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Biomedical subjects

W H Brooks

Publications and source records attributed to W H Brooks.

At least 19 recordsLinked to original sources

Suppression of high affinity IL-2 receptors on mitogen activated lymphocytes by glioma-derived suppressor factor.

Previously we have reported that human glial tumor cells secrete a factor(s) which suppresses the mitogen responsiveness of normal human peripheral blood lymphocytes (PBL) in a dose dependent manner. In this study we extend these observations and explore the possible mechanisms by which glioma-derived suppressor factor(s) (GSF) modulates lymphocyte reactivity. Preincubation of lymphocytes with GSF for 2 hrs induces suppression of lymphocyte mitogen responsiveness. GSF also inhibits production of interleukin-2 (IL-2) by mitogen activated human T-cells. Addition of delectinated or recombinant IL-2 to mitogen activated human T-cells in the presence of GSF does not restore the normal proliferative response of these cells. These findings suggest that GSF induces a defect in the expression of the receptor for IL-2 (IL-2R) on activated T-cells. Binding studies with radiolabeled IL-2 demonstrated that GSF suppresses and in some cases completely inhibits the expression of functional high affinity IL-2R on activated T-cells, thereby, preventing association of IL-2R with its receptor and the subsequent progression of the cell into the proliferative stage of the cell cycle. These cellular defects induced by GSF closely parallel the observed defects noted in T-cells obtained from patients with gliomas, indicating that the factors elicited from glial tumors may be responsible for the immunological deficits observed in patients with primary malignant intracranial tumors.

Animals

Inability of mitogen-activated lymphocytes obtained from patients with malignant primary intracranial tumors to express high affinity interleukin 2 receptors.

Patients with primary malignant brain tumors manifest a variety of abnormalities in cell-mediated and humoral immunity. Diminished T cell reactivity has been shown in these patients to be linked to deficiencies in interleukin 2 (IL-2) production that cannot be overcome by exogenous IL-2. In this study, specific binding of radiolabeled IL-2 to PHA-stimulated lymphocytes from brain tumor patients demonstrates that the number of high affinity interleukin 2 receptors (IL-2R) is greatly reduced. FACS analysis indicates that the relative density of the p55 protein (Tac protein) is lower on the mitogen-activated lymphocytes obtained from patients than on comparably treated lymphocytes from normal individuals. These data indicate that mitogen-stimulated lymphocytes obtained from patients have fewer functional high affinity IL-2R principally because of the failure to express sufficient levels of the p55 protein for association with the p75 protein. Northern analysis of total RNA isolated from mitogen-stimulated T cells from patients demonstrates normal levels of steady state mRNA, which codes for the p55 protein. Moreover, there is no defect in the postranslational processing of the primary translation product of this mRNA suggesting that normal levels of the p55 protein are produced in activated T cells from patients.

Brain Neoplasms

Common injuries in horseback riding. A review.

The most common location of horse-related injuries is the upper extremity (24% to 61%) with injuries to the lower extremity second in frequency (36% to 40%). The head and face sustain 20% of horse-related injuries. The most common type of injury is a soft tissue injury (92% to 1%), followed by a fracture (57% to 3%). Concussion is the third most common type of injury (63% to 2%). The most frequent cause of hospitalisation is concussion (38% to 4%) with fracture second. The most common injury which leaves residual impairment is injury to the central nervous system. The age at which most injury occurred is less than 21 years. In the latest NEISS report (1987-1988), injuries have decreased in the younger riders, but have increased in the older riders (above 24 years). More women are injured than men, but over the age of 44 years more men are injured than women, with the difference more marked in the 1987-1988 NEISS report. Previous horse-related injuries are reported frequently (37% to 25%). In mortality studies from Australia and the United States, head injuries caused the majority of deaths (78% and 60%), followed by chest injuries (9%). In the Australian study each sex had 50% of the deaths. In the United States, 60% were male, 40% female. Above the age of 24 years male deaths increasingly predominate, being 15 male deaths to 1 female above the age of 64. Concussion is divided into 3 divisions of severity which require different medical evaluation and treatment: mild in which rider is stunned or disoriented for a brief period; moderate in which there is loss of consciousness for less than 5 minutes; and severe in which there is a loss of consciousness for more than 5 minutes. Investigative need is cited in the areas of previous horse-related injury, lessons, experience vs knowledge, epilepsy, drowning, gender, deaths, safety helmets, stirrups, and body protectors. No horse is a safe horse; some are safer than others but the horse is a potentially lethal animal. Prevention of accidents and injuries is dependent upon using knowledge previously obtained from studying horse activities. Much more information is available than in the past through the medical studies that have been done and the recommendations made by these investigators. The medical community has a responsibility to educate the horse riding public and to participate in investigations requested by the horse organizations.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Neurotransmitter-lymphocyte interactions: dual receptor modulation of lymphocyte proliferation and cAMP production.

Stimulation of the beta-adrenergic receptor on lymphocytes can decrease the proliferative response of these cells to mitogens. We have found that simultaneous stimulation of T cells with the beta-adrenergic agonist isoproterenol and mitogens (phytohemagglutinin (PHA) and OKT3 monoclonal antibody) results in a 2- to 4-fold increase in cAMP production compared to cells exposed to isoproterenol alone. Mitogens alone have little effect on cAMP synthesis, but do activate the phosphatidylinositol (PI) cycle, suggesting that interactions may be occurring between the second messenger systems resulting in a cAMP synergy. Further experiments suggest that calcium may be involved in inducing the cAMP synergy observed in T cells. It is proposed that the synergy between beta-adrenergic and mitogenic stimulation of T cells for cAMP may be involved in the mechanism of catecholamine modulation of lymphocyte function.

Cyclic AMP

Specific uptake of serotonin by murine macrophages.

In view of the reported immunomodulatory properties of the monoaminergic neurotransmitter, serotonin (5HT), this study aimed to assess whether 5HT specifically associates with immunocompetent cells. Although murine splenocytes appear to lack high-affinity membrane binding sites for 5HT, they do possess a specific, active, 5HT uptake system similar in affinity (Km = 40 nM) to that described in platelets. This uptake system appears to be confined to macrophages. Further, macrophages rapidly metabolize 5HT to its 5-hydroxyindole acetic acid metabolite. Specific uptake of serotonin by macrophages may thus constitute an important mechanism whereby this amine is able to regulate immune function.

Animals

Posttraumatic epilepsy prophylaxis.

Despite a large body of experimental evidence suggesting that posttraumatic epilepsy can be prevented, there is no generally accepted pharmacological regimen for posttraumatic seizure prophylaxis. This article describes a phenytoin anticonvulsant regimen specifically tailored for the patient with acute head injury and designed to provide immediate and sustained plasma concentrations of phenytoin between 10 and 20 microgram/ml. Initially, an intravenous phenytoin dose of 11 mg/kg body weight is immediately followed by an intramuscular dose of 13 mg/kg body weight. This is followed by daily intramuscular maintenance doses, usually 8.8 mg/kg body weight, until oral medication can be tolerated. Maintenance dosage adjustments, when necessary, are based on serial plasma concentrations of the drug. Eighty-four patients with severe head injuries with substantial risk of posttraumatic epilepsy were administered this regimen. Only 6% of these patients had seizures during the first year after injury (first week excluded), and this is considerably less than the rates reported elsewhere in the literature. Only one-third of these patients are known to have continued to take phenytoin after the first month, and only half of these had plasma phenytoin concentrations above the desired minimal level. The greatly reduced incidence of posttraumatic seizures in these patients, despite the low rate of long-term drug compliance, suggests that a prophylactic effect, rather than a suppressive effect, is produced.

Adolescent

A follow-up study of the geographic distribution of selected malignancies among Kentucky residents, 1969-1976.

A study of 533 brain tumors, 339 lung tumors, and 299 breast tumors was made in a contiguous six-county area of Kentucky to determine if a previous clustering of brain tumors with a rate 3.37 times the state rate still existed. No significant difference in incidence by age, sex, or race could be found between this six-county area and the entire state. It was therefore concluded that either the original study constituted a statistical artifact, or that the factors responsible for the initial observed increase are no longer operative.

Age Factors

Traumatic bitemporal hemianopsia: case report.

Bitemporal hemianopsia due to trauma to the optic chiasm is uncommon following head injury. In the patient described, a hemianopic field defect was seen 12 days after frontal basilar skull fracture. We feel the cause is intrachiasmatic contusion, edema, and hemorrhage. Serial ophthalmologic examinations and possibly use of steroids are recommended.

Adult

Treatment for patients with cerebral metastases.

To establish the effectiveness of treatment of patients with intracranial metastatic neoplasms, a retrospective study of survival of patients who had surgical excision, irradiation, or chemotherapy was compared with survival of patients who received no treatment. Our results indicate that although any form of therapy was superior to no treatment, no modality was clearly better than another. Furthermore, the prognosis for survival of patients with solitary lesions from a known primary was only slightly better than that of patients with numerous metastases. The prognosis was slightly improved when the cerebral lesion was detected before finding the primary site of origin. These observations should be considered when planning treatment for patients with brain metastases.

Adolescent

Relationship of lymphocyte invasion and survival of brain tumor patients.

The length of survival of 149 patients harboring primary brain tumors was retrospectively correlated with the presence and location of lymphocytic infiltration. Mononuclear invasion of malignant gliomas confined to the perivascular spaces was the only histolgical finding that correlated significantly with survival. Patients with malignant gliomas containing perivascular infiltration live up to four months longer than those with no lymphocyte infiltration. The survival of patients with brain tumors who had lymphocyte invasion associated with areas of hemorrhage and necrosis beyond and separate from perivascular spaces was the same as far as for those with no lymphocyte involvement.

Astrocytoma

Studies of experimental cervical spinal cord transection. Part I: Hemodynamic changes after acute cervical spinal cord transection.

Two distinct and sequential patterns of hemodynamic alteration were observed after acute cervical spinal cord transection in anesthetized dogs. Interruption of the cord initially caused a 45% increase in mean arterial pressure (p less than 0.01), a 34% increase in systemic vascular resistance (p less than 0.05), and a 92% increase in left ventricular dp/dt (p less than 0.01), reflecting a generalized sympathetic response to trauma. Concomitant bradycardia and escape arrhythmias suggested relative parasympathetic hyperactivity. Resolution of the brief pressor response was followed by a second, more prolonged, period characterized by a fall in arterial pressure to 71% of control levels (p less than 0.05), a 16% decrease in systemic vascular resistance, and a 58.5% decrease in left ventricular dp/dt (p less than 0.01). These latter hemodynamic changes are consistent with sympathetic denervation and failure of regulatory mechanisms mediated by both alpha- and beta-adrenergic peripheral vascular and myocardial receptors.

Animals

General immunocompetence of rats bearing avian sarcoma virus-induced intracranial tumors.

The mitogenic responsiveness of spleen cells obtained from avian sarcoma virus-inoculated Fischer 344 rats was studied. Sixty % of the rats had astrocytomas, 13% had sarcomas, 7% had mixed gliosarcomas, and 20% had no evidence of tumors. Only spleen cells from rats bearing astrocytomas had significantly diminished responses to phytohemagglutinin and concanavalin A (Con A) when compared to control responses. The decreased responsiveness observed with phytohemagglutinin was limited to the optimal concentration range (10 and 20 microgram) while a broader concentration of Con A (0.01 to 50 microgram) induced significant suppression. Moreover, a more profound immunosuppression was observed with Con A. The results also demonstrated that spleen cells from rats with the largest astrocytomas exhibited the greatest suppression. From the results of this study, it appears the avian sarcoma virus-induced astrocytoma in rats is an immunological parallel of the human disease based on the loss of general immunological competence as assessed by responsiveness of lymphocytes to phytohemagglutinin and Con A.

Alpharetrovirus

Effects of preincubating human peripheral blood lymphocytes on their ability to bind sheep red blood cells.

The effect of preincubating human peripheral lymphocytes at 37 degrees C or 4 degrees C various lengths of time on their subsequent ability to form rosettes with sheep red blood cells (SRBC) was investigated. Lymphocytes suspended in either medium or medium containing fetal calf serum (FCS) and preincubated at 37 degrees C for 30 min exhibited marked decrease in rosette formation with a return to normal values by 120 min. However, neither lymphocytes suspended in medium and preincubated at 4 degrees C nor lymphocyte suspended in medium containing normal human serum (HS) and preincubated at 37 degrees C exhibited this phenomenon.

Adult

Gonadal dysgenesis with Graves's disease.

Hashimoto's thyroiditis has previously been associated with gonadal dysgenesis. Recent evidence suggests that Graves's disease and Hashimoto's thyroiditis are disorders of cell-mediated immunity and may have a common genetic predisposition. However, patients with both Graves's disease and the Turner syndrome have been reported only rarely. Three such cases are presented and the relation among gonadal dysgenesis, Hashimoto's thyroiditis, and Graves's disease is discussed.

Adolescent