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Biomedical subjects

O Gross

Publications and source records attributed to O Gross.

17 recordsLinked to original sources
PubMed2006

Multipotent mesenchymal stem cells reduce interstitial fibrosis but do not delay progression of chronic kidney disease in collagen4A3-deficient mice.

Multipotent mesenchymal stem or stromal cells (MSC) have shown to improve outcome of acute renal injury models, but whether MSC can delay renal failure in chronic kidney disease is not known. We injected primary MSC or saline into mice that lack the alpha3-chain of type IV collagen (COL4A3), a model of chronic kidney disease with close similarities to human Alport disease. Weekly injections of MSC from week 6 to 10 of life prevented the loss of peritubular capillaries and reduced markers of renal fibrosis, that is, interstitial volume, numbers of smooth muscle actin-positive interstitial cells, and interstitial collagen deposits as compared to saline-injected COL4A3-deficient mice. However, renal function, that is, blood urea nitrogen, creatinine levels, proteinuria as well as survival of COL4A3-deficient mice were not affected by MSC injections. Although MSC were found to localize to kidneys of COL4A3-deficient mice after injection, differentiation into renal cells was not detected. However, MSC expressed growth factors, that is, vascular endothelial growth factor (VEGF) and bone morphogenetic protein-7 under basal culture conditions. In fact, VEGF mRNA levels were increased in kidneys of MSC-injected COL4A3-deficient mice and MSC supernatants enhance endothelial cell proliferation in vitro. Thus, weekly injections with MSC prevent loss of peritubular capillaries possibly owing to local production of growth factors rather than by differentiation into renal cells. The maintenance of interstitial vasculature is associated with less interstitial fibrosis but, is insufficient to delay renal failure and survival of COL4A3-deficient mice.

Animals↗
PubMed2001

Regulation of mesangial cell function by vasodilatory signaling molecules.

Proliferation of mesangial cells and expansion of mesangial matrix is a hallmark of glomerular disease leading to end-stage renal failure and requiring renal replacement therapy. Independently from the type of injury, e.g. in glomerulonephritis or diabetic nephropathy, the response to injury is remarkably uniform. Chronic glomerular disease is frequently associated with increases in systemic blood pressure and altered intraglomerular hemodynamics. Furthermore, reduction of systemic blood pressure and inhibition of the vasoconstrictor peptide angiotensin II have been shown to delay end-stage renal failure in various types of human kidney disease. Since vasoconstrictors of mesangial cells and efferent glomerular arterioli, such as angiotensin II, are thought to be detrimental for the progression of chronic glomerular disease, we propose that vasodilatory factors which antagonize the effects of angiotensin II, might have beneficial effects during the course of progressive kidney disease. To support this concept we will summarize currently available data on the role of vasodilatory signaling molecules such as natriuretic peptides (ANP, BNP and CNP), nitric oxide (NO), the prostaglandines PGE2 and prostacycline, and the purine mediator adenosine in the regulation of mesangial function.

Adenosine↗
PubMed2000

Expression of the insect parvovirus GmDNV in vivo: the structural and nonstructural proteins are encoded by opposite DNA strands.

The nucleotide sequence of GmDNV, an insect parvovirus, reveals large open reading frames (ORFs) on both strands of the viral replicative form DNA. Previously, we identified two viral transcripts within the polyadenylated RNA fraction of infected host larvae (Gross et al., 1990, J. Invertebr. Pathol. 56, 175-180). In this work we used hybridization of single-stranded, unidirectional probes to RNA blots to show that the two transcripts, synthesized in vivo in GmDNV-infected Galleria mellonella larvae, are of antiparallel orientation. To determine their coding specificities, polyadenylated RNAs were isolated from hybrids with DNA from the left and right halves of the viral genome and translated in a rabbit reticulocyte system. The "right," 2.4-kb hybrid-selected RNA was shown to direct the synthesis of four polypeptides that comigrated with the four viral capsid proteins and were immunoprecipitated with anti-GmDNV serum. Translation of the "left," 1.8-kb RNA yielded three polypeptides, none of which was detected among the viral capsid proteins. This type of expression strategy is unique among vertebrate and most invertebrate parvoviruses, which use only one DNA strand to encode all their proteins. On the other hand, the basic organization of parvoviruses, in which the regulatory and structural proteins are encoded, respectively, by two clusters of ORFs located at the left and right halves of the genome, is conserved.

Animals↗
PubMed2000

Sporadic case of X-chromosomal Alport syndrome in a consanguineous family.

Alport syndrome (AS) is a genetic disorder of basement membranes caused by mutations in type IV collagen genes that is characterized by chronic hematuria and progressive nephropathy leading to renal failure. The main extrarenal features include sensorineural hearing loss and ocular lesions. The mode of inheritance is X-linked dominant in about 80%-85% of the affected families, whereas autosomal transmission is rarely encountered. We report a male patient originating from a healthy consanguineous Lebanese family who presented with an unusual association of obstructive uropathy and AS. Hematuria and proteinuria were initially attributed to a suspected poststreptococcal glomerulonephritis (GN) and high-grade subpelvic ureteral stenosis. Persistence of symptoms after medical treatment of poststreptococcal GN and surgical correction of obstructive uropathy finally led to renal biopsy. The observed ultrastructural changes of the glomerular basement membrane were typical for AS. Molecular genetic studies revealed a previously undescribed de novo mutation in the COL4A5 gene, excluding maternal heterozygotic carrier status. This case report emphasizes the importance of hereditary nephritis in the differential diagnosis of chronic hematuria, and demonstrates the value of molecular studies for genetic counselling in AS.

Basement Membrane↗
PubMed1998

Therapeutic options for critically ill patients suffering from progressive lupus nephritis or Goodpasture's syndrome.

Systemic lupus erythematosus is a chronic disease with many clinical features, while Goodpasture's syndrome usually becomes manifest with progressive glomerulonephritis and pulmonary hemorrhage. Rapidly declining renal function and even pulmonary hemorrhage may be the common feature. Early and precise diagnosis is most important as it may provide general prognostic information and serve as a guideline for initial therapy. Immunosuppression with oral cyclophosphamide and high dose corticosteroids together with plasmapheresis is used in Goodpasture's syndrome. Progressive lupus nephritis requires high dose corticosteroids together with i.v. pulses of cyclophosphamide for at least six months, followed by maintenance immunosuppression. The benefits of therapy must always be weighed against the risks. Nevertheless, current therapy remains less than optimal. A better understanding of the pathogenesis of systemic lupus erythrematosis (SLE) and Goodpasture's syndrome may provide more specific information about the nature and the role of the immune response and thus lead to new treatment strategies.

Anti-Glomerular Basement Membrane Disease↗
PubMed1997

The influence of surface loading and irradiation time during curing on mechanical properties of a composite.

PURPOSE: The aim of this study was to determine the influence of different surface loadings during curing with various irradiation times on hardness and diametral tensile strength of a light-cured composite. MATERIAL AND METHODS: A mold was fabricated to allow loading during curing of cylindrical specimens of a composite. Four surface loadings of 0, 0.35, 0.87, and 1.73 MPa and four irradiation times of 20, 40, 60, and 180 seconds were used (n = 15). Each specimen was subjected to a microhardness test and to a diametral tensile strength test. RESULTS: Surface loading during curing affected both hardness and strength properties, whereas irradiation time influenced only the hardness of the material. Both parameters gained between 15% and 20% improvement when the material was loaded with 0.87 MPa surface pressure and cured by 60-second irradiation time. Higher loading or longer irradiation times did not improve these properties. CONCLUSION: Loading composite during curing improves its mechanical properties, probably through decreasing flaws and air voids of the material.

Air↗
PubMed1996

Cell cycle defect in connection with oxygen and iron sensitivity in Fanconi anemia lymphoblastoid cells.

Fanconi anemia (FA) is an autosomal recessive disorder involving progressive pancytopenia, skeletal malformations, and a predisposition to leukemia. The in vitro growth of FA fibroblasts is impaired, due to a defective G2 phase traverse of the cell cycle. Analyzing the cell cycle of lymphoid cell lines (LCLs) obtained from peripheral blood of FA patients by transformation with Epstein-Barr virus, we found a similar G2 phase defect, which was dependent upon the oxygen concentration. In addition, FA cells exhibited hypersensitivity toward cis-dichlorodiammineplatinum and mitomycin C, and moderate sensitivity toward trans-dichlorodiammineplatinum. FA cells, however, showed no elevated sensitivity toward paraquat, an intracellular generator of superoxide radicals, or cumene hydroperoxide, a model organic peroxide. Chelating iron with low concentrations of o-phenanthrolin improved cell proliferation and G2 phase transit of FA cells at 20% oxygen, but little at 5% oxygen. LCL cultures from healthy subjects were inhibited in their proliferation rate at all concentrations of o-phenanthrolin. Exposure to excess iron, on the other hand, was very toxic to FA cells at 20%, but less toxic at 5% oxygen. In conclusion, the FA mutation leads to a cell cycle defect, which is expressed in cultures of lymphoid cells from FA patients, and involves hypersensitivity toward bifunctional alkylating agents, oxygen, and iron.

Alkylating Agents↗
PubMed1990

Expression of densonucleosis virus GmDNV in Galleria mellonella larvae: size analysis and in vitro translation of viral transcription products.

The RNA of densonucleosis virus type 1 (GmDNV), isolated from GmDNV-infected Galleria mellonella larvae, was shown by Northern blotting to contain five polyadenylated, viral-specific RNA species with sizes of 1.8, 2.4, 3.5, 4.0, and 5.0 kb. Poly(A)-containing RNA from whole larvae and hybrid-selected viral RNA were translated in a rabbit reticulocyte lysate system and the translation products were coelectrophoresed with proteins extracted from CsCl-purified virus. All four virion-associated proteins, namely p49, p55, p65, and p94, were present in the in vitro-translated products. However, in the majority of the experiments the most abundant translation product was a 30K polypeptide which is absent from virion extracts. The most abundant viral protein is p49, and the 49K polypeptide was also the most abundant translation product in about 30% of the preparations. The 1.8 kb transcript, which constitutes about half of the total viral RNA, is only slightly larger than the template required for a 30K polypeptide, suggesting that the latter may be a primary translation product of the smallest RNA transcript. The similarities in gene expression between densoviruses and mam malian parvoviruses are discussed.

Animals↗
PubMed1990

Cytokine secretion effected by synergism of the immunomodulator AS101 and the protein kinase C inducer bryostatin.

AS101, a synthetic organotellurium compound, was found to have immunomodulating properties by initiation of cytokine production in vitro and in vivo. Phase I/II clinical trials currently in progress on AIDS and cancer patients treated with AS101 show significant increases in various immunological parameters, with minimal toxicity. Recently, AS101 and the protein kinase C (PKC) inducer, phorbol myristate acetate (PMA), were shown to synergize in the secretion of interleukin-2 (IL-2) and colony-stimulating factor (CSF) in vitro, by human and mouse lymphoid cells. The bryostatins, a group of natural macrocyclic lactones isolated from marine invertebrates (Bugula neritina) have been reported to be potent PKC activators with no tumour promoting activity. In this study, we investigated the synergistic effect of AS101 and a partially purified preparation of bryostatin on the production of several cytokines. Our data confirm the presence of synergism, which greatly enhances cell proliferation, IL-2, tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma) secretion by human mononuclear cells (MNC) and the production of IL-2 and TNF by mouse cells. The absence of tumour-promoting activity of the bryostatins makes them particularly good candidates, in combination with AS101, for immunomodulation in vivo in clinically immunosuppressed conditions.

Adjuvants, Immunologic↗
PubMed1978

[Blood cholinesterase and hepatic function: a comparison with BSP and galactose elimination as well as serum albumin concentration].

Although quantitative tests of some hepatic functions have been well established, the determination of serum cholinesterase activity continues to be commonly used in their stead. A critical comparison of the serum cholinesterase activity with these quantitative tests, however, is still lacking. Serum cholinesterase activity was therefore simultaneously compared with galactose elimination capacity (GEC), initial BSP-disappearance rate (BSP-ki), and serum albumin levels in 19 healthy control subjects and 46 patients with various chronic liver diseases. Serum cholinesterase activity was less discriminating between controls and patients than BSP-ki. It appears poorly suited, therefore, as a screening test for mild liver disease. Rank correlations between serum cholinesterase activity and GEC, BSP-ki, and serum albumin were statistically higher significant (r = 0.65, r = 0.74, and r = 0.80 respectively). On a statistical basis, serum cholinesterase activity may, therefore, be regarded as an index of the functional reserve of the liver. Evaluation of individual cases, however, revealed some clinically relevant discrepancies. It is concluded, therefore, that for accurate follow-up studies measurements of serum cholinesterase activity may be insufficient substitutes for the quantitative tests.

Adult↗