Interferon-gamma (IFN-gamma) and IL-4 expressed during mercury-induced membranous nephropathy are toxic for cultured podocytes.

The subepithelial immune deposits of Dorus Zadel Black (DZB) rats with mercury-induced membranous nephropathy consist of autoantibodies directed to laminin P1 and of complement. The animals develop massive proteinuria within 10-14 days which is associated with obliteration of foot processes of glomerular visceral epithelial cells (GVEC), or podocytes. Previous studies indicate that these autoantibodies are probably not the sole mediator of proteinuria and GVEC damage. In this study we investigated whether circulating or macrophage-derived cytokines can contribute to the GVEC changes as detected in vivo. In vivo at the height of the proteinuria, increased intraglomerular IFN-gamma immunoreactivity was found. In diseased rats a five-fold increase in intraglomerular macrophages was found, but we could not detect intraglomerular IFN-alpha, IFN-beta, IL-1 beta or tumour necrosis factor-alpha (TNF-alpha) by using immunohistology. Subsequently, we exposed cultured GVEC to these cytokines to investigate their cytotoxic effects on several physiological and structural parameters. IFN-gamma and IL-4 were the only cytokines that exerted toxic effects, resulting in a rapidly decreased transepithelial resistance of confluent monolayers, which was closely associated with altered immunoreactivity of the tight junction protein ZO-1. IL-4 also affected vimentin and laminin immunoreactivity. IFN-gamma and IL-4 only interfered with monolayer integrity when added to the basolateral side of the GVEC, indicating specific (receptor-mediated) effects. Only IL-4 decreased the viability of the cells, and treated monolayers demonstrated an increased passage of the 44-kD protein horseradish peroxidase. From our experiments we concluded that IFN-gamma subtly affected monolayer integrity at the level of the tight junctions, and that IL-4 additionally induced cell death. We hypothesize that the toxic effects of the cytokines IFN-gamma and IL-4 as seen with cultured podocytes are necessary together with the autoantibodies, for the ultimate induction of proteinuria in mercury nephropathy in the DZB rat.     

Randomized controlled trial assessing the effect of vitamin A supplementation on maternal morbidity during pregnancy and postpartum among HIV-infected women

OBJECTIVE: To determine whether low-cost treatment of HIV using vitamin A would be beneficial, we examined the effect of vitamin A supplementation on morbidity of HIV-1 infected women. METHODS: We conducted a randomized, double blind placebo-controlled trial at King Edward VIII Hospital, in Durban, South Africa. In total, 312 HIV-seropositive pregnant women between 28 and 32 weeks' gestation were recruited into this trial. Patients were randomized to receive placebo or 5,000 IU retinyl palmitate and 30 mg beta-carotene daily. At delivery of their children, patients received placebo or 200,000 IU retinyl palmitate. The main outcome measures were pre- and postnatal report of HIV-related symptoms. RESULTS: Vitamin A did not confer any significant beneficial effect on the report of either HIV or pregnancy-related symptoms during the pre- or postnatal period. CONCLUSION: In this study of HIV-infected pregnant women, vitamin A supplementation given in doses designed to decrease mother-to-infant transmission did not result in significant beneficial effect on reported symptoms pre- or postnatally. Further investigation with larger number of participants, tailoring supplementation for specific clinical conditions, outside the context of pregnancy, is required to help clarify the possible clinical benefits of vitamin A.     

PG-M1: A New Monoclonal Antibody Directed against a Fixative-Resistant Epitope on the Macrophage-Restricted Form of the CD68 Molecule

A new anti-macrophage monoclonal antibody (PG-M1) was produced by immunizing BALB/c mice with fresh spleen cells from a patient with Gaucher's disease. PG-M1 reacts strongly with a fixative-resistant epitope of an intracytoplasmic molecule, selectively expressed by virtually all macrophages of the human body. Although attempts to immunoprecipitate the molecule recognized by PG-M1 have failed so far, the reactivity of the antibody with COS-1 and WOP cells transfected with a human complementary DNA clone encoding for the CD68 antigen suggests that PG-M1 is a new member of the CD68 cluster. However, unlike other CD68 antibodies (KP1, EBM11, etc.), which react with both macrophages and myeloid cells, PG-M1 detects a fixative-resistant epitope on the macrophage-restricted form of the CD68 antigen. In 957 routinely fixed, paraffin-embedded samples, PG-M1 showed a more restricted reactivity with elements of the monocyte/macrophage lineage than the previously described monoclonal antibodies MAC-387 (anti-calgranulins), KP1 (CD68) and Ki-M1P. Among hematological malignancies, PG-M1 only labels acute leukemias of M4 and M5 type and rare examples of malignant histiocytosis/true histiocytic sarcoma. In contrast, acute leukemias of the M1, M2, M3, M6, M7, and L1-L3 types, non-Hodgkin's lymphomas, and Hodgkin and Reed-Sternberg cells of Hodgkin's disease are consistently PG-M1-negative. In the daily diagnostic practice, PG-M1 seems to be particularly valuable for the diagnosis of myelomonocytic or monocytic leukemia and neoplasms of true histiocytic origin in routine paraffin sections.     

Licht- und elektronenmikroskopische Untersuchungen zur Histopathogenität vonMacracanthorhynchus hirudinaceus (Archiacanthocephala) in experimentell infizierten Hausschweinen

Zusammenfassung Die vonMacracanthorhynchus hirudinaceus verursachten Läsionen im Dünndarm von experimentell infizierten Hausschweinen (7 Tage p.i. und 84 Tage p.i.) wurden licht- und elektronenmikroskopisch untersucht. Die Würmer der 84 Tage alten Infektion waren tiefer in die Darmwand eingedrungen als die 7 Tage alten Würmer. Ihr Präsoma wurde von Entzündungsbzw. Bindegewebe umhüllt, das zahlreiche Plasmazellen enthielt. Bei 7 Tage alten Infektionen wurde noch keine Fibrose nachgewiesen. Eosinophilen-ähnliche Granulozyten, die an den Proboscishaken akkumulierten, herrschten in der Läsion vor. Eine osmiophile Gleitflüssigkeit, die offenbar an der Basis der Proboscishaken ausgeschieden wurde, schien eine stark antigene Wirkung auf die Leukozyten des Schweins auszuüben. In keinem Fall wurden Würmer angetroffen, die die gesamte Darmwand perforiert hatten, wie es in China bei Menschen beschrieben wurde.

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Light and electron microscopical investigation of the histopathogenicity ofMacracanthorhynchus hirudinaceus in experimentally infected swine

One and 12 weeks after infection the lesions in the small intestine of two domestic pigs caused byMacracanthorhynchus hirudinaceus were studied by means of light and electron microscopy. Worms of 7 d.p.i. were found to have penetrated with their presoma into the tunica propria and partly into the tunica muscularis where they had caused local mechanic destructions and heavy eosinophilic-like and hemorrhagic reactions. Most eosinophilic-like granulocytes were attracted to the proboscis hooks, at the base of which an osmiophilic substance apparently was excreted. Worms of 84 d.p.i. had penetrated with their proboscis deeply into the tunica muscularis. The presoma had become encapsulated by a solid capsule of necrotic/inflammatory tissue in its inner part and by filamentous connective tissue in its outer part. The predominant leucocytes in the inflammatory tissue now were plasma cells indicating a progressive immune reaction. No worms were found to have perforated the entire intestinal wall as was described from human patients in China.

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Unterstützt durch ein Stipendium der VR China für Herrn Bin Zhao     

Lymphatic absorption and metabolism of orally administered testosterone undecanoate in man

Summary [³H]-testosterone undecanoate ([³H]TU) was administered orally to 4 patients with a thoracic duct catheter after neck dissection surgery.Appearance of radioactivity in lymph, plasma and urine was measured at different times. Metabolites of TU in these fluids were investigated. Peak levels of radioactivity appeared simultaneously in lymph and plasma (2.5–5 h after administration) while the excretion in urine was highest approximately 2 h after the plasma and lymph peak. The main compounds appearing in the lymph were TU and 5-dihydrotestosterone undecanoate (5-DHTU), but 5-DHTU could not be detected. In plasma almost all metabolites were probably conjugated.During the first 24 h approximately 40% of the administered radioactivity was excreted in the urine. The total amount of radioactivity excreted in the urine during the first week was 45–48%. The predominant urinary metabolites were testosterone- and androsterone-glucuronide.The results indicate that TU is metabolized partly in the intestinal wall. The remaining TU and newlyformed 5-DHTU, at least partly, are absorbed via the lymphatic system.     

Stoffwechseluntersuchungen bei tiefer Hypothermie unter 20° und langdauerndem artefiziellem Kreislaufstillstand

Ohne Zusammenfassung     

Somatoform pain disorder in the general population

BACKGROUND: Chronic pain disorder is assumed to represent a frequent and disabling condition. However, data on the prevalence of somatoform pain symptoms and somatoform pain disorder in the community are limited to date. METHODS: German versions of the Composite International Diagnostic Interview were administered to a representative national sample of 4,075 people. Somatoform pain disorder was diagnosed by standardized diagnostic algorithm based on the DSM-III-R criteria (absence of adequate physical findings). One subgroup was identified as also meeting the DSM-IV criterion B for 'significant distress or psychosocial impairment due to the somatoform pain'. RESULTS: A lifetime prevalence rate of somatoform pain disorder according to DSM-III-R of 33.7% and a 6-month rate of 17.3% was found. When applying the DSM-IV B criterion, the prevalence rate dropped to 12.3 and 5.4%, respectively. In both groups more than 95% of the probands had contacted their doctor because of the pain. In 25% of the probands the pain was positively assigned to psychological factors. A female:male ratio of 2:1 was found. CONCLUSIONS: Somatoform pain disorder (DSM-III-R) is a frequent condition. However, only about one third of these subjects is severely distressed or impaired by the pain. A clear operationalized concept of the DSM-IV criterion C 'psychological factors are judged to have an important role in the onset, severity, exacerbation or maintenance of the pain' should be provided in the further development of the diagnosis 'pain disorder' in order to make this diagnosis suitable for general population surveys.     

Cyst-like cerebral lesions in tuberous sclerosis

Known brain manifestations of tuberous sclerosis (TSC) are cortical sclerotic tubera, giant cell astrocytomas, subependymal calcified nodules in the lateral walls of the lateral ventricles, and white matter heterotopias. In addition, small cyst-like lesions in the white matter have been described. We report on three TSC patients with hitherto undescribed large cyst-like cerebral lesions in subcortical and white matter locations. We emphasize that cystoid brain degeneration is a rare but typical cerebral manifestation of TSC and suggest that, in patients with such lesions, TSC should be taken into consideration.