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L Haley

Publications and source records attributed to L Haley.

At least 19 recordsLinked to original sources
PubMed2001

Comparative structure, proximal promoter elements, and chromosome location of the human eosinophil major basic protein genes.

Human eosinophil major basic protein (MBP) is strongly implicated as a mediator of disease, especially bronchial asthma. We recently isolated a highly divergent human homologue of MBP (MBPH). Given human MBP's importance in disease and the restricted expression of it and human MBPH, we isolated the 4.6-kb human MBPH gene (HGMW-approved symbol PRG3). Comparisons among the human MBP (PRG2), human MBPH, and murine MBP-1 (mMBP-1; Prg2) genes suggest that the human MBP and mMBP-1 genes are more closely related than either is to the human MBPH gene. Proximal promoters of these three genes show conservation of potential binding sites for IK2 and STAT and of a known GATA site. However, a known C/EBP site is altered in the human MBPH gene's proximal promoter. The human MBP and MBPH genes localized to chromosome 11 in the centromere to 11q12 region. Thus, the human MBP and MBPH genes have diverged considerably, probably following a gene duplication event. Furthermore, the identified conserved and distinct proximal promoter elements likely contribute to the eosinophil-restricted and relatively reduced transcription of the human MBPH gene.

Animals↗
PubMed2001

Diversity in emergency medicine--a model program.

Emergency medicine's (EM's) development as a specialty has spanned the last 25 years, with the first certifying examination administered by the American Board of Emergency Medicine in 1980. National census data project that the new millennium will bring a U.S. population that will be 40% minority. In the year 2000, the U.S. population had a projected minority population of 28%. The diversity of the patients we treat demonstrates the need for EM programs to diversify their faculty and residency staff. Strategies include expanding recruitment and supporting retention of underrepresented students, faculty, and trainees, addressing barriers that may exist for promotion of underrepresented women and minorities, mentoring underrepresented minority (URM) faculty in research and education, providing opportunities for URMs to advance in the field, and mentoring URMs at the junior high and high school levels in the sciences to expand the applicant pool in the field. The authors describe an academic EM program that is a model program for diversity within our specialty.

Academic Medical Centers↗
PubMed1997

Histopathology of in-stent restenosis in patients with peripheral artery disease.

BACKGROUND: Clinical studies have suggested that smooth muscle cell (SMC) hyperplasia is the most likely cause of in-stent restenosis. However, pathological data regarding this issue are limited. Specifically, direct evidence of proliferative activity in tissues excised from stenotic stents has not been previously reported. METHODS AND RESULTS: Tissue specimens were retrieved by directional atherectomy from 10 patients in whom in-stent restenosis complicated percutaneous revascularization of peripheral artery disease. Analysis of cellular composition was performed quantitatively after cell-specific immunostaining. For specimens preserved in methanol (7 of 10), cellular proliferation was evaluated by use of antibodies to proliferating cell nuclear antigen (PCNA), cyclin E, and cdk2. TUNEL staining for apoptosis was performed on 8 paraformaldehyde-preserved specimens. Each of the 10 specimens contained extensive foci of hypercellularity composed predominantly of SMCs (mean+/-SEM, 59.3+/-3.0%). Evidence of ongoing proliferative activity was documented in all 7 methanol-preserved specimens: 24.6+/-2.3% of SMCs were PCNA-positive, 24.8+/-3.1% were cyclin E-positive, and 22.5+/-2.2% were cdk2-positive. Apoptotic cells were detected in all 8 specimens that had been appropriately preserved to permit DNA nick-end labeling. Macrophages and leukocytes were identified in each of the 10 specimens but accounted for a proportionately smaller number of cells (14.5+/-1.9% and 9.5+/-1.4%, respectively). Organized thrombus was observed in 6 of the 10 specimens. CONCLUSIONS: These findings support the notion that in-stent restenosis results from SMC hyperplasia and suggest that adjunctive therapies designed to inhibit SMC proliferation may further enhance the utility of endovascular stents.

Aged↗
PubMed1997

Restenosis of endovascular stents from stent compression.

OBJECTIVES: We sought to determine the basis for restenosis within superficial femoral arteries (SFAs) and hemodialysis conduits treated with balloon-expandable stents. BACKGROUND: Use of stents within coronary and peripheral vessels continues to increase exponentially. The mechanism of restenosis within stents placed at various vascular sites is not well understood. In particular, the implications of deploying a balloon-expandable stent in a compressible site are not well understood. METHODS: After the serendipitous detection of stent deformation during intravascular ultrasound (IVUS) examination of a restenosed dialysis fistula, we evaluated a consecutive series of patients with stents placed in compressible vascular sites, including the SFA (six patients) and hemodialysis fistulae (five patients). Clinical, angiographic and IVUS examinations were performed to evaluate mechanisms of restenosis. RESULTS: Stent compression was identified as the principal cause of restenosis in all dialysis conduits and SFAs. Stent deformity was not reliably identified by angiography; however, IVUS identified compression of two forms: eccentric deformation, implicating two-point compressive force, and complete circumferential encroachment of stent struts around the catheter, suggesting multidirectional compressive force. Despite redilation, secondary restenosis resulting from recurrent compression recurred in most sites. CONCLUSIONS: Restenosis within balloon-expandable endovascular stents may occur as a result of stent compression, a phenomenon readily detected by IVUS, but often not by angiography. These findings have significant implications for the use of balloon-expandable stents within vascular sites subject to extrinsic compression, such as hemodialysis conduits, the adductor canal segment of the SFA and carotid arteries.

Aged↗
PubMed1997

A possible role for L-selectin in the release of polymorphonuclear leukocytes from bone marrow.

Previous studies from our laboratory have shown that the expression of L-selectin on polymorphonuclear leukocytes (PMN) is higher in the bone marrow than in peripheral blood. The present study was designed to determine the location of this L-selectin loss as the PMN pass from the hematopoietic tissue into venous sinusoids of the bone marrow. Bone marrow and peripheral blood samples were collected at the beginning, during, and just after five normothermic cardiopulmonary bypass procedures in which there was active marrow release and compared with five hypothermic procedures in which marrow release was suppressed by lowering body temperature to 27 degrees C. L-selectin expression was measured on PMN in the hematopoietic tissue and venous sinusoids in the bone marrow using quantitative histology and immunocytochemistry. At baseline there was more L-selectin on PMN in the bone marrow hematopoietic tissue than in the sinusoids (24.7 +/- 3.5 vs. 10.3 +/- 2.5%, P < 0.004). Bone marrow release during normothermic cardiopulmonary bypass procedure was associated with a rise in peripheral blood band cells (0.18 +/- 0.7 vs. 2.98 +/- 0.56 x 10(9)/l, P < 0.01) and a further reduction of L-selectin expression on PMN in the sinusoids (P < 0.03). Hypothermia (27 degrees C) prevented both the rise in peripheral blood band cells and the reduction in L-selectin on PMN in the sinusoids. In vitro studies showed that lowering the temperature had a similar effect on shedding of L-selectin from PMN. We conclude that PMN shed L-selectin as they move from the hematopoietic compartment into the venous sinusoids of the bone marrow and postulate that this could control the release of PMN from the marrow.

Adult↗
PubMed1996

Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb.

BACKGROUND: Preclinical findings suggest that intra-arterial gene transfer of a plasmid which encodes for vascular endothelial growth factor (VEGF) can improve blood supply to the ischaemic limb. We have used the method in a patient. METHODS: Our patient was the eighth in a dose-ranging series. She was aged 71 with an ischaemic right leg. We administered 2,000 micrograms human plasmid phVEGF165 that was applied to the hydrogel polymer coating of an angioplasty balloon. By inflating the balloon, plasmid DNA was transferred to the distal popliteal artery. FINDINGS: Digital subtraction angiography 4 weeks after gene therapy showed an increase in collateral vessels at the knee, mid-tibial, and ankle levels, which persisted at a 12-week view. Intra-arterial doppler-flow studies showed increased resting and maximum flows (by 82% and 72%, respectively). Three spider angiomas developed on the right foot/ankle about a week after gene transfer; one lesion was excised and revealed proliferative endothelium, the other two regressed. The patient developed oedema in her right leg, which was treated successfully. INTERPRETATION: Administration of endothelial cell mitogens promotes angiogenesis in patients with limb ischaemia.

Aged↗
PubMed1996

Species distribution in human immunodeficiency virus-related mycobacterial infections: implications for selection of initial treatment.

Management of mycobacterial infection is species specific; however, treatment is prompted by positive smears or cultures, often several weeks before species identification. The objective of this study was to determine the species distribution of mycobacterial isolates from various body sites in patients infected with human immunodeficiency virus (HIV). All mycobacterial isolates recovered at St. Paul's Hospital (Vancouver, British Columbia, Canada) from April 1989 to March 1993 were reviewed. Among 357 HIV-positive patients with mycobacterial infections, 64% (96) of the sputum isolates were Mycobacterium avium complex (MAC), 18% were Mycobacterium tuberculosis, and 17% were Mycobacterium kansasii. Lymph node involvement (25 patients) was due to either MAC (72%) or M. tuberculosis (24%). Two hundred ninety-eight episodes of mycobacteremia were due to MAC (98%), M. tuberculosis (1%), and M. kansasii (1%). Similarly, cultures of 84 bone marrow biopsy specimens (99%), 19 intestinal biopsy specimens (100%), and 30 stool specimens (97%) yielded predominantly MAC. These results have implications for initial therapy, particularly in areas where rapid methods for species identification are not readily available. Because of considerable geographic variation, development of guidelines for selection of initial therapy depends on regional determination of species distribution in HIV-related mycobacterial infections.

AIDS-Related Opportunistic Infections↗
PubMed1996

Variation in plasma RNA levels, CD4 cell counts, and p24 antigen levels in clinically stable men with human immunodeficiency virus infection.

Short-term variability in CD4 cell counts, plasma RNA levels, and p24 antigenemia was measured in clinically stable men with human immunodeficiency virus infection. Blood samples were obtained three times in each of 2 weeks 4 weeks apart. Differences between duplicate assays were considered to be due to technical factors; variation among visits was attributed to physiologic factors. Median enrollment values of CD4 cell counts, plasma RNA levels, and immune complex-dissociated (ICD) p24 antigenemia were 400 cells/mm3, 3.4 log10 copies/mL, and 38 pg/mL, respectively. Median absolute differences between duplicate CD4 cell counts, plasma RNA levels, and ICD p24 antigen were 16 cells/mm3, 0.21 log10 copies/mL, and 9.3 pg/mL. Median intraindividual ranges were 119 cells/mm3, 0.83 log10 copies/mL, and 18 pg/mL. Above 500 copies/mL, plasma RNA levels have a variability of 0.5 log10; the test is unreliable below this level.

CD4 Lymphocyte Count↗
PubMed1995

L-selectin expression increases on peripheral blood polymorphonuclear leukocytes during active marrow release.

The cell adhesion molecule L-selectin is highly expressed on mature bone marrow polymorphonuclear leukocytes (PMN), and the release of these cells from the bone marrow could produce a population of circulating PMN expressing high levels of L-selectin. Because L-selectin initiates the interaction of PMN with activated endothelium, these cells could be important in the pathogenesis of multiorgan failure following sepsis and septic shock. The present study was designed to test the hypothesis that the release of PMN from the bone marrow increases the expression of L-selectin on circulating PMN. Peripheral blood and bone marrow samples were obtained immediately after sternotomy (BM1) and during (BM2) and just before closing the sternum (BM3) in five normothermic and five hypothermic cardiopulmonary bypass (CPB) procedures. L-selectin was measured using both immunocytochemistry and flow cytometry. The results showed that L-selectin expression on bone marrow PMN was greater than on peripheral blood PMN (p < 0.01) in all patients at baseline. Bone marrow release of PMN during normothermic CPB was associated with a rise in peripheral blood band cells (0.18 +/- 0.7 versus 0.56 x 10(9)/L) (p < 0.01) and an increase in the percentage of PMN expressing high levels of L-selectin (9 +/- 3.3 to 36 +/- 6.6%, p < 0.03) and the L-selectin mean fluorescence intensity (MFI) on PMN (p < 0.05). The expression of L-selectin on band cells was higher than on segmented PMN in the circulation (p < 0.01). Hypothermia (27 degrees C) prevented the release of band cells into the circulation and the increased expression of L-selectin on the PMN.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Quantification of the variation due to laboratory and physiologic sources in CD4 lymphocyte counts of clinically stable HIV-infected individuals.

We have conducted a study to quantify the amount of variation in the CD4 lymphocyte counts of HIV-infected individuals due to laboratory and physiological factors. Thirty HIV-infected male volunteers had blood drawn on six occasions: three times in each of 2 weeks, 4 weeks apart. Two tubes of blood were drawn at each visit, and duplicate measurements were obtained from one of the tubes of blood. Differences between duplicate measurements from a single tube of blood and between CD4 counts obtained from two tubes of blood drawn on the same day were attributed to laboratory factors. Differences between CD4 counts obtained on different days were attributed to a combination of laboratory factors and physiologic factors, which included the effects of exercise, tobacco, and the consumption of alcohol and caffeine. The mean absolute CD4 count at the first visit was 450 (range 86-1,081). The short-term coefficient of variation of CD4 count was 13.7 (95% CI: 12.9, 14.6). Physiologic and laboratory factors accounted for 85% and 15% of the variation in CD4 counts, respectively. Variation in the absolute white blood cell count, lymphocyte percentage, and CD4 percentage accounted fo 52%, 29%, and 19% of the physiologic variation in CD4 counts, respectively. Our results confirm a high degree of short-term variability of CD4 counts among HIV-infected individuals, which can be largely attributed to physiological factors. This variability can be minimized more effectively by repeating CD4 counts over time than by repeating measurements at a single visit.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Variability in leukocyte subset measurements among five laboratories in Vancouver.

Cell counts and percentages of CD4 are widely used in the prognostic and clinical management of HIV-infected patients, and as surrogate outcomes in clinical trials involving HIV-infected individuals. Considerable variability in CD4 counts has been documented due to physiologic and methodologic factors. While studies of variability of CD4 counts among American and French laboratories have been reported in the literature, no published data are available for Canadian laboratories. This paper describes the results of a study to determine the variability of leukocyte subsets among 5 laboratories in Vancouver, British Columbia. Samples were collected in a prospective fashion from 52 HIV-negative patients from July 1991 to November 1993. Coefficients of variation (CV) were calculated for leukocyte subset percentages and absolute cell counts among laboratories. Our results demonstrate that the variability in leukocyte subsets among 5 Vancouver laboratories was lower than or comparable with published findings. The variability remained stable over the time period of the study, although 4 of the 5 laboratories participated in quality assurance programs. This suggests a plateau in the impact of this program. Since the variability among laboratories is less than the variability attributable to physiologic factors, further research efforts to reduce this variability should focus on physiologic sources.

British Columbia↗
PubMed1992

The effect of cigarette smoking on lymphocyte subsets and progression to AIDS in a cohort of homosexual men.

We investigated the effect of cigarette smoking on the percentage of CD4 and CD8 cells (CD4%, CD8%) within a prospective study of homosexual men in Vancouver, Canada and compared progression rates to AIDS among seroincident smokers and non-smokers. Serial measurements of CD4% and CD8% obtained from four annual visits were available for 299 men and were compared with respect to smoking status and serologic group. CD4% was significantly elevated (p less than 0.025) and CD8% was significantly lower (p less than 0.002) in seronegative smokers compared to non-smokers. However, no effect of smoking was observed in the seropositive group for either of these variables. In a prospective analysis of 122 seroincident subjects, we failed to find a significant association between smoking and progression to AIDS (p = 0.829) or Pneumocystis carinii pneumonia (p = 0.894). At 72 months, cumulative AIDS progression was 29.1% in seroincident smokers compared to 25.2% in seroincident non-smokers. These data suggest that in the absence of HIV, smoking is associated with higher CD4% and lower CD8% but these effects are not present in seropositive subjects with longer durations of infection. Cigarette smoking does not appear to be associated with an altered rate of progression to AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1991

The second amino acid of alfalfa mosaic virus coat protein is critical for coat protein-mediated protection.

Transgenic plants expressing the coat protein (CP) of alfalfa mosaic virus (AIMV) are resistant to infection by AIMV. A mutation was introduced into the second amino acid of the cDNA for the CP of AIMV. Three different transgenic tobacco lines expressing the mutant CP and two different transgenic tobacco lines expressing the wild-type CP at similar levels were challenged with AIMV virions and viral RNA. Whereas the lines expressing the wild-type CP were highly resistant to infection by AIMV virions and viral RNA, the lines expressing the mutant CP were susceptible to infection by both. The binding affinity of the mutant and the wild-type CPs for the 3' terminal protein binding site on AIMV RNAs was similar, as determined by electrophoretic mobility shift assay. A mixture of AIMV genomic RNAs 1-3 was infectious on the plants expressing the mutant CP but not on vector control plants or plants expressing the wild-type CP, indicating that the mutant CP can activate the AIMV genomic RNAs for infection. These results demonstrate that the second amino acid of the AIMV CP is critical for protection from AIMV but not for the initial interaction between the AIMV RNA and CP, suggesting that this initial interaction does not play a major role in CP-mediated protection.

Journal Article↗
PubMed1991

Red blood cell alloimmunization in transfused patients on AZT.

Significant numbers of patients receiving azidothymidine (AZT) develop anaemia requiring an adjustment of AZT dosage. Fear of red blood cell (RBC) alloimmunization may act as a deterrent to exposing a patient to long-term transfusion therapy which is the alternative to AZT dosage reduction or discontinuation. This retrospective study was done to assess the incidence of RBC alloimmunization in transfused patients on AZT. Records of 72 patients receiving long-term AZT were analysed to assess the incidence of alloimmunization. Other study parameters included duration of transfusion therapy, total number of pRBC units transfused/patient, alloantibody specificity, rates of autoantibody detection and their specificity. For comparison, a parallel analysis was carried out on 188 male patients transfused during the same period of time for chronic renal failure (CRF). Only one of 72 AZT patients (1.4%) developed an alloantibody compared with seven of the 118 CRF patients (5.9%) (P = NS). The incidence of autoantibodies and positive direct antiglobulin testing in the AZT and CRF populations was found to be similar (9.7% v. 7.6% respectively; P = NS). The two populations were similar with respect to mean number of pRBC units transfused (AZT: 10.5 v. CRF: 11.5 units; P = NS); however, there was a significant difference in the mean duration of transfusion therapy (AZT: 4.5 months v. CRF 19.4 months; P less than 0.001). We conclude there is an insignificant incidence of alloimmunization in the multiply-transfused AZT population. Furthermore, in this study the incidence of RBC autoantibodies in AZT patients appears to be low and no different from that of patients with chronic renal failure.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Catecholamine levels in pregnant physicians and nurses: a pilot study of stress and pregnancy.

As a pilot study of occupational stress and pregnancy, we measured urinary catecholamine excretion in ten pregnant physicians and three intensive care nurses between 26-37 weeks' gestation, once during a work day and again during a non-work day. Urinary catecholamines were increased by 58% (P less than .03) during work periods compared with non-work periods. Catecholamine levels were also increased by 64% (P less than .025) over those of a working non-physician control group of similar gestational age. Urinary catecholamine levels are a direct reflection of plasma catecholamine levels. Catecholamine levels are known to increase with physical stress, such as standing, and with mental stress, such as difficult problem-solving. Catecholamines are also known to decrease uterine blood flow. Measurement of catecholamines may be a helpful marker in investigating the relationship between occupation and pregnancy outcome.

Catecholamines↗
PubMed1990

Engineering resistance to mixed virus infection in a commercial potato cultivar: resistance to potato virus X and potato virus Y in transgenic Russet Burbank.

Potato virus X (PVX) and potato virus Y (PVY) infection in potato may result in the loss of certification of seed potatoes and affect quality and yield of potatoes in commercial production. We transformed a major commercial cultivar of potato, Russet Burbank, with the coat protein genes of PVX and PVY. Transgenic plants that expressed both CP genes were resistant to infection by PVX and PVY by mechanical inoculation. One line was also resistant when PVY was inoculated with viruliferous green peach aphids. These experiments demonstrate that CP protection is effective against mixed infection by two different viruses and against mechanical and aphid transmission of PVY.

Amino Acid Sequence↗
PubMed1989

Fine-needle aspiration cytology in lymphomas and related disorders.

Fine-needle aspiration (FNA) is a useful technique in the care of patients with lymphomas and related diseases. It is most effective when the aspiration and interpretation are performed by the same individual and when a Romanowsky stain is the primary stain. Special studies that are applicable to lymph nodes biopsies can also be utilized in specimens obtained by FNA. In the previously undiagnosed patient, where a presumptive diagnosis of lymphoma is made by FNA, a subsequent open biopsy will usually be necessary. At that time, all the measures necessary for the precise classification of the lymphoma can be undertaken under ideal conditions. If a lesion appears reactive by FNA, then a period of clinical observation is required. In the patient with a previously diagnosed lymphoma, FNA is chiefly useful to exclude other coincidental disease and to confirm or exclude transformation of low-grade lymphoma to a more aggressive phase.

Biopsy, Needle↗