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Biomedical subjects

P Baron

Publications and source records attributed to P Baron.

At least 19 recordsLinked to original sources
PubMed2006

Successful living related kidney transplantation across an anti-donor HLA antibody.

In preconditioning highly sensitized kidney transplant candidates, renal allograft outcomes have been better when the serum titer for class I anti-HLA donor-specific antibody (DSA) is low in the recipient at the time of transplantation. However, the ideal level to which the titer should be lowered is still controversial. We report a primary living related kidney transplant in a 34-year-old highly sensitized woman (pretransplant panel-reactive antibody=70%) with end-stage renal disease secondary to chronic glomerulonephritis. We sought to desensitize by lowering the DSA titer specifically to 1:4 pretransplant. A standard complement-dependent cytotoxicity cross-match with her donor (sister) was repeatedly negative, although she was positive for class I antibody against her mismatched HLA antigen (A*2402) at a titer up to 1:16 by the single-antigen flowbead assay. The target DSA titer of 1:4 before transplant was achieved by 12 sessions of plasmapheresis (PP) over 7 weeks, plus two intravenous immune globulin infusions (IVIG) (500 mg/kg/infusion). The patient outcome was excellent. Neither IVIG nor PP was needed posttransplant. The serum creatinine ranged between 0.5 mg/dL and 1.2 mg/dL, and no rejection episode was documented at 28 weeks posttransplant. Therefore, we encourage the use of IVIG and PP to lower the DSA titer to at least 1:4 before kidney transplantation in highly sensitized patients. Large prospective trials are needed to establish a consensus for pretransplant risk assignment and to evaluate the need for desensitization.

Adult↗
PubMed2003

[Scoring system for chronic open glaucoma].

PURPOSE: The aim of this study was to evaluate a scoring system for chronic open-angle glaucoma. We devised an empirical scoring system grading severity of the disease and correlated this with treatment. MATERIAL: and methods: Ninety patients were evaluated on 11 parameters: 1) Family history of glaucoma: blindness (2), yes (1) no (1); 2) Age: infantile (4), juvenile (4); 3) Race: Caucasian (0), Asian (1), Afro-Caribbean (2); 4) Myopia: 0-6 diopters (1), 6-12 diopters (2),>12 diopters (3); 5) Pigment dispersion or pseudoexfoliation (1); 6) Intraocular pressure without treatment:>30 mmHg (4); 25-30 mmHg (3), 20-25 mmHg (2); 7) Corneal central thickness:<500 micro m (3),>500 micro m (0); 8) Optic disc appearance: suspect (1), pathological (4); 9) Visual field defect: early (1), moderate (3), advanced (5); 10) Vascular risk factors: yes (1), no (0); 11) Loss of eyesight in one eye due to glaucoma (4). Scoring values were 2-34. We correlated this score with patient treatment: medical or surgical, number of glaucoma medications. RESULTS: Patients were divided into three groups: group 1 (36 patients), score 0-8; group 2 (24 patients), score 9-13; group 3 (30 patients), score above 13. Distribution between patients treated with medicine (mean number of medications) and patients with filtering surgery was: group 1, medical treatment with 1.63+/-0.73 medications, surgery 4/36; group 2, medical treatment with 2.00+/-0.7 medications, surgery 17/24 and group 3, medical treatment with 2.12+/-0.67 medications, surgery 27/30. In group 1, 88% of the patients did not have filtering surgery, but 90% of the patients in group 3 had filtering surgery. CONCLUSION: This scoring system seems to be an easy and practical tool to evaluate chronic open-angle glaucoma, which could also be used to evaluate target pressure. Other studies are necessary to validate this scoring system.

Adolescent↗
PubMed2001

Production of IL-6 by human myoblasts stimulated with Abeta: relevance in the pathogenesis of IBM.

OBJECTIVE: To determine whether amyloid-beta protein (Abeta) can induce the production of proinflammatory cytokines by cultured normal muscle cells. BACKGROUND: Sporadic inclusion body myositis (IBM) is characterized by the presence of rimmed vacuoles and fibrillary inclusions of Abeta in muscle fibers, and often inflammatory cells. Endomysial expression of proinflammatory molecules has suggested an ongoing immune process, but the site of sensitization and the mechanisms that trigger an inflammatory reaction is unknown. METHOD: The authors used Northern blot analysis and specific immunoassays to study the expression and secretion in cell-free supernatants of tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) by purified human myoblasts and C2C12 mouse skeletal muscle cells incubated with Abeta[1-42] or Abeta[25-35] peptides. RESULTS: Nonstimulated muscle cells produced detectable IL-6, whereas secretion of IL-1beta and TNFalpha was absent. Incubation with Abeta peptides increased IL-6 production, whereas TNFalpha and IL-1beta levels remained undetectable. Northern blot analysis of Abeta-stimulated human myoblasts revealed an increase in IL-6 mRNA expression. CONCLUSIONS: Cultured muscle cells increase the constitutive production of IL-6 in response to local deposition of Abeta in sporadic IBM. IL-6 could be a CD8(+) proliferation and differentiation agent, an autocrine proteolysis-inducing factor of damaged myotubes, and a proliferation-stimulating agent for satellite cells to replace the destroyed myofibers in IBM.

Adult↗
PubMed2001

Factors influencing choice between mastectomy and lumpectomy for women in the Carolinas.

BACKGROUND AND OBJECTIVES: The Carolinas have been documented to have a low rate of breast-conserving surgery. The purpose of this study was to determine factors that influence women's choice between mastectomy and lumpectomy. METHODS: An anonymous questionnaire was designed for the study and was mailed to women on the mailing lists of cancer organizations in North and South Carolina. Women who had initially been treated in 1995-1998 were included. RESULTS: The rate of breast-conserving surgery (BCS) was 18% and actually declined from a high of 23% in 1995. The highest rate of BCS was in private hospitals rather than academic health science centers. Fifty-four of the 212 respondents believed they were given a choice between mastectomy and BSC and, of these, only 15% (n = 80) chose BSC. Women in the two treatment groups differed in education and income. Sources of treatment-related information included cancer organizations, popular media, friends, family, and the Internet. The most important factor to both groups was perceived probability of cure. Avoidance of radiation treatments was a factor among the mastectomy group. CONCLUSIONS: The low rate of BCS for the region was confirmed. Many women are still unconvinced that BSC offers as great a likelihood of cure as mastectomy.

Adult↗
PubMed2001

Protein zero is necessary for E-cadherin-mediated adherens junction formation in Schwann cells.

Protein Zero (P0), the major structural protein in the peripheral nervous system (PNS) myelin, acts as a homotypic adhesion molecule and is thought to mediate compaction of adjacent wraps of myelin membrane. E-Cadherin, a calcium-dependent adhesion molecule, is also expressed in myelinating Schwann cells in the PNS and is involved in forming adherens junctions between adjacent loops of membrane at the paranode. To determine the relationship, if any, between P0-mediated and cadherin-mediated adhesion during myelination, we investigated the expression of E-cadherin and its binding partner, beta-catenin, in sciatic nerve of mice lacking P0 (P0(-/-)). We find that in P0(-/-) peripheral myelin neither E-cadherin nor beta-catenin are localized to paranodes, but are instead found in small puncta throughout the Schwann cell. In addition, only occasional, often rudimentary, adherens junctions are formed. Analysis of E-cadherin and beta-catenin expression during nerve development demonstrates that E-cadherin and beta-catenin are localized to the paranodal region after the onset of myelin compaction. Interestingly, axoglial junction formation is normal in P0(-/-) nerve. Taken together, these data demonstrate that P0 is necessary for the formation of adherens junctions but not axoglial junctions in myelinating Schwann cells.

Adherens Junctions↗
PubMed2000

Activation of mitogen-activated protein kinase p38 and extracellular signal-regulated kinase is involved in glass fiber-induced tumor necrosis factor-alpha production in macrophages.

In a previous study, we demonstrated that the length of glass fibers was a critical determinant of fiber potency in induction of tumor necrosis factor (TNF)-alpha and that activation of NF-kappaB was an important factor in this response. In the present study, we analyzed the role of mitogen-activated protein (MAP) kinases in the induction of TNF-alpha by glass fibers. Glass fibers induced phosphorylation of MAP kinases, p38, and ERK in primary rat alveolar macrophages, and this phosphorylation was associated with TNF-alpha gene expression. Long fibers were more potent than short fibers in activation of MAP kinases. Results from mechanistic analysis support that MAP kinases activate transcription factor c-Jun. The activated c-Jun acts on the TNF-alpha gene promoter through two binding sites, the cyclic AMP response element and the activator protein 1-binding site. These results suggest that in addition to the NF-kappaB pathway for TNF-alpha production, glass fibers are able to activate c-Jun through MAP kinase pathways that lead to induction of TNF-alpha expression.

Animals↗
PubMed2000

Absence of P0 leads to the dysregulation of myelin gene expression and myelin morphogenesis.

P0, the major peripheral nervous system (PNS) myelin protein, is a member of the immunoglobulin supergene family of membrane proteins and can mediate homotypic adhesion. P0 is an essential structural component of PNS myelin; mice in which P0 expression has been eliminated by homologous recombination (P0-/-) develop a severe dysmyelinating neuropathy with predominantly uncompacted myelin. Although P0 is thought to play a role in myelin compaction by promoting adhesion between adjacent extracellular myelin wraps, as an adhesion molecule it could also have a regulatory function. Consistent with this hypothesis, Schwann cells in adult P0-/- mice display a novel molecular phenotype: PMP22 expression is down-regulated, MAG and PLP expression are up-regulated, and MBP expression is unchanged. As in quaking viable mutant mice (qk(v)), which have uncompacted myelin morphologically similar to that found in P0-/- mice, neither the qKI-6 or qKI-7 proteins are expressed in P0-/- peripheral nerve. In addition to these changes in gene expression in the P0 knockout, PLP/DM-20 accumulates in the endoplasmic reticulum of P0-/- Schwann cells, whereas MAG accumulates in redundant loops of uncompacted myelin, not at nodes of Ranvier or Schmidt-Lantermann incisures. Taken together, these results demonstrate that P0 is involved, either directly or indirectly, in the regulation of both myelin gene expression and myelin morphogenesis.

Animals↗
PubMed2000

The human astrocytoma cell line U373MG produces monocyte chemotactic protein (MCP)-1 upon stimulation with beta-amyloid protein.

Astrocytes associated with beta-amyloid (Abeta) accumulate in senile plaques of Alzheimer's disease (AD). To investigate the biological effects of Abeta/astrocyte interaction, we examined chemokine production by the human astrocytoma cell line U373MG stimulated with Abeta peptides. Northern blot analysis and specific immunoassays demonstrate that Abeta [1-42] and Abeta [25-35] induce mRNA expression and release of monocyte chemotactic protein (MCP)-1 but not of gamma-interferon inducible protein (IP)-10 by U373MG cells. The observation that Abeta induces astrocyte production of the potent microglia chemoattractant MCP-1 contributes to understanding mechanism of damage exerted by Abeta in AD senile plaques.

Amyloid beta-Peptides↗
PubMed2000

Synergistic effect of beta-amyloid protein and interferon gamma on nitric oxide production by C2C12 muscle cells.

Nitric oxide (NO) is an important mediator of diverse physiological and pathological responses. NO-induced oxidative stress has been proposed in the pathogenesis of muscle tissue damage in inclusion-body myositis (IBM), which is characterized by deposition of beta-amyloid protein (Abeta) in vacuolated muscle fibres. To determine whether Abeta can induce NO production in skeletal muscle, we stimulated C2C12 mouse skeletal muscle cells in vitro with Abeta[1-42] or Abeta[25-35] peptides in the presence or absence of interferon gamma (IFN-gamma). Neither Abeta peptides nor IFN-gamma were able to stimulate nitrite (NO(2)(-)) production by C2C12 cells when given alone. However, combination of IFN-gamma with either Abeta[1-42] or Abeta[25-35] resulted in significant NO(2)(-) release into cell-free supernatants. Northern blot analysis of RNA obtained from Abeta/IFN-gamma-stimulated C2C12 cells revealed increased mRNA accumulation of inducible nitric oxide synthase (iNOS). Moreover, approximately 4% of muscle cells incubated with Abeta peptides and IFN-gamma showed ultrastructural features of DNA fragmentation. These findings, taken together, indicate that the association of Abeta with IFN-gamma stimulates NO(2)(-) production via induction of iNOS gene expression in skeletal muscle cells, with occasional evidence for nuclear changes suggesting apoptotic morphology. These data further support a role for Abeta deposition in the pathogenesis of postulated oxidative damage in IBM.

Amyloid beta-Peptides↗
PubMed2000

Detection and quantitation of human immunodeficiency virus type 1 in the female genital tract. The Division of AIDS Treatment Research Initiative 009 Study Group.

Human immunodeficiency virus type 1 (HIV-1) was detected in the genital tracts of 59% of 225 women by RNA PCR and in 7% of the women by culture. In a comparison of two sampling methods, endocervical swabs were more sensitive than cervicovaginal lavage for HIV-1 RNA detection by PCR but not by culture and their sensitivity was independent of the concentration of HIV-1 RNA.

Cross-Sectional Studies↗
PubMed1999

Induction of adhesion molecules on human schwann cells by proinflammatory cytokines, an immunofluorescence study.

The presence of cytokines in the peripheral nerve was positively correlated to the induction and progression of inflammation during experimental allergic neuritis (EAN) and Guillain Barré syndrome (GBS). We investigated the induction of adhesion molecules such as L-selectin, E-selectin, ICAM-1, VCAM-1 and Mac-1 on Schwann cells by proinflammatory cytokines. Cultured human Schwann cells from normal adult, fetal and diabetic nerves were studied by immunofluorescence at basal condition and after stimulation with cytokines for 6, 24, 48 and 96 h. Incubation of human Schwann cells with TNFalpha, IFNgamma and IL-1beta induces the expression of ICAM-1 starting at 6 h and reaching a peak at 24 h on more than 90% of cells. VCAM-1 expression was induced after 6 h of treatment with TNFalpha and IL-1beta on almost 100% of Schwann cells. Surprisingly, stimulation with TNFalpha, IFNgamma and IL-1beta also induced the expression of L-selectin on fetal and diabetic Schwann cells, but not on normal adult cells. E-selectin, an adhesion molecule classically upregulated during inflammation, as well as Mac-1, a ligand for ICAM-1, were not expressed on human Schwann cells at basal condition or after treatment with cytokines. No ICAM-1, VCAM-1 and L-selectin expression was found on unstimulated Schwann cells. Our results suggest that upregulation of adhesion molecules on Schwann cells may have a role in the pathogenesis of inflammation in the peripheral nerve.

Adult↗
PubMed1999

Alpha-MSH peptides inhibit production of nitric oxide and tumor necrosis factor-alpha by microglial cells activated with beta-amyloid and interferon gamma.

Alpha-melanocyte stimulating hormone (alpha-MSH) is an ancient tridecapeptide with potent inhibitory activity in all major forms of inflammation. The anti-inflammatory message sequence of alpha-MSH resides in the COOH-terminal tripeptide alpha-MSH[11-13]. We tested the influence of alpha-MSH[1-13] and of alpha-MSH[11-13] in a cultured murine microglia cell line known to produce nitric oxide (NO(-)(2)) and tumor necrosis factor (TNFalpha) when stimulated with beta-amyloid protein (Abeta). Melanocortin peptides significantly inhibited release of both NO(-)(2) and TNFalpha into cell-free supernatants from microglia stimulated with Abeta[1-42] or Abeta[25-35] peptides and interferon gamma (IFNgamma). Northern blot analysis demonstrated that alpha-MSH[1-13] and alpha-MSH[11-13] inhibited accumulation of inducible nitric oxide synthase (iNOS) and TNFalpha mRNA was triggered by Abeta stimulation. Abeta/microglial interaction is believed to promote the progression of inflammatory and neurodegenerative changes in senile plaques in Alzheimer's disease. Our data indicate that alpha-MSH peptides might be used to modulate the local response of the brain to Abeta deposition in this neurodegenerative disease.

Amyloid beta-Peptides↗
PubMed1999

The absence of myelin P0 protein produces a novel molecular phenotype in Schwann cells.

In order to better understand the pathogenesis of demyelination in P0 knockout (P0-/-) mice, we analyzed the myelin gene expression and the localization of myelin proteins in P0 null mouse sciatic nerve. We have demonstrated that the severe demyelinating neuropathy of P0-knockout mouse is associated with changes in the program of myelin gene expression. Some changes in myelin gene expression occur early, others occur during adulthood. We also provide evidence that the absence of P0 is associated with changes in the localization of specific paranodal proteins in the peripheral nerve. These data suggest that P0 plays an important role, either directly or indirectly, in the program of Schwann cell gene expression and in the specific distribution of peripheral myelin proteins. Furthermore, myelin gene dysregulation and improper localization of paranodal proteins may account, in part, for the pathogenesis of demyelination in P0-knockout mice, as well as in human demyelinating peripheral neuropathy associated with mutations in the P0 gene.

Animals↗
PubMed1999

Proinflammatory profile of cytokine production by human monocytes and murine microglia stimulated with beta-amyloid[25-35].

Growing evidence indicates that amyloid (A beta) deposition and phagocyte activation participate in inflammatory reactions in the brain during the course of Alzheimer's disease. To further investigate the effects of A beta-phagocyte interaction, we examined the production of proinflammatory (IL-1beta, IL-6), chemotactic (MIP-1alpha, IP-10) and inhibitory (IL-1Ra, IL-10 and TGFbeta1) cytokines by cultured human monocytes and mouse microglial cells upon stimulation with A beta[25-35]. Northern blot analysis and specific immunoassays demonstrated that A beta[25-35] triggers mRNA expression and release of IL-1beta, IL-1Ra and MIP-1alpha but not of IL-6, IL-10, TGFbeta1 and IP-10 from human monocytes. Similar results were obtained by examining the production of IL-1beta, IL-6 and IL-10 from mouse microglial cells in the same experimental conditions. Taken together, these data indicate that A beta-phagocyte interaction can drive a different response towards cytokine production by monocytes and microglia, with a particular proinflammatory trend, and further support a role for A beta deposition as a triggering factor of inflammatory events in Alzheimer's disease.

Alzheimer Disease↗