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Biomedical subjects

J Gordon

Publications and source records attributed to J Gordon.

At least 433 records · Page 24Linked to original sources

Prolonged exposure to antigen induces specific unresponsiveness of mixed leukocyte culture-activated cells.

One-way mixed leukocyte cultures, supplemented by the daily addition of small numbers of fresh stimulating cells between days 5 and 15 of incubation, failed to give a secondary proliferative or cell-mediated lympholytic response upon challenge with activating concentrations of the same stimulating. cells. However, these cultures could be fully activated by blastogenic factor (BF). The unresponsiveness induced was immunologically specific: when responding cells were primed simultaneously with stimulating cells from two donors and one stimulator was added daily, the cultures were unresponsive to challenge with cells of the stimulator which were added daily, but good secondary responses were elicited both by cells of the other stimulator used in priming and by BF. The induced unresponsiveness may be a consequence of specific inactivation of helper cells.

Antigens↗

Isolation and characterization of leukaemic B-lymphocytes: influence of anticoagulant on C3-receptor detection, humoral killing and capping of cell surface immunoglobulin.

Guinea pig L2C neoplastic B-lymphocytes processed from leukaemic blood collected into EDTA as anticoagulant exhibited high affinity rosetting for EAC mouse indicator cells. Partial blocking of the C3-receptors was apparent with blood collected into heparin or citrate as anticoagulant. This could be minimized by keeping the temperature at 4 degrees C and avoided by ensuring a high final concentration of citrate (greater than or equal to 40 mM). Results from experiments in vitro suggested that receptor blocking may have been a consequence of complement activation by the L2C cells occurring via the alternative pathway. No injury to the cells was evident with any of the anticoagulants used, and their susceptibility to antibody-dependent complement-mediated lysis was independent of anticoagulant and unaffected by the irregular presence of membrane-bound C3. In experiments where the antibody-induced redistribution of L2C surface immunoglobulin was investigated, it was found that cells processed from blood collected into EDTA showed poor ability to cap and interiorize their surface immunoglobulin in comparison with cells processed from heparinized or citrated blood. Inhibition of capping was found to be dependent on the concentration of EDTA and could be avoided by collecting blood into a large volume of low molarity EDTA as opposed to a small volume of high molarity EDTA. Some practical and theoretical consequences of our observations are discussed.

Animals↗

Regulation of 40S ribosomal protein S6 phosphorylation in Swiss mouse 3T3 cells.

Addition of serum to resting cultures of Swiss mouse 3T3 cells causes an immediate multiple phosphorylation of 40S ribosomal protein S6. After 60 min of stimulation, changing to medium containing no serum led to the net dephosphorylation of S6. During this same period, a second protein, as yet unidentified, became increasingly phosphorylated. Incubation of cells with cycloheximide prior to the addition of serum almost completely blocked the activation of protein synthesis. There was no effect on the serum-induced phosphorylation of S6. If cells were stimulated in the presence of cAMP phosphodiesterase inhibitors theophylline or SQ 20006, both S6 phosphorylation and the activation of protein synthesis were inhibited. Stimulation of cells with serum also led to an immediate drop in total intracellular cAMP levels. This was blocked by prostaglandin E1 (PGE1), which caused a 10 fold increase in total intracellular cyclic AMP. However, PGE1 had no effect on protein synthesis or S6 phosphorylation.

Animals↗

Preliminary experience in treating lymphocytic leukaemia with antibody to immunoglobulin idiotypes on the cell surfaces.

Tumour-specific antiserum was raised in sheep against idiotypic determinants on the surface immunoglobulin of neoplastic lymphocytes from a patient with chronic lymphocytic leukaemia (prolymphocytic variant). The complement-activating IgG1 subclass of the anti-idiotype was prepared from the serum in monodisperse form for infusion. Two treatments of 480 and 1200 mg caused the white-cell count to fall by one-third and one-half respectively. However, there was a rapid resurgence, so that by 8 days after each treatment the counts were restored to approximately 85% of their former levels. No change was noted in the size of spleen or lymph nodes. Each treatment probably destroyed 4-8 X 10(11) cells, some 10% of the total tumour load. The antibody was rapidly consumed, and there was evidence of heavy utilization of complement.

Aged↗

Melatonin and the thyroid.

Chronic melatonin administration (100 microgram daily for 21 days) to male weanling rats increased basal TSH without altering peripheral hormone levels. There was an increase in radioactive thyroidal iodine uptake in the melatonin treated animals. Melatonin increased the thyroid gland size relative to body weight and increased the total T4 content and T4:T3 ratio in the thyroid gland. There was no effect of melatonin on TSH response to TRH or hypothalamic TRH content. Optic nerve section increases serum TSH and T3 levels. The increase in T3, but not TSH, is abolished by pinealectomy. The alterations in circulating thyroid hormone levels after optic nerve section were not altered by chronic melatonin administration.

Animals↗

Purification of a factor that restores translation of vesicular stomatitis virus mRNA in extracts from poliovirus-infected HeLa cells.

It was previously shown that the poliovirus-induced inhibition of translation of capped mRNAs can be reversed by a protein found in preparations of the eukaryotic initiation factor eIF-4B [Rose, J. K., Trachsel, H., Leong, K. & Baltimore, D. (1978) Proc. Natl. Acad. Sci. USA 75, 2732--2736]. This "restoring factor" has now been purified from a high-salt wash of rabbit reticulocyte ribosomes by taking advantage of its tight association with factor eIF-3 at low salt concentrations. It did not copurify with the major Mr 80,000 polypeptide of eIF-4B preparations but did copurify with a Mr 24,000 polypeptide previously shown to bind to the cap structures of mRNAs [Sonenberg, N., Rupprecht, K. M., Hecht, S. M. & Shatkin, A. J. (1979) Proc. Natl. Acad. Sci. USA 76, 4345--4349]. Both the electrophoretic mobility and the tryptic peptide pattern of the restoring factor were indistinguishable from those of the cap-binding protein, and the restoring factor could be crosslinked to the 5'-terminal cap on mRNA. Thus, is appears that poliovirus inhibits cellular protein synthesis by inactivation of some crucial property of the cap-binding protein.

Carrier Proteins↗

Zinc deficiency, chronic starvation, and hypothalamic-pituitary-thyroid function.

Male Sprague-Dawley rats were fed a zinc-deficient diet to study its effects on the hypothalamic-pituitary-thyroid axis. As zinc-deficient animals fail to gain weight, they were compared to pair-fed growth restricted animals as well as ad libitum fed controls. The growth velocity curves were superimposable for the zinc-deficient animals and the pair-fed controls; both were markedly reduced compared to the ad libitum controls. Both the zinc-deficient and the pair-fed controls had lower triiodothyronine (T3) and thyroxine levels compared to the ad libitum controls. In addition T3 values were lower in the zinc-deficient animals compared to the pair-fed controls (P < 0.05). Hypothalamic thyrotrophin-releasing hormone content was decreased in the zinc-deficient rats (162 +/- 32 pg/ml) compared to the ad libitum controls (305 +/- 102; P < 0.01). The 125I thyroidal uptakes were not significantly different between the zinc-deficient and the pair-fed controls. Zinc deficiency lowers T3 more than comparable caloric restriction; this suggests that zinc deficiency may impair extrathyroidal production of T3.

Animals↗

Caudal extradural injection for the treatment of low back pain.

The technique of large volume caudal extradural injection of a solution containing bupivacaine hydrochloride, hydrocortisone acetate and methylprednisolone acetate for low back pain is described. The results of 500 such injections are reviewed. The technique provides a rapid safe method for the treatment of low back pain. Pain was relieved in over half the patients treated by a single injection.

Anesthesia, Caudal↗

Women in medical school and beyond.

The increasing proportion of female students in Australian medical school warrants an appraisal of the particular factors which may influence their success in their undergraduate and post-graduate careers. Past shortages of medical manpower are giving way to a projected over-abundance of doctors in the near future. New South Wales has three medical schools, and in 1979 women constituted a significant percentage of the total number of students entering the first year. In the Newcastle school that percentage has exceeded 50. Because the majority of women combine their careers with child-bearing and child-raising, they face special problems in medical shcool and beyond. The fulfilment of dual roles frequently creates significant conflicts for women, but there are signs that women are gradually overcoming such conflicts. In fact, some male students are now beginning to question their tradition of full-time commitment to a stressful profession with little free time left for their families or other interests. To make the best use of medical manpower, planning towards more flexible training schemes and more innovative roles in medical practice is essential. Women in particular can help one another by co-operation and imaginative planning.

Attitude of Health Personnel↗

Immunoglobulin synthesis by neoplastic cells: models of a clonal transition from IgM to IgG synthesis.

Tumour populations from two B cell neoplasms were investigated for their capacity to synthesise immunoglobulin in vitro. Neoplastic cells from a patient with chronic lymphocytic leukaemia and an IgG lambda paraproteinaemia co-expressed surface IgG lambda and IgM lambda and synthesised both IgG lambda and IgM lambda in short-term culture. In the second patient with non-Hodgkin's lymphoma, the neoplastic cells expressed surface IgM lambda but synthesised both IgM lambda and IgG lambda in vitro. The findings are discussed in terms of a model for the clonal switch from IgM to IgG synthesis.

Aged↗

Immunoglobulin synthesis by neoplastic B lymphocytes: free light chain synthesis as a marker of B cell differentiation.

Immunoglobulin synthesis has been investigated in 55 cases of B lymphocytic disease. Free light chain was the predominant product of Ig synthesis and the sole secreted Ig product from neoplasms lacking surface Ig or expressing sparse surface IgM as detected by fluorescent-labeled antibody. In contrast, neoplastic cells expressing strong surface IgM or IgG synthesized and secreted balanced amounts of heavy and light chain. Intermediate patterns of synthesis were shown by neoplastic cells expressing IgM with IgD. These patterns of synthesis occurred irrespective of the disease entity and are discussed in relation to models of B cell maturation.

Animals↗

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Carrageenan↗