Jewish Hospital

About: Jewish Hospital is a healthcare organization based out in Cincinnati, Ohio, United States. It is known for research contribution in the topics: Antigen & Population. The organization has 3881 authors who have published 3414 publications receiving 123044 citations.

Hematopoietic Stem Cell Transplantation for Multiple Sclerosis

Abstract: Rationale Phase I/II studies of autologous hematopoietic stem cell transplantation (HSCT) for multiple sclerosis (MS) were initiated, based on results of experimental transplantation in animal models of multiple sclerosis and clinical observations in patients treated concomitantly for malignant disease. Patients Eighty-five patients with progressive MS were treated with autologous HSCT in 20 centers and reported to the autoimmune disease working party of the European Group for Blood and Marrow Transplantation (EBMT). 52 (61 %) were female, median age was 39 [20-58] years. The median interval from diagnosis to transplant was 7 [1-26] years. Patients suffered from severe disease with a median EDSS score of 6.5 [4.5-8.5]. Active disease prior to transplant was documented in 79 of 82 evaluable cases. Results The stem cell source was bone marrow in 6 and peripheral blood in 79, and stem cells were mobilized into peripheral blood using either cyclophosphamide combined with growth factors or growth factors alone. Three patients experienced transient neurological complications during the mobilization phase. The high dose regimen included combination chemotherapy, with or without anti-lymphocyte antibodies or, with or without, total body irradiation. The stem cell transplants were purged of lymphocytes in 52 patients. Median follow-up was 16 [3-59] months. There were 7 deaths, 5 due to toxicity and infectious complications, 2 with neurological deterioration. The risk of death of any cause at 3 years was 10 (±7)% (95 % confidence interval). Neurological deterioration during transplant was observed in 22 patients; this was transient in most but was associated with MS progression in 6 patients. Neurological improvement by ≥ 1 point in the EDSS score was seen in 18 (21 %) patients. Confirmed progression-free survival was 74 (±12)% at 3 years being 66 (±23)% in patients with primary progressive MS but higher in patients with secondary progressive or relapsing-remitting MS, 78 (±13)%; p = 0.59. The probability of confirmed disease progression was 20 (±11)%. MRI data were available in 78 patients before transplant showing disease activity (gadolinium enhancing, new or enlarging lesions) in 33 %. Posttransplant MRI showed activity at any time in 5/61 (8 %) evaluable cases. Conclusion Autologous HSCT suggest positive early results in the management of progressive MS and is feasible. These multicentre data suggest an association with significant mortality risks especially in some patient groups and are being utilised in the planning of future trials to reduce transplant related mortality.

Inhibition of hypoxia/reoxygenation-induced apoptosis in metallothionein-overexpressing cardiomyocytes.

Abstract: To study possible mechanisms for metallothionein (MT) inhibition of ischemia-reperfusion-induced myocardial injury, cardiomyocytes isolated from MT-overexpressing transgenic neonatal mouse hearts and nontransgenic controls were subjected to 4 h of hypoxia (5% CO2-95% N2, glucose-free modified Tyrode's solution) followed by 1 h of reoxygenation in MEM + 20% fetal bovine serum (FBS) (5% CO2-95% air), and cytochrome c-mediated caspase-3 activation apoptotic pathway was determined. Hypoxia/reoxygenation-induced apoptosis was significantly suppressed in MT-overexpressing cardiomyocytes, as measured by both terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling and annexin V-FITC binding. In association with apoptosis, mitochondrial cytochrome c release, as determined by Western blot, was observed to occur in nontransgenic cardiomyocytes. Correspondingly, caspase-3 was activated as determined by laser confocal microscopic examination with the use of FITC-conjugated antibody against active caspase-3 and by enzymatic assay. The activation of this apoptotic pathway was significantly inhibited in MT-overexpressing cells, as evidenced by both suppression of cytochrome c release and inhibition of caspase-3 activation. The results demonstrate that MT suppresses hypoxia/reoxygenation-induced cardiomyocyte apoptosis through, at least in part, inhibition of cytochrome c-mediated caspase-3 activation.

Selective up-regulation of human alveolar macrophage collagenase production by lipopolysaccharide and comparison to collagenase production by fibroblasts.

Abstract: Collagenase catalyzes the initial and rate-limiting step in interstitial collagen degradation. Human alveolar macrophages produce both a fibroblast-like procollagenase and tissue inhibitor of metalloproteinases (TIMP). To define the potential of macrophages to express collagenase and TIMP, we have studied the effects of certain cell culture variables and LPS on in vitro production of these proteins. Our data indicate: 1) human macrophages cultured in a 1/1 (v/v) mixture of HAM F-12:DME produce two- to three-fold greater quantities of procollagenase (but not TIMP) as compared to HAM F-12, DME, or alpha-MEM alone; 2) maximal collagenase expression requires the further addition of LPS, whereas TIMP production is optimized by 5% fetal bovine serum alone; 3) the up-regulation of macrophage procollagenase by LPS represents a highly selective biologic response when compared to changes induced in other secreted and intracellular proteins; 4) measurements of steady state procollagenase mRNA by Northern blot analysis suggest that the LPS effect is mediated at a pre-translational level; and finally 5) on a per cell basis, human alveolar macrophages cultured under optional conditions secrete approximately 20% of the collagenase and approximately 10% of the TIMP elaborated by stimulated human fibroblasts. We conclude that procollagenase and TIMP secretion by human alveolar macrophages in vitro is strikingly responsive to variations in cell culture conditions and that an especially noteworthy selective upregulation of procollagenase secretion by LPS is probably modulated by a transcriptional mechanism. The macrophage synthetic potential for procollagenase suggests a potentially important role for these cells in directly mediating collagen turnover.

Diagnostic value of MR elastography in addition to contrast-enhanced MR imaging of the breast—initial clinical results

Abstract: The purpose of the study was to assess the additional value of magnetic resonance (MR) elastography (MRE) to contrast-enhanced (ce) MR imaging (MRI) for breast lesion characterisation. Fifty-seven suspected breast lesions in 57 patients (mean age 52.4 years) were examined by ce MRI and MRE. All lesions were classified into BI-RADS categories. Viscoelastic parameters, e.g. α0 as an indicator of tissue stiffness, were calculated. Histology of the lesions was correlated with BI-RADS and viscoelastic properties. The positive predictive value (PPV) for malignancy, and the sensitivity and specificity of ce MRI were calculated. Receiver-operating characteristics (ROC) curves were separately calculated for both ce MRI and viscoelastic properties and conjoined to analyse the accuracy of diagnostic performance. The lesions (mean size 27.6 mm) were malignant in 64.9% (n = 37) of cases. The PPV for malignancy was significantly (p < 0.0001) dependent on BI-RADS classification. The sensitivity of ce MRI for breast cancer detection was 97.3% (36/37), whereas specificity was 55% (11/20). If ce MRI was combined with α0, the diagnostic accuracy could be significantly increased (p < 0.05; AUCceMRI = 0.93, AUCcombined = 0.96). In this study, the combination of MRE and ce MRI could increase the diagnostic performance of breast MRI. Further investigations of larger cohorts and smaller lesions (in particular those only visible on MRI) are necessary to validate these results.