Antibodies to types I, II, IX, and XI collagen in the serum of patients with rheumatic diseases

Antibodies to native types I, II, IX, and XI collagen were measured, using a 125I-solid-phase radioimmunoassay, in serum from 104 patients with rheumatic diseases (rheumatoid arthritis, osteoporosis, Paget's disease, or osteoarthritis). In all disease groups, antibodies to type II collagen occurred with greater frequency than antibodies to type I collagen (11-35% versus 5-23%). Antibodies to type XI collagen were the most frequent: They were present in approximately 50% of the patients in the rheumatoid arthritis, Paget's disease, and osteoporosis groups. Antibodies to type IX collagen were found at a high frequency in the rheumatoid arthritis group only (44%). Analysis of the clinical data suggested that the presence of antibodies to collagen was associated with disease that was less severe or of shorter duration.     

Circulating immune complexes: optimization and characteristics of the C1q(I125) fixation test

The present paper describes the optimisation of a liquid phase [125I] C1q binding assay for the detection of circulating immune complexes. Blood must be collected without any anticoagulant. The serum can be stored or transported as usual without damage. A 90 min incubation is needed to reach the equilibrium of the reaction; polyethylene glycol (2,5% final concentration) is added to precipitate the [125I] C1q-CIC complex. By its simplicity and reproducibility, this test can be currently employed, especially in the case of treatment by plasmapheresis.     

Value of computed tomography in the staging of testicular tumors

To analyze the value of computed tomography (CT) for the exact staging of testicular tumors, 2 groups of 28 patients each were examined. All patients underwent retroperitoneal lymph node dissection in the course of their treatment. Pretherapeutic stages as determined by CT were compared to the histologically verified definite tumor stages. In 68% of the patients, the stage found by CT was correct but 3 (5%) false-positive and 13 false-negative results were obtained. Thus, almost 40% (13/33) of the patients with clinical stage I disease presumably would have had a progression if managed by a surveillance strategy. It can be concluded that this strategy should be restricted to certain centers with guaranteed long-term standardized patient observation and extremely high patient compliance.     

The effects of arotinoids on rat mammary carcinogenesis

Summary The influence of two retinoids, Ro 13–6298, an arotinoid ethyl ester, and Ro 15–1570, an arotinoid ethyl sulfone, on rat mammary carcinogenesis was investigated. Mammary carcinomas were induced by oral administration of 15 mg dimethylbenz(a)anthracene (DMBA) to 50-day-old female Sprague-Dawley rats. Oral administration of the two retinoids significantly inhibited the development of tumors. The number and volume of mammary neoplasms were influenced in a dose-dependent manner.     

Subtype-specific expression and genetic alterations of the chemokinereceptor gene CXCR4 in medulloblastomas

Recent findings indicate that the chemokine receptor Cxcr4 is essential for normal development of the cerebellar cortex. As medulloblastomas (MBs), the most common malignant brain tumors of childhood, are believed to arise from neuronal cerebellar precursors, we asked whether there is a potential role for Cxcr4 in the pathogenesis of MB. RT-PCR and immunohistochemistry revealed expression of Cxcr4 in different variants of MBs. Whereas 18/20 classic MBs showed very low levels of CXCR4 mRNA, high amounts were expressed in 17/18 desmoplastic and 6/7 extensively nodular MBs. In addition, a significant correlation of high CXCR4 mRNA levels and presence of the neurotrophin receptor p75NTR or expression of ATOH1 and GLI1 suggests that CXCR4 is a reliable marker for tumors derived from the cerebellar external granular layer. Because Cxcr4 is important for migration and cell cycle control of granular precursors, we screened for mutations in the coding region by SSCP and gene sequencing. In a series of 90 MBs and 8 MB cell lines, we found one germline and one somatic mutation resulting in amino acid substitutions in the first (Ile53Leu) and second (Asp97Asn) transmembrane regions, respectively. These data suggest that Cxcr4 may be involved in the pathogenesis of MBs.     

EGF suppresses hydrogen peroxide induced Ca2+ influx by inhibiting L-type channel activity in cultured human corneal endothelial cells

Endogenous generated hydrogen peroxide during eye bank storage limits viability. We determined in cultured human corneal endothelial cells (HCEC) whether: (1) this oxidant induces elevations in intracellular calcium concentration [Ca2+]i; (2) epidermal growth factor (EGF) medium supplementation has a protective effect against peroxide mediated rises in [Ca2+]i. Whereas pathophysiological concentrations of H2O2 (10 mM) induced irreversible large increases in [Ca2+]i, lower concentrations (up to 1 mM) had smaller effects, which were further reduced by exposure to either 5 microM nifedipine or EGF (10 ng ml(-1)). EGF had a larger protective effect against H2O2-induced rises in [Ca2+]i than nifedipine. In addition, icilin, the agonist for the temperature sensitive transient receptor potential protein, TRPM8, had complex dose-dependent effects (i.e. 10 and 50 microM) on [Ca2+]i. At 10 microM, it reversibly elevated [Ca2+]i whereas at 50 microM an opposite effect occurred suggesting complex effects of temperature on endothelial viability. Taken together, H2O2 induces rises in [Ca2+]i that occur through increases in Ca2+ permeation along plasma membrane pathways that include L-type Ca2+ channels as well as other EGF-sensitive pathways. As EGF overcomes H2O2-induced rises in [Ca2+]i, its presence during eye bank storage could improve the outcome of corneal transplant surgery.     

The Talinolol Double-Peak Phenomenon Is Likely Caused by Presystemic Processing After Uptake from Gut Lumen

Purpose. Evaluation of the double-peak phenomenon during absorption of the ₁-selective blocker talinolol relative to paracetamol, which is well absorbed from all parts of the gut, and relative to vitamin A, which is absorbed via the lymphatic pathway.Methods. Talinolol was given with paracetamol and retinyl palmitate in fast-disintegrating, enteric-coated, and rectal soft capsules to 8 fasting male healthy subjects (21–29 years, 68–86 kg). To evaluate whether the talinolol double-peak is associated with processes of food absorption, a breakfast was served 1 h after administration of a fast disintegrating capsule.Results. Bioavailability of talinolol in enteric-coated and rectal capsules was significantly reduced by about 50% and 80%, respectively, despite unchanged bioavailability of paracetamol. Double-peaks appeared after 2–3 h and 4–6 h with talinolol given as fast-liberating capsules. Food increased the maximum concentrations significantly (223 ± 76 g/ml vs. 315 ± 122 g/ml, p ‹ 0.05) and shifted the second peak of talinolol to shorter t_max values (3.8 ± 1.2 h vs. 2.1 ± 0.6 h, p ‹ 0.05), which was associated with faster absorption of retinyl palmitate. Pharmacokinetic model fits showed that about half of the oral talinolol dose given with and without meal is drained from the intestine via a presystemic storage compartment.Conclusions. The double-peak phenomenon of talinolol is likely caused by a presystemic storage compartment, which represents the complex interplay of heterogeneous uptake and kick-back transport processes along the intestinal-hepatic absorption pathway.