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Biomedical subjects

R A Axelsen

Publications and source records attributed to R A Axelsen.

At least 37 records · Page 2Linked to original sources
PubMed1988

Cell death by apoptosis following X-irradiation of the foetal and neonatal rat kidney.

A light and electron microscopic study was undertaken to determine the type of cell death induced by X-irradiation in the developing kidney. Five-day-old Sprague-Dawley rats were exposed to a whole-body dose of either 2 or 5 Gy, and foetuses in the eighteenth day of development were exposed to a dose of 4 Gy. The kidneys were examined at 4, 8 and 24 h, and at 1 and 2 weeks post-irradiation. The dying cells from both control and treated kidneys showed the morphological features of apoptosis, a distinct form of cell death that has been identified in mammalian tissues under physiological as well as pathological conditions. Necrosis was not detected. Apoptosis was infrequent in control kidneys and insignificant in extent when compared with the proliferative activity of the cells of the superficial nephrons. There was a pronounced increase in apoptosis during the first day after irradiation. The findings are in agreement with recent ultrastructural studies which report the presence of apoptosis following irradiation of rapidly proliferating adult cell populations, and irradiation of other immature mammalian tissues. There is evidence that apoptosis involves active cellular self-destruction, and it has been suggested that activation of apoptosis might bring about selective elimination of cells with critical DNA damage in irradiated tissues, thus minimizing propagation of genetic abnormalities.

Animals↗
PubMed1988

Scrotal calcinosis: origin from dystrophic calcification of eccrine duct milia.

Scrotal calcinosis is a rare benign disorder considered idiopathic by most recent authors, although an origin from dystrophic calcification of epidermoid cysts has been proposed. In 3 of 4 cases which were otherwise typical of scrotal calcinosis, there was calcification of the contents of small cysts lined by stratified squamous epithelium. These structures were identified as eccrine duct milia because some of them communicated with eccrine ducts and there were ultrastructural features of eccrine duct differentiation in one case. The eccrine nature of the milia was confirmed using the immunoperoxidase technique for the demonstration of carcinoembryonic antigen (CEA) which serves as a marker of eccrine sweat glands. Since a transition could be seen between degenerating calcified milia and typical nodules, it appeared that the calcific deposits of scrotal calcinosis result from the breakdown of such lesions. Staining of deposits unassociated with cyst walls with the technique for the demonstration of CEA supported this conclusion. An advanced stage of evolution of the disease could account for the absence of visible cysts in many cases. We propose the term "hidrocalcinosis of the scrotum" for this distinctive form of cutaneous calcification.

Adult↗
PubMed1988

Functioning lipoadenoma of the parathyroid gland.

A lipoadenoma of the parathyroid gland was discovered at autopsy as the result of a search for the cause of terminally detected hyperparathyroidism in an elderly man who had suffered cerebral infarction. It is the only case known to the authors in which this uncommon cause of hyperparathyroidism was found at post-mortem examination after hypercalcemia and raised levels of serum immunoreactive parathormone were documented during life.

Adenoma↗
PubMed1988

Granulomatous lobular mastitis: report of a case with previously undescribed histopathological abnormalities.

A 41-yr-old multiparous woman presented with a discrete breast lump which proved histologically to be an example of granulomatous lobular mastitis. The clinical and histological features were similar to those noted in previous reports. Additional histological features in the present case were an intense mononuclear cell infiltration of lobular and ductal epithelium, associated with nuclear fragments morphologically suggestive of apoptosis. These appearances, which have not previously been described, are illustrated, together with the more classical features of the condition well demonstrated by the present case. The novel histological features noted here suggest that the development of granulomatous lobular mastitis may be at least in part immunologically mediated, and that the cellular infiltrates seen may be a manifestation of cell-mediated destruction of mammary epithelium.

Adult↗
PubMed1988

Melanosis coli. A consequence of anthraquinone-induced apoptosis of colonic epithelial cells.

A condition closely resembling human melanosis coli was induced in the guinea pig large intestine by daily oral administration of the anthraquinone danthron. Each treatment caused a transient, dose-related wave of apoptosis of the colonic surface epithelial cells. Most of the resulting apoptotic bodies were phagocytosed by intraepithelial macrophages and carried by them through fenestrae in the epithelial basement membrane to the lamina propria. Here, the apoptotic bodies were transformed into typical lipofuscin pigment in macrophage heterolysosomes. Continued danthron administration caused progressive accumulation of pigmented macrophages in the bowel wall, whereas ongoing migration of pigmented macrophages to regional lymph nodes resulted, after danthron was ceased, in sequential loss of the pigmented cells from the superficial and deep lamina propria. Examination of colonic biopsies from patients with melanosis coli shows increased numbers of apoptotic bodies in the surface epithelium and lamina propria, suggesting implication of the same cellular processes in the formation of the pigment in man.

Animals↗
PubMed1987

Genesis of renal tubular atrophy in experimental hydronephrosis in the rat. Role of apoptosis.

A morphological study was undertaken to assess the role of cell deletion by apoptosis in experimental hydronephrosis. Male Sprague-Dawley rats (200 +/- 20 gm) were used. The left ureter was ligated or a sham operation was carried out. Animals were killed from 4 days to 12 weeks after operation. Two parallel studies were undertaken: one to demonstrate and quantitate specific morphological changes in the affected kidney using light and electron microscopy, and the other to measure changes in dry kidney weights. Renal tubular atrophy is an inevitable consequence of chronic occlusion of the ureter. As expected, the present study showed a progressive loss of tissue mass in the hydronephrotic kidney. This occurred from 1 week after permanent ureteric ligation, and was most rapid between 2 and 4 weeks. The tubular epithelium contained cells undergoing a distinct form of cell death termed apoptosis, characterized ultrastructurally in its early stage by the presence of rounded cells with condensed cytoplasm and condensed and marginated nuclear chromatin, and later by the presence of discrete membrane-bounded intact cellular fragments (apoptotic bodies), which were phagocytosed and digested by adjacent viable cells, or were shed into the tubular lumens. Numbers of apoptotic cells or clusters of apoptotic bodies were increased significantly in all animals with ureteric obstruction in comparison with controls. The greatest increases occurred at 2 and 4 weeks, when loss of renal mass was occurring rapidly. Diminished blood flow in hydronephrosis has been well-documented by others, and therefore our results are consistent with studies which have shown mild ischemia to be the cause of tissue atrophy involving apoptosis. We conclude that cell deletion by apoptosis plays an important role in the pathogenesis of renal tubular atrophy associated with hydronephrosis.

Animals↗
PubMed1986

Renal and urinary tract complications following the intravesical instillation of formalin.

The case is reported of a 10-yr-old girl who developed intractable hematuria from hemorrhagic cystitis following chemotherapy for a malignant lymphoma. Following the intravesical instillation of formalin, which controlled the hematuria, she developed oliguria attributable to ureteric stenosis and fibrotic contraction of the renal pelves. Bilateral nephrostomies were constructed, but recurrent pyelonephritis and further renal pelvic obstruction developed. A series of renal biopsies and ultimately bilateral nephrectomy revealed severe, chronic interstitial nephritis, massive renal interstitial accumulation of deposits probably containing Tamm-Horsfall protein and, in the left nephrectomy specimen, a florid interstitial chronic granulomatous inflammatory reaction. Although ureterohydronephrosis has been described by others as a complication of the intravesical instillation of formalin, fibrotic contraction of the upper urinary tract and the florid interstitial nephritis with granulomata as described herein have not previously been reported. It is proposed that vesicoureteric reflux of formalin, perhaps accompanied by intrarenal reflux, caused or contributed to these pathological changes.

Administration, Intravesical↗
PubMed1985

Glomerular transplant rejection: a distinctive pattern of early graft damage.

Five hundred seventy-six consecutive biopsy or nephrectomy specimens obtained during the first 6 months of transplantation from 300 grafts in 431 recipients were examined by light microscopy for focal or diffuse endocapillary hypercellularity. Forty-seven (8.2%) of the 576 specimens obtained from 37 (12.3%) of the 300 grafts exhibited segmental or global occlusion of capillaries by swollen cells in 40-100% of glomeruli per biopsy. The lesions occurred at any time after transplantation, but 34 (72.3%) were present by day 60 and 7 (14.9%) before day 10. Immunofluorescence in 39 affected biopsies revealed focal or segmental glomerular staining in 18 (46.2%), among which IgM was found most frequently, and was considered to be non-specific. Electron micrographs of 17 biopsies from 14 grafts revealed that glomerular capillaries were narrowed or occluded by mononuclear cells of uncertain type, possibly monocytes, as well as lymphocytes and a few neutrophils. Complement-fixing antibody titers to cytomegalovirus rose at least fourfold in 10 (45.5%) of the 22 patients studied, but glomerular lesions were no more severe in the seroconverters than in the non-converters, and there was no consistent temporal relationship between the occurrence of glomerular changes and seroconversion. Cellular or vascular rejection was present in most biopsies. One year graft survival was 34% among 35 accessed grafts with glomerular lesions, compared to 55% among 243 biopsied grafts with no glomerular changes. We consider that these lesions do not have a consistent association with cytomegalovirus infection and that they represent a distinctive form of glomerular rejection. Whether they indicate a poor graft survival, as the present results suggest but do not prove, requires further studies of other series of cases.

Cytomegalovirus Infections↗
PubMed1984

Impaired renal concentrating capacity in the rat after surgical resection of the papilla.

Renal cortical and medullary function was examined in rats 4 weeks after surgical resection of the distal portion of the renal papilla had been performed. Glomerular filtration rate (GFR), obtained during the determination of free water reabsorption (TcH2O) at high rates of urine flow, did not differ significantly among controls (1.62 +/- 0.19 ml/min, n = 5), sham operated animals (1.45 +/- 0.16, n = 4) and papillectomized animals (1.49 +/- 0.21, n = 7). Maximum urinary osmolality (Umax) was 2216 +/- 293 mOsm/kg in controls, and was significantly reduced in sham operated (1737 +/- 261, P less than 0.05) and papillectomized animals (889 +/- 143, P less than 0.0001). TcH2O was normal in sham operated animals at high rates of osmolar clearance (Cosm), but was significantly impaired after resection of the renal papilla. These results suggest that removal of the terminal collecting ducts and interruption of nephrons with long loops extending into the papilla impair the maximal generation of solute free water.

Animals↗
PubMed1984

Recurrent focal glomerulosclerosis in renal transplants.

Among 431 renal transplants in 380 patients, 4 patients were identified with focal glomerulosclerosis characterized by presentation with corticosteroid-resistant nephrotic syndrome, early development of histological lesions, mesangial proliferation and rapid progression into chronic renal failure. After transplantation, all patients had early proteinuria and the 4 grafts surviving beyond 3 months developed recurrent glomerular lesions with severe nephrotic syndrome and progression to graft failure. In one patient, recurrent disease developed in two successive grafts. Focal glomerulosclerosis is a nonspecific glomerular lesion, but identification of specific clinical and pathological features may provide guidelines that will predict the risk of its recurrence in transplanted kidneys.

Adult↗
PubMed1983

Effects of indomethacin on renal concentrating capacity in lithium-treated rats.

An investigation was carried out to determine whether or not the administration of indomethacin to Li-treated rats would raise PLi2, and whether or not there would be any change in the type or severity of Li-induced renal functional abnormalities. It was found that indomethacin increased PLi, apparently by decreasing CLi. Umax, already reduced by Li, was further impaired by the additional administration of indomethacin. The Li-induced impairment of TcH2O was not worsened by added indomethacin, but a wide variance of the data might have masked any effect. Significant inverse correlations were found between Umax and PLi and between maximum TcH2O and PLi, suggesting that the indomethacin-induced impairment in renal concentrating capacity is attributable to the increased PLi.

Animals↗
PubMed1982

Localization of medullary functional abnormalities in experimental papillary necrosis.

Renal function was investigated in rats 3 d or 4 wk after an injection of 2-bromoethylamine hydrobromide (BEA) 40-125 mg/kg body weight. Animals developed necrosis of renal papillary structures other than collecting ducts (subtotal renal papillary necrosis) (RPN) or necrosis of all structures in the distal papilla, including collecting ducts (total RPN). Glomerular filtration rate (GFR) was reduced in animals with total RPN (667 +/- SD 168 microliters/min/100 g body weight, n = 5) in comparison with controls (1065 +/- 103, n = 5; P less than 0.001) but was unimpaired in animals with subtotal RPN (1162 +/- 200, n = 4; P greater than 0.3). Maximum urinary osmolality (Umax) was significantly decreased in subtotal RPN (1241 +/- 388 mOsm/kg, n = 4) and in total RPN (626 +/- 293, n = 5) in comparison with controls (2216 +/- 293, n = 5). Free water reabsorption (TcH2O) was impaired in animals with total RPN but was not significantly reduced in the presence of subtotal RPN. Total RPN did not affect free water formation (CH2O). It is concluded that impaired TcH2O occurs in RPN because of the damage to the collecting duct, and not because of necrosis of the thin limbs juxtamedullary nephrons.

Animals↗
PubMed1980

Nephrotoxicity of mild analgesics in the Gunn strain of rat.

1 Homozygous members of the Gunn strain of rat, mutant Wistars jaundiced from lack of the enzyme uridine diphosphate glucuronyl transferase, are highly susceptible to analgesic-induced renal papillary necrosis. 2 A single oral dose of aspirin, phenacetin or paracetamol will produce the lesion, a circumstance which does not occur in other strains. 3 The reasons for this susceptibility have not been determined, but the experimental model should prove useful in further studies of the nephrotoxicity of analgesic drugs.

Acetaminophen↗
PubMed1978

Experimental renal papillary necrosis in the rat: the selective vulnerability of medullary structures to injury.

Acute renal papillary necrosis was produced in rats by the administration of ethyleneimine. Low doses resulted in necrosis of interstitial cells, thin limbs of the loops of Henle and vasa recta, while collecting ducts were spared (subtotal renal papillary necrosis). High doses resulted in necrosis of all elements of the papilla (total renal papillary necrosis). Athough the ranges of the doses that produced these two patterns of necrosis overlapped, it is clear that there is a dose dependent selective vulnerability or renal medullary structures to injury by the toxic agent studied.

Animals↗