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Biomedical subjects

C Rosenbaum

Publications and source records attributed to C Rosenbaum.

At least 19 recordsLinked to original sources
PubMed2002

The heart-pump interaction: effects of a microaxial blood pump.

BACKGROUND: When we use rotary blood pumps as an assist device, an interaction takes place between the pump performance and the native heart function (native heart influences pump performance and vice versa). The interaction between native heart and rotary blood pump can be useful to predict recovery of the failing heart. METHODS: The rotary blood pumps used were microaxial catheter-mounted pumps with an external diameter of 6.4 mm (Impella, Aachen, Germany). The pump-heart interaction was studied in five juvenile sheep with a mean body weight of 68.5 +/- 8.7 kg. The pumps were introduced via the left carotid artery and placed in transvalvular aortic position. Recorded parameters were pump speed (rpm), generated flow (L/min) and differential pressure (mm Hg) obtained at high frequency rate of data recordings (25 sets of data per second). This allowed continuous analysis of the pump performance during cardiac cycle. Under clinical conditions the interaction was studied in a 60-year-old male, in whom the device was applied due to postcardiotomy heart failure after myocardial infarction. RESULTS: Heart-pump interaction was analyzed based on pump flow differential pressure. This relationship, analyzed continuously during cardiac cycle, presents as a loop. The dynamic contribution of the heart to the flow generated by the pump leads to continuous fluctuation in the pressure head and the creation of hysteresis. The improved function of the failing heart under clinical conditions after seven days of mechanical support was expressed by: increased hysteresis of the loop caused by increased gradient of flow generated during cardiac cycle, a more pronounced venticular ejection phase that indicates more dynamic heart contribution to the generated flow, and finally increased gradient of the differential pressure during cardiac cycle, caused predominantly by increased aortic pressure and decreased left ventricle pressure during diastolic phase. CONCLUSIONS: The heart-pump interaction based on the pump flow-differential pressure relationship can be useful in predicting the possibility to wean the patient from the device.

Animals↗
PubMed2001

HIV-1 protein Tat reduces the glutamate-induced intracellular Ca2+ increase in cultured cortical astrocytes.

The trans-activator protein Tat of the human immunodeficiency virus type 1 (HIV-1) is regarded as an injurious molecule in the pathogenesis of HIV-1 associated encephalopathy (HIVE). We investigated the effects of Tat on neuroligand-induced intracellular Ca2+ increase in cultured astroglial cells. Rat cortical astrocytes, human glioblastoma cells and glial restricted precursor cells, from a human embryonic teratocarcinoma cell line, were incubated with recombinant Tat (100 ng/mL for 60 min) which induced a significant reduction of glutamate or ATP-induced intracellular Ca2+ increase ("glutamate response", "ATP response"). The reduction of the glutamate response was also observed following cell incubation with cell extracts of HeLa-T4+ cells transiently transfected with an expression plasmid coding for Tat. However, inactivation of the transcriptional trans-activity of Tat, by using a mutant form of Tat, as well as inhibition of de novo protein synthesis by cycloheximide abolished the effect on the glutamate response. This suggests that Tat acts upon induction of a so far unknown cellular gene whose gene product causes the reduction of glutamate responses. As the effect of Tat resembles the effect of TNFalpha on glutamate responses [Köller et al. (2001) Brain Res., 893, 237-243] which is locally released within the brains of HIVE patients, we also tested for synergistic effects of Tat and TNFalpha on the glutamate response. Low concentrations of Tat in combination with subthreshold concentrations of TNFalpha also elicited a marked reduction of astroglial glutamate responses. Our data suggest that Tat and TNFalpha, both by itself and synergistically, induce astroglial dysfunction.

AIDS Dementia Complex↗
PubMed2000

Long-term culture and characterization of human neurofibroma-derived Schwann cells.

Neurofibromas are benign tumors arising from the peripheral nerve sheath and are a typical finding in neurofibromatosis type 1 (NF1). Schwann cells are the predominant cell type in neurofibromas and thus are supposed to play a major role in the pathogenesis of these tumors. It is not known, however, if NF1 mutations in Schwann cells result in an altered phenotype that subsequently leads to tumor formation. To characterize the biological properties of neurofibroma-derived Schwann cells we developed cell culture techniques that enabled us to isolate Schwann cells from neurofibromas and grow them in vitro for several weeks without significant fibroblast contamination. Neurofibroma-derived Schwann cells were characterized by altered morphology, heterogeneous growth behavior, and increased expression of the P0 antigen while several other features of normal human Schwann cells were retained. We conclude that neurofibroma-derived Schwann cells exhibit a distinct phenotype in vitro but that the observed abnormalities by themselves are insufficient to explain neurofibroma formation. Application of our improved culture conditions makes neurofibroma-derived Schwann cells readily available for further studies to define their role in tumorigenesis in neurofibromatosis type 1.

Adolescent↗
PubMed2000

Enhanced proliferation and potassium conductance of Schwann cells isolated from NF2 schwannomas can be reduced by quinidine.

Neurofibromatosis type 2 (NF2) is an autosomal dominant disease that is characterized mainly by schwannomas, as well as menigiomas and gliomas. The NF2 gene product merlin/schwannomin acts as a tumor suppressor. Schwann cells derived from NF2 schwannomas showed an enhanced proliferation rate, and electrophysological studies revealed larger K(+) outward currents as compared with controls. Schwann cells isolated from schwannomas of NF2 patients or multiorgan donors were treated with different concentrations of the K(+) current blockers quinidine, tetraethylammonium chloride, and 4-aminopyridine and K(+) outward currents and proliferation rates of these cells were compared. K(+) outward currents of both cell types can be blocked by quinidine. Importantly, treatment with quinidine reduces proliferation of NF2 Schwann cells in a concentration dependent manner but did not reduce proliferation of normal Schwann cells. Therefore, the use of quinidine or quinidine-like components would possibly provide a novel adjuvant therapeutic option for NF2 patients to slow down or freeze growth of schwannomas.

Antineoplastic Agents↗
PubMed1999

Cellular contaminants of adeno-associated virus vector stocks can enhance transduction.

Transduction efficiency of different types of recombinant (r)AAV-2 based vectors preparations markedly differed, with apparently no correlation with the replicative titers. Using HeLa cells as target for transduction, 105 and 30 infectious units were necessary to observe one transductant using respectively cesium-chloride-purified rAAV and crude lysates of producer cells obtained by sonication. The purified vectors were however able to transduce HEK-193 cells efficiently, but transgene expression was detected with some delay compared with crude lysates. The unexpected high transduction efficiency of sonicated crude lysates was due to virally mediated gene transfer, since similar sonicated crude lysates, but with no AAV rep and cap genes, did not lead to detection of transgene products after incubation with HeLa cells. Furthermore, sonicated cellular extracts of 293 or 293/T cells given in trans stimulate transduction of HeLa cells by purified rAAV. In contrast, neither extracts from the adenovirus E1-transformed 911 cell line, nor from other cell lines not harboring any adenovirus gene, had enhancing effect on rAAV-mediated transduction. These data suggest that 293 sonicated extracts contain factors which stimulate rAAV-mediated transduction of cells that are normally poorly transduced and offer a system to identify such factors and to characterize further the steps limiting the transfer of gene by AAV vectors.

Dependovirus↗
PubMed1999

Neuroligand-mediated calcium signaling in cultured human schwannoma cells.

Intracellular Ca2+ release regulates proliferation of nonexcitable cells, however, it is not known whether and which neuroligands modulate the free intracellular Ca2+ concentration in human schwannoma cells. Confocal laser scanning microscopy was used for the study of neuroligand-induced Ca2+ signaling in cultured human schwannoma cells loaded with the Ca2+-sensitive fluorescent dyes Calcium Green-1 and Fura Red. Intracellular Ca2+ transients were observed during bath application of ATP (90% of cells tested), endothelin (60%), and norepinephrine (20%); histamine, serotonin, glutamate, and bradykinin did not have this effect. Two types of P2Y nucleotide receptor subtypes involved in ATP-induced Ca2+ transients could be separated by application of different P2Y receptor agonists and cross desensitization experiments: P2Y1 (rank order of potency: 2-MeSADP > 2-MeSATP > ADP > ATP) and P2Y2 (sensitive to UTP and ATP). Endothelin-induced Ca2+ signaling was also seen during application of [Ala(1,3,11,15)]ET-1; this suggests the presence of an ET(B) receptor subtype. The results indicate that the presence of receptors linked to neuroligand-triggered Ca2+ signaling does not seem to be abnormal in a human Schwann cell tumor, i.e. schwannoma cells retain this characteristic of peripheral glia.

Adenosine Diphosphate↗
PubMed1998

Improved culture methods to expand Schwann cells with altered growth behaviour from CMT1A patients.

A duplication of the gene for myelin protein PMP22 is by far the most common cause of the hereditary demyelinating neuropathy CMT1A. A role for PMP22 in cell growth in addition to its function as a myelin protein has been suggested because PMP22 is homologous to a gene specifically upregulated during growth arrest. Furthermore, transfected rat Schwann cells overexpressing PMP22 show reduced growth. In addition, abnormal Schwann cell differentiation has been described in nerve biopsies from CMT1A patients. To analyse whether the duplication of the PMP22 gene in CMT1A neuropathy primarily alters Schwann cell differentiation and to exclude nonspecific secondary responses, we improved human Schwann cell culturing. This allowed us long-term passaging of human Schwann cells with unchanged phenotype, assessed by expression of different Schwann cell markers. Subsequently we established Schwann cell cultures from CMT1A nerve biopsies. We find decreased proliferation of Schwann cells from different CMT1A patients in all passages. We also demonstrate PMP22 mRNA overexpression in cultured CMT1A Schwann cells. We conclude that decreased proliferation in cultured Schwann cells that carry the CMT1A duplication indicates abnormal differentiation of CMT1A Schwann cells. The identification of an abnormal phenotype of CMT1A Schwann cells in culture could possibly lead to an in vitro disease model.

Antigens↗
PubMed1998

Isolation and characterization of Schwann cells from neurofibromatosis type 2 patients.

Neurofibromatosis type 2 (NF2) is an autosomal dominant disease of the nervous system characterized by multiple schwannomas. The NF2 gene product, termed schwannomin or merlin, was hypothesized to function as a cytoskeleton-membrane linking protein due to homology to members of the protein 4.1 superfamily and to function as a tumor suppressor. We isolated and characterized pure Schwann cell cultures from schwannomas derived from neurofibromatosis 2 patients with identified germline mutations and loss of heterozygosity. We describe striking differences between NF2 and control Schwann cells in morphology, cell-cell contacts, and growth. NF2 Schwann cells form multiple long processes with filopodial and lamellopodial extensions. NF2 Schwann cells lack contact inhibition, grow in multiple layers, and show a higher proliferation rate than control cells. For the first time Schwann cells derived from patients with the NF2 genotype were cultured and characterized in vitro. These cultures are highly valuable for investigating the effects of NF2 mutations and the development of therapies.

Cell Division↗
PubMed1998

Influence of polarity reversal on defibrillation success with biphasic shocks and a transvenous/subcutaneous defibrillator system in a porcine animal model.

Clinical studies show that polarity reversal affects defibrillation success in transvenous monophasic defibrillators. Current devices use biphasic shocks for defibrillation. We investigated in a porcine animal model whether polarity reversal influences defibrillation success with biphasic shocks. In nine anesthetized, ventilated pigs, the defibrillation efficacy of biphasic shocks (14.3 ms and 10.8 ms pulse duration) with "initial polarity" (IP, distal electrode = cathode) and "reversed polarity" (RP, distal electrode = anode) delivered via a transvenous/subcutaneous lead system was compared. Voltage and current of each defibrillating pulse were recorded on an oscilloscope and impedance calculated as voltage divided by current. Cumulative defibrillation success was significantly higher for RP than for IP for both pulse durations (55% vs 44%, P = 0.019) for 14.3 ms (57% vs 45%, P < 0.05) and insignificantly higher for 10.8 ms (52% vs 42%, P = ns). Impedance was significantly lower with RP at the trailing edge of pulse 1 (IP: 44 +/- 8.4 vs RP: 37 +/- 9.3 with 14.3 ms, P < 0.001 and IP: 44 +/- 6.2 vs RP: 41 +/- 7.6 omega with 10.8 ms, P < 0.001) and the leading edge of pulse 2 (IP: 37 +/- 5 vs RP: 35 +/- 4.2 omega with 14.3 ms, P = 0.05 and IP: 37.5 +/- 3.7 vs RP: 36 +/- 5 omega with 10.8 ms, P = 0.02). In conclusion, in this animal model, internal defibrillation using the distal coil as anode results in higher defibrillation efficacy than using the distal coil as cathode. Calculated impedances show different courses throughout the shock pulses suggesting differences in current flow during the shock.

Animals↗
PubMed1998

Voltage-dependent membrane currents of cultured human neurofibromatosis type 2 Schwann cells.

Previous experimental observations indicate that inhibition of voltage-dependent K+ currents suppresses proliferation of normal Schwann cells. In the present study we tested the opposite relationship, i.e., whether Schwann cells from tumors with abnormally high rates of proliferation would have an increase in membrane K+ currents. Whole-cell membrane currents were studied in cultured cells from schwannomas of two neurofibromatosis type 2 (NF2) patients (n = 53), one patient with a sporadic schwannoma (n = 22), and two control subjects (n = 41). Five different types of voltage-dependent membrane currents were found in all of the Schwann cells tested. Membrane depolarization activated outward K+ and Cl- currents; quinidine was found to block the K+ current (IC50 approximately 1 microM), and NPPB reduced the Cl- current. Ba2+-sensitive inward rectifier K+ currents, fast Na+ currents, and a transient, inactivating K+ current were less frequently observed. On average, NF2 cells were found to have statistically significant higher membrane potential and larger non-inactivating K+ outward current as compared to controls. Electrophysiological parameters of Schwann cells from a sporadic schwannoma showed a tendency for larger outward currents; however, the difference did not reach statistical significance. Together the data support the suggestion of a possible link between K+ outward current and proliferation of Schwann cells.

Chloride Channels↗
PubMed1997

Schwann cells express NDF and SMDF/n-ARIA mRNAs, secrete neuregulin, and show constitutive activation of erbB3 receptors: evidence for a neuregulin autocrine loop.

Cultured Schwann cells secreted low levels (30 pg/ml/1.5 x 10(6) cells) of a 45-kDa neuregulin protein and showed constitutive activation of a neuregulin receptor, Erb-B3, suggesting the existence of an autocrine loop involving neuregulins in Schwann cells. RT-PCR analyses indicated that Schwann cells and fibroblasts in culture produced SMDF/n-ARIA and NDF but not GGF neuregulin messages. Schwann cell and fibroblast neuregulin messages encoded both beta and alpha domains; Schwann cell transcripts encoded only transmembrane neuregulin forms while fibroblast messages encoded transmembrane and secreted forms. SMDF/n-ARIA and NDF messages were also expressed in early postnatal rat sciatic nerve, suggesting a role for neuregulins in peripheral nerve development. An anti-neuregulin antibody inhibited the mitogenic response of Schwann cells to cultured neurons and to extracts of cultured neurons or embryonic brain, consistent with the accepted paracrine role of neuregulins on Schwann cells. Surprisingly, the same antibody inhibited Schwann cell proliferation stimulated by several unrelated mitogens including bFGF, HGF, and TGF-beta1. These data implicate both paracrine and autocrine pathways involving neuregulin form(s) in Schwann cell mitogenic responses.

Animals↗
PubMed1997

Lack of immune responses to immediate or delayed implanted allogeneic and xenogeneic Schwann cell suspensions.

Previous studies have shown that Schwann cell implantation offers a potential therapeutic approach to a variety of neurodegenerative disorders and traumatic injuries. In a clinically relevant paradigm, however, the implantation of autologous Schwann cells is problematic and the use of heterogenetic Schwann cells will be required. In the present study we addressed this important issue and analysed the immunogenicity and survival of allogeneic and xenogeneic Schwann cell suspension grafts in a prelesioned CNS fiber tract, the transected postcommissural fornix of the adult Wistar rat. Cultured Schwann cells from Wistar rat or human peripheral nerve were injected either immediately or after a delay into the transection site and the spatio-temporal pattern of leukocyte infiltration and of major histocompatibility antigen expression was characterized and semiquantified with immunocytochemical methods. Our main findings are that (1) invasive cerebral lesions induce the expression of MHC class I and II antigens, but only sparse infiltration of T-lymphocytes, (2) both allogeneic and xenogeneic discordant Schwann cell suspension grafts, from either neonatal or adult peripheral nerve, survive without any overt signs of rejection for up to 10 weeks after implantation; and (3) delayed implantation procedures have no effect on immune responses to allogeneic Schwann cell grafts. These results demonstrate that there is no marked ongoing immune reactions to heterogenetic Schwann cell suspension grafts and that long-term survival of cross-species Schwann cell grafts can be achieved in the absence of any immunsuppressive treatment. Thus the conditions for functional transplantation of Schwann cells across immunological barriers seem to be favourable and will have implications for future cross-species studies, and possibly also for clinical application.

Animals↗
PubMed1996

Hydrolysis of N-formylmethionyl chemotactic peptides by endopeptidase 24.11 and endopeptidase 24.15.

Endopeptidase 24.11 (EP 24.11), a membrane-bound cell surface enzyme, modulates chemotactic responsiveness of neutrophils to f-Met-Leu-Phe. It is unknown if the enzyme degrades potent formylmethionyl tetrapeptides or if an enzyme with similar activities, endopeptidase 24.15 (EP 24.15), degrades formylated chemotactic peptides. In a study of five formylmethionyl tetrapeptides and f-Met-Leu-Phe, we found that EP 24.11 had high affinity for all peptides evaluated, although it did not effectively degrade f-Met-Ile-Leu-Phe. EP 24.15 had high affinity for three of the tetrapeptides, and for f-Met-Leu-Phe, although, for unclear reasons, it did not degrade f-Met-Ile-Leu-Phe or f-Met-Leu-Phe, the apparent natural products of Staphylococcus aureus and Escherichia coli, respectively.

Amino Acid Sequence↗
PubMed1995

Degradation of lysylbradykinin by endopeptidase 24.11 and endopeptidase 24.15.

Lysylbradykinin (LBK), a potent bioactive peptide with pleiotropic actions, is the major kinin generated in the extravascular space. To explore possible mechanisms of inactivation of this peptide in tissues, we evaluated its degradation by endopeptidase 24.11 (EP 24.11) and endopeptidase 24.15 (EP 24.15), two zinc metalloenzymes widely distributed in tissues. EP 24.11 cleaved LBK at the Gly5-Phe6 and Pro8-Phe9 bonds, whereas EP 24.15 cleaved the Phe6-Ser7 bond. Determination of kinetic constants for degradation of LBK by the two enzymes yielded kcat/Km ratios of 5.2 x 10(5) and 8.4 x 10(5) for EP 24.15 and EP 24.11, respectively, indicating that LBK is a good substrate for both enzymes. The findings demonstrate that both EP 24.11 and EP 24.15 efficiently degrade LBK and thus may contribute to the inactivation of this peptide in tissues.

Amino Acid Sequence↗
PubMed1993

Isolation of the TYE2 gene reveals its identity to SWI3 encoding a general transcription factor in Saccharomyces cerevisiae.

The TYE2 gene was identified by recessive mutations which result in a significant reduction of Ty-mediated ADH2 expression. We cloned the TYE2 gene and analyzed its sequence. A large open reading frame of 825 codons was found encoding a rather hydrophilic, 93-kilodalton protein which contains a highly acidic region at its N-terminus. By sequence comparison we found that TYE2 is identical to gene SWI3 which has recently been shown to encode a nuclear protein which may function as a global transcription activation factor. The TYE2/SWI3 protein is necessary for the initiation of Ty1 transcription at its major initiation site in the delta element. Furthermore TYE2 function seems to be important for the expression of a variety of Ty-unrelated functions such as ADH1 expression, sporulation, growth on maltose, galactose, raffinose, and on non-fermentable carbon sources.

Blotting, Northern↗
PubMed1993

Chemical warfare: disaster preparation in an Israeli hospital.

The situation in the Middle East makes it imperative that Israeli hospitals be prepared for disaster, particularly that associated with chemical warfare. To prepare for the impact of chemical warfare, Israeli hospitals have designed mass trauma programs, which include staff training and simulated disaster drill exercises. These have been incorporated in the conventional disaster program since 1989. This article provides a brief overview of the trauma program at Beilinson Medical Center in Petach Tikva, Israel, including definition of four stages of injury, guidelines for intervention, and a discussion of the role of the social worker in the disaster plan.

Adult↗
PubMed1988

Tamoxifen in advanced prostate cancer: an ECOG pilot study.

A group of 19 patients with advanced (Stage D) prostate cancer were treated with one of three dose levels of the anti-estrogen tamoxifen, 10 mg (3 patients), 20 mg (8 patients), or 30 mg (8 patients) daily. Five patients had received no prior systemic therapy. The treatment was tolerated well, but no objective responses occurred.

Cerebral Cortex↗