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Biomedical subjects

J S Goodwin

Publications and source records attributed to J S Goodwin.

At least 19 recordsLinked to original sources

Cyclic adenosine monophosphate response to prostaglandin E2 on subpopulations of human lymphocytes.

Receptors for prostaglandin E2 or histamine were measured on subpopulations of human lymphocytes, using the cyclic AMP increase after exposure to prostaglandin or histamine as an indicator for the presence of receptors. The cyclic AMP response to prostaglandin E2 was similar in unfractionated lymphocytes and the T-enriched and T-depleted fractions. Within the T-enriched population, T cells bearing a receptor for the Fc portion of IgG (T gamma-cells) had a 27.4-fold rise in cyclic AMP after exposure to prostaglandin E2, whereas the remaining T cells (non-T gamma cells) had a fourfold increase. It would appear that prostaglandin receptors are concentrated on a small subfraction of T gamma cells, comprising approximately 15% of the T-cell population. The cyclic AMP response to histamine was less than twofold in all lymphocyte fractions.

Binding Sites

Psychiatric symptoms in disliked medical patients.

Twenty-two patients seen in a clinic for systemic lupus erythematosus were tested for organicity, depression, anxiety, and hostility. Four of the clinic's physicians ranked these patients from most liked to least liked. In three of the four physicians, dislike was significantly correlated with the patient's degree of organicity. Ten of the patients were ranked among the three most disliked patients by one or more of the ranking physicians. This group of most disliked patients contained all patients with signs of organic brain damage and all suicidal patients. Dislike of a patient by the physician may be a clue to serious psychiatric impairment.

Adolescent

Rhizopus osteomyelitis. A case report and review.

Mucormycosis osteomyelitis has previously been described exclusively in association with contiguous infections of rhinocerebral mucormycosis. In a patient with corticosteroid-dependent neutropenia and anemia osteomyelitis of the femur developed caused by the Mucoraceae Rhizopus. Although a primary focus was not identified, we believe this infection was hematogenous in origin. Mitogen stimulation to phytohemagglutinin (PHA) of the patient's lymphocytes revealed depressed cellullar immunity; however, there was specific response to Rhizopus extract. Treatment with systemic amphotericin B prevented further progression of the infection. A review of mucormycosis osteomyelitis is presented.

Adolescent

Increased sensitivity to prostaglandin E2 in old people.

Prostaglandin E2 acts as a feedback inhibitor on the actions of many hormones and other stimuli. For example, mitogens will cause leukocytes to produce prostaglandin E2, and the prostaglandin E2 inhibits the proliferative response of the leukocytes to the mitogen. We have shown that lymphocytes from healthy subjects over age 70 are much more sensitive to inhibition by prostaglandin E2 than are lymphocytes from younger individuals. In this paper, I hypothesize that there is a generalized increase in sensitivity in all tissues in aging humans, and that this increased sensitivity accounts for many of the physiologic changes of aging.

Aged

Sensitivity of lymphocytes to prostaglandin E2 increases in subjects over age 70.

We examined the sensitivity of lymphocytes from different age groups to inhibition by prostaglandin E2. Phytohemagglutinin-stimulated cultures of peripheral blood mononuclear cells from 12 healthy subjects over the age of 70 were much more sensitive to inhibition by exogenously added prostaglandin E2 than were cells from 17 young controls (ID50 congruent to 10 nM for the subjects over 70 vs. greater than 3 micronM for the young controls). The more senstivie lymphocytes from a subject over 70 were to prostaglandin E2, the lower was his or her response to phytohemagglutinin (r = 0.75, P less than 0.01). The mean responses to phytohemagglutinin of the peripheral blood mononuclear cells from the subjects over 70 were significantly depressed compared to the young controls. Addition of indomethacin, a prostaglandin synthetase inhibitor, to the cultures resulted in an increase in [3H]thymidine incorporation of 140 +/- 16% in the cells of the subjects over 70 vs. a 36 +/- 3% increase in the young controls (mean +/- SEM, P less than 0.001). The mean phytohemagglutinin response of the subjects over 70 was 40% of the control response without indomethacin. With addition of indomethacin the response of subjects over 70 rose to 72% of control. Thus, increased sinsitivity to prostaglandin E2 appears to be responsible in part for the depressed mitogen response of peripheral blood mononuclear cells from healthy subjects over 70.

Adult

Suppressor cell function in sarcoidosis.

We investigated the role of suppressor cells in the depressed cellular immunity of patients with sarcoidosis. The mean response in 16 patients with active sarcoidosis to three concentrations of phytohemagglutinin was significantly (P less than 0.01) less than control values. Passage of the cells over glass wool resulted in a 116% increase in response to phytohemagglutinin in patients and a 39% decrease in control subjects. Addition of indomethacin to phytohemagglutinin cultures increased the response of cells in patients with sarcoidosis by 192% +/- 32% versus a 112% +/- 18%-increase for control subjects (mean +/- SEM, P less than 0.05). Patients had an increased percentage of monocytes in peripheral blood mononuclear cell preparations, and the percent monocytes correlated with the percent increase in phytohemagglutinin response after glass wool passage (r = 0.62, P less than 0.05). Thus, several factors contribute to the depressed phytohemagglutinin response in sarcoidosis patients: an increased suppression by the prostaglandin-producing suppressor cell, an increased percentage of monocytes, and an as yet undefined factor.

Adult

Knowledge and use of placebos by house officers and nurses.

Sixty house officers and 39 registered nurses in a university teaching hospital were surveyed to ascertain their knowledge of placebo action and their patterns of placebo use. The majority of physicians and nurses greatly underestimated the percentage of patients who experience pain relief when given placebo. Placebos typically were given to disliked patients who were suspected of exaggerating their pain or had failed to respond to usual medical regimens, or both. Positive responses to placebo medication were then interpreted by the physicians as evidence that the pain had no physiologic basis. Many studies have shown that overdemanding and complaining patients are, if anything, less likely to respond to placebo than patients well liked by the hospital staff. Nevertheless the results of our survey suggest that this is precisely the type of patient "at risk" for placebo treatment.

Adult

Incontinentia pigmenti. Evidence for both neutrophil and lymphocyte dysfunction.

A child with incontinentia pigmenti (Bloch-Sultzberger syndrome) had recurrent pneumococcal meningitis and pneumococcal bacteremia with associated subdural hematomas. Immunologic evaluation revealed defective neutrophil chemotaxis with normal neutrophil chemiluminescense. In addition, lymphocytes showed a depressed proliferative response to phytohemagglutinin stimulation. An immunologic defect may prove to be part of this syndrome.

Chemotaxis, Leukocyte

Prostaglandin E inhibition of mitogen stimulation in patients with multiple sclerosis.

Kirbey et al have reported that leukocyte function from patients with multiple sclerosis is not suppressed by PGE2, as are normal leukocytes. We examined the ability of PGE2 (0.01-0.5 microgram/ml) to suppress Phytohemagglutinin induced 3H-thymidine incorporation in peripheral blood lymphocytes from multiple sclerosis patients and normals. There was no difference in sensitivity between the two groups. There was also no difference in activity of the prostaglandin producing suppressor cell between the multiple sclerosis patients and controls.

Humans

Effect of indomethacin in vivo on humoral and cellular immunity in humans.

We studied the effect of indomethacin on intradermal skin testing and antibody responses in humans. Since we and others have shown that prostaglandins are suppressor cell mediators, it was probable that in vivo inhibition of prostaglandin synthesis might enhance the humoral and/or cellular immune response. Administration of indomethacin (Indocin) in a dosage of 100 mg/day to 15 normal men and women resulted in a significantly increased antibody titer to A-Victoria (P less than 0.025) as compared with age- and sex-matched controls. There was no difference in titer to A-New Jersey. Since 90% of the subjects had antibody titers to A-Victoria before inoculation, whereas none had detectable titers to A-New Jersey, we interpret this data as suggesting that indomethacin enhances the secondary but not the primary humoral immune response. Indomethacin administration did not alter the intradermal skin test responses.

Adult

Age-dependent variations in polymorphonuclear leukocyte chemiluminescence.

Polymorphonuclear leukocytes from 46 adults (age 18 to 35), 19 adults (age 70 to 91), 10 children (age 1 to 3), and 22 neonates (cord blood samples) were tested for their chemiluminescence response to opsonized zymosan. Results indicated that both cord blood leukocytes and those from individuals over 70 were significantly lower (P less than 0.05) in their chemiluminescence response. Furthermore, when the latter group was divided into two subsets, one containing subjects over 80 years of age and the other containing subjects between 70 and 80 years of age, those over 80 showed a chemiluminescence response significantly lower (P less than 0.05) than those between 70 and 80. The kinetics of the chemiluminescence response was similar with all samples except the neonatal cells, where the response appeared to peak and subside more slowly. These data demonstrate that polymorphonuclear leukocyte chemiluminescence is depressed in the very young and the very old.

Adolescent

Prostaglandin suppression of mitogen-stimulated lymphocytes in vitro. Changes with mitogen dose and preincubation.

In this study we further characterize the properties of the prostaglandin-producing suppressor cell. Overnight preincubation of peripheral blood mononuclear cells results in an increased response of the cells to phytohemagglutinin or Concanavalin A compared to the response of fresh cells. This increase in mitogen response with preincubation was similar in magnitude to the increase in mitogen response of fresh cells after the addition of indomethacin. The two manipulations were not additive; that is, after preincubation, indomethacin caused much less enhancement of mitogen stimulation of peripheral blood mononuclear cells (100 +/- 12% increase before preincubation vs. 12 +/- 6% after preincubation; mean+/-SEM, P < 0.001). Preincubated cells also lose sensitivity to inhibition by exogenous prostaglandin E(2). It requires the addition of 100- to > 1,000-fold more exogenous PGE(2) to produce comparable inhibition of phytohemagglutinin-stimulated preincubated cells than is required for inhibition of phytohemagglutinin-stimulated fresh cells. The enhancing effect of indomethacin increases with decreasing doses of phytohemagglutinin. Indomethacin causes a 1,059+/-134% increase in [(3)H]thymidine incorporation at the lowest dose of phytohemagglutinin (0.2 mug/ml), and a 4+/-3% increase at the highest dose (20 mug/ml). This increase in response to indomethacin with a lower dose of phytohemagglutinin is due to increased sensitivity to inhibition by PGE(2) at lower mitogen doses. The prostaglandin-producing suppressor cell assay and the short-lived suppressor cell assay measure over-lapping phenomena. The increased suppressive effect of the prostaglandin-producing suppressor at suboptimal mitogen dose must be taken into account in the interpretation of any study where the response to a range of mitogen doses is studied.

Adult