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Biomedical subjects

D L Smalley

Publications and source records attributed to D L Smalley.

At least 19 recordsLinked to original sources

Environmental immunogens and T-cell-mediated responses in fibromyalgia: evidence for immune dysregulation and determinants of granuloma formation.

Thirty-nine patients with fibromyalgia syndrome (FMS) according to American College of Rheumatology criteria were studied for cell-mediated sensitivity to environmental chemicals. Lymphocytes were tested by standard [(3)H]thymidine incorporation in vitro for T cell memory to 11 chemical substances. Concanavalin A (Con A) was used to demonstrate T cell proliferation. Controls were 25 contemporaneous healthy adults and 252 other concurrent standard controls without any aspect of FMS. Significantly higher (P < 0.01) stimulation indexes (SI) were found in FMS for aluminum, lead, and platinum; borderline higher (0.05 > P > 0.02) SI were found for cadmium and silicon. FMS patients showed sporadic responses to the specific substances tested, with no high-frequency result (>50%) and no obvious pattern. Mitogenic responses to Con A indicated some suppression of T cell functionality in FMS. Possible links between mitogenicity and immunogenic T cell proliferation, certain electrochemical specifics of granuloma formation, maintenance of connective tissue, and the fundamental nature of FMS are considered.

Adult↗

Dynamics of wound healing after silicone device implantation.

A large surgical wound is required for implantation of silicone mammary devices. Formation of capsules around silicone devices follows wound healing processes except that the healing is conformed and significantly delayed by the physical presence of the implant. Multilayered capsules are thicker and lymphocytic and plasmalymphocytic vasculitis, markers for delayed hypersensitivity, also correlate with thicker capsules. Polyurethane-coated devices induce very thick capsules that remain so for over 20 years. By contrast, gel and saline content devices show maximum thickness at 6. 5 years. Active T(H) lymphocyte memory does not differ by implant type for individuals with devices in place and that for gel content devices peaks at 10.5 years. There was a significant decrease in T cell indexes only after the removal of saline content devices. Comparison of the rate of formation of the periprosthetic capsule with the healing time of large wounds of similar size indicates that silicone devices interfere with the healing process, requiring substantially more time. This extended period has the potential for enhancing autoimmune conversion as a consequence of persistent delayed hypersensitivity.

Breast Diseases↗

The immunopathology of siliconosis. History, clinical presentation, and relation to silicosis and the chemistry of silicon and silicone.

Recent evidence confirms the fundamental involvement of the human immune system in the reaction to implantation of silicone-based medical devices. An as yet-to-be particularized epitope of many complex substances sharing siloxane structures is presented through the MHC-II apparatus with development and retention of T cell memory. This memory can be tested for in practical terms using one or more forms of silica, which links the immuno-histopathology and autoimmune attributes of "silicosis" with those of "siliconosis." The lesions of siliconosis are typical of those for persistent antigens and delayed, cell mediated hypersensitivity. The basic descriptive pathology of the reaction to silicone has been known since soon after introduction of silicones in medical procedures, with the exception of some details related to the more recent discoveries on the role of cytokines in the immunopathic process. The clinical consequences of siliconosis are common and can be severe in some individuals implanted with silicone devices.

Autoimmune Diseases↗

The sequence and phylogenetic analysis of a novel hepatitis E virus isolated from a patient with acute hepatitis reported in the United States.

A variant of hepatitis E virus (HEV), designated HEV US-1, was identified in a hepatitis patient in the United States (US); the patient had no history of travel to areas where HEV is endemic. Nucleotide sequences were obtained from the 5' end of open reading frame (ORF) 1 (1418 nt), the 3' end of ORF1 (1359 nt), the entire ORF2 and ORF3 regions, and the 3'-untranslated region (2127 nt). The HEV US-1 strain is significantly divergent from other human HEV isolates with nucleotide identities ranging from 76.8 to 77.5%. Phylogenetic analyses indicate that HEV US-1 and a recently discovered HEV variant from swine may represent separate isolates of a new strain of HEV, significantly divergent from the Mexican and Burmese strains. Synthetic peptides derived from the carboxyl amino acids of ORF2 and ORF3 were shown to be useful for detecting exposure to HEV. In addition, IgM class antibodies directed against HEV US-1 synthetic peptides were detected in the US patient infected with HEV US-1, but were absent using synthetic peptides from the Burmese or Mexican strains of HEV. A preferential reactivity to HEV US-1 specific peptides has lead to the identification of a second isolate of this virus also from a patient with acute hepatitis from the US. The discovery of these HEV variants may be important in understanding the worldwide distribution of HEV infection.

Acute Disease↗

Monocyte-dependent stimulation of human T cells by silicon dioxide.

Mononuclear cells were isolated by Ficoll-Hypaque density gradient centrifugation from randomly selected silicone breast implant recipients for testing. Restricted antibody to HLA-DR (28-33 kD) depleted the concanavalin A mitogenic response which was expected but failed to inhibit the proliferative response to silicon dioxide. Further testing with monoclonal antibodies to HLA-DP, -DQ, and a second -DR with specificity for the NS1 region of the MHC class II genome, all markedly inhibited proliferation of T cells despite otherwise adequate stimulation by concanavalin A or silicon dioxide. Monoclonal antibodies directed against B7-1 also inhibited proliferation of T cells following stimulation with concanavalin A or silicon dioxide. These results confirm the T-cell response to silicon dioxide is monocyte-dependent and not a superantigen as has been speculated.

Antibodies, Monoclonal↗

Hepatitis E virus infection in an immigrant to the United States.

A patient who had recently traveled from India to Tennessee was found to have acute hepatitis E. Improved recognition and serologic testing have increased the diagnosis of hepatitis E in the United States. For those at risk, hepatitis E should be considered in the differential diagnosis of acute hepatitis.

Adult↗

Ten-year summary of human immunodeficiency virus serology in west Tennessee.

Since the isolation of human immunodeficiency virus (HIV), numerous laboratory tests have been developed to confirm the immunologic response to the virus. In 1991, the state of Tennessee mandated that clinical laboratories performing Western blot analyses for HIV report all new cases of confirmed HIV infection. This report is a summary of HIV confirmed cases evaluated by this facility from 1985 until July 1, 1995. During each year, the laboratory screens approximately 20,000 persons for HIV and all positive screens are confirmed by an FDA-approved Western blot. During the period described, the laboratory has confirmed HIV serologic positivity in 4,096 individuals, principally from Shelby County and surrounding Tennessee counties. Although these data are not complete, they clearly indicate that we have a continuing problem with this infectious disease. Based on the current rate of positive cases seen thus far in 1995, this facility may confirm nearly 900 new cases of HIV infection in this year alone.

Adolescent↗

Immunologic stimulation of T lymphocytes by silica after use of silicone mammary implants.

Difficulties in showing the biologic activity of silicones in vitro have contributed to the controversy over effects of silicone mammary implants in vivo. We adapted a standard lymphocyte stimulation test to detect evidence of cellular immunity in patients with silicone gel implants. Initially, lymphocytes were harvested from 70 implant patients, 76 normal controls without implants or symptoms, and 18 patients with classic rheumatic disorders and without a history of silicone implants. The harvested lymphocytes were stimulated with PWM, PHA, Con A, and pharmaceutical grade colloidal silicon dioxide (silica). Implant patients showed increased SI compared to controls and those with rheumatic disorders. The mean SI of implant patients was 195.0 +/- 19.3, 18-fold that of normal controls (< 0.0001). Patients with rheumatic disease showed the same SI as controls (P = 0.3577). A follow-up study included 220 normal controls without implants, 942 silicone gel implant patients with demonstrable rheumatic symptoms, and 34 implant patients without symptoms at the time of the study. The average SI for the 220 normal controls was 10.0 +/- 0.41. Among the symptomatic implant women, 860 (91.3%) had SI significantly above those of the normal controls. Of these, 171 (18.2%) had SI between 25 and 50, 316 (33.5%) had SI between 50 and 100, and 373 (39.6%) had SI over 100. The data presented confirms that silicone implant patients respond immunologically to the silicon dioxide contained in mammary prostheses.

Adult↗

Caregivers of Alzheimer's disease and stroke patients: immunological and psychological considerations.

Demands of caregiving for Alzheimer's Disease (AD) patients have been reported to affect the psychological and immunological health of the caregivers. The question of whether the observed psychological and immunological changes were unique to AD caregivers was addressed in this study. The subjects were 25 caregivers of AD patients, 25 caregivers of stroke patients, and 25 noncaregiving individuals. Comparisons of all subjects made on several psychologic and immunologic indices indicated that the AD caregiving group was more psychologically distressed than the stroke group, and both of these groups were more psychologically distressed than a control group. With respect to immunologic function, there were no differences among the three groups. Implications of the findings are discussed.

Aged↗

Evaluation of a new western blot strip for human immunodeficiency virus.

With the isolation of the human immunodeficiency virus (HIV), numerous assays have been developed to detect antibodies to the retrovirus. The manufacturers' recommend that all sera exhibiting a positive enzyme immunoassay be confirmed by the more specific Western blot test (WBT). Recently, a new WBT strip was released for detection of antibodies to HIV. Four hundred patients' sera and 22 CDC proficiency samples were each tested with these strips and with a WBT strip prepared within the laboratory using the CDC techniques. The strips were then evaluated for banding pattern with the reactions recorded on a scale of 0 to 4+ for each band consistent with HIV response. Criteria for positive results were based on the ASTPHLD/CDC criteria. Primary emphasis was on antibody banding to gp41 (envelope protein) and p24 (core protein). The new strips showed appropriate changes in level of antibody, especially for declining antibody to p24. When the banding pattern for antibody to gp41 was compared to the standard strips, the new strips showed a sensitivity of 99.6% and specificity of 99.4%. The presence or absence of antibody to p24 on the new strips versus the standard strips showed a sensitivity of 93.7% and specificity of 99.5%.

Antibodies, Viral↗