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Biomedical subjects

R Jones

Publications and source records attributed to R Jones.

At least 307 records · Page 17Linked to original sources
PubMed1998

Accuracy and reproducibility of blood lead testing in commercial laboratories.

OBJECTIVE: To assess the proficiency of commercial laboratories in analyzing lead in clinical blood samples from subjects without overt lead exposure. DESIGN: We submitted masked duplicate blood lead specimens to 8 masked laboratories. Each laboratory received blood aliquots immediately following drawing (time 1) and 2 weeks later (time 2) from 7 human subjects and 3 bovine blood samples with known lead levels of 0.26, 0.57, and 0.79 micromol/L (5.4, 11.8, and 16.4 microg/dL). Of the 8 laboratories, 5 were commercial laboratories, 1 was a state laboratory, 1 was a research laboratory, and 1 was the Centers for Disease Control and Prevention reference laboratory. OUTCOME MEASURES: Correlation coefficients were calculated, and differences within and between laboratories were assessed by analysis of variance. RESULTS: Results were obtained for all specimens, with all the human subjects' overall mean lead levels being less than 0.48 micromol/L (<10 microg/dL). Each laboratory reported all human blood specimens appropriately, as having lead levels less than 0.48 micromol/L (<10 microg/dL) and within 0.14 micromol/L (3 microg/dL) of the overall mean for that subject. All internal reproducibilities were very high (range, 0.92-1.00) except for one (0.60), possibly lower because of 1 pair of specimens. Mean differences between blood samples analyzed at time 1 and time 2 ranged from -1.4 to 1.2, with only 2 laboratories having significant differences (P<.01). CONCLUSIONS: Overall, there was strong reproducibility within and among laboratories, with no overall time trend or interlaboratory or intralaboratory variance. The storage conditions did not seem to affect the aggregate results. The data suggest that through implementation of the Centers for Disease Control and Prevention/Wisconsin Blood Lead Proficiency Testing Program, the Centers for Disease Control and Prevention's Blood Lead Laboratory Reference System, and mandated federal and state proficiency programs, laboratories in this geographic region have improved their performance as compared with previous published studies and an unpublished study.

Humans↗
PubMed1998

Expression of a testis-specific putative actin-capping protein associated with the developing acrosome during rat spermiogenesis.

Actin-capping proteins are ubiquitous components of mammalian cells. They are known to regulate the polymerization state of actin and hence indirectly control the activity of the cytoskeleton and cell shape. As part of our investigation into the molecular mechanisms that direct differentiation of a round spermatid into an elongating spermatozoa, we report on a testis-specific 1.7-kb transcript from rat testis with sequence similarities to the alpha subunit of actin-capping proteins (ACPs) from somatic cells. The transcript contains a putative cAMP-responsive motif (CREM) upstream of the initiation codon in the DNA sequence and is expressed postmeiotically, first appearing between 20 and 30 days of postnatal development. The primary amino acid sequence is 90% identical to that of a previously identified testis-specific mouse protein, gsg3, both showing approximately 40% homology to the alpha subunit of somatic ACPs. An affinity-purified polyclonal antibody to a synthetic peptide derived from the rat transcript identified a 32-kDa protein on Western blots of testicular extracts. Indirect immunofluorescent localization of the protein on frozen sections of adult rat testis showed that it is intracellular and accumulates asymmetrically in the cytoplasm of round spermatids coincident with the position of the developing acrosome. This spatial expression parallels the distribution of F-actin during sperm differentiation, supporting the hypothesis that testis-specific ACPs have an important role in determining the final shape of mature sperm heads. A disturbance in the expression of these ACPs may underlie many of the abnormalities in sperm morphology observed in infertile semen.

Acrosome↗
PubMed1998

Characterization of the functional domains of boar acrosin involved in nonenzymatic binding to homologous zona pellucida glycoproteins.

During the first steps of the gamete interaction, the proacrosin/acrosin system seems to play a crucial role in the secondary binding, holding acrosome-reacted spermatozoa during their passage through the zona pellucida. To analyze the functional domains of acrosin, we decided to express recombinant boar acrosin proteins in bacteria and to study their binding capacities to zona pellucida glycoproteins (ZPGPs). The expressed proteins were immunodetected by Western blot with a polyclonal antiacrosin antibody. The recombinant truncated beta-acrosin has a typical hyperbolic curve of a zymogen enzymatic activation. Three of the five recombinant forms (truncated beta-acrosin, Ser/Ala222-truncated beta-acrosin, and truncated beta-acrosin "heavy chain") had the ability to bind ZPGPs. The two shorter forms (the amino and carboxy termini of truncated beta-acrosin) failed to bind. The catalytic site mutant (Ser/Ala222) of truncated beta-acrosin does not differ from the recombinant truncated beta-acrosin in its mechanism of interaction to ZPGPs, indicating that this secondary binding is done by a nonenzymatic process. Our results show that binding between acrosin and ZPGPs depends on the secondary and tertiary structures of acrosin and does not depend on an active catalytic site.

Acrosin↗
PubMed1998

Site-directed mutagenesis of boar proacrosin reveals residues involved in binding of zona pellucida glycoproteins.

Proacrosin, the zymogen form of the serine protease beta-acrosin, is thought to function as a secondary binding molecule between mammalian gametes during fertilization (Jansen et al., 1995: Int J Dev Biol 39, 501-510). The interaction involves strong ionic bonds between positively charged amino acids on proacrosin and negatively charged polysulphate groups on zona pellucida glycoproteins. In this investigation, we identified the basic residues on proacrosin that are important for this binding. Site-directed mutagenesis shows that two groups of amino acids comprising His47, Arg50, and Arg51 together with Arg250, Lys252, and Arg253 are crucial because their deletion or replacement severely reduces affinity for zona glycoproteins. Molecular models of proacrosin reveal that these residues are located along one face of the protein on two exposed surface loops that project over and around the catalytic site. These findings support the hypothesis that polysulphate binding sites on proacrosin are formed by a restricted number of basic amino acids on the surface of the protein, presenting a specific orientation that is complementary to negatively charged sulphate groups on zona glycoproteins. Identification and elucidation of the stereochemistry of these charged moieties will aid design of new kinds of nonsteroidal antifertility agents.

Acrosin↗
PubMed1998

Scopolamine-induced cognitive impairment as a predictor of cognitive decline in healthy elderly volunteers: a 6-year follow-up.

OBJECTIVE: To determine if scopolamine-induced cognitive impairment in healthy elderly people predicts cognitive decline 6 years later. DESIGN: Prospective cohort study. SETTING: Elderly care research unit. PARTICIPANTS: Healthy elderly people who were part of a volunteer panel of research subjects. INTERVENTIONS: Scopolamine 0.2 mg administered subcutaneously at baseline. MAIN OUTCOME MEASURES: Cognitive drug research computerized cognitive testing battery pre- and post-scopolamine, with repeat testing over 6 years later. MAIN RESULTS: 16/24 subjects were retested. Although marked decrements in cognitive functioning were seen with scopolamine, there was little change in performance over 6 years, and no significant association was seen between scopolamine-induced decrement and change over time. CONCLUSIONS: The scopolamine challenge test is not likely to play a role in the preclinical diagnosis of Alzheimer's disease.

Aged↗
PubMed1998

Comparison of fixation disparities obtained by objective and subjective methods.

Fixation disparities (FD) were measured as a function of forced vergence using binocular scleral search coils and simultaneously with nonius lines. The slope of the objective FD curve was significantly greater than the subjective FD curve for three of five subjects. This indicates an alteration in retinal correspondence of up to one degree, that shifts Panum's area to avoid the diplopia normally present with large disparities. This process allows for fusion in the presence of large objective fixation disparities which would normally cause diplopia. The shift in correspondence enhances the range of forced vergence, since the larger objective FDs serve as more effective stimuli to fusional vergence. The remaining subjects who lacked this effect had "flat" FD curves indicative of high vergence adaptation.

Adult↗
PubMed1998

The effect of forced vergence on retinal correspondence.

The spatial characteristics of the changes in retinal correspondence produced by forced convergence were studied. The vertical extent of lateral shifts in binocular correspondence were quantified by comparing the convergence of the eyes measured with binocular search coils to the convergence of the eyes as determined using nonius lines having vertical separations (gaps) between the nonius lines of 0.5-4.8 degrees. Lateral shifts in binocular correspondence only occurred for nonius gaps < 3-4 degrees. The effects of horizontal retinal eccentricity on lateral shifts in correspondence were determined by measuring the nonius horopter of the subject under forced convergence, using 11 nonius line eccentricities between 4.5 degrees left and right. The nonius horopter was shifted toward the fusion target maximally near the fixation point. There was no shift beyond 3 degrees of eccentricity. We conclude that the nonius horopter is 'dimpled' vertically and horizontally, facilitating local fusion by shifting the line horopter and the region of single binocular vision toward the point of regard over a region of 3 degrees around the fixation point.

Adult↗
PubMed1998

Elimination of free radionuclide by a chelating agent improves tumor-to-nontumor ratios following radioimmunotargeting with antibody labeled with 67Ga.

To circumvent radionuclide accumulation in nontarget tissues when employing metallic radionuclides for radioimmunoscintigraphy or radioimmunotherapy, we have investigated the effect of the chelating agent deferroxamine (DFO) on the biodistribution of 67Ga following its administration attached to intact monoclonal antibody MAb35 and its F(ab')2 fragment. Following administration of 67Ga-labeled MAb35, DFO accelerated whole-body elimination of 67Ga and reduced its accumulation in several normal tissues, including liver, spleen and kidney. No reduction in tumor accumulation of 67Ga was observed. Following administration of 67Ga-labeled F(ab')2 fragment, kidney accumulation was higher than with the intact antibody (29% and 4% ID/g, respectively) and blood levels lower (0.69% and 5% ID/g, respectively). Again, no alteration in tumor accumulation of 67Ga was seen following DFO, although liver, kidney and blood levels were reduced and whole-body elimination accelerated.

Animals↗
PubMed1998

Surveillance for Creutzfeldt-Jakob disease among persons with hemophilia.

BACKGROUND: Although Creutzfeldt-Jakob disease (CJD) has been shown to be transmissible through blood components in rodent models, no human blood-to-blood transmission has been documented. If blood transmission were possible in humans, persons with hemophilia in the United States would be at higher risk of contracting CJD, because they receive large numbers of blood components. Nearly one-half of the hemophilia population contracted HIV in the 1980s, and many of these people have since died with neurologic complications. This study investigated whether some hemophilia patients with neurologic disorders may have died with CJD. STUDY DESIGN AND METHODS: Hemophilia treatment Centers across the United States were invited to participate in this retrospective surveillance study. The centers were asked to send any available formalin-fixed paraffin block brain samples from hemophilia decedents. Slides were prepared at the Centers for Disease Control and Prevention and reviewed by three expert neuropathologists. Two slides were stained for the prion protein at the request of one of the neuropathologists. RESULTS: Specimens from 24 decedents with genetic bleeding disorders were collected and reviewed.The panel found no evidence of CJD in any of the specimens. CONCLUSIONS: Although the study sample is small, these results support the growing evidence that CJD is not being transmitted in the nation's blood supply.

Adult↗
PubMed1998

Macaque MDC family of proteins: sequence analysis, tissue distribution and processing in the male reproductive tract.

A large number of sequence-related, cysteine-rich membrane proteins containing metalloproteinase-like and disintegrin-like domains (the MDC protein family) have been identified in mammalian tissues from a variety of species. Previous studies in the macaque (Macaca fascicularis) have led to the cDNA cloning and sequence analysis of a number of MDC proteins which are abundantly expressed in the male reproductive tract. We now describe the distribution of seven of these macaque MDC transcripts in a range of different tissues. This description includes a novel macaque testis-derived MDC, tMDC III, whose full-length sequence is reported for the first time. In addition, polyclonal antisera have been used to localize a number of these MDC proteins to spermatogenic cells in testis sections, and to demonstrate their processing on the sperm surface during epididymal transit.

ADAM Proteins↗
PubMed1998

Cellular distribution and molecular heterogeneity of MAC393 antigen (clusterin, beta-chain) on the surface membrane of bull spermatozoa.

The distribution and size of a surface membrane antigen identified by a monoclonal antibody (MAC9393) have been examined in testicular and epididymal bovine sperm preparations. Western blots indicated a substantial decrease in molecular mass of the antigen during epididymal maturation from approximately 87 kDa in the testis to approximately 35 kDa in the cauda epididymidis. This was accompanied by a change in its cellular localization from the neck and whole head to the acrosomal region. N-terminal microsequencing identified MAC393 antigen as the beta-chain of clusterin. A polyclonal antiserum to the alpha-chain of clusterin recognized both testicular and epididymal forms and revealed that the heterodimer was present on the sperm tail as well as the acrosome. These findings are explained by the co-existence of dimeric and monomeric pools of clusterin on spermatozoa. The polyclonal antiserum recognizes both testicular and epididymal forms of the heterodimer and although the monoclonal antibody binds to the testicular heterodimer, it only recognizes the beta-chain monomer of epididymal clusterin. These findings support previous observations made on human spermatozoa that two forms of clusterin, the beta-chain monomer and the heterodimer, are present on the surface membrane and in seminal plasma.

Amino Acid Sequence↗
PubMed1998

Regionalized lipid diffusion in the plasma membrane of mammalian spermatozoa.

The plasma membrane of mammalian spermatozoa shows pronounced lateral asymmetry with many glycoproteins restricted to specific domains. Some of these antigens are freely diffusing throughout the membrane whereas others appear static in position. It is not clear whether these concepts also apply to membrane lipids. In this investigation we have used fluorescence recovery after photobleaching (FRAP) techniques to spatially resolve lipid dynamics in various surface domains of 5 species of mammalian spermatozoa (bull, boar, ram, mouse, and guinea pig). Sperm plasma membranes were loaded with 5-(N-octadecanoyl)aminofluorescein (ODAF) reporter probe, and its diffusion was measured in various domains by FRAP analysis. Results showed that in live bull, boar, ram, and mouse spermatozoa, diffusion coefficients (D) were significantly higher over the acrosome and postacrosome than on the midpiece and principal piece of the tail. In dead or permeabilized cells, on the other hand, large immobile phases developed, particularly on the sperm tail, that severely reduced D values. ODAF diffusion was also sensitive to temperature and cross-linking of protein components within the membrane with paraformaldehyde. Guinea pig spermatozoa were different in almost all respects from those of the other species tested. It is concluded that lipid diffusion in the plasma membrane of live spermatozoa varies significantly between surface domains, because of either compositional heterogeneity, or differences in bilayer disposition, or the presence of intramembranous barriers that impede free exchange between domains. This study emphasizes the important role of membrane lipids in regulating polarized migration of sperm surface antigens during developmental processes such as maturation and capacitation.

Acrosome↗
PubMed1998

Noninvasive positive-pressure ventilation in chronic obstructive pulmonary disease.

Interest in noninvasive positive-pressure ventilation both as an alternative to intubation and mechanical ventilation and as a unique therapy has grown over recent years. Clinical and patient acceptance is highest in neuromuscular deficits, but supporting evidence for its use in chronic obstructive pulmonary disease is highly dependent on the application. This review considers the clinical implementation of noninvasive positive-pressure ventilation in acute respiratory failure, as a postextubation weaning alternative, in stable severe hypercapnic chronic obstructive pulmonary disease, in overlap syndrome, and for nocturnal oxygen desaturation. Some applications are well supported, leading to a cautious recommendation for its utilizatip4, whereas for others evidence is starkly conflicting. The clinical efficacy of noninvasive positive-pressure ventilation is vastly dependent on equipment, equipment-patient interface, pressure settings, physician's bedside manner, and experience of the center. Interpretation of the studies must take into account the foregoing factors along with the various ventilatory techniques and differing primary outcome measures. Generalizations can be made regarding indications and contraindications, but this is an area rife with exceptions. The subtle message from the clinical studies describes the importance of the clinical art applied from the palette of science and technology.

Acute Disease↗