PubMed Health⌕ Search

Biomedical subjects

G B Lindop

Publications and source records attributed to G B Lindop.

At least 37 records · Page 2Linked to original sources
PubMed1993

Collagen-linked fluorescence in human atherosclerotic plaques.

Advanced glycosylation endproducts (AGE) are intraprotein crosslinks which form in the late stages of the Maillard (browning) reaction. It is unknown whether local changes in AGE-modified collagen occur within arteries. We measured AGE-modified collagen as collagen-linked fluorescence (CLF) in human arterial tissue and in various forms of atherosclerotic plaque. All tissues showed single fluorescence peak at excitation wavelength 340 nm and emission wavelength 420-440 nm. CLF in the aorta was 27.9 +/- 8.5 units/mg, in the coronary arteries 25.9 +/- 6.3 units/mg and in the tendon 47.8 +/- 11.5 units/mg. CLF in the skin correlated with CLF in the aorta (r = 0.467, P = 0.025) but not with CLF in coronary arteries (P = 0.935). In areas of aorta covered by superficial plaque, CLF was decreased compared with adjacent, atheroma-free segments (22.2 +/- 5.2 units/mg vs. 27.9 +/- 8.5 units/mg; P = 0.01). The CLF of collagenous plaques correlated with CLF of the atheroma-free regions. Individuals with low to moderate atheroma had lower (20.0 units/mg) CLF in superficial atherosclerotic plaques than patients with severe atheroma (22.5 units/mg; P = 0.0466). Our results indicate that local changes in vascular AGE-collagen concentration occur in atherosclerosis. This finding may have pathogenetic significance in atherosclerosis.

Aged↗
PubMed1993

Hormonal control of atrial natriuretic peptide synthesis and secretion from cultured atrial myocytes.

We have established optimal culture conditions for growing well-differentiated atrial myocytes from newborn rats. These myocytes show the morphological features of myocytes in intact atria; including perinuclear endocrine storage granules, contractile apparatus and numerous mitochondria. The cells synthesise, store and secrete immunoreactive ANP. Stored ANP is of similar molecular weight to pro-ANP (1-126); secreted ANP is the active form ANP (99-126) but processing appears to take place slowly after secretion. ANP secretion is stimulated by endothelin. Synthesis and secretion of ANP are markedly reduced by the beta-adrenergic agonist isoproterenol, and by forskolin.

Animals↗
PubMed1993

Atrial natriuretic hormone: a paracrine or endocrine role within the human placenta?

There is evidence to suggest that the human placenta may synthesize atrial natriuretic hormone (ANH). To test this hypothesis we examined specimens of normal term placenta obtained at elective caesarean section for evidence of either storage or synthesis of this peptide. No immunocytochemical or ultrastructural evidence of ANH storage was found. RNA extracted from cultured cytotrophoblast cells, the chorionic or decidual plates, or from placental villi contained no ANH-encoding messenger RNA by Northern blot analysis. Polymerase chain reaction amplification of these RNA extracts using primers directed to the midportion of the ANH gene failed to demonstrate any evidence of ANH-encoding RNA. We conclude that ANH is neither stored nor synthesized within the normal term placenta, and thus a purely endocrine role for this peptide within the fetoplacental compartment is proposed.

Atrial Natriuretic Factor↗
PubMed1992

Peripolar cells, granulated glomerular epithelial cells, and their relationship to the juxtaglomerular apparatus in malignant hypertension.

We have examined 12 autopsy kidneys from cases of malignant hypertension and compared them with normal controls. Peripolar cells and other granulated glomerular epithelial cells were counted in serial paraffin sections, and renin-containing cells were quantified using an immunoperoxidase technique and a human renin antiserum. There were significantly more peripolar cells and other granulated glomerular epithelial cells in the cases of malignant hypertension. Most granulated glomerular epithelial cells were podocytes, situated at the periphery of the tuft. Peripolar cells correlated in number with other granulated glomerular epithelial cells and they had a similar distribution within the renal cortex, but there was no correlation between either of these cells and the number of renin-containing cells. There was hyperplasia of renin-containing cells in some juxtaglomerular apparatuses (JGAs), although the proportion of renin-positive JGAs was unaltered. These results suggest that peripolar cells and other glomerular epithelial cells react in a similar way in malignant hypertension, but they do not support the hypothesis that peripolar cells are part of the JGA.

Epithelium↗
PubMed1992

Non-granulated peripolar cells exist in the rat glomerulus.

The peripolar cell is a unique cell type in the mammalian glomerulus. Peripolar cells are said to be identifiable during light microscopy by their cytoplasmic granules and by their position at the vascular pole; and during scanning electron microscopy by their distinctive surface morphology. We used both techniques to count peripolar cells in 6 normal rat kidneys. Scanning microscopy revealed that 55(+/- 5)% of glomeruli contained at least one peripolar cell whereas light microscopy revealed granulated peripolar cells in only 4(+/- 2)% of glomeruli. Vascular poles which contained peripolar cells previously identified by scanning were then examined by light and by transmission electron microscopy. Serial sections through these peripolar cells demonstrated the absence of cytoplasmic granules. Our observations suggest that the majority of peripolar cells in the rat contain no granules.

Animals↗
PubMed1992

The renin-secreting cell and the glomerular peripolar cell in renal artery stenosis and Addison's disease.

The glomerular peripolar cell may be a secretory component of the juxtaglomerular apparatus. To investigate this hypothesis we studied kidneys with the renin-angiotensin system activated by two different stimuli in order to compare the responses of peripolar cells and renin-secreting cells. We examined 10 human kidneys, removed for renal artery stenosis and 11 autopsy cases of Addison's disease with appropriate controls. We counted granulated peripolar cells in serial paraffin-embedded sections and renin-containing cells were quantified using an immunoperoxidase technique with an antiserum to human renin. There was a five-fold increase in the number of renin-containing cells in both renal artery stenosis and in untreated, but not in treated, Addison's disease. Peripolar cells were increased in number in three cases of renal artery stenosis, but were unaltered in both treated and untreated Addison's disease. Therefore, neither a reduction in renal perfusion pressure (renal artery stenosis), nor sodium depletion (Addison's disease) consistently affect peripolar cells in humans. These findings do not support the hypothesis that the peripolar cell is part of the juxtaglomerular apparatus.

Addison Disease↗
PubMed1992

Distribution of renin-containing cells in the developing human kidney: an immunocytochemical study.

OBJECTIVE: To characterize the pattern of renin containing cells (RCC) within the human kidney between 20 weeks of gestation and 6 months of postnatal life. DESIGN: Descriptive study using paraffin-embedded blocks of kidney stored following postmortem examination. METHODS: Sections of kidney were stained immunocytochemically using an antibody to human renin; the proportion of RCC within each of three zones (superficial, middle and deep) of the cortex, and their anatomical relation to individual glomeruli were determined. The cases were divided into five groups for analysis to gestational or postnatal age. RESULTS: Fetal RCC were usually at the vascular pole of the most mature glomeruli within the deeper areas of the cortex and were occasionally located within glomeruli. This distribution persisted until birth, even when the kidney was histologically mature. By contrast there were fewer RCC in neonatal and infant kidneys and, as in adult kidneys, these were located predominantly in the superficial cortex. CONCLUSION: The change in RCC distribution around the time of normal birth may relate to the transition to independent renal function. The location and density of RCC during fetal life may influence renal perfusion and amniotic fluid production.

Gestational Age↗
PubMed1992

Three-dimensional reconstruction of human juxtaglomerular apparatus (JGA).

A three-dimensional and morphological study of the human JGA was undertaken to establish a background for understanding the changes in this vital apparatus during various physiological and pathological conditions. Three-dimensional reconstruction was carried out using a computer program "GLOM". Serial sections of normal human kidneys were used after staining with specific human renin antiserum. Three-dimensional reconstruction revealed renin-positive cells in the afferent and efferent arterioles and interlobular arteries away from the JGA area. A close contact was demonstrated between renin-positive cells and the macula densa. The frequency of positively stained JGAs was significantly higher in the superficial glomeruli compared to the deep glomeruli. The high renin content of the superficial glomeruli suggests higher generation of angiotensin, which may contribute to the regulation of the GFR as proposed by other workers. This preliminary study on normal human JGA is to be extended to hypertensive and renal failure patients.

Adult↗
PubMed1992

The glomerular peripolar cell--an immunohistochemical study.

The peripolar cell is a recently described glomerular epithelial cell which may be a new secretory component of the juxtaglomerular apparatus (JGA). The purposes of this study were to identify immunohistochemical markers specific for peripolar cells and to elucidate the composition of their cytoplasmic granules. We examined tissue from normal human and sheep kidneys with a variety of monoclonal antibodies and antisera. A minority of peripolar cells showed immunoreactivity for vimentin but no other intermediate filament. Neuroendocrine markers were negative. The granules of peripolar cells contain a variety of plasma proteins with the exception of IgM. It is likely that peripolar cells absorb plasma proteins from the glomerular filtrate. The reason for this is uncertain; however, their unique position at the vascular pole of normal kidneys suggests a specialized function.

Animals↗
PubMed1992

Peripolar cells and other granulated epithelial cells in renal biopsies.

The peripolar cell is a recently described glomerular epithelial cell which is situated within Bowman's capsule at the vascular pole. It contains cytoplasmic granules which contain plasma proteins, although it may also have a secretory function. The relationship between peripolar cells, other granulated glomerular epithelial cells and tubular epithelial cells is unclear. We have studied 242 biopsies from 19 types of renal disease for peripolar cells, other granulated epithelial cells and granulated tubular epithelial cells. Peripolar cells were most numerous in mesangioproliferative glomerulonephritis, IgA nephropathy, focal segmental glomerulosclerosis, membranous glomerulonephritis and lupus nephropathy. Other granulated glomerular epithelial cells were most prominent in diffuse lupus nephropathy, focal glomerulonephritis, acute vascular transplant rejection, crescentic glomerulonephritis and mesangioproliferative glomerulonephritis. Granulation of the tubular epithelium was most prominent in minimal change nephrotic syndrome and amyloidosis. It is likely that the granules in tubular epithelial cells represent lysosomes containing plasma proteins which have been absorbed from the tubular fluid. However, granulation of glomerular cells may represent a more specific response to glomerular damage. In addition, peripolar cells are prominent in only certain diseases, suggesting a specialized function.

Amyloidosis↗
PubMed1992

Dexamethasone-induced differentiation of atrial myocytes in culture.

Atrial and ventricular myocytes from fetal and newborn rats were cultured in medium supplemented with fetal or newborn calf serum with and without glucocorticoid. Myocyte morphology was examined by light and electron microscopy, and the amount of stored and secreted atrial natriuretic peptide (ANP) was measured. Without dexamethasone, neonatal atrial myocytes cultured for 7 days contained myofibrils organized into sarcomeres and numerous endocrine granules containing immunostainable ANP. Secretion of immunoreactive ANP reached a peak between days 7 and 9 of culture. Myocytes from fetal rats secreted ANP but contained few endocrine granules, and myofilaments were poorly organized. By contrast, the addition of dexamethasone (1 nM-1 microM) to the culture medium of newborn myocytes promoted development of numerous endocrine storage granules, mitochondria, and myofibrils with prominent Z-bands. Dexamethasone also increased the cellular content of ANP and ANP-specific mRNA in both atrial and ventricular myocytes. In the presence of dexamethasone myocytes maintained their structural integrity for periods of at least 45 days.

Animals↗
PubMed1991

Chronic pyelonephritis: the significance of renal renin and the vascular changes in the human kidney.

Hypertension complicates chronic pyelonephritis. Since arterial narrowing is common in the damaged kidney, activation of the renin-angiotensin system due to renal ischaemia has been suggested as a pathogenetic mechanism. We used an antiserum to human renin and an immunoperoxidase technique to study the anatomy of renin-containing cells (RCC) in 18 kidneys removed for pyeloneophritis. We independently assessed the degree of arterial narrowing and correlated these variables with the clinical findings. There was histological evidence of hyperplasia of RCC in 5 of the 6 hypertensive patients and in 7 of the 12 non-hypertensive cases. There was no difference in the apparent number or distribution of RCC between the hypertensive and the non-hypertensive cases. Also, the degree of arterial narrowing did not correlate with either the hyperplasia of RCC or the blood pressure of the patients. Our results do not support the hypothesis that narrowing of the intrarenal arteries is important in the pathogenesis of hypertension in pyelonephritis. In our cases, the renal veins were more severely damaged than the arteries and their lumina were often obliterated by organized thrombus. We suggest that such widespread obliteration of the renal venous tree could impair blood flow and contribute to the tissue damage in the pyelonephritic kidney.

Adolescent↗
PubMed1991

Unilateral papillary necrosis complicating renal artery stenosis--evidence of activation of the intrarenal renin-angiotensin system?

We report an association between renal artery stenosis and papillary necrosis. We studied three kidneys with renal artery stenosis, two of which showed ipsilateral acute papillary necrosis. In all three cases there had been a sudden fall in perfusion of the ischaemic kidney. In the case with intact papillae, immunostainable renin was normal in amount and distribution, whereas both kidneys with papillary necrosis showed hyperplasia of renin-containing cells, and these were mainly in the JGAs of the juxtamedullary cortex. Since the contralateral kidneys were spared, we suggest that in an ischaemic kidney with hyperplasia of renin-secreting cells in the deep cortex, local activation of the renin-angiotensin system could cause acute papillary necrosis due to vasoconstriction.

Adult↗
PubMed1991

Inactive renin levels in recurrent nephroblastoma.

A prospective study of four children with nephroblastoma has demonstrated elevation of plasma inactive renin levels at the time of detection of recurrent disease. Three of the four children had been shown to have elevated inactive renin levels at their initial presentation with primary nephroblastoma. These levels returned to normal following operation and chemotherapy. The observation provides further evidence that plasma inactive renin may be a useful tumour marker for nephroblastoma.

Child↗
PubMed1991

The effect of conversion from cyclosporin to azathioprine on renin-containing cells in renal allograft biopsies.

Renal biopsies were examined from 17 renal transplant recipients before and after conversion from cyclosporin to azathioprine, and in 17 patients who remained on cyclosporin. All patients had stable renal function. We used an immunoperoxidase technique with an antiserum to human renin to identify renin-containing cells. We demonstrated hyperplasia of renin-containing cells in patients treated with cyclosporin. Numbers of renin-containing cells decreased after conversion to azathioprine. We suggest that local activation of the intrarenal renin-angiotensin system could mediate the effects of cyclosporin on renal haemodynamics. This could play a role in the pathogenesis of cyclosporin nephrotoxicity and cyclosporin hypertension.

Azathioprine↗
PubMed1991

The juxtaglomerular apparatus of the spontaneously hypertensive rat.

Spontaneously hypertensive rats (SHR) are used to study the pathogenesis of essential hypertension. This study investigates the role of the renin-angiotensin system (RAS) in the pathogenesis of hypertension in SHRs and the morphometry of the JGA by a three-dimensional computer reconstruction program "GLOM" and electron microscopy. Systolic blood pressure (SBP) (tail cuff method) was higher in SHRs compared to controls (P less than 0.001). Plasma renin concentration (PRC) was lower in SHRs than in controls (P less than 0.001). Reconstruction of the JGA revealed granulated JG cells in the afferent and efferent arterioles and in the vascular tree away from the JGA area. Electron microscopy showed granulated JG cells in the afferent and efferent arterioles. The percentage volume of the granulated JG cells in SHR was significantly higher than in controls (P less than 0.01). A relationship was found between the percentage volume of granulated JG cells and the SBP in SHRs (r = 0.933, P less than 0.05). The wall/lumen perimeter ratio was also significantly higher in the SHRs compared to the controls (P less than 0.05). Low PRC in SHRs has been reported by several workers. The apparent hyperactivity of the JGA may indicate failure of renin release or an abnormal synthesis/secretion rate.

Animals↗