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Biomedical subjects

G B Lindop

Publications and source records attributed to G B Lindop.

At least 55 records · Page 3Linked to original sources

The glomerular peripolar cell: a review.

There is now morphological evidence from several species that the peripolar cell is a distinctive glomerular cell which may have a secretory function, although a secretory product has not been identified. Peripolar cells, like other glomerular epithelial cells, probably absorb plasma proteins from the glomerular filtrate. Peripolar cells may participate in regulation of sodium balance and the changes in renal function which occur at the time of birth. They are ideally situated to monitor the composition of the glomerular filtrate and/or the calibre of the glomerular arterioles. The relationship between peripolar cells and other granulated glomerular epithelial cells must be clarified, however their morphology and unique anatomical site is suggestive of a specialised function.

Animals↗

Renin gene expression in nephroblastoma.

Most cases of nephroblastoma have high plasma levels of prorenin which is biologically inactive. Plasma prorenin levels fall to normal following nephrectomy. In order to ascertain whether renin synthesis occurs in nephroblastomas we decided to search for renin-specific mRNA using a cDNA probe and Northern blot analyses on total RNA purified from snap-frozen human tumour tissue obtained at nephrectomy. We demonstrated renin-specific mRNA in 5/11 (45 per cent) nephroblastomas. It was 1.6 Kb in length, similar to the mRNA detected in normal kidney tissue and in kidneys with renal artery stenosis. In one of the cases of nephroblastoma, in which we could detect no normal renin mRNA at 1.6 Kb, the cDNA probe hybridized with a higher molecular weight mRNA 3 Kb in length. We conclude that some nephroblastomas synthesize renin.

Gene Expression↗

The renin-secreting cell in polyarteritis--an immunocytochemical study.

We studied kidney sections from 15 cases of polyarteritis using an immunocytochemical technique to demonstrate cells containing immunoreactive renin. Ten cases of classical polyarteritis nodosa showed hyperplasia of renin-containing cells in areas of renal cortex with histological evidence of ischaemia--appearances indistinguishable from those seen in renal artery stenosis. Histologically normal cortex showed little or no immunostainable renin. In the ischaemic areas there was loss of the normal gradient of renin-containing cells from superficial to deep cortex. In many cases this gradient was abolished or even reversed; in some cases most renin-containing cells were in juxtaglomerular apparatuses. This alteration in the distribution of immunoreactive renin has only been described in renal artery stenosis in man. In five cases of microscopic polyarteritis there were fewer than normal numbers of renin-containing cells. We suggest that in classical polyarteritis nodosa, focal ischaemia causes activation of the renin-angiotensin system analogous to the changes caused by renal artery stenosis. This may be important in the pathogenesis of hypertension in this condition. By contrast, in microscopic polyarteritis, the appearances of the juxtaglomerular apparatus and the reduced amounts of immunostainable renin suggest suppression of renin synthesis.

Adolescent↗

The distribution of renin-containing cells in kidneys with renal artery stenosis--an immunocytochemical study.

In 10 kidneys removed for hypertension due to renal artery stenosis, the histological appearances varied from negligible ischaemic damage to end-stage ischaemic atrophy. We stained the renin-containing cells in tissue sections using an antiserum to pure human renin and an immunoperoxidase technique. In all kidneys there was hyperplasia of the renin-containing cells both in juxtaglomerular apparatuses (JGAs) and in arteries outside the JGA, where these cells extended proximally as far as the interlobular arteries. We mapped the distribution of renin-containing cells and found them in all zones of the renal cortex; in three kidneys they were predominantly in the superficial cortex; in four they were distributed more evenly throughout the width of the cortex; but in three kidneys the normal gradient was reversed, with most of the cells being in the juxtamedullary cortex and, in two of the cases, little or no stainable renin in the superficial cortical JGAs. We suggest that these abnormalities in the distribution of renin-containing cells could affect both the pattern of intrarenal blood flow and the site in the kidney at which secreted renin enters the blood.

Humans↗

The peripolar cell: a distinctive cell type in the mammalian glomerulus. Morphological evidence from a study of sheep.

We used scanning electron microscopy to study the glomerular peripolar cell in the kidneys of seven sheep. Peripolar cells were present in a variable proportion (3.6-100%) of glomeruli. Although on average two peripolar cells were present at each vascular pole, up to ten were seen on occasion. They were more often related to the afferent than to the efferent arteriole. Mapping the relative position of each cell failed to reveal any zonal distribution in the renal cortex. Scanning electron microscopy showed that they were globular in shape and had a bossellated surface. We showed by examination of cells which had been broken open that this appearance was due to the presence of cytoplasmic granules that produced bulging of the cell membrane. We suggest that scanning electron microscopy is a suitable method for studying this cell in the mammalian kidney.

Animals↗

A scanning electron-microscopic study of the peripolar cell of the rat renal glomerulus.

The interior of Bowman's capsules of rat kidneys has been examined by scanning electron microscopy, and a distinctive population of cells around the exposed vascular poles of glomerular tufts were identified. The cells were situated in the annular groove at the root of the glomerulus, between the parietal epithelial cells and the podocytes. These peripolar cells were dendritic cells with long processes embracing the glomerular arterioles. Up to three peripolar cells were present at each vascular pole and they were mainly distributed in the glomeruli of the outer third of the renal cortex. This first detailed study of the surface morphology of the glomerular peripolar cell supports the suggestion that changes in the diameter of the polar region of the glomerular tuft may cause variations in stretching of the cuff of peripolar cells, and hence modulation of their secretory activity.

Animals↗

Endomyocardial biopsy pathology in insulin-dependent diabetic patients with abnormal ventricular function.

We have previously shown impaired ventricular function in asymptomatic middle-aged type 1 (insulin-dependent) diabetic patients who had no evidence of coronary artery disease. The diabetic patients had normal coronary angiograms but reduced ventricular ejection fraction on exercise. To examine the possible contribution of small vessel disease to this functional abnormality, we compared endomyocardial biopsies from seven symptom-free type 1 diabetic patients with biopsies from seven age- and sex-matched non-diabetic subjects. Interstitial fibrosis was present in three diabetic patients, arteriolar hyalinization in three patients and arteriolar thickening was observed in five patients. Morphometry performed on electron micrographs showed no significant difference in the thickness of the capillary basal lamina between diabetics and controls. While the functional significance of the abnormalities on light microscopy is unclear, our findings indicate that the abnormality of cardiac function described in diabetes is not associated with thickening of the myocardial capillary basal lamina.

Adult↗

The anatomy of the renin-secreting cell in adult polycystic kidney disease.

We used a human renin antiserum and an immunoperoxidase method to investigate the distribution of renin-containing cells in 19 adult polycystic kidneys: 9 autopsy and 10 nephrectomy cases. These cells were present in residual normal kidney, in scarred renal parenchyma and in area of fibrous tissue. They were situated mainly in juxtaglomerular apparatuses (JGAs) and in the walls of arteries and arterioles. A semi-quantitative analysis showed hyperplasia of JGA renin-containing cells in the untreated autopsy cases. In both groups there was an abnormal distribution of renin-containing cells; only 50% were located in the JGAs the remainder were mainly in the walls of small arteries. These were often thin, attenuated vessels in the walls of cysts. Cells containing renin were also found isolated in fibrous tissue separate from the arterial tree. This abnormal location of the renin-containing cells suggests that they may respond to different stimuli than those in normal kidneys, and their abnormal distribution could affect both the intrarenal action of renin and also its release into the blood.

Adult↗

Inactive renin: a tumor marker in nephroblastoma.

Renin-containing cells have been identified in nephroblastoma. A prospective study of eight children with nephroblastoma has demonstrated abnormally high levels of total renin. The increase in total renin was due to increased levels of inactive renin (prorenin), rather than the active renin. These high levels decreased to normal after operation. The plasma level of inactive renin could be a useful biochemical tumor marker in nephroblastoma.

Child↗

ANF (99-126) and its propeptide, ANF (1-16) are secreted simultaneously from the human atrial myocyte.

We have raised antisera to two synthetic peptides representing different portions of the human pro-atrial natriuretic factor (ANF) molecule; one antiserum identifies active human ANF, the 28-amino-acid sequence on the C-terminal end of the prohormone [ANF (99-126)], and the other detects ANF (1-16), the first 16-amino-acid sequence at the N-terminal end of the prohormone. With ultrastructural immunocytochemistry we have studied the distribution staining for both peptides within the myocytes in surgically excised human auricular appendages. Most of the endocrine granules stained with equal density for both ANF (1-16) and ANF (99-126). Also, double immuno-staining techniques on the same tissue section showed that both the C-terminal peptide and the N-terminal peptide co-existed within the same endocrine granules. It has been shown that, like other endocrine cells, atrial myocytes secrete their stored peptides by exocytosis of their granules. Therefore, our observations suggest that both the main active hormone, ANF (99-126), and the N-terminal propeptide ANF (1-16) are secreted simultaneously from the cell.

Atrial Natriuretic Factor↗

Mixed follicular-parafollicular carcinoma of the thyroid.

We present a case of mixed follicular-parafollicular carcinoma of the thyroid. Immunohistochemical studies demonstrated the presence of both thyroglobulin and calcitonin within tumour cells. The recognition of thyroid tumours showing this mixed differentiation may have implications for existing concepts of C-cell and follicular cell development in the human thyroid.

Adenocarcinoma↗

Immunocytochemistry of renin in renal tumours.

We used a panel of two polyclonal antisera and two monoclonal antibodies to human renin to assess the tissue distribution of immunoreactive renin in a range of tumours and normal human tissues. The only tissue showing positive staining for renin was kidney and all four antisera stained the myoepithelioid cells in the renal cortex. In the survey of tumours we found immunoreactive renin only in renal tumours, namely, renal cell carcinoma, and nephroblastoma (Wilms' tumour). The renin-positive cells were sparse and distributed mainly along the course of the tumour blood vessels. They stained positively with all four antibodies and, in pairs of serial sections, we showed that the same cell reacted with two different antisera. This suggests that renal cell carcinoma and nephroblastoma have within them cells which contain renin.

Antibodies, Monoclonal↗

Renin and inactive renin (prorenin) in the plasma of patients with malignant renal tumours.

Plasma active and inactive renin (porenin) concentrations were measured in 26 adults with renal carcinoma and 8 children with nephroblastoma. In patients with carcinoma, plasma total renin concentration was slightly raised in 8 patients and markedly in one, in whom the increase was due to a more than 10-fold excess of inactive renin. Total renin concentration was raised in 7 out of 8 cases of nephroblastoma, the increase being due to excess inactive renin. It is likely that this represented oversecretion of a renin precursor, as inactive renin from the plasma of a patient with renal carcinoma showed similar biochemical characteristics to pure human prorenin.

Adult↗

Cardiac function and coronary arteriography in asymptomatic type 1 (insulin-dependent) diabetic patients: evidence for a specific diabetic heart disease.

Cardiac function was examined in 63 asymptomatic Type 1 (insulin-dependent) diabetic patients, aged 30-50 years, using radionuclide ventriculography and exercise electrocardiography to investigate the possible existence of a specific diabetic heart disease. Comparisons were made with 45 age- and sex-matched non-diabetic controls. Radionuclide ventriculography was performed at rest and during the physiological stresses of isometric exercise, cold-pressor testing and dynamic exercise. Scans were technically satisfactory in 56 of the diabetic patients and 38 of the control subjects. The resting left ventricular ejection fractions and the responses to isometric exercise and cold-pressor testing were similar in the diabetic patients and controls. A smaller rise in the left ventricular ejection fraction during dynamic exercise was observed in male diabetic patients compared with male control subjects (9 +/- 1% (mean +/- SEM) vs 14 +/- 1% (p less than 0.005)). A similar trend was observed in female diabetic patients, with a rise of 5 +/- 1% on dynamic exercise compared with a rise of 8 +/- 1% in the control group. Sixteen diabetic patients (29%) demonstrated an abnormal response to dynamic exercise, and 5 of these had an abnormal exercise electrocardiogram. Cardiac catheterisation and coronary arteriography were performed in eight of these 16 patients, and all 8 had normal coronary arteries. Endomyocardial biopsy revealed arteriolar thickening and interstitial fibrosis in 5 patients, and in 2 patients basement membrane thickening was conspicuous. Thus, in diabetic patients cardiac function may be abnormal without evidence of coronary heart disease, and some patients appear to have the histological changes consistent with a diabetic microangiopathy involving the heart.

Adult↗

Anatomy of the renin-angiotensin system in the normal and pathological kidney.

In this review we describe the contributions made by immunocytochemistry to our knowledge of the renin-angiotensin system in the normal and the pathological kidney. Most of the renin-secreting cells appear to be on the outer aspect of the vessel wall, supporting the view that renin is secreted mainly into the interstitium of the kidney rather than into the lumen of the vessel. Angiotensin II immunoreactivity is present within renin-secreting cells. The angiotensin II appears to be present in high concentration in the renin storage granules and is therefore presumably secreted from the cell with renin. The pathways by which renin is secreted from the cell have also been clarified. In pathological kidneys, the reactions of renin-secreting cells to variation in functional demand have been confirmed. Renin-containing cells have also been found in most types of renal tumours and occasional cases probably secrete renin or prorenin into the blood. In renal tumours and in the developing kidney (in all species studied) the renin-containing cells are also intimately associated with blood vessels.

Angiotensinogen↗

Malignant hypertension due to a renin-secreting renal cell carcinoma--an ultrastructural and immunocytochemical study.

This is a case report of a 14-year-old girl who presented with malignant hypertension. She had high plasma levels of both active and inactive renin and investigation revealed a renal tumour. The tumour, a renal cell carcinoma, was removed by nephrectomy following which the blood pressure and the plasma renin levels fell to normal. An immunocytochemical study using an antibody to pure human renin showed no detectable renin in the kidney but the tumour contained a population of granular cells which showed strong positive staining for immunoreactive renin. We present the clinical, biochemical, histological, immunocytochemical and ultrastructural features of this case as evidence that this was a renin-secreting renal cell carcinoma.

Adolescent↗