Ultrathin films of cobalt on Fe{001} and the effect of oxygen.
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Journal Article↗
Biomedical subjects
C Petersen
Publications and source records attributed to C Petersen.
Availability of intravenous quinidine for falciparum malaria.
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Child, Preschool↗
Potential antifolate resistance determinants and genotypic variation in the bifunctional dihydrofolate reductase-thymidylate synthase gene from human and bovine isolates of Cryptosporidium parvum.
We have determined the nucleic acid sequences of a gene encoding the bifunctional enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS) from bovine and human AIDS isolates of Cryptosporidium parvum. THe DHFR-TS gene was isolated from genomic DNA libraries by hybridization with a probe amplified from C. parvum genomic DNA using generic TS primers in the polymerase chain reaction. Genomic Southern and electrophoretic karyotype analyses reveal C. parvum DHFR-TS is a single-copy gene on a 1200-kb chromosome. The DHFR-TS nucleic acid sequence contains no introns and the single 1563-bp open reading frame encodes a 179 residue N-terminal DHFR domain connected by a 55 amino acid junction peptide to a 287 residue C-terminal TS domain. The sequences of the DHFR-TS gene from the bovine and human C. parvum isolates differ at two positions in the 5'-flanking sequence and at 38 positions in the encoding sequence. These DNA sequence polymorphisms will provide a powerful probe to examine the genotypic diversity and genetic population structure of C. parvum. The two sequences encode identical TS domains which share all except one of the phylogenetically conserved amino acid residues identified among reported TS sequences. The predicted DHFR domain sequences contain nine amino acid differences; these polymorphisms all map to non-active site, surface locations in known DHFR structures. The C. parvum DHFR active site contains novel residues at several positions analogous to those at which point mutations have been shown to produce antifolate resistance in other DHFRs. Thus C. parvum DHFR may be intrinsically resistant ti inhibition by some antifolate DHFR inhibitors which may explain why cryptosporidiosis is refractory to treatment with the clinically common antibacterial and antiprotozoal antifolates.
Amino Acid Sequence↗
Cryptosporidium and the food supply.
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AIDS-Related Opportunistic Infections↗
Plasmodium falciparum: D260, an intraerythrocytic parasite protein, is a member of the glutamic acid dipeptide-repeat family of proteins.
Members of a serologically cross-reacting family of proteins including Ag332 and Pf11.1, megadalton proteins of schizont-infected red blood cells, and gametocytes, respectively, and Pf155-RESA, a 155-kDa protein of ring-infected red blood cells, have been reported to share amino acid repeat sequences. These repeats are rich in glutamic acid dipeptides postulated to be involved in generating serologic cross-reactivity. We report the identification and characterization of another member of this cross-reacting family, a 260-kDa glutamic acid-rich intraerythrocytic protein. Human antibodies affinity purified on the 260-kDa region of Western boots of trophozoite proteins of Plasmodium falciparum were used to screen a trophozoite-stage lambda gt11 cDNA library. A 1.8-kb clone was identified and human antibodies were affinity purified on the expressing clone. Using this affinity-purified antibody and the 1.8-kb clone, the corresponding protein, its gene, and its chromosomal location were investigated. The 260-kDa corresponding protein serologically cross-reacts with Pf155-RESA, but is the product of a different gene. The 260-kDa protein is Triton X-100 soluble and is variable in molecular weight in different isolates. Immunoprecipitation of [35S]methionine-labeled infected red blood cells indicates that the protein is synthesized throughout the intraerythrocytic cycle but is most prominent in schizonts. The protein, as has been shown previously, is not immunoprecipitated from 125I surface-labeled infected red blood cells and is thus not PfEMP1, the antigen associated with cytoadherence. Indirect fluorescent antibody studies using fixed infected red blood cells suggest that the protein is localized to the periphery of the intraerythrocytic parasite.
Amino Acid Sequence↗
Experience with repair of 120 hypospadias using Mathieu's procedure.
Between 1985 and 1993 120 boys with distal hypospadias (from distal penile shaft to glandular position) were treated using Mathieu's procedure at the department of pediatric surgery, Hannover Medical School, Germany. The outcome of these cases has been analysed. Fistula-rate was 12.5%. Results are compared with published reports, recent developments and changes in treatment are discussed.
Adolescent↗
An examination of Cyriax's passive motion tests with patients having osteoarthritis of the knee.
BACKGROUND AND PURPOSE: We explored the construct validity and test-retest reliability of the passive motion component of the Cyriax soft tissue diagnosis system. We compared the hypothesized and actual patterns of restriction, end-feel, and pain/resistance sequence (P/RS) of 79 subjects with osteoarthritis (OA) of the knee and examined associations among these indicators of dysfunction and related constructs of joint motion, pain intensity, and chronicity. SUBJECTS: Subjects had a mean age of 68.5 years (SD = 13.3, range = 28-95), knee stiffness for an average of 83.6 months (SD = 122.4, range = 1-612), knee pain averaging 5.6 cm (SD = 3.1, range = 0-10) on a 10-cm visual analogue scale, and at least a 10-degree limitation in passive range of motion (ROM) of the knee. METHODS: Passive ROM (goniometry, n = 79), end-feel (n = 79), and P/RS during end-feel testing (n = 62) were assessed for extension and flexion on three occasions by one of four experienced physical therapists. Test-retest reliability was estimated for the 2-month period between the last two occasions. RESULTS: Consistent with hypotheses based on Cyriax's assertions about patients with OA, most subjects had capsular end-feels for extension; subjects with tissue approximation end-feels for flexion had more flexion ROM than did subjects with capsular end-feels, and the P/RS was significantly correlated with pain intensity (rho = .35, extension; rho = .30, flexion). Contrary to hypotheses based on Cyriax's assertions, most subjects had noncapsular patterns, tissue approximation end-feels for flexion, and what Cyriax called pain synchronous with resistance for both motions. Pain intensity did not differ depending on end-feel. The P/RS was not correlated with chronicity (rho = .03, extension; rho = .01, flexion). Reliability, as analyzed by intraclass correlation coefficients (ICC[3,1]) and Cohen's kappa coefficients, was acceptable (> or = .80) or nearly acceptable for ROM (ICC = .71-.86, extension; ICC = .95-.99, flexion) but not for end-feel (kappa = .17, extension; kappa = .48, flexion) and P/RS (kappa = .36, extension; kappa = .34, flexion). CONCLUSION AND DISCUSSION: The use of a quantitative definition of the capsular pattern, end-feels, and P/RS as indicators of knee OA should be reexamined. The validity of the P/RS as representing chronicity and the reliability of end-feel and the P/RS are questionable. More study of the soft tissue diagnosis system is indicated.
Adult↗
Respiratory disorders and atopy in Danish refuse workers.
This survey describes respiratory and mucosal symptoms of garbage-handling and recycling workers in Denmark. The study includes 20 paper-sorting workers, eight compost workers, and 44 garbage-handling workers. As a control group, 119 workers from water purification plants of Copenhagen were chosen; workers in our study had a lower mean age and shorter mean employment time than did members of the control group. There was no significant difference in tobacco consumption between the groups. Garbage-handling workers were exposed to a significantly higher mean concentration (SD) of total dust than were water supply workers-0.74 (0.77) mg/m3 compared with 0.42 (0.25) mg/m3 (p < 0.05). Total count of microorganisms was significantly higher in garbage-handling and composting areas compared with paper-sorting as well as water supply areas 0.46 (0.125) x 10(5), 0.54 (0.77) x 10(5), 4.7 (5.89) x 10(3), and 0.08 (0.04) x 10(3) cfu/m3, respectively (p < 0.05). This difference could not be explained as an effect of differential growth requirements. Significantly higher amounts of gram-negative bacteria were found in composting and garbage-handling plants than in water-supply plants. In garbage-handling plants only, there were significantly higher amounts of endotoxins than in paper-sorting plants. Significantly higher prevalence of chest tightness (14%), flu-like symptoms (14%), itching eyes (27%), itching nose (14), and sore or itching throat (21%) were found among garbage-handling workers, compared with, respectively, 1, 1, 11 and 0% among water-supply workers. Furthermore, prevalence of nausea and vomiting or diarrhea rose from 2% and 7% among the water-supply workers to 19% and 27% among the garbage workers.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Management of medically fragile infants and children.
Medically fragile infants and children present a host of challenges. The neonatal intensive care unit (NICU) is initially the mainstay of care for these infants, but it does not meet the critical developmental interactive needs of the child and parents to ensure positive psychosocial bonding. The care of these infants is further complicated by high daily costs (ranging from $1,000 to $2,500 per neonatal intensive care bed day) and lengthy, expensive inpatient stays (typically ranging from one week to five months or more). FHP Utah, a managed care organization, met these challenges through an innovative case management-oriented home care program called "Welcome Home." The program has produced a major impact on the quality and the cost of care for medically fragile infants. This article summarizes the first year's experience in implementing and operating the program.
Home Care Services↗
[Death in bronchial asthma. Findings and forensic importance].
In 23,707 forensical and 25,564 clinical post-mortem examinations a total number of 196 deaths from bronchial asthma were determined retrospectively. Furthermore investigated were 29 cases in which asthma had the importance of a pathological side finding. Described are the histories, epidemiological data as well as morphological and histological findings. The characteristic morphological triad of thickening of the epithelial basement membrane, hypertrophy of the muscle coat in the bronchi and mucus plugging were found in almost all cases of asthma death. Regarding to forensical and insurance medical aspects it is important to consider the accompanying circumstances and supporting facts of the death, therapeutical procedures and death causing concurrent non-natural organ damages. They form the basis for reproaches in terms of neglected help or accidental homicide and can call the way of death in question,--which is illustrated in examples.
Adolescent↗
Cellular biology of Cryptosporidium parvum.
With the emergence of Cryptosporidium parvum as a major pathogen encountered in human and veterinary clinical practice, a need for increased knowledge of the cellular- and immuno-biology of this Apicomplexan parasite has developed. Initial work has used paradigms taken from other Apicomplexans, especially Plasmodium, Toxoplasma and Eimeria, as a starting point. In this article, Carolyn Petersen discusses the observation that in these organisms, molecular targets of antibodies (which have protective value, in vivo, against disease) have frequently been located in the apical complex or on the surface of the invasive stages of the parasite and appear to mediate biologically crucial processes including motility, attachment to the host cell, modification of the host membrane, and entry into the host cell. Molecular-biology approaches to the study of enzymes and of structural proteins which mediate motility are also considered. Invasion mechanisms, biochemical pathways and motility may involve molecules that will prove susceptible to immunotherapeutic or chemotherapeutic interruption of cryptosporidiosis.
Journal Article↗
Structural analysis and demonstration of the 29 kDa antigen of pathogenic Entamoeba histolytica as the major accessible free thiol-containing surface protein.
The 29 kDa protein of pathogenic Entamoeba histolytica is a cysteine-rich surface antigen which we recently characterized by cDNA sequencing and by using monoclonal antibodies which differentiated between pathogenic and non-pathogenic clinical isolates. To determine the structure and biochemical attributes of this protein, a repertoire of immunological techniques using monoclonal antibodies, and radiolabelling were employed. We demonstrated that the 29 kDa protein forms a 60 kDa dimer and a high-molecular-mass oligomer(s) on the surface of the organism through disulphide bonds, and is the major accessible free thiol-containing surface protein of E. histolytica. The deduced amino acid sequence encoding the 29 kDa protein was found to share a common amino acid domain with sequences reported for Helicobacter pylori, Salmonella typhimurium, MER5 gene expressed in murine erythroleukemia cells, Clostridium pasteurianum, and a Bacillus spp.
Amino Acid Sequence↗
Anti-Cryptosporidium parvum antibodies inhibit infectivity in vitro and in vivo.
Cryptosporidium parvum causes acute diarrhea in immunocompetent individuals and a severe life-threatening disease in immunocompromised individuals, including AIDs patients. No efficacious therapy for cryptosporidiosis has yet been reported. However, treatment of some patients with cryptosporidiosis with hyperimmune bovine colostrum has ameliorated or eliminated clinical symptoms. Consequently, it is important to identify and characterize C. parvum antigens which are the targets of protective antibodies to facilitate the development of more efficacious therapy. We report that hyperimmune bovine colostral immunoglobulin inhibits C. parvum infectivity in a reproducible in vitro assay, and we correlate this inhibition with the protective capacity of the bovine colostrum in vivo. We have also identified the major C. parvum sporozoite antigens recognized on Western blots (immunoblots) by this colostral immunoglobulin preparation. Antibodies that recognize some surface molecules of other Apicomplexan parasites are protective in vivo. Consequently, we radioiodinated membrane proteins of sporozoites and immunoprecipitated 19 molecules which are the target of immunoglobulin that is protective in vivo and in vitro.
Animals↗
Antibody screening of expression libraries.
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Animals↗
Adherence of infected erythrocytes to venular endothelium selects for antigenic variants of Plasmodium falciparum.
Erythrocytes (E) infected with asexual forms of malaria parasites exhibit surface antigenic variation. In Plasmodium falciparum infections, the variant Ag is the P. falciparum E membrane protein 1 (PfEMP1). This molecule may also mediate the adherence of infected E to host venular endothelium. We show here that parasite lines selected for increased adherence to endothelial cells have undergone antigenic variation. Three adherent lines selected from the same P. falciparum clone reacted with the same agglutinating antiserum that failed to agglutinate the parental clone. Immunoprecipitation experiments with the agglutinating anti-serum demonstrated that the selected lines expressed cross-reactive forms of PfEMP1 that were of higher m.w. and antigenically distinct from PfEMP1 of the parental clone. When one of the adherent lines was cloned in the absence of selection, a range of variant antigenic types emerged with differing cytoadherence phenotypes. These findings show that selection for cytoadherence in vitro favors the emergence of antigenic variants of P. falciparum and suggest that the requirement for cytoadherence in vivo may restrict the range of antigenic variants of P. falciparum in natural infections.
Animals↗
Gene inactivation of Pf11-1 of Plasmodium falciparum by chromosome breakage and healing: identification of a gametocyte-specific protein with a potential role in gametogenesis.
We report the identification of the product of the Plasmodium falciparum Pf11-1 gene and demonstrate that it is a gametocyte-specific protein that has a potential role in the rupture of the host erythrocyte and emergence of the gametes (gametogenesis). The Pf11-1 gene is a large locus (30 kb) whose sequence predicts a glutamic acid-rich polypeptide. Our identification of the Pf11-1 gene product as gametocyte specific was greatly facilitated by the isolation of a mutant parasite clone in which greater than 90% of the Pf11-1 gene was deleted. Molecular analysis of the mutant locus suggests that the underlying genetic mechanism is chromosome breakage and subsequent healing by the addition of telomere repeats. PCR-based analysis showed that similar DNA rearrangements occur commonly in small subpopulations of most laboratory strains, suggesting that the Pf11-1 locus represents a fragile chromosome region. Northern blot analysis demonstrates that a large Pf11-1 gene-specific transcript (much greater than 10 kb) is present in gametocytes but not in asexual blood stage parasites. The Pf11-1 protein was localized by electron microscopy to granules in the cytoplasm of gametocytes adjacent to the membrane of the parasitophorous vacuole. Following in vitro stimulation of gametogenesis, the Pf11-1 protein was found in the membrane of lysed erythrocytes, suggesting a role for Pf11-1 in erythrocyte rupture within the mosquito gut.
Animals↗
Isolation, sequence and molecular karyotype analysis of the actin gene of Cryptosporidium parvum.
Actin is an ubiquitous and highly conserved microfilament protein which is hypothesized to play a mechanical, force-generating role in the unusual gliding motility of sporozoan zoites and in their active penetration of host cells. We have identified and isolated an actin gene from a Cryptosporidium parvum genomic DNA library using a chicken beta-actin cDNA as an hybridization probe. The nucleotide sequences of two overlapping recombinant clones were identical and the amino acid sequence deduced from the single open reading frame was 85 % identical to the P. falciparum actin I and human gamma-actin proteins. The predicted 42 106-Da Cryptosporidium actin contains 376 amino acids and is encoded by a single-copy gene which contains no introns. The nucleic acid coding sequence is 72% biased to the use of A or T in the third position of codons. Chromosome-sized DNA released from intact C. parvum oocysts was resolved by OFAGE into 5 discrete ethidium bromide-staining DNAs ranging in size from 900 to 1400 kb; the cloned C. parvum actin gene hybridized to a single chromosomal DNA of approximately 1200 kb.
Actins↗
Cryptosporidiosis in patients infected with the human immunodeficiency virus.
Infection caused by Cryptosporidium species has proved to be one of the most taxing and frustrating conditions faced by clinicians caring for patients with AIDS. Unfortunately, this unique organism, which was identified as a human pathogen only shortly before the AIDS epidemic began to manifest itself, has received only minimal attention during the past decade. Dr. Carolyn Petersen, an assistant professor of medicine at the University of California, San Francisco, and a member of the Division of Infectious Diseases at San Francisco General Hospital, is a molecular parasitologist whose investigative career is focused on elucidating the biology of Cryptosporidium species. In this AIDS Commentary Dr. Petersen provides an update on recent developments in this field.
AIDS-Related Opportunistic Infections↗