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Biomedical subjects

U Gross

Publications and source records attributed to U Gross.

At least 109 records · Page 6Linked to original sources

Reactivation of chronic toxoplasmosis: is there a link to strain-specific differences in the parasite?

The protozoan parasite Toxoplasma gondii comprises three clonal lineages that are associated with the clinical outcome in infected individuals. Whereas group C strains are mainly found in animals, group A and B strains are associated with human disease (Howe and Sibley, 1995). An increased level of transcripts of the tachyzoite-specifically expressed gene SAG1 could be identified in group A T. gondii strains compared to group B strains. Since SAG1-mediated host-cell invasion seems to be important for parasite replication, the observed higher replication rate in group A T. gondii strains might explain the association with clinically overt symptoms at the acute stage in patients who are infected with this group of parasite strains. The presence of external stress factors, such as interferon-gamma (IFN-gamma)-mediated nitric oxide (NO) formation has been identified to stabilize the cyst stage, most likely by activation of promoter(s) which drive the expression of genes encoding bradyzoite-specific antigens. Reactivation of chronic toxoplasmosis thus might occur in the absence of external stress factors, as has been observed in AIDS patients with decreases levels of IFN-gamma. Since group B T. gondii strains might form more cysts in infected individuals due to an increased potential to convert into bradyzoites, reactivation with resulting toxoplasmic encephalitis could be a more common event in those AIDS patients who were infected with persistent cysts of this group of parasite strains.

Animals↗

Toxoplasma gondii strain-specific transcript levels of SAG1 and their association with virulence.

Toxoplasma gondii isolates can be classified into mouse-virulent and -avirulent strains. Since the major surface antigen of Toxoplasma gondii, SAG1, has been shown to be important for the invasion process and might thus be involved in mouse virulence as well, we analyzed the corresponding gene of mouse-virulent and -avirulent strains. In addition to eight mismatches, mouse-virulent strains harbored five copies of an up-stream 27-bp repeat in the promotor region of SAG1 as compared with four copies in avirulent strains. Reverse-transcriptase polymerase chain reaction revealed that SAG1 expression levels in the mouse-virulent T. gondii strains were at least 4-fold those in the avirulent strains. Since SAG1 seems to mediate invasion, it is suggested that the possibly higher steady-state expression of SAG1 in mouse-virulent strains of T. gondii is associated with virulence and facilitates faster invasion by these strains in comparison with avirulent strains.

Animals↗

Developmental differentiation between tachyzoites and bradyzoites of Toxoplasma gondii.

An important event in the pathogenesis of toxoplasmosis is the interconversion between the bradyzoite and the tachyzoite stage of Toxoplasma gondii within the intermediate host. The factors that influence either cyst formation (bradyzoites) or reactivation (tachyzoites) are unknown. Uwe Gross, Wolfgang Bohne, Martine Soête and Jean François Dubremetz here describe current knowledge about the mechanisms that might lead to the induction of stage differentiation of this protozoan parasite.

Journal Article↗

Human tissue responses to metal stents implanted in vivo for the palliation of malignant stenoses.

BACKGROUND: We sought to determine the histologic effects of metal stent placement on tumor tissue and on normal tissue proximal and distal to the tumor in patients with expandable metal stents implanted in vivo. METHODS: Twelve patients with 10 to 16 mm uncovered Wallstents were studied, 5 with esophageal stents, 4 with biliary stents and 3 with antral-duodenal stents. Stent duration ranged from 18 days to 15 months. Eleven autopsy specimens and one surgical specimen were examined. The organs with the stent in place were removed, and histologic specimens were obtained using a special saw-microtome that cuts through the tissue and the material of the stent. RESULTS: In all organs examined, the stent was incorporated into the material of the tumor to a varying degree. In the normal areas above and below the stenosis, the stent was incorporated into the wall of the organ and was covered by a collagenous reactive layer on the luminal aspect. The collagenous reaction was limited and did not cause exuberant growth or obstruction in any of the cases. CONCLUSIONS: The struts of uncovered Wallstents of 10 to 16 mm in diameter migrate into the submucus space above and below the tumor, probably by pressure necrosis, and become incorporated into the wall of the organ.

Aged↗

Massive osteolysis (Gorham-Stout syndrome) in the maxillofacial region: an unusual manifestation.

An unusual case of massive osteolysis affecting the left side of the mandible, the maxilla, the zygoma, and the orbit is reported. The disease extended over a period of 25 years. The special feature of this case is that there were, before the osteolysis appeared, enlargement and sclerosis of the maxillofacial bones reaching up to the middle cranial fossa. Histopathologic examination of the affected mandible revealed that the bone was replaced by fibrous tissue.

Adult↗

Procollagen alpha 1(I) transcripts in cells near the interface of coralline implants in rats, detected by in situ hybridization.

Cells procollagen alpha 1(I) transcripts were demonstrated at the interface of natural coral mineral implanted in the femur of rats after 7, 14, 21 and 28 days by in situ hybridization with digoxigenin-labelled RNA probes. Procollagen alpha 1(I) transcripts were detectable in osteoblasts between 7 and 28 days after implantation. As early as 7 days after implantation, procollagen alpha 1(I) RNA expression was also demonstrated in fibroblasts; the transcripts steady state levels decreased until the 28th day, when they subsided completely. The development of bone was significantly during the 4 weeks of implantation. Inhibition of bone development by the coralline material could not be recorded.

Animals↗

Heterogeneity of acute intermittent porphyria: a subtype with normal erythrocyte porphobilinogen deaminase activity in Germany.

Patients with acute intermittent porphyria can be subdivided into three groups, according to the porphobilinogen deaminase activity in their erythrocytes. The first group has lowered, the second overlapping and the third normal porphobilinogen deaminase activity. Of 385 acute intermittent porphyria patients 5% had normal porphobilinogen deaminase activity. Gene carriers of acute intermittent porphyria, which have normal porphobilinogen deaminase activity but display slight, moderate or high aberrations of excretion, are recognized by analysis of urinary haem precursors and faecal porphyrins. Six individuals suffering from acute intermittent porphyria were detected in three families with normal porphobilinogen deaminase. There were no differences in the latent and clinical phases of acute intermittent porphyria between patients with lowered and those with normal porphobilinogen deaminase. One female with normal activity in erythrocytes, in which the porphyria disease process is triggered by barbiturates and carbamazepine, is presented. After therapy with high doses of glucose and omission of inducing agents, this woman was free of symptoms, and the excretion of different urinary porphyrin precursors and porphyrins decreased by between 65 and 93%.

Erythrocytes↗

High incidence of toxoplasmosis during pregnancy in Nigeria.

Sera from 606 women of child-bearing age from the Benue River Basin area of Nigeria were screened by serological tests to determine the incidence of toxoplasmosis in Nigeria; 43.7% had serologic evidence of infection, increasing from 25% in the group of 15 to 18-year-old women to 71.4% in the 39-42 year age group. Using a previously published epidemiological model, the incidence rate for each age group varied from 0.5% for 15 years old women to 5.3% in the age group 37 years, with an overall rate of 1.8%. Extending this model as it applies to the estimation of incidence of infection during pregnancy, a 5.4% expected rate of seroconversion was found.

Adolescent↗

[Intra-articular B-cells in the pathogenesis of rheumatoid arthritis].

B-cells of the rheumatoid synovial tissue are constant and in some cases dominant elements of the inflammatory infiltrate and are located near to the site of tissue destruction. The pattern of B-cell distribution, the pattern and the relationship to the corresponding antigen presenting cells (follicular dendritical reticulum cells; FDC's) shows a great variation: B cells exhibit a follicular organisation forming secondary follicles, follicle like patterns with irregular formed FDC's networks and a diffuse pattern of and isolated FDC's. Molecular analysis of immunoglobulin genes from synovial B-cell clones and synovial tissue demonstrates the occurrence of immunoglobulin gene hypermutation as well as germline configuration. The FDC formations in the synovial tissue may therefore serve as an environment for B-cell maturation which is involved in the generation of autoantibodies. An autoantibody may be only defined as "pathogenic" if the antibody fulfills the Witebsky-Rose-Koch criteria for classical autoimmune disease: definition of the autoantibody, induction of the disease by transfer of the autoantibody and isolation of the autoantibody from the disease specific lesion. B-cells of rheumatoid synovial tissue show specificity for FcIgG, collagen 2, sDNA, tetanus toxoid, mitochondrial antigens (M2) and bacterial HSP's and the contribution of these antibodies to the pathogenesis of RA are still hypothetic. Antibody with specificity for bacterial HSP's which have arose during contact with an infectious agent and may due to crossreactivity with eukaryotic HSP of synovial tissue perpetuate the local inflammatory process. The characteristic pattern, the localisation within the area of tissue destruction and the exclusive function of B-cells to recognize conformation dependent antigens suggests a central role of B-cells in the inflammatory process. The analyzation of the synovial tissue B-cell therefore will help to characterise antigens which are responsible for the pathogenesis of RA.

Antibody Specificity↗

The facilitating effect of one-DR antigen sharing in renal allograft tolerance induced by donor bone marrow in rhesus monkeys.

Infusion of donor bone marrow cells (DBMC), a long-standing, successful strategy for inducing tolerance in experimental rodent transplantation models, can promote long-term acceptance of life-sustaining renal allografts in rhesus monkeys with no maintenance immunosuppression. To investigate the immunological basis for heterogeneity in duration of long-term graft acceptance following infusion of the DR-/dim fraction of DBMC into RATG-treated rhesus monkeys, we examined the relationship of recipient-donor major histo-compatibility class I and II DR matching to the development of antidonor antibody-dependent cellular cytotoxicity (ADCC) and renal allograft survival. The findings indicate a requirement for sharing one DR allele to achieve long-term graft acceptance. The observed immunological consequence of DR sharing that correlated with functional graft tolerance in this model was the suppression of early antidonor ADCC+ IgG antibody responses. Significant associations were observed between graft survival and suppression of ADCC antibody (P < 0.0005), graft survival and DR sharing (P < 0.005), and DR sharing and suppression of ADCC (P < 0.02). Early antidonor ADCC antibody responses associated with failure to maintain graft tolerance and were most consistently directed to donor class I. The required one DR antigen sharing in DBMC-induced suppression of antidonor class I antibody suggests a restriction for recipient DR, implying critical regulation of a response to donor antigen presented on recipient cells. We hypothesize a DBMC tolerogenic mechanism in which presentation of donor class I peptide by a shared DR allele configuration allows a veto effect by DBMC. Thus DR sharing would allow DBMC veto cells to reduce clonal expansion elicited by both the direct and indirect antigen presentation pathways.

Animals↗

Nanoapatite and organoapatite implants in bone: histology and ultrastructure of the interface.

This article reports on the reaction of bone to a new family of nanocrystalline hydroxyapatite biomaterials with crystal sizes similar to those of human bone. Pure nanoapatite cylinders and organoapatite cylinders containing a synthetic nanopeptide were analyzed 28 days after implantation into the spongy bone of Chinchilla rabbits. The experimental techniques used for analysis were light microscopy, scanning electron microscopy, and transmission electron microscopy. Both implant types were well incorporated, and interface events were found to be similar to those observed on human bone surfaces with regard to resorption by osteoclast-like cells and bone formation by osteoblasts. Different types of giant cells were observed resorbing the outermost surfaces of implants. There seemed to be both dissolution of the implant and particulate biodegradation leading to less dense implant regions near the interface, whereas the bulk of the implants remained denser. Transmission electron micrographs revealed that bone bonding occurred with and without an afibrillar intervening layer. Given the biologic reaction observed, these implant materials should be suitable for bone replacement and the organoapatite form could be useful for additional functions such as the release of drugs and optimized release of antibiotics, growth factors, or other substances. The organic component can also be used to control physical properties in a bony implantation bed.

Animals↗

[Experimental studies of the load capacity of DHS osteosyntheses after various kinds of osteotomy in the area of the femoral trochanter].

Standardized osteotomies were performed to mimic fractures classified as (a) stable, (b) partly unstable and (c) complete unstable (according to Evans) in 32 postmortem femoral bones. The stability of all preparations was examined after the performance of an osteosynthesis with a dynamic hip screw. Cycled loadings were increased stepwise every 500 N to the maximum loading capacity (load of fracture). In addition, the distortion at 2000 N was measured. There were no statistically significant differences between the three groups (a), (b), and (c). The average maximum load capacity was significantly lower in group (c) than in groups (a) and (b). Nevertheless, the lowest value (2275 N) recorded for the maximum loading capacity in our study means that in a normal weight person full weight-bearing can be allowed postoperatively.

Aged↗

Limited value of cerebrospinal fluid for direct detection of Toxoplasma gondii in toxoplasmic encephalitis associated with AIDS.

The diagnosis of acquired immunodeficiency syndrome-associated toxoplasmic encephalitis (TE), a typically focal disease resulting from reactivation of tissue cysts, relies mainly on indirect diagnostic methods. In a prospective study, we investigated the value of detection of Toxoplasma gondii in cerebrospinal fluid (CSF) by using the polymerase chain reaction and the mouse inoculation test. Twenty-four patients with 26 episodes of TE, 2 HIV-infected patients with primary acute Toxoplasma infection, and 38 HIV-infected control patients with latent Toxoplasma infection were investigated. Detection of T. gondii in CSF by both methods was possible in only 3 of the TE patients (11.5%), the remaining patients being negative with either of the methods. In contrast, T. gondii DNA was detected in both of the acutely infected patients, indicating that in primary acute toxoplasmosis parasites may easily be found in the CSF, whereas in the majority of TE cases in immunocompromised patients, T. gondii parasites do not gain access to the CSF drawn by lumbar puncture.

AIDS-Related Opportunistic Infections↗

Hormonal oral contraceptives, urinary porphyrin excretion and porphyrias.

The influence of hormonal oral contraceptives on the urinary porphyrin excretion of 40 healthy females has been studied. Two different hormonal oral contraceptives (combinations of gestoden or desogestrel, respectively, and ethinylestradiol) were applied for half a year. In each case twenty women received one of these two combinations. Porphyrin precursors delta-aminolevulinic acid and porphobilinogen were normal in all subjects as well as the mean of uroporphyrin and coproporphyrin. One healthy female developed a mild secondary coproporphyrinuria. In this case coproporphyrin isomer I was slightly enhanced and isomer III slightly lowered. Furthermore it could be shown that three females with repeated premenstrual clinical expression of an acute hepatic porphyria (acute intermittent porphyria and hereditary coproporphyria) could be treated successfully with a hormonal oral contraceptive or other exogenous hormones to stabilize the latent, subclinical phase of the disease.

Adult↗

Cloning and characterization of a bradyzoite-specifically expressed gene (hsp30/bag1) of Toxoplasma gondii, related to genes encoding small heat-shock proteins of plants.

Stage conversion between the tachyzoite and bradyzoite forms of the protozoan parasite Toxoplasma gondii is an important aspect in the pathogenesis of toxoplasmosis. In an initial investigation of molecular regulation of stage conversion in T. gondii, we describe the cloning and characterization of a bradyzoite-specifically expressed gene (hsp30/bag1). Bradyzoite formation was induced in cell culture by alkaline pH, and this was followed by purification of this parasitic stage using magnetic cell sorting. A bradyzoite cDNA library was constructed by random amplification using the polymerase chain reaction. Screening with a bradyzoite-specific monoclonal antibody identified a reactive clone. The amino acid sequence derived from the 687 bp open reading frame showed similarity to the conserved C-terminal region of small heat-shock proteins from plants. Stage-specific expression of the naturally occurring 30 kDa antigen in bradyzoites was confirmed by polyclonal antisera generated against the recombinant antigen. Immunoelectron microscopy indicated a cytosolic location of this antigen in bradyzoites. The expression of HSP30/BAG1 seems to be regulated at the mRNA level, since reverse polymerase chain reaction using bradyzoite-specific primers amplified transcripts in bradyzoites only, not in tachyzoites.

Amino Acid Sequence↗