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J Cohen

Publications and source records attributed to J Cohen.

At least 127 records · Page 7Linked to original sources
PubMed2001

Specific missense mutations in NEMO result in hyper-IgM syndrome with hypohydrotic ectodermal dysplasia.

The gene that encodes nuclear factor kappaB (NF-kappaB) essential modulator (or NEMO, also known as IKKgamma) is required for activation of the transcription factor NF-kappaB. We describe mutations in the putative zinc-finger domain of NEMO that result in an X-linked primary immunodeficiency characterized by hyper-IgM syndrome and hypohydrotic ectodermal dysplasia (XHM-ED). These mutations prevent CD40 ligand (CD40L)-mediated degradation of inhibitor of NF-kappaB alpha (IkappaB-alpha) and account for the following observations: B cells from XHM-ED patients are unable to undergo immunoglobulin class-switch recombination and antigen-presenting cells (APCs) are unable to synthesize the NF-kappaB-regulated cytokines interleukin 12 (IL-12) or tumor necrosis factor alpha (TNF-alpha) when stimulated with CD40L. Nevertheless, innate immunity is preserved in XHM-ED patients because APCs retain the capacity to respond to stimulation by lipopolysaccharide or Staphylococcus aureus Cowan's antigen (SAC). Overall, the phenotype observed in XHM-ED patients shows that the putative zinc-finger domain of NEMO has a regulatory function and demonstrates the definite requirement of CD40-mediated NF-kappaB activation for B cell immunoglobulin class-switching.

Adolescent↗
PubMed2001

KIN241: a gene involved in cell morphogenesis in Paramecium tetraurelia reveals a novel protein family of cyclophilin-RNA interacting proteins (CRIPs) conserved from fission yeast to man.

In this study, we report cloning, by functional complementation of the KIN241 gene involved in Paramecium cell morphogenesis, cortical organization and nuclear reorganization. This gene is predicted to encode a protein of a novel type, comprising a cyclophilin-type, peptidyl-prolyl isomerase domain, an RNA recognition motif, followed by a region rich in glutamate and lysine (EK domain) and a C-terminal string of serines. As homologues of this protein are present in the genomes of Schizosaccharomyces pombe, Caenorhabditis elegans, Drosophila melanogaster, Arabidopsis thaliana and Homo sapiens, the Kin241p predicted sequence defines a new family of proteins that we propose to call 'CRIP', for cyclophilin-RNA interacting protein. We demonstrate that, in Paramecium, Kin241p is localized in the nucleus and that deletion of some nuclear localization signals (NLSs) decreases transport of the protein into the nucleus. No Kin241-1 protein is present in mutant cells, suggesting that the C-terminal serine-rich region is responsible for protein stability.

Amino Acid Motifs↗
PubMed2001

Young patients with colorectal cancer: how do they fare?

BACKGROUND: Younger patients with colorectal cancer (CRC) have long been thought to have a poorer prognosis than older patients. Recent overseas reports, however, have disputed this. The aim of the present study was to conduct a review of data on patients with colorectal cancer collected over a 29-year period at Princess Alexandra Hospital (PAH) to ascertain the outcome of a younger subset of patients at this hospital. METHODS: The PAH Colorectal Project records on 2495 patients with malignancies of the colon, rectum and anus who were treated and followed since 1971, were analysed to determine clinical presentation, treatment and outcome. A group of 61 patients with colo-rectal adenocarcinoma was identified who were aged less than 40 years at presentation. Their clinical data were then compared with the larger group of older patients. RESULTS: There were 30 male and 31 female patients in the younger group. A positive family history was the most consistent risk factor, present in 34% of patients. Despite this, only one patient out of 61 had been diagnosed as a result of a screening programme. The Australian Clinico-Pathological Stage (ACPS), histology and distribution of tumours corresponded to that of the older patients. The overall 5-year survival among younger patients was 53%. The 5-year survival rates in younger patients were better than that for older patients for ACPS A and B, reaching statistical significance for both of these stages. CONCLUSIONS: Our results indicate that younger patients with colorectal cancer have the potential to do just as well as older ones. With the influence of a family history of colorectal cancer being very apparent in this group, greater emphasis should be placed on an adequate screening programme for them.

Adenocarcinoma↗
PubMed2001

Intracellular replication of Salmonella typhimurium strains in specific subsets of splenic macrophages in vivo.

We used flow cytometry and confocal immunofluorescence microscopy to study the localization of Salmonella typhimurium in spleens of infected mice. Animals were inoculated intragastrically or intraperitoneally with S. typhimurium strains, constitutively expressing green fluorescent protein. Independently of the route of inoculation, most bacteria were found in intracellular locations 3 days after inoculation. Using a panel of antibodies that bound to cells of different lineages, including mononuclear phagocyte subsets, we have shown that the vast majority of S. typhimurium bacteria reside within macrophages. Bacteria were located in red pulp and marginal zone macrophages, but very few were found in the marginal metallophilic macrophage population. We have demonstrated that the Salmonella SPI-2 type III secretion system is required for replication within splenic macrophages, and that sifA(-) mutant bacteria are found within the cytosol of these cells. These results confirm that SifA and SPI-2 are involved in maintenance of the vacuolar membrane and intracellular replication in vivo.

Animals↗
PubMed2001

Learning-Service Community Partnership Model: a pediatric program evaluation.

Pediatric clinical learning experiences in which service provision is offered present a challenge to nursing faculty and students. The Learning-Service Community Partnership Model is a framework in which innovative learning and service provision are an integral part of the pediatric nursing clinical experience. This article discusses a program evaluation of a pediatric community-based health promotion program based on this model. The result from this program evaluation shows that a service program can be effectively managed and provided by pediatric nursing faculty and students. This article describes the shift in moving pediatric learning experiences into the community and validates its importance.

Child Day Care Centers↗
PubMed2001

Comparison of past and current barriers to novice nurse practitioner practice: The California perspective.

Novice nurse practitioners (NPs) face unique obstacles to practice. Few studies examine factors influencing early NP clinical performance. Therefore, this research project was designed to collect data from members of an NP professional organization who were asked to identify barriers encountered within the first 3 years of practice. Responses were received from 243 beginning and more experienced NPs. The top three barriers named were lack of public knowledge, lack of positions for NPs, and a lower salary than anticipated. The promotion of NP assets through expanded media coverage and individual educational efforts, the national standardization of the role, and the elimination of restrictive practice legislation can help reduce current barriers. Through the efforts of individuals, NP professional groups, and legislators, existing practice constraints can be mitigated, potential barriers anticipated, and solutions generated to ensure the continued success of this essential advanced practice role.

Adult↗
PubMed2001

How to avoid multiple pregnancies in assistive reproductive technologies.

Since 1980, there has been a worldwide dramatic increase in multiple births. This seems to be due to an increase in the age of reproduction, the use of ovulation induction, and the use of in vitro fertilization. Scarce data suggest that each of these causes is responsible for about one-third of the problem, although quintuplets and more are almost invariably due to ovulation induction. There has been little or no effort to issue guidelines or regulations with respect to ovulation induction, but there has been much advice as to how to control the problem in in vitro fertilization by limiting the number of embryos to be transferred. In sum, a good selection of high-quality embryos on day 3 would allow a high rate of pregnancy with the transfer of one or two blastocysts. Good results of cryopreservation must be part of an agreement in an in vitro fertilization program. If singleton live birthrates were considered to be the principal outcome of assisted reproductive technologies reported by centers and registry, twin and triplet rates should also be reported separately. And finally, if financial considerations would not limit the cost of reimbursement to in vitro fertilization procedures, the number of procedures could be increased with fewer embryos transferred.

Adult↗
PubMed2001

Is nicotine dependence related to smokers' support for restrictions on smoking?

OBJECTIVES: To examine the relationship between nicotine dependence and attitudes, predicted behaviours and support regarding restrictions on smoking. DESIGN: Population-based, computer-assisted, telephone survey of adults in Ontario, Canada using a two-stage stratified sampling design; 1764 interviews were completed (65% response rate) yielding 424 (24%) cigarette smokers, of whom 354 (83%) smoked daily. The Heaviness of Smoking Index was used as a measure of nicotine dependence. MAIN OUTCOME MEASURE: Attitudes toward smoking restrictions, predicted compliance with more restrictions, and support for total smoking bans. RESULTS: Attitudes favorable to smoking restrictions tended to decrease with increased nicotine dependence, but the associations were not statistically significant after adjusting for demographic variables. Predicted compliance with more restrictions on smoking decreased with higher levels of dependence, as did support for a total ban on smoking in restaurants, workplaces, bingo halls, and hockey arenas. Support for smoking bans in food courts, family fast food restaurants, and bars and taverns did not vary significantly with level of nicotine dependence. CONCLUSIONS: Level of nicotine dependence is associated with intended behaviors and support for smoking restrictions in some settings. These results have implications for tobacco control programs and policies.

Adolescent↗
PubMed2001

Genetic taste responses to 6-n-propylthiouracil among adults: a screening tool for epidemiological studies.

Genetically mediated taste responsiveness to 6-n-propylthiouracil (PROP) has been linked to reduced acceptance of some bitter foods. In this community-based study male (n = 364) and female (n = 378) adults enrolled in a self-help dietary intervention trial were screened for PROP taster status. Respondents, aged 18--70 years, were mailed filter papers impregnated with PROP or with aspartame solutions. They received instructions to rate taste intensity and hedonic preference using nine point category scales. Women rated PROP as more bitter than did men. Both sweetness and bitterness ratings were lower for older adults. Taste responsiveness to PROP was unrelated to body mass index in women or men. Higher bitterness ratings for PROP were weakly associated with higher sweetness ratings for aspartame, but were unrelated to sweet taste preferences. Successful administration of PROP filter papers by mail suggests new avenues for the screening of taste phenotypes in epidemiological studies.

Adolescent↗
PubMed2001

ND9P, a novel protein with armadillo-like repeats involved in exocytosis: physiological studies using allelic mutants in paramecium.

In Paramecium, a number of mutants affected in the exocytotic membrane fusion step of the regulated secretory pathway have been obtained. Here, we report the isolation of one of the corresponding genes, ND9, previously suspected to encode a soluble protein interacting with both plasma and trichocyst membranes. Nd9p is a novel polypeptide that contains C-terminal Armadillo-like repeats. Point mutations were found in the first N-terminal quarter of the molecule and in the last putative Armadillo repeat, respectively, for the two thermosensitive mutants, nd9-1 and nd9-2. The different behaviors of these mutants in recovery experiments upon temperature shifts suggest that the N-terminal domain of the molecule may be involved in membrane binding activity, whereas the C-terminal domain is a candidate for protein-protein interactions. The nonsense nd9-3 mutation that produces a short N-terminal peptide has a dominant negative effect on the nd9-1 allele. We show here that, when overexpressed, the dominant negative effect can be produced even on the wild-type allele, suggesting competition for a common target. We suggest that Nd9p could act, like some SNARE proteins, at the membrane-cytosol interface to promote membrane fusion.

Algorithms↗
PubMed2001

Mitochondria in human offspring derived from ooplasmic transplantation.

Ooplasmic transfer from fertile donor oocytes into potentially compromised recipient patient oocytes has led to the birth of nearly 30 babies worldwide. Cytoplasmic transplantation has caused apprehension, since the mixing of human ooplasm from two different maternal sources may generate mitochondrial (mt) heteroplasmy (both recipient and donor mtDNA) in offspring. This investigation traced the mitochondrial donor population both during the ooplasmic transfer technique and in the bloods of two 1 year old children using mtDNA fingerprinting. Donor ooplasm stained for active mitochondria was transferred into recipient ooplasm and the mitochondria were visualized by confocal microscopy after the microinjection procedure and fertilization. Heteroplasmy was found in the blood from each of the children. This report is the first case of human germline genetic modification resulting in normal healthy children.

Cytoplasm↗
PubMed2001

Developmental ability of chromosomally abnormal human embryos to develop to the blastocyst stage.

BACKGROUND: A correlation between morphology, developmental competence and chromosome abnormalities is established. However, since absolute correlations are rare, embryo selection remains one of the most arduous tasks in assisted reproduction. This study was undertaken in order to determine which chromosomal abnormalities are compatible with development to the blastocyst stage. METHODS: Embryos diagnosed by preimplantation genetic diagnosis (PGD) as chromosomally abnormal or unsuitable for transfer were cultured to day 5 or 6. Morphology and development were observed daily. After extended culture, embryos were fixed and analysed by two rounds of FISH with the same probes used for PGD. RESULTS: Some types of numerical chromosome abnormalities do not preclude full differentiation in vitro. For instance, extensive mosaicism was detected in blastocysts and trisomic embryos reached the blastocyst stage with a frequency of 37%. Interestingly, only those monosomies compatible with first trimester development (monosomy X and 21) were detected at blastocyst stage. CONCLUSION: Even though there is a strong selection against chromosomally abnormal embryos, extended culture to day 5 or 6 cannot be used as a reliable tool to select against clinically relevant chromosome abnormalities such as trisomies.

Adult↗
PubMed2001

Food supplementation with milk fermented by Lactobacillus casei DN-114 001 protects suckling rats from rotavirus-associated diarrhea.

Group A rotavirus is the leading cause of diarrhea among children aged 3-36 mo worldwide. Introducing fermented milk products into the infant diet has been proposed for the prevention or treatment of rotavirus diarrhea. The preventive effect of milk fermented by the Lactobacillus casei strain DN-114 001 was studied in a model of germfree suckling rats supplemented daily from d 2 of life and infected with SA11 rotavirus at d 5 (RF group). One group was supplemented with nonfermented milk (RM) and two uninfected groups (CM and CF) received either nonfermented or fermented milk. Frequency and severity of diarrhea were observed. Rats were killed at various times from 0 to 120 h postinfection (p.i.). Bacteria were measured in the intestine, and rotavirus antigens were detected by ELISA in fecal samples and in different parts of the intestine. Histologic observations were made, including vacuolation, morphology of intestinal villi and number of mucin cells. RM rats had diarrhea for 6 d; compared with the CM group, they had alterations of the intestinal mucosa characterized by cellular vacuolation 48 and 72 h p.i. and a lower number of sulfated mucin cells 72 and 96 h p.i. (P: < 0.05). Early supplementation with fermented milk significantly decreased the clinical signs of diarrhea from 24 to 144 h p.i. (P: < 0.05) and prevented rotavirus infection in all sections of the intestine. Histologic lesions of the small intestine were greatly reduced (P: < 0.05) and the number of mucin cells remained unchanged. The data are discussed with respect to the possibility of reducing rotavirus diarrhea in young children by consumption of fermented milk.

Animals↗
PubMed2001

Association between spindle assembly checkpoint expression and maternal age in human oocytes.

The spindle assembly checkpoint modulates the timing of anaphase initiation in response to the improper alignment of chromosomes at the metaphase plate. If defects are detected, a signal is transduced to halt further progression of the cell cycle until correct bipolar attachment to the spindle is achieved. The mitotic arrest deficient (MAD2) and budding uninhibited by benomyl (BUB1) genes encode conserved kinetochore-associated proteins believed to be components of the checkpoint regulatory pathway. A failure in this surveillance system could lead to genomic instability that may underlie the increased incidence of aneuploidy in the gametes of older women. To explore this possibility, the concentrations of these transcripts in human oocytes at various stages of maturation were determined by real-time rapid cycle fluorescent reverse transcription-polymerase chain reaction (RT-PCR). The results obtained following quantitative analysis suggest that these messages degrade as oocytes age. Potentially, this may impair checkpoint function in older oocytes and may be a contributing factor in age-related aneuploidy.

Adult↗