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Biomedical subjects

K B Meyer

Publications and source records attributed to K B Meyer.

At least 37 records · Page 2Linked to original sources
PubMed1996

Correlation of pediatric echocardiographic Doppler and catheter-derived valvar aortic stenosis gradients and the influence of aortic regurgitation.

This report suggests that in the absence of aortic regurgitation, Doppler peak and mean gradients are useful predictors of catheter peak-to-peak aortic stenosis gradients >50 mm Hg; however, in the presence of aortic regurgitation, the predictive value diminishes dramatically, but improves when electrographic data are incorporated. We present potentially useful equations to help predict the need for interventional catheterization for valvar aortic stenosis.

Adolescent↗
PubMed1996

The Ig kappa 3'-enhancer triggers gene expression in early B lymphocytes but its activity is enhanced on B cell activation.

Ig kappa gene expression is controlled by two enhancers, one located within the major intron (Ei) and the other located downstream of C kappa (E3'). Whereas loss of E3' has previously been shown to diminish kappa expression, we show here that a rearranged kappa transgene lacking Ei is well expressed, even at the pre-B cell stage. This suggests that E3' alone might be sufficient to give properly regulated transcription throughout B cell development. Indeed, we show that a transgene composed of a beta-globin reporter linked to E3' is expressed in a B cell-specific manner, becoming activated at the late pro-B to pre-B cell stage but with dramatically enhanced activity on B cell activation. Thus, E3' becomes active as a transcription enhancer at the stage when V kappa-J kappa rearrangement is being initiated and is sufficient to yield an expression pattern in a linked reporter gene similar to that of fully rearranged kappa genes.

Animals↗
PubMed1996

An epidemiologic study of early biologic effects of benzene in Chinese workers.

Benzene is a recognized hematotoxin and leukemogen, but its mechanisms of action in humans are still uncertain. To provide insight into these processes, we carried out a cross-sectional study of 44 healthy workers currently exposed to benzene (median 8-hr time-weighted average; 31 ppm), and unexposed controls in Shanghai, China. Here we provide an overview of the study results on peripheral blood cells levels and somatic cell mutation frequency measured by the glycophorin A (GPA) gene loss assay and report on peripheral cytokine levels. All peripheral blood cells levels (i.e., total white blood cells, absolute lymphocyte count, platelets, red blood cells, and hemoglobin) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume, which was higher among exposed subjects. In contrast, peripheral cytokine levels (interleukin-3, interleukin-6, erythropoietin, granulocyte colony-stimulating factor, tissue necrosis factor-alpha) in a subset of the most highly exposed workers (n = 11) were similar to values in controls (n = 11), suggesting that benzene does not affect these growth factor levels in peripheral blood. The GPA assay measures stem cell or precursor erythroid cell mutations expressed in peripheral red blood cells of MN heterozygous subjects, identifying NN variants, which result from loss of the GPA M allele and duplication of the N allele, and N phi variants, which arise from gene inactivation. The NN (but not N phi) GPA variant cell frequency was elevated in the exposed workers compared with controls (mean +/- SD, 13.9 +/- 8.4 mutants per million cells versus 7.4 +/- 5.2 per million cells, (respectively; p = 0.0002), suggesting that benzene produces gene-duplicating but not gene-inactivating mutations at the GPA locus in bone marrow cells of exposed humans. These findings, combined with ongoing analyses of benzene macromolecular adducts and chromosomal aberrations, will provide an opportunity to comprehensively evaluate a wide range of early biologic effects associated with benzene exposure in humans.

Adult↗
PubMed1996

Transmembrane passage of cytokine-inducing bacterial products across new and reprocessed polysulfone dialyzers.

The widespread use of bicarbonate dialysate and reprocessed high-efficiency and "high-flux" dialyzers has raised concerns about the increased risk of reverse-transfer of dialysate contaminants into the blood compartment. To evaluate this concern, the reverse-transfer of bacterial products from contaminated bicarbonate dialysate into the blood compartment was compared during in vitro dialysis with new or reprocessed high-flux polysulfone dialyzers. In vitro dialysis was carried out at 37 degrees C by use of a counter-current recirculating loop dialysis circuit with either new high-flux polysulfone dialyzers or dialyzers reprocessed once or 20 times with formaldehyde (0.75%) and bleach (< 1%) with an automated system. Heparinized whole blood from healthy volunteers was circulated through the blood compartment, and bicarbonate dialysate was circulated in the dialysate compartment. The dialysate was challenged sequentially by 1:1000 and 1:100 dilutions of a sterile Pseudomonas aeruginosa culture supernatant (bacterial challenge). Samples were drawn from the blood and dialysate compartments 1 h after each challenge. Peripheral blood mononuclear cells (PBMC) were harvested by Ficoll-Hypaque separation from whole blood in the blood compartment and a 5 x 10(6) PBMC/mL cell suspension was prepared. Likewise, dialysate samples (0.5 mL) were added to 0.5 mL suspension of 5 x 10(6) PBMC/mL drawn at baseline. All PBMC suspensions were incubated upright in a humidified atmosphere at 37 degrees C with 5% CO2 for 24 h, and total interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF alpha) cytokine production (cell-associated and secreted) was measured by radioimmunoassay. Eight experiments were performed for each arm of the study with the same donor for each arm. One hour after contaminating the dialysate with a 1:1000 dilution of the bacterial challenge, IL-1 alpha production by PBMC harvested from the blood compartment was 160 +/- 0, 171 +/- 11, and 270 +/- 35 pg, respectively, for new dialyzers, dialyzers reprocessed once, and dialyzers reprocessed 20 times (P = 0.004). One hour after challenging the dialysate with 1:100 dilution, IL-1 alpha production by PBMC harvested from the blood compartment was 188 +/- 20, 228 +/- 35, and 427 +/- 67 pg, respectively, for new dialyzers, dialyzers reprocessed once, and dialyzers reprocessed 20 times (P = 0.006). IL-1 alpha production by PBMC from dialyzers reprocessed 20 times was significantly greater than both new and dialyzers reprocessed once. However, there were no significant differences between new dialyzers and dialyzers reprocessed once. Similarly, after the 1:1000 challenge, TNF alpha production by PBMC harvested from the blood compartment was 160 +/- 0, 160 +/- 0, and 213 +/- 22 pg, respectively, for new dialyzers, dialyzers reprocessed once, and dialyzers reprocessed 20 times (P = 0.008). After the 1:100 challenge, TNF alpha production was 168 +/- 8, 188 +/- 20, and 225 +/- 32 pg, respectively, for new dialyzers, dialyzers reprocessed once, and dialyzers reprocessed 20 times (P = 0.20). These results demonstrate that reprocessing of high-flux polysulfone dialyzers with bleach increases the risk of reverse-transfer of bacterial products from contaminated dialysate, and this risk appears to increase with the number of reuses. Consequently, units that reprocess membranes with bleach and have suboptimal water quality might subject their patients to a higher risk of cytokine-related morbidity.

Anti-Bacterial Agents↗
PubMed1996

Characterization of plasmid DNA transfer into mouse skeletal muscle: evaluation of uptake mechanism, expression and secretion of gene products into blood.

The expression of naked plasmid DNA coding for firefly luciferase (pRSVluc) or a secreted protein, human-alpha-1-antitrypsin (pRcCMVhAAT) in mouse skeletal muscle was characterized following administration by an improved intramuscular injection technique. Injection guided by intense illumination along the longitudinal axis of the mouse quadriceps muscle and parallel to the myofibers yielded 200-fold higher levels of luciferase expression than perpendicular injection. Luciferase expression was inhibited by an excess of non-coding DNA or dextran sulfate suggesting that muscle DNA uptake mechanism(s) can be saturated. Injected plasmid DNA was rapidly eliminated from the muscle as evidenced by tissue distribution studies of radiolabeled hAAT plasmid and Southern analysis. However, PCR analysis demonstrated that hAAT cDNA persisted in the muscle for at least 1 month after injection. Immunohistochemistry techniques indicated that the hAAT gene was expressed by the muscle fibers. ELISA analysis of serum samples collected from intramuscularly injected mice demonstrated that secreted hAAT protein concentration peaked in serum by day 7, started to decline by day 14 and was barely detectable 21 days post-injection. RT-PCR analysis demonstrated that hAAT transcript persisted at the site of injection for at least 1 month indicating that the decline of serum hAAT concentration 21 days post-injection was not due to the absence of hAAT transcript. However, the decline of hAAT protein concentration in the serum was inversely correlated with accumulation of murine anti-hAAT antibodies in circulation.

Adenosine Triphosphate↗
PubMed1995

Repression of the immunoglobulin heavy chain 3' enhancer by helix-loop-helix protein Id3 via a functionally important E47/E12 binding site: implications for developmental control of enhancer function.

The activity of the immunoglobulin 3' enhancer is restricted to the late stages of B lymphoid development. Here we further examine the molecular basis for the temporally restricted activity of the B-lymphoid IgH 3' enhancer. We demonstrate that a binding site (E5 site) for the E47 and/or E12 proteins is functionally important for enhancer activity. The multimerized E5 site acts as a B cell-specific enhancer and, when assayed in COS cells, can be transactivated by E47/E12 proteins. This transactivation in COS cells, as well as the activity of the full length 3' enhancer in plasma cells, can be repressed by overexpression of the dominant negative nuclear regulator Id3. When examining the tissue distribution of Id3 in murine cell lines, we find that Id3 is expressed throughout the pre-B and B cell stages, but is down-regulated at the plasma cell stage. Thus, Id3 may contribute to the temporal regulation of the IgH 3' enhancer.

Animals↗
PubMed1995

The outcomes of ESRD and its treatment.

In recent years, the notion that studying outcomes is a distinct form of clinical research has gained currency. This article offers a conceptual framework for thinking about outcomes research in end-stage renal disease and examines one issue in detail. Although the meaning of the term "outcome" is often assumed, it is currently used in two ways. In the broader sense, outcomes are the results of health care. These may include survival and the presence or absence of symptoms and clinical signs of disease. As it has recently been used in the medical literature, however, the term outcomes frequently connotes outcomes with respect to patient function and experience. Patient experience comprises functional status, general well-being, and satisfaction with care. The principle that the outcomes of end-stage renal disease should be studied has been established. A substantial body of knowledge has accumulated regarding characteristics of the patient population, of the treatments administered, and of the consequences with respect to survival. Whether the investigation and practice of renal replacement therapy should encompass the measurement of patient experience has been a subject of controversy. Reasons to perform such measurements are enumerated, and countervailing arguments are examined critically. The technological prerequisites for success in the widespread measurement of patient experience are set forth.

Humans↗
PubMed1995

Screening for acquired cystic kidney disease: a decision analytic perspective.

Acquired cystic kidney disease (ACKD) increases the risk of renal malignancy, and many authors suggest routine screening of dialysis patients for ACKD and renal tumors. However, they have defined neither the target population, the optimal screening strategy, the magnitude of its benefit, nor its risk. We used decision analysis to evaluate strategies of performing either computed tomography (CT) or ultrasound every three years on all dialysis patients and annually on patients found to have cysts. We compared these strategies to a strategy of seeking cysts and cancer only if these are clinically suspected. The baseline analysis shows that both CT and ultrasound may decrease cancer deaths by half for patients with a life expectancy of 25 years. Screening for ACKD offers these patients as much as a 1.6 year gain in life expectancy. However, for the majority of patients beginning renal replacement therapy, age or comorbid disease substantially limits life expectancy. For such patients, the gain in life expectancy from an ACKD screening program is measured in days. Sensitivity analyses show that the benefit of screening depends on the rate of malignant transformation, which needs better definition. The gain in life expectancy does not appear to be large enough to justify an ACKD screening program for the entire ESRD population. However, for the youngest and healthiest patients, a screening program would be of benefit. The magnitude of this benefit is uncertain, because the analysis was consistently biased in favor of the screening strategies.

Decision Support Techniques↗
PubMed1995

Regulated activity of the IgH intron enhancer (E mu) in the T lymphocyte lineage.

The activity of the IgH (E mu) enhancer in the T lymphocyte lineage has been investigated using both transgenic mice and transfection studies. Thymocyte fractionation experiments indicate that a transgene consisting of the bacterial chloramphenicol acetyl transferase (CAT) gene, linked to E mu and the SV40 early promoter (E mu-CAT), is expressed only in thymocytes with a mature medullary phenotype and not in immature cells. Transfection of this same construct into two thymoma cell lines representing different stages of thymocyte development mimics the pattern of activity observed in vivo. Further transfection experiments suggest that this pattern of expression might be attributed to the differential activity of the E2E3 and octanucleotide motifs of E mu during development. In contrast, an Ig lambda transgene (linked to E mu and an Ig V lambda promoter) is expressed in the majority of thymocytes. We envisage that the different patterns of expression of the two transgenes reflect interactions between their respective promoters and the factors which are bound to E mu at different stages of thymocyte development. Although differing in their pattern of expression within the thymus, the two transgenes share the property of extinction in peripheral T lymphocytes. These results indicate that the expression of E mu-linked transgenes in the thymus cannot simply be explained by activation of the enhancer in a lymphoid progenitor cell prior to B/T lineage divergence. Rather, the enhancer (or components of it) must be independently activated (and inactivated) during T lymphocyte development. Furthermore, this activity is consistent with the developmental timing of Ig DH-JH rearrangements in these cells.

Animals↗
PubMed1995

Intratracheal gene delivery to the mouse airway: characterization of plasmid DNA expression and pharmacokinetics.

Intratracheal administration of plasmid DNA resulted in gene expression in mouse airways in the absence of any enhancing agent. Administration of plasmid DNA encoding the chloramphenicol acetyltransferase gene (CAT) in sterile water lead to CAT transgene expression that peaked between 1 and 3 days and was detected up to 28 days after DNA administration. Transgene expression was independent of mouse gender, age and strain. Levels of expression from DNA in various isotonic solutions did not differ from levels obtained with DNA administered in water, suggesting that transfection is not dependent on damage to airway cells caused by a hypo-osmotic delivery vehicle. Pharmacokinetic studies using radiolabeled plasmid DNA showed that DNA was rapidly degraded, while higher levels of radioactivity were retained for longer duration following administration of cationic liposome-DNA complexes in the airway. Southern blot and PCR analysis confirmed that DNA complexed with DOTMA-DOPE was retained in the airways for a longer period. However, cationic liposomes DOTMA-DOPE (1:1) or DOTAP complexed with DNA, did not enhance expression over DNA alone. These results suggest that 'naked' plasmid DNA should be included as a control in all studies on intratracheal gene delivery using nonviral systems.

Animals↗
PubMed1994

Activation of the immunoglobulin kappa 3' enhancer in pre-B cells correlates with the suppression of a nuclear factor binding to a sequence flanking the active core.

Both the kappa intron and the kappa 3' enhancer are required for high levels of immunoglobulin kappa gene expression. The activity of both enhancer elements can be induced by LPS in pre-B cells. While the LPS induction of the kappa intron enhancer is mediated by NF-kappa B, this factor is not responsible for activation of the 3' enhancer. Dissection of the 3' enhancer has shown that in pre-B cells the activity of the kappa 3' enhancer is repressed by a region flanking an active core element. We have now scanned this flanking region for nuclear factor binding sites and have identified sites for B-cell specific E47/E12-like proteins and two ubiquitous nuclear proteins. Furthermore, we have identified a nuclear factor in pre-B cells whose binding activity is suppressed in response to LPS. In its tissue-distribution and binding specificity this factor appears to be identical to the lymphoid specific protein LEF-1. The position of the LEF-1 binding site within the 3' enhancer and its response to LPS raise the possibility that LEF-1 may be the target for a second pathway able to mediate LPS induction of immunoglobulin kappa gene transcription.

Animals↗
PubMed1994

Monitoring dialysis patients' health status.

We report 3 years of experience with quarterly assessments of the self-reported health of dialysis outpatients using the Short Form-36 (SF-36) Health Survey. The SF-36 measures eight different dimensions of health: physical function, role limitations due to physical problems, bodily pain, general health perceptions, vitality, social function, role limitations due to emotional problems, and general mental health. On each dimensions, the respondent receives a score from 0 to 100. A higher score indicates better health. Program logistics and results are described, including reliability coefficients, standard deviations, and standard errors of measurement for the SF-36 in this patient population. The SF-36 was completed an average of 4.4 times by 112 patients over an average 14-month follow-up; 40 patients responded at least six times. On most dimensions, the dialysis patients' scores were lower and more variable than those of a sample of the general US population matched for age and sex. For example, mean initial physical function score (+/- SD) was 48.5 +/- 31.2 for the dialysis patients and 84.8 +/- 23.3 for the general population. The mean initial general health perception score of the dialysis patients was 43.7 +/- 23.9 with 71.9 +/- 20.3 for the general population. In contrast, general mental health scores were more comparable. The mean initial general mental health score was 69.6 +/- 17.5 for our patients and 75.5 +/- 18.0 for the general population. Reliability (Cronbach's alpha) ranged from 0.77 for general mental health to 0.93 for physical function. The 95% confidence intervals around individual scores were approximately 20 points, except for role-physical and role-emotional, which were both approximately 30 points. Two case reports compare information obtained from the SF-36 with the dialysis team's assessments of the patient, as recorded in the medical record. The two patients' comments on reviewing their SF-36 results are also summarized. Patient reactions to the health status assessment program are explored, and potential benefits and areas for further work are outlined. Serial measurement of the health status of dialysis patients allows the recognition of clear patterns in individual patient responses. These patterns sometimes suggest that the patient is either substantially more or less impaired than the dialysis team had thought. Changes in these patterns, both transient and protracted, frequently exceed 95% confidence intervals for patient-level scores. Longitudinal health status profiles of individual dialysis patients, accumulated by repeated self-assessment using the SF-36, enhance rather than merely restate the providers' intuitive judgments expressed in the medical record.

Adolescent↗
PubMed1994

Vascular occlusion with a balloon-expandable stent occluder.

PURPOSE: To evaluate the effectiveness of a new vascular occlusion device. MATERIALS AND METHODS: The device was created by coating a balloon-expandable stent with a silicone sleeve that tapers to a blind-ended nozzle at its leading end. Once crimp-mounted on an angioplasty balloon catheter, the device is introduced over a guide wire through a small end hole in the nozzle. RESULTS: The device was tested for stability and occlusive ability. No migration was measured over a pulsatile pulse range of 50-300 mm Hg, and mean flow rate in the occluded vessel was reduced from 443 mL/min +/- 99 (standard deviation) to 1.9 mL/min +/- 2.7. Subsequently, 12 arteries were occluded in three dogs, and immediate vascular occlusion was achieved in all vessels. An arteriovenous fistula was created in another six dogs and was successfully occluded with the device. Follow-up arteriography at 3 months demonstrated persistent occlusion with no migration of the device. CONCLUSION: This new occlusive device offers immediate vascular occlusion with excellent stability.

Angioplasty, Balloon↗
PubMed1994

Cisplatin nephrotoxicity.

Cisplatin treatment causes tubulointerstitial injury to the kidneys. Common clinical syndromes associated with its use include acute renal failure and a magnesium wasting state. Routine fluid infusion therapy has markedly reduced the incidence of acute renal failure. However, methodologic limitations of most recent studies preclude confident conclusions regarding long-term effects of cisplatin treatment on renal function. Experimental and clinical evidence suggests that sulfhydryl metabolism and oxidative stress are central to cisplatin renal injury. Both in animals and humans, a variety of agents appear to alter renal uptale of cisplatin and its hemodynamic consequences, thus modulating nephrotoxicity. Thiosulfates and related agents have received most study. Other agents examined have included calcium channel blockers, bismuth, selenium, glycine, cimetidine, and probenecid.

Acute Kidney Injury↗
PubMed1993

Benzene and its phenolic metabolites produce oxidative DNA damage in HL60 cells in vitro and in the bone marrow in vivo.

Benzene, an important industrial chemical, is myelotoxic and leukemogenic in humans. It is metabolized by cytochrome P450 2E1 to various phenolic metabolites which accumulate in the bone marrow. Bone marrow contains high levels of myeloperoxidase which can catalyze the further metabolism of the phenolic metabolites to reactive free radical species. Redox cycling of these free radical species produces active oxygen. This active oxygen may damage cellular DNA (known as oxidative DNA damage) and induce genotoxic effects. Here we report the induction of oxidative DNA damage by benzene and its phenolic metabolites in HL60 cells in vitro and in the bone marrow of C57BL/6 x C3H F1 mice in vivo utilizing 8-hydroxy-2'-deoxyguanosine as a marker. HL60 cells (a human leukemia cell line) contain high levels of myeloperoxidase and were used as an in vitro model system. Exposure of these cells to phenol, hydroquinone, and 1,2,4-benzenetriol resulted in an increased level of oxidative DNA damage. An increase in oxidative DNA damage was also observed in the mouse bone marrow in vivo 1 h after benzene administration. A dose of 200 mg/kg benzene produced a 5-fold increase in the 8-hydroxydeoxyguanosine level. Combinations of phenol, catechol, and hydroquinone also resulted in significant increases in steady state levels of oxidative DNA damage in the mouse bone marrow but were not effective when administered individually. Administration of 1,2,4-benzenetriol alone did, however, result in a significant increase in oxidative DNA damage. This represents the first direct demonstration of active oxygen production by benzene and its phenolic metabolites in vivo. The conversion of benzene to phenolic metabolites and the subsequent production of oxidative DNA damage may therefore play a role in the benzene-induced genotoxicity, myelotoxicity, and leukemia.

Animals↗
PubMed1993

Sonographic assessment of fetal cardiac arrhythmias.

The fetus with an arrhythmia may be at high risk both from the arrhythmia itself and from the condition that provoked it. Incorrect diagnosis and inappropriate or delayed treatment may further compound the hazard. Although echocardiography can specifically identify the arrhythmia, this technique requires very skilled and careful examination by a physician who fully understands how to differentiate optimally between similar-appearing but mechanistically different arrhythmias. Congenital heart disease may also be present and must be evaluated specifically. This report describes ultrasound recording techniques used to diagnose arrhythmias and includes a discussion of M-mode echocardiography, two-dimensional imaging, pulsed Doppler, and color-flow Doppler. It also differentiates specific arrhythmias--premature atrial contractions, ventricular tachycardia, atrial flutter, complete heart block, and supraventricular tachycardia--and presents the optimal diagnostic tools for each.

Arrhythmias, Cardiac↗