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Biomedical subjects

D Nelson

Publications and source records attributed to D Nelson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Bacteremia and skin/bone infections in two patients with X-linked agammaglobulinemia caused by an unusual organism related to Flexispira/Helicobacter species.

Two patients with Bruton's X-linked agammaglobulinemia are described with bacteremia and skin/bone infection due to an organism which by 16S rRNA gene sequence analysis was most closely related to "Flexispira" rappini (and thus designated a Flexispira-like organism, FLO) and more distantly related to the Helicobacter species. The organism required microaerobic conditions and, supplemental H(2) gas for growth and was reliably stained with acridine orange. In common with Helicobacter cinaedi infections, the focus of the FLO infection was in one case in the blood vessels or lymphatics of an extremity and in the other case in the skin and adjacent bone of an extremity. In both cases, prolonged IV antibiotic therapy was necessary to clear the infection. The susceptibility of XLA patients to FLO infection appears to be related to the fact that XLA is associated with severe B cell (humoral) immunodeficiency and thus these patients have difficulty with intravascular or intralymphatic infection. These findings elucidate the nature of FLO infections in humans and point the way to their detection and treatment.

Adult↗
PubMed2000

The prevalence of thromboembolic events among women with extended bed rest prescribed as part of the treatment for premature labor or preterm premature rupture of membranes.

OBJECTIVE: This study was undertaken to determine the prevalence of thromboembolic events among women with extended bed rest prescribed as part of the treatment of premature labor or preterm premature rupture of membranes. STUDY DESIGN: A retrospective chart review was undertaken of all women who had bed rest of >/=3 days' duration prescribed as part of the treatment of premature labor or preterm premature rupture of membranes in the Akron General Medical Center Perinatal Unit during the period January 1, 1997-December 31, 1998. The prevalence of thromboembolic events in this population was determined. The charts of all additional gravid women with antepartum or postpartum deep vein thrombosis or pulmonary embolism diagnosed during the study period were also reviewed. The prevalence of these disorders among the pregnant population for whom extended bed rest was not prescribed as part of the treatment of premature labor or preterm premature rupture of membranes was also calculated. Statistical comparison of the prevalences in the 2 populations was undertaken by means of the chi(2) analysis with the Fisher exact test. RESULTS: There were 192 patients admitted during the study period who had extended bed rest prescribed as part of the treatment of premature labor or preterm premature rupture of membranes. Three of these women had thromboembolic events, for a prevalence of 15.6 cases per 1000 women. Five additional gravid women were admitted for the treatment of deep vein thrombosis or pulmonary embolism. There were 6164 deliveries among women not treated with extended bed rest for premature labor or preterm premature rupture of membranes during this period. Thus the prevalence of these phenomena among the remaining pregnant women was 0.8 cases per 1000 women. The prevalences of these disorders in the 2 populations were highly significantly different. CONCLUSION: The prevalence of thromboembolic events among women for whom extended bed rest is prescribed as part of the treatment of premature labor or preterm premature rupture of membranes is significantly increased with respect to that among gravid women who do not receive this therapy and is substantially higher than previously reported. If this finding is confirmed in other populations, it may be prudent to undertake further studies to determine whether this prevalence can be reduced.

Bed Rest↗
PubMed2000

Emerging family of proline-specific peptidases of Porphyromonas gingivalis: purification and characterization of serine dipeptidyl peptidase, a structural and functional homologue of mammalian prolyl dipeptidyl peptidase IV.

Porphyromonas gingivalis is an asaccharolytic and anaerobic bacterium that possesses a complex proteolytic system which is essential for its growth and evasion of host defense mechanisms. In this report, we show the purification and characterization of prolyl dipeptidyl peptidase IV (DPPIV) produced by this organism. The enzyme was purified to homogeneity, and its enzymatic activity and biochemical properties were investigated. P. gingivalis DPPIV, like its human counterpart, is able to cleave the N terminus of synthetic oligopeptides with sequences analogous to those of interleukins 1beta and 2. Additionally, this protease hydrolyzes biologically active peptides including substance P, fibrin inhibitory peptide, and beta-casomorphin. Southern blot analysis of genomic DNA isolated from several P. gingivalis strains reveal that a single copy of the DPPIV gene was present in all strains tested.

Amino Acid Sequence↗
PubMed2000

Trends in fruit and vegetable consumption among adults in 16 US states: Behavioral Risk Factor Surveillance System, 1990-1996.

OBJECTIVES: This study examined trends in fruit and vegetable consumption among adults in 16 US states. METHODS: Data from telephone surveys were used to stratify respondents by sociodemographic and health-related characteristics. RESULTS: The proportion of adults who consumed fruits and vegetables at least 5 times daily was 19%, 22%, and 23% in 1990, 1994, and 1996, respectively. While the proportion increased among those with active leisure-time physical activities and normal weight, it remained almost the same among inactive people and dropped among the obese. CONCLUSIONS: Progress in fruit and vegetable intake from 1990 to 1994 was encouraging, but it changed little between 1994 and 1996.

Adolescent↗
PubMed2000

Association of ureaplasma urealyticum with abnormal reactive oxygen species levels and absence of leukocytospermia.

PURPOSE: Ureaplasma urealyticum is a commensal of the lower genitourinary tract of many sexually active adults. The organism is more common in partners of infertile than fertile marriages. We conducted a prospective study at our tertiary care center to confirm a possible association between U. urealyticum and abnormal sperm function parameters. MATERIALS AND METHODS: A total of 50 consecutive male patients seeking general urology consultation for lower urinary tract symptoms characteristic of chronic prostatitis were evaluated. Urine and semen localization cultures were performed with additional semen cultures for U. urealyticum, Chlamydia trachomatis and Mycoplasma hominis. Specimens from 21 healthy men were used as controls. Specimens were analyzed by a computer assisted semen analyzer, and verified manually for concentration, percent motility and morphology. Leukocytospermia was measured by the Endtz test. Semen specimens were also analyzed for reactive oxygen species (ROS), acrosome reaction and mannose binding assay. RESULTS: Of the patients 17 had positive U. urealyticum cultures and the other cultures were negative. Patients with U. urealyticum had significantly higher ROS levels (log [ROS + 1] = 2.52 +/- 0.25) than those without U. urealyticum (1.49 +/- 0.20, p = 0.002) or controls (1.31 +/- 0.19, p = 0.002). Leukocytospermia was detected in only 1 of the 17 (6%) positive specimens and 4 (12%) negative specimens. CONCLUSIONS: Seminal ROS levels are elevated among patients with U. urealyticum. ROS induces lipid peroxidation, which reduces membrane fluidity and sperm fertilization capability, and may be the mechanism by which U. urealyticum impairs sperm function. Absence of leukocytospermia does not exclude U. urealyticum.

Adult↗
PubMed2000

Chronic orthotopic aortic valve implantation model.

BACKGROUND AND AIM OF THE STUDY: The ideal animal model to assess implanted prosthetic aortic valves has yet to be universally accepted. The majority of mechanical valves are used for aortic valve replacement (AVR), yet historically animal models have provided data mainly after mitral valve implantation, due to the poor survival of animals undergoing AVR. Proposed regulations will require data from site-specific models. Thus, we modified previously reported chronic ovine models used for orthotopic implantation of aortic valves, to conduct preclinical aortic valve evaluation and to establish a predictive animal model needed for safety, hemodynamics, pathology and handling. METHODS: Fourteen sheep underwent AVR with 19 mm mechanical valves. Each animal was placed on cardiopulmonary bypass and the prosthetic valve implanted using a complete transverse ascending aortic transection. Hemodynamic data and aortography were obtained intraoperatively and again after 20 weeks, at which time hemodynamic studies, aortography, and pathological examination were performed. RESULTS: There were two operative deaths, but no significant complications in the other 12 sheep, 11 of which survived for 20 weeks. One animal died two weeks before sacrifice due to valve thrombosis. Chronic hemodynamic and aortographic data were within normal limits for all 11 sheep, and gross pathology of the implanted valve revealed no abnormalities. CONCLUSION: This study demonstrated the feasibility of the ovine model for orthotopic AVR, thus allowing greater confidence in the predictive value of in vivo hemodynamic and angiographic data gathered before clinical trials. Compared with other species, this ovine model provided improved rates of morbidity and mortality, reproducibility, ease of postoperative care, availability and acceptable anatomical similarities to humans. Future aortic valve studies at Medtronic will build on this knowledge base, making ovines - with this surgical technique - our animal model of choice.

Animals↗
PubMed2000

BP: developing excellence in the global enterprise.

World-class supply management organizations like Honda of America, John Deere, Chrysler, Hewlett Packard, and Motorola all understand the power of continuous improvement in the supply base. The best supplier management and development programs help suppliers--on a long-term basis--develop their own strength and expertise in suggestion systems, new product development, and high quality production results.

Benchmarking↗
PubMed1999

Wiskott-Aldrich syndrome protein regulates podosomes in primary human macrophages.

Wiskott-Aldrich syndrome protein (WASp) is a hematopoietic-specific, multidomain protein whose mutation is responsible for the immunodeficiency disorder Wiskott-Aldrich syndrome. WASp contains a binding motif for the Rho GTPase CDC42Hs as well as verprolin/cofilin-like actin-regulatory domains, but no specific actin structure regulated by CDC42Hs-WASp has been identified. We found that WASp colocalizes with CDC42Hs and actin in the core of podosomes, a highly dynamic adhesion structure of human blood-derived macrophages. Microinjection of constitutively active V12CDC42Hs or a constitutively active WASp fragment consisting of the verprolin/cofilin-like domains led to the disassemly of podosomes. Conversely, macrophages from patients expressing truncated forms of WASp completely lacked podosomes. These findings indicate that WASp controls podosome assembly and, in cooperation with CDC42Hs, podosome disassembly in primary human macrophages.

Actins↗
PubMed1999

Reduced mRNA for G3BP in fragile X cells: evidence of FMR1 gene regulation.

Although fragile X syndrome is caused by the absence of fragile X gene expression, little is known about the pathogenic processes underlying the mental retardation. Recent findings that the fragile X protein, FMRP, contains RNA binding motifs and nuclear transport signals and associates with ribosomes suggest that FMRP may be involved in either mRNA processing, transport, or translation. To test the hypothesis that absence of FMRP may affect the processing of specific transcripts, we have used an RNA differential display assay (RDDA) to identify differentially expressed transcripts in lymphoblast lines derived from fragile X syndrome patients. A 0.9-kb cDNA fragment that showed reduced expression in a fragile X lymphoblast cell line was found to be identical to G3BP (Ras-GTPase-Activating protein SH3-domain-binding protein). Quantitative reverse transcriptase-polymerase chain reaction showed that the expressed levels of G3BP mRNA in fragile X lymphoblast cell lines were significantly less than controls. Our results indicate that G3BP mRNA may be regulated by FMRP and supports the hypothesis that FMRP may modulate the transcription of specific transcripts.

Base Sequence↗
PubMed1999

Tumor antigens are constitutively presented in the draining lymph nodes.

Tumor growth is rarely associated with a strong specific CTL response, suggesting that the immune system is ignorant of the presence of tumor because the Ags are not readily available to or are sequestered from potential effector cells. We studied the in vivo activation of naive TCR transgenic hemagglutinin (HA)-specific CD8+ T cells adoptively transferred into mice bearing HA-expressing tumor using 5,6-carboxy-succinimidyl-fluorescein-ester labeling, which allows the identification of proliferating HA-specific T cells. We demonstrate that tumor Ags are constitutively presented in the lymph nodes draining tumors and are powerfully mitogenic for responding T cells despite the absence of anti-tumor CTL responses. Importantly, this proliferative signal occurs throughout tumor growth and is still detectable 6 mo after tumor inoculation when tumor is not palpable. These results provide the first evidence that there is constitutive presentation of tumor Ags in draining lymph nodes.

Animals↗
PubMed1999

Purification and characterization of a novel cysteine proteinase (periodontain) from Porphyromonas gingivalis. Evidence for a role in the inactivation of human alpha1-proteinase inhibitor.

Periodontal disease is characterized by inflammation of the periodontium manifested by recruitment of neutrophils, which can degranulate, releasing powerful proteinases responsible for destruction of connective tissues, and eventual loss of tooth attachment. Although the presence of host proteinase inhibitors (serpins) should minimize tissue damage by endogenous proteinases, this is not seen clinically, and it has been speculated that proteolytic inactivation of serpins may contribute to progression of the disease. A major pathogen associated with periodontal disease is the Gram-negative anaerobe Porphyromonas gingivalis, and in this report, we describe a novel proteinase that has been isolated from culture supernatants of this organism that is capable of inactivating the human serpin, alpha1-proteinase inhibitor, the primary endogenous regulator of human neutrophil elastase. This new enzyme, referred to as periodontain, belongs to the cysteine proteinase family based on inhibition studies and exists as a 75-kDa heterodimer. Furthermore, periodontain shares significant homology to streptopain, a proteinase from Streptococcus pyogenes, and prtT, a putative proteinase from P. gingivalis. Clearly, the presence of this enzyme, which rapidly inactivates alpha1-proteinase inhibitor, could result in elevated levels of human neutrophil elastase clinically detected in periodontal disease and should be considered as a potential virulence factor for P. gingivalis.

Amino Acid Sequence↗
PubMed1999

Prolyl tripeptidyl peptidase from Porphyromonas gingivalis. A novel enzyme with possible pathological implications for the development of periodontitis.

Porphyromonas gingivalis possesses a complex proteolytic system, which is essential for both its growth and evasion of host defense mechanisms. In this report we characterized, both at a protein and genomic level, a novel peptidase of this system with prolyl tripeptidyl peptidase activity. The enzyme was purified to homogeneity, and its enzymatic activity and biochemical properties were investigated. The amino acid sequence at the amino terminus and of internal peptide fragments enabled identification of the gene encoding this enzyme, which we refer to as PtpA for prolyl tripeptidyl peptidase A. The gene encodes an 82-kDa protein, which contains a GWSYGG motif, characteristic for members of the S9 prolyl oligopeptidase family of serine proteases. However, it does not share any structural similarity to other tripeptidyl peptidases, which belong to the subtilisin family. The production of prolyl tripeptidyl peptidase may contribute to the pathogenesis of periodontal tissue destruction through the mutual interaction of this enzyme, host and bacterial collagenases, and dipeptidyl peptidases in the degradation of collagen during the course of infection.

Amino Acid Sequence↗
PubMed1999

Identification of an integration center for cross-talk between protein kinase C and G protein modulation of N-type calcium channels.

The modulation of presynaptic calcium channel activity by second messengers provides a fine tuning mechanism for neurotransmitter release. In neurons, the activation of certain G protein-coupled receptors reduces N-type channel activity by approximately 60%. In contrast, activation of protein kinase C (PKC) results in an approximately 50% increase in N-type channel activity, and subsequent G protein inhibition is antagonized. Here, we describe the molecular determinants that control the dual effects of PKC-dependent phosphorylation. The double substitution of two adjacent PKC consensus sites in the calcium channel domain I-II linker (Thr422, Ser425) to alanines abolished both PKC-dependent up-regulation and the PKC-G protein cross-talk. The single substitution of Ser425 to glutamic acid abolished PKC up-regulation but had no effect on G protein modulation. Replacement of Thr422 with glutamic acid eliminated PKC-dependent up-regulation and mimicked the effects of PKC phosphorylation on G protein inhibition. Our data suggest that Thr422 mediates the antagonistic effect of PKC on G protein modulation, while phosphorylation of either Thr422 or Ser425 are sufficient to increase N-type channel activity. Thus, Thr422 serves as a molecular switch by which PKC is able to simultaneously trigger the up-regulation of channel activity and antagonize G protein inhibition.

Amino Acid Sequence↗
PubMed1999

Effect of seminal oxidative stress on fertility after vasectomy reversal.

OBJECTIVE: To evaluate seminal oxidative stress in men after vasectomy reversal and to determine whether seminal oxidative stress could predict fertility after vasectomy reversal. DESIGN: Measurement of seminal reactive oxygen species (ROS) and total antioxidant capacity (TAC) in normal donors, men who were fertile after vasectomy reversal, and men who were infertile after vasectomy reversal. SETTING: A male infertility clinic of a tertiary care center. PATIENT(S): Thirty men who underwent vasectomy reversal and 17 normal donors. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen characteristics, seminal ROS, and TAC were measured with chemiluminescence assays in samples from donors and reversal patients. RESULT(S): Mean adjusted seminal ROS (log [ROS+1]) was higher in infertile reversal patients (2.38+/-0.25) than in normal donors (1.30+/-0.14). Seminal ROS was also higher in all (fertile and infertile reversal combined) reversal patients than in donors. Total antioxidant capacity did not differ between groups. The ROS-TAC score, a composite index of seminal oxidative stress, was a significant predictor of fertility. A ROS-TAC score of 45 or greater had a positive predictive value of 73% in predicting fertility. CONCLUSION(S): Seminal oxidative stress is associated with vasectomy reversal. The ROS-TAC score is a possible predictor of infertility after vasectomy reversal.

Adult↗
PubMed1999

Clinical application of a new disposable lithotripter: a prospective multicenter study.

BACKGROUND: Mechanical lithotripsy has become a well-accepted method of bile duct stone fragmentation and removal. The Olympus lithotripter (Olympus American, Melville, NY) is the standard reusable lithotripter at the institutions that participated in this study. A disposable device with a preassembled pistol grip may perform equally well and facilitate operation. METHODS: Twenty patients with bile duct stones were evaluated as part of a multicenter prospective study. Data were obtained regarding stone size and number, bile duct diameter, and configuration, ease of cannulation, basket function, stone capture and crushing success, and complications. RESULTS: The maximum stone size averaged 16.5 +/- 1.2 mm (range 10 to 30 mm). Sixteen patients had multiple stones (median 5, range 2 to 12). The mean bile duct diameter was 20.5 +/- 1.5 mm (range 12 to 38 mm). Cannulation was successful in all within 5 attempts. Basket deployment failed in 1 patient because of stone size and the basket was misshapen in 14. Bile duct clearance was complete in 16 subjects (80%), incomplete in 2 patients, and failed in 2 patients. Abnormal duct configuration (sigmoid, stricture) was noted in 2 of 4 patients with failed capture and 7 of 16 patients with successful clearance. No statistically significant difference was observed between the bile duct diameter, maximum stone size, number of stones, and successful clearance. CONCLUSION: The disposable lithotripter is easy to use and, compared with the published results for the reusable lithotripter, performs almost as well.

Adult↗