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Biomedical subjects

S Roberts

Publications and source records attributed to S Roberts.

At least 289 records · Page 16Linked to original sources

The effect of desferrioxamine on transferrin receptors, the cell cycle and growth rates of human leukaemic cells.

The effect of the iron chelator, desferrioxamine, on transferrin binding, growth rates and the cell cycle was investigated in the human leukaemic cell line, K562. At all concentrations of the chelator (2-50 microM) binding of 125I-transferrin was increased by 24 h and reached a maximum at 72-96 h. Maximum binding (6-8-fold increased) occurred in cells treated with 20 microM-desferrioxamine, in contrast with control cells which, at 96 h, showed a 50% decrease over initial binding. Scatchard analysis at 4 degrees C showed that this increased binding was due to an increase in the number of receptors, as the Kd was similar in induced (1.8 nM) and control (1.5 nM) cells. After 96 h cells, cultured with 20 and 50 microM-desferrioxamine accumulated 59Fe from bovine transferrin at over twice the rate found with control cells, reflecting the increase in transferrin receptors. Although iron uptake was unimpaired by the chelator there was a dose-dependent inhibition of cell growth, with control cells completing three divisions in 96 h and those in 10 microM-desferrioxamine only two divisions. At the highest concentration (50 microM), cell division was abrogated although cell viability was maintained (85%). In contrast, DNA synthesis was not markedly affected, except at 50 microM-desferrioxamine when incorporation of [3H]thymidine was 52% of that in control cells. Flow cytometry revealed that there was a progressive accumulation of the cells in the active phases of their cycle (S, G2 + M). Desferrioxamine may increase transferrin receptors in two ways: by chelating a regulatory pool of iron within the cell, and by arresting cells in S phase when receptors are maximally expressed.

Cell Cycle↗

Evidence in a nematode for regulation of transposon excision by tissue-specific factors.

The transposable element Tc1 in Caenorhabditis elegans undergoes an excision reaction, which can be detected in a Southern hybridization as the appearance of empty chromosomal insertion sites. This excision reaction is under tissue-specific regulation in that it occurs at much higher frequency in somatic cells than in the germ line. We show here that this regulation is likely to be due to the action of tissue-specific factors that either promote excision in somatic tissues or repress it in the germ line. The rate of excision of elements at five distinct chromosomal sites has been measured by a method that avoids ambiguities due to cell division. All these elements are found to undergo excision at closely similar rates during the L1 larval stage. No distinct difference exists among the elements at different sites that would suggest regulation by flanking sequences.

Animals↗

Isolation and characterization of human blood-coagulation factor X cDNA.

Using synthetic oligodeoxynucleotides as probes, we have isolated factor X cDNA from human liver cDNA library. We sequenced the 1430-bp cDNA which spans the coding region of the mature factor X and contains the polyadenylation signal and poly(A) tail. The amino acid (aa) sequence is in agreement with the published aa sequence. The nucleotide (nt) sequence of cDNA confirmed that factor X is synthesized and secreted as a single-chain precursor, and then converted into dimeric form by proteolytic cleavage of an internal tripeptide. From the nt sequence, it was also predicted that like other secretory proteins, human factor X is synthesized with a leader sequence (prepro-protein). The 5'-coding region of factor X cDNA is 60 and 40% homologous to the corresponding regions of factor IX and prothrombin genes, respectively. This supports the hypothesis of gene evolution by gene duplication followed by divergence.

Amino Acid Sequence↗

Comparative in-vitro activity of antibiotics incorporated in acrylic bone cement.

We compared the persistence of antibacterial activity around antibiotic-impregnated acrylic bone cement discs which were serially transferred on seeded agar plates. On plates inoculated with Staphylococcus aureus ATCC 25923, CMW1 discs containing 2.5% by dry weight of cephalothin, coumermycin or fusidic acid (as diethanolamine fusidate) produced zones of inhibition for four to eight weeks when transferred daily. In contrast, ceftriaxone, cotrimoxazole, rifampicin and vancomycin ceased to be inhibitory within a week. Discs made of 'Palacos-R with Garamycin,' which contains gentamicin 1.25%, had an intermediate duration of activity. When Escherichia coli ATCC 25922 was used as the test organism, ceftriaxone and 'Palacos-R with Garamycin' showed activity for almost three weeks, cephalothin and cotrimoxazole were briefly inhibitory and the remainder not at all. When discs were transferred each week instead of daily, the ranking of antibiotics was similar but antibacterial activity persisted for longer. A combination of gentamicin plus fusidic acid in CMW1 was active for a much shorter time than either fusidic acid alone or 'Palacos-R with Garamycin'. We conclude that coumermycin is a promising new agent for incorporation in acrylic cement.

Acrylates↗

A controlled study of oral prednisolone in frozen shoulder.

Forty patients with frozen shoulder were randomly allocated to a treated group who received oral prednisolone or a nontreatment group who received no specific therapy. All the patients were encouraged to perform home pendular exercise. The improvement in pain at night showed a significantly different pattern in the two groups (p less than 0.05), with the treated group improving more rapidly. Pain on movement and at rest and the recovery in the range of movement was not significantly different in the two groups. There was no difference between the patient groups at the end of the study (8 months follow-up) and patients still had a marked restriction in range (p less than 0.0001) when compared to normal controls of similar age and sex.

Administration, Oral↗

Mechanical and biochemical properties of human articular cartilage in osteoarthritic femoral heads and in autopsy specimens.

We studied the mechanical and biochemical properties of articular cartilage from 22 osteoarthritic femoral heads obtained at operation and 97 femoral heads obtained at autopsy. Cartilage from the zenith and from the antero-inferior aspect of each head was tested both in tension and in compression. Water content, swelling ability and proteoglycan content were measured, the cartilage was examined histologically and the density of the underlying bone was assessed. Fifty-five of the autopsy specimens were defined as macroscopically normal because they exhibited no progressive fibrillation patterns on staining with Indian ink; but significant changes in water content, bone density and tensile strength related to age were seen in this group. In 20 pairs of femoral heads which were both macroscopically normal, we found, surprisingly, that cartilage from the left and right sides of the same patient was sometimes very different. Compared with the normal autopsy specimens the osteoarthritic specimens had a significantly increased swelling ability, a lower proteoglycan content and impaired mechanical properties, being both weaker in tension and softer in compression. Abnormal autopsy specimens had values intermediate between those of osteoarthritic and normal groups. Results from this abnormal group suggest that there is no primary loss of proteoglycan in early osteoarthritis.

Adolescent↗

Mechanical and biochemical properties of human articular cartilage from the femoral head after subcapital fracture.

Articular cartilage from the femoral heads of 27 patients having an arthroplasty for subcapital fracture was studied, and its mechanical and chemical properties compared to those of a group of 33 age-matched macroscopically normal autopsy specimens. Water and proteoglycan contents were measured, as were swelling ability, compressive and tensile strength of the cartilage, and the density of the underlying bone. Cartilage from the fracture specimens had a significantly reduced proteoglycan content, as measured by fixed charge density, and increased swelling ability. These results indicate that this group differs from the "normal" population and care should be taken before they are accepted as control material for studies on osteoarthritic cartilage. Another finding was that bone density was much the same in the fracture and the normal group. This casts some doubt upon the concept that patients who sustain subcapital fractures are more osteoporotic than the average for the same age range.

Adolescent↗

Intracellular processing of transferrin and iron by isolated rat hepatocytes.

Transferrin bound by isolated rat hepatocytes is rapidly endocytosed and enters a compartment of low density. Little was found associated with the lysosomes, even though the protein was subsequently lost from the cells. Iron entering the cells on transferrin was subsequently found in a number of intracellular components: transferrin, haem, ferritin and a residual fraction. After 2 h incubation with 59Fe-transferrin almost 70% of the iron was in ferritin, and this proportion increased to 80% during a 'chase' experiment. Residual iron, because of its rapid increase at the start of the incubation and its decline during the 'chase', probably represents an intracellular transit pool, which at steady state was present at 23 pg/10(6) cells.

Animals↗

Collagen of the calcified layer of human articular cartilage.

The distribution patterns of collagen types I, II and III were studied using immunofluorescent staining techniques in human articular cartilage, including the calcified layer. Tissue taken from femoral heads was stained with the appropriate antiserum. Adjacent sections were stained with von Kossa or Alizarin red to determine the distribution of calcium salts. Results indicate that endochondral ossification at this site occurs by calcium being deposited initially within a matrix of type II collagen.

Calcification, Physiologic↗

Effect of classical conditioning on an internal clock.

Six experiments with rats used a psychophysical choice procedure to study the internal clock used to discriminate duration. They investigated if the clock is sensitive to the signal value (associative strength) of a stimulus. The experiments involved two types of trials. On choice trials, a stimulus lasted a short (e.g., 3 s) or long (e.g., 12 s) duration; then the rats chose between two levers. The rewarded choice depended on the duration of the stimulus. On conditioning trials, the stimulus used on choice trials was presented, but it ended without food (extinction trials) or with food (pairing trials) regardless of what the rat did. The main stimulus minus accuracy with the long stimulus. Experiment 1 showed that extinction trials increased short bias relative to training without conditioning trials or to training with pairing trials. The rest of the experiments tested explanations of these results. The same results were found when extinction trials were the same duration as the short stimulus (Experiment 2), when extinction trials were a random duration (Experiment 5), and when the signal value of the conditioned stimulus was changed in another way (Experiment 6). The effect of conditioning trials was modality specific (Experiments 3 and 4). Of the explanations considered, the best one--the only one not contradicted at least once--is that changing the signal value of a stimulus changes how the clock times the stimulus. Reducing signal value reduces the measured duration.

Animals↗

Evaluation of flatbed reciprocal motion agitators for resuspension of stored platelet concentrates.

We studied the storage characteristics of platelet concentrates prepared in polyolefin (PL-732) and thin-film polyvinyl chloride (CLX) plastic bags and stored on a newly designed flatbed reciprocal motion agitator with a 1.5 inch (3.8 cm) lateral movement and an oscillation frequency of 70 cycles/min. We also studied the ability of this device to resuspend the platelet button formed after preparative centrifugation. Results showed that platelet concentrates stored on the 1.5-inch shaker had storage characteristics equivalent to those reported for the conventional 70 cycles/min, 1-inch (2.5-cm) lateral movement flatbed shaker. Due to a more rapid acceleration and deceleration rate, however, the 1.5-inch shaker resuspended the platelet button formed after preparative centrifugation much more efficiently than did the less dynamic 1-inch shaker. Furthermore, with either agitator, platelet aggregates in the CLX bag were more readily resuspended than were aggregates in the PL-732 bag due in part to differences in plastic bag wall elasticity.

Blood Platelets↗

Reproductive performance and profitability of heifers fed to weigh 272 or 318 kg at the start of the first breeding season.

Reproductive performance and weaning weight of the first calf was determined in 221 Brahman crossbred heifers fed to weigh either 272 (TW1) or 318 kg (TW2) at the start of their first breeding season (target weight). Heifers were divided into light- (below average) and heavyweight (above average) groups on the basis of initial weight. Within each target weight, heifers were fed in three lots. One lot contained lightweight heifers, the second contained heavy heifers and the third was composed of one-half heavy- and one-half lightweight heifers. Heifers were fed for 200 d before the start of the first breeding season. More heifers in TW2 showed estrus and became pregnant in the first 20 d of the breeding season and more were pregnant at the end of the first breeding season. These same differences in reproductive performance were also noted the second year. Each heifer exposed in TW2 weaned 43.4 kg more calf than those in TW1. An average heifer in TW2 was fed 220 kg more corn and 100 kg less hay than a corresponding heifer in TW1. Estrus and pregnancy rate for lightweight heifers in TW1 and TW2 were not improved by sorting and feeding them separately.

Animals↗

Comparison of timing and classical conditioning.

Four experiments with rats investigated if the timing of a stimulus (sound) correlated with the strength of a conditioned response (CR) to the stimulus. The timing (effective duration) of the stimulus was measured using the peak procedure, similar to a discrete-trials fixed-interval procedure. The rats were trained so that their response rate reached a maximum about 40 s or 60 s after the onset of a light; the time of the maximum measured from the start of the light (peak time) was the measure of timing. On some trials, the light was preceded by a short (5 s) or long (20 s or 30 s) interval of sound. We assumed that the difference in peak time after long and short sounds reflected the timing of the sound--if the sound was timed, the longer sound would produce a lower peak time; if the sound was not timed, the two durations of sound would produce the same peak time. The CR was lever-pressing during the sound. The sound was treated in various ways: presented alone (Experiments 1, 3, and 4), followed by food (Experiments 1, 3, and 4), preceded by food (Experiment 3), and followed by food after 20 s (Experiment 4). Treatments that produced no timing of sound produced no CR, and treatments that increased (or diseased) timing also increased (or decreased) the CR. The results suggest that there is overlap between the mechanisms that produce time discrimination and the mechanisms that produce classical conditioning.

Animals↗