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A Schwartz

Publications and source records attributed to A Schwartz.

At least 145 records · Page 8Linked to original sources
PubMed1997

T cell lymphokines modulate bFGF-induced smooth muscle cell fibrinolysis and migration.

Smooth muscle cell (SMC) fibrinolysis is necessary for SMC migration. To determine whether the T cell lymphokines interleukin 4 (IL-4) and interferon-gamma (IFN-gamma) modulate SMC fibrinolysis and migration induced by basic fibroblast growth factor (bFGF), we examined the effects of IL-4 and IFN-gamma on human SMC tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (UPA), and plasminogen activator inhibitor 1 (PAI-1) antigen production, determined by enzyme-linked immunosorbent assays. Although IL-4 had no effects on SMC tPA, UPA, and PAI-1 production, it potentiated bFGF-induced tPA, UPA, and PAI-1 antigens. IL-4 plus bFGF resulted in a net increase in SMC fibrinolytic activity. IFN-gamma did not significantly affect bFGF induction of SMC tPA and PAI-1 antigens. However, IFN-gamma significantly decreased bFGF-mediated induction of SMC UPA antigen. IFN-gamma decreased the IL-4 plus bFGF induction of both tPA and UPA antigens. IL-4 increased and IFN-gamma abrogated bFGF induction of in vitro SMC migration through a modified micro-Boyden chamber. Therefore, IL-4 and IFN-gamma modulate bFGF-mediated induction of in vitro vascular SMC fibrinolysis and migration.

Antigens↗
PubMed1997

Properties of three COOH-terminal splice variants of a human cardiac L-type Ca2+-channel alpha1-subunit.

There is growing evidence for diversity of cardiac-type (class C) voltage-dependent calcium-channel alpha1-subunits arising from the alternative splicing of a primary transcript. In this study, we show the existence of carboxy-terminal variability in the human cardiac alpha1-gene by genomic cloning. We found that the genomic DNA segment encoding the COOH-terminal tail of the protein is composed of nine invariable and two alternative exons. The alternative utilization of these latter two exons gives rise to the formation of three message variants for this region. Reverse transcription followed by polymerase chain reaction and radioanalytic quantitation of the reverse transcription-polymerase chain reaction products showed significant variations in the distribution of these isoforms (hHt alpha1, rHt alpha1, fHt alpha1) in distinct parts of the heart, the aorta, and fibroblasts. Expression of the three alpha1-isoforms in Xenopus oocytes or in HEK-293 cells and analysis of the kinetics and voltage dependence of the induced calcium-channel currents revealed only insignificant differences in the behavior of these isoforms. When the alpha1-isoforms were coexpressed with a human beta-subunit, no alpha1-specific divergences were observed, but the effects of beta-subunit coexpression on alpha1-isoform biophysical properties were confirmed. The differential abundance of the three isoforms and the influence of an accessory subunit are of potential physiological significance.

Alternative Splicing↗
PubMed1997

Power Doppler imaging of carotid artery stenosis. Comparison with color Doppler flow imaging and angiography.

BACKGROUND AND PURPOSE: Power Doppler imaging (PDI) is a new sonographic technique that has recently been introduced for vascular application. Since the technical principles of PDI may provide increased sensitivity to visualize the continuity of blood flow in arterial stenoses, we investigated the diagnostic significance of PDI and the intermethod relationship for the measurement and classification of internal carotid artery (ICA) stenosis in comparison with both color Doppler flow imaging (CDFI) and angiography. METHODS: One hundred patients with a total of 128 ICA stenoses (50% to 69%, n = 37; 70% to 79%, n = 27; 80% to 99%, n = 64) and 12 ICA occlusions were consecutively investigated by means of PDI, CDFI, and intra-arterial angiography (n = 48). Reduction of the intrastenotic lumen was measured on longitudinal and transverse views of PDI and CDFI for the calculation of the degree of diameter and area stenosis, respectively. Angiographic stenosis was determined with the use of the North American Symptomatic Carotid Endarterectomy Trial (NASCET), European Carotid Surgery Trial (ECST), and common carotid (CC) methods. RESULTS: PDI provided significantly more excellent or good (92% versus 79%; P < .01) displays of the intrastenotic lumen than CDFI, particularly in complicated high-grade stenosis. While linear regression analysis demonstrated a high overall correlation between PDI and CDFI for diameter (r = .88; P < .001) and area stenosis (r = .79; P < .001), categorization of ICA stenosis revealed best agreement for 80% to 99% area stenoses. Since angiography frequently either underclassified (NASCET method) or overclassified (ECST, CC methods) the degree of ICA stenosis in comparison to both PDI and CDFI, the sonographic-angiographic correlation was only moderate (regression coefficients ranged from .62 to .70; P < .001). CONCLUSIONS: PDI further improves the assessment of ICA stenosis by providing better visualization of the stenotic vascular lumen than CDFI. Sonographic imaging of the stenotic plaque on both PDI and CDFI provided a direct measurement of the local degree of stenosis, while the angiographic grade of stenosis essentially depended on the method used for evaluation.

Adult↗
PubMed1997

Interleukin-2 production by human pre-implantation embryos.

The study was conducted to determine whether pre-implantation embryos secrete interleukin-2. Conditioned media of 27 embryos derived from women during in vitro fertilization (IVF) cycles were analyzed for interleukin-2 concentration. The results showed that conditioned embryo medium from the two pronuclei stage to 24 hours later contains interleukin-2. Endometrial large granular lymphocytes, which are probably involved in placentation, replicate in response to interleukin-2. It may therefore be speculated that interleukin-2 secreted by human embryos may modulate the function and replication of large granular lymphocytes.

Blastocyst↗
PubMed1997

Loss of uteroglobin expression in prostate cancer: relationship to advancing grade.

We have shown previously that the secretory protein uteroglobin (UG) is highly expressed in normal human prostate tissue but this expression is either lost or altered in human prostate cancer cell lines. Treatment of these cell lines with recombinant human UG inhibits their ability to invade human reconstituted basement membrane by up to 90%, implying that the loss of normal UG expression may be related to the invasive potential of prostate cancer. Because invasion represents a critical step in metastasis, the expression patterns of UG could provide a unique and relevant indicator of cancer progression. In this study, we present the immunohistochemical analyses of fresh frozen prostate tissues from surgical specimens taken from 50 patients. Eight slides per patient were analyzed for UG staining. Slides from 26 patients showed evidence of prostate cancer, whereas slides from the remaining 24 patients showed only benign glands. The results demonstrate UG immunoreactivity in normal prostate, benign prostatic hyperplasia, and prostatic atrophy; low but clearly positive expression in prostatic intraepithelial neoplasia; positive expression in cancerous glands of Gleason's pattern </=2; and complete loss of UG immunoreactivity in cancerous glands of Gleason's pattern 3 or greater. In addition, in the one case of metastatic prostate cancer that we examined, the prostate cancer cells within the lymph node lacked UG expression. These findings suggest that the loss of UG expression may be an indicator of prostate cancer progression and possibly a component of the molecular natural history of prostate cancer, which may have prognostic value.

Adult↗
PubMed1996

Intracoronary irradiation: dose response for the prevention of restenosis in swine.

PURPOSE: Restenosis after percutaneous transluminal coronary angioplasty represents, in part, a proliferative response of vascular smooth muscle at the site of injury. We have previously shown that high-dose radiation (20 Gy), delivered via an intracoronary 192Ir source, causes focal medial fibrosis and markedly impairs the restenosis process after balloon angioplasty in swine. This study sought to delineate the dose-response characteristics of this effect. METHODS AND MATERIALS: Forty juvenile swine underwent coronary angiography; a segment of the left coronary artery was chosen as a target for balloon injury. In 30 swine, a 2 cm ribbon of 192Ir was positioned at the target segment and 20, 15, or 10 Gy were delivered to the vessel wall (10 animals/dose). Subsequently, overdilatation balloon angioplasty was performed at the irradiated segment. In 10 control swine, overdilatation balloon angioplasty was performed without previous irradiation. Thirty-eight animals survived until sacrifice at 30 +/- 3 days. Histopathological analysis was performed by a pathologist in a blinded manner. The area of maximal luminal compromise within the target segment was analyzed via computer-assisted planimetry. RESULTS: Neointimal area was decreased by 71.4% at 20 Gy and by 58.3% at 15 Gy compared with control animals (p < 0.05 for both). A stimulatory effect on smooth muscle cell proliferation was noted at 10 Gy, with a 123% increase in neointimal area compared with controls (p < 0.05). Mean percent area stenosis was also reduced by 63% at 20 Gy and by 74.8% at 15 Gy compared with controls (p < 0.05 for both). CONCLUSIONS: Intracoronary irradiation prior to overstretch balloon angioplasty markedly reduces neointima formation; this effect is dose dependent, with evidence of a significant stimulatory effect at 10 Gy. The effective therapeutic dose range for the prevention of restenosis in this model begins at approximately 15 Gy delivered to the vessel wall.

Angioplasty, Balloon, Coronary↗
PubMed1996

Molecular studies of the asymmetric pore structure of the human cardiac voltage- dependent Ca2+ channel. Conserved residue, Glu-1086, regulates proton-dependent ion permeation.

Proton transfer to calcium channels results in rapid fluctuations between two non-zero conductance levels when the current is carried by monovalent cations. A combination of site-directed mutagenesis and single-channel recording techniques were used to identify the unique proton acceptor site as Glu-1086, a conserved glutamate residue located in the S5-S6 linker of motif III of calcium channels. Glu-1086 is part of an array of four glutamate residues in the pore-lining region of the channel conferring the high selectivity of calcium channels. Titration of Glu-1086 yielded a pKa value of 7.91 which is different from that expected for a free glutamic acid side-chain carboxyl. Proposed electrostatic interactions between charged nearby residues can account only in part for this phenomenon since individual elimination of the other three glutamate residues only slightly decreased the pKa of Glu-1086. These data, in addition to identifying the proton acceptor site, provide evidence for the influence of the microenvironment in forming the asymmetry of the conducting pathway of calcium channels.

Animals↗
PubMed1996

Dissection of antigenic and irritative effects of epicutaneously applied haptens in mice. Evidence that not the antigenic component but nonspecific proinflammatory effects of haptens determine the concentration-dependent elicitation of allergic contact dermatitis.

Allergic contact dermatitis differs from most other immune reactions by its strict dose dependence during the elicitation phase. Moreover, almost all known contact allergens can also induce dose-dependent irritative dermatitis and in general only elicit allergic contact dermatitis in sensitized individuals when applied within a narrow dose range. Therefore, we hypothesized that elicitation of contact hypersensitivity (CHS) may require two signals, antigen-specific effector cell activation and a non-antigen-specific proinflammatory signal, both of which are provided by application of a sufficient dose of hapten. To dissociate these putative two signals, oxazolone-sensitized mice were ear challenged with a dose of the specific hapten which was too low to elicit CHS. At the same time, an unrelated hapten was applied in a conventional concentration to the same skin site. Whereas neither treatment alone elicited a significant CHS response, application of both compounds together resulted in a strong CHS response that was indistinguishable from that elicited by the full dose of the specific hapten. Upon coadministration of the irrelevant hapten, allergic contact dermatitis could be elicited even when the dose of the specific hapten was further reduced by a factor of 10(3). In contrast, a dose reduction of the irrelevant hapten by a factor of two resulted in the loss of the CRS response. These data indicate that non-antigen-specific effects of epicutaneously applied haptens significantly contribute to the elicitation of CHS responses and that the capacity of the hapten to evoke this proinflammatory stimulus rather than its antigenicity is responsible for the strict concentration dependence.

Administration, Cutaneous↗
PubMed1996

Sequence-independent inhibition of in vitro vascular smooth muscle cell proliferation, migration, and in vivo neointimal formation by phosphorothioate oligodeoxynucleotides.

Phosphorothioate oligodeoxynucleotides (PS oligos) are antisense (sequence-specific) inhibitors of vascular smooth muscle cell (SMC) proliferation when targeted against different genes. Recently an aptameric G-quartet inhibitory effect of PS oligos has been demonstrated. To determine whether PS oligos manifest non-G-quartet, non-sequence-specific effects on human aortic SMC, we examined the effects of S-dC28, a 28-mer phosphorothioate cytidine homopolymer, on SMC proliferation induced by several SMC mitogens. S-dC28 significantly inhibited SMC proliferation induced by 10% FBS as well as the mitogens PDGF, bFGF, and EGF without cytotoxicity. Moreover, S-dC28 abrogated PDGF-induced in vitro migration in a modified micro-Boyden chamber. Furthermore, S-dC28 manifested in vivo antiproliferative effects in the rat carotid balloon injury model. S-dC28 suppressed neointimal cross-sectional area by 73% and the intima/media area ratio by 59%. Therefore, PS oligos exert potent non-G-quartet, non-sequence-specific effects on in vitro SMC proliferation and migration as well as in vivo neointimal formation.

Animals↗
PubMed1996

[Head and neck sarcoma].

We reviewed patients with primary soft tissue and bone sarcomas treated in our department. Malignant tumors arising in somatic, connective, soft tissues, especially those of the head and neck, are uncommon and few reports have been published. Between 1980 and 1995 15 patients with head and neck sarcoma were seen. The major sites involved included: paranasal sinuses and orbits (2 patients), neck (4) and 1 each in the forehead, temporal region, mandible, parapharyngeal space, tongue, hypopharynx, larynx, cervico-mediastinal region and nasal cavity. Follow-up ranged from 1-16 years. The youngest patient was a 12-year-old male. Rhabdomyosarcoma, one of the most common mesenchymal tumors found in the head and neck, especially in children, was excluded from our study because of its different clinical behavior and its chemosensitivity, unlike other sarcomas. Most of our patients were treated with wide-field resection; 12 received postoperative radiation, and 3 combined surgery and chemotherapy. Wide excision with negative margins is considered an important, positive, prognostic factor, as the extent and adequacy of excision largely determines survival and the incidence of local recurrence. All our patients underwent initial, wide, local excision of the lesion. Our observations strongly suggest that wide resection is the most effective means of therapy for sarcoma of the head and neck. Radical neck dissection was not only performed for manifest regional neck metastases, but was also used for completing the enlarged, wide-excisions of liposarcomas. The worst survival was in patients with osteosarcoma, angiosarcoma and fibrosarcoma, with an absolute 5-year survival of 60% (9/15).

Adult↗
PubMed1996

Involution of the lactating mammary gland is inhibited by the IGF system in a transgenic mouse model.

Development of the mammary gland during puberty, pregnancy, and lactation is controlled by steroid and peptide hormones and growth factors. To determine the role of the insulin-like growth factors (IGFs) in this process we developed a transgenic model using the whey acidic protein (WAP) gene to direct expression of rat IGF-I and human IGF binding protein-3 (IGFBP-3) to mammary tissue during late pregnancy and throughout lactation. High levels of expression of transgenic IGF-I and IGFBP-3 were seen in lobular-alveolar cells by in situ hybridization. There was no obvious effect on mammary development during pregnancy and lactation; indeed, mothers were capable of nursing their pups normally and the only structural difference seen in the mammary glands at peak lactation was an overall smaller size of the alveoli. We also evaluated the role of IGF-I and IGFBP-3 in the remodeling of mammary tissue during involution. Compared with control animals, the process of involution was modified in both transgenic lines. The degree of apoptotic cells was lower in the WAP-IGF-I and WAP-BP-3 expressing mice. In addition, there was a more quiescent pattern of involution with residual lobular secretary ability and a muted host inflammatory reaction with fewer lumenal microcalcifications. These results demonstrate that IGF-I and IGFBP-3 may modulate the involutionary process of the lactating mammary gland.

Animals↗
PubMed1996

Lack of involvement of protein kinase A phosphorylation in voltage-dependent facilitation of the activity of human cardiac L-type calcium channels.

Phosphorylation by protein kinase A is thought to be involved in voltage-dependent facilitation of calcium channels. Here we have shown that the subunit complex of a cloned human cardiac calcium channel, expressed in Xenopus oocytes, responds to voltage-dependent facilitation by an approximately 50% increase of the calcium channel peak current. The removal of all protein kinase A consensus sequences by site-directed mutagenesis decreased but did not eliminate the response to prepulse facilitation. Moreover, Rp-cAMP-S, an inhibitor of protein kinase A, could not prevent facilitation of the wild-type calcium channel currents. Similarly, AMP-PNP a nonhydrolyzable analog of ATP, while significantly decreasing the whole-cell current amplitude, failed to reduce the response to double-pulse facilitation. Therefore, we conclude that the voltage-dependent facilitation of cloned calcium channel currents is not due to enhancement of phosphorylation, but probably to some type of voltage-induced conformational change in the channel.

Adenylyl Imidodiphosphate↗
PubMed1996

Standardizing flow cytometry: construction of a standardized fluorescence calibration plot using matching spectral calibrators.

Calibration of flow cytometers is becoming an increasingly important issue for both quality control of instrument performance and quantitation of antibody binding capacity of cells. Due to the numerous different instruments and analysis software currently available, a standardized method of calibration is necessary if interlaboratory comparison of instrument performance and antibody binding is to be achieved. This report describes a new methodology to obtain a standard calibration plot that can be derived from all instruments and from which specific instrument-independent performance parameters may be calculated that can be used to directly compare the performance and setup of these instruments. The requirements that the calibrated standards must meet are discussed, as well as the acceptable ranges proposed for the instrument-independent performance parameters. In addition, data are presented from standard calibration plots generated by different flow cytometers in numerous laboratories. The corresponding Primary Performance Parameters calculated from these plots are presented and compared. It is expected that the use of this calibration method may help standardize flow cytometric measurements and will provide instrument-independent performance parameters to monitor quality control of instruments and reagents.

Calibration↗
PubMed1996

Topography of cerebral infarction associated with carotid artery dissection.

Because the pathogenesis of cerebral ischaemia in internal carotid artery dissection (ICAD) is controversial we studied the topography of cerebral infarction that results from ICAD according to pathophysiology of embolic and haemodynamic stroke. Sixty-four patients with 67 ICADs diagnosed by angiography, Doppler duplex sonography and magnetic resonance imaging (MRI) were studied prospectively during the past decade. According to current pathophysiological concepts, cortical territorial infarcts and large subcortical lenticulostriate infarcts revealed by CT or MRI were classified as embolic, while smaller infarcts in the subcortical junctional zone and infarcts in the cortical borderzone between the middle (MCA) and anterior cerebral artery were interpreted as haemodynamic infarcts. Of the 67 dissections 37 (55%) were associated with brain infarcts, of which territorial MCA infarcts of variable size accounted for 60%. These were combined with infarcts of the anterior and posterior cerebral artery in 5%; 8% of the patients had complete MCA infarction. Large lenticulostriate infarcts were present in 11%. Haemodynamic infarcts involved the subcortical junctional zone in 16% but never the anterior cortical borderzone. Although different abnormal Doppler findings indicated haemodynamically significant carotid obstruction in all symptomatic ICADs, only the characteristic high-resistance Doppler signal was significantly associated with the occurrence of brain infarction (in 66%, P < 0.01). The angiographic features of ICAD did not correlate with the incidence or with the topography of cerebral infarction. Patterns of infarction in ICAD indicate a predominantly embolic causation probably due to thrombus formation in the dissected carotid artery in the presence of severe haemodynamic obstruction, as demonstrated by Doppler sonography.

Adolescent↗
PubMed1996

External protons enhance the activity of the hyperpolarization-activated K channels in guard cell protoplasts of Vicia faba.

Hyperpolarization-activated K channels (KH channels) in the plasmalemma of guard cells operate at apoplastic pH range of 5 to over 7. Using patch clamp in a whole-cell mode, we characterized the effect of varying the external pH between 4.4-8.1 on the activity of the KH channels in isolated guard cell protoplasts from Vicia faba leaves. Acidification from pH 5.5 to 4.4 increased the macroscopic conductance of the KH channels by 30-150% while alkalinization from pH 5.5 to 8.1 decreased it only by roughly 15%. The voltage-independent maximum cell conductance, increased by -60% between pH 8.1 and 4.4 with an apparent pKa of 5.3, most likely owing to the increased availability of channels. Voltage-dependent gating was affected only between pH 5.5 and 4.4. Acidification in this range shifted the voltage-dependent open probability by over 10 mV. We interpret this shift as an increase of the electrical field sensed by the gating subunits caused by the protonation of external negative surface charges. Within the framework of a surface charge model the mean spacing of these charges was approximately 30 A and their apparent dissociation constant was 10(-4.6). The overall voltage sensitivity of gating was not altered by pH changes. In a subgroup of protoplasts analyzed within the framework of a Closed-Closed-Open model, the effect of protons on gating was limited to shifting of the voltage-dependence of all four transition rate constants.

Fabaceae↗