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Biomedical subjects

J Boyer

Publications and source records attributed to J Boyer.

At least 19 recordsLinked to original sources
PubMed1995

Multicentre prospective controlled study of Barrett's oesophagus and colorectal adenomas. Groupe d'Etude de l'Oesophage de Barrett.

Previous studies have suggested that patients with Barrett's oesophagus may be at increased risk of colorectal neoplasia, though the association is disputed. In a multicentre prospective study we compared the prevalence of colorectal adenomas in patients with Barrett's oesophagus and controls. Barrett's oesophagus patients (n = 104) had histological confirmation of columnar epithelium extending more than 3 cm above the gastro-oesophageal junction. The 537 controls were patients with symptoms suggesting irritable bowel syndrome. No participant had a personal history of colonic neoplasm. Each patient underwent colonoscopy. Histologically proven adenomas were found in 26 Barrett's patients (25%) and 75 controls (14%). Three colorectal cancers were discovered in each group. The prevalence of adenomas was greater in the Barrett's oesophagus group than in the control group (p < 0.01) but the relation became non-significant after adjustment for age and sex and control for other known risk factors by a logistic regression model (odds ratio 1.4 [0.7-2.7]). The relative risk of adenoma was significantly higher in patients older than 59 than in younger patients (2.2 [1.3-3.5]) and in men than in women (3.4 [2.0-5.7]). Other factors contributing significantly to the risk of adenoma were a family history of colorectal cancer (2.3 [1.1-4.8]), rectal bleeding (2.1 [1.1-3.9]), previous colonic investigation (0.3 [0.1-0.7]), and complete as opposed to partial colonoscopy (6.4 [0.8-48.3]). We conclude that Barrett's oesophagus is not an independent risk factor for colorectal neoplasia and, therefore, is not, in itself an indication for colorectal screening.

Adenoma↗
PubMed1995

Induction of humoral and cellular immune responses to the human immunodeficiency type 1 virus in nonhuman primates by in vivo DNA inoculation.

DNA inoculation has the potential to produce antigens in a native as well as a host-"customized" form for presentation to the immune system. As such this technology may have relevance for vaccine/immune therapeutic strategies for a variety of infectious pathogens. In rodents in vivo inoculation of plasmid expression vectors encoding HIV-1 gene products leads to production of HIV-1 antigens in vivo, resulting in the production of both cellular and humoral immune responses. In primates only preliminary studies of serology have been reported. Here we report further evaluation of this new technology as a method to induce humoral and particularly cellular immune responses against a human pathogen, the HIV-1 virus, in nonhuman primates. Following inoculation and boosting of animals with an HIV gp160 plasmid expression vector we observed the induction of neutralizing responses against two diverse HIV-1 isolates in 2 of 3 vaccinated animals. T cell proliferative responses to HIV antigens were also observed in all plasmid-inoculated animals and specific cross-reactive cytotoxic T lymphocyte responses were developed in vaccinated animals. This report establishes the ability of DNA inoculation to induce cellular immune responses in nonhuman primates and suggests that further investigation of this technology with regard to human vaccine or immune therapeutic development is therefore warranted.

AIDS Vaccines↗
PubMed1995

Reversible inhibition by ethanol of Mg(2+)-dependent phosphatidate phosphohydrolase: an in vitro study in the rat reticulocyte.

By using a tracer method, we demonstrate that short-term in vitro exposure of intact rat reticulocytes to ethanol elicits a biphasic response of cell-bound Mg(2+)-dependent phosphatidate phosphohydrolase (PAP). An initial concentration-dependent (200-750 mM) activity decrease is rapidly (< 10 min) followed by reversal of the inhibition in the presence of ethanol, suggesting the development of a cell resistance to the inhibitory agent. Addition to the cell suspension of propranolol (100 microM), a known PAP inhibitor, does elicit PAP inhibition but unlike ethanol, inhibition is not followed by a return with time to control value. Ethanol-induced inhibition of cell-bound PAP was also demonstrated in cell-free extracts, where the Mg(2+)-dependent activity was decreased both in the particulate and soluble fractions. In the intact cells, the transient PAP inhibition occurs in concomitance with an overall increase in total glycerolipid biosynthesis, which is constant over 60-min incubation. We suggest that the biphasic mode of response to ethanol of Mg(2+)-dependent PAP activity may play a role in the mechanism of membrane adaptation to ethanol, and thereby to the pathogenesis of alcoholism.

Adaptation, Physiological↗
PubMed1995

Differential in vitro effects of ethanol on glycerolipid acylation and biosynthesis in rat reticulocytes.

Earlier reports have shown that, in human and rat red blood cells (RBC), ethanol modulates acylation reaction sin several membrane glycerolipid components. Little is known, however, about the kinetics and the mechanisms involved in the acylation changes. In the present study, we show that short-term in vitro exposure of intact rat reticulocytes to ethanol differentially modifies within minutes the incorporation of [3H]oleic acid in glycerolipids. A concentration-dependent inhibition of acyl incorporation was measured in phosphatidylcholine (PC) and phosphatidylethanolamine (PE). This effect did not involve inhibition of the corresponding acyltransferase activities and is likely to be due to ethanol-dependent decreases in phospholipase activities. In contrast, ethanol markedly stimulated [3H]oleic acid incorporation in phosphatidic acid (PA), diacylglycerol (DG) and, to a lesser extent, in triacylglycerol (TG). To determine the mechanisms of the latter increases, reticulocytes were pulsed with [14C]glycerol and assayed as a function of time for labeled biosynthetic precursors and products. We observed a very close correlation between time courses and amplitudes of the ethanol stimulation of acylation and biosynthesis reactions, suggesting that stimulation of acylation in PA, DG and TG is causally related at least partly to their increased biosynthesis. Further studies revealed that increases in glycerolipid acylation and biosynthesis in reticulocytes were: (a) readily reversible upon ethanol withdrawal; (b) detectable for clinically relevant concentration (50 mM) of ethanol; and (c) associated with concomitant increases in cell resistance to hemolysis. These changes may be relevant to the development of tolerance to ethanol.

Acylation↗
PubMed1995

Alcohol and injury. A case-crossover study.

OBJECTIVE: To determine whether and to what extent alcohol consumption increases the risk of injury. DESIGN: The case-crossover study is a new research design for assessing rare acute events (such as trauma) in relation to intermittent exposures (such as alcohol use) that have transient effects. All interviewed patients serve as their own controls, and the study design compares exposure during a "case" period, such as the 6 hours prior to injury, with exposure during a "control" period, such as the same 6-hour window on the previous day. SETTING: Emergency centers of a university hospital and a private not-for-profit hospital in a small midwestern city. PATIENTS: Three hundred fifty adults who presented with an injury within 48 hours of the event. DATA COLLECTED: Retrospective self-report of alcohol use in each of the 28 days and each of the 30 hours prior to injury, demographic variables, drug use prior to injury, patients' attributions regarding causes of their injury, and weather factors. RESULTS: Primary analysis was based on pairs of observations that were discordant for alcohol use in the 6 hours prior to injury and the same 6-hour window on the previous day. The odds ratio for one or more standard drinks vs none was 2.5 (95% confidence interval, 1.2 to 5.4); for four or more drinks vs three or fewer, 5.0 (95% confidence interval, 1.4 to 27). CONCLUSION: Alcohol use in the 6 hours prior to injury is associated with an increased risk of injury. The findings are consistent with a dose-response effect, but with this sample size no threshold of risk was found.

Adult↗
PubMed1995

High-affinity interaction of long-chain fatty acids with serum albumin in nephrotic syndrome.

1. We have examined the effect of hypoalbuminaemia, a hallmark of nephrotic syndrome, on the albumin-fatty acid equilibrium in the plasma of 11 adult patients with nephrosis compared with 12 healthy subjects and six subjects with normoalbuminaemic hyperlipoproteinaemia. 2. We used a dialysis exchange rate method which allows the evaluation in relative terms of the binding affinity of albumin for plasma fatty acid and the fatty acid availability, tentatively equated with the unbound fatty acid fraction. 3. In nephrotic patients, an increase (P < 0.001) in albumin affinity for fatty acid was seen compared with healthy subjects, which was negatively correlated with albuminaemia (r = -0.69, P < 0.02). No change in fatty acid availability was seen for the group as a whole, but individual values showed a wide scatter, with the highest values in four patients with the highest fatty acid-albumin molar ratios. The increase in albumin affinity for fatty acid was specific to nephrotic syndrome since no such effect was seen in subjects with hyperlipoproteinaemia, who only showed a moderate increase (P < 0.01) in fatty acid availability. 4. The increased albumin affinity for fatty acid in nephrotic syndrome supports the hypothesis that an albumin component with lower affinity for fatty acid might filter out through the diseased glomerular membrane and leave the high-affinity albumin in plasma.

Adolescent↗
PubMed1995

Antral motility in patients with cirrhosis with or without gastric antral vascular ectasia.

Gastric motility has not been extensively studied in patients with cirrhosis and gastric antral vascular ectasia (GAVE) may be associated with antropyloric dysfunction. This study therefore looked at antral motility using ultrasound in patients with alcoholic cirrhosis with or without GAVE. Twenty six patients were included: 10 patients with cirrhosis without GAVE, eight patients with cirrhosis and GAVE, and eight controls without liver disease. Measurement of antral area and antral contractions (amplitude and frequency) was performed for three hours after ingestion of a standardised solid-liquid meal. Antral area half time (mean (SD)) was not significantly increased in patients with cirrhosis without GAVE (84 (42) min), but increased by 120% (123 (43) min; p < 0.01) in patients with GAVE compared with controls (56 (26) min). GAVE patients exhibited the same frequency and amplitude of antral contractions at each time point as controls and had the same tendency to increase these values over time although this was attenuated in the late postprandial phase. In contrast, cirrhotic patients without GAVE exhibited a significantly higher frequency and amplitude of antral contractions during the initial postprandial phase but showed no change in either frequency or amplitude over time. In conclusion, in cirrhosis there is an abnormal antral motor response to a meal, which has a different pattern over time in patients with or without GAVE.

Aged↗
PubMed1995

[Evaluation of the teaching of echo-endoscopy. Application to the assessment of invasiveness of cancer of the esophagus and the cardia].

OBJECTIVES: Learning endosonography (EES) is known to be difficult, and the theory must be understood before performing EES routinely. The aim of the study was to evaluate the diagnostic indexes of EES in the staging of cardio-oesophageal cancer after a period of theoretical apprenticeship of EES and a learning period in a centre experienced in EES since 1989. METHODS: Five observers, having never used EES, followed to EES examinations for a 3-6 month period. They then reviewed the standardized records of 29 patients with cardio-oesophageal cancer. They had to evaluate the degree of tumour infiltration within oesophageal wall and the site of metastatic lymph nodes. Results were compared with the diagnosis of 5 experienced senior endoscopists. Interobserver agreement was estimated with kappa statistics and considered excellent for k > or = 0.75, good to moderate if 0.75 > k > or = 0.40, and poor if k < 0.40. RESULTS: Inter-observer agreement was poor for the topographic diagnosis of lymph nodes (kappa index from -0.09 to 0.33), lower to that of the 5 senior observers (0.33 to 0.77). It was satisfactory for degree of tumour infiltration (T1: k = 0.66; T2: k = 0.58; T3: k = 0.56; T4: k = 0.46). The individual sensitivities were weak according to lymph nodes site, but good for presence of lymph nodes (86 to 100%), with a specificity of 40 to 73%. CONCLUSIONS: After theoretical training of EES, agreement and diagnostic performances are good enough to diagnose pathological images (except for T4 tumors), and poor for localizing images in the mediastinum. This emphasizes the difficulties in learning echo-anatomy and gives useful guidelines for training programs in EES.

Cardia↗
PubMed1994

Complete DNA sequence of yeast chromosome XI.

The complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome XI has been determined. In addition to a compact arrangement of potential protein coding sequences, the 666,448-base-pair sequence has revealed general chromosome patterns; in particular, alternating regional variations in average base composition correlate with variations in local gene density along the chromosome. Significant discrepancies with the previously published genetic map demonstrate the need for using independent physical mapping criteria.

Base Sequence↗
PubMed1994

DNA inoculation as a novel vaccination method against human retroviruses with rheumatic disease associations.

There are a number of rheumatologic manifestations of human retroviral infections associated with human immunodeficiency virus type I (HIV-I) and the human T-cell leukemia virus type I (HTLV-I) including arthritis, Sjøgren's syndrome-like symptoms as well as other varied autoimmune phenomena. Infection with HTLV-1 may be directly involved in the etiology and/or pathogenesis of an arthritic condition similar to rheumatoid arthritis. We have been characterizing a new vaccination strategy against human retroviral infections, designated DNA inoculation. This procedure involves the intramuscular injection of DNA plasmids which express specific human retroviral antigens. This technique results in the development of humoral and cellular immune responses against these proteins. Specifically, this method has been successfully used to develop immune responses against HIV-I and HTLV-I. The availability of rat and rabbit infection models for HTLV-I, coupled with the successful development of immune responses in these animals after DNA inoculation with an HTLV-I envelope expressing plasmid, will allow the efficacy of this vaccination technique to be evaluated with protection against in vivo viral challenge as an endpoint.

Animals↗
PubMed1994

Triacylglycerol in biomembranes.

A better knowledge of the biochemical and biophysical properties of cell membranes has revealed fundamental concepts concerning the regulation of cell functions by intrinsic components of the lipid matrix. Membrane lipids exhibit high chemical heterogeneity, with hundreds of distinct chemical species; studies of structure-function relationships have unraveled new roles for an increasing number of these lipids as determinants of membrane structure, anchors for membrane-associated proteins or signalling agents. Recent observations have confirmed triacylglycerol (TG) as a quantitatively minor intrinsic membrane component which seems to play a specific role in important metabolic events such as cell stimulation or transformation and metastatic processes. The rapid turnover of the acyl chains into TG of cell membranes suggests an active metabolism. In the plasma membrane, TG appears to be implicated in the generation of transient non-bilayer domains suspected to be associated with specific cellular events. This paper summarizes the current information on TG metabolism and focuses on the potential role of this neutral lipid species on the structure and function of cell membranes.

Animals↗
PubMed1994

Facilitated DNA inoculation induces anti-HIV-1 immunity in vivo.

Vaccine design against HIV-1 is complicated both by the latent aspects of lentiviral infection and the diversity of the virus. The type of vaccine approach used is therefore likely to be critically important. In general, vaccination strategies have relied on the use of live attenuated material or inactivated/subunit preparations as specific immunogens. Each of these methodologies has advantages and disadvantages in terms of the elicitation of broad cellular and humoral immune responses. Although most success has been achieved with live attenuated vaccines, there is a conceptual safety concern associated with the use of these vaccines for the prevention of human infections. In contrast, subunit or killed vaccine preparations enjoy advantages in preparation and conceptual safety; however, their ability to elicit broad immunity is more limited. In theory, inoculation of a plasmid DNA that supports in vivo expression of proteins, and therefore presentation of the processed protein antigen to the immune system, could be used to combine the features of a subunit vaccine and a live attenuated vaccine. We have designed a strategy for intramuscular DNA inoculation to elicit humoral and cellular immune responses against expressed HIV antigens. Uptake and expression are significantly enhanced if DNA is administered in conjunction with the facilitating agent bupivacaine-HCl. Using this technique we have demonstrated functional cellular and humoral immune responses against the majority of HIV-1 encoded antigens in both rodents and non-human primates.

AIDS Vaccines↗
PubMed1994

Bioactive Arg-Gly-Asp conformations in anti-integrin GPIIb-IIIa antibodies.

Antibodies can mimic the biological function of physiological ligands, yet few examples indicate the structural similarity between antibodies and the ligands that they mimic. Originally, the competition of antibodies for ligand binding sites was conjectured to be through similar three-dimensional conformations, which represent the "internal image" of the given ligand. Here we show that residues in a complementary determining region (CDR) can adopt the same bioactive structures observed in ligands. Structure-function studies of three anti-GPIIb-IIIa murine monoclonal antibodies, PAC-1, LJ-CP3, and OP-G2, indicate that the RYD sequence in their H-CDR3 domain occupies the same conformational space as RGD in conformationally constrained, bioactive, GPIIb-IIIa cell-surface adhesion ligands. The relative location of the guanidinium and carboxylate groups in the RXD regions is identified as an important recognition feature, and the conformational space occupied by this region in the antibodies is only slightly larger than that in the most bioactive peptides. Additionally, we show that antibodies can unveil other potential bioactive sequences, which may impart specificity. Thus antibodies are an exquisite probe for identifying motifs of short adhesion stretches, thereby revealing amino acid sequences and restricted geometries that might be used as lead compounds in drug design.

Amino Acid Sequence↗
PubMed1994

DNA inoculation induces protective in vivo immune responses against cellular challenge with HIV-1 antigen-expressing cells.

Direct DNA inoculation induces immune responses through the delivery of nonreplicating transcription units that drive the synthesis of specific foreign proteins within the inoculated host. These proteins are processed within host cells and through association with relevant MHC antigens that can become the subject of immune surveillance and elicit immune responses against pathogens. Direct introduction of DNA into mice has been reported to be antigenic as demonstrated by the use of this technique to develop immune responses against human growth hormone, influenza proteins, as well as HIV-1 proteins. Most recently the demonstration of the use of this technology to produce anti-HIV-1 immune responses has been reported in nonhuman primates. Accordingly a more detailed analysis of this technology could generate important insight into the generality of this approach for immune therapy or vaccine design. In this article we further our investigation of direct DNA inoculation as a tool for induction of relevant immune responses against HIV-1 in vivo. We demonstrate expression of HIV-1 antigens in the inoculated muscle of animals. Inoculated animals demonstrate significant cytotoxic T cell responses against HIV-1 antigen-expressing targets. Furthermore, using a novel challenge system, we demonstrate that the majority of immunized animals can reject lethal, HIV-1 antigen-expressing cell challenge in an antigen-specific manner. This technology has relevance for the development of immunization strategies against HIV as it provides for specific antigen production in vivo without the use of infectious agents.

AIDS Vaccines↗