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S Schwartz

Publications and source records attributed to S Schwartz.

At least 91 records · Page 5Linked to original sources

Early effects of exogenous arginine after the implantation of prosthetic material into the rat abdominal wall.

We have investigated the effects of high arginine (Arg) levels (7.5 mg/100 g body weight per hour) on the early integration of biocompatible mesh grafts into the rat abdominal wall. Studies were performed over implantation intervals of 6, 12, 24 or 48 hours (n=12, each). Arginine and related compounds were quantified in plasma, wound fluids and multiple tissues. Plasma nitric oxide (NO) production was studied. Strips were taken from the polypropylene fiber-host tissue interfaces (PTIs) for optical microscopic analysis and for immunohistochemical analysis using rat-specific antibodies against type I and type III collagens. Exogenous Arg was metabolized at the peripheral tissues but reliably reached the wound space. High amounts of Arg and ornithine (Orn) were detected in the specimens considered. No changes on citrulline (Ctr) or NO concentrations were observed, overall suggesting that, during the period studied, the arginase pathway predominated. The acute scarring response differed significantly in the two placements considered. The P-SS interface evidenced more extensive new tissue growth than the P-DS interface. Forty-eight hours after mesh implantation cellular infiltration, fibroblast proliferation, and mesh-surrounding angiogenesis were higher in the arginine-treated rats. Type III collagen staining was related to arginine treatment, being higher (++) in the study group. In conclusion, and independently of the site of mesh placement, supplemental Arg seemed to favorably affect early local collagen deposition. This could be potentially helpful to ameliorate the integration of biomaterials into the tissues and, consequently, to allow for the design of more selective therapeutic strategies to prevent hernia recurrence rates.

Abdominal Muscles↗

arrow encodes an LDL-receptor-related protein essential for Wingless signalling.

The Wnt family of secreted molecules functions in cell-fate determination and morphogenesis during development in both vertebrates and invertebrates (reviewed in ref. 1). Drosophila Wingless is a founding member of this family, and many components of its signal transduction cascade have been identified, including the Frizzled class of receptor. But the mechanism by which the Wingless signal is received and transduced across the membrane is not completely understood. Here we describe a gene that is necessary for all Wingless signalling events in Drosophila. We show that arrow gene function is essential in cells receiving Wingless input and that it acts upstream of Dishevelled. arrow encodes a single-pass transmembrane protein, indicating that it may be part of a receptor complex with Frizzled class proteins. Arrow is a low-density lipoprotein (LDL)-receptor-related protein (LRP), strikingly homologous to murine and human LRP5 and LRP6. Thus, our data suggests a new and conserved function for this LRP subfamily in Wingless/Wnt signal reception.

Animals↗

Web-based visualization tools for bacterial genome alignments.

With the increase in the flow of sequence data, both in contigs and whole genomes, visual aids for comparison and analysis studies are becoming imperative. We describe three web-based tools for visualizing alignments of bacterial genomes. The first, called Enteric, produces a graphical, hypertext view of pairwise alignments between a reference genome and sequences from each of several related organisms, covering 20 kb around a user-specified position. Insertions, deletions and rearrangements relative to the reference genome are color-coded, which reveals many intriguing differences among genomes. The second, Menteric, computes and displays nucleotide-level multiple alignments of the same sequences, together with annotations of ORFs and regulatory sites, in a 1 kb region surrounding a given address. The third, a Java-based viewer called Maj, combines some features of the previous tools, and adds a zoom-in mechanism. We compare the Escherichia coli K-12 genome with the partially sequenced genomes of Klebsiella pneumoniae, Yersinia pestis, Vibrio cholerae, and the Salmonella enterica serovars Typhimurium, Typhi and Paratyphi A. Examination of the pairwise and multiple alignments in a region allows one to draw inferences about regulatory patterns and functional assignments. For example, these tools revealed that rffH, a gene involved in enterobacterial common antigen (ECA) biosynthesis, is partly deleted in one of the genomes. We used PCR to show that this deletion occurs sporadically in some strains of some serovars of S.enterica subspecies I but not in any strains tested from six other subspecies. The resulting cell surface diversity may be associated with selection by the host immune response.

DNA, Bacterial↗

Analphoid 3qter markers.

Two cases of marker chromosomes derived from a non-centromeric location were studied to determine the characteristics of these markers with respect to the presence of functional centromeres and whether an associated phenotype could be described. The markers were characterized by fluorescence in situ hybridization and centromeric protein studies. Assessments were done to identify clinical features. Case 1 is a girl referred at age 1.5 years with swirly areas of hyperpigmentation, bilateral preauricular pits, hypotonia, developmental delay, and seizures. Case 2 is a male first evaluated as a newborn and then later during the first year of life. He had streaky hypopigmentation, right preauricular pit, accessory nipples, postaxial polydactyly, asymmetric cerebral ventricles, duplicated right kidney, a right pulmonary artery stenosis, and seizures. Mosaicism for an extra marker from the 3qter region was present in both cases. Both markers had a constriction near one end and were C-band negative. Centromeric protein studies indicated absence of CENP-B, presence of CENP-C (data for case 1 only), and presence of CENP-E. Marker chromosomes were thus identified with a chromosomal origin far from their usual centromeric region and yet appeared to have functional centromeres. These two cases did not permit a specific clinical phenotype to be ascribed to the presence of tetrasomy for 3q26.2 approximately 3q27.2-->3qter.

Autoantigens↗

Molecular and cytogenetic analysis of familial Xp deletions.

Five families in which an Xp deletion is segregating and two families in which an X chromosome rearrangement including a deletion of the short arm is segregating were ascertained for study. Normal fertility was seen in all families. Members from 5 of the 7 families manifested short stature (height <5th centile), while normal height was present in two families. Studies of both the FMR-1 and the androgen receptor loci using PCR based X-inactivation analysis demonstrated that in all families analyzed, there is preferential inactivation of one X chromosome. Molecular cytogenetic analysis showed that members of 3 of the 7 families share a common breakpoint in an approximate 2-3 Mb region at Xp22.12, suggesting a possible hotspot for chromatin breakage. Previous genotype-phenotype correlations and deletion mapping have indicated that a gene for stature resides within the pseudoautosomal region in Xp22.33. Our findings indicate that the loss of this region is not always associated with short stature, suggesting that other factors may be involved.

Body Height↗

HuR, a protein implicated in oncogene and growth factor mRNA decay, binds to the 3' ends of hepatitis C virus RNA of both polarities.

To identify cellular factors that interact with hepatitis C virus RNA, cellular extracts were subjected to UV cross-linking to radiolabeled RNAs corresponding to the hepatitis C virus 5' and 3' untranslated regions of positive and negative polarities. Our results demonstrate that the U-rich region of the hepatitis C virus 3' untranslated region of the positive RNA strand is a hot spot for cellular RNA binding proteins. Two of these proteins were identified as the ELAV-like HuR protein and hnRNP C. Interestingly, HuR and hnRNP C also interacted with the 3' end of the RNA representing the negative strand of the HCV genome. The binding of HuR and hnRNP C to the 3' ends of the HCV RNAs of both negative and positive polarities suggests that HuR and hnRNP C may be involved in the transcription of the HCV RNA genome. Alternatively, they act by protecting the HCV RNAs from premature degradation by binding to their 3' ends. However, we were unable to demonstrate an effect on HCV RNA stability by the HuR protein. These interactions may be necessary for the establishment of chronic active infections that may develop into cirrhosis or hepatocellular carcinoma.

Antigens, Surface↗

Coaching for a winning dental team.

In 1943, Abraham Maslow, the "father of humanistic psychology," formulated his "Hierarchy of Needs Theory." Maslow proposed people have needs that must be satisfied, and these needs will motivate until they are satisfied. The needs are arranged in a hierarchy or pyramid ranging from basic needs to higher needs with an individual needing to satisfy a lower need before a higher need can motivate. The five needs of the hierarchy are: physiological needs, safety needs, social needs, esteem needs, and self-actualization. This article discusses adaptation of the hierarchy of needs to the dental practice to motivate staff to perform at a higher level.

Dental Staff↗

Prostate cancer and other xenografts from cells in peripheral blood of patients.

Good models for the investigation of human prostate cancer are few. Cells from approximately 9.2-21 ml of peripheral blood from patients with metastatic prostate cancer or metastatic colon cancer were injected s.c. into nude mice. Prostate cancer from 2 of 11 patients and colon cancer from 1 of 3 patients were found to be growing as metastases in the lungs of the nude mice. To our knowledge, this is the first report of the formation of xenografts from carcinoma cells taken directly from the peripheral blood of patients. Expanding circulating cancer cells with this approach may have important translational applications including: (a) development of models of human cancers; and (b) sampling of cancers from specific patients for novel molecular and therapeutic approaches.

Animals↗

Human immunodeficiency virus type 1 Nef epitopes recognized in HLA-A2 transgenic mice in response to DNA and peptide immunization.

We investigated the immune response against a human immunodeficiency virus type 1 (HIV-1) nef DNA sequence administered epidermally in mice transgenic for the human major histocompatibility complex (MHC) class I molecule HLA-A201. Ten potential HLA-A2 binding 9-mer Nef peptides were identified by a computer-based search algorithm. By a cell surface MHC class I stabilization assay, four peptides were scored as good binders, whereas two peptides bound weakly to HLA-A2. After DNA immunization, cytotoxic T lymphocyte (CTL) responses were predominantly directed against the Nef 44-52, 81-89, and 85-93 peptides. Interestingly, the 44-52 epitope resides outside the regions of Nef where previously described CTL epitopes are clustered. Dominance among Nef-derived peptides did not strictly correlate with HLA-A2 binding, in that only one of the high-affinity binding peptides was targeted in the CTL response. The 44-52, 85-93, and 139-147 peptides also generated specific CTLs in response to peptide immunization. T helper cell proliferation was detected after stimulation with 20-mer peptides in vitro. Three Nef regions (16-35, 106-125, and 166-185) dominated the T helper cell proliferation. The implications of these results for the development of DNA-based vaccines against HIV is discussed.

AIDS Vaccines↗

Mosaic tetrasomy 8q: inverted duplication of 8q23.3qter in an analphoid marker.

We observed an analphoid marker chromosome stable through cell division in a 16-year-old girl with developmental delay, short stature, limb contractures, and ovaries containing multiple cysts. She also developed myasthenia gravis at 15 years. The marker chromosome, present in 75% of metaphases (and in 90% of transformed lymphoblastoid cells), was C-band negative, and had no pan alpha-satellite sequences detectable by fluorescence in situ hybridization (FISH). The 8q origin of the marker was determined by use of subtelomeric probes and was confirmed by chromosome 8 painting probes. The marker was shown to be an inversion duplication of 8q when subtelomeric, telomeric, and c-myc FISH probes hybridized to both ends of the marker. The karyotype was 47,XX,+inv dup(8)(qter--> q23.3::q23.3-->[neocen]-->qter), resulting in tetrasomy for 8q23.3qter. The parents had normal karyotypes. Centromeric proteins CENP-C and CENP-E were present, but alpha associated centromere protein CENP-B was absent at a position defining a neocentromere.

Abnormalities, Multiple↗

Molecular cytogenetic analysis of eight inversion duplications of human chromosome 13q that each contain a neocentromere.

Neocentromeres are fully functional centromeres that have arisen in previously noncentromeric chromosomal locations on rearranged chromosomes. The formation of neocentromeres results in the mitotic stability of chromosomal fragments that do not contain endogenous centromeres and that would normally be lost. Here we describe a unique collection of eight independent patient-derived cell lines, each of which contains a neocentromere on a supernumerary inversion duplication of a portion of human chromosome 13q. Findings in these patients reveal insight into the clinical manifestations associated with polysomy for portions of chromosome 13q. The results of FISH and immunofluorescent analysis of the neocentromeres in these chromosomes confirm the lack of alpha-satellite DNA and the presence of CENtromere proteins (CENP)-C, -E, and hMAD2. The positions of the inversion breakpoints in these chromosomes have been placed onto the physical map of chromosome 13, by means of FISH mapping with cosmid probes. These cell lines define, within chromosome 13q, at least three distinct locations where neocentromeres have formed, with five independent neocentromeres in band 13q32, two in band 13q21, and one in band 13q31. The results of examination of the set of 40 neocentromere-containing chromosomes that have thus far been described, including the 8 neocentromere-containing chromosomes from chromosome 13q that are described in the present study, suggest that chromosome 13q has an increased propensity for neocentromere formation, relative to some other human chromosomes. These neocentromeres will provide the means for testing hypotheses about sequence requirements for human centromere formation.

Aneuploidy↗

Risk factors for a causal intermediate and an endpoint: reconciling differences.

When a risk factor influences the intermediary but not progression to the endpoint, it has been shown that the relative risk estimate for the causal intermediate is identical to that for the endpoint under a single pathway framework. When there are multiple pathways, the relative risk estimate for the endpoint is reduced. The authors examine how the reduction of the effect size from a risk factor's association with the causal intermediate to that with the endpoint relates to the proportion of endpoint cases arising through other pathways, and the measure of effect used. For multiple pathways, all measures of effect are reduced and the reduction increases as the proportion of endpoint cases arising through other pathways increases. For single pathways, the relative rate ratio and odds ratios are reduced. In particular, the reduction in the odds ratio may be dramatic because of the commonness of causal intermediates relative to the endpoint. Comparisons of causal intermediate studies with those for the endpoint should consider the influences of multiple pathways, the prevalence of the causal intermediate, the measure of effect used, and the multiple effects a risk factor may have along the pathway when interpreting the differences observed across the causal chain.

Colorectal Neoplasms↗

A multicenter investigation with D-FISH BCR/ABL1 probes.

Twenty-eight laboratories evaluated a new fluorescence in situ hybridization (FISH) strategy for chronic myeloid leukemia. In a three-part study, bcr/abl1 D-FISH probes were used to study bone marrow specimens. First, laboratories familiarized themselves with the strategy by applying it to known normal and abnormal specimens. Then, collectively the laboratories studied 20 normal and 20 abnormal specimens blindly and measured workload. Finally, each laboratory and two experts studied six serial dilutions with 98-0% abnormal nuclei. Using the reported normal cutoff of < 1% abnormal nuclei, participants reported no false-negative cases and 15 false-positive cases (1-6.6% abnormal nuclei). Results provided by participants for serial dilutions approximated the expected percentages of abnormal nuclei, but those from the experts exhibited greater precision. The clinical sensitivity, precision, nomenclature, workload, recommendations for training, and quality assurance in methods using D-FISH in clinical practice are discussed.

Bone Marrow↗

Isolation and molecular analysis of inv dup(15) and construction of a physical map of a common breakpoint in order to elucidate their mechanism of formation.

An inverted duplication of chromosome 15 [inv dup(15)] is the most common supernumerary marker chromosome, comprising approximately 50% of all chromosomes in this class. Structurally, the inv dup(15) is a mirror image with the central axis defining a distal break within either the heterochromatic alpha-satellite array or along the euchromatin in the long (q) arm of the chromosome. There are several types of inv dup(15), classified by the amount of euchromatic material present. Generally, they are bisatellited, pseudodicentric and have a breakpoint in 15q11-q14. A suggested mechanism of formation of inv dup(15) involves illegitimate recombination between homologous chromosomes followed by nondisjunction and centromere inactivation. The proximal portion of chromosome 15 contains several low-copy repeat sequence families and it has been hypothesized that errors in pairing among these repeats may result in structural rearrangements of this chromosome including the inv dup(15). To test this hypothesis and to determine the mechanism of formation, the inv dup(15) from four cases was isolated in somatic cell hybrids and polymerase chain reaction microsatellite markers were used to determine the origin of exchange. Two appeared to result from interchromosomal and two from intrachromosomal exchange, one of which occurred post-recombination. In addition, a detailed physical map of the breakpoint region in the largest inv dup(15) was constructed placing eight new sequence-tagged sites and ten new bacterial artificial chromosome markers in the region.

Base Sequence↗

"Whole body" mobility after one year of intraoral appliance therapy in children with cerebral palsy and moderate eating impairment.

The reciprocal influence of body postures on the oral structures, but also of the oral structures on body postures, has been proposed by clinicians and is taken into consideration when treating children with poor postural control and moderate to severe eating impairments. However, this relationship has not been rigorously investigated. The purpose of this study was to document the possible relationships among oral-motor, postural, and ambulatory control. Ambulatory skills [exclusive use of wheelchair (w/c) vs w/c and ambulation], postural control when sitting, "pathologic" reflexes, and lip and tongue posture were recorded before and after one year of therapy with an intraoral appliance (ISMAR) in 20 children with cerebral palsy and moderate eating impairment. Significant improvement occurred in sitting (head-trunk-foot control) following one year of ISMAR therapy. Ambulatory status also significantly improved above the level of maturation. Half of the children showed marked improvement in oral posture, i.e., their resting mouth posture was closed rather than open. These results support an hypothesis of interaction between oral structures and postural control of the "whole body." Further studies are needed to determine the controls of such a relationship.

Adolescent↗

Inhibitory activity of the human papillomavirus type 1 AU-rich element correlates inversely with the levels of the elav-like HuR protein in the cell cytoplasm.

We have analysed the activity of the negative element in the late 3' untranslated region of the cutaneous human papillomavirus type 1 (HPV-1) mRNAs in a panel of epithelial cells, of both mucosal and cutaneous origin. The inhibitory activity was cell line dependent. Determination of the levels of heterogeneous ribonucleoprotein C1/C2 and HuR that have been shown previously to interact specifically with the HPV-1 negative RNA element revealed that low levels of the HuR protein in the cytoplasmic fraction correlated with high inhibitory activity of the HPV-1 element, whereas cell lines displaying low inhibitory activity contained high levels of HuR in the cytoplasm. These results suggested that the HuR protein has a positive effect on HPV-1 late gene expression.

3' Untranslated Regions↗