Split tolerance to a viral antigen expressed in thymic epithelium and keratinocytes

When expressed as a transgene from the keratin 14 (K14) promoter in an MHC class II-deficient mouse, I-Ab expressed in thymic cortical epithelium promotes positive but not negative selection of I-Ab-restricted CD4+ T cells (Laufer, T. M. et al., Nature 1996. 383:81-85). Transgenic mice expressing the E7 protein of human papilloma virus 16 from the K14 promoter were studied to determine the consequence of expression of a cytoplasmic/ nuclear protein from the K14 promoter. K14E7-transgenic mice express E7 in the thymus and skin without evidence for autoimmunity to E7. Repeated immunization of FVB(H-2q) or F1(C57BL/6JxFVB) mice with E7 elicited similar antibody responses to the defined B cell epitopes of E7 in K14E7-transgenic and non-transgenic animals. In contrast, for each genetic background, a single immunization with E7 elicited demonstrable T cell proliferative responses to the major promiscuous T helper epitope of E7 in the transgenic but not the non-transgenic animals. Further, E7-immunized non-transgenic F1 (FVBxC57BL/6J) animals developed strong E7-specific cytotoxic T lymphocyte (CTL) responses and were protected against challenge with E7+ tumors, whereas similarly immunized K14E7-transgenic animals had a markedly reduced CTL response to E7 and no E7-specific tumor protection was observed, although the antibody and CTL response to ovalbumin was normal. Expression of E7 protein as a transgene from the K14 promoter in the skin and thymus thus induces E7-specific tolerance in the cytotoxic T effector repertoire, together with expansion of the E7-specific T helper repertoire. These findings demonstrate that limited tissue distribution of an autoantigen may result in "split" tolerance to that autoantigen.     

Mesothelioma-associated antiphospholipid antibody syndrome presenting with cutaneous infarction and neuropathy

OBJECTIVE: To evaluate for the presence of oxidatively modified lipid-protein complexes in endometriosis and endometrium of women with endometriosis and controls. DESIGN: Controlled clinical study. SETTING: Academic tertiary care center. PATIENT(S): Women undergoing surgery for pelvic pain, infertility, endometriosis, or tubal ligation controls. INTERVENTION(S): Biopsy of endometrium and endometriosis. MAIN OUTCOME MEASURE(S): Staining with antibodies to oxidatively modified lipid proteins (HNE-7, MDA2), macrophages (HAM-56), and muscle cell actin (HHF-35). RESULT(S): Both endometrium and endometriosis tissues contain stromal cells that immunostain with HAM-56 and show immunostaining (both intracellular and extracellular) with HNE-7 and MDA2. Some endometriotic implants show patchy staining with HHF-35. Endometrium was devoid of staining with HHF-35. Control staining with nonimmune sera in both tissues was also devoid of staining. CONCLUSION(S): These data strongly implicate the occurrence of oxidative stress in endometriosis tissue. These data also suggest that oxidative modification is a normal physiological process in endometrium.     

Hepatocellular dysfunction after severe hypotension in the absence of blood loss is associated with the increased IL-6 and PGE2

Activation of ATP-sensitive K+ channels is involved in the coronary vascular response to decreases in perfusion pressure and ischemia. Since activation of ATP-sensitive K+ channels in collateral vessels may be important in determining flow to collateral-dependent myocardium, the ability of collaterals to respond to activation of the channel was tested. In the beating heart of dogs, we compared responses of non-collaterals less than 100 microns in diameter to collaterals of similar size using computer-controlled stroboscopic epi-illumination of the left ventricle coupled to a microscope-video system. Aprikalim, a selective activator of ATP-sensitive K+ channels (0.1-10 microM) produced similar dose-dependent dilation of non-collaterals and collaterals. Relaxation was decreased by inhibition of ATP-sensitive K+ channels with glibenclamide, but not by inhibition of nitric oxide synthase with nitro-L-arginine. Bradykinin (10-100 microM) produced similar dilation of non-collaterals and collaterals which was decreased by nitro-L-arginine but not glibenclamide. Thus, in microvascular collaterals, relaxation to both nitric oxide and activation of ATP-sensitive K+ channels is similar to non-collaterals.     

Photomodification of the cell membrane complex of wool-the effect on dyeability

Wool fibres have been selectively stained in the region of the cell membrane complex with eosin Y, fluorescein and rose bengal. Dye distribution patterns were determined by fluorescence microscopy and electron-induced X-ray emission (in conjunction with scanning transmission electron microscopy). Irradiation of the stained fibres with visible light caused a reduction in the rate of dye uptake when the wool was subsequently treated with an aqueous solution of the dye CI Acid Red 18. The change in the dyeability of wool was attributed to selective photomodification of the cell membrane complex.     

Risk contexts and risk behaviors in the Euregion Maas-Rhein: the Boule de Neige intervention for AIDS prevention among drug users

Using targeted sampling, self-reported data of 1,767 drug users in the Euregion Maas-Rhein were collected over 3 years. Forty-two percent of the injection drug users shared syringes with sexual partners and 47.8% with friends. Eighty-one percent of the total sample had sexual contact in the last 6 months, half of whom with one person and half with two or more. Significant predictors of high-risk drug use were injecting in the presence of others, injection onset before the age of 20, female gender, and not living in The Netherlands. Participation in needle exchange or methadone programs and sufficient knowledge of risk factors was not significantly related to a reduction of high-risk drug use behavior. High-risk sexual behavior was found to be related to male gender, under the age of 30 and to multiple sexual partners. We conclude that in a social context where needle exchange, methadone programs, and sufficient knowledge of risk factors among the drug user population exist, AIDS prevention can be improved through behavioral skills training and developing specific interventions that target the peer group environments, rituals, partner relationships, and lifestyles of drug users.     

Acute renal failure: factors influencing nephrology referral and outcome

We investigated the incidence, factors affecting referral and outcome of acute renal failure (ARF), in an unselected (predominantly Caucasian) population in the Grampian region of Scotland served by a single renal unit. Case-notes were examined for all patients with a serum creatinine > or = 300 mumol/l. ARF (311 patients) was defined as a temporary rise in serum creatinine > or = 300 mumol/l, or, if the patient died during the acute illness, clinical features indicating acute deterioration of previously normal renal function. Advanced ARF at presentation (51 of the 311 with ARF) was defined as a first recorded serum creatinine > or = 500 mumol/l. Patients were classified into low-, medium-, and high-risk groups according to presence of comorbidity and age. The annual incidence of ARF was 620/million population (pmp), that of advanced ARF 102 pmp. The age-related incidence of ARF ranged from 30 pmp in the age group (0-19 years) to 4266 pmp in the age group > 80 years. Overall, 22% were referred to a nephrologist (34% after excluding those with advanced cancer and age > 80 years). Referral of patients decreased from 100% in the age group 0-19 to 5% in those > 80 years. Referrals in the low-, medium- and high-risk groups were 75%, 30% and 14%, respectively. Patient survival at 2 years was 80%, 42% and 19% for low-, medium-, and high-risk groups, respectively (86%, 44% and 32% for referred patients). Referral and outcome in patients with ARF were significantly influenced by age and presence of comorbidity at presentation.