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Biomedical subjects

E Young

Publications and source records attributed to E Young.

At least 91 records · Page 5Linked to original sources
PubMed1995

Serological diagnosis of feline immunodeficiency virus infection using recombinant transmembrane glycoprotein.

We developed an antibody detection enzyme-linked immunosorbent assay (ELISA) using recombinant surface (SU), transmembrane (TM) and capsid (CA) antigens of feline immunodeficiency virus (FIV) expressed in Escherichia coli. The three antigens were tested with sera collected from experimentally infected cats in order to follow the course of seroconversion and of the antibody levels throughout the infection. An early and marked increase of TM antibodies was observed. Antibodies to TM were demonstrated at high levels throughout the observation period. The immune response to SU and to CA was less pronounced and in some cats the level of antibodies to SU and CA tended to decline 6 months after infection. In addition, 413 FIV negative and positive cat sera were tested in order to define for each antigen the diagnostic sensitivity, specificity and efficiency. TM showed the highest diagnostic sensitivity (98%) while its specificity was 97%. Its diagnostic efficiency of 97% was better than that of SU and CA and exceeded that of tests utilizing conventionally grown and gradient purified FIV. Therefore, recombinant TM can be considered a very important antigen for FIV ELISA testing. An interesting perspective is offered in the combination of TM with other recombinant antigens in a dot assay form.

Animals↗
PubMed1995

Allogeneic bone marrow transplantation for fucosidosis.

Bone marrow transplantation was performed on an 8-month-old boy who was diagnosed as having fucosidosis following the diagnosis of the disease in his older brother. Although he was asymptomatic and his development was normal, abnomalities were found on an MRI scan prior to transplant. In the absence of a suitable related donor, an unrelated volunteer donor was used. Conditioning for the transplant consisted of busulphan and cyclophosphamide. Graft-versus-host disease prophylaxis consisted of in vitro T cell-depletion of the bone marrow and in vivo administration of cyclosporin. The post-transplant period was complicated by moderately severe graft-versus-host disease. Engraftment was documented by the presence of donor levels of alpha-fucosidase, donor blood group and tissue type (difference in the DQ antigen), and chromosomal polymorphism pattern of donor origin. Eighteen months after transplant, there is evidence of mild neurodevelopmental delay. By contrast, his elder sibling showed far greater developmental delay at the same age. The patient's MRI scan shows improvement. We believe this to be the first case of human fucosidosis treated by bone marrow transplantation.

Bone Marrow Transplantation↗
PubMed1994

A population study of food intolerance.

We did a population study to identify the prevalence of reactions to eight foods commonly perceived to cause sensitivity in the UK. A cross-sectional survey of 7500 households in the Wycombe Health Authority area and the same number of randomly-selected households nationwide was followed up by interviews of positive respondents from the Wycombe Health Authority area. Those who agreed entered a double-blind, placebo-controlled food challenge study to confirm food intolerance. 20.4% of the nationwide sample and 19.9% of the High Wycombe sample complained of food intolerance. Of the 93 subjects who entered the double-blind, placebo-controlled food challenge, 19.4% (95% confidence interval 11.4%-27.4%) had a positive reaction. The estimated prevalence of reactions to the eight foods tested in the population varied from 1.4% to 1.8% according to the definition used. Women perceived food intolerance more frequently and showed a higher rate of positive results to food challenge. There is a discrepancy between perception of food intolerance and the results of the double-blind placebo-controlled food challenges. The consequences of mistaken perception of food intolerance may be considerable in financial, nutritional, and health terms.

Adolescent↗
PubMed1994

Prevalence of fluoroscopic coronary calcific deposits in high-risk asymptomatic persons.

Coronary calcific deposits are always associated with coronary atherosclerosis. Sensitive radiographic technology can detect coronary calcium before atherosclerosis becomes symptomatic. A total of 1461 asymptomatic high-risk adult subjects were studied with digital subtraction fluoroscopy to detect coronary calcium. Risk factor data were recorded including age, sex, family history, smoking history, diabetes history, body mass index, systolic blood pressure, left ventricular hypertrophy on ECG, total serum cholesterol level, high-density lipoprotein (HDL) cholesterol, and total cholesterol/HDL ratio. Digital subtraction fluoroscopy in the left anterior oblique projection was performed in all subjects. The prevalence of calcific deposits in at least one major coronary artery was high (58.3%). Eleven percent had coronary calcium in all three major arteries. Multivariate logistic regression analysis showed significant correlations (p < 0.05) between the prevalence of coronary calcium and age, smoking history (relative risk = 1.30), diabetes history (relative risk = 1.24), and family history (relative risk = 1.26). In older subjects (at least 65 years of age), smoking and serum lipoproteins assumed greater importance as contributors to coronary calcium, whereas in younger subjects a history of diabetes was more significant. Coronary calcific deposits are prevalent in high-risk asymptomatic subjects. Their occurrence is closely related to most known risk factors.

Age Distribution↗
PubMed1994

Prognostic significance of cardiac cinefluoroscopy for coronary calcific deposits in asymptomatic high risk subjects.

OBJECTIVES: This research investigated the prognostic significance of radiographically detectable coronary calcific deposits. BACKGROUND: Coronary calcific deposits are almost always associated with coronary atherosclerosis. We investigated the association between fluoroscopically determined coronary calcium and coronary heart disease end points at 1 year of follow-up. METHODS: This prospective population-based cohort study was conducted in the suburbs of Los Angeles. Fourteen hundred sixty-one asymptomatic adults with an estimated > or = 10% risk of having a coronary heart disease event within 8 years underwent cardiac cinefluoroscopy for assessment of coronary calcium at initiation of the study. Clinical status including angina, documented myocardial infarction, myocardial revascularization and death from coronary heart disease were determined after 1 year. RESULTS: The prevalence of calcific deposits was high (47%). A follow-up examination at 1 year was successfully completed in 99.9% of subjects. Six subjects (0.4%) had died from coronary heart disease and 9 (0.6%) had had a nonfatal myocardial infarction. Thirty-seven subjects (2.5%) reported angina pectoris, and 13 (0.9%) had undergone myocardial revascularization. Fifty-three subjects had at least one event during the 1-year period. Radiographically detectable calcium was associated with the presence of at least one of these end points, with a risk ratio of 2.7 (confidence limits 1.4, 4.6). The presence of coronary calcium was an independent predictor of at least one end point when controlling for age, gender and risk factors. However, three deaths due to coronary heart disease and two nonfatal myocardial infarctions occurred in subjects without detectable coronary calcium. CONCLUSIONS: The presence of coronary calcific deposits incurs an increased risk of coronary heart disease events in asymptomatic high risk subjects at 1 year. This increased risk is independent of that incurred by standard risk factors.

Aged↗
PubMed1994

Superinfection of cats with feline immunodeficiency virus subtypes A and B.

The ability of feline immunodeficiency virus (FIV) isolates from subtypes A and B to superinfect cats and cell cultures was tested. Three specific pathogen-free (SPF) cats were first inoculated with 10 ID50 of subtype B virus (FIVBang) and 30 weeks later inoculated with 100 ID50 of subtype A virus (FIVPet). On the basis of subtype-specific PCR analysis, both FIV subtypes were detected in the peripheral blood lymphocytes (PBLs) of two of three cats from 9 to 30 weeks following the second inoculation. Only the first virus was detected in the bone marrow (BM) cells of these two cats until 30 weeks following the second inoculation, at which time the second virus was finally detected in their BM cells. Both cats developed significant virus-neutralizing (VN) antibodies to the second virus by 15 weeks following the second inoculation; but only one cat had high VN titers to the first virus, which remained at the same level even after the second inoculation. The two control cats inoculated with only the second virus developed VN titers specifically to the second virus and were consistently PCR positive for the virus in PBLs and BM cells starting 9 weeks postinoculation. Thus a delay in BM infection with the second virus was observed in the two superinfected cats. In contrast, one of three cats had neither VN antibodies to the second virus nor PCR signal of the second virus in its PBLs, BM, and lymph node throughout the 30 weeks of study and it appeared to be resistant to superinfection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Analysis of myocardial response to significant weight loss in obese rats.

We evaluated cardiac response to weight loss induced by a very-low-energy (VLE) diet similar to commercially available protein-sparing diets. Such diets have been implicated in sudden death, and whether organ and tissue responses to them are untoward is not known. Rapid weight loss was induced in rats with weights ranging from obese to normal, and cardiac mass and myocardial histomorphometry were assessed. Over 3 wk body weight dropped from 544 +/- 12 to 417 +/- 21 g (P < 0.001). Heart weight was less in the VLE group than in obese controls (1246 +/- 115 vs 1625 +/- 179 mg, P < 0.001), as were the weights of the left ventricle (805 +/- 81 vs 1061 +/- 134 mg, P < 0.001) and right ventricle (198 +/- 27 vs 265 +/- 40 mg, P < 0.002). Reduction in heart weight was commensurate with loss of body weight (r = 0.89). Myocyte cross-sectional area was reduced in the VLE group (452.6 +/- 108.6 to 331.8 +/- 41.5 microns 2, P < 0.05), with no structural abnormalities. We conclude that weight loss in the weight range studied is accompanied by proportional reduction in cardiac mass and myocyte size. Myocardial regression is not accompanied by myocyte dropout or edema, and likely represents a simple adaptation to reduced body size.

Animals↗
PubMed1994

Reproducibility of digital subtraction fluoroscopic readings for coronary artery calcification.

RATIONALE AND OBJECTIVES: Digital subtraction fluoroscopy, an inexpensive screening test for coronary atherosclerosis, is highly sensitive in detecting coronary calcifications. However, no previous study has reported interobserver agreement for this test. METHODS: Six hundred and thirty-one subjects underwent digital subtraction fluoroscopy in the 60 degrees left anterior oblique projection. Images were acquired with pulsed fluoroscopy at 15 frames per second. An averaged mask was subtracted from successive images. These fluoroscopic images were stored on a digital disk and replayed in cine loop format. An observer, blinded to clinical information, read the fluoroscopic studies for the presence of calcium in the left main-left anterior descending artery, circumflex artery, and right coronary artery. The images were then stored on digital tape and reread by a second blinded observer. RESULTS: The percentages of interobserver agreement regarding the presence and absence of calcium in left main-left anterior descending, circumflex, and right coronary arteries, were 91.9%, 92.9%, and 92.2%, respectively. The overall kappa values, which are 0.85, 0.77, and 0.82 in left main-left anterior descending, circumflex, and right coronary arteries, respectively, show a highly significant level of agreement (P < .0001). CONCLUSION: Digital subtraction fluoroscopy is a reliable screening test for coronary calcifications.

Calcinosis↗
PubMed1994

Transesophageal echocardiography in diagnosis of infective endocarditis.

STUDY OBJECTIVE: To determine whether transesophageal echocardiography (TEE) was superior to transthoracic echocardiography (TTE) in defining valvular vegetations and diagnosing clinical infective endocarditis (IE) in patients suspected of having this infection. PATIENTS AND METHODS: Between April 1989 and May 1991, 64 febrile patients with clinical and/or microbiologic risk factors for IE were prospectively enrolled. Patients underwent both TEE and TTE, which were interpreted in a blinded fashion as to the patient's clinical status. Clinical criteria for the diagnosis of IE were compared with TEE and TTE findings to delineate the ability of the two echocardiographic techniques to define valvular vegetations and to establish the clinical diagnosis of vegetative IE. RESULTS: Thirty-four valves had typical valvular vegetations demonstrated by either TEE or TTE. Transesophageal echocardiography was more sensitive than TTE in identifying valvular vegetations (33/34 vs 23/34 instances, respectively; p = 0.004). Also, TEE was better at identifying smaller vegetations (< 1 cm) than TTE; 12 patients with such vegetations were identified by TEE as compared with only 5 of 12 identified by TTE (p = 0.02). Of the 64 patients enrolled, 30 (47 percent) were classified as having "definite" or "probable" IE by modified von Reyn criteria. Among these 30 patients, TEE was significantly more sensitive than TTE at documenting vegetative valvular lesions (26/30 [87 percent] vs 18/30 [60 percent], respectively) (p < 0.01). Both TEE and TTE were highly specific (91 percent) in delineating valvular vegetations in this patient population; two of the three false-positive TEE studies for valvular vegetations occurred in patients with a history of IE. All nine periannular complications of IE were identified by TEE, as compared with only two being defined by TTE (p = 0.001). CONCLUSIONS: Transesophageal echocardiography is significantly more sensitive than TTE and highly specific in both confirming the clinical diagnosis of IE, as well as in identifying valvular vegetations in patients at risk for this infection. Our data also support the concept that TEE is the echocardiographic method of choice for defining small vegetations and periannular complications in IE.

Abscess↗
PubMed1994

The experience of two-epidural-catheter for painless labor.

'Two epidural-catheters' method was used to relieve labor pain during the first and second stage of labor course. Six milliliters of a mixture of '0.15% bupivacaine +0.03% xylocaine +0.0005% fentanyl' was the main agent given through the epidural catheter every 2 hours when the cervix was 3-4 cm dilated with 4 ml of 1% xylocaine as test dose. Addition doses of the mixture were given when needed. Fifty two, ASA I-II, parturients (primigravida: 43, multipara: 9) were included in this study. The mode of delivery was: 59.6% by vacuum, 36.4% by normal spontaneous delivery (NSD), and 4% by Cesarean Section (C/S). 88.5% of newborns had Apgar score > or = 7 at 1 minute and all had Apgar score > or = 7 at 5 minutes. 38(73%) of 52 parturients were fully satisfied with the analgesic effect during the whole labor course and 14(27%) of 52 parturients were partially satisfied with the analgesic effect owing to 1) intolerable lower abdominal pain (11 cases), 2) mild painful episiotomy (1 case), and backache (2 cases). No motor block was noted. Good analgesic effect during the second stage labor course could be obtained by our 'Two-Epidural-Catheter' method and no significant complications of newborns and parturients were noted in our study.

Adolescent↗
PubMed1994

Ex-vivo and in-vitro evidence that low molecular weight heparins exhibit less binding to plasma proteins than unfractionated heparin.

We have compared the non-specific binding of unfractionated heparin (UFH) with that of low molecular weight heparin (LMWH) to plasma proteins both ex-vivo and in-vitro. Non-specific binding to plasma proteins was assessed by comparing the heparin levels measured as anti-factor Xa activity before and after the addition of low affinity heparin, which is essentially devoid of anti-factor Xa activity, in order to displace heparin bound to plasma proteins. For the ex-vivo studies, we compared the recovery of UFH and a LMWH (ardeparin) from the plasma of patients participating in a randomized trial of post-operative venous thrombosis prophylaxis. For the in-vitro studies, we compared the recovery of UFH and 4 different LMWHs when added to the plasma from healthy volunteers and from patients with suspected venous thromboembolic disease. The results indicate that the recovery of LMWH is much less affected by nonspecific binding to plasma proteins both ex-vivo and in-vitro. In addition, there are differences between the LMWHs with respect to their plasma protein-binding.

Blood Proteins↗
PubMed1993

Comparison of the non-specific binding of unfractionated heparin and low molecular weight heparin (Enoxaparin) to plasma proteins.

The non-specific binding of anticoagulantly-active heparin to plasma proteins may influence its anticoagulant effect. We used low affinity heparin (LAH) essentially devoid of anti-factor Xa activity to investigate the extent and possible mechanism of this non-specific binding. The addition of excess LAH to platelet-poor plasma containing a fixed amount of unfractionated heparin doubled the anti-factor Xa activity presumably because it displaces anticoagulantly-active heparin from plasma proteins. Although dextran sulfates of varying molecular weights also increased the anti-factor Xa activity, less sulfated heparin-like polysaccharides had no effect. These findings suggest that the ability to displace active heparin from plasma protein binding sites is related to charge and may be independent of molecular size. In contrast to its effect in plasma containing unfractionated heparin, there was little augmentation in anti-factor Xa activity when LAH was added to plasma containing low molecular weight heparin (LMWH), indicating that LMWH binds less to plasma proteins than unfractionated heparin. This concept is supported by studies comparing the anticoagulant activity of unfractionated heparin and LMWH in plasma with that in buffer containing antithrombin III. The anti-factor Xa activity of unfractionated heparin was 2-fold less in plasma than in the purified system. In contrast, LMWH had identical anti-factor Xa activity in both plasma and buffer, respectively. These findings may be clinically relevant because the recovered anti-factor Xa activity of unfractionated heparin was 33% lower in plasma from patients with suspected venous thrombosis than in plasma from healthy volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗
PubMed1993

The additive effect of low molecular weight heparins on thrombin inhibition by dermatan sulfate.

The aim of this study was to investigate the mechanism by which the anticoagulant activity of dermatan sulfate (DS) is increased by low molecular weight heparin (LMWH). In platelet poor plasma, LMWH enhances the effect of DS on thrombin (IIa) inhibition as determined by thrombin clotting times and with a chromogenic substrate assay. Analysis of the results of the chromogenic assays using either the algebraic fractional or the graphic isobole method suggests that LMWH has an additive effect on the anti-IIa activity of DS. This additive effect was lost when the experiments were repeated in plasma immunodepleted of antithrombin III (ATIII), indicating that the anti-IIa activity of LMWH is ATIII-dependent. To further explore the mechanism of the interaction between LMWH and DS, 125I-labeled IIa was added to plasma in the presence or absence of DS and/or LMWH and the formation of IIa-inhibitor complexes was assessed using SDS-PAGE followed by autoradiography. DS addition selectively increases the formation of heparin cofactor II (HCII)-IIa complexes, whereas LMWH enhances ATIII-IIa complex generation. Compared to plasma containing DS alone, the formation of ATIII-IIa complexes also is increased when the combination of DS and LMWH is added. These findings suggest that the additive effect of LMWH on the anti-IIa activity of DS reflects their different modes of IIa inhibition; DS potentiates IIa inhibition by HCII, while LMWH catalyses ATIII-dependent IIa inactivation. The potential clinical significance of these findings requires further investigation.

Amino Acid Sequence↗
PubMed1993

Monocyte 1 alpha-hydroxylase regulation: induction by inflammatory cytokines and suppression by dexamethasone and uremia toxin.

Alveolar macrophages acquire 1 alpha-hydroxylase activity in inflammation, and thereby metabolize 25 hydroxyvitamin D3 (25 D3) to the active metabolite, 1 alpha,25-dihydroxyvitamin D3 (1,25 D3, calcitriol). Calcitriol is a potent differentiation agent that modulates mononuclear phagocyte activation and effector functions. The mediators that induce macrophage 1 alpha-hydroxylase activity are not well delineated. Furthermore, it is unclear whether calcitriol is a product only of terminally differentiated macrophages or whether less mature mononuclear phagocytes can produce it as well. The ability of newly recruited monocytes to produce calcitriol as an autocrine differentiation agent is particularly important in inflammation, as it may substantially expand the functional repertoire of these cells. To assess the effects of cytokines on 1 alpha-hydroxylase activity, blood monocytes were cultured in the presence and absence of human recombinant tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukins 1 and 2 and then incubated with 25 D3 substrate. The conditioned media were assayed for calcitriol by high-performance liquid chromatography and competitive receptor binding assay. No detectable calcitriol was produced by unstimulated monocytes. However, all the cytokines markedly increased monocyte calcitriol production (range 133-151 pg/mg protein; in all cases P < .001). We then determined whether calcitriol production was suppressed by preincubation with either dexamethasone or the putative uremia toxin guanidinosuccinic acid (GSA). Dexamethasone pretreatment significantly inhibited subsequent cytokine-induced calcitriol production by monocytes, as did GSA (average 69 and 63% of control, respectively).

Calcitriol↗
PubMed1993

Enhanced expression, secretion, and large-scale purification of recombinant HIV-1 gp120 in insect cell using the baculovirus egt and p67 signal peptides.

The expression of glycosylated and secreted recombinant mammalian proteins in baculovirus-infected insect cells is often much less efficient than that of other foreign proteins in this system. In an effort to improve the expression and secretion of such proteins we have constructed baculovirus vectors which contain the signal peptide coding regions from two baculovirus proteins, an ecdysteroid UDPglucosyltransferase (egt) and the envelope glycoprotein gp67. We used these vectors to express HIV-1 gp120, inserting the baculovirus signal peptides in place of the HIV-1 envelope signal peptide. When Sf9 cells infected with recombinant baculoviruses made from these vectors (vegt120 and vp67120) were compared with cells infected with the normal gp120 baculovirus a 6- to 20-fold increase in expression and secretion of gp120 was observed. When the HIV-1 signal peptide was used only 40% or less of the total gp120 produced in Sf9 cells was secreted. However, using the egt or p67 signal peptides, up to 70% of the total gp120 produced was secreted. Therefore, not only was more gp120 produced from these modified viruses but secretion of gp120 was more efficient. Large-scale expression and purification of egt-gp120 from a 5-liter airlift fermenter or a 6-liter spinner flask resulted in a yield of 10 to 15 mg of purified protein per liter. Using these baculovirus-derived signal peptides in baculovirus expression vectors is thus likely to aid in increasing expression and yield of heterologous secreted proteins in insect cells.

Amino Acid Sequence↗
PubMed1993

Expression of alkaline phosphatase in the mature mouse placenta visualized by in situ hybridization and enzyme histochemistry.

Alkaline phosphatases (APs) are a family of cell surface glycoproteins that are expressed in a variety of tissues. Their physiological functions are still unclear. Three different AP genes have been found to be expressed in mice, and AP cloned from the placenta is of the tissue non-specific (TNAP) type. We have in investigated the location of TNAP mRNA and active AP in mature mouse placenta, using in situ hybridization and enzyme histochemistry on serial sections. Digital image analysis was used to estimate relative amounts of TNAP mRNA. Tissue non-specific alkaline phosphatase messenger was detected only in the placental labyrinth, whereas active AP was present both in the labyrinth and in a zone of cells at the margin of the decidua basalis, bordering the myometrium and the metrial gland. This latter location of AP activity has not been described previously. The AP-positive zone of the decidua had a condensed appearance and a central defect in the zone was visible on sections taken from the middle of the placenta. No TNAP messenger was found in the zone of AP-positive decidual cells.

Alkaline Phosphatase↗