Search PubMed⌕ Search

Biomedical subjects

S Lang

Publications and source records attributed to S Lang.

At least 109 records · Page 6Linked to original sources
PubMed2000

Radiation synovectomy using 165Dy ferric-hydroxide and oxidative DNA damage in patients with different types of arthritis.

UNLABELLED: Radiation synovectomy is an effective treatment for chronic synovitis refractory to pharmacological treatment in patients with rheumatoid or seronegative arthritis. Concerns persist about possible radiation-induced cytogenetic damage after radiation synovectomy leading to recommendations to use this technique only in the elderly. Micronucleus (MN) frequency in lymphocytes and urinary excretion of 8-hydroxy-2'-deoxyguanosine (8OHdG) as an indicator of cellular oxidative DNA base damage are biomarkers of radiation-induced cytogenetic damage. The course of both biomarkers was studied in patients with different types of chronic synovitis undergoing radiation synovectomy with very short-lived 165Dy-ferric-hydroxide (DFH). METHODS: Radiation synovectomy of the knee was performed in 13 men and 12 women (mean age, 44+/-15 y) using a mean activity of 9.48+/-1.65 GBq 165Dy-DFH in 27 consecutive treatments. MN frequency in lymphocytes and urinary excretion of 8OHdG, measured by high-performance liquid chromatography, were assessed before and 4 (MN only) and 20 h after radiation synovectomy. RESULTS: Urinary excretion of 8OHdG in patients (in micromol/mol creatinine; pretreatment mean, 3.1+/-3.4; median, 2.27) was not significantly different from that in healthy volunteers (mean, 2.0+/-1.2; median, 1.87) and not altered by radiation synovectomy (post-treatment mean, 2.5+/-1.5; median, 2.04, NS). An increase in 8OHdG levels after radiation synovectomy of more than 1 SD was found in only 1 patient, who experienced leakage to the lymph nodes but who already had elevated urinary 8OHdG levels before treatment. The frequency of MN/500 binucleated cells (BNCs) was slightly lower in patients (pretreatment mean, 4.3+/-2.6; median, 4.25) than in healthy volunteers (mean, 5.4+/-2.3; median, 5.3) and did not significantly change after therapy, either (4-h post-treatment mean, 3.9+/-2.1, median, 3.8; 20-h post-treatment mean, 4.1+/-2, median 3.8 MN/500 BNC). In 22 of 27 treatments, no leakage to nontarget organs could be monitored, whereas leakage to the local lymph nodes and the liver was detected after 5 treatments. CONCLUSION: Radiation synovectomy using 165Dy-DFH causes no significant radiation burden to most patients as indicated by the absence of adverse changes in levels of biomarkers of cytogenetic damage and a low incidence of leakage. These data suggest that the risk of malignancy may not be elevated.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

[Socio-demographic and life-style factors in a Swiss study of HIV non-progression].

OBJECTIVES: The study investigates associations between socio-demographic or lifestyle factors and the progression of HIV. METHODS: We recruited a Swiss cohort (n = 56) of long-term survivors and conducted a cross-sectional study of laboratory data as well as factors concerning socio-demography, life-style, and psychology. On the basis of laboratory results, the cohort was divided into 2 subgroups, non-progressors (n = 31) and slow progressors (n = 25), which were subsequently compared. RESULTS: The comparison of socio-demographic factors showed that non-progressors were younger and had a higher income than slow progressors. Our data do not show an association between lifestyle and disease progression. DISCUSSION: Younger age as a cofactor of non-progression confirms various other studies. The association between income and disease progression, also found in another cohort, cannot be explained by unequal access to therapies since, in accordance with the inclusion criteria, no one in our cohort had received antiretroviral therapies. Further research in this field seems important to determine possible links between socio-economic status and disease progression. The lack of association between disease progression and lifestyle factors such as drug use, physical activity or nutrition is in contrast to a common view of HIV in our study population, but is confirmed by a majority of the research in this field.

Adult↗
PubMed1999

Simultaneous activation of T cells and accessory cells by a new class of intact bispecific antibody results in efficient tumor cell killing.

Bispecific Abs (bsAb) are promising immunological tools for the elimination of tumor cells in minimal residual disease situations. In principle, they target an Ag on tumor cells and recruit one class of effector cell. Because immune reactions in vivo are more complex and are mediated by different classes of effector cell, we argue that conventional bsAb might not yield optimal immune responses at the tumor site. We therefore constructed a bsAb that combines the two potent effector subclasses mouse IgG2a and rat IgG2b. This bispecific molecule not only recruits T cells via its one binding arm, but simultaneously activates FcgammaR+ accessory cells via its Fc region. We demonstrate here that the activation of both T lymphocytes and accessory cells leads to production of immunomodulating cytokines like IL-1beta, IL-2, IL-6, IL-12, and DC-CK1. Thus this new class of bsAb elicits excellent antitumor activity in vitro even without the addition of exogenous IL-2, and therefore represents a totally self-supporting system.

Animals↗
PubMed1999

Potential role of CD4+ T cell-mediated apoptosis of activated astrocytes in Theiler's virus-induced demyelination.

Intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV) into susceptible mouse strains results in a chronic, immune-mediated demyelinating disease similar to human multiple sclerosis. Here, we examined the role of astrocytes as an APC population in TMEV-induced demyelination and assessed the potential consequences of T cell activation following Ag presentation. IFN-gamma-pretreated astrocytes were able to process and present all the predominant T cell epitopes of TMEV to virus-specific T cell hybridomas, clones, as well as bulk T cells. Despite low levels of proliferation of T cells due to prostaglandins produced by astrocytes, such Ag presentation by activated astrocytes induced the production of IFN-gamma, a representative proinflammatory cytokine, in TMEV-specific Th cell clones derived from the CNS of virus-infected mice. Furthermore, these Th cell clones mediate lysis of the astrocytes in vitro in a Fas-dependent mechanism. TUNEL staining of CNS tissue demonstrates the presence of apoptotic GFAP+ cells in the white matter of TMEV-infected mice. These results strongly suggest that astrocytes could play an important role in the pathogenesis of TMEV-induced demyelination by activating T cells, subsequently leading to T cell-mediated apoptosis of astrocytes and thereby compromising the blood-brain barrier.

Amino Acid Sequence↗
PubMed1999

p53 gene mutations in neoplastic transformation of C3H 10T1/2 and severe combined immunodeficiency fibroblasts.

The relevance of p53 mutations to the neoplastic malignant transformation of rodent fibroblasts by genotoxic physical and chemical agents is not clear. In the present study, we investigated p53 mutations (in exons 5-8) in non-transformed and neoplastically transformed C3H 10T1/2 and severe combined immunodeficiency (SCID) cells. No p53 mutations were detected in 15 neoplastically transformed (two spontaneous, one 3-methylcholanthrene-induced, seven gamma-ray-induced and five 'hot particle'-induced) and two non-transformed 10T1/2 cells. Wild-type p53 gene was also detected in all non-transformed (immortalized) SCID cell lines analyzed (four lines) whereas all three neoplastically transformed (two spontaneous, one gamma-ray-induced) cell lines displayed missense mutations in the p53 gene. These mutations were all transitions: A > G in codon 123, G > A in codon 152, and C > T in codon 238. We conclude that mutation in the p53 gene appears to be an infrequent event in 10T1/2 cells regardless of the transforming agent, but a frequent event in the neoplastic transformation of immortalized SCID cells. Non-transformed SCID cells are deficient in repair of DNA double-strand breaks, and neoplastically transformed cells are assumed to be deficient as well.

Animals↗
PubMed1999

Gene therapy--phase I trial for primary untreated head and neck squamous cell cancer (HNSCC) UICC stage II-IV with a single intratumoral injection of hIL-2 plasmids formulated in DOTMA/Chol.

Recombinant IL-2 protein has shown many immunostimulatory effects in a variety of human tumors. However, the clinical use of rIL-2 is limited by common and serious side effects after systemic administration. IL-2 expression plasmids may circumvent these drawbacks, producing high local IL-2 concentrations that cause limited or no systemic side effects. Due to the superficial growth of squamous cell carcinoma of the head and neck (HNSCC) are readily accessible for direct intratumoral injection and therefore an optimal target for such a gene therapy approach. There has been evidence for local and systemic activation of immune cells by peritumoral injections of IL-2 in patients with advanced HNSCC (Whiteside et al. 1993; Cortesina et al. 1994; De Stefani et al. 1996). We now perform a placebo-controlled, dose-rising study of the safety and tolerability of a single intratumoral injection of hIL-2 plasmid at four dose levels formulated in DOTMA/Chol in patients with primary untreated head and neck squamous cell cancer (HNSCC) TNM stage II-IV. The patients will be monitored for the occurrence of any adverse reactions to the given medication. In addition, we will determine whether the intratumoral administration of the plasmid induces and or enhances tumor-specific host responses at the immunological and or clinical level.

Carcinoma, Squamous Cell↗
PubMed1999

Impairment of T-cell activation in head and neck cancer in situ and in vitro: strategies for an immune restoration.

BACKGROUND: The rationale for the study was based on the hypothesis that decreased or absent expression on tumor cells of adhesion molecules, the class I or class II major histocompatibility complex (MHC) molecules, or costimulatory molecules might be responsible, in part, for the poor ability of squamous cell carcinoma of the head and neck (SCCHN) to induce generation of antitumor effector cells in vitro and in vivo. OBJECTIVE: To investigate expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function associated antigen-3 (LFA-3) and distribution of the costimulatory molecules, B7.1, B7.2, and CD40, and of class I and class II MHC molecules on SCCHN cells in situ and on SCCHN cell lines. SETTING: University medical centers. DESIGN: Expression of ICAM-1, LFA-3, MHC molecules, B7.1, B7.2, and CD40 was evaluated in human SCCHN biopsy specimens by immunohistochemistry and on SCCHN cell lines by flow cytometry. To confirm our hypothesis that impaired T-cell activation observed in patients with SCCHN is caused by the absence of costimulatory B7 molecules, a B7-negative SCCHN cell line was transduced with the B7.1 gene, using a retroviral vector, and tested in mixed lymphocyte tumor cocultures. RESULTS: In contrast to abundant expression of ICAM-1, LFA-3, class I MHC molecules, and CD40, the absence of B7.1, B7.2, and class II MHC molecules on tumor cells was observed in situ and in vitro. Lymphocytes and antigen-presenting cells in inflammatory infiltrates surrounding tumor cell clusters expressed both costimulatory and adhesion molecules. The SCCHN lines negative for B7.1 and class II MHC antigens failed to induce proliferation of T cells in mixed lymphocyte tumor cocultures. However, when these cell lines were transduced with the B7.1 gene, their ability to induce T-cell proliferation in mixed lymphocyte tumor cocultures was restored. CONCLUSIONS: The absence of B7 protein or class II MHC antigen expression on human SCCHN cells is responsible for the failure of these tumors to induce proliferation of T cells in vitro. Transduction of the B7.1 gene into SCCHN restores the ability of the tumor to induce T-cell proliferation in vitro.

Adult↗
PubMed1999

Rhamnose lipids--biosynthesis, microbial production and application potential.

Biosurfactants containing rhamnose and beta-hydroxydecanoic acid and called rhamnolipids are reviewed with respect to microbial producers, their physiological role, biosynthesis and genetics, and especially their microbial overproduction, physicochemical properties and potential applications. With Pseudomonas species, more than 100 g l-1 rhamnolipids were produced from 160 g l-1 soybean oil at a volumetric productivity of 0.4 g l-1 h-1. The individual rhamnolipids are able to lower the surface tension of water from 72 mN m-1 to 25-30 mN m-1 at concentrations of 10-200 mg l-1. After initial testing, rhamnolipids seem to have potential applications in combating marine oil pollution, removing oil from sand and in combating zoosporic phytopathogens. Rhamnolipids are also a source of L-rhamnose, which is already used for the industrial production of high-quality flavor components.

Alkanes↗
PubMed1999

Transforming growth factor-beta type II receptor confers tumor suppressor activity in murine renal carcinoma (Renca) cells.

OBJECTIVES: To demonstrate that the introduction of the transforming growth factor-beta (TGF-beta) type II receptor (TbetaR-II) decreases tumorigenicity in an aggressive murine renal carcinoma line, Renca. These cells do not express TbetaR-II. Because the presence of TbetaR-II in benign epithelial cells is ubiquitous, the ability to restore tumor suppressor activity in the Renca cell line with its introduction would elucidate the role of TbetaR-II as a tumor suppressor gene. METHODS: Renca cells were stably transfected with a retrovirus-mediated TbetaR-II expression vector. In vitro sensitivity to growth inhibitory effect of TGF-beta was assessed by the 3H-thymidine incorporation assay. For in vivo testing, xenograft tumors were produced by subcutaneous injection of tumor cells into immunodeficient nude mice. The tumorigenicity of these TbetaR-II transfected cells was tested. Wild-type Renca cells and cells transfected with the control vector were also tested for comparison. RESULTS: Expression of TbetaR-II mRNA was evident in Renca cells after transfection with the TbetaR-II construct. In vitro sensitivity to the growth inhibitory effect of TGF-beta was restored. This effect of TGF-beta was reversible with a neutralizing antibody specific for the extracellular domain of TbetaR-II. Xenografts grown from TbetaR-II transfected cells were significantly smaller, weighed less, and developed tumors later than those developed from wild-type Renca cells and those transfected with the control vector. CONCLUSIONS: We conclude that TbetaR-II is a central mediator of tumorigenicity in Renca cells. As with other tumor suppressor genes, the loss of TbetaR-II expression allows for the development of an aggressive phenotype.

Animals↗
PubMed1999

Modulation of EphA receptor function by coexpressed ephrinA ligands on retinal ganglion cell axons.

The Eph family is thought to exert its function through the complementary expression of receptors and ligands. Here, we show that EphA receptors colocalize on retinal ganglion cell (RGC) axons with EphA ligands, which are expressed in a high-nasal-to-low-temporal pattern. In the stripe assay, only temporal axons are normally sensitive for repellent axon guidance cues of the caudal tectum. However, overexpression of ephrinA ligands on temporal axons abolishes this sensitivity, whereas treatment with PI-PLC both removes ephrinA ligands from retinal axons and induces a striped outgrowth of formerly insensitive nasal axons. In vivo, retinal overexpression of ephrinA2 leads to topographic targeting errors of temporal axons. These data suggest that differential ligand expression on retinal axons is a major determinant of topographic targeting in the retinotectal projection.

Animals↗
PubMed1999

Regulation of mesangial cell proliferation.

Regardless of the source of injury, an imbalance in the control of mesangial cell proliferation appears to play a direct role in the degree of progressive renal injury and glomerulosclerosis. Some of the regulatory mechanisms include specific soluble or non-soluble extracellular factors and a complex array of receptor-mediated signals that control the progression of the cell cycle or cell death. Understanding these regulatory processes could lead to novel therapeutic strategies to alleviate or arrest proliferative glomerular disease.

Adult↗
PubMed1999

The genomic diversity of coagulase-negative staphylococci associated with nosocomial infections.

A total of 117 isolates of coagulase-negative staphylococci (CNS) were collected from patients in three medical centres. They were genotyped by pulsed-field gel electrophoresis (PFGE) following digestion with restriction enzymes SmaI and SstII. The isolates included Staphylococcus epidermidis, S. simulans, S. hominis, S. lugdunensis, S. capitis, S. saprophyticus, S. caprae and S. sciuri. They were collected at random from 82 patients and were associated with infected central venous lines, continuous ambulatory peritoneal dialysis (CAPD) catheters, endocarditis, osteomyelitis of prosthetic hips and internally fixed fractures. The genetic heterogeneity of the strains was demonstrated by PFGE profiles and two dendrograms. Though the strains were segregated into species, there was no clustering of the strains by type of infection, associated medical unit or geographical location of the patient. Numerous genotypes were identified, suggesting that no specific strains of CNS are associated with prosthetic related infection.

Analysis of Variance↗
PubMed1999

[Induction of antitumor immune response in the mouse model after vaccination with B7.1 expressing tumor cells].

The aim of the study was the induction of an antitumor immune response by genetic modification of tumor cells. This was done by transfecting the costimulatory molecule B7.1 into a murine tumor cell line SCCVII/SF in order to increase T cell recognition and to install an immunologic memory. One cohort of immunocompetent mice C3 H/HeN were injected with B7.1 expressing tumor cells, while the control group received parental B7.1 negative tumor cells. In a second step those immunized mice were rechallenged by parental tumor cells and tumor growth was compared to a new control group. Transfection with B7.1 prohibits outgrowth of the SCCVII cell line. Animals that have been vaccinated in this way are partially immune towards a secondary exposition to B7.1 negative tumor cells. Outgrowth of this recurrent tumor is slowed down. Such an immunization builds up an immunologic memory. Vaccination with B7.1 expressing tumor cells lead to a partial protective tumor immunity in the SCCVII-C3 H/HeN mouse model.

Animals↗
PubMed1999

Neuromucosal prelaminated flaps for reconstruction of intraoral lining defects after radical tumor resection.

To reconstruct intraoral lining defects after radical tumor resection by reinnervated vascularized mucosa, eight distal radial forearm flaps and two fibula flaps were prelaminated. Prelamination was performed by exposing the vascularized fascia, onto which the split distal end of a sural graft was fixed. The fascia and the sural nerve graft were covered by device-meshed mucosa or small full-thickness mucosa pieces. These structures again were covered by a Silastic sheet as large as the future flap, and the wound was closed by the elevated skin and subcutaneous tissue. Coverage by a Silastic sheet enabled mucosal spreading on the fascia, and the final flaps were thin, mucus-producing, and larger than the originally inserted mucosa. The 10 neuromucosal prelaminated flaps were harvested together with the inserted sural nerve graft after 8 to 10 weeks. During this time, the patient underwent radiotherapy and chemotherapy. Donor sites were closed directly by the preserved skin and subcutaneous tissue. Intraoral defects were reconstructed successfully by eight neuromucosal prelaminated distal radial forearm flaps and two neuromucosal prelaminated fibula flaps. The sural nerve grafts, inserted between the fascia and the mucosa, were coaptated eight times with the lingual nerve and two times with the inferior alveolar nerve. Intended reinnervation of the mucosa could already be proved clinically and histologically in the first two patients after 11 and 9 months. Preservation of skin and subcutaneous tissue considerably lowered donor-site morbidity. Neuromucosal prelamination enables reconstruction of intraoral lining defects by reinnervated mucus-producing tissue. Reconstruction of other mucosa-lined structures by this method seems feasible. Avoidance of skin islands for reconstruction lowers donor-site morbidity.

Adult↗
PubMed1999

Aneurysmal bone cyst. A population based epidemiologic study and literature review.

Aneurysmal bone cyst is a rare nonneoplastic expansile osteolytic bone lesion of unknown etiology. To the best of the authors' knowledge, no epidemiologic study concerning its incidence has been reported. The authors performed a retrospective, population based analysis of 94 patients with primary aneurysmal bone cyst and a literature review of 1002 patients regarding gender and age predilection. The annual incidence of primary aneurysmal bone cyst was 0.14 per 10(5) individuals. The male to female ratio was 1:1.04, and the median age was 13 years (range, 1-59 years). The results of this study and data compiled from the literature show that aneurysmal bone cysts occur significantly more often in female patients.

Adolescent↗
PubMed1999

The neoplastic transformation of SCID cells by radiation.

Severe combined immunodeficiency (SCID) cells are hypersensitive to killing by ionizing radiation because of deregulation of DNA-dependent protein kinase (DNA-PK) and a concomitant deficiency in the repair of DNA double-strand breaks. The effect of this condition on the neoplastic transformation of SCID fibroblasts, designated SCID 3T1, has been investigated. The spontaneous transformation rate was approximately 2 x 10(-5) at early passages and increased up to approximately 7 x l0(-3) at later passages. The radiation survival curves of transformed cells had thresholds and therefore appeared to be qualitatively similar to the survival curves of C3H 10T(1/2) mouse fibroblast cells, but the initial slopes were steeper. In contrast, per unit dose, SCID cells were more sensitive to transformation than 10T(1/2) cells. Eight transformed clones were tested for tumorigenicity, and all produced fibrosarcomas in athymic nude mice. Properties associated with the tumor suppressor Trp53 (formerly known as p53) were examined in three of the clones. In these clones, although Trp53 protein was overexpressed, a lower expression of Cdkn1a (formerly known as p21, Cip1) protein was observed compared to parental cells. The expression of Trp53 and Cdkn1a and the G(1)-phase arrest (one set of data on G(1)-phase delay is included as an example) was not induced by ionizing radiation in these transformed clones; each clone carried a point mutation in Trp53. This suggests that the deficiency in the repair of DNA double-strand breaks increased the tumorigenicity and the genomic instability of transformed SCID cells.

Animals↗