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Biomedical subjects

J Peterson

Publications and source records attributed to J Peterson.

At least 37 records · Page 2Linked to original sources

Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains.

Virulence and immunity are poorly understood in Mycobacterium tuberculosis. We sequenced the complete genome of the M. tuberculosis clinical strain CDC1551 and performed a whole-genome comparison with the laboratory strain H37Rv in order to identify polymorphic sequences with potential relevance to disease pathogenesis, immunity, and evolution. We found large-sequence and single-nucleotide polymorphisms in numerous genes. Polymorphic loci included a phospholipase C, a membrane lipoprotein, members of an adenylate cyclase gene family, and members of the PE/PPE gene family, some of which have been implicated in virulence or the host immune response. Several gene families, including the PE/PPE gene family, also had significantly higher synonymous and nonsynonymous substitution frequencies compared to the genome as a whole. We tested a large sample of M. tuberculosis clinical isolates for a subset of the large-sequence and single-nucleotide polymorphisms and found widespread genetic variability at many of these loci. We performed phylogenetic and epidemiological analysis to investigate the evolutionary relationships among isolates and the origins of specific polymorphic loci. A number of these polymorphisms appear to have occurred multiple times as independent events, suggesting that these changes may be under selective pressure. Together, these results demonstrate that polymorphisms among M. tuberculosis strains are more extensive than initially anticipated, and genetic variation may have an important role in disease pathogenesis and immunity.

Bacterial Proteins↗

Identification of a neuronal nitric oxide synthase in isolated cardiac mitochondria using electrochemical detection.

Mitochondrial nitric oxide synthase (mtNOS), its cellular NOS isoform, and the effects of mitochondrially produced NO on bioenergetics have been controversial since mtNOS was first proposed in 1995. Here we functionally demonstrate the presence of a NOS in cardiac mitochondria. This was accomplished by direct porphyrinic microsensor measurement of Ca(2+)-dependent NO production in individual mitochondria isolated from wild-type mouse hearts. This NO production could be inhibited by NOS antagonists or protonophore collapse of the mitochondrial membrane potential. The similarity of mtNOS to the neuronal isoform was deduced by the absence of NO production in the mitochondria of knockout mice for the neuronal, but not the endothelial or inducible, isoforms. The effects of mitochondrially produced NO on bioenergetics were studied in intact cardiomyocytes isolated from dystrophin-deficient (mdx) mice. mdx cardiomyocytes are also deficient in cellular endothelial NOS, but overexpress mtNOS, which allowed us to study the mitochondrial enzyme in intact cells free of its cytosolic counterpart. In these cardiomyocytes, which produce NO beat-to-beat, inhibition of mtNOS increased myocyte shortening by approximately one-fourth. Beat-to-beat NO production and altered shortening by NOS inhibition were not observed in wild-type cells. A plausible mechanism for the reversible NO inhibition of contractility in these cells involves the reaction of NO with cytochrome c oxidase. This suggests a modulatory role for NO in oxidative phosphorylation and, in turn, myocardial contractility.

Animals↗

Microbial genes in the human genome: lateral transfer or gene loss?

The human genome was analyzed for evidence that genes had been laterally transferred into the genome from prokaryotic organisms. Protein sequence comparisons of the proteomes of human, fruit fly, nematode worm, yeast, mustard weed, eukaryotic parasites, and all completed prokaryote genomes were performed, and all genes shared between human and each of the other groups of organisms were collected. About 40 genes were found to be exclusively shared by humans and bacteria and are candidate examples of horizontal transfer from bacteria to vertebrates. Gene loss combined with sample size effects and evolutionary rate variation provide an alternative, more biologically plausible explanation.

Animals↗

Setting system suitability criteria for detectability in high-performance liquid chromatography methods using signal-to-noise ratio statistical tolerance intervals.

For pharmaceutical products, one approach developed to assure that different chromatographic systems are capable of generating valid results is the system suitability test. Typically, a system suitability test involves numerical limits for predefined chromatographic parameters such as theoretical plates, tailing factor, injector reproducibility, etc. An estimation of the ratio of signal compared to baseline is one way to measure system performance, according to a valid method, independent of the instrument. However, since this comparison relates the height of the signal to the height of the noise, it is difficult to relate to the peak area measurements that are typically used for quantification of samples. Additionally, although peak area and peak height may be highly correlated over a wide region, peak area at very low concentrations can be more sensitive to all components of noise due to peak shape. To establish a system suitability criterion, one can use the ratio of the area signal to the baseline noise for replicate injections for samples prepared at concentration equal to the limit of quantitation during the validation studies. A lower limit for this ratio can be derived using statistical tolerance intervals. This lower limit can be applied as a system suitability criterion to measure that any system is performing adequately for measuring low level components in the sample for all future use of the method.

Chromatography, High Pressure Liquid↗

Therapeutic ultrasound for osteoarthritis of the knee.

BACKGROUND: Therapeutic ultrasound is one of several physical therapy modalities suggested for the management of pain and loss of function due to OA. OBJECTIVES: To assess the effectiveness of therapeutic ultrasound therapy for treating OA. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group trials register, and MEDLINE, up to the end of December 2000, using the sensitive search strategy developed by the Cochrane Collaboration. The search was complemented with bibliography searching of the reference list of the trials retrieved from the electronic search. Key experts in the area were contacted for further published and unpublished articles. SELECTION CRITERIA: All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing therapeutic ultrasound against placebo or another active intervention in patients with OA were selected. DATA COLLECTION AND ANALYSIS: Two reviewers determined the studies to be included based on inclusion and exclusion criteria (LB, VW). Data were independently abstracted by two reviewers (VW, LB), and checked by a third reviewer (BS) using a pre-developed adapted form for the OA sub-group of the Cochrane Musculoskeletal Group. The same two reviewers, using a validated scale, assessed the methodological quality of the RCTs and CCTs independently. OA outcome measures were extracted from the publications. The pooled analysis was performed using weighted mean differences (WMDs) for joint counts, pain, global and functional assessments. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout and random effects for outcomes showing heterogeneity. MAIN RESULTS: Three trials, including 294 patients with knee OA were included. Only one trial (n=74) compared therapeutic ultrasound to placebo. This trial showed no difference in range of motion, pain or gait velocity after 4 weeks of therapeutic ultrasound. Two trials compared therapeutic ultrasound to an active therapy (n=220). These trials showed no statistical difference between galvanic current or short wave diathermy for the outcomes of pain and patient-assessed improvement. REVIEWER'S CONCLUSIONS: Ultrasound therapy appears to have no benefit over placebo or short wave diathermy for patients with knee OA. These conclusions are limited by the poor reporting of the characteristics of the device, of the population, of the OA,and therapeutic application of the ultrasound and low methodological quality of the trials included. No conclusions can be drawn about the use of ultrasound in smaller joints such as the wrists or hands.

Adult↗

Do silicone breast implants cause rheumatologic disorders? A systematic review for a court-appointed national science panel.

OBJECTIVE: To assist in evaluating expert testimony and scientific evidence presented in law suits brought against silicone breast implant manufacturers, a US District Court Order established a National Science Panel to assess whether existing studies provide scientific evidence of an association between silicone breast implants and systemic classic/accepted connective disease, atypical connective disease, and certain signs and symptoms identified by plaintiffs in the law suits. Local disorders potentially associated with these implants were not addressed in this review. Therefore, we performed a systematic review of published studies on the association between silicone breast implants and systemic connective tissue disorders. METHODS: Data from relevant studies (human cohort, case-control, or cross-sectional studies with > or = 10 participants and appropriate controls) were identified through literature searches of Medline, Current Contents, HealthStar, Biological Abstracts, EMBase, Toxline, and Dissertation Abstracts. Two independent reviewers, using standard collection forms, extracted data from the included studies. Adjusted relative risks (RRs) in cohort studies and odds ratios (ORs) in case-control and cross-sectional studies were reported if provided; otherwise, unadjusted RRs and ORs were calculated. RESULTS: Twenty-four studies meeting inclusion criteria were identified. No association was evident between breast implants and any established or atypical connective tissue disorder. There was discordance among studies in reports of arthralgias, lymphadenopathy, myalgias, sicca symptoms, skin changes, and stiffness. CONCLUSION: The panel found no evidence to support expert testimony suggesting an association between silicone breast implants and connective diseases. Discordance for symptoms may reflect differences in symptoms included in various categories, the small number of cases, and the effect of having single subjects with > 1 symptom represented in analyses of each symptom reported. The process presented here is an early example of the use of independent scientific panels to help courts clarify scientific evidence in legal proceedings.

Breast Implants↗

Identification of respiratory complexes I and III as mitochondrial sites of damage following exposure to ionizing radiation and nitric oxide.

In 32D cl 3 hematopoietic progenitor cells, the overexpression of manganese superoxide dismutase (MnSOD, SOD2), the enzyme normally found in mitochondria, protects against the damaging effects of ionizing radiation. In the presence of a nitric oxide donor, which exacerbates the damage, inhibition of mitochondrial function can be demonstrated to be associated with respiratory complexes I (NADH dehydrogenase) and III (cytochrome c reductase), but not II (succinate dehydrogenase), IV (cytochrome c oxidase), or V (ATP synthase). The same pattern of inhibition is observed in the case of isolated bovine heart mitochondria exposed to ionizing radiation and the nitric oxide donor. The addition of authentic peroxynitrite (ONO2(-)) to isolated mitochondria also results in damage to complexes I and III (but not II, IV, and V), as shown by assays of electron-transfer activities and electron paramagnetic resonance (EPR) spectroscopic measurements, suggesting ONO2(-) to be responsible for most of the observed radiation damage in both the cultured cell lines and isolated mitochondria. It is argued that, in general, production of ONO2(-) is an important contributor to radiation damage in biological systems and the implications of these findings in relation to possible mechanisms of oxidant-linked apoptosis are briefly considered.

Adenosine Diphosphate↗

Connexin43 expression during Xenopus development.

The spatio-temporal expression of connexin43 in Xenopus laevis embryos was studied by in situ hybridization. Cx43 expression is first detected at stage 25 in the developing eye. In stage 32, expression was found in the margin of the lens placode, the cement gland, notochord, and in stage 37 in the branchial arches. Early limb buds show strong expression of Cx43 distally while later on expression is confined to sites of precartilage condensation.

Amino Acid Sequence↗

The outcome of endodontic resurgery: a systematic review.

AIM: The aim of this paper is to establish an outcome standard for the assessment of healing radiographically after resurgery of persistent periradicular lesions by systematically reviewing the results from published studies. METHODOLOGY: The systematic review process requires the definition of predetermined criteria delineating the inclusion parameters of studies reviewed. Of 42 papers that were reviewed, eight qualified for inclusion. A weighted-average was calculated from the results taken from the eight eligible, peer-reviewed studies, published between 1970 and 1997. RESULTS: Three hundred and thirty patients out of 2375 (14%) from the included studies underwent resurgery for failure of healing as determined radiographically. Of this population, 35.7% healed successfully after resurgery, 26.3% healed with uncertain results and 38% did not heal at the one-year follow-up. CONCLUSIONS: Although there is nearly equal distribution of results between all categories, a 35.7% rate of healing as assessed radiographically is essentially equivalent to the 38% failure rate. This paper will allow an evaluation of current research results to establish an outcome standard and enable techniques and filling materials to be evaluated and compared. Furthermore, the outcome standard can assist in defining demographic and aetiological factors that contribute to the potential outcome of resurgery cases.

Follow-Up Studies↗

Efficacy of a hepatitis C virus core antigen enzyme-linked immunosorbent assay for the identification of 'window-phase' blood donations.

BACKGROUND AND OBJECTIVES: Recent studies have suggested that potentially infectious donations provided during the antibody-negative 'window' phase of hepatitis C virus (HCV) infection may be identified by testing for viral RNA or HCV core protein. We therefore evaluated the performance of an HCV antigen enzyme-linked immunosorbent assay (ELISA) for identification of window-phase donations and for prospective screening of blood donors. MATERIALS AND METHODS: One-hundred and twenty-eight archived plasma donations containing HCV RNA, but lacking antibody to HCV (anti-HCV), were tested by using the HCV antigen ELISA, together with 9951 freshly collected serum and plasma specimens from blood donors. RESULTS: HCV core antigen was detected in 94% (120/128) of window-phase plasma donations. Overall specificity in freshly collected blood donor specimens was 99.74%. Two putative window-phase donations containing HCV core protein and viral RNA were identified from paid plasma donors by prospective testing with the HCV antigen ELISA. CONCLUSION: These results indicate that an HCV antigen ELISA can identify almost all (94%) of viraemic donations given during the seronegative window phase of infection. The performance of the HCV antigen ELISA appears to be suitable for large-scale screening of blood donations.

Antibodies, Viral↗

Further refinement of the MYP2 locus for autosomal dominant high myopia by linkage disequilibrium analysis.

INTRODUCTION: High myopia (>-6.00 diopters) is a complex common disorder that predisposes individuals to retinal detachment, glaucoma, macular degeneration, and premature cataracts. A recent linkage analysis of seven families with autosomal dominant high myopia has identified one locus (MYP2) for high myopia on chromosome 18p11.31 (Young et al.: Am J Hum Genet 1998;63:109-119). Haplotype analysis revealed an initial interval of 7.6 centimorgans (cM). METHODS: Transmission disequilibrium tests (TDT) with both the Statistical Analysis for Genetic Epidemiology (SAGE) 3.1 TDTEX and GENEHUNTER 2 (GH2) programs were performed using chromosome 18p marker alleles for this interval. RESULTS: Using SAGE analysis, the following p values were obtained for markers in marker order in this region: D18S1146 (p = 0.227), D18S481 (p = 0.001), D18S63 (p = 0.062), D18S1138 (p = 0.0004), D18S52 (p = 1.79 x 10(-6)), and D18S62 (p = 0.141). GH2 TDT analysis revealed the following p values for the best allele for the markers: D18S1146 (p = 0.083), D18S481 (p = 0.108), D18S63 (p = 0.034), D18S1138 (p = 0.011), D18S52 (p = 0.007), and D18S62 (p = 0.479). CONCLUSION: These data suggest that the gene for 18p11.31-linked high myopia is most proximal to marker D18S52, with a likely interval of 0.8 cM between markers D18S63 and D18S52. Due to the contraction of the interval size by TDT, these results provide a basis for focused positional cloning and candidate gene analysis at the MYP2 locus.

Chromosomes, Human, Pair 18↗

Regulated expression of the X. tropicalis connexin43 promoter.

The spatio-temporal expression pattern of the connexin43 gene during Xenopus development has been described (Van der Heyden et al. 2001). To further investigate the regulation and function of connexin43 (Cx43) in amphibians, we have isolated the gene from Xenopus tropicalis (Xt) and determined its structure. The X. tropicalis Cx43 gene displays the typical two exon-one intron connexin configuration, where the first exon is non-coding. The predicted amino acid sequence of the XtCx43 protein is highly homologous to that of X. laevis, chicken and mammals. Expression of XtCx43 cDNA in N2A cells results in gap-junction plaque formation. Promoter activity of a 3.5 kb upstream region of the X. tropicalis Cx43 gene, including exon 1, mimics endogenous timing of expression after injection of reporter constructs in X. laevis embryos.

Amino Acid Sequence↗

Double-chambered right ventricle in an adult patient.

A 65-year-old male was referred for to our facility for right and left heart catheterization and coronary angiography for evaluation of a ventricular septal defect and to rule out significant coronary artery disease. During the procedure, the patient was diagnosed with a double-chambered right ventricle (DCRV). Most DCRV cases are diagnosed at a young age; presentation in an adult is extremely rare.

Aged↗

Sequence and analysis of chromosome 1 of the plant Arabidopsis thaliana.

The genome of the flowering plant Arabidopsis thaliana has five chromosomes. Here we report the sequence of the largest, chromosome 1, in two contigs of around 14.2 and 14.6 megabases. The contigs extend from the telomeres to the centromeric borders, regions rich in transposons, retrotransposons and repetitive elements such as the 180-base-pair repeat. The chromosome represents 25% of the genome and contains about 6,850 open reading frames, 236 transfer RNAs (tRNAs) and 12 small nuclear RNAs. There are two clusters of tRNA genes at different places on the chromosome. One consists of 27 tRNA(Pro) genes and the other contains 27 tandem repeats of tRNA(Tyr)-tRNA(Tyr)-tRNA(Ser) genes. Chromosome 1 contains about 300 gene families with clustered duplications. There are also many repeat elements, representing 8% of the sequence.

Arabidopsis↗

Sequence and analysis of chromosome 3 of the plant Arabidopsis thaliana.

Arabidopsis thaliana is an important model system for plant biologists. In 1996 an international collaboration (the Arabidopsis Genome Initiative) was formed to sequence the whole genome of Arabidopsis and in 1999 the sequence of the first two chromosomes was reported. The sequence of the last three chromosomes and an analysis of the whole genome are reported in this issue. Here we present the sequence of chromosome 3, organized into four sequence segments (contigs). The two largest (13.5 and 9.2 Mb) correspond to the top (long) and the bottom (short) arms of chromosome 3, and the two small contigs are located in the genetically defined centromere. This chromosome encodes 5,220 of the roughly 25,500 predicted protein-coding genes in the genome. About 20% of the predicted proteins have significant homology to proteins in eukaryotic genomes for which the complete sequence is available, pointing to important conserved cellular functions among eukaryotes.

Arabidopsis↗

Partner violence, partner notification, and women's decisions to have an HIV test.

OBJECTIVES: Reports of partner violence against HIV-positive women after they have disclosed their serostatus have led some to reassess partner notification strategies and to speculate that fear of partner violence following partner notification may influence women's HIV testing decisions. We studied whether associations exist between women's declining to have an HIV test and history of partner violence, fear of partner violence, previous experience with partner notification, or beliefs about partner notification. METHODS: In this cross-sectional study, we interviewed women seen at Newark and Miami sexually transmitted disease clinics. The women were at least 18 years old, not known to be HIV positive, not tested for HIV in the previous 3 months, and offered HIV testing during the clinic visit. Women who declined testing were compared with women who accepted. RESULTS: Of 490 participants (89% of eligible women), 16% reported partner violence in the past year, and 28% declined HIV testing. Declining the test was not significantly (p >.05) associated with history or fear of partner violence, previous experience with partner notification, or beliefs about partner notification. When specifically asked, only 2 women responded that their declining the test was related to fear that their partner or partners might harm them if the women tested positive. CONCLUSIONS: Among women seen at these clinics, we did not find evidence that declining the HIV test was strongly influenced by partner violence, previous experience with partner notification, or beliefs about partner notification. However, many women reported partner violence. Therefore, providers should assess the potential for partner violence and be prepared to make appropriate referrals.

AIDS Serodiagnosis↗

NG2-positive oligodendrocyte progenitor cells in adult human brain and multiple sclerosis lesions.

Multiple sclerosis (MS) is characterized by multifocal loss of myelin, oligodendrocytes, and axons. Potential MS therapies include enhancement of remyelination by transplantation or manipulation of endogenous oligodendrocyte progenitor cells. Characteristics of endogenous oligodendrocyte progenitors in normal human brain and in MS lesions have not been studied extensively. This report describes the distribution of cells in sections from normal adult human brain and MS lesions by using antibodies directed against NG2, an integral membrane chondroitin sulfate proteoglycan expressed by oligodendrocyte progenitor cells. Stellate-shaped NG2-positive cells were detected in the white and gray matter of normal adult human brain and appeared as abundant as, but distinct from, astrocytes, oligodendrocytes, and microglia. Stellate-shaped or elongated NG2-positive cells also were detected in chronic MS lesions. A subpopulation of the elongated NG2-positive cells expressed the putative apoptotic signaling molecule p75(NTR). TUNEL-positive cells in three active, nine chronic active, and four chronic inactive lesions, however, were p75(NTR)-negative. These studies identify cells with phenotypic markers of endogenous oligodendrocyte progenitors in the mature human CNS and suggest that functional subpopulations of NG2-positive cells exist in MS lesions. Endogenous oligodendrocyte progenitor cells may represent a viable target for future therapies intended to enhance remyelination in MS patients.

Adult↗