Our data strongly suggest that AI, thought to be restricted to the liver, accounts for high arginase activity at inflammatory sites where it may limit high output nitric oxide production and generate polyamines and proline essential for cell proliferation and matrix production. This identification of AI in inflamed tissue is an important step for understanding the consequences of increased arginase activity.

Acute Disease↗
PubMed1998

Heme oxygenase is induced in nephrotoxic nephritis and hemin, a stimulator of heme oxygenase synthesis, ameliorates disease.

Heme oxygenase (HO) catalyses degradation of heme to biliverdin, iron and carbon monoxide (CO). Two isoforms exist, a constitutive form and an inducible form (HO-1). Induction of HO-1 may have protective effects in inflammation. We studied heterologous (HNTN) and accelerated (ANTN) nephrotoxic nephritis in Lewis rats. Hemin, an inducer of HO-1, (30 mumol/kg) was administered 18 hours before induction of nephritis and 72 hours later in ANTN. HO-1 was not detected immunohistochemically in normal glomeruli but was present in HNTN and ANTN in cells with the morphology of macrophages. HO-1 induction was confirmed by RT-PCR. In normal rats hemin induced glomerular HO-1 mRNA at 18 hours. In HNTN hemin markedly reduced proteinuria at 24 hours (10 +/- 4 mg/24 hr; control 54 +/- 16; P < 0.05), neutrophil infiltration at two hours (29.8 +/- 1.8 vs. 22.3 +/- 1.5 neutrophils/glomerulus, P < 0.05), and glomerular macrophage number at two hours (2.1 +/- 0.1 vs. 3.1 +/- 0.4 cells/glomerulus, P < 0.05). In ANTN proteinuria was reduced at day 1 and day 4 (36 +/- 11 vs. 60 +/- 15 and 36 +/- 7 vs. 86 +/- 9 mg protein/24 hr, respectively, P < 0.001), glomerular thrombi were reduced by hemin at day 1 and 4 (1.5 +/- 2.7 vs. 2.7 +/- 0.2 and 1.3 +/- 0.01 vs. 2.9 +/- 0.02, respectively, P < 0.001) and glomerular macrophage infiltration was reduced on day 4 (11.2 +/- 0.8 cells/glom; control 15.9 +/- 0.8, P < 0.01). Possible mechanisms by which HO-1 ameliorates disease include anti-complement or anti-oxidant effects of bilirubin and vasodilator and anti-platelet effects of carbon monoxide.

Animals↗
PubMed1998

Anti-GBM glomerulonephritis in mice lacking nitric oxide synthase type 2.

Nitric oxide is synthesized in experimental immune complex glomerulonephritis due to local induction of type 2 nitric oxide synthase (NOS2). To determine the role of NOS2, the course of accelerated anti-glomerular basement membrane glomerulonephritis (anti-GBM) was examined in mice homozygous for disruption of the NOS2 gene compared with heterozygous littermates. Disease in the wild type strain (129Sv) was characterized by heavy albuminuria, glomerular neutrophil and macrophage infiltration and glomerular thrombosis. NOS2, interleukin 1B (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) mRNA were induced by 24 hours. The NOS2-deficient mutant mice and the heterozygous mice displayed early (24 hr) and full autologous phase (day 6) injury indistinguishable from the wild-type mice. The equivalent degree of albuminuria and glomerular inflammation indicates that NOS2 does not play an essential role in this form of glomerulonephritis in the mouse.

Animals↗
PubMed1998

Arginase activity is modulated by IL-4 and HOArg in nephritic glomeruli and mesangial cells.

Arginase shares a common substrate, L-arginine, with nitric oxide synthase (NOS). Both enzymes are active at inflammatory sites. To understand regulation of arginase and its relationship to nitric oxide (NO) production, we studied effects of NG-hydroxy-L-arginine (HOArg) and interleukin-4 (IL-4) on urea and NO2- synthesis by glomeruli during rat immune glomerulonephritis and compared these with macrophages and glomerular mesangial cells (MC). In nephritic glomeruli, elicited macrophages, and MC stimulated with IL-1 and adenosine 3',5'-cyclic monophosphate agonists, increased arginase and induced NOS activity was found. Urea production was inhibited by HOArg and increased by IL-4. NO inhibition [NG-monomethyl-L-arginine (L-NMMA)] increased arginase activity in nephritic glomeruli and macrophages but not MC. NO2- synthesis was inhibited by L-NMMA and IL-4. It was increased with HOArg under conditions of NO inhibition. In contrast, in normal glomeruli and basal MC, where there was no induced NO synthesis, IL-4 had no effect on arginase activity, whereas HOArg consistently reduced it in glomeruli only. Type II arginase (Arg II) mRNA was detected in normal glomeruli; nephritic glomeruli expressed both Arg I and Arg II mRNAs. This is the first demonstration of arginase modulation in glomeruli and MC and of the expression of arginase isoforms in glomeruli. The differential responses to two endogenous compounds generated by inflammation suggest this may be part of coordinated regulation of arginase and inducible NOS in immune injury, whereby arginase is inhibited during high-output NO production and stimulated with NO suppression. This, together with control of arginase and NOS isoforms, may be important in controlling the balance of inflammatory and repair mechanisms.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Antinuclear autoantibodies and lupus nephritis in transgenic mice expressing interferon gamma in the epidermis.

Systemic lupus erythematosus (SLE) is a potentially fatal non-organ-specific autoimmune disease that predominantly affects women. Features of the disease include inflammatory skin lesions and widespread organ damage caused by deposition of anti-dsDNA autoantibodies. The mechanism and site of production of these autoantibodies is unknown, but there is evidence that interferon (IFN) gamma plays a key role. We have used the involucrin promoter to overexpress IFN-gamma in the suprabasal layers of transgenic mouse epidermis. There was no evidence of organ-specific autoimmunity, but transgenic animals produced autoantibodies against dsDNA and histones. Autoantibody levels in female mice were significantly higher than in male transgenic mice. Furthermore, there was IgG deposition in the glomeruli of all female mice and histological evidence of severe proliferative glomerulonephritis in a proportion of these animals. Our findings are consistent with a central role for the skin immune system, acting under the influence of IFN-gamma, in the pathogenesis of SLE.

Animals↗
PubMed1996

L-arginine depletion inhibits glomerular nitric oxide synthesis and exacerbates rat nephrotoxic nephritis.

Nitric oxide (NO) synthesis is induced in glomeruli in glomerulonephritis; its role in the pathogenesis of glomerular injury is unknown. Interpretation of its role using the currently available analogues of L-arginine as in vivo inhibitors of NO is complicated by their lack of specificity for inducible NO synthase (iNOS). As NO synthesis by iNOS depends on extracellular L-arginine, we have here examined effects of L-arginine depletion on glomerular NO synthesis and the course of accelerated nephrotoxic nephritis (NTN). Arginase, which converts L-arginine to urea and L-ornithine, was used to achieve L-arginine depletion. A single dose of i.v. arginase produced complete depletion of plasma arginine for four hours. Two forms of NTN were induced in preimmunised rats by nephrotoxic globulin: (1) the systemic form of the model by intravenous nephrotoxic globulin; or (2) the unilateral form of model by left kidney perfusion with nephrotoxic globulin, which avoids the complications of systemic administration of nephrotoxic globulin. Arginase reduced plasma arginine levels and the synthesis of nitrite (the stable end-product of NO) by NTN glomeruli (95% inhibition). Proteinuria was exacerbated. There was no effect on early (24 hr) leukocyte infiltration. In the systemic form of the model arginine depletion by i.v. arginase increased glomerular thrombosis at 24 hours, and the severity of histological changes at four days, accompanied by systemic hypertension. In the unilateral form of the model, where i.v. arginase did not induce hypertension, there was no increase in thrombosis or histological severity of nephritis. These results show that arginine depletion, which inhibits glomerular NO synthesis in NTN, leads to increased proteinuria. Where injury is severe, or accompanied by systemic hypertension, the disease is further exacerbated by glomerular thrombosis. These results suggest that NO has an important role in limiting acute glomerular injury.

Animals↗