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Biomedical subjects

G Dixon

Publications and source records attributed to G Dixon.

At least 19 recordsLinked to original sources

Amyloid tumour of the urethra presenting as non-specific urethritis.

Amyloid tumour involving the urethra is a well recognised but rare occurrence. Chronic inflammation secondary to gonococcal urethritis is thought to be a possible predisposing factor. We report the case of a young man who presented with non-gonococcal urethritis and haematuria and was subsequently found to have primary amyloid of the urethra.

Adult

Ganglion cell survival in embryonic rabbit retina transplanted to the midbrain of neonatal rats.

Fetal rabbit retinae can grow and differentiate when transplanted to the collicular region of neonatal rats. In addition, the observed survival of retinal ganglion cells within grafts is associated with the extension of axons into the superior colliculus of the host brain, suggesting that the factors influencing the guidance of axons and the survival of ganglion cells may be homologous across different mammalian orders.

Animals

Activation of mouse peritoneal macrophages by maintenance in serum-free medium.

Normal mouse peritoneal macrophages maintained in a serum-free medium for 48-72 h and then stimulated with phorbol myristate acetate, zymosan or bacteria, released large amounts of hydrogen peroxide. Opsonized zymosan and bacteria stimulated greater release than their unopsonized counterparts. Enhanced peroxide production was not a consequence of increased uptake of particles. Addition of serum to the serum-free medium abolished activation. The addition of interferon-gamma to the serum-free medium enhanced the effect of the serum-free treatment of macrophages from C3H/HeJ mice but abolished the effect of serum free treatment of macrophages from CFLP mice. The results are discussed in terms of negative regulation of receptor-oxidase linkage by serum.

Animals

Grafting of fetal pancreata into neonatal rat brain.

Undigested fetal pancreatic tissue has been previously shown to have immunogenic properties, even after transplantation into the adult rat brain, a relatively immunoprivileged site. In the present study, iso-, allo-, and xenografts of fetal pancreas were placed into neonatal rat brain parenchyma and ventricles in order to determine the extent and quality of its survival in this environment. Adult recipients of the same tissue types were used as controls. Selective survival of insulin-staining beta cells was observed in neonates (n = 33) over the 6-week period of the experiment. Ducts and acini were gradually destroyed in allo- and xenografts, disappearing completely by the 42nd day, while there were no such changes in the isografts. The absence of an acute inflammatory reaction was noted, but there were varying degrees of lymphocytic infiltration, though small (20 +/- 4 lymphocytes per average graft area of 0.16 mm2) in all but one graft. This infiltrate was greatest in allografts, with a significant increase observed after 14 days, corresponding to the time when the ducts started to disappear. Other structures present included fibroblasts and blood vessels. The latter increased significantly with time after transplantation. Unlike isografts placed in the parenchyma of adult rats, allo- and xenografts were rejected from the earliest time observed, 7 days postoperatively. In summary, these data show that beta cells in rat fetal pancreas will survive when grafted across major allogeneic and xenogeneic barriers for up to 6 weeks, without utilization of any form of immunosuppression, provided the recipients are neonates.

Age Factors

Human tolerance to 100% oxygen at 9.5 psia during five daily simulated 8-hour EVA exposures.

Extravehicular activity (EVA) currently involves decompression to 4.3 psia. This degree of decompression carries a significant potential for decompression sickness (DCS) which could be alleviated if a pressure of 9.5 psia could be maintained in the pressure suit. Previous studies have not evaluated the potential for oxygen toxicity at 9.5 psia. Twenty-one subjects were exposed to 100% oxygen at 9.5 psia for 5 consecutive days, 8 h.d-1 while performing moderate exercise to simulate a typical work-week in the proposed pressure suit environment. No DCS or venous gas bubbles were detected. Pulmonary function tests, physical exams, blood analyses, arterial oxygen saturation monitoring, and X-rays showed no evidence of oxygen toxicity under these conditions. These results suggest that a 100% oxygen, 9.5 psia pressure suit environment could avoid both DCS and oxygen toxicity during EVAs of comparable duration and physical activity.

Adult

Increased expression of adhesive proteins on leukocytes by TNF alpha.

To further elucidate the role of tumor necrosis factor alpha (TNF alpha) in cell adhesion, we investigated the effect of TNF alpha on the expression of surface adhesive protein. After treatment with TNF alpha for 1 h, the increased expression of surface adhesive proteins (beta subunit) was observed on granulocytes but not on monocytes or lymphocytes. The expression of Mac-1 (3,4-fold increase) was consistently enhanced more than p 150,95 (1.4-fold increase) and LFA-1 expression was unchanged. Dose-response and time course studies indicated a parallel relationship between TNF alpha-increased expression of surface adhesive proteins and TNF alpha-induced granulocyte adhesion. The anti-inflammatory drug Dexamethasone suppressed both TNF alpha-induced granulocyte adhesion and TNF alpha-induced expression of surface adhesive proteins. The inhibition of granulocyte adhesion correlated with the reduction of surface adhesive protein expression. The data suggest that one contributing factor in the mechanism by which Dexamethasone inhibited TNF alpha-induced granulocyte adhesion may be diminished expression of surface adhesive proteins.

Antigens, Surface

Effects of exposure to factor concentrates containing donations from identified AIDS patients. A matched cohort study.

We compared recipients of eight lots of factors VIII and IX voluntarily withdrawn from distribution because one donor was known to have subsequently developed the acquired immunodeficiency syndrome with a nonexposed cohort matched by age, sex, and factor use. The factor VIII recipient cohorts did not differ in prevalence of antibody to human immunodeficiency virus (HIV) (exposed, 75%; nonexposed, 86%), T-cell subset numbers (median: exposed, 619 T-helper cells per cubic millimeter; nonexposed, 659 T-helper cells per cubic millimeter), T-helper to T-suppressor ratios, or immunoglobulin levels. Exposed individuals had higher levels of immune complexes by C1q binding and staphylococcal binding assays and lower responses to phytohemagglutinin and concanavalin A. However, only the staphylococcal binding assay values were outside the normal range for our laboratory. Factor IX recipient cohorts did not differ in HIV antibody prevalence (exposed, 30%; nonexposed, 40%) or any immune tests. Although exposed and nonexposed individuals did not differ from each other in a clinically meaningful fashion at initial testing, both the exposed and nonexposed cohorts had high rates of HIV seroprevalence. Market withdrawals were clearly insufficient means of limiting the spread of HIV in hemophilic patients; however, the currently available methods of donor screening and viral inactivation of blood products will prevent continued exposure within this population.

Acquired Immunodeficiency Syndrome

HTLV-III/LAV antibody and immune status of household contacts and sexual partners of persons with hemophilia.

We evaluated the human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) antibody and immune status of 88 persons living with and/or sexual partners of 43 hemophiliacs, 12 of whom had AIDS, five of whom had AIDS-related complex (ARC), 17 of whom were clinically well but HTLV-III/LAV antibody positive, and nine of whom were well and HTLV-III/LAV antibody negative. No nonhemophilic household contacts (0/50) of healthy hemophiliacs were HTLV-III/LAV antibody positive; two of 33 nonhemophilic AIDS/ARC contacts were positive. One was a spouse and one a sexual partner of a hemophiliac. One of these antibody-positive contacts herself had AIDS, and one had ARC. Antibody-negative, nonhemophilic contacts of AIDS/ARC and of antibody-positive hemophiliacs had significantly lower numbers of lymphocytes, T helper lymphocytes, and T suppressor lymphocytes than did contacts of antibody-negative hemophiliacs. We conclude that risk of HTLV-III/LAV transmission may exist for spouses and/or sexual contacts of hemophiliacs with AIDS/ARC, but we cannot now determine the risk for contacts of asymptomatic hemophiliacs.

Acquired Immunodeficiency Syndrome

Human T-lymphotropic retrovirus type III/lymphadenopathy-associated virus antibody. Association with hemophiliacs' immune status and blood component usage.

We studied the human T-lymphotropic retrovirus type III/lymphadenopathy-associated virus (HTLV-III/LAV) antibody status of 234 factor VIII concentrate recipients, 36 factor IX concentrate recipients, 69 long-term recipients of frozen packed red blood cells, and 47 persons not receiving routine transfusion therapy. Factor VIII concentrate recipients had a significantly higher rate of seropositivity (74%) than any other group. Factor IX concentrate recipients had a significantly higher rate (39%) than recipients of frozen packed red blood cells (4%) or nontransfused persons (4%). In factor VIII concentrate recipients, HTLV-III/LAV seropositivity was significantly associated with more severe hemophilia, greater factor dosage, elevated immunoglobulin and immune complex levels, lower T-helper lymphocyte numbers, and lower ratios of T-helper to T-suppressor lymphocytes. For factor IX concentrate recipients, seropositivity was associated with more severe hemophilia. Antibody-positive factor IX concentrate recipients had a lower rate of seropositivity to HTLV-III/LAV p41 membrane antigen than did antibody-positive factor VIII concentrate recipients, but factor VIII and factor IX concentrate recipients had similar rates of seropositivity to core antigens. We conclude that both factor VIII and factor IX concentrates may transmit HTLV-III/LAV. For factor VIII recipients, HTLV-III/LAV seropositivity is associated with altered immune test results.

Adolescent

Immune status of blood product recipients.

Persons with hemophilia are at risk of the acquired immunodeficiency syndrome (AIDS), and clinically asymptomatic hemophiliacs have shown a high incidence of AIDS-like immune abnormalities, facts leading to speculation that many hemophiliacs have been exposed to the AIDS agent through their blood products. We therefore evaluated the immune status of three groups of blood product recipients without AIDS in New York City, including 47 persons with hemophilia A receiving factor VIII concentrate, 50 persons with homozygous beta-thalassemia, and 27 persons with sickle cell anemia receiving frozen-packed RBCs and 20 healthy persons who had not received a transfusion. Hemophiliac participants had significantly lower lymphocyte counts (median, 1,826/cu mm) than did the thalassemic (6,110/cu mm) or anemic (4,443/cu mm) participants, had lower numbers of T-helper lymphocytes (median, 533 cells/cu mm v 1,733 cells/cu mm and 1,554 cells/cu mm), and had a lower T-helper/suppressor ratio (median, 0.8 v 1.8 and 2.1). These differences remained after adjustment for age and sex. Thus, AIDS-like immune abnormalities were found in patients receiving factor concentrate, but not in those receiving RBCs. These defects could be due to both an immunosuppressive effect of the lyophilized factor itself and to contact with the AIDS agent.

Acquired Immunodeficiency Syndrome

Inspiratory muscle conditioning using a threshold loading device.

We demonstrate the effectiveness of a new conditioning technique for increasing the strength and endurance of the inspiratory muscles. The technique employs a threshold loading device which allows for maximization of exercise intensity with a minimum of exercise duration. After ten weeks, with approximately 25 minutes of exercise time per week, four test subjects showed an average increase in maximum inspiratory pressure (PImax) of 50 (+/- 9 SD) cm H2O (p less than 0.02), whereas four control subjects undergoing submaximal inspiratory muscle exercise showed no significant change. The time the test subjects could endure 65 percent of their prestudy PImax increased from an average of 3.58 +/- 1.65 SD min to over 10 min in all four subjects. No significant change was seen in control subjects. Further testing showed the test subjects could endure 100 percent of their prestudy PImax after conditioning for an average duration 5.15 +/- 1.65 min. This technique should be useful for conditioning the inspiratory muscles in subjects with pulmonary disease.

Adolescent

Hypothalamic function in amenorrheic runners.

We have examined temperature regulation in eight amenorrheic runners and gonadotropin response to an opioid antagonist in seven amenorrheic runners, 18 to 29 years of age, running 20 to 70 miles a week. Following equilibration, oral temperature was measured continuously, first in a cold room at 39 degrees F and then in a sauna at 172 degrees F in eight amenorrheic runners, in eight eumenorrheic runners, and in eight control subjects in the early follicular phase of the menstrual cycle. Studies were terminated if a subject's temperature fell below 94 degrees F or rose above 102 degrees F, and all studies were conducted in the afternoon. The rates of temperature change, calculated from total net temperature change divided by elapsed time in the test chamber, were not significantly different among the three groups of women. Seven other amenorrheic runners failed to have any significant changes in luteinizing hormone or follicle-stimulating hormone levels in response to the opioid receptor antagonist naloxone administered as an intravenous infusion at 1.6 mg/hour for 4 hours. If opioids inhibit gonadotropin secretion in exercise-associated amenorrhea, an increase in gonadotropins in response to naloxone would have been anticipated. Although it is possible that the dose of naloxone selected was inappropriate and that temperature responses under other conditions might differ from those of normal women, these data suggest that endogenous opiates do not play a direct role in the amenorrhea associated with exercise and that temperature regulatory centers in the hypothalamus are intact in this disorder, compared with other causes of amenorrhea such as anorexia nervosa. Further studies of hypothalamic function are warranted to test these possibilities.

Adolescent