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Biomedical subjects

J Saxton

Publications and source records attributed to J Saxton.

At least 55 records · Page 3Linked to original sources
PubMed1988

Posterior spinal cord block: a dosimetric study.

To determine the optimal width of a midline posterior spinal block (MPSB) (to avoid delivering too great a dose to the cord and too small a dose to adjacent tissue), the authors determined with magnetic resonance (MR) imaging normal ranges of cord depth and width and correlated them with film dosimetric data. In 59 randomly selected patients there was a wide range for both depth and width. The average depths of the anterior and posterior surfaces of the cord were 6.7 cm +/- 1.4 and 5.4 cm +/- 1.3, respectively. The average cord width was 1.6 cm +/- 0.4. Optimal cord block width as a function of cord width was determined for a 6-MV photon beam. The optimal cord block width at the surface (half-value layer [HVL] thickness = 6) varied from 1.5 to 3.0 cm for cord widths of 0.8-2.4 cm, which correspond to two standard deviations from the average. There was no significant dependence on depth of the cord. For optimal treatment outcome, the MPSB width may have to be determined for each patient individually.

Film Dosimetry↗
PubMed1987

Effects of preincubation of primary monolayer cultures of rat hepatocytes with low- and high-density lipoproteins on the subsequent binding and metabolism of human low-density lipoprotein.

1. There are two distinct binding sites (Site 1 and Site 2) for human low-density lipoprotein (LDL) on rat hepatocytes in monolayer culture [Salter, Saxton & Brindley (1986) Biochem. J. 240, 549-557]. 2. Binding of 125I-LDL to Site 1, but not to Site 2, is up-regulated between 20 and 44 h in culture by preincubation of the cells with human high-density lipoprotein 3 (HDL3). 3. A similar preincubation with HDL2 had no significant effect on binding to either site. 4. Preincubation with human LDL led to a partial down-regulation of subsequent binding of 125I-LDL to Site 1. Since binding after incubation with LDL was measured at 37 degrees C, binding to Site 2 could not be distinguished from LDL that had been internalized by the cells. 5. Hepatocytes were shown to degrade 125I-LDL, resulting in the accumulation of [125I]iodotyrosine in the medium. Evidence was found that iodotyrosine may be further degraded by deiodinase produced by the cells. 6. Regulation of binding to Site 1 by preincubation with LDL or HDL3 was found to lead to a parallel regulation of LDL degradation. 7. It is concluded that rat hepatocytes not only bind but also metabolize human LDL and that these processes are under metabolic regulation.

Animals↗
PubMed1987

Normal rates of forgetting of verbal and non-verbal material in Alzheimer's disease.

Recent work has suggested that patients with damage to temporal lobe structures, such as patients with Alzheimer's Disease (AD), lose information from memory at an abnormally rapid rate. In contrast, data from other studies suggest that the rate of forgetting in AD is normal. In the present study, 62 patients with mild to moderate AD and 64 elderly controls were tested for their immediate and delayed recall of a short verbal passage and a modified Rey complex figure. The results suggest that although AD patients recalled less than controls, they did not forget at a faster rate during the 30 minute retention interval, supporting the finding that these memory impaired patients do not have an abnormal rate of forgetting. The data also suggest that poor initial encoding of the stimuli may be the cause of the AD patients' impaired recall.

Aged↗
PubMed1986

Characterization of the binding of human low-density lipoprotein to primary monolayer cultures of rat hepatocytes.

The binding of human low-density lipoprotein labelled with 125I to rat hepatocytes in monolayer culture was measured at 4 degrees C. Evidence for two different specific binding sites was obtained. Binding to Site 1 was characterized by: being displaced by dextran sulphate or heparin; being dependent on Ca2+; having a Kd value of about 15 micrograms of protein/ml; not being significantly displaced by a 20-fold excess unlabelled low-density lipoprotein that had been reductively methylated; being displaced by approx. 40% by a 20-fold protein excess of unlabelled human high-density lipoprotein, HDL3, and increasing with time in culture when newborn-calf serum was present in the medium. The binding to Site 2 had the following properties: it was not displaced by sulphated polysaccharides; it was only partially Ca2+-dependent, and the presence of EDTA increased the Kd value; the apparent Kd value in the presence of Ca2+ was approx. 30 micrograms of protein/ml, which was significantly higher than for Site 1; it was displaced by approx. 30% with a 20-fold excess of low-density lipoprotein that had been methylated; it was displaced by unlabelled HDL3 to a similar extent to Site 1; it did not increase significantly with time in culture. The characteristics of binding to Sites 1 and 2 are discussed in relation to the receptors for low-density lipoproteins that have previously been described in various cell types. It is proposed that the experimental system described in this paper is suitable for studying the regulation of the binding of low-density lipoproteins to hepatocytes.

Animals↗
PubMed1985

Regulation of the translocation of phosphatidate phosphohydrolase between the cytosol and the endoplasmic reticulum of rat liver. Effects of unsaturated fatty acids, spermine, nucleotides, albumin and chlorpromazine.

The translocation of phosphatidate phosphohydrolase between the cytosol and the microsomal membranes was investigated by using a cell-free system from rat liver. Linoleate, alpha-linolenate, arachidonate and eicosapentenoate promoted the translocation to membranes with a similar potency to that of oleate. The phosphohydrolase that associated with the membranes in the presence of [14C]oleate or 1mM-spermine coincided on Percoll gradients with the peak of rotenone-insensitive NADH-cytochrome c reductase, and in the former case with a peak of 14C. Microsomal membranes were enriched with the phosphohydrolase activity by incubation with [14C]oleate or spermine and then incubated with albumin. The phosphohydrolase activity was displaced from the membranes by albumin, and this paralleled the removal of [14C]oleate from the membranes when this acid was present. Chlorpromazine also displaced phosphatidate phosphohydrolase from the membranes, but it did not displace [14C]oleate. The effects of spermine in promoting the association of the phosphohydrolase with the membranes was inhibited by ATP, GTP, CTP, AMP and phosphate. ATP at the same concentration did not antagonize the translocating effect of oleate. From these results and previous work, it was concluded that the binding of long-chain fatty acids and their CoA esters to the endoplasmic reticulum acts as a signal for more phosphatidate phosphohydrolase to associate with these membranes and thereby to enhance the synthesis of glycerolipids, especially triacylglycerol. The translocation of the phosphohydrolase probably depends on the increased negative charge on the membranes, which could also be donated by the accumulation of phosphatidate. Chlorpromazine could oppose the translocation by donating a positive charge to the membranes.

Animals↗
PubMed1985

Possible relationships between changes in body weight set-point and stress metabolism after treating rats chronically with D-fenfluramine. Effects of feeding rats acutely with fructose on the metabolism of corticosterone, glucose, fatty acids, glycerol and triacylglycerol.

Rats were maintained on a corn oil diet and treated with D-fenfluramine at doses of 2.5 mg/kg twice a day for 11 days or with 10 mg or 25 mg/kg once a day for 12 days. The lower dose of D-fenfluramine produced no marked changes in body weight and after 11 days of treatment the weights of the rats on average were only 2% lower than the controls. The food intake of these rats was only decreased on the first day. The two higher doses of D-fenfluramine decreased the food consumption for about 3 days but thereafter it was similar to that of the control rats. The body weight of these rats fell on the first day, but after about four days the gain in body weight paralleled rather than approached that of the control rats. Increasing the dose of D-fenfluramine progressively decreased the relative size of the epididymal fat pad. At the end of the treatment period the rats were fed acutely with fructose to increase the circulating concentrations of corticosterone and to stimulate triacylglycerol synthesis. All three doses of D-fenfluramine decreased the concentration of circulating triacylglycerol after fructose feeding. The 10 mg/kg dose also decreased the basal concentration of triacylglycerol. The two higher doses of fenfluramine decreased the rises in the circulating concentrations of corticosterone, glycerol and fatty acids that are produced by fructose feeding. The basal concentrations of these compounds in the absence of fructose feeding were not significantly affected by the 10 mg/kg dose of D-fenfluramine. The possible relationship between the effect of chronic treatment with D-fenfluramine in decreasing a metabolic stress response and lipolysis is discussed relative to its hypotriglyceridaemic action and its effect on body weight-set point. The results demonstrate that D-fenfluramine produced persistent changes in metabolism at a time when the treated rats were growing at the same rate as the control rats and when they were eating similar quantities of food.

Adipose Tissue↗
PubMed1983

Parathyroid gland responsiveness to acute hypocalcemia in dialysis osteomalacia.

The majority of chronic hemodialysis patients have elevated serum iPTH levels and bone disease characterized by osteitis fibrosa. However, a small group of patients develop osteomalacic bone disease associated with normal or slightly elevated iPTH values and a tendency to hypercalcemia which occurs either spontaneously or after treatment with small doses of vitamin D sterols. To examine the causes of the relatively low iPTH levels, we evaluated the change in serum iPTH levels that occurred in response to acute hypocalcemia, produced by dialysis using a low calcium dialysate, in 11 patients with osteomalacia and 8 control hemodialysis patients. Dialysis against a dialysate free of calcium for 60 to 90 min led to a fall in serum calcium to 7.5 +/- 0.2 and 7.2 +/- 0.2 mg/dl in the osteomalacic and control patients, respectively. Serum iPTH rose in controls from 1380 +/- 287 to 1960 +/- 287 pg/ml (P less than 0.01), whereas in patients with osteomalacia it rose from 360 +/- 58 to 507 +/- 104 pg/ml (P less than 0.05), a value only slightly above normal for this PTH assay. These data suggest that the relatively low basal levels of serum iPTH do not arise as a consequence of physiologic suppression of parathyroid gland function. This reduction in parathyroid function could contribute to the pathogenesis of low turnover osteomalacia.

Adult↗
PubMed1982

Protein degradation in mammary gland explants. Evidence for limited heterogeneity of protein degradation rates.

Mammary gland explants in organ culture were subjected to hormonal manipulation, and rates of protein degradation during 1 and 2 day periods were measured by a double-isotope method. Isotope ratios for protein subunits in subcellular fractions were measured after resolution by two-dimensional polyacrylamide gel electrophoresis. Frequency distribution analysis shows that isotope ratios for each fraction are grouped predominantly in exponential distributions corresponding to populations of protein subunits with different mean degradation rates. The results also suggest that heterogeneity of protein degradation rates within each population is limited. There is no consistent correlation of degradation rate with protein isoelectric point or subunit molecular weight either overall or within any population of degradation rates. Therefore, the similarity of protein degradation rates within each population is clearly related to these molecular properties of the proteins.

Animals↗
PubMed1980

Protein degradation during terminal cytodifferentiation. Studies on mammary gland in organ culture.

1. In mammary gland explants subjected to experimental manipulation, average rates (during 24 h periods) of degradation of fatty acid synthase, casein and cytosol-fraction proteins were measured by a double-isotope method. Rates of degradation of fatty acid synthase were also computed from measurements of changing enzyme amount and rate of synthesis. 2. During the period of most rapid enzyme accumulation there is a transient decrease in the computed rate of degradation of fatty acid synthase. Removal of hormones produces a rapid increase in the computed rate of degradation of the enzyme. 3. The average rate of degradation of fatty acid synthase measured by the double-isotope method is low in the presence of hormones, and increases on hormone removal. This increase in degradation rate is inhibited by adrenaline and further blocked by insulin. NH4Cl (10 mM) also partially inhibits the increase in protein degradation on hormone removal. 4. The pattern of changes in the average rate of degradation of cytosol-fraction proteins is similar to that for fatty acid synthase alone. There is no relationship between subunit molecular weight and rate of degradation under all experimental conditions. 5. Isotope ratios for resolved cytosol protein mixtures are transformed logarithmically to make the standard deviations an estimate of heterogeneity of degradation rates. By this analysis, in some conditions there appears to be significant measureable heterogeneity of degradation rates. 6. Little degradation of casein is measured in the presence of hormones, but a marked increase in the rate of degradation can be measured when hormones are removed. Whereas at 24-48h NH4Cl (10 mM) has little effect on this enhanced rate of degradation, at 48-72h it causes a large decrease in degradation rate. 7. Results are discussed in terms of a two-component degradation system in mammary gland explants.

Animals↗
PubMed1979

Use of surgery and postoperative radiation in the treatment of advanced squamous cell carcinoma of the pyriform sinus.

Forty-seven patients with very advanced cancer of the pyriform sinus were treated with surgery and immediate postoperative radiation in a planned sequential manner. Eradication of the cancer above the clavicles was obtained in 81% of the patients, with a treatment mortality of 8%. Most of the patients' tumors were resected with primary closure, which obviated the need for complicated reconstructive procedures. The survival rate of 23% at 2 years and the high rate of distant metastasis reflect the aggressive biologic behavior of this cancer. The need to find an adjuvant treatment that will act upon the systemic spread of this cancer is obvious.

Carcinoma, Squamous Cell↗
PubMed1977

The clinical significance of retinitis pigmentosa without pigment: a computer assisted analysis.

Sixty-eight consecutive patients with retinitis pigmentosa were studied to determine the frequency of the non-pigmented form of the disease. There was an overall incidence of 22%. Fifty percent of all cases had no characteristic pigmentation, if the duration of night vision difficulty was three years or less. The study lends statistical support to the concept that the non-pigmented form of retinitis pigmentosa is frequently an early stage of the disease and not an unusual or atypical variant. Patient without the pigmentary changes characteristic of the disorder also showed less functional impairment: the ERG b-wave was more apt to be recordable, although impaired; and the rod threshold, as determined by dark adaptation measurement, was less elevated. The clinician should suspect retinitis pigmentosa, even in the absence of pigmentary changes, if there is a family history of the disorder, night blindness, peripheral field loss, and an impaired or non-recordable electroretinographic response.

Dark Adaptation↗
PubMed1976

Unilateral retinitis pigmentosa sine pigmento.

A patient presented with unilateral findings of night blindness shown by impaired rod function and dark adaptation, constricted visual fields with good central acuity, a barely recordable electro-retinographic b-wave, and a unilaterally impaired electro-oculogram. There were none of the pigmentary changes usually associated with retinitis pigmentosa. The unaffected right eye was normal in all respects. Therefore the case is most probably one of unilateral retinitis pigmentosa sine pigmento.

Adult↗
PubMed1975

Pigmented paravenous retinochorodial atrophy.

Three male patients had paravenous pigmented retinochoroidal atrophy. Extensive retinal function tests showed characteristic retinal pigment epithelial abnormalities on fluorescein angiography, loss of peripheral visual field, diminution of the electroretinographic b-wave, and elevated rod threshold on dark adaptometry. The disease appears to be more progressive than previously indicated, and in late stages, may cause legal blindness through involvement of the posterior pole. No treatment is known.

Adult↗
PubMedDate not supplied

Cognitive test performance and presence of subclinical cardiovascular disease in the cardiovascular health study.

The purpose of the present study was to investigate the relationship between performance on a comprehensive battery of neuropsychological tests and the presence of clinical, subclinical or no cardiovascular disease in an elderly community-dwelling population. The results confirm previous reports of significant associations of age, education and gender with test performance. When performance was examined controlling for these variables, significant associations of disease group were seen with five measures emphasizing speed of performance; Parts A and B of the Trail Making Test, the WAIS-R Digit Symbol and Block Design subtests and category verbal fluency. These results add to the evidence that, in addition to other health implications, cardiovascular disease is related to cognitive functioning in the elderly even at subclinical levels.

Aged↗