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Biomedical subjects

W Lee

Publications and source records attributed to W Lee.

At least 289 records · Page 16Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Position change and central hemodynamic profile during normal third-trimester pregnancy and post partum.

Central hemodynamic response to position change was assessed in 10 normotensive primiparous patients between 36 and 38 weeks' gestation. Studies were repeated between 11 and 13 weeks post partum. Compared with the left lateral position, we observed a mean 9% fall in cardiac output in the supine position and an 18% fall when patients were standing. When standing, these patients had a 30% increase in pulse and a 21% fall in left ventricular stroke work index. The orthostatic response after pregnancy was much more labile than that during the third trimester. These findings have important descriptive implications for the understanding of the human response to orthostasis during pregnancy, as well as clinical implications for patients at risk of uteroplacental insufficiency and for working women during pregnancy.

Adult↗

Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 1. (+/-)-(3-pyridinylbicycloheptyl)alkanoic acids.

The design, synthesis, and in vitro pharmacology of a new class of compounds exerting both thromboxane receptor antagonist and thromboxane synthase inhibitory activities is described. [(3-Pyridinyl)bicycloheptyl] alkanoic acid 9 and its analogues, designed with the help of molecular modeling, were synthesized and found to be inhibitors of thromboxane A2 (TxA2) biosynthesis in a human platelet microsomal preparation. The compounds were also found to antagonize both platelet and vascular TxA2 receptors. The compounds inhibited the U 46619 induced aggregation of human washed platelets and platelet-rich plasma and the U 46619 induced contraction of the dog saphenous vein.

Blood Platelets↗

Physiologic observations of pregnant women undergoing prophylactic erythrocytapheresis for sickle cell disease.

Five women in the second or early third trimester of pregnancy underwent prophylactic partial red cell exchange by automated erythrocytapheresis for sickle cell disease. The purpose of this pilot study was to characterize the hematologic, hemodynamic, and metabolic changes associated with this procedure. Pretransfusion hematocrit increased 49 percent by 3 to 5 days after the transfusion. Paired observations indicate a 14-percent drop in maternal oxygen consumption. There was a slight tendency for reduced posttransfusion cardiac output that resulted primarily from changes in maternal heart rate and not from changes in stroke volume. Left ventricular contractility also tended to decrease after transfusion. Neither fetal bradycardia nor alteration in the umbilical circulation by Doppler ultrasound was observed during the transfusion procedures. Despite substantial hematologic alterations, this procedure is associated with small or negligible changes in maternal hemodynamic and metabolic function for minimally symptomatic pregnant patients with sickle cell disease.

Anemia, Sickle Cell↗

Identification of a gene encoding an HPr-like protein in Aspergillus fumigatus.

The gene encoding a histidine-containing protein (HPr)-like protein was identified in a cDNA library of Aspergillus fumigatus. The predicted amino acid sequence of the fungal HPr showed greater homology with HPr from Gram-positive bacteria than from Gram-negative bacteria. Since other components of the phosphoenolpyruvate: carbohydrate phosphotransferase system have not been identified in eukaryotes, this raises the question of what regulatory function the HPr-like protein might have evolved in this fungus.

Amino Acid Sequence↗

Urinary sediment changes in severe preeclampsia.

We analyzed the urinary sediment of 30 patients with severe preeclampsia every 4 hours during early labor, delivery, and the postpartum period. Fifteen normal control patients were also followed in a similar fashion. No casts were noticed in the urine samples of the control group. However, the urinary sediment of preeclamptic patients revealed the same uniform pattern regardless of the state of coagulation, or the presence or absence of oliguria or eclamptic seizures. Numerous granular and hyaline casts, red-cell, and tubular cell casts were identified during microscopic evaluation. These data reflect both glomerular and tubular damage in preeclampsia. We conclude that urinary sediment analysis in severe preeclampsia uniformly reflects renal parenchymal damage and does not correlate with or predict the clinical course of the disease.

Adult↗

The protein-coding region of c-myc mRNA contains a sequence that specifies rapid mRNA turnover and induction by protein synthesis inhibitors.

The stability of certain mRNAs is known to be affected by translation. Some mRNAs appear to be protected from rapid degradation by translation, whereas degradation is coupled to translation for other mRNAs. The molecular determinants of this selective effect of translation are unknown. One example of this effect is the induction of early-response gene mRNAs in the presence of translation inhibitors. To define the molecular basis of induction of early-response gene mRNA expression by inhibitors of protein synthesis, we have performed a mutational analysis of one member of the early response gene family, the c-myc gene. We find that induction by cycloheximide is due to stabilization of c-myc transcripts. The requirements for increased expression of c-myc mRNA by cycloheximide are the presence of the sequence encoding c-myc amino acids 335-439 on a mRNA that can be translated; all other portions of the c-myc gene are dispensable, and this sequence can confer induction of mRNA expression by protein synthesis inhibitors on a heterologous gene. By direct measurement of mRNA turnover in the absence of transcription-blocking drugs, we show that this sequence can function as a selective mRNA destabilizing element, that turnover mediated by this element is translation dependent, and turnover mediated by this element is inhibited by actinomycin D. Our results support the hypothesis that degradation of c-myc mRNA is coupled to translation, that the sequences specifying this form of degradation are contained in the protein-coding sequence, and that translation inhibitors induce expression of c-myc mRNA by blocking turnover mediated by this element.

Cell Line↗

Collagenase activity in recurrent periodontitis: relationship to disease progression and doxycycline therapy.

Previous reports have suggested that active progression of periodontitis may be correlated with increased collagenolytic activity, and that improved clinical conditions after tetracycline treatment may be explained by inhibition of host collagenase. Eighty-two patients with a recent history of periodontal abscesses and/or loss of gingival attachment level (GAL) despite active periodontal therapy were enrolled in a double-blind, randomized, placebo-controlled trial. Clinical measurements, sampling of gingival crevicular fluid (GCF) and subgingival scaling were performed every 2 months. If any site exhibited greater than 2 mm loss of GAL or a periodontal abscess, patients were administered either 100 mg doxycycline per day for 3 weeks or placebo. During 12 months of monitoring, 55 patients exhibited recurrent active disease and were then randomly assigned to either the doxycycline (n = 30) or placebo (n = 25) groups. Analysis of active collagenase and latent collagenase in GCF samples were determined by functional assays and quantitated after SDS-PAGE and fluorography. Collagenase activities were assayed at sites exhibiting active destruction (study site), at sites with pocket depth comparable to the study site but without active destruction, and at healthy sites. Clinical measurements of GAL and collagenase activity were made at intervals between 1 wk and 7 months after completion of the drug regime. Within 7 months, 15 out of 19 patients on placebo exhibited recurrent disease compared to 13 out of 29 patients on doxycycline. Collagenase activity exhibited large variations among patients and was analyzed as presence or absence of active collagenase with a logistic model.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Engineering a Bacillus subtilis expression-secretion system with a strain deficient in six extracellular proteases.

We describe the development of an expression-secretion system in Bacillus subtilis to improve the quality and quantity of the secreted foreign proteins. This system consists of a strain (WB600) deficient in six extracellular proteases and a set of sacB-based expression vectors. With the inactivation of all six chromosomal genes encoding neutral protease A, subtilisin, extracellular protease, metalloprotease, bacillopeptidase F, and neutral protease B, WB600 showed only 0.32% of the wild-type extracellular protease activity. No residual protease activity could be detected when WB600 was cultured in the presence of 2 mM phenylmethylsulfonyl fluoride. By using TEM beta-lactamase as a model, we showed that WB600 can significantly improve the stability of the secreted enzyme. To further increase the production level we constructed an expression cassette carrying sacY, a sacB-specific regulatory gene. This gene was placed under the control of a strong, constitutively expressed promoter, P43. With this cassette in the expression vector, an 18-fold enhancement in beta-lactamase production was observed. An artificial operon, P43-sacY-degQ, was also constructed. However, only a partial additive enhancement effect (24-fold enhancement) was observed. Although degQ can stimulate the production of beta-lactamase in the system, its ability to increase the residual extracellular protease activity from WB600 limits its application. The use of the P43-sacY cassette and WB600 would be a better combination for producing intact foreign proteins in high yield.

Bacillus subtilis↗

Cardiorespiratory alterations during normal pregnancy.

Maternal cardiorespiratory changes can hinder satisfactory evaluation of gravid women. Alterations in the maternal cardiorespiratory system may be further modified by pain, labor, surgery, maternal posture, and gestational age. Critical illness during pregnancy demands an aggressive multidisciplinary approach by health care professionals who are familiar with these changes. This article reviews pertinent issues that should assist physicians treating complex medical complications during pregnancy.

Blood Pressure↗

The impact of a community based health education program on the incidence of diarrheal disease in southern Thailand.

This study has demonstrated that additional training of service providers [village health volunteers (VHVs), village health communicators (VHCs)] in combination with the mobilization of village leaders and influentials to promote selective preventive health behavior, can have a marked impact upon the effective practice of these behaviors and diarrheal incidence. Further, this impact can be achieved through the existing staff structure, ie, VHV/VHCs of the national health program. For example, increased contact between these service providers and mothers of children under 5 years through home visits and attendance at meetings held by the service providers, contributed positively to the practice of selected preventive behaviors. If the national program provided similar training inputs on the promotion of selected preventive behaviors and increased service provider contacts, the program's impact upon diarrheal disease would be enhanced.

Child, Preschool↗

Physiological and perceptual responses to cycle and treadmill exercise during pregnancy.

We compared physiological and perceptual responses to non-weight bearing (cycle) and weight bearing (treadmill) exercise in 16 sedentary women throughout a normal term pregnancy. Subjects were recruited late in the first trimester (less than 13 wk gestation) and were studied at 4 wk intervals throughout pregnancy and 4 wk postpartum (PP). Exercise consisted of four 5 min protocols; two were performed on the cycle (C1 = 50 W; C2 = 75 W) and two on the treadmill (T1 = 66 m.min-1, 2.5% grade; T2 = 66 m.min-1, 12% grade). Measured variables included oxygen consumption (VO2), heart rate (HR), minute ventilation (VE), and ratings of perceived exertion (RPE, 10-point Borg scale). Absolute VO2 (ml.min-1) during cycle exercise increased (P less than 0.001) by 25 wk gestation, while relative VO2 (ml.kg-1.min-1) during treadmill walking was unchanged through late pregnancy and PP. This suggests that cycle exercise is not a true non-weight bearing exercise within a given group of women throughout gestation. Subjects' VO2max values were estimated at each test interval and found to increase (P less than 0.001) by 25-28 wk gestation. Heart rate and RPE responses to exercise remained constant throughout gestation and decreased (P less than 0.01) PP. Although they did not participate in a regular exercise program, it appears that our subjects experienced a mild aerobic training effect during late pregnancy.

Adult↗