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1.  Antiviral Activities in Human Saliva 
Advances in Dental Research  2011;23(1):34-37.
In this review, the authors survey the large number of antibacterial and antiviral proteins present in human saliva. Of interest, most of these antibacterial proteins display antiviral activity, typically against specific viral pathogens. The review focuses on one protein that interacts with both bacteria and viruses—gp340, originally referred to as salivary agglutinin. In the oral cavity, soluble gp340 binds to and aggregates a variety of bacteria, and this is thought to increase bacterial clearance from the mouth. However, when bound to the tooth surface, gp340 promotes bacterial adherence. In the oral cavity, most gp340 is found soluble in saliva and can function as a specific inhibitor of infectivity of HIV-1 and influenza A. In contrast, in the female reproductive track, most gp340 is bound to the cell surface, where it can promote HIV-1 infection.
doi:10.1177/0022034511399282
PMCID: PMC3144043  PMID: 21441478
HIV; AIDS; viral; antiviral; innate immune system
2.  Effective Transplantation of Photoreceptor Precursor Cells Selected Via Cell Surface Antigen Expression 
Stem cells (Dayton, Ohio)  2011;29(9):1391-1404.
Retinal degenerative diseases are a major cause of untreatable blindness. Stem cell therapy to replace lost photoreceptors represents a feasible future treatment. We previously demonstrated that postmitotic photoreceptor precursors expressing an NrlGFP transgene integrate into the diseased retina and restore some light sensitivity. As genetic modification of precursor cells derived from stem cell cultures is not desirable for therapy, we have tested cell selection strategies using fluorochrome-conjugated antibodies recognizing cell surface antigens to sort photoreceptor precursors. Microarray analysis of postnatal NrlGFP-expressing precursors identified four candidate genes encoding cell surface antigens (Nt5e, Prom1, Podxl, and Cd24a). To test the feasibility of using donor cells isolated using cell surface markers for retinal therapy, cells selected from developing retinae by fluorescence-activated cell sorting based on Cd24a expression (using CD24 antibody) and/or Nt5e expression (using CD73 antibody) were transplanted into the wild-type or Crb1rd8/rd8 or Prph2rd2/rd2 mouse eye. The CD73/CD24-sorted cells migrated into the outer nuclear layer, acquired the morphology of mature photoreceptors and expressed outer segment markers. They showed an 18-fold higher integration efficiency than that of unsorted cells and 2.3-fold higher than cells sorted based on a single genetic marker, NrlGFP, expression. These proof-of-principle studies show that transplantation competent photoreceptor precursor cells can be efficiently isolated from a heterogeneous mix of cells using cell surface antigens without loss of viability for the purpose of retinal stem cell therapy. Refinement of the selection of donor photoreceptor precursor cells can increase the number of integrated photoreceptor cells, which is a prerequisite for the restoration of sight.
doi:10.1002/stem.694
PMCID: PMC3303132  PMID: 21774040
Retina; Cell transplantation; Cell surface markers; fluorescence-activated cell sorting; Stem cell transplantation; Fluorescent protein reporter genes; Microarray; Embryonic stem cells
4.  Cone and rod photoreceptor transplantation in models of the childhood retinopathy Leber congenital amaurosis using flow-sorted Crx-positive donor cells 
Human Molecular Genetics  2010;19(23):4545-4559.
Retinal degenerative disease causing loss of photoreceptor cells is the leading cause of untreatable blindness in the developed world, with inherited degeneration affecting 1 in 3000 people. Visual acuity deteriorates rapidly once the cone photoreceptors die, as these cells provide daylight and colour vision. Here, in proof-of-principle experiments, we demonstrate the feasibility of cone photoreceptor transplantation into the wild-type and degenerating retina of two genetic models of Leber congenital amaurosis, the Crb1rd8/rd8 and Gucy2e−/− mouse. Crx-expressing cells were flow-sorted from the developing retina of CrxGFP transgenic mice and transplanted into adult recipient retinae; CrxGFP is a marker of cone and rod photoreceptor commitment. Only the embryonic-stage Crx-positive donor cells integrated within the outer nuclear layer of the recipient and differentiated into new cones, whereas postnatal cells generated a 10-fold higher number of rods compared with embryonic-stage donors. New cone photoreceptors displayed unambiguous morphological cone features and expressed mature cone markers. Importantly, we found that the adult environment influences the number of integrating cones and favours rod integration. New cones and rods were observed in ratios similar to that of the host retina (1:35) even when the transplanted population consisted primarily of cone precursors. Cone integration efficiency was highest in the cone-deficient Gucy2e−/− retina suggesting that cone depletion creates a more optimal environment for cone transplantation. This is the first comprehensive study demonstrating the feasibility of cone transplantation into the adult retina. We conclude that flow-sorted embryonic-stage Crx-positive donor cells have the potential to replace lost cones, as well as rods, an important requirement for retinal disease therapy.
doi:10.1093/hmg/ddq378
PMCID: PMC2972691  PMID: 20858907
5.  Targeted Disruption of Outer Limiting Membrane Junctional Proteins (Crb1 and ZO-1) Increases Integration of Transplanted Photoreceptor Precursors Into the Adult Wild-Type and Degenerating Retina 
Cell transplantation  2010;19(4):487-503.
Diseases culminating in photoreceptor loss are a major cause of untreatable blindness. Transplantation of rod photoreceptors is feasible, provided donor cells are at an appropriate stage of development when transplanted. Nevertheless, the proportion of cells that integrate into the recipient outer nuclear layer (ONL) is low. The outer limiting membrane (OLM), formed by adherens junctions between Müller glia and photoreceptors, may impede transplanted cells from migrating into the recipient ONL. Adaptor proteins such as Crumbs homologue 1 (Crb1) and zona occludins (ZO-1) are essential for localization of the OLM adherens junctions. We investigated whether targeted disruption of these proteins enhances donor cell integration. Transplantation of rod precursors in wild-type mice achieved 949 ± 141 integrated cells. By contrast, integration is significantly higher when rod precursors are transplanted into Crb1rd8/rd8 mice, a model of retinitis pigmentosa and Lebers congenital amaurosis that lacks functional CRB1 protein and displays disruption of the OLM (7,819 ± 1,297; maximum 15,721 cells). We next used small interfering (si)RNA to transiently reduce the expression of ZO-1 and generate a reversible disruption of the OLM. ZO-1 knockdown resulted in similar, significantly improved, integration of transplanted cells in wild-type mice (7,037 ± 1,293; maximum 11,965 cells). Finally, as the OLM remains largely intact in many retinal disorders, we tested whether transient ZO-1 knockdown increased integration in a model of retinitis pigmentosa, the rho−/− mouse; donor cell integration was significantly increased from 313 ± 58 cells without treatment to 919 ± 198 cells after ZO-1 knockdown. This study shows that targeted disruption of OLM junctional proteins enhances integration in the wild-type and degenerating retina and may be a useful approach for developing photoreceptor transplantation strategies.
doi:10.3727/096368909X486057
PMCID: PMC2938729  PMID: 20089206
Stem cell; Migration; Transplantation; Degeneration; Müller glia
6.  Using NVDRS data for suicide prevention: promising practices in seven states 
Injury Prevention  2006;12(Suppl 2):ii28-ii32.
Objectives
This article describes how seven states participating in a new public health surveillance system for violent death in the US, the National Violent Death Reporting System (NVDRS), have used data to support local suicide prevention activities.
Setting
The NVDRS is unique in that it augments death certificate data with event and circumstance information from death investigation reports filed by coroners, medical examiners, and law enforcement. These data illuminate why the victim ended his or her life, fatal injury patterns, and toxicological findings at death.
Results
Current suicide prevention efforts using these data fall into three categories: describing the problem of suicide and identifying opportunities for intervention; collaborating on statewide suicide prevention plans; and forming new partnerships for targeted prevention initiatives. Taken together, these three areas show early promise for state suicide prevention efforts.
Conclusions
In each of the states, NVDRS data analyses are being shared with injury prevention colleagues, suicide prevention planning groups and policymakers, and adapted to respond to unique state and local suicide problems. A powerful surveillance tool, the NVDRS is bringing new clarity and direction to these state‐based efforts. The NVDRS can serve as a model for other countries looking to establish timely suicide surveillance systems and data driven prevention strategies.
doi:10.1136/ip.2006.012443
PMCID: PMC2563480  PMID: 17170167
7.  Impaired cough reflex in patients with recurrent pneumonia 
Thorax  2003;58(7):645-646.
doi:10.1136/thorax.58.7.645-b
PMCID: PMC1746728  PMID: 12832690
8.  Underestimates of unintentional firearm fatalities: comparing Supplementary Homicide Report data with the National Vital Statistics System 
Injury Prevention  2002;8(3):252-256.
Objective: A growing body of evidence suggests that the nation's vital statistics system undercounts unintentional firearm deaths that are not self inflicted. This issue was examined by comparing how unintentional firearm injuries identified in police Supplementary Homicide Report (SHR) data were coded in the National Vital Statistics System.
Methods: National Vital Statistics System data are based on death certificates and divide firearm fatalities into six subcategories: homicide, suicide, accident, legal intervention, war operations, and undetermined. SHRs are completed by local police departments as part of the FBI's Uniform Crime Reports program. The SHR divides homicides into two categories: "murder and non-negligent manslaughter" (type A) and "negligent manslaughter" (type B). Type B shooting deaths are those that are inflicted by another person and that a police investigation determined were inflicted unintentionally, as in a child killing a playmate after mistaking a gun for a toy. In 1997, the SHR classified 168 shooting victims this way. Using probabilistic matching, 140 of these victims were linked to their death certificate records.
Results: Among the 140 linked cases, 75% were recorded on the death certificate as homicides and only 23% as accidents.
Conclusion: Official data from the National Vital Statistics System almost certainly undercount firearm accidents when the victim is shot by another person.
doi:10.1136/ip.8.3.252
PMCID: PMC1730887  PMID: 12226128
10.  Assisted discharge for patients with exacerbations of COPD 
Thorax  2001;56(5):417-418.
doi:10.1136/thorax.56.5.417c
PMCID: PMC1746053  PMID: 11336054
11.  Experimental mate replacement does not increase extra-pair paternity in tree swallows 
Before the onset of female fertility, we removed 12 early-settling male tree swallows (Tachycineta bicolor) from their nest-boxes and mates, and allowed replacement males which had been floaters to settle with the original female residents. We predicted that females which had their original mate choice altered (experimentals) would be more likely to obtain extra-pair fertilizations than females which remained paired with their original, early-settling mates (controls). The proportion of females obtaining extra-pair fertilizations, however, did not differ between controls and experimentals, indicating that mating tactics of female tree swallows were unaffected by mate replacement. However, differences between early-settling and replacement males did exist. Replacement males had shorter wing chords than early-settling males, suggesting that they were younger. Moreover, a significantly greater proportion of replacement males than early-settling males were unringed and thus new to the study site. Our results suggest that if females are choosing males for good genes, then early-settling males are not superior in genetic quality to the smaller replacement males which had originally been floaters.
doi:10.1098/rspb.1998.0557
PMCID: PMC1689505
12.  Plant-parasitic Nematodes of New Zealand Recorded by Host Association 
Journal of Nematology  1997;29(4S):640-656.
A list of plant-parasitic nematodes associated with hosts in New Zealand is provided comprising 703 records, including 207 new associations for New Zealand.
PMCID: PMC2619821  PMID: 19274264
new records; New Zealand; plant-parasitic nematodes; pasture nematodes
13.  When bullets don't kill. 
Public Health Reports  1996;111(6):482-493.
The Massachusetts Department of Public Health has created the first statewide surveillance system in the nation that tracks both fatal and nonfatal weapon injuries. The authors summarize findings for 1994 and discuss their public health implication. Suicides were the leading cause of firearm fatality, while self-inflicted injuries accounted for only 3% of nonfatal firearm injuries. Risk of violence-related injuries varied dramatically across the state. In Boston, one in 38 black male teenagers ages 15 to 19 was shot or stabbed in 1994, in contrast to one in 56,000 for white females of any age living in suburban communities. In Boston, non-Hispanic black male teenagers were at 41 times higher risk than white male teenagers for gun injuries. Shooting homicides increased sixfold during the late 1980s among black Boston males, while homicides by other means remained stable. In other Massachusetts cities, injury rates were higher among 20 to 24-year-olds than among teenagers, and, in some areas, incidence rates were as high or higher among Hispanic males than among non-Hispanic black males. Between 1985 and 1994, the proportion of firearm injuries caused by semiautomatic pistols increased from 23% to 52%, according to police ballistics data.
Images
PMCID: PMC1381894  PMID: 8955693
14.  Assessment of E-coding practices and costs in Massachusetts hospitals. 
Public Health Reports  1993;108(5):633-636.
Hospital discharge data are a potentially useful information resource for documenting the epidemiology of nonfatal injuries. However, hospitals often do not include E-codes that identify external causes of injury in discharge abstracts. One barrier has been assumed to be the cost of assigning E-codes to medical records. Directors of medical records at hospitals in Massachusetts were surveyed to assess the validity of a cost-assessment study by Rivara and coworkers and to determine what resources they would need to E-code all injury discharges. According to Rivara's estimates, injury coding an additional 500 hospital discharges would entail a continuing cost to each hospital of about $600 a year. More than half of the survey's 101 respondents believed that the estimates were accurate, 16 percent believed that the estimates were inaccurate, and 27 percent were unable to assess the potential costs. Among the resources needed to E-code all injury-related discharges, respondents most often cited training for those who assign the codes and the approval of the hospital administration. Only 20 percent of the respondents cited needs directly related to ongoing costs. The perception by hospitals of the cost of E-coding, frequently cited as a major barrier to the use of hospital discharge data as an injury surveillance source, did not emerge in this survey as an overriding concern.
PMCID: PMC1403439  PMID: 8210261
15.  A Xanthomonas campestris pv. campestris protein similar to catabolite activation factor is involved in regulation of phytopathogenicity. 
Journal of Bacteriology  1990;172(10):5877-5883.
A DNA fragment from Xanthomonas campestris pv. campestris that partially restored the carbohydrate fermentation pattern of a cya crp Escherichia coli strain was cloned and expressed in E. coli. The nucleotide sequence of this fragment revealed the presence of a 700-base-pair open reading frame that coded for a protein highly similar to the catabolite activation factor (CAP) of E. coli (accordingly named CLP for CAP-like protein). An X. campestris pv. campestris clp mutant was constructed by reverse genetics. This strain was not affected in the utilization of various carbon sources but had strongly reduced pathogenicity. Production of xanthan gum, pigment, and extracellular enzymes was either increased or decreased, suggesting that CLP plays a role in the regulation of phytopathogenicity.
PMCID: PMC526907  PMID: 2170330
16.  Molecular biology of spiroplasma plasmids. 
With one exception, all spiroplasma strains examined contained extrachromosomal DNA, most of which was in the form of covalently closed circular plasmids. One plasmid, pIJ2000, carried by Spiroplasma citri strain ASP-1, was purified and characterized and used to probe for related plasmids in other strains. Unsuccessful attempts were made to clone pIJ2000 into Escherichia coli using the vectors pAT153 and pBR322. However, spiroplasma chromosomal DNA fragments could be cloned without difficulty.
Images
PMCID: PMC2590546  PMID: 6382830
17.  The absence of introns within a human fibroblast interferon gene. 
Nucleic Acids Research  1981;9(2):247-266.
Experiments in which immobilised restriction fragments of genomic DNA were hybridised with a cloned human fibroblast interferon cDNA indicate that the homologous chromosomal genes exist in only one basic arrangement. This is in marked contrast to recent studies by Nagata et al. (1) showing that there are at least eight gene arrangements for human leukocyte interferon. Having isolated a chromosomal human fibroblast interferon gene from a gene bank, we conclude from nucleotide sequencing studies that there is a complete absence of introns within the RNA-coding region. In view of a similar observation recently made for a human leukocyte interferon gene (1), it would appear as if interferon genes in general are unlike the vast majority of eukaryote genes in this respect.
Images
PMCID: PMC326690  PMID: 6163136
18.  Deadly Cigarettes 
British Medical Journal  1964;1(5382):563.
PMCID: PMC1813517
21.  Go in Whole-heartedly 
British Medical Journal  1948;1(4559):1005.
PMCID: PMC2090700
23.  National Health Service 
British Medical Journal  1948;1(4548):472.
PMCID: PMC2090341
24.  Prickly Heat 
British Medical Journal  1948;1(4545):317.
PMCID: PMC2093017

Results 1-25 (30)