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P Lynch

Publications and source records attributed to P Lynch.

At least 73 records · Page 4Linked to original sources
PubMed1993

Perturbation of the carboxy terminus of HIV-1 Rev affects multimerization on the Rev responsive element.

Perturbations within the transactivation and carboxy-terminal domains of HIV-1 Rev were examined for effects on Rev responsive element (RRE) binding activities in vitro and biological activity in vivo. Binding affinities, specificities, and multimerization of the transactivation mutants M10 and Rev/Rex M10-16 on the RRE were equivalent to wild-type Rev. Substitution of the Rex transactivation domain within Rev resulted in the incorporation of an internal methionine residue which, when cleaved with CNBr and subsequently purified, produced a protein species (CNBr-Rev) unable to fully multimerize on the RRE. Instead, two discrete protein-dependent species were generated in the gel shift assay. Furthermore, CNBr-Rev was observed to bind to the RRE with high specificity and an equilibrium binding constant of 6 x 10(-10) M. A C-terminal Rev deletion mutant (Rev M9 delta 14) lacking amino acids 68-112 displayed identical RRE binding characteristics to the CNBr-Rev protein. This protein, which lacks both the activation and the C-terminal domains, was biologically inactive but maintained the ability to discriminate the RRE from nonspecific RNA. Deletion of amino acids 92-112 resulted in a Rev mutant (Rev M11 delta 14) which bound to the RRE with wild-type affinity and high specificity. This purified mutant was observed to be aberrant in multimerization activity on the RRE with reduced multimerization apparent in the gel shift assay. However, Rev M11 delta 14 possessed biological activity equivalent to wild-type Rev in a cell-based p24 ELISA assay. These results suggest that polymerization on the RRE is dispensable for Rev activity and that two monomeric Rev proteins bound to the RRE are sufficient for biological activity. Furthermore, in vivo experiments using the Rev/Rex chimeric mutant and the M10 transdominant mutant as well as in vitro dissociation rate studies with Rev M11 delta 14 and Rev M9 delta 14 suggest that the M9 through M11 domain of the protein may be involved in RRE-dependent specific Rev dimerization.

Amino Acid Sequence↗
PubMed1993

Examination gloves as barriers to hand contamination in clinical practice.

OBJECTIVE: To test the effectiveness of vinyl and latex gloves as barriers to hand contamination with gram-negative organisms and enterococci during routine hospital procedures. DESIGN AND INTERVENTIONS: We studied 137 procedures during which a health care worker's gloved hand contacted a patient's mucous membrane and was thus potentially contaminated with gram-negative rods or enterococci. Quantitative hand cultures were obtained from each health care worker before and after the gloved contact using a modified glove juice method, and the exterior glove surface was also quantitatively cultured after patient contact. Used gloves were then tested for leaks using the American Society for Testing and Materials' watertight test. SETTING: Harborview Medical Center, a 330-bed city-county hospital and level I regional trauma and burn center, is both a teaching facility affiliated with the University of Washington and the major provider of care to indigent and uninsured persons in Seattle-King County, Washington. PATIENTS AND OTHER PARTICIPANTS: Respiratory therapists performing endotracheal tube care on intubated intensive care unit patients, registered nurses performing digital rectal stimulation for bowel training on patients with spinal cord injury in the rehabilitation ward, and dentists performing routine dental examinations and procedures on healthy outpatients in the dental clinic. MAIN OUTCOME MEASURE AND RESULTS: Eighty-six of the 135 gloves cultured had gram-negative rods or enterococci on the external surface after use and were thus sources of potential hand contamination. Microbial contamination of the health care worker's hands occurred in 11 (13%; 95% confidence interval, 6% to 20%) of these 86 events, and was more frequent with vinyl (10 of 42) than latex (one of 44) gloves (P < .01). After use, glove leaks were also more frequent in vinyl gloves (26 of 61) than with latex gloves (six of 70) (P < .001). Even when leaks were present, gloves prevented hand contamination in 77% of instances and quantitative counts of microorganisms contaminating hands were 2 to 4 logs less than counts on external glove surfaces. Health care workers reported awareness of the presence of glove leaks in only seven (22%) of the 32 events in which leaks were subsequently demonstrated. CONCLUSIONS: Under conditions of routine use, gloves effectively function as a protective barrier even when leaks are present. Latex gloves were less frequently associated with leaks and hand contamination. Since hand contamination occurred after 13% of exposures and cannot be readily identified by health care workers, routine hand washing should be done after each patient contact.

Enterococcus↗
PubMed1993

Overexpression of an elongation factor-1 gamma-hybridizing RNA in colorectal adenomas.

While it is apparent that colorectal carcinogenesis results from a series of genetic alterations manifested phenotypically by the adenoma-to-carcinoma sequence, the early events that occur in the process of tumorigenesis have not been elucidated. We previously demonstrated that human elongation factor-1 (EF-1) gamma-hybridizing RNA was overexpressed in 25 of 29 colorectal carcinomas. To determine if the overexpression of this mRNA occurs early in tumor development, we examined 25 adenomas and corresponding normal-appearing distant mucosae from 20 patients without familial adenomatous polyposis (FAP). We observed overexpression at a level of twofold or more in 14 (56%) of the 25 adenomas, indicating that overexpression of EF-1 gamma RNA is often a relatively early event in the development of non-FAP colorectal cancer.

Adenoma↗
PubMed1993

Surveillance in hereditary nonpolyposis colorectal cancer: an international cooperative study of 165 families. The International Collaborative Group on HNPCC.

During its second meeting at Amsterdam in 1990, the International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC) decided to carry out a pilot study on colorectal cancer surveillance in HNPCC. The objectives of the study were to ascertain in each of the participating centers the number of HNPCC families, the recommended screening procedures, the age at diagnosis of colorectal cancer (CRC), and the occurrence of interval cancers. Nine centers in seven countries including Denmark, Finland, Italy, Japan, The Netherlands, Switzerland, and the United States participated. Data were derived from a total of 165 families. With respect to screening, half of the centers advise colonoscopy as the only procedure. The interval between the consecutive examinations varies from one to three years. In the majority of the centers, screening begins at 20 to 25 years. Lifelong screening is recommended by three centers, while the rest advise discontinuation at age 60 to 75 years. The family material included 840 patients with colorectal cancer. The mean age at diagnosis was 45 years, and about 15 percent were diagnosed at age 60 or later. A total of 682 high-risk relatives are being followed. After the follow-up of 1 to 10 years in these families, only six cases of interval cancers were encountered.

Adolescent↗
PubMed1993

Perioperative blood contact and exposures: a comparison of incident reports and focused studies.

BACKGROUND: Occupational blood exposures among operating room personnel have been substantially underreported in incident reports. Recent research has indicated several common factors influencing exposure rates: surgical service (thoracic, neurosurgery, orthopedic), length of operation, and emergency status. METHODS: This report examines further data from a study of 8502 surgical cases in nine hospitals, in which a site coordinator and circulating nurses reported consecutive case information, including blood contacts that occurred during the procedures. For three of the participating hospitals, incident reports of blood exposures among operating room personnel that occurred during a 12-month period before the study were also tabulated. RESULTS: Incident reports underreported parenteral exposures (punctures, mucous membrane and nonintact skin contact with patient blood) by as much as a factor of 25. Individual hospital rates of occupational surgical blood exposure varied considerably. CONCLUSIONS: To ensure that resources to prevent occupational blood exposure are allocated appropriately, on the basis of actual risk, among all personnel, hospitals must actively monitor blood exposures in their operating rooms.

Blood-Borne Pathogens↗
PubMed1993

Blood contact and exposures among operating room personnel: a multicenter study.

Blood exposures are increasingly recognized as a risk for health care workers in the operating room. Trained circulating nurses supervised by site coordinators queried surgical team members about blood contact and collected data on 8502 surgical procedures from seven community and two university hospitals in 1992. Blood contact occurred during 864 cases (10.2% case-contact rate) in 1054 health care workers (12.4% person-contact rate). The parenteral exposure (punctures or cuts, mucous membranes, nonintact skin) rate was 2.2% and the cutaneous exposure (intact skin) rate was 10.2%. Blood contacts were twice as likely to be parenteral among surgeons as among other operating room personnel (odds ratio, 2.0; 95% confidence interval, 1.4 to 2.9). Of cutaneous exposures, 46.9% were from unknown sources or were surprise spatters. Logistic regression analyses indicated that risk factors associated with any blood contact (parenteral or cutaneous) were length of procedure (odds ratio, 1.51; 95% confidence interval, 1.46 to 1.56), emergency versus scheduled status (odds ratio, 1.44; 95% confidence interval, 1.21 to 1.66), selected surgical services, and the hospital. Logistic regression analyses of parenteral exposures, as compared with cases in which no contact occurred, indicated that risk factors were length (odds ratio, 1.39; 95% confidence interval, 1.31 to 1.47), thoracic surgery (odds ratio, 2.79; 95% confidence interval, 2.18 to 3.40), and university hospital versus community (odds ratio, 2.26; 95% confidence interval, 1.89 to 2.63). Parenteral exposures are clear risks to health care workers; however, it is also important to study all contact with blood in the operating room to appreciate potential risks and develop appropriate intervention strategies.

Blood-Borne Pathogens↗
PubMed1993

Endoscopic ultrasonography in the quantitative assessment of response to chemotherapy in patients with adenocarcinoma of the esophagus and esophagogastric junction.

We used endoscopic ultrasonography (EUS) to clinically stage eight patients with adenocarcinoma of the esophagus and to monitor their disease after subsequent courses of experimental preoperative chemotherapy. Stage of disease (TNM), tumor area, and tumor width were determined at each session. These results were then compared with barium esophagram and histopathology from resection specimens. EUS provided a consistent interpretation of the stage of disease and accurately predicted histopathologic findings. Measurement of tumor area and maximal width did not reliably correlate with the response to chemotherapy as assessed by barium esophagram. Although this technique seems promising, it cannot yet be recommended as a means of predicting response to chemotherapy.

Adenocarcinoma↗
PubMed1992

Agoraphobic avoidance and panic frequency as predictors of laboratory induced panic reactions.

This study examined the importance of agoraphobic avoidance and frequency of panic as predictors of psychological and physiological responses of panic sufferers to a laboratory based provocation procedure. Psychophysiologic comparisons were made between 22 panic disorder patients and 15 controls, at baseline and across three periods of carbon dioxide gas inhalations (1, 3, 5%; balance oxygen). Subjective measures of anxiety, frightening cognitions and body sensations were obtained across the phases. Physiological measures of minute ventilation, breathing rate, tidal volume, end tidal CO2 and heart rate were also obtained. Between group comparisons revealed significant differences between the groups on the subjective measures with no significant differences occurring on the physiological measures. Within group analyses revealed that pre-session questionnaire measures of agoraphobia avoidance and panic frequency predicted the degree of anxiety, frightening sensations and cognitions during baseline and 5% CO2 inhalation. The results indicated that both self-reported agoraphobic avoidance and panic frequency are strong clinical predictors of psychological reactions of panic sufferers during laboratory provocation.

Adult↗
PubMed1992

Calcium supplementation decreases rectal epithelial cell proliferation in subjects with sporadic adenoma.

The results of three small clinical trials examining the effect of calcium carbonate supplementation on the proliferation cytokinetics of the rectal epithelium in subjects with a current history of sporadic adenoma are reported. In six subjects, a daily administration of 1500 mg of calcium carbonate for 90 days failed to significantly suppress thymidine labeling in normal-appearing mucosa of the rectum. However, a daily dose of 2000 mg of calcium significantly (P = 0.008) altered mucosal proliferation in a second set of six subjects after a 30-day trial. Finally, a placebo-controlled trial of calcium (2000 mg) was conducted in which 20 subjects were randomized to groups receiving a 4-week intervention with calcium (or placebo), followed by the alternative treatment (placebo or calcium). The results of the study show a marked suppression of rectal proliferation during the calcium phase of the study but not during the placebo phase. This study adds to accumulating evidence showing that calcium supplementation regulates the proliferative behavior of colonic epithelium in the individual at high risk for colon cancer. Longer term trials of calcium supplementation will ascertain whether a continuing benefit from increasing dietary calcium translates into inhibition of adenoma recurrence.

Adenoma↗
PubMed1992

Linkage of a variant or attenuated form of adenomatous polyposis coli to the adenomatous polyposis coli (APC) locus.

Adenomatous polyps are an intermediate in the pathway to colon carcinoma. An inherited disorder, familial adenomatous polyposis coli (APC), is characterized by hundreds to thousands of adenomatous polyps. A previously reported family had colon cancer associated with a low average but highly heterogenous number of colonic polyps, this phenotype mapped to the APC locus on 5q. Four new families have been ascertained in which the phenotypic pattern was different from classical polyposis but similar to that of the "prototype" kindred reported earlier. By multilocus linkage analysis, the gene responsible for the disease phenotype was mapped, with a high level of confidence, to the APC locus in two of the four families with the attenuated or variant form of polyposis (AAPC); the results for the two remaining kindreds were inconclusive. A combined maximum LOD score of approximately 7.6 at a recombination fraction of 0 was obtained when the results were summed over the four pedigrees with markers closest to the APC locus. The establishment of genetic linkage in such families may point to the APC locus as having a more significant role in inherited predispositions to colorectal cancer than was previously thought.

Adenomatous Polyposis Coli↗
PubMed1991

Endoscopic laser recanalization is effective for prevention and treatment of obstruction in sigmoid and rectal cancer.

Patients with obstructing cancers are ineligible for preoperative chemotherapy and radiation unless they undergo surgical diversion. Endoscopic laser therapy (ELT) may provide an alternative to colostomy for these patients. We retrospectively reviewed all patients with distal sigmoid and rectal carcinomas who underwent ELT from January 1988 through April 1990. The majority of patients were referred for palliation of advanced disease. Thirty-seven patients underwent 123 ELT sessions (median, 2.5; range, one to 18). In 84% of patients, patency was maintained during a median follow-up of 31.5 weeks (range, one to 123). Morbidity and mortality were 2.5% (3/123) and 5% (1/37), respectively. Sixty-two percent had radiotherapy, chemotherapy, and/or surgery concurrent with ELT. Endoscopic laser therapy can safely and effectively reestablish and maintain luminal patency in patients with obstructing distal cancers. In addition, ELT can enable the administration of preoperative adjuvant radiotherapy and chemotherapy.

Adenocarcinoma↗
PubMed1991

Late BCNU lung: a light and ultrastructural study on the delayed effect of BCNU on the lung parenchyma.

We describe eight patients who developed interstitial pulmonary fibrosis following BCNU (carmustine) therapy for cerebral tumours. The fibrosis presented 12-17 (mean 14) years after exposure to the drug. A distinctive pattern of pulmonary fibrosis with involvement of the apices and subpleural areas was seen in one patient dying of the disease. Light microscopy showed interstitial elastosis and intra-alveolar fibrosis which was often focal with an associated mild lymphoplasmacytic infiltrate, intra-alveolar oedema, macrophages, and some neutrophils. Ultrastructural studies showed electron lucency of type I pneumocytes, with breaks in the cytoplasmic membranes leaving a bare basement membrane. Degenerative change was also seen in endothelial cell cytoplasm along with lipofuscin deposition. While BCNU pulmonary fibrosis has been described up to 2 years after treatment, this complication so late after therapy, though rare, has important implications for the follow-up of patients receiving this drug.

Astrocytoma↗
PubMed1991

The lentivirus regulatory proteins REV and REX are site specific RNA binding proteins.

These studies demonstrate that HIV-1 REV and HTLV-1 REX are site specific RNA binding proteins. In addition, the REV protein studies indicate a protein domain essential for biological function that is not involved in RRE binding. Lentiviruses are unique among retroviruses in providing gene products to switch expression from early to late genes. Rather than transcriptional control, this is accomplished by regulating RNA transport. A further understanding of these lentiviral genes may identify means of inhibiting viruses responsible for insidious human disease.

Amino Acid Sequence↗