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Biomedical subjects

W Lee

Publications and source records attributed to W Lee.

At least 19 recordsLinked to original sources
PubMed1992

Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 2. Synthesis and biological activity of 8-(benzenesulfonamido)-7-(3-pyridinyl)octaonic acid and related compounds.

A series of arylsulfonamide alkanoic acids substituted with a 3-pyridinyl group along the aliphatic chain were synthesized and tested in vitro for their ability to antagonize thromboxane A2 (TxA2) receptors and inhibit thromboxane synthase. These compounds were found to potently inhibit the U 46619-induced aggregation of human platelets and to also inhibit TxA2 biosynthesis in a human microsomal platelet preparation. However, some members of the series, notably compound 21, were found to display agonist activity on the rabbit aorta TxA2 receptor. This unwanted agonist activity appeared to be related to the presence of a substituent beta to the arylsulfonamido group.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 3. Pyridinylalkyl-substituted 8-[(arylsulfonyl)amino]octanoic acids.

A series of 8-[(arylsulfonyl)amino]octanoic acids substituted with a pyridinylalkyl group along the chain were synthesized and tested in vitro for their ability to both antagonize the binding of thromboxane A2 to its receptors and to inhibit the thromboxane synthase enzyme. This series of compounds were found to inhibit the U 46619-induced aggregation of human platelets and the U 46619-induced contraction of dog saphenous vein. The compounds also inhibited TxA2 biosynthesis in a human microsomal platelet preparation. The relative position of the pyridinylalkyl and arylsulfonamide groups had significant effects on the thromboxane receptor antagonist (TxRA) activity and thromboxane synthase inhibitor (TxSI) activity. Compounds with the pyridine ring at the 7- or 8-position of the octanoic acid side chain were weakly active as TxSI but behaved as potent TxRA at the platelet receptor for TxA2. However, these compounds were agonists at the vascular receptor. Substitution of the pyridinylalkyl group at the 2- or 3-position resulted in compounds with potent TxSI activity and weak TxRA activity. The activity profile of the compounds with the pyridinylalkyl substitution at the 4-, 5-, or 6-position was very desirable. Compound 22 with a pyridinylpropyl substituent at the 4-position was found to display extremely potent TxRA and TxSI properties.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 4. 8-[[(4-Chlorophenyl)sulfonyl]amino]-4-(3-(3-pyridinyl) propyl)octanoic acid and analogs.

The title compound (10a) and its analogs were synthesized and found to possess two activities, the inhibition of the biosynthesis of thromboxane A2 and antagonism of its receptors. The in vitro and in vivo profile of these compounds as thromboxane receptor antagonists (TxRAs) and thromboxane synthase inhibitors (TxSIs) is described. 10a and its analogs displayed very potent TxRA activity in human washed platelets (IC50 approximately 10(-7)-10(-9) M) and dog saphenous vein (pA2 approximately 9) and also potent TxSI activity (IC50 approximately 10(-9) M). The good bioavailability and the long duration of action of some of these compounds was demonstrated using ex vivo measurement of the TxRA activity upon oral administration to guinea pigs. Compounds 10a, 20, and 33 potently inhibited arachidonic acid induced bronchoconstriction in guinea pigs.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Use of aminotransferase, hepatitis C antibody, and hepatitis C polymerase chain reaction RNA assays to establish the diagnosis of hepatitis C virus infection in a diagnostic virology laboratory.

Clinical and therapeutic decisions for hepatitis C virus (HCV) infection depend on factors that include documentation of past infection as well as identification of those who might benefit from antiviral chemotherapy with systemic interferon. To evaluate the ability of a diagnostic laboratory to accurately identify such patients, we compared results obtained with serum transaminase assays, two HCV antibody assays (enzyme immunoassay [EIA] and immunoblot), and a polymerase chain reaction (PCR)-based assay for HCV RNA using a group of consecutively submitted samples within our university-based diagnostic virology laboratory and sera from a population of random blood donors. One hundred percent of specimens with R values of greater than 3.0 in the HCV EIA were positive in the confirmatory immunoblot. However, 25% of specimens with EIA R values of between 1.0 and 3.0 were not confirmed by either recombinant immunoblot assay (RIBA) or RNA PCR assay (false-positive specimens). A significant correlation (P less than 0.01) between increasing reactivity in the RIBA and positivity in the RNA PCR assay was found. The incidence of HCV viremia, as determined by the RNA PCR assay, was 73% for confirmed seropositive specimens, 33% for seropositive specimens with indeterminate RIBA results, 12% for seronegative specimens obtained from infected patients, and 2.0% for seronegative specimens obtained from uninfected blood donors. In contrast, serum transaminase testing did not correlate with the RNA PCR assay for HCV. Use of the EIA and immunoblot assay followed by RNA PCR testing will identify most patients who are viremic with HCV.

Alanine Transaminase↗
PubMed1992

Maternal respiration and blood gases during aerobic exercise performed at moderate altitude.

We studied whether maternal acid-base status during aerobic exercise performed at moderate altitude is affected by pregnancy. Seven primiparus women were tested at 37 wk gestation and 12 wk postpartum. Subjects were studied at rest, and during two cycle (50 W, 75 W) and two treadmill (67 m.min-1; 2.5% grade, 67 m.min-1; 12% grade) protocols. Exercise bouts lasted 6 min with a 10-min rest between sessions. Minute (VE) and alveolar (VA) ventilation, tidal volume (VT), and ventilatory equivalent for carbon dioxide (VE/VCO2) were significantly (P less than 0.01) greater when exercise was performed during pregnancy. Physiological dead space (VD) was not affected by pregnancy status and did not differ between rest and exercise. Decreases (P less than 0.01) in arterial pH during exercise averaged 0.04 units in both pregnancy and postpartum. Despite similar change in maternal pH, carbon dioxide tension (PaCO2) remained unchanged during exercise at 37 wk gestation but decreased at 12 wk postpartum. Decreases in arterial bicarbonate [HCO3-] associated with exercise were smaller during pregnancy. Our findings indicate that pregnancy did not compromise maternal acid-base status during aerobic exercise.

Acid-Base Equilibrium↗
PubMed1992

Induction of phenotypically altered mammary epithelial cells by neutrons and gamma rays.

These studies have examined alterations in the in vivo growth properties of mammary epithelial cells isolated at 1, 4, and 16 weeks after in vivo irradiation with -137Cs gamma rays or fission-spectrum neutrons. Altered in vitro growth potential was characterized by the proliferation of epithelial foci (EF) from irradiated animals under conditions in which mammary cells from nonexposed animals senesced. These EF were further characterized based on their ability to be subcultured. Both gamma and neutron irradiation resulted in the appearance of cells capable of forming EF. Further, with increased time in situ between irradiation and cell isolation, the frequency of EF which were capable of being subcultured indefinitely (EFs) increased. Reducing the gamma-ray dose rate resulted in fewer EFs while reducing the neutron dose rate resulted in increased frequencies of EFs. These data confirm earlier observations following gamma irradiation and show these cellular changes are also observed following neutron irradiation. In addition, these data indicate that changes in dose rate primarily influence the emergence of immortalized cell populations.

Animals↗
PubMed1991

Quadruple immunosuppression in renal allografts--the Auckland experience.

Recipients of live related and first cadaveric renal allografts were retrospectively reviewed before and after institution of a standardized regimen incorporating greater immunosuppression, (by the addition of antilymphocyte preparations). The two review groups were comparable with 11 live related and 27 first cadaver grafts in each. Despite a small advantage in terms of graft survival and diminished rejection, this was at the expense of septic morbidity. The implications of this are discussed.

Antilymphocyte Serum↗
PubMed1991

The application of epitope mapping in the development of a new serological test for systemic candidosis.

A new serological test for systemic candidosis was developed by raising a rabbit antiserum probe against a specific epitope on Candida albicans, hsp 90. A major fragment at the carboxy terminal end of this immunodominant candidal antigen was epitope mapped by Geysen's method. An epitope, recognised by all infected patients with antibody to the 47 kDa antigen, was synthesized and conjugated to keyhole limpet haemocyanin. A rabbit was successfully immunized against this synthesized peptide epitope and this antiserum was compared, in a dot-immunobinding assay, with unfractionated hyperimmune rabbit antiserum to C. albicans and an affinity-purified rabbit antiserum to the 47 kDa antigen. The epitope-specific antibody probe was more sensitive than the hyperimmune candidal antiserum but less sensitive than the affinity-purified antibody against the 47 kDa antigen, which recognised multiple epitopes. This probe is technically easy to prepare in large amounts and gives no false positives.

Amino Acid Sequence↗
PubMed1991

Regulatory elements mediating transcription of the human Ha-ras gene.

In order to identify transcriptional regulatory elements controlling the expression of the human Ha-ras gene and to quantitatively assess the role of each element, we made mutations of the transcriptional regulatory region, including 5' and internal deletions, linker scanning and replacement mutations, and combinations of these mutations all fused to the bacterial chloramphenicol acetyltransferase gene. The promoter activity of each of these mutants was determined by measuring the transient expression of chloramphenicol acetyltransferase activity after transfection into human epithelial HeLa cells. We found that the most important regulatory region consists of two closely linked but functionally independent elements, the non-consensus GC-II element, CGGGCGGGC, centered at position -153 from the major transcription start site cluster and a new element, CCGGAA, centered at position -161 directly upstream from GC-II. In addition, there are two functional regulatory elements which make minor contributions to the full promoter activity; a double CCAAT NF-I binding site at position -88 and an unidentified upstream element between positions -199 and -252. Aside from GC-II, the GC boxes, of which there are a total of six between positions -185 and +85, make little or no contribution to Ha-ras promoter activity when individual mutations are tested in growing HeLa cells. The three potential AP2 sites and a weak single NF-I binding site make no contribution. The basal promoter region extending to position -75 from the major start site cluster has no independent activity in this TATA-less gene.

Base Sequence↗
PubMed1991

Identification and comparison of CD34-positive cells and their subpopulations from normal peripheral blood and bone marrow using multicolor flow cytometry.

Four-color flow cytometry was used with a cocktail of antibodies to identify and isolate CD34+ hematopoietic progenitors from normal human peripheral blood (PB) and bone marrow (BM). Mature cells that did not contain colony forming cells were resolved from immature cells using antibodies for T lymphocytes (CD3), B lymphocytes (CD20), monocytes (CD14), and granulocytes (CD11b). Immature cells were subdivided based on the expression of antigens found on hematopoietic progenitors (CD34, HLA-DR, CD33, CD19, CD45, CD71, CD10, and CD7). CD34+ cells were present in the circulation in about one-tenth the concentration of BM (0.2% v 1.8%) and had a different spectrum of antigen expression. A higher proportion of PB-CD34+ cells expressed the CD33 myeloid antigen (84% v 43%) and expressed higher levels of the pan leukocyte antigen CD45 than BM-CD34+ cells. Only a small fraction of PB-CD34+ cells expressed CD71 (transferrin receptors) (17%) while 94% of BM-CD34+ expressed CD71+. The proportion of PB-CD34+ cells expressing the B-cell antigens CD19 (10%) and CD10 (3%) was not significantly different from BM-CD34+ cells (14% and 17%, respectively). Few CD34+ cells in BM (2.7%) or PB (7%) expressed the T-cell antigen CD7. CD34+ cells were found to be predominantly HLA-DR+, with a wide range of intensity. These studies show that CD34+ cells and their subsets can be identified in normal PB and that the relative frequency of these cells and their subpopulations differs in PB versus BM.

Adult↗
PubMed1991

Breast cancer diagnosis by screening mammography: early results of the Central Sydney Area Health Service Breast X-ray Programme.

The Central Sydney Area Health Service (CSAHS) Breast X-ray Programme is a pilot mammography screening project for breast cancer detection funded by the NSW Government. Screening by two-view mammography is carried out in a mobile van and is offered free to women aged over 45 years living in the CSAHS region, the inner western suburbs of Sydney. In the first 18 months of operation from March 1988, 7193 women were screened: 99 women underwent excision biopsy and 53 cancers were diagnosed. This is an overall detection rate of seven cancers per thousand women screened. Sixty per cent of the cancers were impalpable to the examining surgeon; 19% of all cancers were shown to have axillary node metastasis at the time of diagnosis. These results compare well with those of the major European screening studies.

Aged↗
PubMed1991

Gel injection adjustable keratoplasty.

Gel injection adjustable keratoplasty (GIAK) is a new refractive surgical procedure designed for the correction of myopia by injection of a gel substance into the peripheral corneal stroma. This paper describes the GIAK technique and reports the results obtained in 21 fresh cadaveric eyes using the procedure. After a deep interlamellar canal has been dissected with a helicoid spatula surrounding the visual axis, the gel is injected under keratometric control. In the 1st group of 14 eyes, the degree of correction varied from 2.2 to 12.8 D; there was a direct relationship between the amount of gel injected and the keratometric change. In the 2nd group of 7 eyes, the adjustability of the procedure was demonstrated. Through partial extraction of the gel and subsequent modification of the corneal curvature, the previously induced keratometric changes could be reversed or altered to a specific extent. Following the initial injection of gel to a targeted flattest meridian power of 35 D, an average value of 35.8 +/- 0.5 D was achieved in these eyes. We subsequently attempted to increase the flattest meridian to 40 D by partial removal of the gel and achieved a mean value of 40.2 +/- 0.4 D. Average presurgical astigmatism of 1.497 +/- 0.737 D was reduced to a postsurgical reading of 0.941 +/- 0.590 D (P = 0.005, Student's paired t-test), indicating an autocorrection by autodistribution of the gel inside the canaliculus (Laplace's law). GIAK is a simple, inexpensive procedure designed for the correction of myopia that has the added advantage of reducing preexisting astigmatism without encroaching on the visual axis.

Astigmatism↗
PubMed1991

CGS 22745: a selective orally active inhibitor of 5-lipoxygenase.

CGS 22745, and aralkyl hydroxamic acid, inhibited 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriene B4 (LTB4) synthesis in guinea pig leukocytes (IC50 = 0.6 microM). The compound did not appreciably affect cyclooxygenase (ram seminal vesicles), 12-lipoxygenase and thromboxane synthase (human platelets) or 15-lipoxygenase (human neutrophils). CGS 22745 inhibited A23187-induced formation of LTB4 in blood (IC50's of 4.3, 0.56 and 3.2 microM for human, dog and rat, respectively). At 1 mg/kg i.v. in dogs, it caused 96% inhibition of A23187-stimulated LTB4 formation ex vivo after 5 min. Its effective biological half-life was greater than 160 min. In dogs at 3 and 10 mg/kg p.o., CGS 22745 inhibited ex vivo A23187-stimulated LTB4 formation at 3 hr by 48% and 97%, respectively. The inhibition persisted up to 6 hr (26% at 3 mg/kg; 49% at 10 mg/kg). CGS 22745 (3, 10 and 30 mg/kg p.o.) inhibited exudate formation, mononuclear cells and PMN accumulation in a dose-dependent manner during the late phase (48 and 72 hr) of carrageenan-induced pleurisy in the rat.

Administration, Oral↗
PubMed1991

Pulmonary-to-aorta diameter ratio in the normal and abnormal fetal heart.

In an attempt to establish the normal ratio of pulmonary artery to aorta diameters at varying gestational ages, the pulmonary artery and aorta diameters of 316 normally grown fetuses between 14 and 39 weeks' gestational age were measured. The ratios for each fetus were derived, and regression analysis was used to evaluate the relationship between gestational age and each diameter. We conclude that the diameters of the pulmonary artery and aorta are closely related to fetal age but that the ratio is independent of age (mean, 1.09; SD, 0.17). The diameters of the pulmonary artery and aorta in 21 fetuses with proved congenital heart disease were then compared with those of this normal population. The pulmonary artery/aorta ratio was abnormal in 13 of 21 fetuses with congenital heart disease. Actual measurements of the great vessels can be difficult and may be misleading, but a quick comparison of relative size by inspection is feasible.

Aorta↗
PubMed1991

Transverse cerebellar diameter: a useful predictor of gestational age for fetuses with asymmetric growth retardation.

There have been conflicting reports regarding the ability of cerebellar diameter to satisfactorily predict the gestational age of growth-retarded fetuses. Gestational age prediction intervals were derived from 270 normal fetuses between 14 and 40 weeks' gestation for biparietal diameter, head circumference, abdominal circumference, femur length, and transverse cerebellar diameter. We evaluated the ability of these parameters to predict gestational age for 19 small-for-gestational-age fetuses. The cerebellar diameter regression model led to the smallest differences between observed and predicted gestational age for all growth-retarded fetuses. Transverse cerebellar diameter satisfactorily predicted gestational age for all six fetuses with asymmetric intrauterine growth retardation and was associated with the least amount of underestimation bias when compared with other ultrasonographic parameters. However, transverse cerebellar diameter appeared to be no better than biparietal diameter, head circumference, or femur length for accurately predicting gestational age of fetuses with symmetric intrauterine growth retardation (n = 13) despite the finding that cerebellar growth was also relatively spared under these circumstances. We conclude that transverse cerebellar diameter can be used to reliably approximate gestational age in fetuses with asymmetric intrauterine growth retardation. However, caution is warranted when using it to predict the gestational age of fetuses affected by symmetric intrauterine growth retardation.

Anthropometry↗
PubMed1991

Hospital outbreaks with yeasts.

Five previous outbreaks of disseminated candidosis due to Candida albicans are reviewed and a new outbreak on a neonatal unit in Belfast presented. This involved four disseminated cases. The control and definition of outbreaks by morpho-, immunoblot- and DNA-typing is discussed. An outbreak of Torulopsis glabrata infection involving 23 patients is described. This was defined by DNA fingerprinting with the enzyme Xba. There were five deaths attributable either completely or in part to the yeast infection.

Cross Infection↗