Platelet mitochondrial dysfunction is evident in type 2 diabetes in association with modifications of mitochondrial anti-oxidant stress proteins.

OBJECTIVE: Mitochondrial dysfunction and oxidative stress in insulin responsive tissues is implicated in the pathogenesis of type 2 diabetes. Whether these perturbations extend to other tissues and contribute to their pathophysiology is less well established. The objective of this study was to investigate platelet mitochondria to evaluate whether type 2 diabetes associated mitochondrial dysfunction is evident in circulating cells. METHOD: A pilot study of mitochondrial respiratory function and proteomic changes comparing platelets extracted from insulin sensitive (n=8) and type 2 diabetic subjects (n=7). RESULTS: In-situ platelet mitochondria show diminished oxygen consumption and lower oxygen-dependent ATP synthesis in diabetic vs. control subjects. Mass spectrometric identification and confirmatory immunoblot analysis identifies induction of the mitochondrial anti-oxidant enzymes superoxide dismutase 2 and thioredoxin-dependent peroxide reductase 3 in platelets of diabetic subjects. As oxidative stress upregulates anti-oxidant enzymes we assessed mitochondrial protein carbonylation as an index of oxidative-stress. Platelets of diabetic subjects exhibit significantly increased protein carbonylation compared to controls. CONCLUSIONS: As platelets are anuclear fragments of megakaryocytes, our data suggest that the bone marrow compartment in type 2 diabetic subjects is exposed to increased mitochondrial oxidative stress with upregulation of nuclear-encoded antioxidant mitochondrial enzymes. This 'stress-signature' in platelets of diabetic subjects is associated with a diminution of their mitochondrial contribution to energy production and support that mitochondrial perturbations in type 2 diabetes extends beyond the classical insulin responsive tissues. Platelets, as "accessible human tissue", may be useful to measure the mitochondrial modulatory effects of emerging anti-diabetic therapeutics.

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.

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.

Lymphocyte response to silica among offspring of silicone breast implant recipients.

The current study evaluated immune response to silicon dioxide in children born to women with silicone breast implants. In part one of the study, the T lymphocytes of 21 of 24 such children were significantly stimulated by silicon dioxide (silica). Part two consisted of eleven children, four born preimplantation and seven born postimplantation. None of the preimplant offspring showed T cell responses to silica; five of the seven postimplant children were positive for T cell memory for silica. Part three was a blinded study based on statistically significant differences in T cell stimulation with silicon dioxide between postimplant children and controls. These findings indicate a common immune reaction, that of T cell memory, occurs in mothers and their children born after exposure to silicone mammary implants placed prior to pregnancy. Since not all such children were breast fed the result favors transplacental passage of immunogens such as silicone oligomers or through maternofetal cellular traffic.

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.