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Biomedical subjects

J Stanford

Publications and source records attributed to J Stanford.

At least 19 recordsLinked to original sources

Studies of vaccination of persons in close contact with leprosy patients in Argentina.

A total of 670 adults living or working with leprosy patients, were examined for a BCG vaccination scar, and skin-tested with four new tuberculins. Based on the results 513 were vaccinated, 65 with Bacille de Calmette et Guérin (BCG) alone, 66 with BCG plus killed Mycobacterium vaccae and 382 with killed M. vaccae alone. Skin-testing was repeated 2-3 years later on 344 subjects, when all three vaccines were found to have been highly successful in increasing responses to Tuberculin and Leprosin A (p < 0.0005) with increased immune recognition of common and species-specific antigens. Mean diameters of induration to each skin-test were greatest in recipients of BCG alone (p < 0.05), which suggests that better immuno-regulation occurs after receiving vaccines that incorporate M. vaccae. The results suggest 10(8) M. vaccae alone might prove a valuable future vaccine, which would not require selective pre-vaccination procedures.

Adult

Psoriasis patients have T-cells with reduced responsiveness to common mycobacterial antigens.

Heparinised blood samples were obtained from 20 patients with chronic plaque psoriasis and from 13 age-matched healthy controls. After preliminary titration, mononuclear cells separated over Ficoll-Tryoson were cultured for 5 days with 10 microg ml(-1) of 15 mycobacterial preparations, or with pokeweed mitogen and concanavalin A. Stimulation indices were determined for each reagent and means were determined for patients and controls. Results for patients showed a striking reduction of responsiveness to mycobacteria, apparently due to loss of responses to group i, common mycobacterial antigens, and no differences in responses to mitogens. These observations relate psoriasis to certain other diseases, notably mycobacterial infections, rheumatoid arthritis, Chagas' disease and human immunodeficiency virus infection. The observations may be relevant to the aetiology of psoriasis, and to potential immunotherapy for the disease.

Adult

Immunotherapy with Mycobacterium vaccae in the treatment of psoriasis.

A placebo-controlled study of immunotherapy with Mycobacterium vaccae for chronic plaque psoriasis showed improvement in the psoriasis area severity index in 19 of 21 immunotherapy recipients (P<0.005). Minor improvement, not reaching statistical significance for the group, occurred in nine of 14 placebo recipients. There were losses to follow-up and the placebo used, tetanus toxoid, was not ideal. Clinical improvement after immunotherapy persisted for 6 months and another injection of the immunotherapeutic given to a few volunteers from either group resulted in benefits lasting a year. Lymphoproliferative tests were carried out at each clinic visit, and on 50 matched controls. Starting with reduced responses to mycobacterial antigens and concanavalin A, both treatment groups showed a fall after 3 months, and diverged at 6 months with M. vaccae recipients rising to values similar to those of healthy controls, whereas placebo recipients continued to fall. Conclusions reached were that immunotherapy with M. vaccae gave long-lasting clinical benefit to most patients, with minimal side effects. This accompanied a return towards normal cellular immune responsiveness to mycobacterial antigens, which did not follow the use of the placebo.

Adult

Prospective study of histoplasmosis in patients infected with human immunodeficiency virus: incidence, risk factors, and pathophysiology.

Histoplasmosis is a common opportunistic infection in patients with human immunodeficiency virus (HIV) infection who reside in areas where Histoplasma capsulatum is endemic. We undertook a prospective study of a cohort of 304 HIV-Infected patients in Kansas City from October 1990 through March 1993 to define the incidence-specific risk factors, and pathophysiology of histoplasmosis. The annual incidence of histoplasmosis was 4.7%; 74% of the patients with histoplasmosis were symptomatic (all of whom had disseminated disease). A history of exposure to chicken coops, a positive baseline serology for complement-fixing antibodies to Histoplasma mycelium antigen, and a baseline CD4+ lymphocyte count of < 150/microL were associated with an increased risk for histoplasmosis. Histoplasmin reactivity and the presence of pulmonary calcifications were not useful markers for patients at high risk. Symptomatic infection occurred in 9.9% of patients with evidence of prior exposure to H. capsulatum, in 4.0% of patients without documented prior exposure, and in 3.0% of patients who were anergic; these findings suggest that the pathophysiology of histoplasmosis in patients with AIDS involves reactivation of latent infection in some cases and dissemination of exogenously acquired infection in other cases.

AIDS-Related Opportunistic Infections

HIV infection alters the production of both type 1 and 2 cytokines but does not induce a polarized type 1 or 2 state.

OBJECTIVE: To test the T-helper (TH)1/TH2 cytokine paradigm in HIV infection. DESIGN AND METHODS: Cytokine profiles in two separate studies of HIV patients and controls are presented: (i) a longitudinal study of HIV patients with CD4 counts > 500 x 10(6)/l tested at three timepoints compared with controls; (ii) a blinded cross-sectional study of controls and patients with high (> 500 x 10(6)/l) and low (< 500 x 10(6)/l) CD4 counts. Peripheral blood mononuclear cells (PBMC) from patients and controls were tested for the production of two type 1 [interleukin (IL)-2, interferon (IFN)-gamma] and two type 2 (IL-4, IL-10) cytokines by enzyme-linked immunosorbent assay. Both spontaneous and mitogen-induced cytokine production was measured. RESULTS: HIV infection was noted to have the following effects on cytokine production: (i) it led to the in vivo activation of type 2 cytokines in a small group of individuals with high CD4 numbers characterized by the spontaneous release of IL-4 and IL-10. Longitudinal data showed high spontaneous IL-4 and IL-10 to be a consistent feature of the patient group (at each timepoint some patients were high producers) but to be variable in a given individual; (ii) HIV infection impaired the ability of PBMC to respond to stimuli (selected for their ability to optimally induce each cytokine) in terms of IL-2, IL-4 and IL-10 production in patients with both high and low CD4 cell counts; and (iii) conversely, HIV infection led to an overproduction of IFN-gamma in patients with high CD4 counts; patients with low CD4 produced normal levels of IFN-gamma. CONCLUSIONS: Our observations did not suggest polarization of the type 1/type 2 cytokine profile in HIV patients. Instead, the data suggested more complex changes to type 1/type 2 cytokine patterns in HIV infection than originally proposed by the TH1/TH2 dichotomy.

CD4 Lymphocyte Count

Lateral hypothalamus: site involved in pain modulation.

The present study is an attempt to examine the neuronal circuitry of a supraspinal site engaged in pain modulation. Five physiological measures were postulated as the criteria for defining a central nervous system site engaged in the circuitry of pain modulation. The lateral hypothalamus met these five measures: (i) 81% of the lateral hypothalamus neurons (247/304) responded to noxious stimuli using a single cell recording procedure; (ii) stimulation of the periaqueductal gray-dorsal raphe area or the habenula modulated 98% and 87% of the lateral hypothalamus noxious-evoked activity; (iii) microiontophoretically applied morphine modulated 77% of the lateral hypothalamus noxious evoked activity; (iv) electrical stimulation of the lateral hypothalamus produced behavioral analgesia proportional to the stimulus intensity as assessed by the tail flick assay; and (v) morphine application into the lateral hypothalamus produced behavioral analgesia in a dose-response manner using the tail flick assay. In conclusion, the lateral hypothalamus can be considered one of the pain modulation sites.

Animals

The apparent distance of interior and exterior corners: a test of Gregory's misapplied size constancy explanation for the Mueller-Lyer illusion.

Key to Gregory's misapplied size constancy explanation for the Mueller-Lyer illusion is the assumption that subjects perceive the central line segment of the fins-out figure, which is analogous to an interior corner, as projecting from a more distant object than does the central line segment of the fins-in figure, which is analogous to an exterior corner. We examined the validity of this assumption by having 20 college students judge the relative distance of three-dimensional model corners, presented in a monocular viewing box. The interior corner was perceived to be nearer than the exterior corner, indicating that the key assumption in Gregory's theory is either false or unfalsifiable.

Adult

Modulation of pristane-induced arthritis by mycobacterial antigens.

Several prominent mycobacterial protein antigens involved in antibody and T cell responses have been identified as members of highly conserved heat shock protein families. In particular, immune responses to the mycobacterial 65 kD heat shock protein (hsp65) have been implicated in the pathogenesis of autoimmune diseases both in experimental animal models and in man. Additionally, hsp65 has been shown to modulate the course of autoimmune disease in such experimental animal systems. In this report, we have examined the synthesis of heat shock proteins by a fast growing mycobacterial strain, M. vaccae, in heat stressed cultures and used the pristane induced arthritis model to investigate the immunoprophylactic and immunotherapeutic potential of heat killed M. vaccae. Heat shock of M. vaccae cultures at 48 degrees C demonstrated a 43-fold increase in hsp65 over that expressed at 37 degrees C. It is therefore suggested that heat killed M. vaccae contains sufficient hsp that can be presented in the context of appropriate adjuvant properties for use as an effective immunomodulatory agent. Immunisation experiments with M. vaccae revealed that protection or exacerbation of pristane induced arthritis was dependent on the dose (given in an oil or aqueous suspension), route and time of immunisation. In addition, it was demonstrated that the development of arthritis correlated with high levels of agalactosyl IgG and that "protected" animals had significantly depressed levels.

Animals

A biophysical approach to capillary permeability.

In this preliminary report, the capillary leakage that occurs after scald injury is considered a biophysical phenomenon and is treated by sealing the "pores," or endothelial gaps, in the capillary membranes with biodegradable macromolecules of the appropriate size and shape. We have measured albumin leakage from standardized scald burns in the rat jejunum with and without variously sized fractions of intravenous macromolecules of hydroxyethyl starch (HES) used as a sealing agent. The observed reduction of albumin leakage from injured capillaries was attributed to the sealing effect. The fraction HES (Fm) with molecular weights of 100,000 to 300,000 daltons performed significantly better (p less than 0.05) as a sealing agent when compared with HES (F1) fraction molecular weights of 300,000 to 3.4 million daltons, HES (Fs) molecular weight less than 50,000 daltons, and two control groups receiving the intravenous Ringer's lactate solution or serum albumin 5%. This capillary sealing phenomenon was shown to be independent of colloid osmotic pressure effect. It is believed to be related to the size and the shape of the noncharged macromolecules.

Animals