Elevation of plasma thioredoxin levels in HIV-infected individuals

Thioredoxin (Trx), a ubiquitous protein intimately involvedin redox and protein disulfide reductions, has been shown tobe released from cells and to have cytokine-like activities.In addition, Trx has been implicated in the redox regulationof immunological responses and shown to be deficient in tissuesfrom AIDS patients. In studies presented here, plasma Trx levelswere measured by ELISA in plasma samples from HIV-infected individuals(n = 136) and HIV-negative controls (n = 47). To account forthe release of Trx into plasma due to hemolysis, the Trx measurementswere corrected according to the level of hemoglobin in the plasmasample. Data presented show that, in contrast to tissue Trxlevels, corrected plasma Trx levels are significantly higherin HIV-infected individuals than in controls (P < 0.0001).Furthermore, {small tilde}25% of the HIV-infected individualsstudied have plasma Trx levels greater than the highest levelfound in controls (37 ng/ml). Detailed multiparameter FACS analysisof peripheral blood mononuclear cells (PBMC) from the infectedindividuals demonstrates that those with higher plasma Trx levels(37 ng/ml or greater) tend to have lower overall CD4 counts.In addition, increases in plasma Trx levels correlate with decreasesin monochlorobimane staining (indicative of lower intracellularglutathione levels in PBMC) and with changes in surface antigenexpression (CD62L, CD38 and CD20) that occur in the later stagesof HIV infection. These correlations suggest that elevationof plasma Trx levels may be an important component of advancedHIV disease, perhaps related to the oxidative stress that oftenoccurs at this stage.     

Adherence to recommendations and improvement over time in men with erectile dysfunction

Men with erectile problems seen for a comprehensive urology-department-based medical and psychological evaluation were sent questionnaires 2 to 3 years later. A representative sample of 99 (52%) responded. The majority (51%) has taken no action and reported that their sexual function was no better. Patients were more likely to comply with a recommendation for sex therapy than with one for a penile prosthesis. This was related to their attitude towards mental health professionals. These findings suggest the need for more knowledge of patient psychology and expectations.These data were presented in preliminary form at the Tenth Meeting of the International Academy of Sex Research, Cambridge, England, September 1984.     

Crosslinking of fibrinogen and fibronectin by free radicals: a possible initial step in adhesion formation in osteoarthritis of the temporomandibular joint.

PURPOSE: Adhesion formation in osteoarthritis (OA) of the temporomandibular joint (TMJ) typically results in a sustained limitation of joint movement. We propose the hypothesis that free-radical-mediated crosslinking of proteins underlies this adhesion formation in affected joints. Free radicals may cause oxidative modification of proteins, creating an opportunity for the formation of intramolecular and intermolecular crosslinks via covalent bonds. This may stabilize protein aggregates, rendering them more resistant to degradation. In this study, the free-radical-mediated crosslinking of model proteins (fibrinogen and fibronectin) was investigated to test our hypothesis that free radicals contribute to adhesion formation via this mechanism in OA of the TMJ. MATERIALS AND METHODS: Physiological clot formation of fibrinogen by thrombin and free-radical-induced crosslinking of fibrinogen and of fibronectin were analyzed using spectrophotometric turbidity measurements, light-scattering techniques, polyacrylamide gel electrophoresis (PAGE), and rotary shadowing. RESULTS: Fibrinogen was shown to aggregate after free radical treatment, as detected using turbidity measurements and light-scattering techniques. Using PAGE, fibrinogen as well as fibronectin was shown to degrade under low oxidative stress. Under high oxidative stress, however, fragments from both proteins were found to be covalently crosslinked, resulting in high-molecular-weight protein aggregates. The aggregation was shown to be at random with rotary shadowing. CONCLUSION: The study shows that high oxidative stress contributes to the formation of crosslinked proteins that may serve as an initial scaffolding for the development of adhesions frequently seen in OA of the TMJ.     

Many of the IgA producing plasma cells in murine gut are derived from self-replenishing precursors in the peritoneal cavity

Long term B lineage chimeras are used here to study the originof plasma cells in the mouse. Chlmeric mice are constructedby reconstituting lethally irradiated mice with peritoneal cells(PerC) and bone marrow cells from congenic pairs of mice differingIn Igh-C allotype. All conventional B cells in these mice expressthe allotype of the bone marrow donor and nearly all Ly-1 Blineage cells express the allotype of the PerC donor. FACS analysisand immunohistology of these mice shows that virtually all (sig⁺)B cells in peripheral lymphoid organs are derived from the bonemarrow donor. However, despite this overwhelming number of bonemarrow-derived B cells in these animals, immunohistologicalstaining of lymphold organs and gut shows that nearly half ofthe IgM, IgG, and IgA plasma cells derive from the PerC donor.These data demonstrate that the peritoneal cavity contains amajor reservoir of self-replenishing cells that play a significantrole in the mucosal immune response. The possibility that theseare B cells that belong to the Ly-1 B lineage is discussed.     

Short- and long-term impact of neutropenia within the first year after kidney transplantation

The aim of this retrospective single-center study was to investigate the short- and long-term impact of neutropenia occurring within the first year after kidney transplantation, with a special emphasis on different neutropenia grades. In this unselected cohort, 225/721 patients (31%) developed 357 neutropenic episodes within the first year post-transplant. Based on the nadir neutrophil count, patients were grouped as neutropenia grade 2 (<1.5–1.0*10⁹/l; n = 105), grade 3 (<1.0–0.5*10⁹/l; n = 65), and grade 4 (<0.5*10⁹/l; n = 55). Most neutropenia episodes were presumably drug-related (71%) and managed by reduction/discontinuation of potentially responsible drugs (mycophenolic acid [MPA] 51%, valganciclovir 25%, trimethoprim/sulfamethoxazole 19%). Steroids were added/increased as replacement for reduced/discontinued MPA. Granulocyte colony-stimulating factor was only used in 2/357 neutropenia episodes (0.6%). One-year incidence of (sub)clinical rejection, one-year mortality, and long-term patient and graft survival were not different among patients without neutropenia and neutropenia grade 2/3/4. However, the incidence of infections was about 3-times higher during neutropenia grade 3 and 4, but not increased during grade 2. In conclusion, neutropenia within the first year after kidney transplantation represents no increased risk for rejection and has no negative impact on long-term patient and graft survival. Adding/increasing steroids as replacement for reduced/discontinued MPA might supplement management of neutropenia.     

The disease coping of radiation cancer patients compared]

Emotional well-being and physical complaints of 87 outpatients undergoing radiotherapy were compared with those of a variety of other patients. The emotional and physical status were assessed by a list of emotional symptoms (German: "Befindlichkeitsskala") [18] and a list of physical complaints (German: "Beschwerdeliste") [19]. Although they have to cope with a fair amount of physical strain, values of the "oncologic group" rank second lowest, outranked only by healthy controls. The results strengthen the hypothesis of an adaptive denial to cope with the strain of the treatment. In conclusion, concrete suggestions are made for the doctor-patient relationship.     

The status of oncologic patients in radiotherapy--physical and psychological aspects

This study examines the psychological strains experienced by patients undergoing radiotherapy, as well as their somatic complaints and the possible connection between these two aspects. The sample consisted of 87 cancer patients, 64 female, 23 male. We used two standardized clinical instruments, one Zerssen's list of somatic complaints ("Beschwerdeliste" in German) and Zerssen's questionnaire of wellbeing ("Befindlichkeitsskala" in German). These two research instruments were implemented four times: at the beginning, in the middle and at the end of radiation, and three months afterwards. Results: Both the psychological state of well-being and somatic complaints remained at approximately the same level during the whole course of therapy. The state of well-being increased significantly after therapy, which is indicated by the decrease in the number of psychological impairments, whereas the score for somatic complaints remained the same. We observed a general tendency on the part of the patients to play down their situation. Sex differences were not observed. The discussion of the results includes their implication on the doctor-patient relationship.