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Biomedical subjects

W F Ward

Publications and source records attributed to W F Ward.

At least 91 records · Page 5Linked to original sources
PubMed1981

Internalization of cytoplasmic protein by hepatic lysosomes in basal and deprivation-induced proteolytic states.

The hypothesis that cytoplasmic protein in rat liver is internalized and degraded intralysosomally during basal or steady state turnover as well as in deprivation-accelerated states was tested by (a) determining the subcellular location of degradable protein in homogenates and (b) comparing the amounts of this protein pool with rates of long lived protein degradation in livers perfused under the above conditions. Greater than 95% of total proteolysis in homogenates, measured at 37 degrees C from free amino acid generation or the release of [14C]valine in previously labeled livers, was associated with particulate fractions, and it paralleled lysosomal markers closely during graded differential centrifugation after Triton WR-1339 loading. Because 14C-labeled cytosolic proteins were not degraded by intact isolated lysosomes at pH 6 or 7, the protein substrate must have been internalized by lysosomes prior to homogenization. Time courses of intralysosomal proteolysis from maximal deprivation down to and including basal were identical in shape, and each leveled off abruptly after 120-150 min. Although the velocities of proteolysis were reduced in vitro, estimates of the degradable protein pools were closely proportional to corresponding rates of long lived degradation in perfused livers. In absolute terms, they fit recent predictions of internalized cytoplasmic protein based on stereological measurements of lysosomal volumes.

Amino Acids↗
PubMed1981

Intrapancreatic pseudocyst formation: a complication of acrylate pancreatic duct obliteration.

The case of a young woman is presented who, at the age of 33 years, had surgical occlusion of the pancreatic duct by instillation of acrylate glue for chronic relapsing pancreatitis. She presented in mid-1979, after a period of increasing frequency and severity of pain, with intractable narcotic dependency, and was shown to have a pseudocyst in the head of the pancreas. Distal pancreatic resection and cystoenterostomy have resulted in loss of narcotic dependency and a return to reasonably good health, in spite of a late development of insulin-dependent diabetes mellitus which is well controlled. Histological examination of the excised body and tail of the pancreas showed that exocrine atrophy, though advanced, was incomplete. It is suggested that in chronic pancreatitis, complete obliteration of the duct system may not be possible because of preexisting duct lesions. This may allow persistence of exocrine pancreatic tissue and lead to the complications of continuing pancreatitis and pseudocyst formation.

Adult↗
PubMed1981

Radiation-induced pulmonary arterial perfusion defects: modification by D-penicillamine.

D-penicillamine, previously shown to have a beneficial effect on radiation-induced pulmonary histopathology, was tested to determine its effect on function in the irradiated lung. Male rats were irradiated with 60Co gamma rays; half then received 10 mg D-penicillamine per day, and half received no further treatment. One to nine months after irradiation, animals were subjected to lung perfusion scans. Untreated irradiated rats exhibited hyperemia, hypoperfusion, and perfusion defects of the irradiated lung. In penicillamine-treated rats, the appearance of perfusion defects was delayed, the peak incidence and severity of the defects was reduced, and recovery from pulmonary hypoperfusion was accelerated. Thus, using functional criteria, penicillamine appears to improve arterial perfusion and to ameliorate radiation injury in the rat lung.

Animals↗
PubMed1979

Modification of radiation-induced pulmonary fibrosis in rats.

Male rats received 25 Gy (2,500 rad) of gamma rays to the right hemithorax and were killed three or six months later. Microscopic pulmonary abnormalities developed sooner and progressed more rapidly in animals given control feed than in those given the collagen antagonist D-penicillamine (10 mg/day, p.o.). Three and four months after irradiation, hypoperfusion and radiographic hyperlucency of the right lung were observed in both the treated and control animals.

Animals↗
PubMed1977

The effect of intrauterine position on the radiosensitivity of rat embryos.

Rats were exposed to gamma rays or helium ions on one of days 4-9 of gestation. Embryonic survival was recorded as a function of intrauterine position at autopsy on day 20 of gestation. Embryos located at the ovarian and cervical ends of the uterus experienced higher rates of mortality than did their littermates located at the middle of the uterine horn. This effect was observed in litters exposed to both radiation modalities on all days studied. The influence of intrauterine position on embryonic survival was directly proportional to radiation dose and to the number of fetuses occupying the uterus horn. Under the least advantageous conditions (i.e., a crowded uterine horn exposed to a moderately high radiation dose), the cervical embryo's probability of survival was less than half that of the litter as a whole. A disproportionately high rate of embryonic mortality at the cervical position was also observed in litters irradiated under hypoxic conditions, suggesting that the non-random distribution of radiation effect was not the result of variations in oxygen concentration within the uterus. In contrast, there was no indication that intrauterine position influenced the distribution of gross morphologic abnormalities in irradiated litters.

Animals↗
PubMed1977

Developmental effects of the uterine environment: dependence on fetal sex in rats.

Body weight was recorded as a function of intrauterine position for 20-day-old male and female rat fetuses from 83 normal litters. Male fetuses located in the middle of the uterine horn were invariably heavier than males located at the extreme ovarian or cervical positions, those at intermediate positions being intermediate in size. The mean body weight of male fetuses was inversely related to the number of fetuses present in the ipsilateral uterine horn. The body weight of female fetuses appeared independent of both intrauterine position and ipsilateral uterine occupancy. For both sexes, fetal body weight was inversely related to the number of littermates in the contralateral horn. Male fetuses were significantly larger than female fetuses under all but the most adverse intrauterine conditions. Therefore, random fluctuations in sex ratio may distort the true relationshp between mean fetal weight and intrauterine position, if the two sexes are not analysed separately.

Animals↗
PubMed1976

R.b.e. and o.e.r. of extended-Bragg-peak helium ions: survival and development of rat embryos.

Rats were exposed under aerobic or hypoxic conditions to 200-1200 rads of 60Co gamma-rays or extended-Bragg-peak helium ions on the eighth day of gestation. Uterine contents were examined on the twentieth day of gestation. At the 50 per cent embryonic survival level, helium ion r.b.e. was 1(.0) (aerobic) and 1(.2) (hypoxic). Maximum attainable gamma-ray and helium-ion o.e.r.s. were 2(.2) and 1(.7) respectively, indicating an oxygen-effect gain (o.e.g.) of 1(.2). At the 10 per cent survival level helium ion r.b.e. was 1(.1) (aerobic) and 1(.4) (hypoxic). Gamma-ray and helium-ion 0.e.r.s. were 2(.0) and 1(.5) respectively, indicating a helium ion o.e.g. of 1(.3). These data demonstrate that the small fraction of high-LET radiation present in this helium ion beam has a neglible effect on the aerobic r.b.e., but lowers the effective o.e.r. of the beam approximately 25 per cent relative to that of gamma-rays. Helium ions were significantly more effective than gamma-rays in killing embryos under hypoxic conditions, in producing congenital abnormalities under aerobic conditions, and in stunting foetal growth under both conditions.

Animals↗
PubMed1976

Repair of sublethal and potentially lethal radiation damage by rat embryos exposed to gamma rays or helium lons.

Embryonic survival was examined in rats exposed to a 24-hour split-dose regimen of gamma rays or extended-Bragg-peak (EBP) helium ions on the fifth and sixth days of gestation. The data indicate that EBP helium ions, which are known to have a single-dose relative biological effectiveness (RBE) of 1.0, exhibit a split-dose RBE of 1.5 with respect to embryo killing. Using an experimental rat embryo system, delayed implantation, it was also noted that the embryocidal damage induced by EBP helium ions contains a smaller potentially lethal component than that induced by gamma rays.

Animals↗
PubMed1976

Behavior of the lysosomal system during organ perfusion. An inquiry into the mechanism of hepatic proteolysis.

In this chapter we have attempted to provide some insight into a mechanism(s) of protein degradation in liver which we believe is implicated in the physiological regulation of free amino acid pools. The association we have observed between regulatory effects of insulin and amino acids in the perfused rat liver and physical alterations of the lysosomal system in similarly treated livers suggests that the final stage of the process is localized within the lysosomal-vacuolar system. The present studies show that perfusion of the isolated rat liver is in itself a potent stimulus to general proteolysis, an effect which is associated with increases in lysosomal size, density and sensitivity to osmotic shock. Since the osmotic and density alterations can be prevented or reversed by the provision of insulin or amino acid mixtures, we believe these agents normally act to restrain some inherent proteolytic process. Although the attendant lysosomal alterations are similar in many respects to those induced by glucagon, they differ sharply from the latter in having no sequestered organelles or evident membrane structures and the fact that they rise in the absence of any increase in the tissue level of cyclic AMP. Aside from the obvious problem of evaluating the quantitative importance of the lysosomal system in hepatic proteolysis, three interesting problems remain to be solved: (1) the nature of the proteins involved, (2) their mode of acquisition by the lysosome, and (3) the relationship of this inherent proteolytic process to glucagon or cyclic AMP-induced cellular autophagy. With regard to the former it seems reasonably clear from our studies and those of others that protein substrate does not gain access to lysosomal proteases by the direct penetration of lysosomal membranes, but more likely by fusion of a preexisting lysosome with some, as yet undefined, membrane-bound element. Whether such an element is formed in a manner analogous to that of the precursor vacuoles in autophagy (Ericsson 1969) or by some other process is not known. Closely related to this is the question of the nature of the substrate and the factors determining its uptake by the lysosome. Space does not permit us to review evidence from a number of laboratories which suggests that the turnover of intracellular protein may be a function of size (Dehlinger and Schimke 1971; Dice et al. 1973), charge (Dice and Goldberg 1975), or conformational stability (Li and Knox 1972; Ballard et al. 1974). We have no idea at the moment whether the mechanism we have outlined will eventually be shown to encompass a wide range of turnover of intracellular proteins or, alternatively, whether it will be limited to a certain class of proteins that turnover as a unit. While there is undoubtedly far more specificity in the regulation of intracellular proteins than our present data indicate, we do not view this as an incompatibility, but rather as another aspect of a complex problem we are only beginning to understand.

Acid Phosphatase↗