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Biomedical subjects

R D Phemister

Publications and source records attributed to R D Phemister.

At least 19 recordsLinked to original sources

Counting renal corpuscles in tissue sections.

Two stereologic methods of counting renal corpuscles in tissue sections were evaluated. Weibel's stereologic method was found to be an accurate and efficient means of determining the number of corpuscles in normal and diseased kidneys. Weibel's method was preferred over the stereologic method of Elias and Hennig because the former is independent of tissue section thickness and is sensitive to variation in corpuscular size. A modification of Weibel's method eliminated the need for an additional point-counting procedure to determine the volumetric fraction of corpuscles in a kidney. The modification made use of previously completed measurements to calculate the area fraction of corpuscles and then substituted this value for the volumetric fraction of renal corpuscles.

Animals↗

Progressive glomerulosclerosis and renal failure following perinatal gamma radiation in the beagle.

The renal effects of whole body irradiation in the perinatal period were studied in the dog. Ninety-three dogs received a single sublethal exposure in the range of 270 to 435 R in either late gestation (55 days postcoitus) or early postnatal life (2 days postpartum) and were sacrificed at 70 days, 2, or 4 years of age. Early renal lesions in 70-day-old irradiated dogs were characterized by arrested glomerular maturation and degeneration resulting in reduced functional renal mass. Mature glomeruli exhibited mesangial proliferation. At 2 and 4 years of age, surviving irradiated dogs exhibited severe renal disease associated with progressive glomerular damage which was characterized by mesangial proliferation and compression of capillary lumina, epithelial degeneration and focal capsular adhesions, and ultimately obliterative glomerulosclerosis. Twenty-one of the 93 irradiated dogs died in renal failure before 4 years of age with advanced glomerulosclerosis. The pathogenesis of this progressive renal lesion may be related to the interaction of three specific factors. These include (1) the effect of direct radiation damage to mature kidney components; (2) the loss of outer cortical nephrons resulting in increased work load of the surviving nephrons; and (3) the effect of compensatory hypertrophy related to the loss of renal parenchyma as the rapid growth rates associated with kidney maturation.

Acute Kidney Injury↗

Postnatal development of the canine kidney: quantitative and qualitative morphology.

The normal postnatal development of the canine kidney was investigated utilizing qualitative and quantitative histologic methods. Kidneys were examined at 2, 4, 8, 14, 22, 70, and 200 days of age. A subcapsular nephrogenic zone was present in the kidneys until approximately eight days of age. This zone contained tissues which interacted to produce new nephrons and interstitial tissues. Several developmental stages of forming nephrons were identified in this zone. Beneath the nephrogenic zone, renal corpuscles of increasing maturity were located at successively deeper cortical levels. The total number of nephrons was estimated to be 445,000 per kidney. This number did not vary significantly during growth. The corpuscular volume per nephron increased 249% from 14 to 200 days of age. During the same period there was a 303% increase in the tubular volume per nephron. Although the developing kidney differed anatomically from the adult kidney, the individual nephrons maintained volumetric corpuscular-tubular balance during growth.

Animals↗

Radiation injury in the neonatal canine kidney. II. Quantitative morphology.

Quantitative morphology was used to investigate injury induced in the developing canine kidney by ionizing radiation. Irradiation at 2 days of age destroyed nephrogenic tissue in the outer renal cortex and significantly reduced kidney weight and volume through 70 days of age. However, as early as 14 days of age and continuing through 200 days of age, hypertrophy was demonstrated in the surviving middle and inner cortical nephrons of these kidneys. Both corpuscular and tubular components of the nephrons grew at an accelerated rate as compared to controls. The corpuscular volume per nephron increased 559 per cent in irradiated dogs and only 249 per cent in controls from 14 to 200 days of age. The tubular volume per nephron increased 519 per cent in irradiated dogs and 303 per cent in controls during the same period. As a result of the compensatory growth in individual nephrons, the kidneys of irradiated dogs at 200 days of age were as large as the controls when compared on the basis of body weight. The extensive hypertrophy is associated with accelerated development of intercapillary glomerulosclerosis in dogs irradiated around the time of birth.

Animals↗

Density and composition of trabecular and cortical bone in perinatally irradiated beagles with chronic renal failure.

Bone density and composition were studied in trabecular and cortical bone from control 2 and 4 year old beagles and those which had various degrees of renal failure as a result of perinatal irradiation. Changes in the two types of bone were qualitatively similar but consistently greater in trabecular bone. In a group identified as markedly uremic, the decrease (P less than 0.025) from control levels in specific gravity was about 4 times greater in trabecular than in cortical samples. The decrease (P less than 0.025) in grams of ash/ml was 9% in trabecular bone and 2% in cortical bone. These changes were associated with an increase (P less than 0.001) in water content and, on a percent by volume basis, approximately equal decreases in ash (P less than 0.025) and combustible matter (P less than 0.025). In a mildly uremic group there were similar trends in mean values but the only significant difference was an increase (P less than 0.001) in trabecular bone water.

Age Factors↗

Chronic dermatosis and cutaneous squamous cell carcinoma in the beagle dog.

Chronic dermatosis developed in sparsely-haired, lightly pigmented, ventral body skin in 397 of 1 680 beagle dogs by the time the dogs were 5 1/2 years old. Twenty-six of 55 other beagles had developed by 12 years of age. Squamous cells carcinomas developed in the sites of dermatosis in eight of the 397 younger and five of the 26 older beagles. The lesions resembled solar keratosis (solar dermatosis, actinic dermatosis or senile keratosis) in man. They developed under circumstances suggesting that solar radiation is involved in the pathogenesis, as it is in man.

Animals↗

Radiation injury in the neonatal canine kidney. I. Pathogenesis.

The effects of radiation on the developing canine kidney were investigated. Beagles were exposed to 330 R 60Co gamma-radiation on the 2nd postnatal day of life. The kidneys were examined at 2 days (6 hours after irradiation), 4, 8, 14, 22, 70, and 200 days of age with qualitative and quantitative light microscopy and scanning electron microscopy. The primary result of the radiation injury was a failure to form the normal number of nephrons. The kidneys of irradiated dogs had 42 per cent fewer nephrons (260,000) than the control dogs (445,000). In addition, extensive damage to forming nephrons produced dysplastic renal corpuscles and other corpuscles which were arrested in their development. Three mechanisms of radiation injury were identified. First, there was extensive mitosis-linked cell death in the nephrogenic zone. Second, mitotic delay resulted in only one-fifth of the normal mitotic activity in the nephrogenic zone through 2 days postirradiation. Third, there was an immediate and permanent cessation of nephron formation. The extensive injury in the outer renal cortex was compounded by the development of intercapillary glomerulosclerosis in some middle and inner cortical corpuscles by 200 days of age.

Animals↗

Glomerular lesions associated with proteinuria in clinically healthy dogs.

Spontaneous proteinuria in otherwise clinically normal adult Beagles 4-6 years old was studied for 2 years. Eighteen dogs, representing a population of 218 Beagles, were placed into three groups: group I, nonproteinuric; group II, intermittently proteinuric; group III, persistently proteinuric. The groups were alike on the basis of laboratory tests, except urinary protein loss. Proteinuria was persistent in most affected dogs but not progressive during the 2 years. The loss of proteins with high molecular weight, including alpha-, beta-, and gamma-globulins, suggested the proteinuria was of glomerular origin. There were glomerular lesions but no other significant change in the kidneys and urogenital system. Lesions were generalized and characterized by prominent, local or diffuse mesangial proliferation and by thickening, wrinkling, and splitting of the glomerular basement membrane. The subendothelial space was often widened and contained electron-dense deposits. Similar electron-dense deposits, as well as lipid and mineral, were in the mesangium. Alterations in visceral epithelial cells and endothelium were prominent. Periglomerular sclerosis was present but tended not to correlate with the severity of mesangial change in any given renal corpuscle. The severity of both mesangial and periglomerular changes increased with increasing proteinuria. Immunofluoescence studies demonstrated granular discontinuous localization of IgG and betaIC-globulins in the glomerular capillaries and mesangium. Similar localization was seen but to a lesser extent in nonproteinuric dogs. The glomerular lesions seen in these clinically healthy, proteinuric dogs are similar to those described in various canind diseases associated with terminal renal failure.

Animals↗

Levels of lutenizing hormone, estradiol and progesterone in serum during the estrous cycle and pregnancy in the beagle bitch (38491).

Levels of luteinizing hormone (LH), estradiol-17 beta and progesterone were determined by specific radioimmunoassays in sera obtained from Beagle bitches during proestrus, estrus and diestrus. Concentrations of LH (expressed as NIH-LH-SI equivalents) were 2.8 plus or minus 0.1 ng/ml in proestrus, 35.5 plus or minus 10.0 ng/ml during early estrus and 2.2 plus or minus 0.1 ng/ml in early diestrus. Peak levels of estradiol-17beta (68.9 plus or minus 11.0 ng/ml) were detected 24 hr prior to the LH peak, declined rapidly and reached basal levels (17.8 plus or minus 6.3 ng/ml) by five days following the LH peak. Levels of progesterone were 1.7 plus or minus 0.3 ng/ml during proestrus, 3.5 plus or minus 0.3 ng/ml during early estrus and 23.3 plus or minus 2.8 ng/ml on day 5 after the LH peak . Progesterone levels remained elevated through day 28 of diestrus and pregnancy. A significant decrease (p smaller than 0.05) in levels of prosgesterone occurred between day 28 of pregnancy and one day prior to shelping (3.3 plus or minus 1.2 ng/ml, with a further decrease on the day of whelping (1.1 plus or minus 0.2 ng/ml). Levels of estradiol-17beta and LH did not change significantly (p smaller than 0.0k) during diestrus or pregnancy.

Animals↗

Temporal sequence of events in the estrous cycle of the bitch.

Serum concentrations of luteinizing hormone (LH), estradiol-17 beta, and progesteron were compared with the onset of diestrus in Beagle bitches. The LH peak occurred 8.0 (standard error (SE), 0.3) days before the onset of diestrus. Vaginal cytologic characteristics during proestrus were studied, and vaginal cornification was complete 12.1 (SE,0.2) days before the onset of diestrus. A time sequence of hormonal, vaginal cytologic, and developmental events was outlined during proestrus, estrus, and early diestrus.

Animals↗