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Biomedical subjects

R Gruber

Publications and source records attributed to R Gruber.

At least 19 recordsLinked to original sources

[Feasibility of fetal echocardiography at 11-14 weeks scan].

PURPOSE: Sonographic diagnostics are increasingly brought forward into the first trimenon. Lately, more and more expert studies have been published on echocardiography in the context of the Nuchal Translucency (NT) screening (gestational age 11-14 weeks). The aim of this study has been to evaluate the feasibility of early echocardiography on the occasion of first trimenon screening in the context of routine operation. MATERIALS AND METHODS: From February 2003 to March 2004, an echocardiography was prospectively sought in 130 assigned, unselected pregnant women during the first trimenon screening. Three doctors with different OGUM/DEGUM (Austrian and German societies for ultrasound in medicine) qualifications at our ward tried to represent the four-chamber view (4CV) and the outflow tracts (OFT), each via B-mode and color Doppler. The study conditions were "routine", in particular they were temporally limited. In case no sufficient visual representation was achievable with the transabdominal examination, transvaginal sonography was also used. RESULTS: Via B-mode, 4CV was indicated as successful in 86/130, and OFTs in 37/130. Via color Doppler, on the other hand, it was possible to sufficiently represent 4CV in 75/130 and OFTs in 87/130. CONCLUSION: In routine screening, early heart examination is a big challenge and in many cases even with good equipment no complete diagnostic echocardiography can be achieved. The utilisation of the color Doppler is helpful particularly for the representation of the outflow tracts.

Echocardiography↗

Platelet content and growth factor release in platelet-rich plasma: a comparison of four different systems.

BACKGROUND: Different systems for preparation of platelet-rich plasma are commercially available, but data for comparison of these systems have not been published so far. MATERIALS AND METHODS: We investigated the performance of Vivostat PRF Preparation Kit, PCCS Platelet Concentrate Collection System, Harvest SmartPReP 2 APC 60 Process, and Fibrinet Autologous Fibrin & Platelet System. The preparations provided by these systems are platelet concentrates with high numbers of platelets in a small volume of plasma and PDGF-AB is released continuously during the 5 days after preparation. RESULTS: Vivostat PRF Preparation Kit, PCCS Platelet Concentrate Collection System, Harvest SmartPReP 2 APC 60 Process are comparable in platelet yield and total amount of released PDGF-AB after 120 h while with Fibrinet the lowest platelet yield and PDGF-AB content of supernatant was achieved. The ability of growth factor release was equal in all four systems. CONCLUSION: In conclusion, all four systems for preparation of platelet-rich plasma investigated result in considerable growth factor release. In what extent the total content of PDGF-AB as a consequence of platelet yield has an impact on wound healing has to be further investigated.

Blood Platelets↗

Serum antibodies in first-degree relatives of patients with IBD: a marker of disease susceptibility? A follow-up pilot-study after 7 years.

INTRODUCTION: Various disease-specific serum antibodies were described in patients with inflammatory bowel disease and their yet healthy first-degree relatives. In the latter, serum antibodies are commonly regarded as potential markers of disease susceptibility. The present long-term follow-up study evaluated the fate of antibody-positive first-degree relatives. PATIENTS AND METHODS: 25 patients with Crohn's disease, 19 patients with ulcerative colitis and 102 first-degree relatives in whom presence of ASCA, pANCA, pancreatic- and goblet-cell antibodies had been assessed were enrolled. The number of incident cases with inflammatory bowel disease was compared between antibody-positive and antibody-negative first-degree relatives 7 years after storage of serum samples. RESULTS: 34 of 102 (33%) first-degree relatives were positive for at least one of the studied serum antibodies. In the group of first-degree relatives, one case of Crohn's disease and one case of ulcerative colitis were diagnosed during the follow-up period. However, both relatives did not display any of the investigated serum antibodies (p=1). DISCUSSION: The findings of our pilot study argue against a role of serum antibodies as a marker of disease susceptibility in first-degree relatives of patients with inflammatory bowel disease. However, these data have to await confirmation in larger ideally prospective multicenter studies before definite conclusions can be drawn.

Adult↗

[Could it be an immune defect? Background and diagnosis].

With modern immunological and molecular biological laboratory techniques, some 100 primary immunodeficiencies can now be diagnosed and differentiated. The importance of diagnosing a primary immunodeficiency (PID) as early as possible cannot be overemphasized. In patients with PID, recurrent infections can lead to permanent damage and sometimes even to death. On the occasion of a first visit to the physician, the patient usually presents with nonspecific symptoms, in particular recurrent infections, a challenging situation in terms of making the correct diagnosis. Relevant warning signals and a possible family history should also prompt at least such simple laboratory tests as a blood differential and the quantitative determination of immunoglobulins, followed where necessary by more specific evaluations. Early treatment, for example, with immunoglobulins may enable many patients to lead a virtually normal life, and in some cases bone marrow transplantation or gene therapy may even result in a cure.

Adult↗

[Treatment of primary immune defects].

Management of immunodeficient patients includes monitoring of growth, diet, personal hygiene and life habits, including environmental factors. Major therapeutic stays are prevention, early detection and the decisive treatment of infections. Attenuated live vaccines, non-irradiated blood products and blood containing CMV antibodies should not be applied. In the case of antibody defects immunoglobulin substitution is a specific form of treatment. Enzyme replacement is a causal approach to an adenosine deaminase defect. For numerous primary immune defects, bone marrow transplantation represents the best causal therapeutic measure. In the absence of a bone marrow donor, alternative gene therapy is available for the management of severe combined immunodeficiency on the X-chromosome (X-SCID), and adenosine deaminase deficiency (ADA deficiency).

Adult↗

Piezoelectric bone surgery: a revolutionary technique for minimally invasive surgery in cranial base and spinal surgery? Technical note.

OBJECTIVE: Piezoelectric surgery represents an innovative, ultrasonic surgery technique for performing a safe and effective osteotomy or osteoplasty that contrasts with the traditional hard and soft tissue management methods with rotating instruments. METHODS: Because of its physical and mechanical properties, the definitive clinical advantage of piezoelectric bone surgery with regard to precision cutting lies in the sparing of vital neurovascular bundles or general soft tissue and better visualization of the surgical field, thus suggesting its great safety. Piezoelectric bone surgery has been previously described only in oral and maxillofacial operative procedures in adults. RESULTS: Five children between the age of 6 and 84 months were operated on for craniosynostosis, tethered cord, and an extraconal intraorbital tumor. The usefulness of piezoelectric bone surgery during neurosurgical procedures is presented for these cases. This technique is especially recommended when there are anatomic difficulties because of poor intraoperative visibility or the presence of delicate anatomic structures. CONCLUSION: The present preliminary report (comprising illustrative case reports) demonstrates and introduces for the first time the utility of piezoelectric bone surgery in cranial base and spinal surgery in children. Until now, there has been no documented neurosurgical experience of this technique even in adults.

Craniosynostoses↗

Inflammatory bowel disease-specific autoantibodies in HLA-B27-associated spondyloarthropathies: increased prevalence of ASCA and pANCA.

AIMS: An association between inflammatory bowel disease (IBD) and spondyloarthropathies (SpA) has repeatedly been reported. The aim of the present study was to investigate whether serologic markers of IBD, e.g. antibodies against Saccharomyces cerevisiae (ASCA), antibodies against exocrine pancreas (PAB) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) are present in HLA-B27-associated SpA. METHODS: 87 patients with HLA-B27-positive SpA and 145 controls were tested for ASCA, PAB and pANCA employing ELISA or indirect immunofluorescence, respectively. Antibody-positive patients were interviewed regarding IBD-related symptoms using a standardized questionnaire. RESULTS/CONCLUSION: When compared to the controls, ASCA IgA but not ASCA IgG levels were significantly increased in patients with SpA, in particular in ankylosing spondylitis (AS) and undifferentiated SpA (uSpA). pANCA were found in increased frequency in patients with SpA whereas PAB were not detected. The existence of autoantibodies was not associated with gastrointestinal symptoms but sustains the presence of a pathophysiological link between bowel inflammation and SpA.

Adolescent↗

Repair of calvarial defects in rats by prefabricated hydroxyapatite cement implants.

The aim of the present study was to test the hypothesis that calvarial defects can be repaired by using preformed implants of calcium phosphate bone cement (CPBC) in rats. Sixty adult female Sprague-Dawley rats received full-thickness calvarial nonhealing defects with a diameter of 8 mm. Three different CPBCs were used: group 1: tetracalcium phosphate-based powder; group 2: a blend of amorphous and crystalline calcium phosphate precursors; and group 3: an alpha-tricalcium phosphate (alpha-TCP)-based powder. Implants were left to cure for 25-40 min at room temperature in a silicon mold of 7.9 mm and inserted press fit into the defects. Fifteen animals served as unfilled controls. After 13, 26, and 52 weeks, the material was analyzed qualitatively by using surface-stained undecalcified thick-section specimens and quantitatively by using semiautomated histometry. Kruskal-Wallis tests were applied to compare mean values of periimplant bone formation at a significance level of p < 0.05. Three implants of group 1 fractured during insertion. Resorption of CPBC without complementary bone formation was noticed in these implants. Unfractured implants were resorbed with simultaneous apposition of bone on the implant surface. After 52 weeks, the resorption rate varied between 23.1 and 39.3%. Periimplant bone formation increased continuously on average around all implant types, but it reached statistical significance only in group 2. The results showed that repair of calvarial defects can be achieved by preformed CPBC implants. The rate of resorption of preformed implants is, however, much lower than that reported for in vivo cured CPBC.

Animals↗

Proliferation of dental pulp fibroblasts in response to thrombin involves mitogen-activated protein kinase signalling.

AIM: To examine the involvement of mitogen-activated protein kinases (MAPK) signalling on thrombin-stimulated human dental pulp fibroblasts (DPF). METHODOLOGY: Dental pulp fibroblasts were isolated from dental pulp connective tissue of third molars and expanded in vitro. Expression of thrombin receptors was analysed by RT-PCR, and cell proliferation was measured by 3[H]-thymidine incorporation assay. Phosphorylation levels of MAPK were determined by Western blot analysis, and alkaline phosphatase activity was measured to serve as a marker for odontogenic differentiation. Statistical analysis was performed by Student's t-test. RESULTS: Dental pulp fibroblasts express the thrombin receptors protease-activated receptor-1 (PAR-1), PAR-3 and PAR-4. Measurement of 3[H]-thymidine incorporation revealed a dose-dependent increase of DNA synthesis in response to thrombin treatment. The thrombin-induced mitogenic activity was decreased by the extracellular signal-regulated protein kinase (ERK) signalling inhibitor PD98059 (P < 0.05), and by SB203580 (P < 0.05), a p38 MAPK inhibitor. Western blot analysis demonstrated increased phosphorylation of ERK in DPF following stimulation with thrombin, while p38 MAPK and c-Jun NH2-terminal kinase (JNK) were not activated. Alkaline phosphatase activity of DPF remained unchanged upon incubation with thrombin. CONCLUSIONS: These results suggest that signalling via MAPK mediates the mitogenic activity of thrombin on DPF and may thus play a role during the early stages of pulp repair.

Adult↗

Dental pulp fibroblasts contain target cells for lysophosphatidic Acid.

Lysophosphatidic acid (LPA) is a locally produced bioactive phospholipid which is involved in tissue repair. The objective of this study was to determine whether dental pulp tissue also responds to the phospholipid. Effects of LPA on proliferation, differentiation, and mitogen-activated protein kinase (MAPK) signaling of dental pulp fibroblasts (DPF) were examined in vitro. We report that DPF express LPA receptors LPA1, LPA2, and LPA3 and respond to the ligand with increased mitogenic activity. Involvement of extracellular signal-regulated kinase, p38 MAPK, and c-Jun NH(2)-terminal kinase in LPA signaling could be demonstrated by use of specific inhibitors and detection of the phosphorylation status of the kinases. An increased mitogenic activity paralleled a decreased number of alkaline-phosphatase-positive cells and expression levels of dentin sialophosphoprotein and osteocalcin. Together, these results suggest that dental pulp fibroblasts can respond to LPA, a process that may play a role in pulp tissue repair.

Adult↗

Expression of bone morphogenetic protein 6 in healthy and osteoarthritic human articular chondrocytes and stimulation of matrix synthesis in vitro.

OBJECTIVE: To elucidate the role of bone morphogenetic protein 6 (BMP-6) in human articular cartilage, we investigated whether BMP-6 is expressed in adult human articular chondrocytes and analyzed the potential stimulatory effects of BMP-6 on these cells. In addition, we investigated whether osteoarthritic (OA) and normal cartilage chondrocytes behave differently. METHODS: Endogenous expression of the BMP-6 gene was examined by reverse transcription-polymerase chain reaction. BMP-6 protein was detected by Western immunoblotting. Chondrocytes were grown as monolayer cultures for 7 days in a chemically defined serum-free medium, in the absence or presence of recombinant BMP-6. Proteoglycan (PG) synthesis was measured by (35)S-sulfate incorporation into newly synthesized macromolecules. Cell proliferation was assessed by (3)H-thymidine incorporation. RESULTS: BMP-6 was expressed in both healthy and OA chondrocytes at the messenger RNA and protein levels. Total PG synthesis was significantly increased after BMP-6 stimulation of healthy (mean +/- SEM 191 +/- 11%; P < 0.001) and OA (150 +/- 25%; P < 0.03) chondrocyte cultures. A direct comparison between healthy and OA samples revealed no significant difference. The proliferation rates of normal and OA chondrocytes were not affected by BMP-6 treatment. CONCLUSION: BMP-6 is endogenously expressed in chondrocytes obtained from OA and normal adult human articular cartilage. Furthermore, BMP-6 has the potential to stimulate total PG synthesis in human articular chondrocytes derived from normal as well as OA joints. We conclude that the presence of BMP-6 in adult human articular cartilage indicates a functional role for this growth factor in the maintenance of joint integrity.

Adult↗

Velocity scaling of ion neutralization in low energy ion scattering.

The ion fraction P+ is measured for He+ ions scattered by 129 degrees from a Cu surface. Both the primary energy and the angles of incidence and of exit are varied. From our results we conclude the following: along the incoming and outgoing trajectories, neutralization is due to Auger processes and depends on the normal velocity component v( perpendicular ) only. At higher energies, additional charge exchange is due to collision induced neutralization and reionization, both depending on the total ion energy only. Also in this regime P+ depends on v( perpendicular ), but via a two-valued function of the scattering geometry at fixed energy.

Journal Article↗

Cartilage-derived morphogenetic protein-1 and -2 are endogenously expressed in healthy and osteoarthritic human articular chondrocytes and stimulate matrix synthesis.

OBJECTIVE: We investigated whether chondrocytes derived from osteoarthritic cartilage may lose their responsiveness to cartilage-derived morphogenetic protein-1, -2 (CDMP-1, -2) and osteogenic protein-1 (OP-1) compared with healthy cells, thus leading to an impaired maintenance of matrix integrity. DESIGN: Chondrocytes were isolated from articular cartilage from patients with and without osteoarthritic lesions. Cells were grown as monolayer cultures for 7 days in a chemically defined serum-free basal medium (BM) in the presence of recombinant CDMP-1, -2, and OP-1. Glycosaminoglycan synthesis was measured by [35S]Sulfate incorporation into newly synthesized macromolecules. Cell proliferation was investigated by [3H]Thymidine incorporation. The endogenous gene expression of CDMPs/OP-1 and their respective type I and type II receptors was examined using RT-PCR. The presence of CDMP proteins in tissue and cultured cells was detected by Western immunoblots. RESULTS: mRNAs coding for CDMPs and their respective receptors are endogenously expressed not only in healthy, but also in osteoarthritic cartilage. CDMP proteins are present in both normal and osteoarthritic articular cartilage and cultured chondrocytes. CDMP-1, CDMP-2 and OP-1 markedly increased glycosaminoglycan synthesis in both healthy (P< 0.01) and osteoarthritic (P< 0.05) human articular chondrocytes. A comparison of the glycosaminoglycan biosynthetic activity between healthy and osteoarthritic samples revealed no detectable difference, neither in stimulated nor in unstimulated cultures. [(3)H]Thymidine incorporation showed that CDMPs/OP-1 did not affect cell proliferation in vitro. CONCLUSION: CDMPs and OP-1 exert their anabolic effects on both healthy and osteoarthritic chondrocytes indicating no loss in responsiveness to these growth factors in OA. The endogenous expression of CDMPs/OP-1 and their receptors suggest an important role in cartilage homeostasis.

Adult↗

Bispecific single-chain antibodies as effective tools for eliminating epithelial cancer cells from human stem cell preparations by redirected cell cytotoxicity.

High-dose chemotherapy (HDC) with autologous bone marrow or peripheral stem cell transplantation is discussed as one option to treat the extensive stage of a variety of tumors. Effective methods to eliminate contaminating tumor cells from human bone marrow or stem cell grafts may improve the outcome of the patients. We investigated 3 recombinant bispecific single-chain antibodies (bscAbs) directed against 17-1A (EpCAM), c-erbB-2 (HER-2/neu) and LeY on the one and CD3 on the other binding site for their ability to induce lysis of epithelial tumor cells by retargeting autochthonous T lymphocytes present in bone marrow mononuclear cells (BMMC) and in peripheral stem cell mononuclear cells (PSMC). The bscAbs showed remarkable specific lysis of different epithelial tumor cell lines with BMMCs as well as with PSMCs as effector cells. Investigation of the alpha 17-1A-alpha CD3 bscAb revealed a significant correlation between the percentage of CD3(+) cells present in the BMMCs and the rate of lysis as well as the absence of detrimental effects on the viability of hematopoietic progenitor cells as determined by colony-forming unit assays (CFUs). Our results indicate that recombinant bispecific single-chain antibodies could be new tools for purging of human bone marrow and peripheral stem cell grafts from contaminating epithelial cancer cells for patients receiving autologous stem cell transplantation after HDC.

Antibodies, Bispecific↗

Anti-self antibodies selected from a human IgD heavy chain repertoire: a novel approach to generate therapeutic human antibodies against tumor-associated differentiation antigens.

Human antibodies were isolated by phage display from a naturally expressed human antibody repertoire. Antibody selection was carried out against the epithelial cell adhesion molecule (EpCAM) or 17-1A antigen, that in a clinical trial had been successfully used as a target for antibody therapy of minimal residual colorectal cancer. VH chains were selected from the human IgD repertoire expressed on naive B2 and autoreactive B1 lymphocytes. By guiding the selection through a murine template antibody, two EpCAM-specific human antibodies, HD69 and HD70, were obtained that closely resembled the murine therapeutic 17-1A antibody in their binding properties when expressed as complete huIgG1 molecules in CHO cells. However, both human antibodies recruited human cytotoxic effector cells far more efficiently than the murine 17-1A antibody used for clinical trials. Therefore, and in view of the long in vivo half-life of human IgG1 antibodies, HD69 and HD70 are regarded as highly promising third generation versions of the murine therapeutic antibody. Because of their origin from an evolutionary conserved germline VH repertoire, they are expected to exhibit minimal immunogenicity in patients.

Amino Acid Sequence↗

Lowering HIV risk among ethnic minority drug users: comparing culturally targeted intervention to a standard intervention.

To test the efficacy of culturally targeted acquired immunodeficiency syndrome (AIDS) prevention programs on ethnic minority street drug users, 669 African-American and Puerto Rican drug users were assigned to receive either the National Institute on Drug Abuse (NIDA) standard intervention or a culturally competent enhanced intervention in a quasi-experimental study. The standard intervention was a two-session educational program, while both the African-American and Puerto Rican enhanced interventions provided additional AIDS information in a culturally appropriate fashion. Although human immunodeficiency virus (HIV) risk behaviors, as measured by Bell's risk indices, decreased, there were no meaningful significant differences between interventions. However, participants who went into drug treatment programs showed greater reduction in HIV risk behavior. Cultural interventions may provide better outcome if they concentrate on getting participants into drug treatment.

Acquired Immunodeficiency Syndrome↗