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Biomedical subjects

A J Howie

Publications and source records attributed to A J Howie.

At least 91 records · Page 5Linked to original sources
PubMed1992

Renal biopsy findings in hypertensive patients with proteinuria.

27 patients with hypertension and persistent proteinuria were investigated by renal biopsy. The 13 patients without structural glomerular abnormalities were younger and had less proteinuria than the other 14, but otherwise the two groups had similar clinical features. 6 of the 14 had diffuse glomerular abnormalities; the other 8 had segmental sclerosing lesions, which were mainly in the hilum of the glomeruli, as seen in states of glomerular overload. Glomeruli in all groups were larger than those in normotensive people. It is possible that hypertension causes glomerular enlargement, proteinuria, and segmental glomerular lesions because of loss of functioning glomeruli due to ischaemia.

Adult↗
PubMed1992

Effect of cholesterol on the position of segmental lesions in unilaterally nephrectomized rats.

Different positions of segmental lesions within glomeruli may correspond to different pathogenetic mechanisms. The effect of a high cholesterol diet on the position of lesions had not previously been investigated. This was studied in rats following unilateral nephrectomy, as a change in position would suggest a different mechanism of damage. Thirty-two female WAG/ola rats had unilateral nephrectomy. Half the rats were given a diet supplemented with 4 per cent cholesterol and 1 per cent cholic acid. At death, six at 10 weeks after nephrectomy and the rest at 24 weeks, kidney sections were examined microscopically. There were significantly more segmental lesions in the cholesterol-fed rats than in the controls, and these lesions were almost entirely at the glomerular hilum in both groups. Significantly more glomeruli contained foamy cells in the cholesterol-fed group, both within lesions and away from them. These findings confirmed that in reduced renal mass, segmental lesions are mainly hilar. The diet increases the number of glomeruli affected by lesions, but these are still mainly hilar. Therefore one possibility is that hypercholesterolaemia worsens the hyperfiltration effect on glomeruli. The diet also produces foamy cells scattered throughout the glomeruli but these do not appear to develop into segmental lesions.

Animals↗
PubMed1992

Confocal microscopic and other observations on the distal end of the thick limb of the human loop of Henle.

Various antibodies and lectins were used in a histological study of the human renal tubule, particularly of the distal end of the thick limb of the loop of Henle. The thick limb, identified by antibody to Tamm-Horsfall protein, ended abruptly, either at the macula densa or at a variable distance after it. At this point there was an abrupt change in cell size. Confocal microscopy and other techniques showed that this point marked an abrupt beginning of tubular staining by the cytokeratin antibody PKK2 and the lectin UEA 1, with an abrupt end of staining by the lectin DBA. Distal from this point, there were gradual changes in staining of the tubule by various reagents including other antibodies to cytokeratins. These structural findings suggest that there is a fundamental change in the tubule at the end of the thick limb. The abrupt end to the thick limb in man resembles that seen in the rat and the rabbit.

Biomarkers↗
PubMed1992

Arteries and veins formed within renal vessels: a previously neglected observation.

An abnormality of blood vessels was noted in a biopsy of a renal transplant. This took the form of apparent development of a new artery inside and concentric with the old, with elastic laminae and a muscular media, separated from the old internal elastic lamina by poorly cellular tissue. In a systematic study of material from another 119 renal transplants, 13 nephrectomy specimens for chronic pyelonephritis and hydronephrosis, 28 renal biopsies showing interstitial nephritis, and 18 renal biopsies showing small vessel vasculopathy of accelerated hypertensive type, similar arterial changes were seen in another 10 renal transplants that showed chronic vascular rejection, 1 case of chronic interstitial nephritis, and 3 cases of vasculopathy, 2 with accelerated hypertension and 1 with systemic sclerosis. One renal transplant also showed apparent development of new muscular veins inside old veins. Immunohistological study for smooth muscle actin confirmed that the apparently new arterial and venous structures contained smooth muscle cells. The arterial abnormality may be called arterialisation of intrarenal arteries. This change appears to be not rare, is distinctive, and has scarcely been previously recognised or reported as a response of intrarenal blood vessels to damage.

Adult↗
PubMed1992

Comparison of size of juxtamedullary and outer cortical glomeruli in normal adult kidney.

Abnormally large glomeruli are susceptible to hyperfiltration-associated sclerosis. We used an established morphometric method to test the general belief that juxtamedullary glomeruli are larger than those in the outer cortex, in a population with no clinical or pathological evidence of renal disease. Overall, juxtamedullary glomeruli were significantly larger, but this varied according to the amount of global glomerulosclerosis present. Global sclerosis increased with age, particularly in the outer cortex, and the ratio of juxtamedullary to outer cortical glomerular size showed a positive correlation with overall, and outer cortical, global sclerosis. Thus in the truly normal adult kidney, juxtamedullary glomeruli are not significantly larger than outer cortical glomeruli. However, global sclerosis increases with age and is most marked in the outer cortex, and this leads to compensatory enlargement of predominantly the juxtamedullary glomeruli. These findings suggest that in single kidneys, or in conditions characterised by ischaemic glomerulosclerosis such as hypertension, morphological changes related to hyperfiltration may appear first, and therefore become most severe, in juxtamedullary glomeruli.

Adult↗
PubMed1992

Evidence for unique distribution of Kimmelstiel-Wilson nodules in glomeruli.

Different distributions of segmental lesions within glomeruli correspond to different pathogenetic mechanisms. A graphic method of analysis of the position of segmental lesions was applied to 106 Kimmelstiel-Wilson nodules in 10 renal biopsies from patients with diabetic glomerulonephropathy, 4 with IDDM and 6 with NIDDM. The nodules were randomly distributed in a horseshoe-shaped area corresponding to the peripheral or intralobular mesangium. This distribution was different from that of segmental lesions studied previously in the glomerular tip lesion, in vasculitic-type glomerulonephritis, and in hyperfiltration associated with reduced renal mass. Our finding is consistent with ideas that Kimmelstiel-Wilson nodules have a distinct pathogenesis not related to hyperfiltration or any other process previously investigated as a cause of characteristic distribution of segmental lesions.

Adult↗
PubMed1992

Increased prevalence of renal biopsy findings other than diabetic glomerulopathy in type II diabetes mellitus.

It is a widely held view that when a patient with type I diabetes mellitus and diabetic retinopathy or neuropathy develops renal impairment the renal lesion will be diabetic glomerulonephropathy. This has been extrapolated to apply to type II diabetes. We have performed a retrospective study of the clinical data of patients with diabetes mellitus who have had a renal biopsy between November 1980 and December 1990. Seventy-one patients were biopsied, data were available on 68. Nineteen of 22 type I diabetics had diabetic glomerulopathy, two had diabetic glomerulopathy in addition to another lesion only one patient did not have diabetic glomerulopathy. Twenty-three of 46 type II diabetics had diabetic glomerulopathy alone 22 having an alternative diagnosis. Eight further patients were identified who were not known to be diabetic at the time of renal biopsy, but whose biopsies revealed diabetic glomerulopathy. These data suggest that patients with type II diabetes and renal impairment should have a renal biopsy as part of their investigation.

Adult↗
PubMed1991

Immunoreactive Tamm-Horsfall protein in the kidney and skin of the frog Rana temporaria.

Tamm-Horsfall protein (THP) is the main protein in normal human urine, and is found in the thick limb of the Loop of Henle in human kidney, and in other mammalian species. The skin of the frog. Rana temporaria, has similar physiological properties to this mammalian kidney tissue. In the present study, an immunohistological method involving an antibody to human THP was used to investigate the distribution of this distinctive protein in frog kidney and skin, and to compare its distribution with that found in the kidney tubules of rat and rabbit. THP-positive material was detected in the distal renal tubules and nephric duct of frogs, and was also located in the superficial epidermis of skin. It is suggested that its presence in amphibian skin is consistent with the hypothesis that THP is an important component of tissues that absorb sodium and chloride ions, but remain impermeable to water.

Animals↗
PubMed1991

Anti-idiotype and immunosuppressant treatment of murine lupus.

The effect of the administration of a xenogeneic anti-idiotype antibody (anti-Id33) to a cross-reactive idiotype (Id33) present on anti-dsDNA antibody was examined in 6-week-old (NZB/NZW) F1 (BWF1) female mice. The administration of anti-Id33 led to a transient reduction in immunoglobulins expressing Id33, followed by a rise at 30 and 34 weeks that was significantly higher than in untreated mice (P less than 0.05). Likewise, anti-dsDNA antibody levels were significantly higher at 10 and 18 weeks than in untreated mice (P less than 0.01). No differences were seen in survival to 40 weeks, proteinuria or the severity of glomerulonephritis. Concurrent administration of cyclosporin A (CyA) with anti-Id33 markedly ameliorated glomerular injury and proteinuria and improved survival. By contrast, glomerular injury, proteinuria and survival were worse in mice treated with cyclophosphamide plus anti-Id33, compared with untreated mice. Neither CyA nor cyclophosphamide treatment, when given with anti-Id33 altered serum levels of anti-dsDNA, anti-ssDNA or Id33+ immunoglobin, compared with untreated mice. The different effects of CyA and cyclophosphamide on T lymphocytes and their discrepant effects on glomerular injury when given with anti-Id33 in this model lead us to postulate a role for T lymphocytes in the glomerular injury of BWF1 lupus.

Animals↗
PubMed1991

Urinary IL-6: a marker for mesangial proliferative glomerulonephritis?

A prospective study of plasma and urinary interleukin-6 (IL-6) levels was performed in 54 patients undergoing renal biopsy to determine whether detectable urinary IL-6 was a reliable marker for mesangial proliferation. Interleukin-6 was found in both the urine and plasma of seven patients, the urine alone of 15 patients, and the plasma alone of two patients. Interleukin-6 was not detected in the urine or the plasma of the remaining 30 patients, the urine of 10 healthy controls or the urine of 10 patients with rheumatoid arthritis with raised plasma IL-6. Interleukin-6 was found in the urine of only one out of an additional seven patients with lupus nephritis. Urinary IL-6 was associated with a variety of renal abnormalities and was not restricted to those with mesangial hypercellularity. Furthermore, many patients with mesangial hypercellularity did not have detectable urinary IL-6. There was no correlation between urinary IL-6 and plasma IL-6, urinary albumin excretion or urinary creatinine. These results suggest that IL-6 detected in the urine is a marker of renal IL-6 production, but not specifically of mesangial hypercellularity. The patients with IL-6 in the urine had a mean serum creatinine significantly higher than those without IL-6. It is not possible to distinguish at present whether IL-6 contributes to renal dysfunction or whether it reflects renal damage.

Adolescent↗
PubMed1990

Morphometric correlates of renal excretory function.

There is often thought to be little or no correlation between renal excretory function and histological changes in the kidney, especially in acute renal failure and in the kidney examined post-mortem. We studied the relationship between renal function and structure in 28 patients at necropsy and in 41 patients who had a renal biopsy. A point-counting method was used on kidney stained by an immunoperoxidase method using an antiserum to proximal tubule brush border; an antiserum to Tamm-Horsfall protein, which is a marker of thick limbs of the loop of Henle; and a monoclonal antibody to epithelial membrane antigen, normally a marker of all parts of the tubule except proximal tubule. There was a correlation between the reciprocal of plasma creatinine concentration, which is a measure of renal function, and the ratio of brush border positive tubules to negative tubules. There was also a less strong correlation between renal function and ratios of Tamm-Horsfall positive tubules to negative tubules and of cast-containing tubules to others. There was no correlation between renal function and the ratio of tubules expressing epithelial membrane antigen to those not expressing it. The method of point-counting tubules stained by the brush border antiserum was a useful, practical way of correlating renal function and structure which could be used even on post-mortem kidney.

Adolescent↗
PubMed1990

Assessment of glomerular size in renal biopsies including minimal change nephropathy and single kidneys.

A method of assessing glomerular size on sections of post-mortem kidney was adapted for use on needle biopsies of kidney. A semi-automatic image analyser was used to measure the cross-sectional area of the outline of Bowman's capsule on all glomeruli in renal biopsies. The mean of approximately the largest 25 per cent of areas was calculated. The method was used to compare glomeruli in 13 control patients without obvious structural abnormalities with those in 10 patients with a single kidney, 22 with minimal change nephropathy, and 20 with membranous nephropathy. Patients were at least 14 years old. Glomeruli in minimal change nephropathy were significantly smaller than those in all other groups. Glomeruli in single kidneys were significantly larger than those in all other groups. Glomeruli in membranous nephropathy were the same size as controls. Any differences between groups could not be explained by differences in body build. It is possible that in adults glomeruli in minimal change nephropathy are abnormally small. The method of assessing glomerular size can be used on renal biopsies as well as on sections of whole kidney.

Adolescent↗
PubMed1990

Analysis of the position of segmental lesions in glomeruli in vasculitic-type glomerulonephritis and other disorders.

A method was developed of plotting the position of segmental lesions in glomeruli on histological sections of kidney. Using a Leitz Imagan semi-automatic image analyser, the outline of lesions was traced, as was the outline of Bowman's capsule. The centre of gravity of a lesion, computed by the image analyser, was plotted with reference to the line through the hilum and the centre of gravity of the glomerulus, by taking its angle to that line and its proportional distance between that line and Bowman's capsule. Points representing all lesions were transferred onto a circle graphically representing a glomerulus. Lesions in 11 renal biopsies with the glomerular tip lesion were clustered at the tubular origin. Lesions in four necropsy kidneys from patients with one kidney were clustered at both the vascular pole and the tubular origin. Lesions in 13 renal biopsies with acute vasculitic-type glomerulonephritis were shown to be randomly scattered by nearest-neighbour analysis, after allowance had been made for an edge effect due to the method of plotting lesions and for an area where the arterioles passed through Bowman's capsule. Scientific analysis of the position of segmental lesions is possible and has confirmed previous suggestions that there are at least three general sites in which these lesions can be distributed in glomeruli: at the tip, at the vascular pole, and randomly.

Glomerulonephritis↗
PubMed1990

Determinants of glomerular cross-sectional area.

A method of measurement of glomerular cross-sectional area was applied to 267 renal biopsies from 19 groups of patients with well-defined pathological and clinical conditions. There was a correlation between the mean glomerular area for each group and the percentage of global sclerosis in each group. A few groups had glomeruli that were larger than would be expected from their percentage of global sclerosis, probably due to cellular proliferation and/or infiltration. A few groups had glomeruli that were smaller than would be expected from their percentage of global sclerosis, probably due to ischaemic shrinkage. These observations indicate that as well as the known influence of body size on the glomerular area, the number of functioning glomeruli in the body has an important effect on the glomerular area.

Biopsy↗
PubMed1990

Technical improvements in the immunoperoxidase study of renal biopsy specimens.

Sixty five renal biopsy specimens were used to compare a direct immunofluorescence technique on frozen sections with immunoperoxidase techniques on paraffin wax sections. For the immunoperoxidase techniques, dewaxed sections were treated with protease at 37 degrees C. Sections were examined at intervals on a microscope and digestion was stopped when plasma was removed from glomerular capillary loops. This permitted intense staining of immunoproteins on immunoperoxidase. There was agreement between immunoperoxidase and immunofluorescence in the staining for IgG, IgA, and IgM in 50 biopsy specimens and discordant findings did not affect the diagnosis. Immunoperoxidase did not detect C3 in 16 biopsy specimens. Findings with antiserum to another complement component, C9, detected by immunoperoxidase correlated with C3 findings detected by immunofluorescence in 17 biopsy specimens. It is concluded that microscopical observation of the progress of digestion permits optimal staining by immunoperoxidase methods, thus overcoming the problem of variability in proteolytic digestion of sections. Inconsistency in the demonstration of complement deposition can be avoided by staining for C9 rather than C3.

Complement C3↗
PubMed1989

Different types of segmental sclerosing glomerular lesions in six experimental models of proteinuria.

From 133 to 615 glomeruli were examined in sections of kidneys from each of 60 animals, representing six rodent models of proteinuria. Particular attention was paid to the position of segmental lesions. Lewis rats given sheep anti-rat glomerular basement membrane antibodies had lesions almost exclusively at the glomerulo-tubular junction. Wistar rats on a diet of 24 per cent casein or with subtotal nephrectomy and a diet of 24 per cent soya had lesions mainly at the hilum. Wistar rats given bovine serum albumin had global lesions but virtually no segmental lesions. Wistar rats given puromycin aminonucleoside had lesions at the glomerulo-tubular junction and global mesangial abnormalities shortly after the treatment but later developed segmental lesions at all parts of the glomerulus. Untreated BUF/Mna rats had lesions at the glomerulo-tubular junction early in life but later had lesions at all parts of the glomerulus. Untreated NZB/NZW hybrid mice had various types of glomerulonephritis and also had lesions at the glomerulo-tubular junction. These findings showed that (1) segmental lesions at the glomerulo-tubular junction, or glomerular tip, occur in experimental animals, a fact not previously reported, and these tip changes are a common feature in several different models of proteinuria; (2) hilar segmental lesions are seen in conditions with hyperfiltration of protein; and (3) segmental lesions at various parts of the glomerulus are seen in some models of proteinuria and probably indicate late effects of random toxic damage to the glomerulus. Thus, there are at least three different types of segmental glomerular lesions in experimental animals--tip, hilar, and random--with different morphology and pathogenesis. It is likely that these findings can be extended to human renal diseases with segmental glomerular lesions. This will help to clarify the controversial and unsatisfactory term focal segmental glomerulosclerosis.

Animals↗