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Biomedical subjects

R Fox

Publications and source records attributed to R Fox.

At least 235 records · Page 13Linked to original sources

HIV-related symptoms and psychological functioning in a cohort of homosexual men.

The authors administered the Center for Epidemiological Studies Depression (CES-D) Scale to 4,954 homosexual men in the Multicenter AIDS Cohort Study. HIV antibody status at enrollment was a less important predictor of psychological distress than were reported physical symptoms. Multivariate analysis showed an association between a high score on each CES-D Scale component and the number of self-reported possible AIDS- or HIV-related symptoms, perceived lymphadenopathy, and absence of "someone to talk to about serious problems." This relationship between self-reported physical symptoms and psychological distress suggests a possible etiologic relationship between perceived AIDS risk and psychological symptoms in men at risk of AIDS.

Acquired Immunodeficiency Syndrome↗

Detection of clonally expanded salivary gland lymphocytes in Sjögren's syndrome.

Recurrent swelling of the parotid and submandibular salivary glands occurs in some patients with Sjögren's syndrome (SS). Using Southern blot methods, we analyzed immunoglobulin and T cell antigen receptor (TCAR) gene rearrangements in DNA obtained from salivary gland lymphocytes of 9 SS patients. Based on histologic appearance of the biopsy specimens, these patients were diagnosed as having myoepithelial sialadenitis. We found oligoclonal rearrangements of the kappa gene (4 patients) and lambda gene (1 patient), and oligoclonal rearrangement of the TCAR beta chain in 2 additional SS patients. Patients with Ig gene rearrangements did not show rearrangements of their TCAR gene, nor did patients with TCAR rearrangements exhibit Ig rearrangements. The observed oligoclonal rearrangements probably derive from 5-10% of the salivary gland B cells or T cells. Three of these SS patients developed non-Hodgkin's lymphoma 2-8 years after the initial biopsy. Our results suggest that minor populations of B cells or T cells may clonally expand in the salivary gland tissues of SS patients with pseudolymphoma, and that such lymphocyte expansions may be controlled by the endogenous immune response and/or medications. However, continued lymphoproliferation in these salivary gland tissues may eventually lead to emergence of a neoplastic clone that escapes immunologic control and develops into a non-Hodgkin's lymphoma as a result of a multistep process.

Adult↗

Expression of the human T cell antigen receptor complex in advanced age.

Several studies of T cell-associated surface marker expression in older subjects "with no evidence of diseases known to affect immune function" have suggested that diminished expression of the constant portion (CD3) of the human T cell antigen-receptor complex (CD3/Ti) may be associated with aging. To determine if there is a decrease with age in expression of this complex, we determined the percent of cells positive for WT31, an antibody that recognizes a constant epitope on Ti alpha-beta heterodimers, CD3, CD4 and CD8 by immunofluorescence on peripheral blood lymphocytes from young controls (19-31 years), and 2 well characterized populations of older donors (greater than 69 years). The first group of older donors had no history of chronic or recent acute illness and saw a physician only for routine medical care. The second group was selected from patients seen in a geriatrics clinic for diagnoses that included osteoarthritis and cardiopulmonary disorders. There were no significant differences in the percent of cells positive with WT31, or with antibodies to CD4 and CD8 between young adults and the 2 groups of older donors. The clinic subjects showed a consistent decrease in percent of CD3+ lymphocytes in peripheral blood mononuclear cells compared to young adults (5-10% reduction) with less difference between the healthy older subjects and young adults. In the clinic subjects this reduction appears to be due to a decrease in CD3+, WT31-lymphocytes. These cells represent about 5-6% of the total T cell population in the young and healthy older group and are known to express CD3 in combination with Ti gamma-delta dimers. We show here that these cells are about equally distributed in high and low density lymphocytes after Percoll fractionation. We conclude that significant quantitative reduction in expression of the CD3/Ti antigen-receptor complex on human T cells is not a feature of the primary aging process and cannot account for diminished in vitro proliferative response of healthy subjects with age. However, diminished abundance of T cells expressing products of the Ti gamma-chain in less healthy older subjects may predispose to or result from diseases not usually associated with altered immune function.

Adult↗

Effect of granulocyte colony stimulating factor on neutropenia induced by cytotoxic chemotherapy.

A phase I/II study of granulocyte colony stimulating factor (G-CSF) was undertaken in patients with advanced malignancy receiving melphalan to determine the granulocyte response, side-effects, and pharmacokinetics. Patients received doses of 1-60 micrograms/kg intravenously. There were 3 patients at each dose level. Before chemotherapy the immediate effect of G-CSF was a transient depression in circulating neutrophils followed by a dose-dependent rise. Neutrophil counts up to 80 X 10(9)/l were achieved. G-CSF administration following melphalan reduced the period of neutropenia caused by melphalan. G-CSF was well tolerated and the only clinical observation that appeared related to G-CSF administration was slight bone pain during some infusions. G-CSF was rapidly cleared from the blood with a mean half-life of 110 min for the second phase. Reductions in the number of days of neutropenia following cytotoxic chemotherapy may reduce the morbidity and mortality of chemotherapy.

Aged↗

Anisotropies in global stereoscopic orientation discrimination.

Human orientation discrimination of long rectangular targets formed from dynamic random-element stereograms was assessed at four orientations (horizontal, vertical, left, and right oblique) as a function of width, disparity direction and magnitude using a temporal two-alternative, forced-choice paradigm. The results revealed the presence of an oblique effect in cyclopean orientation discrimination. In addition, observers discriminated targets with crossed disparity better than targets with uncrossed disparity, and had lower discrimination thresholds when the targets were oriented horizontally than vertically. These results demonstrate the existence of the oblique effect in the hypercyclopean domain comparable in magnitude to that present in the luminance domain.

Depth Perception↗

Epstein-Barr virus and human autoimmune diseases: possibilities and pitfalls.

Epidemiologic studies suggest that human autoimmune disease involves both genetic and environmental components. Although a great deal has been learned about genetic components (i.e. histocompatibility antigens), little is known about the environmental factors. Because of its ubiquitous nature and ability to stimulate lymphoid responses, Epstein-Barr virus (EBV) has been examined as a potential candidate, particularly in rheumatoid arthritis and systemic lupus erythematosus. No convincing evidence has been produced that it plays a primary etiologic role in these disorders. Nevertheless, EBV or a related herpesvirus may play an indirect role in perpetuating the disorder or in the development of extra-articular manifestations such as Sjögren's syndrome (an autoimmune disorder involving the salivary glands). Current data indicates increased EBV reactivation in some patients with autoimmune diseases, as evidenced by increased viral DNA in their saliva and increased number of circulating B-cells containing EBV in their blood. These patients also have modestly elevated anti-EBV antibody titers and altered antiviral T-cell responses, as measured by the ability to prevent outgrowth of autologous EBV infected B-cells. However, the relevance of these 'abnormalities' to pathogenesis remains unknown. It is hoped that new techniques such as polymerase chain reaction will provide new insights into these questions by allowing detection of viral DNA from tissue biopsies obtained early in the course of disease and by providing a method to identify viral isolates that do not grow well in vitro.

Arthritis, Rheumatoid↗

Spontaneous carotid cavernous fistula in Ehlers Danlos syndrome.

A patient is described with Ehlers Danlos syndrome presenting with spontaneous carotid cavernous fistula, in whom there was biochemical evidence for defective type III collagen synthesis. Despite the risks associated with arterial manipulation, the fistula was successfully closed by interventional neuroradiology and the patient has since remained well. This outcome is in contrast with the results in previous reports.

Adult↗

Pharmacokinetics of human granulocyte-macrophage colony-stimulating factor using a sensitive immunoassay.

A sensitive and reliable sandwich enzyme-linked immunosorbent assay (ELISA) has been developed for recombinant human granulocyte-macrophage colony-stimulating factor (hGM-CSF). The assay is quantitative between 100 pg/mL and 2.5 ng/mL for bacterially synthesized hGM-CSF in human serum and is more sensitive and specific than the semisolid agar bioassay. As part of a phase I study, the pharmacokinetics of intravenous (IV) bolus injection and subcutaneous (SC) administration of hGM-CSF were studied. Following a single IV dose, an initial high blood level of hGM-CSF occurred, followed by a rapid decrease occurring in two apparent phases with a half-life (t1/2)alpha of less than five minutes and a t1/2 beta of 150 minutes. After an SC injection, detectable serum levels occurred within 15 to 30 minutes, and serum levels were sustained for a variable time depending on the dose. At the highest SC dose (10 micrograms/kg), a serum level of greater than 1 ng/mL (65 pmol/L) was maintained for greater than 12 hours after a single injection. This corresponds to the concentration of hGM-CSF supporting near-maximum proliferation in vitro.

Adult↗

Deficits in stereoscopic depth perception by mildly mentally retarded adults.

The ability of mildly mentally retarded adults to perceive specific perceptual phenomena attendant to global stereopsis produced by random element stereograms was investigated. From the standpoint of computational vision, these phenomena are difficult to process, yet nonretarded persons perceive them effortlessly and without error. Retarded subjects in this study, however, exhibited large qualitative deficits not attributable to an absence of stereopsis or a failure to comprehend. These results suggest that the computational requirements of the stimuli exceeded resources and imply the presence of a substantial structural deficit in an automatic preattentive perceptual stage quite distant from the domain of cognition.

Adult↗

Comparison of T cell receptor gene rearrangements in patients with large granular T cell leukemia and Felty's syndrome.

Felty's syndrome (FS) refers to the occurrence of rheumatoid arthritis, splenomegaly, and neutropenia. A subset of these patients has recently been described with a chronic T cell leukemia of large granular lymphocytes (LGCL). To examine the spectrum of lymphocyte abnormalities in FS and LGCL, we examined phenotypic and genotypic properties of lymphocytes from eight FS patients. In two of these FS patients, we observed an elevated proportion of T cells with an unusual phenotype (CD3+/Leu-7+/Leu-8-/CR3+) (46 +/- 5% of mononuclear cells). The FS lymphocytes had large granular morphology on Wright-Giemsa stain and were active in antibody-dependent cellular cytotoxic activity. This phenotype, morphology, and activity was similar to LGCL patients except that the latter T cells additionally expressed the Fc-IgG receptor recognized by monoclonal antibody Leu-11 (CD 15). In the remaining six FS patients, the proportion of CD3+/Leu-7+/CR 3+ T cells was only 10 +/- 8%, which was not significantly different from age-matched normal subjects (6.6 +/- 2.2%). To determine the clonality of T lymphocytes in FS and LGCL, we examined DNA for rearrangements of the T cell antigen receptor beta-chain (Ti beta) and gamma-chain (Ti gamma) genes by using Southern blotting techniques. We found a clonal rearrangement of the Ti beta 1 and Ti gamma genes in both LGCL patients. In contrast, no clonal rearrangements of Ti beta or Ti gamma genes were detected in lymphocytes from the FS patients. These results indicate that FS patients are heterogeneous in their phenotype and that one subset exhibits polyclonal expansion of an unusual lymphocyte subset.

Antibody-Dependent Cell Cytotoxicity↗

Predictors of the acquired immunodeficiency syndrome developing in a cohort of seropositive homosexual men.

In a cohort of 1835 homosexual men who were seropositive for human immunodeficiency virus (HIV) on entry into a prospective study, the acquired immunodeficiency syndrome (AIDS) developed in 59 during a median follow-up of 15 months. We matched 5 seropositive controls to each case according to study center and date of enrollment and performed a case-control analysis to determine factors predictive of AIDS. In a multivariate analysis, a decreased number of T helper lymphocytes, an increased number of T suppressor lymphocytes, a low level of antibody to HIV, a high titer of cytomegalovirus antibody, and a history of sex with someone in whom AIDS developed were independently associated with subsequent AIDS. Separate analyses of risk factors for Kaposi's sarcoma and opportunistic infections failed to support previously reported associations between the use of nitrites or an elevated cytomegalovirus-antibody titer and Kaposi's sarcoma. These variables may be markers rather than determinants of disease progression. A vigorous antibody response to HIV infection may confer at least temporary protection against the progression of immunodeficiency to AIDS, or a low level of antibody to HIV may reflect a later stage of infection. The increased risk associated with a history of sex with someone in whom AIDS developed may indicate earlier infection in cases or infection with a more virulent strain of HIV. These results may be useful in counseling HIV-seropositive persons and in designing studies of clinical interventions.

Acquired Immunodeficiency Syndrome↗

Delayed hypersensitivity skin testing and anergy in a population of gay men.

Anergy is almost universal among patients with the acquired immunodeficiency syndrome (AIDS). To determine the prevalence and correlates of anergy in a population at risk for AIDS, we performed skin tests in 1120 gay men who were enrolled in a prospective study of the natural history of human immunodeficiency virus (HIV) infection. Anergy, defined as no induration to any of four intradermal antigens, was present in 12%. Individually, no induration was detected in response to tetanus toxoid (41%), mumps (28%), candida (47%), and trichophyton (72%). Anergy was strongly associated with the presence of antibody to HIV and with a reduced number of T helper lymphocytes, but not independently with generalized lymphadenopathy, the number of reported male sexual partners in the previous 2 years, the number of T suppressor lymphocytes, or with high titers of antibodies to cytomegalovirus. Nine percent of HIV antibody-negative subjects and 20% of antibody-positive subjects were anergic; anergy is not specific for serologically documented HIV infection in this population. Skin testing with only tetanus toxoid, candida, and mumps antigens may be sufficient to detect anergy. In the presence of HIV antibody, the ability of anergy to predict progressive immunodeficiency remains to be determined.

AIDS-Related Complex↗

The Ames window illusion: perception of illusory motion by human infants.

The sensitivity of human infants, 5 1/2-9 months of age, to the illusory oscillation of the Ames window was assessed in three experiments that employed some variant of the habituation-dishabituation and forced-choice preferential looking paradigms. In Experiment 1, three groups--5 1/2, 7 1/2, and 9 months of age--were given a visual choice between rotating rectangular and Ames windows after exposure to a rotating circular form. The two older groups preferred the Ames window. The results of Experiment 2 showed that this preference is not based on structural differences between the two windows. In Experiment 3, familiarization with an Ames window produced a preference for rotary motion while familiarization with a rectangular window produced a preference for oscillatory motion. These results suggest that sensitivity to the illusion emerges around 7 1/2 months of age, an outcome consistent with the emergence, at this time, of sensitivity to pictorial cues to depth.

Child Development↗

Detection of early antibodies in human immunodeficiency virus infection by enzyme-linked immunosorbent assay, Western blot, and radioimmunoprecipitation.

A current concept of the serological response to human immunodeficiency virus (HIV) infection in humans is that antibodies to core antigens (p55, p24, and p15) are detectable earlier during initial stages of antibody production than antibodies against envelope antigens (gp160, gp120, and gp41). Comparative studies of Western blot (immunoblot), radioimmunoprecipitation assay (RIPA), and enzyme-linked immunosorbent assay (ELISA) during initial antibody production are limited to case reports and have not resolved the issue. Thirty of the 37 participants who are part of a prospective study had at least one specimen that was negative for anti-gp41 but had one or more other bands on Western blot. Twenty-seven of these 30 specimens were reactive for anti-gp120/160 in the RIPA. Of the same 30 specimens, kits from Bionetics identified 2 (7%), ElectroNucleonics 4 (13%), Abbott 13 (43%), Du Pont 25 (83%), and Genetic Systems 25 (83%). All participants had evidence of serological progression by Western blot, including a gp41 band, on subsequent visits; the ELISA kits of all manufacturers identified these later specimens with greater accuracy. These data show that the RIPA detects anti-envelope antibodies that may be not detectable by Western blot and that the production of anti-envelope antibodies approximately parallels the production of anti-core antibodies. The false-negative results by ELISA would permit transmission of HIV by blood transfusion from donors in early stages of infection. The sensitivity of licensed ELISA kits should be improved to identify antibody as soon as possible after infection.

Acquired Immunodeficiency Syndrome↗