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Biomedical subjects

S Katz

Publications and source records attributed to S Katz.

At least 19 recordsLinked to original sources
PubMed2006

Modulation of ERK 1/2 and p38 MAPK signaling pathways by ATP in osteoblasts: involvement of mechanical stress-activated calcium influx, PKC and Src activation.

There is evidence that extracellular nucleotides, acting through multiple P2 receptors, may play an important role in the regulation of bone metabolism by activating intracellular signaling cascades. We have studied the modulation of mitogen-activated protein kinase (MAPK) signaling pathways and its relationship to changes in intracellular calcium concentration ([Ca(2+)](i)) induced by ATP in ROS-A 17/2.8 osteoblastic cells. ATP and UTP (10 microM) increased [Ca(2+)](i) by cation release from intracellular stores. We have found that when the cells are subsequently subjected to mechanical stress (medium perturbation), a transient calcium influx occurs. This mechanical stress-activated calcium influx (MSACI) was not observed after ADP stimulation, indicating that P2Y(2) receptor activation is required for MSACI. In addition, ERK 1/2 and p38 MAPK were activated by ATP in a dose- and time-dependent manner. This activation was almost completely blocked using neomycin (2.5mM), an inhibitor of phosphoinositide-phospholipase C (PI-PLC), Ro 318220 (1 microM), a protein kinase C (PKC) inhibitor, and PP1 (50 microM), a potent and selective inhibitor of the Src-family tyrosine kinases. Ca(2+)-free extracellular medium (containing 0.5mM EGTA) and the use of gadolinium (5 microM), which suppressed MSACI, prevented ERK 1/2 and p38 phosphorylation by ATP. Altogether, these results represent the first evidence to date suggesting that P2Y(2) receptor stimulation by ATP in osteoblasts sensitizes mechanical stress activated calcium channels leading to calcium influx and a fast activation of the ERK 1/2 and p38 MAPK pathways. This effect also involves upstream mediators such as PI-PLC, PKC and Src family kinases.

Adenosine Diphosphate↗
PubMed2005

A pilot study of immunosuppression minimization after pancreas-kidney transplantation utilizing thymoglobulin induction and sirolimus maintenance therapy.

AIMS: To determine outcomes utilizing thymoglobulin and sirolimus immunosuppression, with early steroid withdrawal in low-immune responder pancreas-kidney (SPK) recipients, and conversion from cyclosporine (CsA) to mycophenolic acid (MPA) in all recipients at 6 months posttransplantation. METHODS: SPK recipients received thymoglobulin, sirolimus, and reduced-dose CsA immunosuppression. Low immune responders (non-African-Americans with a pretransplant PRA < 30%) were withdrawn from prednisone on posttransplant day 5 and high immune responders were continued on prednisone. All recipients were converted from CsA to MPA at 6 months posttransplantation. During conversion, recipient immune response was monitored by flow PRA and a T-cell stimulation assay (Cylex). RESULTS: With a mean follow-up of 9 +/- 4 months, one pancreas was lost to pancreatitis, with no patient or kidney losses and no acute rejection episodes. All eight low immune responder patients were steroid-free at 9 +/- 5 months posttransplantation. Seven patients (five low and two high immune responders) with at least 6-month follow-up were converted from CsA to MPA. One high immune responder with a pretransplant PRA of 43% remained with a PRA of 53% +/- 2% postconversion. The second high immune responder had a pretransplant PRA of 34% and a postconversion PRA of 0%. The five low immune responders had a mean pretransplant PRA of 16% +/- 15% and a postconversion PRA of 0% (P < .01). The Cylex assay resulted in 67% low responsiveness for both high and low immune responders. CONCLUSION: Thymoglobulin induction with sirolimus maintenance therapy permitted immunosuppression minimization in selected pancreas transplant recipients. Posttransplant evaluation revealed a diminished (regulated) immune response in six of seven patients.

Animals↗
PubMed2004

Evidence that TRPC3 is a molecular component of the 1alpha,25(OH)2D3-activated capacitative calcium entry (CCE) in muscle and osteoblast cells.

In chick skeletal muscle and in rat osteoblast-like cells (ROS 17/2.8), 1alpha,25-dihydroxy-Vitamin-D(3) [1alpha,25(OH)(2)D(3)] stimulates release of Ca(2+) from inner stores and extracellular cation influx through both voltage-dependent and capacitative Ca(2+) entry (CCE) channels. We investigated the involvement of TRPC proteins in CCE induced by 1alpha,25(OH)(2)D(3). Two fragments were amplified by RT-PCR, exhibiting >85% sequence homology with human TRPC3. Northern and Western blots employing TRPC3-probes and anti-TRPC3 antibodies, respectively, confirmed endogenous expression of a TRPC3-like protein. Both cell types transfected with anti-TRPC3 antisense oligodeoxynucleotides showed reduced CCE and Mn(2+) entry induced by either thapsigargin or 1alpha,25(OH)(2)D(3). In muscle cells, anti-VDR antisense inhibited steroid-induced Ca(2+) and Mn(2+) influx and co-immunoprecipitation of TRPC3 and VDR was observed, suggesting an association between both proteins and a functional role of the receptor in 1alpha,25(OH)(2)D(3) activation of CCE. In osteoblasts, two PCR fragments showing high homology with human INAD-like sequences were obtained. Northern blot and antisense functional assays suggested the involvement of the INAD-like protein in CCE regulation by the hormone. Therefore, we propose that an endogenous TRPC3 protein mediates 1alpha,25(OH)(2)D(3) modulation of CCE in muscle and osteoblastic cells, which seems to implicate VDR-TRPC3 association and the participation of a INAD-like scaffold protein.

Animals↗
PubMed2004

The effect of pancreas transplantation on peripheral vascular disease complications.

BACKGROUND: We sought to determine whether pancreas transplantation reduced the incidence of peripheral vascular complications in diabetics with renal insufficiency. METHODS: A retrospective single-center review was done of 36 kidney-pancreas (KP) and 88 kidney-alone (KA) recipients with a diagnosis of diabetes and end-stage renal disease (ESRD) transplanted between May 1997 and July 2002. Risk factors studied included type of transplant, age, gender, history of smoking, coronary artery disease, hypertension, and peripheral vascular disease (PVD). The endpoint was first peripheral vascular event occurring after transplantation, defined as either an amputation or revascularization procedure. RESULTS: The mean age of the cohort was 51 +/- 9 years, 64% of patients were of male gender, 20% with a history of smoking, 98% with hypertension, 15% with coronary artery disease (CAD), and 12% with a history of PVD. With a median follow-up of 45 months (12 to 79 months), 3/36 (8%) of KP recipients suffered a PVD complication, compared to 10/88 (11%) of KA recipients (P = NS). Similarly, age, gender, a past history of smoking, CAD, and hypertension were not predictive of PVD complications. Five of 15 patients (33%) with a pretransplant history of PVD suffered a postoperative PVD event compared to only 8 of 109 patients (7%) with no prior history of PVD (P =.008). CONCLUSIONS: Restoration of normoglycemia by pancreas transplantation did not reduce the risk of PVD complications in diabetics with renal failure. A pretransplant history of PVD was the only risk factor associated with posttransplant PVD events.

Adult↗
PubMed2004

Outcome of non-invasive positive pressure ventilation in paediatric neuromuscular disease.

BACKGROUND: Non-invasive positive pressure ventilation (NPPV) has a beneficial effect on nocturnal hypoventilation and hospitalisation rates in adults with static or slowly progressive neuromuscular disease and respiratory failure. Its role in children affected with similar disease processes, however, remains unclear. AIMS: To investigate the impact of NPPV on hospitalisations and sleep related respiratory parameters in children with neuromuscular disease. METHODS: Fifteen children (mean age 11.7, range 3.4-17.8 years) diagnosed with neuromuscular disease who had been started on nocturnal NPPV and had at least one year of follow up since the initiation of such therapy were studied. Patients served as their own controls and comparison was made of the years preceding and following the initiation of NPPV. RESULTS: Children spent 85% fewer days in hospital (mean pre-NPPV 48.0 days, mean post-NPPV 7.0 days) and 68% less days in intensive care after initiation of NPPV (mean pre-NPPV 12.0 days, mean post-NPPV 3.9 days). Sleep study parameters including number of desaturations, apnoea-hypopnoea index and transcutaneous pCO2 levels improved after initiation of NPPV. CONCLUSIONS: NPPV can decrease hospitalisations for children with neuromuscular disease and improves sleep related respiratory parameters. A prospective study is now needed to further delineate the role of NPPV in this population of children.

Adolescent↗
PubMed2004

1alpha,25(OH)2D3 induces capacitative calcium entry involving a TRPC3 protein in skeletal muscle and osteoblastic cells.

This work describes the involvement of TRPC proteins in capacitative calcium entry (CCE) induced by 1alpha,25-dihydroxy-vitamin-D3 [1alpha,25(OH)2D3] in chick skeletal muscle and in rat osteoblast-like cells (ROS 17/2.8) and the role of the vitamin D receptor (VDR) in this non-genomic rapid response mediated by the hormone. We propose that an endogenous TRPC3 protein mediates 1alpha,25(OH)2D3 modulation of CCE in these cells, which seems to implicate VDR-TRPC3 association and the participation of an INAD-like scaffold protein.

Animals↗
PubMed2003

Repifermin (keratinocyte growth factor-2) for the treatment of active ulcerative colitis: a randomized, double-blind, placebo-controlled, dose-escalation trial.

BACKGROUND: Repifermin (keratinocyte growth factor-2) has been shown to reduce inflammation in animal models of colitis. AIM: To evaluate repifermin for the treatment of active ulcerative colitis. METHODS: Eighty-eight patients with active ulcerative colitis were enrolled in a 6-week, double-blind trial. Patients were randomized to receive treatment for five consecutive days with intravenous repifermin at a dose of 1, 5, 10, 25 or 50 microg/kg, or placebo. The primary objective of the study was to evaluate the safety of repifermin. The primary efficacy outcome was clinical remission at week 4, defined as a score of zero on the endoscopic appearance and stool blood components of the Mayo score and a score of zero or unity on the stool frequency and physician's global assessment components. RESULTS: At week 4, the rates of clinical remission in the 1, 5, 10, 25 and 50 microg/kg repifermin groups were 19%, 9%, 0%, 0% and 0%, respectively, and 11% for the placebo group (P = 0.32 for repifermin vs. placebo). The frequencies of commonly occurring adverse events and severe adverse events were similar in both groups. CONCLUSIONS: Intravenous repifermin at a dose of 1-50 microg/kg was very well tolerated, but there was no evidence that repifermin was effective for the treatment of active ulcerative colitis at these doses. An additional study to determine the efficacy of repifermin at doses of > 50 microg/kg or for a longer treatment duration may be warranted, as the maximally tolerated dose was not reached in the present study.

Adult↗
PubMed2003

Intention to apply or accept an alternative job among participants of extended employment programs.

The research studied 249 people employed in extended employment programs in northern Israel with respect to their intention to apply for an alternative job (an active step) or to accept a new job offer (a passive step). Findings indicated that young, single people who were living with their parents and perceived their level of disability as mild indicated more intention to apply for an alternative job or to accept a new job offer. Furthermore, people with low monthly wages, less satisfaction with their income and with the extended employment program in general, and a lack of participation in non-employment activities expressed a greater inclination to apply for an alternative job or to accept a new job offer. The only difference between people's intentions to apply for an alternative job (an active step) or to accept a job offer (a passive step) was in regard to their perception of their disability. The intention to apply for an alternative job was associated with mild disability, whereas the acceptance of a new job offer was related to mild and moderate disability.

Adolescent↗
PubMed2001

The AP-1 repressor, JDP2, is a bona fide substrate for the c-Jun N-terminal kinase.

The Jun dimerization protein 2 (JDP2) is a novel member of the basic leucine zipper family of transcription factors. JDP2 binds DNA as a homodimer and heterodimer with ATF2 and Jun proteins but not with c-Fos proteins. JDP2 overexpression represses activating protein 1 transcription activity. Whereas JDP2 mRNA and protein levels are stable following different cell stimuli, JDP2 is rapidly phosphorylated upon UV irradiation, oxidative stress and low levels of translation inhibitor. The c-Jun N-terminal kinase phosphorylates JDP2 both in vitro and in vivo. JDP2 contains a putative consensus JNK docking-site and a corresponding phosphoacceptor site. Substitution of threonine 148 to an alanine residue blocks JNK-dependent JDP2 phosphorylation. Our data indicate that JDP2 is a bona fide substrate for the c-Jun N-terminal kinase. The precise role of JDP2 phosphorylation on its function is not yet known.

Animals↗
PubMed2001

Final results of a randomized trial comparing the NIR stent to the Palmaz-Schatz stent for narrowings in native coronary arteries.

The NIR stent is a novel second generation tubular stent that was designed to overcome some of the limitations of the earlier Palmaz-Schatz (PS) stent design. The NIR Vascular Advanced North American (NIRVANA) trial randomized 849 patients with single coronary lesions to treatment with the NIR stent or the PS stent. The study was an "equivalency" trial, designed to demonstrate that the NIR stent was not inferior to (i.e., equivalent or better than) the PS stent, for the primary end point of target vessel failure (defined as death, myocardial infarction, or target vessel revascularization) by 9 months. Successful stent delivery was achieved in 100% versus 98.8%, respectively, with a slightly lower postprocedural diameter stenosis (7% vs. 9%, p = 0.04) after NIR and PS stent placement, respectively. Major adverse cardiac events (death, myocardial infarction, repeat target lesion revascularization) were not different at 30 days (4.3% vs. 4.4%). The primary end point of target vessel failure at 9 months was seen in 16.0% of NIR versus 17.2% of PS patients, with the NIR proving to be equal or superior to the PS stent (p <0.001 by test for equivalency). Angiographic restudy in 71% of a prespecified cohort showed no significant difference in restenosis (19.3% vs 22.4%). Thus, the NIR stent showed excellent deliverability with slightly better acute angiographic results and equivalent or better 9-month target vessel failure rate when compared with the PS stent.

Aged↗
PubMed2001

Genotyping of clinical Serratia marcescens isolates: a comparison of PCR-based methods.

The polymerase chain reaction (PCR)-based procedures of randomly amplified polymorphic DNA (RAPD) and repetitive element (RE)-based PCR were used to amplify total DNA prepared from each of 62 clinical Serratia marcescens isolates. Three different random primers, designated 1060, 1254 and 1283, were used individually in RAPD-PCR. Primers representing enterobacterial repetitive intergenic consensus (ERIC) sequences, extragenic palindromic (REP) elements, and polymorphic GC-rich repetitive sequences (PGRS) constituted the repetitive element-PCR. We were able to generate 40, 40 and 58 genotypic groupings using the 1060, 1254 and 1283 RAPD primers, respectively. Using the ERIC, REP and PGRS primers, 19, 54 and 60 unique genotypic profiles were yielded, respectively. The PGRS primers, which were developed to amplify GC-rich repetitive sequences in the genome of Mycobacteria, were the most discriminatory. These data indicate that both of these PCR-based approaches are a valid means of discriminating strain differences among isolates of S. marcescens and the amount of differentiation depends on the primer used. These techniques should prove useful for routine surveillance or in examining outbreaks of S. marcescens in clinical settings.

Bacterial Typing Techniques↗
PubMed2001

Sirolimus improves the two-year outcome of renal allografts in African-American patients.

The present study evaluated whether the addition of sirolimus to a cyclosporine (CyA)/prednisone (Pred) regimen mitigated the greater proclivity to acute rejection episodes and graft loss characteristic of African-American renal transplant recipients. Using Kaplan-Meier and log-rank tests, African-American renal transplant recipients treated with either CyA/Pred (n = 90) or sirolimus/CyA/Pred (n = 47) were compared with 120 Caucasian patients treated with sirolimus/CyA/Pred for 2-year rates of patient and graft survival as well as acute rejection episodes. Mean laboratory values were compared using analysis of variance and F-tests. Addition of sirolimus to the CyA/Pred regimen reduced the incidence of acute rejection episodes in African-Americans from 43.3% to 19.2% (P = 0.004), a value similar to Caucasian patients. The 97.9% 2-year graft survival rate among 47 African-American patients treated with sirolimus/CyA/Pred was significantly higher than the 85.6% rate shown among the 90 CyA/Pred-treated African-American transplant recipients (P = 0.0479) and similar to that in Caucasians. The 95.7% patient survival rate among the African-American sirolimus/CyA/Pred group was similar to the 97.8% rate in the African-American CyA/Pred cohort. Interestingly, there was no evident toxicity from the addition of sirolimus. The addition of sirolimus to a CyA-based regimen reduced acute rejection episodes and graft loss experienced by African-American renal transplant recipients.

Acute Disease↗
PubMed2001

Three-dimensional computed tomography-guided monotherapeutic pararectal brachytherapy of prostate cancer with seminal vesicle invasion.

PURPOSE: To treat patients with prostate cancer and seminal vesicle invasion with monotherapeutic three dimensional computed tomography (3-DCT)-guided posterior pararectal brachytherapy. METHODS AND MATERIALS: Three hundred and sixty two patients with clinical stage T1 a,b or T2 a,b of prostate cancer were referred for 3-DCT-guided brachytherapy. Each underwent ftirther staging with 3-D CT-guided pararectal biopsy of the seminal vesicles under local anesthesia during the pre-treatment CT-planning. Forty-three patients (12%) were upstaged to T3 cNoMo disease. In the set of 43 patients, Eight had Gleason's score< or =6, 24 Gleason's score=7, and 11 patients > or =8. Initial PSA was <10 ng/ml in 14 patients, 10-20 ng/ml in 11 patients, and >20 in 18 patients. Of the 43 patients, 37 patients were treated monotherapeutically with 3-D CT-guided brachytherapy. No patients received hormone therapy after the implant. The prescribed dosage to the seminal vesicles and prostate is 120 Gy with Pd-103 seeds and 144 Gy with 1-125 seeds. RESULTS: The prescribed dosage was achieved in all 37 patient's throughout the seminal vesicles whose range of target radiation extended 5-10 mm outside the target in the adjacent fat as calculated with post-implant CT-dosimetry with Varian Brachy Vision or MMS software. Prostate Specific Antigen (PSA) outcome data were available in 34 patients treated with monotherapy and follow up ranged from 12-56 months (median, 24 months). Decreased PSA levels were stratified into six groups based on the presenting Gleason's score and initial PSA. In the first group (with Gleason's score< or =6 and initial PSA <20 ng/ml), PSA levels decreased to less than 0.5 ng/ml in all seven patients (100%) after brachytherapy. In the second group (with Gleason's=7 and initial PSA<20 ng/ml), PSA levels decreased to less than 1 ng/ml in 11 of 13 patients (85%); additionally PSA levels decreased to less than 0.5 ng/ml in ten patients (77% in this group). In the third group (with Gleason's score=7 and initial PSA> 20 ng/ml), PSA decreased to less than 0.5 ng/ml in four out of eight patients (50%). All of the patients in the fourth group (with Gleason's score> or =8 and initial PSA<20 ng/ml) decreased their PSA levels to less than 0.5 ng/ml in three of three patients. PSA decreased less than 0.5 ng/ml in two out of three patients (67% in the last group with Gleason's score> or =8 and initial PSA> 20 ng/ml). There were no patients with Gleason's score of 1-6 and greater than 20 ng/ml initial PSA. Patients, irrespective of the Gleason's score and PSA, had an overall response of decreased PSA (less than 1 ng/ml) of 79%. CONCLUSION: 3-D CT-guided brachytherapy delivers adequate dosage to the seminal vesicles. Clinical and biochemical results are encouraging in patients with low initial PSA levels regardless of their Gleason's scores, but longer-term data in a greater number of patients is necessary.

Aged↗
PubMed2001

Bidirectional experimental effects.

Bidirectional experimental effects cannot be demonstrated by comparing measures of central tendency. Three approaches to the problem were considered: a test of homogeneity of variance, a comparison of control and experimental quartile frequencies by means of the chi-square test of association, and the cumulative-percentage-difference (CPD) curve--a graphic tool for demonstrating bidirectional effects. Two tests of significance were developed based on the CPD curve's maximum and minimum values. All 3 tests were first put to use analyzing simulated data, which incorporated 6 different patterns of experimental effect. The results of 100 repetitions of the simulations are summarized. Next, the results of a lexical-decision experiment with partial-word preview were analyzed using the procedures considered. The report ends with a presentation of guidelines for the use of the bidirectional tests.

Humans↗
PubMed2001

Etanercept for active Crohn's disease: a randomized, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: We evaluated etanercept, a human soluble tumor necrosis factor receptor: Fc fusion protein, for the treatment of active Crohn's disease. METHODS: Forty-three patients with moderate to severe Crohn's disease were enrolled in an 8-week placebo-controlled trial. Patients were randomized to subcutaneous etanercept 25 mg or placebo twice weekly. The primary outcome measure was clinical response at week 4, defined as a decrease in the baseline Crohn's Disease Activity Index score > or =70 points or a Crohn's Disease Activity Index score <150 points. RESULTS: At week 4, 39% of etanercept-treated patients had clinical response as compared with 45% of placebo-treated patients (P = 0.763). The frequency of common adverse events including headache, new injection site reaction, asthenia, abdominal pain, Crohn's disease-related anemia, and skin disorders was similar in both groups. Likewise, the frequency of severe or serious adverse events was similar in both groups. CONCLUSIONS: Subcutaneous etanercept at a dose of 25 mg twice weekly is safe, but not effective, for the treatment of patients with moderate to severe Crohn's disease. The dose of etanercept administered in this study is that approved for rheumatoid arthritis. Higher doses or more frequent dosing may be required to attain a response in patients with active Crohn's disease.

Adult↗
PubMed2001

Congenital short-bowel and malrotation: clinical presentation and outcome of six affected offspring in three related families.

Newborns with congenital short small bowel associated with malrotation and intestinal dysmotility have a uniformly bad prognosis. However, few long-term survivors have been reported, suggesting that the disorder is not invariably fatal. The majority of cases previously reported were familial. We report on six affected siblings in three related families. The aim of this report is to assess the mode of inheritance, the expression of this disorder, and to point to the correlation between the onset of gastrointestinal symptoms and the outcome.

Adolescent↗