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Biomedical subjects

J Read

Publications and source records attributed to J Read.

29 records · Page 2Linked to original sources

Cytolethal effects of glucocorticoids in human lymphoblastoid cell lines.

Glucocorticoid hormones penetrate rapidly into intact lymphoblastoid cells and are retained with the same high affinity and specificity as with cytoplasmic extracts. Optimal conditions for lethal glucocorticoid responses in vitro were determined for a series of human lymphoblastoid cell lines by using different glucocorticoid preparations, and steroid solvents and by varying the cell density. Kinetic studies revealed that lethal glucocorticoid effects are dose-dependent and that continuous exposure of cells to steroid is necessary for progression of lethal effects to occur. Even under optimal conditions, human lymphoblastoid cells only exhibit a marked cytolethal response to glucocorticoids at concentrations which greatly exceed both physiological and therapeutically attainable steroid levels. They are also greatly in excess of steroid levels required to saturate the cytoplasmic receptors of intact or disrupted lymphoblastoid cells. It is suggested that either lethal steroid mechanisms in vitro differ fundamentally from those in vivo or the pharmacological activity of glucocorticoids in vivo does not involve a direct cytolethal action.

Burkitt Lymphoma

The second oncogenic step.

Three theories of the development of a malignant change which each involve two successive steps are described. Armitage, Doll (1957) proposed that two homologous chromosomes each contained a region which was critical in the control of cell division. The two steps were mutations in these regions brought about by random exposure to carcinogenic agents. Comings (1973) proposed a similar theory but the two steps were considered to be spontaneous mutatons. This paper points out that if one mutation has occurred this can become dominant in at least six ways which mostly involve chromosome translocations. The synergism between oncogenic agents and ionizing radiation and the ability to breed out high and low cancer incidence stocks of animals from a common stock can be explained on the same lines.

Animals

Measurement of 3,3',5'-Triiodothyroinine (reverse T3), 3,3'-L-diiodothyronine, T3 and T4 in human amniotic fluid and in cord and maternal serum.

In order to assess fetal function at term, we have investigated parameters of thyroid hormone secretion and degradation in human amniotic fluid and in cord and maternal sera at delivery. The parameters measured included 3,3' L-diiodothyronine (3,3'T2), 3,3',5'-triiodothyronine (reverse T3), 3,3',5'-triiodothyronine (T3), thyroxine (T4), dialyzable T3 and T4, thyroxine binding globulin (TBG),and total iodine. The mean (+/- SE) 3,3'T2 concentrations in cord sera, amniotic fluid, and maternal sera were 20 +/- 1 ng/100 ml, 20 +/- 2 ng/100 ml,and 27 +/- 3 ng/100 ml, respectively. The normal range of this metabolite in the sera of non-pregnant adult subjects was 7 to 29 ng/100 ml. The mean (+/- SE) concentration of reverse T3 was higher in cord sera (315 +/- 16 ng/100 ml), amniotic fluid (82 +/- 25 ng/100 ml) and maternal sera (79 +/- 5 ng/100 ml) than in the sera of normal subjects (mean +/- 2 SD; 60 +/- 12 ng/100 ml). In amniotic fluid, T3, T4, and TBG were low, per cent dialyzable T3 and T4 were increased, and iodine concentrations were relatively normal in comparison to their respective serum levels in euthyroid adults. Since T3 and T4 were low in amniotic fluid our data indicate that measurements of 3,3'T2, reverse T3, or per cent dialyzable T3 and T4 in amniotic fluid would be the potentially most useful in establishing the diagnosis of congenital hypothyroidism before birth. In addition, these studies demonstrate that 3,3'T2 is normally present in the peripheral circulation and suggest that reverse T3 is the major source of 3,3'T2 in both amniotic fluid and cord blood.

Amniotic Fluid

The lethal effect on bacteria of dimethylnitrosamine used without an activating agent.

Survival curves have been obtained for various strains of bacteria treated with dimethylnitrosamine (DMN) solutions of different concentrations. The results are compatible with the conclusion that DMN kills the bacteria by an attack on their deoxyribonucleic acid (DNA) and the damage so caused can be repaired by the same systems that repair damage created by ultraviolet light or X radiation. No activating agent was added to the DMN solutions and under these circumstances their activities were in proportion to the squares of their concentrations. It is suggested that this is because two molecules of DMN plus one of oxygen produce two carbonium ions, two hydroxyl ions, two formaldehyde molecules and two nitrogen molecules.

DNA Repair

Traumatic hyphema: surgical vs medical management.

We undertook a prospective study of traumatic hyphema during the years 1970 through 1972 to compare the effects of medical management and surgical evacuation in the more severe hyphemas. A protocol for sutdy of the two regimens enabled us to compare the results of therapy. The findings indicate that medical management is preferable for the initial 4 days in major hyphemas. Surgical intervention does not offer improvement in the poor prognosis of total hyphemas during this early period. The incidence of complications and the incidence of permanent poor visual results are higher in surgically treated patients than in those managed medically. Surgical intervention should be reserved for cases showing: (1) microscopic corneal blood staining; (2)total hyphemas with intraocular pressures of 50 mm Hg or more for 5 days (to prevent optic nerve damage); (3) hyphemas that are initially total and do not resolve below 50% at 6 days with intraocular pressures of 25 mm Hg or more (to prevent corneal blood staining); and (4) hyphemas that remain unresolved for 9 days (to prevent peripheral anterior synechiae). A brief review of problems that may be encountered in the various forms of surgical management is included in an effort to prevent repeating similar pitfalls.

Adult