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Biomedical subjects

J Schultz

Publications and source records attributed to J Schultz.

At least 55 records · Page 3Linked to original sources
PubMed1999

Protein families in multicellular organisms.

The complete sequence of the nematode worm Caenorhabditis elegans contains the genetic machinery that is required to undertake the core biological processes of single cells. However, the genome also encodes proteins that are associated with multicellularity, as well as others that are lineage-specific expansions of phylogenetically widespread families and yet more that are absent in non-nematodes. Ongoing analysis is beginning to illuminate the similarities and differences among human proteins and proteins that are encoded by the genomes of the multicellular worm and the unicellular yeast, and will be essential in determining the reliability of transferring experimental data among phylogenetically distant species.

Animals↗
PubMed1999

Reduced melanoma tumor formation in mice immunized with DNA expressing the melanoma-specific antigen gp100/pmel17.

Plasmid DNA encoding gene products of viruses or other pathogens has recently been applied by intramuscular injection as a novel type of vaccine. It can induce cytotoxic T cell response in small animals and protect against challenge with influenza A viruses. Combinations with cytokines or DNA-encoding cytokines have been applied in order to increase the efficiency of protection. A DNA vaccine has been analyzed here against malignant melanoma encoding gp100/pmel17, a melanoma-associated antigen. A small animal model was used by injection of B16 melanoma cells to syngeneic C57Bl/6 mice. DNA vaccination before tumor cell challenge leads to about 50% reduction of tumor size. The cytokine gene coding for GM-CSF did not increase the efficiency but also led to tumor size reduction when applied alone.

Animals↗
PubMed1999

Development of a percutaneous fiberoptic hepatic venous localization catheter.

OBJECTIVE: To develop a liver-specific biosensor system/catheter assembly that can be used to localize and cannulate the hepatic venous system without the need for fluoroscopic imaging. This would permit the bedside placement of a hepatic venous catheter for monitoring purposes without radiographic guidance. DESIGN: Experimental, in vitro. STUDY SETTING: Experimental laboratory at a university center. SUBJECT: This was a simulation study to evaluate the ability of a cardiovascular monitoring catheter mounted with a liver-specific biosensor to anatomically identify a side arm tributary. The experimental system used for this study mimics the hepatic vein draining into the inferior vena cava and allows its localization without the need for assisted imaging. The biosensor design and catheter/sensor assembly function were studied in this in vitro model. INTERVENTIONS: A liver-specific biosensor was developed by housing a homogeneous affinity fluorescence assay system sensitive to galactose in a microdialysis hollow fiber receptacle. A polyvinyl chloride tube containing a side arm was constructed to mimic the confluence of a venous tributary (i.e., the hepatic vein) with a major vascular channel (i.e., the vena cava). In this simulation, the side arm was continuously perfused with a liver-sensitive analyte (galactose) and the main channel was perfused with galactose-free buffer. A cardiovascular catheter containing a fiberoptic waveguide mounted with a galactose-sensitive fluorescent probe was advanced along the main conduit to assess its ability to identify the location of the galactose side arm infusion site. MEASUREMENTS AND MAIN RESULTS: The response of the fiberoptic sensor to different galactose concentrations was assessed and found to be almost linear over the concentration range of 0 to 2 mM, which encompasses the expected utilization range of this system. The variability in identifying the galactose infusion point (simulated hepatic vein) in a 15-cm conduit was 1.7 to 2.8 mm, or 1.1% to 1.9%. CONCLUSIONS: The construction of a catheter/sensor system with the ability to provide accurate spatial/anatomical localization data for the hepatic venous system is feasible. This assembly will eliminate the need for ancillary imaging systems for catheter/sensor delivery to an individual organ system and potentially can be positioned at the bedside in a fashion similar to the pulmonary artery flotation catheter.

Bias↗
PubMed1999

Fluorescence studies of lens epithelial cells and their constituents.

Steady-state and time-resolved fluorescence measurements have been made of human and rabbit lens epithelial cells and their total soluble protein. Excitation at 350 nm results in broad fluorescence spectra peaking at 450 nm and stretching into the visible past 650 nm. The fluorescence excitation spectra peak around 350 nm. We assign the species responsible for this absorption and fluorescence as NADPH. Because the absorption of near-UV light (300-400 nm) is responsible for cell damage and death, we postulate that excited states of NADPH are implicated in the mechanisms of cell damage. Preirradiation with 355 nm light leads to a loss of NADPH fluorescence but with no change in decay kinetics. Possible mechanisms for cell damage are explored.

Animals↗
PubMed1998

SMART, a simple modular architecture research tool: identification of signaling domains.

Accurate multiple alignments of 86 domains that occur in signaling proteins have been constructed and used to provide a Web-based tool (SMART: simple modular architecture research tool) that allows rapid identification and annotation of signaling domain sequences. The majority of signaling proteins are multidomain in character with a considerable variety of domain combinations known. Comparison with established databases showed that 25% of our domain set could not be deduced from SwissProt and 41% could not be annotated by Pfam. SMART is able to determine the modular architectures of single sequences or genomes; application to the entire yeast genome revealed that at least 6.7% of its genes contain one or more signaling domains, approximately 350 greater than previously annotated. The process of constructing SMART predicted (i) novel domain homologues in unexpected locations such as band 4.1-homologous domains in focal adhesion kinases; (ii) previously unknown domain families, including a citron-homology domain; (iii) putative functions of domain families after identification of additional family members, for example, a ubiquitin-binding role for ubiquitin-associated domains (UBA); (iv) cellular roles for proteins, such predicted DEATH domains in netrin receptors further implicating these molecules in axonal guidance; (v) signaling domains in known disease genes such as SPRY domains in both marenostrin/pyrin and Midline 1; (vi) domains in unexpected phylogenetic contexts such as diacylglycerol kinase homologues in yeast and bacteria; and (vii) likely protein misclassifications exemplified by a predicted pleckstrin homology domain in a Candida albicans protein, previously described as an integrin.

Amino Acid Sequence↗
PubMed1998

The effect of anti-diuretic hormone on the endolymphatic sac of the inner ear.

The anti-diuretic hormone vasopressin (AVP) regulates water excretion from the kidney by increasing the water permeability of the collecting duct. AVP binds to V2-receptors and induces the translocation of aquaporin-2 water channels (AQP-2) into the apical plasma membrane of principal cells. By this mechanism AVP controls water reabsorption in the kidney. The effects of AVP on the endolymphatic sac (ES) of the inner ear, which is thought to mediate reabsorption of endolymph, were investigated. Both the V2-receptor and the AQP-2 water channel were found to be expressed in the ES epithelium. In the ES AVP binds to receptors most probably of the V2-subtype. Application of AVP to organotypically cultured ES inhibits membrane turnover in ribosomal-rich cells of the ES epithelia, which is thought to mediate translocation of AQP-2 into the surface membrane. This suggests that AVP has contrasting effects in the inner ear and kidney, which may be physiologically useful for maintaining endolymphatic pressure during severe hypovolemia. Animal experiments show that AVP causes endolymphatic hydrops after systemic application to guinea-pigs, which suggests a causal role for the increased AVP levels found in humans suffering from Ménière's disease.

Animals↗
PubMed1998

Specific interactions between the syntrophin PDZ domain and voltage-gated sodium channels.

Syntrophins are modular proteins belonging to the dystrophin associated glycoprotein complex and are thought to be involved in the regulation of the muscular system. Screening of peptide libraries revealed selectivity of the synotrophin PDZ domain toward the motif R/K/Q-E-S/T-X-V-COO- found to be highly conserved in the alpha-subunit C-terminus of vertebrate voltage gated sodium channels (VGSCs). The solution structure of the domain in complex with the peptide G-V-K-E-S-L-V shows specific interactions between the conserved residues in the peptide and syntrophin-characteristic residues in the domain. We propose that syntrophins localize VGSCs to the dystrophin network through its PDZ domain.

Amino Acid Sequence↗
PubMed1998

Vision screening of preschool children: evaluating the past, looking toward the future.

Vision problems of preschool children are detectable with a comprehensive eye examination; however, it is estimated that only 14% of children below the age of 6 years receive an eye examination. Screening is advocated as a cost-effective alternative to identify children in need of further vision care. Thirty-four states recommend or require vision screening of preschool children. Although laws and guidelines exist, only 21% of preschool children are actually screened for vision problems. There is little agreement concerning the best screening methods, and no validated, highly effective model for screening vision of preschool children. Newer screening tests have been designed specifically for preschool populations, and can be administered by lay screeners. Many have not been validated. Several are recommended by states or organizations without convincing scientific evidence of their effectiveness. This paper summarizes current laws and guidelines for preschool vision screening in the United States, reviews advantages and disadvantages of several test procedures, and provides recommendations for developing future preschool vision screening programs.

Child, Preschool↗
PubMed1998

Prediction of 10 repetition maximum for short-arc quadriceps exercise from hand-held dynamometer and anthropometric measurements.

Short-arc quadriceps exercise are commonly prescribed in physical therapy for strengthening knee extensor musculature. Determining the appropriate starting resistance has traditionally been a trial-and-error procedure. Therefore, developing an expedient method of estimating the correct starting resistance may lead to a more accurate exercise prescription. The primary purpose of this study was to establish a technique for predicting an individual's 10 repetition maximum (10 RM) based on hand-held dynamometer (HHD) strength recording and additional anthropometric predictor variables. Fifty healthy subjects (31 males and 19 females), aged 22-53 years, participated in the study. A prediction equation for determining 10 RM using HHD strength recording, weight, gender, and age was developed. By implementing this equation, clinicians can predict a normal, healthy, young to middle-aged adult's 10 RM within +/- 4.17 kg with a 95% confidence level (SEE = 2.13 kg).

Adult↗
PubMed1998

Superantigen-targeted therapy: phase I escalating repeat dose trial of the fusion protein PNU-214565 in patients with advanced gastrointestinal malignancies.

Antibody-directed, superantigen-induced cytotoxicity has been shown to have potent in vitro and in vivo antitumor effects in preclinical models. In the present study, PNU-214565, a recombinant fusion protein consisting of the Fab of the monoclonal antibody C242 and staphylococcal enterotoxin A (SEA), was used in an escalating repeat dose Phase I clinical trial in patients with advanced gastrointestinal malignancies. A prior single-dose Phase I clinical trial had demonstrated safety at doses of 1.5 ng/kg with toxicities of fever and hypotension that were not dose related. Twenty-seven patients (age range, 36-75 years; median, 62; 14 males and 13 females; 23 colorectal and 4 pancreatic) were treated in the present study with one cycle of four consecutive daily 3-h infusions of PNU-214565 at doses of 0.15 ng/kg (n = 3); 0.5 ng/kg (n = 3), 1.5 ng/kg (n = 4), 2.75 ng/kg (n = 12), and 3.5 ng/kg (n = 5). All patients had a good performance status [Eastern Cooperative Oncology Group: PS = 0 (n = 15), PS = 1 (n = 12)]. As in the single-dose trial, fever and hypotension were the most common toxicities. Dose-limiting toxicity (DLT), consisting of transient hypotension responsive to dopamine, was experienced by one patient treated at the 2.75 ng/kg dose level. One patient with pancreatic cancer metastatic to the liver experienced a partial response of hepatic metastases with stable pancreatic head abnormalities by computed tomography scan. Further dose escalation was suspended when two patients treated in a companion repeat dose Phase I study experienced DLT at the 4 ng/kg dose level. Multiparameter analyses on all patients treated in the two companion single-dose and two-repeated-dose Phase I trials revealed that the levels of patients' pretreatment anti-SEA antibodies protected against toxicity at a given drug dose. By jointly considering weight and the baseline anti-SEA concentration in a patient, it is possible to assign a PNU-214565 dose that will induce systemic cytokine release (a surrogate test to assess for the presence of uncomplexed drug and its ability to induce systemic cellular activation) without DLT. This pharmacodynamically based dosing scheme will be tested in future repeated-dose clinical trials and will define maximally tolerated doses of this powerful new immunotherapy approach.

Adult↗
PubMed1997

Capillary Rise for Thermodynamic Characterization of Solid Particle Surface

Surface properties in terms of surface free energy of solid particles were investigated using capillary rise experimental methods based on Washburn's equation. Two different approaches related to height and weight gain measurements were validated by silica flour and calcium carbonate surface studies. Dispersive components of the surface free energy and nondispersive components of solid-liquid energy of interaction were computed. Some differences observed are related to experimental data acquisitions. Many experimental difficulties, which led in the past to inaccurate wettability characteristics, have been controlled. A new link to the so-called geometrical factor of Washburn's equation has also been established after comparison of theoretical and experimental static and hydrodynamic radii. The high precision of the weight gain approach was achieved by strict control of experimental parameters such as temperature, powder packing, and sintered glass porosity.

Journal Article↗
PubMed1997

SAM as a protein interaction domain involved in developmental regulation.

More than 60 previously undetected SAM domain-containing proteins have been identified using profile searching methods. Among these are over 40 EPH-related receptor tyrosine kinases (RPTK), Drosophila bicaudal-C, a p53 from Loligo forbesi, and diacyglycerol-kinase isoform delta. This extended dataset suggests that SAM is an evolutionary conserved protein binding domain that is involved in the regulation of numerous developmental processes among diverse eukaryotes. A conserved tyrosine in the SAM sequences of the EPH related RPTKs is likely to mediate cell-cell initiated signal transduction via the binding of SH2 containing proteins to phosphotyrosine.

Amino Acid Sequence↗
PubMed1997

Induction of multiple anti-c-erbB-2 specificities accompanies a classical idiotypic cascade following 2B1 bispecific monoclonal antibody treatment.

The bispecific monoclonal antibody (bsmAb) 2B1, targeting the extracellular domain of c-erbB-2, the protein product of the HER-2/neu proto-ocogene, and Fc gamma RIII (CD16), expressed by human natural killer cells, neutrophils and differentiated monocytes, mediates the specific cytotoxic activity of these effector cells to tumor cells. A group of 24 patients with c-erbB-2-overexpressing tumors were treated with intravenously administered 2B1 in a phase I clinical trial and followed after treatment to evaluate the diversity and extent of the 2B1-induced humoral immune responses. As expected, 17 of 24 patients developed human anti-(murine Ig) antibodies (HAMA) to whole 2B1 IgG in a range from 100 ng/ml to more than 50000 ng/ml; 10 of these patients (42%) had strong (at least 1000 ng/ml) HAMA responses, some of which were still detectable at day 191. These responses were usually associated with similar reactivity to the F(ab')2 fragments of the parental antibodies 520C9 (anti-c-erbB-2) and 3G8 (anti-CD16). We sought evidence of an idiotypic cascade induction, indicating a prolonged specific treatment-induced effect on at least one selected target of 2B1. Using competition-based enzyme-linked immunosorbent assays, specific anti-idiotypic antibodies (Ab2) were detectable against 520C9 in 11 patients and against 3G8 in 13 patients. Peak anti-idiotypic antibodies generally occurred 3-5 weeks from treatment initiation, with a downward trend thereafter. There was a statistically significant correlation among the induction of significant HAMA responses, anti-idiotypic antibody production and the development of antibodies to c-erbB-2. The anti-c-erbB-2 responses, which were distinct from anti-anti-idiotypic (Ab3) antibodies, were detected in the post-treatment sera of 6/16 patients examined. No obvious correlation could be made between the development of humoral immune responses, the dose received, and the clinical response. Future investigation involving 2B1 therapy will concentrate on investigating an association of these humoral responses to any c-erbB-2-specific cellular responses. Manipulations of 2B1 therapy effects that augment immunity to c-erbB-2 could provide additional avenues for immunotherapy with this and other bispecific antibodies.

Adenocarcinoma↗
PubMed1997

Cytoplasmic signalling domains: the next generation.

Since the late 1980s, when Src-homology SH2 and SH3 domains were identified, the repertoire of non-catalytic signalling domains has increased to number over 30. As it is expected that further regulatory domains shall be found, unravelling the complex network of their interactions remains an on-going challenge.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1997

Regulation of the human IgE receptor (Fc epsilonRII/CD23) by Epstein-Barr virus (EBV): Ku autoantigen binds specifically to an EBV-responsive enhancer of CD23.

An early and critical event in immortalization of human B cells by Epstein-Barr virus (EBV) is induction of CD23 expression. CD23 is constitutively expressed in all EBV-immortalized B cells and its expression is tightly linked with immortalization. We have previously shown that activation of CD23 by EBV occurs at the transcriptional level and is mediated, in part, by EBV-responsive enhancer elements in the region of the type a promoter. We have localized one EBV-responsive enhancer (designated EBVRE) to a 37 bp sequence in intron 1 of type a CD23 that contains a GC-rich sequence that binds nuclear protein(s) from EBV-positive but not EBV-negative cells with sequence specificity. This EBVRE-binding activity was enhanced by protein phosphorylation and did not react with antibodies to the ubiquitous GC box transcription factor, Sp1. We have now shown by protein purification with peptide sequencing and immunological reactivity that p70/p80 Ku autoantigen [the DNA-binding component of DNA-dependent protein kinase (DNA-PK)] binds to this EBVRE with high affinity and sequence specificity. Although Ku autoantigen is ubiquitously expressed, an EBV-specific DNA-protein complex that contains Ku was elicited from EBV-positive but not EBV-negative nuclear extracts. Furthermore, the formation of this EBV-specific DNA-Ku complex was dramatically enhanced by protein phosphorylation. Thus, we have identified EBVRE-binding activity that contains the Ku autoantigen, is DNA sequence specific and is present in EBV-positive but not EBV-negative nuclear extracts. The possible functional significance of the Ku autoantigen-EBVRE interaction is discussed in light of the role of DNA-PK in phosphorylation and activation of several transcription factors. We suggest that phosphorylation of the EBV-specific EBVRE-binding activity by DNA-PK may modulate its activity as a transcription factor.

Amino Acid Sequence↗