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Biomedical subjects

J Shaw

Publications and source records attributed to J Shaw.

At least 307 records · Page 17Linked to original sources

In vitro analysis of allogeneic lymphocyte interaction. V. Identification and characterization of two components of allogeneic effect factor, one of which displays H-2-restricted helper activity and the other, T cell-growth factor activity.

An allogeneic effect factor (AEF) derived from mixed lymphocyte reaction (MLR) cultures of alloactivated A.SW (H-2s) responder T cells and irradiated A/WySn (H-2a) stimulator spleen cells helps an in vitro primary anti-erythrocyte plaque-forming cell PFC response of BALB/c nude spleen cels and also A/WySn but not A.SW T cell-depleted spleen cells. AEF activity is adsorbed by anti-Ik and anti-I-Ak but not by anti-I-Jk, anti-I-ECk, and anti-Is. Gel filtration of ACA 54 resolves AEF into two main components that which appear in the 50,000- to 70,000-mol wt (component I) and 30,000- to 35,000-mol wt (component II) regions, respectively. Component I has a mol wt of 68,000, elutes from DEAE-Sephacel at 0.05-0.1 M NaCl, and has an isoelectric point (pI) of 5.8. It helps A/WySn but not A.SW B cells and, therefore, is H-2 restricted. Component II is not H-2 restricted, because it helps both A.SW and A/WySn B cells. It also stimulates (a) the growth of a long-term cytotoxic cell line in vitro, (b) Con A-induced thymocyte mitogenesis, and (c) the generation of cytotoxic T cells. The latter three properties of component II are not shared by component I. In addition, component II elutes from DEAE-Sephacel at 0.15-0.2 M NaCl and has a pI of 4.3 and 4.9. Ia determinants and Ig VH, CH, L-chain, and idiotypic determinants are not present on either component I or component II. The properties of component II are identical to that of a T cell growth factor produced by Con A-stimulated spleen cells. It is suggested that the H-2-restricted component I of AEF might be an MLR-activated responder T cell-derived Ia alloantigen receptor.

Animals↗

Effect of a monoclonal anti-lyt-1.1 on the functional activity of precursor, effector, and regulatory cells specific for murine alloantigens.

A monoclonal anti-Lyt-1.1 serum has been characterized in terms of its effect on various cell populations involved in cell-mediated immune responses. The monoclonal serum was compared to a conventionally prepared anti-Lyt-1.1 serum. Cytotoxic T cell precursors and effectors were found to be Lyt-1.1+. Helper T cells which participate in the induction of a cytotoxic response were also Lyt-1.1+ as were suppressor T cells which inhibit cytotoxic responses. The T cell that is required for the production of a nonspecific stimulatory factor, costimulator, and that has been shown to bear the same Ly markers as does the helper T cell, bears Lyt-1.1. Finally, the effector cell which mediates delayed-type hypersensitivity reactions to alloantigens has been shown to be Lyt-1.1+. In all of these cases treatment with the monoclonal anti-Lyt-1.1 and complement had the same effect as did treatment with a conventional anti-Lyt-1.1 and complement. The distribution of Lyt-1.1 on various cell types as determined using the monoclonal anti-Lyt-1.1 is in complete agreement with the Lyt-1.1 distribution obtained with conventional anti-Lyt-1.1 sera, and is quite different from the reactivity of an anti-Thy-1 serum as determined by strain distribution. The distribution of the Lyt-1.1 specificity on the T cells within a given strain is identical to that seen with the conventional anti-Lyt-1.1 serum and, as reported by many others, does not differ from the distribution of Thy-1 specificities.

Animals↗

A comparison of the effects of hydrallazine, diazoxide, sodium nitrite and sodium nitroprusside on human isolated arteries and veins.

1 Human common palmar digital arteries and dorsal metacarpal veins have been studied in vitro to investigate the responses of arterial and venous muscle to hydrallazine, diazoxide, nitroprusside and sodium nitrite. 2 Tissues were removed at autopsy, cut into helical strips and suspended in organ baths under identical conditions. The contractile response to noradrenaline was tested in the presence of the same concentrations of the vasodilator drugs in arteries and veins. 3 Hydrallazine antagonised contraction of arteries, but not veins to noradrenaline. Diazoxide, nitroprusside or sodium nitrite antagonised responses in both arteries and veins. Diazoxide and nitrite were more effective on arteries and nitroprusside was more effective on veins. 4 These results are in accord with clinical observations and confirm that there are differences in the susceptibility of human arterial and venous smooth muscle to vasorelaxant drugs.

Arteries↗

Dumb blond syndrome.

In a retrospective study of sixteen female psychiatric patients who had received treatment over long periods of time, it was found that the patients' below-average intellectual functioning was an unrecognized primary factor in misdiagnosis and inappropriate treatment. All these patients had received psychotherapy (individual and group) and a wide variety of psychotropic medication. Several had been treated with ECT, also without benefit. We remind doctors that the presentation of the well-groomed, well-spoken, attractive female patient with social supports may conceal an element of intellectual handicap. We suggest awareness of this possibility may modify diagnostic and treatment procedures, so that the dangers of subsequent iatrogenic illness may be avoided.

Adult↗

Interleukin 2 in cell-mediated immune responses.

The lymphokine Interleukin 2(IL2) restores T cell responses in a number of in vitro systems where immunogenicity has been compromised. UV irradiation of the stimulating allogeneic cells in a mixed leukocyte culture eliminates the production of cytotoxic T lymphocytes and greatly reduces the DNA synthesis response. IL2 restores both parameters. UV-irradiated stimulators are also unable to induce the normal production of IL2 which is observed in a mixed leukocyte culture. The cytotoxic activity of allogeneically stimulated thymocytes is almost completely lost within 24 hours after removal of IL2 at 5 days, indicating that the lymphokine is continuously required to maintain CTL. Thymocytes in 4-day cultures do not adsorb IL2 unless they are simultaneously activated with a mitogen. Finally, IL2 does not adequately restore a secondary response to the purified protein derivative of tuberculin (PPD) in adherent-cell-depleted cultures, indicating that macrophages, in addition to being required for IL2 production, have other functions. These probably include the presentation of soluble antigens to responding cells.

Animals↗

Variability in heparin effect on serum drug binding.

Heparinized saline was given to seven men and one woman, aged 21 to 42 yr, after a 14-hr fasting period and 2 hr after breakfast; blood was collected in nonoheparinized tubes. Diazepam (D alpha) and warfarin (W alpha) free fractions were determined in serum by equilibrium dialysis to which radiolabeled drug was added. After 50 U heparin (Harris LO14) intravenously, the maximum effect on D alpha, W alpha, and free fatty acids (FFA) developed in 5 min and lasted 20 to 30 min. D alpha rose and W alpha fell (p < 0.01) at 5 min. Cumulative doses of heparin increased FFAs (F4,16 = 18.29, p < 0.0005). D alpha rises (r = 0.73, p < 0.001) and W alpha falls (r = -0.74, p < 0.001) correlated with changes in FFAs. D alpha rises and W alpha falls were greater postprandially than in the fasted state (p < 0.01). Five subjects were randomly assigned up to 400 U intravenously of each of two different heparin lots (Harris LO14, and Organon LA39.) The FFA rises (reflecting heparin lipolytic activity, F1,32 = 179.62, p < 0.0005), D alpha rises (F1,32 = 34.22, p < 0.0005), and the W alpha falls (F1,32 = 33.20, p < 0.0005) by heparin Harris LO14 were greater than those by heparin Organon LA39. Although small doses of heparin, such as those in heparin locks, can affect drug binding, the extent and variability of the effect depends on the biologic activity of the heparin, and varies with manufacturer and lot, exact time of sampling, and eating.

Adult↗

An assessment of the clinical use of glyceryl trinitrate in a hospital outpatient population.

Despite the availability of information on the use of glyceryl trinitrate (GTN) in standard texts, in practice many patients fail to obtain maximum benefit from GTN. This study of an Outpatient population, documents the patients' knowledge of the use and precautions which should apply to GTN and records the ways in which these patients took the drug. Fifty patients who regularly took GTN (greater than 5 tablets per week) were asked a series of questions by the same interviewer. Forty-nine of the 50 patients took GTN for the relief of chest pain, but only 34 patients knew that the drug could be used to prevent chest pain. Although 48 patients kept their bulk supply of GTN in the original container, over 40% transferred some or all of the tablets to other containers and locations. Seventy per cent of patients knew that GTN tablets deteriorate with time. However, knowledge of the factors which influence the rate of deterioration was lacking. Less than half the patients knew that the prompt relief of pain or the local effects on the buccal mucosa could be used as simple tests of the activity of tablets. It is recommended that all physicians should take more time to explain to their patients how to use glyceryl trinitrate correctly.

Aged↗

Prejunctional receptors in human digital arteries.

A human digital artery preparation obtained postmortem has been used to study factors influencing 3H-norepinephrine release evoked by periarterial nerve stimulation. Tetrodotoxin nearly abolished the stimulation-induced tritium outflow and the associated vasoconstrictor response. Increasing the frequency of stimulation from 1 to 6 Hz (constant number of 480 pulses) markedly enhanced the stimulation-induced tritium outflow per pulse. Cocaine only modestly increased the outflow. Phentolamine considerably increased, and clonidine significantly decreased, the stimulation-induced tritium outflow, thus indicating the presence of presynaptic alpha-adrenoceptors. Angiotensin also considerably enhanced the stimulation-induced tritium outflow. The results suggest that both frequency of stimulation and presynaptic receptors are of major importance in determining neurotransmitter release in the peripheral vasculature in man.

Angiotensin II↗

Observations on the psychological impact of diethylstilbestrol exposure and suggestions on management.

The emotional impact of diethylstilbestrol (DES) exposure is described in a series of 50 mothers and daughters interviewed by psychiatrists. Patterns of response to this trauma and methods of resolution are discussed, and opportunities for preventive intervention by gynecologists are suggested. Specific, open dialogue about DES with the patient as a colleage can minimize the emotional sequelae of the experience.

Affective Symptoms↗

Ciramadol. A new analgesic.

Ciramadol (WY 15705), a new analgesic and narcotic antagonist was studied on oral-dose form in 16 patients (15 of whom were suffering from malignant disease) to evaluate the analgesic dose and toxicity. Patients with mild or moderate pain experienced effective relief with doses of from 20 mg to 60 mg (mean dose, 47 mg). In patients with moderate to severe pain, effective pain control was not achieved (mean dose, 82 mg). There was no consistent effect on blood pressure level, heart rate, or respiratory rate. Mild or moderate sedation occurred in eight patients. Nausea and vomiting occurred in two patients.

Adult↗

Inter- and intrasubject variation in diazepam free fraction.

The extent of intersubject variation in diazepam free fraction was measured in fasting plasma of 74 unrelated subjects. Free fraction differences between subjects were significant and ranged from 0.97% to 1.99%. Diazepam free fraction in 29 males was normally distributed about a mean of 1.25% (range, 1.05% to 1.47%), but the distribution in females was skewed to higher free fractions and 40% had values above the highest in males. Albumin concentration (r = -0.27, p less than 0.002) and age (r = 0.44, p less than 0.001) only accounted for a small part of the variation. Within-pair variances were not greater in 11 dizygotic than in 18 monozygotic twin pairs, indicating a greater contribution of environmental than of genetic factors to diazepam binding. The prehemodialysis free fractions of diazepam in 9 uremic patients ranged from 3.44% to 6.69%, and decreased (p less than 0.005) in 7 after 6 hr of hemodialysis. In 10 subjects determination of intrasubject variation in diazepam free fraction between 14-hr fasting and 2-hr postprandial plasma samples indicated that because subjects differ in their pattern of change in free fraction (p less than 0.001), the overall decrease in mean free fraction did not achieve statistical significance (p = 0.10). The mean relative percent change in free fraction within subjects after feeding was 15.2%.

Adult↗