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Biomedical subjects

M E Robbins

Publications and source records attributed to M E Robbins.

67 records · Page 4Linked to original sources
PubMed1989

Residual radiation-induced injury in dermal tissue: implications for retreatment.

The evidence for residual radiation-induced injury has been investigated in the dermal vascular/connective tissue of pig skin at intervals of 17-52 weeks after irradiation. The primary irradiation was a single dose of 18 Gy, which represents the upper limit of "tolerance" to X irradiation of pig dermal tissue. Re-irradiation was with graded single doses of X rays in order to establish dose-effect relationships for the incidence of late ischaemic dermal necrosis of the skin; dose-effect curves obtained for previously irradiated skin were compared with those obtained using previously unirradiated skin in the same group of animals. At intervals of 17, 35 and 52 weeks after the primary treatment the resulting ED50 values for dermal necrosis were not significantly different from those obtained for previously unirradiated skin. This suggests little or no effective residual injury at these time intervals after a primary full "tolerance" dose. This conclusion was supported by the findings for the latency time for the development of dermal necrosis, which were similar in re-irradiated and previously unirradiated skin. Epithelial desquamation was not induced by the doses used in these studies, either after the primary treatment or after re-irradiation; however, the early erythema reactions seen in re-irradiated skin were markedly reduced, particularly when this was carried out after 35 and 52 weeks, when compared with skin that had not previously been irradiated. This suggests that the early erythema reaction may be a particularly poor predictor of late effects after the re-irradiation of the skin. Although the present results suggest that dermal and subcutaneous tissues may safely be retreated with a full tolerance dose at relatively early times after an initial radical treatment, caution is recommended in extrapolating these results to other late-responding normal tissues. In other tissues some persistent injury may be present even at very long time intervals after the primary treatment.

Animals↗
PubMed1988

Effects of single doses of X-rays on renal function in the pig after the irradiation of both kidneys.

Irradiation of a single kidney in the pig with relatively low doses of X-rays, in the order of 8 Gy, produces a pronounced reduction in both glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). This apparent high radiosensitivity may be due, in part, to the compensatory hypertrophy displayed by the contralateral unirradiated kidney. This could suppress any potential for recovery by the irradiated kidney. To test this hypothesis, both kidneys of 14-week-old Large White pigs were sequentially irradiated with single doses of 250 kV X-rays, in the range 8.8 to 12.6 Gy. Sequential measurements of individual kidney GFR and ERPF were made for periods up to 24 weeks after irradiation. Time-related changes in haematocrit (Hct) were also studied. Two weeks after irradiation, GFR and ERPF increased markedly in all irradiated kidneys; levels then declined in a dose-dependent manner. Following a dose of 8.8 Gy renal haemodynamics returned to control values within 4 weeks of irradiation and remained essentially constant throughout the study. After higher doses, GFR and ERPF decreased markedly and remained below control values up to 24 weeks after irradiation. Associated with these changes in renal haemodynamics was a fall in Hct within 3 weeks of irradiation, with minimal levels being found approximately 8 weeks after irradiation. Although there was some recovery between weeks 12 and 24, Hct values remained below those of age-matched controls. At all doses the mean functional status of irradiated kidneys in animals in which both kidneys were irradiated (BI) was significantly greater than that previously observed in the irradiated kidney of pigs in which only one kidney was irradiated (UI). Moreover, in BI pigs there appeared to be a marked imbalance between the contribution each kidney makes to the total renal function. In terms of ERPF, the functional status of the right kidney, relative to that of the left kidney, showed a dose-related decline. These findings support the hypothesis that the compensatory response exhibited by the contralateral unirradiated kidney in UI pigs suppresses the potential for functional recovery by the irradiated kidney. The findings also indicate that individual kidneys in the same animal may differ in their response to a similar nephrotoxic insult.

Animals↗
PubMed1988

The response of the pig kidney to the combined effects of cisplatin and unilateral renal irradiation.

Seven mature Large White female pigs, approximately 10 months of age received a single dose of cis-dichlorodiammineplatinum(II), c-DDP (2.5 mg/kg body weight). Prior to, and 4 weeks after c-DDP administration, individual kidney glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by [99mTc]DTPA and [131I]hippuran renography. Of the 5 pigs surviving the c-DDP treatment most exhibited a reduction in both GFR and ERPF; the mean reduction in GFR (36.2 +/- 18.9%) was more pronounced than that for ERPF (12.6 +/- 19.4%). However, the difference in the severity of the impairment in these two parameters was not significant (p greater than 0.55). Haematocrit, haemoglobin and red blood cell counts were markedly reduced 14 days after c-DDP infusion, and despite some recovery evident 21 days after treatment, all three haematological parameters were still reduced 28 days after c-DDP administration. The right kidneys of these 5 animals, plus 5 pigs which did not receive c-DDP, were irradiated with a single dose of 11.9 Gy of 60Co gamma-rays. Individual kidney GFR and ERPF was routinely measured up to 24 weeks after irradiation. Pigs in which only the right kidney was irradiated showed a marked increase in both GFR and ERPF values 2 weeks after irradiation. This was followed by a decline in function with a reduction of 50% in terms of ERPF 16 weeks after irradiation. Values then showed some evidence of a recovery in function. There was a concomitant compensatory response by the contralateral unirradiated kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The relative biological effectiveness of fractionated doses of fast neutrons (42 MeVd----Be) for normal tissues in the pig. I. Effects on the epidermis and dermal vascular/connective tissues.

The effects of fractionated doses of fast neutrons (42 MeVd----Be) on the early epithelial and later dermal response of pig skin have been assessed and compared with those after X irradiation. For the early epithelial reaction, i.e. moist desquamation, the relative biological effectiveness (RBE) of the neutron beam increased with the decreasing size of the X-ray dose/fraction. There was an experimentally observed upper RBE value of approximately 2.75 for X-ray doses/fraction of between 2 and 5 Gy. For the late reaction of ischaemic dermal necrosis the RBE was greater than 3.0 for X-ray doses/fraction of less than 3 Gy and, based on the assumptions made in the linearquadratic model of cell survival, an upper limiting RBE of 4.32 +/- 0.39 was calculated for infinitely small doses/fraction. These findings were compared with other radiobiological data and the conclusions drawn from the results of clinical trials. It was concluded that for the sparing of late effects in skin and subcutaneous tissues, relative to acute reactions, a relatively small number of fractions in a short overall treatment time may be optimal for fast neutron therapy.

Animals↗
PubMed1986

Functional recovery in the irradiated kidney following removal of the contralateral unirradiated kidney.

The right kidneys of seven Large White female pigs, approximately 14 weeks of age, were irradiated with single doses of 7-12.6 Gy of 250 kV X-rays. Sequential measurements of individual kidney glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were carried out using 99mTc-DTPA and [131I]hippuran renography for time periods up to 24 weeks after irradiation. From this data, kidneys receiving a dose of 7 Gy were found to be functioning (F), while kidneys which received greater than or equal to 8.8 Gy were assessed as having no significant function (NF). When the pigs were approximately 10 months of age the contralateral unirradiated kidney was removed; the left kidney of three age-matched unirradiated pigs was also removed. The response of the right kidney to unilateral nephrectomy (UN) in these animals was assessed in terms of changes in haemodynamics (i.e. GFR and ERPF) for periods up to 24 weeks after UN. At post-mortem, the length and weight of the remaining kidney was measured. A marked increase in renal length was observed in irradiated kidneys following UN. In addition, the weights of irradiated kidneys following UN were greater than those of irradiated kidneys in age-matched pigs where the unirradiated kidney had not been removed. Four weeks after UN there was a pronounced increase in GFR and, in particular, ERPF in previously NF irradiated kidneys. The mean increase in these parameters, measured at the end of the follow-up period, when compared with the pre-surgery values, was 350.1 +/- 84.3 and 781.8 +/- 151.0% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effects of single doses of X-rays on renal function in unilaterally irradiated pigs.

The right kidney of 13 Large White female pigs was irradiated with single doses of 250 kV X-rays in the range 7-12.6 Gy. Sequential measurements of individual kidney glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were carried out by means of 99mTc-DTPA and 131I-hippuran renography for periods up to 24 weeks after irradiation. GFR levels increased in irradiated and unirradiated contralateral kidneys 2 weeks after treatment compared with age-matched controls. ERPF values exhibited a small increase in a proportion of animals. Renal function then declined in irradiated kidneys in a dose-dependent manner. A dose of 7 Gy resulted in a decline followed by subsequent recovery. After doses of greater than or equal to 8.8 Gy GFR and ERPF declined rapidly, reaching minimal levels by 6-12 weeks, the time depending on the dose. The reduction in ERPF was quantitatively greater than that for GFR. In animals receiving greater than 8.8 Gy the irradiated kidney contributed in the order of only 10% of the total ERPF. The reduction in GFR resulted in a prompt functional compensatory response in GFR in the unirradiated contralateral kidney. In terms of ERPF, a compensatory response was not evident until weeks 20-24. The results indicated that the radiation tolerance dose of the pig kidney following unilateral irradiation with single doses of X-rays was approximately 8 Gy.

Animals↗
PubMed1984

Techniques for the quantitative measurement of individual kidney function in the pig.

A prerequisite for elucidating the effect of radiation on porcine renal function is the development of non-invasive methods for accurate quantification of unilateral glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). The techniques presented here are (a) measurement of unilateral kidney filtration fraction (FF) determined by analysis of the early rise of the kidney's time-activity curves following the injection of tubular ([131I]hippuran) and glomerular ([99mTc]DTPA) tracers, and (b) deconvolution of the respective renogram. Unilateral FF values are obtained by calculating the ratio of glomerular to tubular clearances. Results for 23 female large white pigs indicate a highly significant correlation (r = 0.91, P less than 0.001) between computed FF values and those obtained from the plasma disappearance curves of [99mTc]DTPA and [131I]hippuran. Deconvolution of the renogram allows estimation of the mean transit time (MTT) for [99mTc]DTPA and [131I]hippuran, these are 6.94 +/- 1.87 and 6.86 +/- 1.44 min respectively. In addition, FF values calculated from the H0 values are significantly correlated (r = 0.7, P less than 0.05) with estimates from plasma disappearance curves of the tracers. Therefore these techniques appear to provide accurate non-invasive methods for determining individual porcine kidney function.

Animals↗
PubMed1984

Single injection techniques in determining age-related changes in porcine renal function.

Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined in 32 anaesthetised female Large pigs, aged 4-24 months, from the plasma disappearance curves of [99mTc]DTPA and [131I]hippuran respectively. Clearance was also monitored by external counting over the heart. GFR and ERPF increased markedly with age in pigs up to 12 months old, reaching mean values of 242.06 +/- 5.89 and 919.39 +/- 79.01 mL/min. In pigs aged 12-24 months ERPF increased slightly, but renal function remained essentially unchanged after 1 yr of age. These results for renal function were similar to previous estimates, using continuous infusion techniques inferring that GFR and ERPF could be accurately monitored using single injection procedures.

Aging↗
PubMed1976

Seizure resistance in albino gerbils.

Albino gerbils (Meriones unguiculatus) and their agouti litter mates were tested once per week for 10-16 weeks for spontaneous epileptiform seizures when transferred to a novel environment. Only 16% of the albinos had seizures compared with 41% among the agoutis (P less than 0-05).

Animals↗
PubMedDate not supplied

Peroxisome proliferator-activated receptor- gamma expression in human malignant and normal brain, breast and prostate-derived cells.

The constitutive and gamma -linolenic acid (GLA)-induced expression of peroxisome proliferator-activated receptor gamma (PPAR gamma) immunoreactive protein in a panel of human malignant brain (U87MG, T98G); breast (MCF-7, MB MDA-231, MB MDA 435) and prostate (ALVA, DU-145, LNCaP, PC3) cell lines have been compared with those for their normal cell counterparts, the human normal astrocyte (NHA), mammary epithelial (HMEC) and prostate epithelial (PrEC) cells, respectively. Constitutive levels of expression for PPAR gamma protein were significantly higher in the malignant cell lines relative to their normal cells. GLA supplementation did not affect the protein expression in malignant cells but caused 6- and 3-fold increases in normal breast and prostate cells, respectively. Since activation of PPAR gamma protein in some human malignant cell lines has been demonstrated to induce tumour cell death, these findings signal the need to exploit the significantly elevated expression of this protein in the therapy of human cancer.

Blotting, Western↗