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Biomedical subjects

D B Brewer

Publications and source records attributed to D B Brewer.

At least 37 records · Page 2Linked to original sources
PubMed1983

A morphometric, biochemical and histochemical comparison of puromycin aminonucleoside and hyperalbuminaemic induced proteinurias in the female Wistar rat.

Biochemical, immunological, histochemical and electron microscope morphometric techniques were used to monitor the changes in urinary protein composition, albumin clearance and glomerular ultrastructure induced in female Wistar rats following i.p. injection of puromycin aminonucleoside (PAN) or bovine albumin (BSA). BSA injected rats maintained a high degree of selectivity with albumin constituting 90 per cent. of the total protein excreted even when mean protein excretion was in the order of 500 mg/24 hr. A similar degree of selectivity was only evident in PAN nephrotic rats at low levels of proteinuria. Levels of 500 mg/24 hr only 57 per cent. of the total protein was albumin. These differences correlated well with the increased number of glomeruli from PAN nephrotics compared with hyperalbuminaemic rats which, at these high levels of proteinuria, had bare areas of glomerular basement membrane caused by epithelial cell detachment (88 and 7 per cent. respectively). Detailed electron microscope morphometric and immunohistochemical studies showed that there were also important quantitative differences in a number of superficially similar glomerular structural alterations. In PAN nephrotic rats all glomeruli showed very marked epithelial cell foot process loss and reduced staining with colloidal iron. In glomeruli from hyperalbuminaemic rats there was a wide variation in the extent of epithelial cell foot process loss and reduced colloidal iron staining was only demonstrable in those glomeruli which had swollen epithelial containing large numbers of vacuoles and protein droplets. Similarly, while protein droplets were smaller and less numerous in glomeruli from PAN-injected rats, they were present in most glomeruli whereas their distribution was much more variable in glomeruli from BSA-injected rats. All the data collected therefore indicated that there were important differences in the types of proteinuria and glomerular ultrastructural damage present in PAN nephrotic and hyperalbuminaemic rats and suggested that their induction may have involved entirely different mechanisms. Evidence gathered from one experimental model should thus only be used with extreme caution to aid in interpretation of data obtained from the other.

Albuminuria↗
PubMed1983

An electron microscopic study of the effects of vinblastine sulphate on the ultrastructure of the kidney, trachea, liver, peripheral nerve and small intestine of the rat.

The effects of vinblastine in high doses on the kidney, liver, trachea, peripheral nerve and small intestine of rats have been studied by scanning and transmission electron microscopy. Dramatic structural changes were seen in glomerular visceral epithelial cells, hepatocytes and small intestinal epithelial cells which appear to be due to the effect of vinblastine on microtubules and possibly also on other proteins and cell membranes. Ciliary microtubules appeared resistant to vinblastine effects.

Animals↗
PubMed1983

Extra-tubular deposits of Tamm-Horsfall protein in renal allografts.

Sections from 266 renal allografts that had been transplanted and removed were studied to determine the prevalence of deposits of Tamm-Horsfall protein outside tubules and resulting from tubular rupture, detected by the periodic acid-Schiff (PAS) reaction. The PAS-positive material was shown to be Tamm-Horsfall protein by an indirect immunoperoxidase method. Deposits were found in 152 kidneys (57.1 per cent.), and were commonest at the cortico-medullary junction and in arcuate veins. Deposits were rarely associated with thrombosis or an inflammatory response, and often contained tubules that were reforming. The lesions were rare in grafts totally infarcted from occlusion of the main vessels. Deposits were mostly found in kidneys that had tubular damage from acute rejection reactions, often with ureteric damage, but a few had ureteric obstruction alone. Old deposits were identified in kidneys showing chronic vascular rejection. No features of the deposits themselves could separate cases with ureteric obstruction alone from the other cases. Not every case with ureteric obstruction had the lesions. Extra-tubular deposits of Tamm-Horsfall protein are common in renal allografts and only rarely indicate a specific, surgically-correctable cause of graft dysfunction, namely ureteric obstruction.

Basement Membrane↗
PubMed1982

Studies on the relationship between proteinuria and glomerular ultrastructural change in hyperalbuminaemic female Wistar rats.

Increased albumin filtration was shown to cause glomerular epithelial cell foot process loss in female Wistar rats made hyperalbuminaemic by means of a series of intraperitoneal bovine albumin injections. It appeared to act by stimulating glomerular epithelial cell endocytosis with the result that protein droplets and vacuoles accumulated within the epithelium causing marked cytoplasmic swelling which forced the foot processes to spread out and fuse. The severity of this glomerular ultrastructural damage rose with increasing bovine albumin dose and correlated well with induced proteinuria.

Animals↗
PubMed1982

A biochemical and immunological investigation into the physiological basis of the increased albumin filtration induced in hyperalbuminaemic female Wistar rats.

1. The level of proteinuria induced in female Wistar rats after bovine albumin injection intraperitoneally was highly dose dependent. 2. The proteinuria remained highly selective, with albumin constituting approximately 90% of the total protein excreted, even in the most severely affected rats. 3. Calculations relating the amount of bovine albumin available in the serum for filtration to the amount excreted in the urine indicated that complete saturation of the reticuloendothelial and tubular protein reabsorption systems may have occurred during the course of the 5 day injection period in rats given more than 3.5 mg of bovine albumin day-1 g-1 body wt. 4. When this situation was attained there appeared to be no further increase in glomerular permeability to either rat or bovine albumin and an equilibrium state seemed to exist where, when serum albumin levels were raised above the normal level, all the excess albumin passed across the glomerular filter to be excreted in the urine. 5. The passage of these large quantities of albumin across the glomerular filter may have resulted not from ultrastructural damage to the filter itself but rather from the generation of vastly increased concentration gradients across the glomerular basement membrane, which were sufficiently large to overcome the electrostatic repulsive forces which normally severely restrict albumin filtration.

Albumins↗
PubMed1981

A scanning and transmission electron microscopic study of glomerular damage in the rat following heterologous serum albumin overload.

Female Wistar strain rats injected intraperitoneally with 1 g of BSA per day for 5 days, a total of 5 g of BSA, developed heavy proteinuria. Characteristic morphological abnormalities were seen by both TEM and SEM in the large majority of glomeruli from these animals and were similar overall, but not identical to, those seen in puromycin aminonucleoside nephrosis. The heterologous protein overload model seems to present considerable opportunity for study of the basic mechanisms of glomerular visceral epithelial cell handling of protein.

Albuminuria↗
PubMed1981

Normal urinary protein composition in the female Wistar rat and its relationship to the proteinuria induced by intraperitoneal bovine albumin.

1. Normal female Wistar rats showed a wide range of baseline protein excretion and albuminuria and could be divided into two distinct groups: (a) low-to-intermediate excretors, where daily baseline albumin excretion was below 1.8 mg/24 h and (b) high excretors, where daily baseline albumin excretion was 1.8-22 mg/24 h. 2. In low-to-intermediate excretors "sex-associated' by urinary specific proteins, supposedly present only in male rat urine, were excreted in larger quantities than albumin which constituted only 10-15% of the total urinary protein. 3. In high excretors up to 50% of the urinary protein was albumin and other serum proteins were also present in relatively larger quantities than the urinary specific proteins. 4. Baseline albumin excretion appeared to be a good indicator of the inherent efficiency of the glomerular filter and this was reflected in the response to intraperitoneal injection of heterologous serum albumin since, during periods where no significant glomerular epithelial cell foot-process loss had been incurred, the levels of proteinuria induced correlated well with baseline albuminuria.

Albuminuria↗
PubMed1981

Effect of strain and sex on the induction of hyperalbuminaemic proteinuria in the rat.

1. Male and female rats representing the four inbred strains [Wistar (albino), Sprague-Dawley (albino), DA (brown) and PVG (hooded) rats] were injected intraperitoneally with 4 . 5-5 . 5 mg of Cohn V bovine albumin day-1 g-1 body wt. 2. The levels of proteinuria and glomerular ultrastructural damage induced in response to hyperalbuminaemia varied widely with the strain and sex of rat studied, being highest in the male Wistar and lowest in the male Sprague-Dawley. 3. A survey of the relevant literature shows that these results probably explain most of the reported inconsistencies and anomalies concerning the effect of parenteral protein injection in the rat.

Animals↗
PubMed1980

Cadmium-induced osteomalacia.

The detailed study of a battery plate maker, who had worked with cadmium for 36 years, showed that proteinuria, typical of renal tubular dysfunction, had been observed for 25 years and during the last 12 years of his life the patient had suffered increasing disability from gross bone disease. Several bone biopsies and detailed metabolic studies showed typical severe osteomalacia, which responded well initially to calcium and vitamin D treatment. Examination of the liver both in life and after death showed a gross excess of cadmium. This was also found in the kidneys after death. Previously unreported changes were present in the bones, especially the lumbar vertebrae which were probably more the result of gross bone deformity than cadmium deposition. The mechanism of development of the severe acquired Fanconi syndrome was thought to be a combination of dietary calcium and vitamin D deficiency and impaired calcium absorption from abnormal vitamin D synthesis, related to the cadmium deposition in the renal tubules, which also caused the defect in renal tubular reabsorption.

Aged↗
PubMed1977

Irreversible glomerular damage following heterologous serum albumin overload.

Rats injected intraperitoneally with 1 g of bovine serum albumin (BSA) daily for 5 days develop heavy proteinuria and there is swelling and loss of the foot processes of the glomerular epithelial cells. Initially the urinary protein consists of about 55 per cent. BSA and about 40 per cent. rat serum albumin. Proteinuria persists when the injections of BSA are stopped. BSA disappears from the urine and 80-90 per cent. of the urinary protein is rat serum albumin. The persisting proteinuria is caused by glomerular damage resulting from disruption and necrosis of the glomerular epithelial cells leading to complete sclerosis of glomeruli. This damage does not appear to be immunologically determined.

Albuminuria↗
PubMed1977

Measurement of thyroid hormone in experimental thyroid tumours in rats.

Rats treated with 131I and propylthiouracil were shown to develop thyroid tumours 7--9 months after treatment. In this group, the levels of total thyroxine and tri-iodothyronine, and free thyroxine and tri-iodothyronine in the serum were low, and that of TSH was raised. In a group of rats treated with 131I and then propylthiouracil and thyroxine, thyroid tumours were found despite normal concentrations of total and free thyroxine and tri-iodothyronine in the serum. The level of TSH in the serum was significantly raised in this group. Thyroid tumours were not found in the various control groups of rats.

Animals↗
PubMed1976

Degranulation of chicken heterophil leucocytes during phagocytosis, studied by phase contrast and interference microscopy.

The dynamic aspects of degranulation of chicken heterophil leucocytes during phagocytosis have been studied by phase contrast and interference microscopy. Both standard (8 fps) and high-speed (400 fps) cine-photomicrographic recordings of this process under phase contrast are presented. Lysis of individual granules is usually completed in less than 60 milliseconds. During lysis of each granule a rounded phase dense body is ejected into the phagocytic vacuole. Measurements made by interference microscopy show that there is usually a substantial fall from a protein concentration of c. 100 per cent. w/v for intact granules to a concentration of 16 per cent. w/v for the vacuole resulting from their lysis; this can only be explained by a rapid intake of water into the granule matrix following membrane fusion. The intake of water that accompanies granule lysis causes swelling of the granule matrix, and is thought to explain the mechanism of ejection of the phase dense body. Granule lysis is not dependent on the intake of water, since occasional vacuoles have been observed which showed no fall in protein concentration relative to the intact granules. The membrane around the intact granule effectively excludes the entry of water into the concentrated hygroscopic granule matrix, but once membrane fusion occurs this barrier to the entry of water is usually lost.

Animals↗
PubMed1976

The morphometry of the glomerular epithelial cell and its foot processes after the injection of bovine serum albumin or egg albumin.

The intraperitoneal injection of 1 g of bovine serum albumin daily for 5 days was shown by electron-microscope morphometry to cause swelling of the glomerular epithelial cells and very severe loss of foot processes. However, these changes were found in only 70 per cent. of glomeruli and the other 30 per cent. remained normal. After 7 days' recovery following five daily injections of 1 g of bovine serum albumin, the swelling of the glomerular epithelial cells had subsided and the foot process reappeared. These changes were accompanied by severe proteinuria which resolved only slowly when the injections were stopped. After daily injections of 0-8 g of egg albumin for 5 days there was no swelling of the glomerular epithelial cells and only very slight loss of foot processes detectable only by morphometry. There was a less severe proteinuria than after injections of bovine serum albumin and it resolved more rapidly when injections were stopped. It is suggested that these differences arise from the fact that bovine serum albumin is reabsorbed by the glomerular epithelial cell but egg albumin is not. Two of four rats allowed to recover for 7 days after five daily injections of 1 g of bovine serum albumin had unusual glomerular lesions.

Animals↗
PubMed1976

Echocardiographic manifestations of single ventricle.

Eight patients with single ventricle were studied echocardiographically. In six, the ventricular septum was not detectable; in two, a septal-like bulboventricular ridge was identified. Two atrioventricular (A-V) valves were found in all patients; in six, both valves were identified simultaneously with the transducer held stationary along the left sternal edge. Dextro-transposition of the great arteries was noted in three patients. The echocardiogram of one of four patients with levotransposition of the great arteries was consistent with later proved left A-V valve stenosis associated with Ebstein's malformation. Mitral-semilunar valve continuity was presented in five cases. Echocardiographically, the absence of the ventricular septum in a patient with two A-V valves make a diagnosis of single ventricle likely. The presence of ventricular septal-like echoes does not exclude the diagnosis of single ventricle since the right ventricular infundibulum may remain as a small outlet chamber separated from the left ventricle by an eccentric bulboventricular ridge.

Adult↗
PubMed1976

Fibrogenesis imperfecta ossium.

The case history, clinical course and laboratory findings in a 66-year-old woman with fibrogenesis imperfecta ossium are reported, the sixth case in the literature. The condition is characterized clinically by intractable skeletal pain and progressive immobility. Though serum alkaline phosphatase has been raised in all patients, there are no specific haematological or biochemical findings. The radiological features of coarse and dense trabecular pattern with symmetrical and diffuse involvement of all bones without expansion or change of shape, together with periosteal reactions and soft tissue calcification are characteristic. The macroscopic appearance of bone shows large areas of opaque white and brittle trabeculae. The histological findings mimic those of osteomalacia unless examined under polarized light which shows the loss of normal birefringence. On electron microscopy the normal lamellar pattern made up of orientated collagen fibrils all about 80 nm diameter is replaced by a random tangled pattern of much thinner irregularly curved fibrils, some as thin as 5nm. The condition appears to be acquired, leading to erosion of the normal skeleton and replacement with an abnormal fibre deficient matrix. There is no definitive therapy at present.

Aged↗
PubMed1975

Combined light and electron-microscope morphometric studies of acute puromycin aminonucleoside nephropathy in rats.

Morphometric observations were made on rats injected subcutaneously daily with puromycin aminonucleoside after two, four, six and eight daily injections. As a result it was possible to correlate the morphological alterations of the various glomerular components with the biochemical manifestations of the nephrotic syndrome particularly the onset of proteinuria. There was already significant loss of foot processes of the glomerular epithelial cells by the 2nd day, that is before the onset of proteinuria, suggesting that the loss of foot processes is a consequence of some metabolic impairment produced by the puromycin aminonucleoside which also subsequently causes the proteinuria. Swelling of the glomerular epithelial cells became significant by the 6th and 8th day of injection after the development of proteinuria, suggesting that it is a consequence of the increased amount of protein in the glomerular filtrate. Two independent morphometric methods suggest a decrease in the amount of glomerular basement membrane. Unfortunately because of difficulties in the determination of mean glomerular volumes it is not possible to be absolutely certain that this is a true finding, however it is what would be expected if the synthesis of basement membrane was depressed by the puromycin aminonucleoside.

Acute Disease↗