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J Parrish

Publications and source records attributed to J Parrish.

At least 19 recordsLinked to original sources
PubMed2001

Mitochondrial endonuclease G is important for apoptosis in C. elegans.

Programmed cell death (apoptosis) is a tightly regulated process of cell disassembly in which dying cells and their nuclei shrink and fragment and the chromosomal DNA is degraded into internucleosomal repeats. Here we report the characterization of the cps-6 gene, which appears to function downstream of, or in parallel to, the cell-death protease CED-3 of Caenorhabditis elegans in the DNA degradation process during apoptosis. cps-6 encodes a homologue of human mitochondrial endonuclease G, and its protein product similarly localizes to mitochondria in C. elegans. Reduction of cps-6 activity caused by a genetic mutation or RNA-mediated interference (RNAi) affects normal DNA degradation, as revealed by increased staining in a TUNEL assay, and results in delayed appearance of cell corpses during development in C. elegans. This observation provides in vivo evidence that the DNA degradation process is important for proper progression of apoptosis. CPS-6 is the first mitochondrial protein identified to be involved in programmed cell death in C. elegans, underscoring the conserved and important role of mitochondria in the execution of apoptosis.

Amino Acid Sequence↗
PubMed2001

Vancomycin-resistant enterococci colonization in patients at seven hemodialysis centers.

BACKGROUND: Vancomycin-resistant enterococci (VRE) are increasing in prevalence at many institutions, and are often reported in dialysis patients. We studied the prevalence of and risk factors for VRE at seven outpatient hemodialysis centers (three in Baltimore, MD, USA, and four in Richmond, VA, USA). METHODS: Rectal or stool cultures were performed on consenting hemodialysis patients during December 1997 to April 1998. Consenting patients were recultured during May to July 1998 (median 120 days later). Clinical and laboratory data and functional status (1 to 10 scale: 1, normal function; 9, home attendant, not totally disabled; 10, disabled, living at home) were recorded. RESULTS: Of 478 cultures performed, 20 (4.2%) were positive for VRE. Among the seven centers, the prevalence of VRE-positive cultures varied from 1.0 to 7.9%. Independently significant risk factors for a VRE-positive culture were a functional score of 9 to 10 (odds ratio 6.9, P < 0.001), antimicrobial receipt within 90 days before culture (odds ratio 6.1, P < 0.001), and a history of injection drug use (odds ratio 5.4, P = 0.004). CONCLUSIONS: VRE-colonized patients were present at all seven participating centers, suggesting that careful infection-control precautions should be used at all centers to limit transmission. In agreement with previous studies, VRE colonization was more frequent in patients who had received antimicrobial agents recently, underscoring the importance of judicious antimicrobial use in limiting selection for this potential pathogen.

Cross Infection↗
PubMed2001

A prospective study of vascular access infections at seven outpatient hemodialysis centers.

Vascular access infections are a major cause of morbidity and mortality in hemodialysis patients, and the use of antimicrobials to treat such infections contributes to the emergence and spread of antimicrobial-resistant bacteria. To determine the incidence of and risk factors for vascular access infections, we studied hemodialysis patients at 7 outpatient dialysis centers (4 in Richmond, VA, and 3 in Baltimore, MD) during December 1997 to July 1998. Vascular access infections were defined as local signs (pus or redness) at the vascular access site or a positive blood culture with no known source other than the vascular access; and hospitalization or receipt of an intravenous (IV) antimicrobial. A total of 796 patients were followed for 4,134 patient-months. The vascular access infection rate was 3.5/100 patient-months, ie, patients had a 3.5% risk of infection each month. Independent risk factors were the specific dialysis unit where the patient was treated (relative hazard varying from 1.0 to 4.1 among the 7 centers), catheter access (relative hazard, 2.1 v implanted access), albumin level (relative hazard, 2.4 for lowest v highest quartile), urea reduction ratio (relative hazard, 2.2 for lowest v highest quartile), and hospitalizations during the previous 90 days (relative hazard, 4.9 for >/=6 v zero hospitalizations). These data confirm that vascular access infections are common in hemodialysis patients and that infection rates differ substantially among different centers. Catheter use should be minimized to reduce these infections. Additionally, the possibility that improved serum albumin and urea reduction ratio could reduce vascular access infections should be evaluated.

Aged↗
PubMed2000

Demonstration of the in vivo interaction of key cell death regulators by structure-based design of second-site suppressors.

Demonstrating in vivo interaction of two important biomolecules and the relevance of the interaction to a biological process have been difficult issues in biomedical research. Here, we report the use of a homology modeling approach to establish the significance of protein interactions in governing the activation of programmed cell death in Caenorhabditis elegans. A protein interaction cascade has been postulated to mediate activation of cell death in nematodes, in which the BH3-domain-containing (Bcl-2 homology region 3) protein EGL-1 binds the cell-death inhibitor CED-9 and induces release of the death-activating protein CED-4 from inhibitory CED-4/CED-9 complexes. We show here that an unusual gain-of-function mutation in ced-9 (substitution of glycine 169 to glutamate) that results in potent inhibition of most nematode cell deaths impairs the binding of EGL-1 to CED-9 and EGL-1-induced release of CED-4 from CED-4/CED-9 complexes. Based on a modeled EGL-1/CED-9 complex structure, we generated second-site compensatory mutations in EGL-1 that partially restore the binding of EGL-1 to CED-9(G169E) and EGL-1-induced release of CED-4 from CED-4/CED-9(G169E) complexes. Importantly, these mutations also significantly suppress the death-protective activity of CED-9(G169E) in vivo. These results establish that direct physical interaction between EGL-1 and CED-9 is essential for the release of CED-4 and the activation of cell death. The structure-based design of second-site suppressors via homology modeling should be widely applicable for probing important molecular interactions that are implicated in fundamental biological processes.

Amino Acid Sequence↗
PubMed1995

A 4-megabase YAC contig that spans the Langer-Giedion syndrome region on human chromosome 8q24.1: use in refining the location of the trichorhinophalangeal syndrome and multiple exostoses genes (TRPS1 and EXT1).

We have constructed a physical map covering over 4 Mb of human chromosome 8q24.1 and used this map to refine the locations of the genes responsible for Langer-Giedion syndrome. The map is composed of overlapping YAC clones that were identified and ordered in relation to sequence tagged sites mapped to the Langer-Giedion chromosomal region on somatic cell hybrids. The minimal region of overlap of Langer-Giedion syndrome deletions, previously identified by analysis of 15 patients, was placed on the map by analysis of 2 patients whose deletions define the endpoints. The chromosome 8 breakpoint of a balanced t(8;9)(q24.11;q33.3) translocation from a patient with trichorhinophalangeal syndrome (TRPS I) was found to be located just within the proximal end of the minimal deletion region. A deletion of 8q24.11-q24.3 in a patient with multiple exostoses was found to overlap the distal end of the LGS deletion region, indicating that the EXT1 gene is distal to the TRPS1 gene and supporting the hypothesis that Langer-Giedion syndrome is due to loss of functional copies of both the TRPS1 and the EXT1 genes.

Animals↗
PubMed1994

Synergistic induction of thermotolerance in murine natural killer cells by interferon alpha and mild heat shock.

Splenic lymphocytes from C3H/HeN mice were primed in vivo or in vitro with the interferon inducer poly inosine:cytosine (Poly IC) or in vitro with interferon alpha (IFN alpha) and evaluated for their natural killer (NK) activity after exposure to hyperthermia for defined periods. Lytic activity against cells of the NK-susceptible Moloney lymphoma cell line YAC by Poly I:C- or IFN alpha-primed spleen cells exhibited thermotolerance to 41, 42 and 43 degrees C exposure compared to unprimed cells. Spleen cells were also incubated for 1 h at 40 or 37 degrees C prior to exposure to 42 degrees C. Incubation at 40 degrees C produced a modest increase in thermal resistance to 42 degrees C by otherwise unprimed spleen cells. Spleen cells that had been primed by Poly I:C or IFN alpha followed by 1 h at 40 degrees C were rendered even more resistant to hyperthermia at 42 degrees C. These data suggest that two host responses to viral infection, fever and production of IFN alpha, may endow cells involved in the inflammatory response (in this case NK cells) with resistance to more severe stress. Further, IFN alpha and fever may synergize in this protective mechanism.

Animals↗
PubMed1992

Human chromosome 8 linkage map based on short tandem repeat polymorphisms: effect of genotyping errors.

A linkage map consisting of 21 dinucleotide repeat polymorphisms, 1 tetranucleotide repeat polymorphism, and 3 RFLPs was constructed for human chromosome 8. The map spanned most of the chromosome length from near pter to q23-q24 on the distal portion of the long arm. The total 186 cM length of the female map was over two times the 84 cM length of the male map. Cytogenetic mapping of the polymorphisms using a panel of hybrids containing rearranged chromosomes was completely consistent with the linkage map. Special effort was made to remove as many genotyping errors, including parental phase errors, as possible. Removal of errors, in agreement with recent theoretical predictions, led to reduction of the total length of the sex-equal map by 10% from 145 to 130 cM.

Alleles↗
PubMed1984

Autoreactivity to collagen in a murine lupus model.

MRL/l mice exhibit many characteristics of human systemic lupus erythematosus including antinuclear antibodies, circulating immune complexes, glomerulonephritis, and death secondary to renal failure. In addition, these mice have elevated levels of rheumatoid factor and spontaneously develop arthritis that has many similarities to human rheumatoid arthritis. Our present studies indicate that, with age, they also develop reactivity to types I and II collagen. The levels of antibodies against native or denatured types I and II collagen in the sera of 4-5-month-old MRL/l mice are significantly higher than those in the sera of age-matched Balb/c or MRL/n mice. The specificity of these antibodies for collagen was demonstrated by a competitive binding assay. The T cells from 1- or 2-month-old MRL/l mice exhibited a significant proliferative response in the presence of type I collagen and a mild or no response to type II collagen. Both antigenic and mitogenic responses decreased with age. The results suggest that the development of autoimmunity to collagen may play an important role in the perpetuation of arthritis, vasculitis, and glomerulonephritis in MRL/l mice.

Animals↗
PubMed1981

A laboratory report on iron supplementation in blood donors. I.

Blood donation at the accepted frequency of one donation every 8 weeks is generally regarded as excessive for preservation of donor iron reserves, especially in women. A double-blind study was conducted of 627 individuals who had previously donated blood to determine the effect of iron supplementation on iron reserves. Half the donors received ferrous fumarate at a dosage of 66.6 mg elemental iron daily for 45 days. The other half received placebo. Eight blood variables reflecting the iron status of the donors were determined at the time of the initial donation and again 2 months later at the time of their second donation. Statistical analysis of the blood variables indicated that the prescribed amount of ferrous fumarate should be considered the minimal effective dose for maintenance of reduced iron storage in blood donors. However, the data are furnished for the analysis of panels of experts for any conclusions and recommendations concerning this study. Feostat, the iron supplement, was tolerated well by the participating donors. Gastrointestinal upset occurred in eight donors receiving Feostat and in 10 donors receiving placebo.

Adolescent↗
PubMed1979

Inhibition of estrous cyclicity in golden hamsters by melatonin administration on the day of proestrus.

Single injections of melatonin (25 micrograms) were administered to female hamsters, 15 minutes before lights-out (14L:10D), during either the early diestrous (day 1) or proestrous (day 4) phase of the estrous cycle. Hamsters which received melatonin only on the evening of proestrus became anovulatory by three weeks of treatment, while those that were injected with melatonin during diestrus, or administered oil on either day 1 or 4, continued to exhibit normal estrous cycles. These results indicate that quartan injections of melatonin can suppress reproductive function in female hamsters, and that the effectiveness of the injections may be dependent upon the stage of the estrous cycle at which they are administered.

Animals↗
PubMed1978

Oral psoralen photochemotherapy of atopic eczema.

Oral administration of 8-methoxypsoralen followed by exposure to a high-intensity longwave ultraviolet treatment system resulted in clearing of atopic eczema in 15 patients. Paired-comparison studies demonstrated that this treatment was superior both to conventional ultraviolet light therapy and to no treatment. Short-term observation suggests that regular therapy is necessary to maintain remission of the disease.

Adolescent↗