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Biomedical subjects

D Meyer

Publications and source records attributed to D Meyer.

At least 145 records · Page 8Linked to original sources
PubMed1999

Therapeutic monitoring of von Willebrand disease: interest and limits of a platelet function analyser at high shear rates.

We have evaluated the position of the Platelet Function Analyzer PFA-100TM in the management of 41 patients with von Willebrand disease (VWD) receiving either desmopressin (23 patients with type 1, five with type 2M, three with type 2A and three with type 2B) or von Willebrand factor (VWF) concentrates (four patients with type 3, two with type 2M 'type B', two with type 2A and one type 1 'platelet low'). In all patients the following were studied before and 30 min after infusion of desmopressin and/or VWF concentrates: VWF ristocetin cofactor activity (VWFRCo), bleeding time (BT) and closure time with the PFA-100 using ADP (CT-ADP) as well as epinephrine (CT-Epi) cartridges. After the infusion of desmopressin, the CT was modified in the same way as the VWFRCo levels, being always normalized in patients with type 1 and not constantly corrected in those with type 2. Thus, our results indicated that the measurement of the CT enabled a quick and accurate evaluation of the response to desmopressin which, in fact, measured the releasable VWF cellular compartment containing the highly multimerized forms of VWF. For patients with type 2 or 3 VWD who were non-responsive to desmopressin, VWF concentrates corrected the VWFRCo defect but not the CT as none of these patients had a normal platelet VWF content and the VWF concentrates did not contain the ultralarge VWF multimers. In conclusion, the very high shear conditions in the PFA-100 make it very sensitive to the contribution of platelet VWF and to the ultralarge VWF multimers, indicating that the evaluation of the CT is a very simple and rapid tool to discriminate between good and non-responders to desmopressin.

Adolescent↗
PubMed1999

Locus and population specific evolution in HLA class II genes.

The population genetics of the HLA class II loci was studied with reference to variation in the frequency of (a) alleles at a locus and (b) amino acids at specific sites. Variation was surveyed at 4 loci (DRB1, DQA1, DQB1, and DPB1) in 22 populations from the Twelfth International Histocompatibility Workshop (Saint-Malo, 1996). Allele and amino acid variation was measured by computing heterozygosity and the effective number of alleles. Substantial variations in polymorphism were observed among the various populations and loci studied. In the majority of the populations, DRB1 has the highest heterozygosity and effective number of alleles. As previously shown, the Amerindian populations have lower levels of allelic diversity when compared to other populations. At the amino acid level, DRB1 antigen recognition sites (ARS) have the highest heterozygosities and effective number of alleles. For the other loci (DPB1, DQA1, and DQB1) for which there is no crystal structure and for which ARS sites were inferred from DRB1, non-ARS sites were often among the sites with highest levels of variation. It is possible that these putative non-ARS sites do play a role in antigen presentation. The homozygosity test for neutrality was applied to allele and amino acid data. Of the four HLA class II loci studied, only DPB1 failed to show evidence of balancing selection. DQB1 and DQA1 depart significantly from neutrality in the largest number of populations. Genetic distances between populations were computed based on frequency of alleles and amino acids at ARS sites.

Alleles↗
PubMed1999

The function of PTB domain proteins.

Phosphotyrosine binding (PTB) domains have been identified in a large number of proteins. In proteins like Shc and IRS-1, the PTB domain binds in a phosphotyrosine-dependent fashion to peptides that form a b turn. In these proteins, PTB domains play an important role in signal transduction by growth factor receptors. However, in several other proteins, the PTB domains have been found to participate in phosphotyrosine-independent interactions. The X11 family of proteins contains a PTB domain that binds peptides in a phosphotyrosine-independent fashion. The homologue of X11 in C. elegans is the lin-10 gene, a gene crucial for receptor targeting to the basolateral surface of body wall epithelia. The X11/Lin-10 proteins are found in a complex with two other proteins, Lin-2 and Lin-7, which have also been implicated in basolateral targeting in worm epithelia. This protein complex is also likely to be important in the targeting of cell surface proteins in mammalian neurons and epithelia. The ability of the PTB domain to bind peptides in a phosphotyrosine-dependent and -independent fashion allows this domain to be involved in diverse cellular functions.

Animals↗
PubMed1999

Photoablation of meningiomas and neurinomas by Holmium Yag laser radiation.

Cranial rat bone was irradiated by 2.1 microns Holmium Yag laser radiation. Quantitative edge rates were calculated. Histologic sections were investigated by light and electron microscopy. Eighteen cases of hard fibrous or calcified spinal and cranial meningiomas and neurinomas were operated upon using pulsed laser beam. In rat cranial bone ablation rate ranged between 0.3-0.5 mm per pulse. Perifocal thermal damage was observed in a zone of 20-90 microns around the lesion. In all human cases tumors could be removed totally without additional neurological deficit. In vivo heat development was measured by an i.r.-camera.

Animals↗
PubMed1999

Induction of cytotoxic and helper T cell responses by modified simian immunodeficiency virus hypervariable epitope constructs.

We previously reported the broad humoral immunogenicity of peptides synthesized according to the cumulative variability of an epitope (1,16). These peptides, hypervariable epitope constructs (HECs), are designed to represent the envelope glycoproteins of several isolates of the simian immunodeficiency virus (SIV). When HEC peptides were conjugated to palmitic acid and palmitic acid ester (lipoHECs), they promoted the induction of cellular immune responses. SIV envelope lipoHEC immunization of BALB/c and ICR mice resulted in up to 80% cytotoxic T lymphocyte (CTL) lysis of SIV envelope-expressing target cells and SIV envelope-specific delayed type hypersensitivity (DTH). This DTH response was significantly higher than that of single peptide controls, and the response peaked at 24 hours. Strong SIV envelope-specific T-cell proliferative responses were also induced in mice with stimulation indexes higher than 20 for spleen cells and higher than 10 for lymph node cells. Overall, our results demonstrate that conjugation of these variable synthetic peptides to a lipid moiety results in an immunogen capable of inducing strong and cross-reactive cellular immune responses.

Amino Acid Sequence↗
PubMed1999

Implementation of outreach telephone counseling to promote mammography participation.

To increase mammography participation, the authors implemented an outreach intervention translating concepts from expectancy value theory into a motivational interviewing telephone intervention that included the opportunity to schedule a screening appointment. Process data are presented from 491 women who had not scheduled a mammogram within 2 months of receiving a mailed invitation from a managed care organization's centralized breast cancer screening program. A total of 83% of targeted women accepted the counseling calls. Counselors rated 84% of completed calls as either receptive or neutral in tone. Women with prior mammography experience were more likely to be receptive and to schedule a screening appointment during the calls than were women with no prior experience. Topics discussed during the calls also differed between women with and without prior mammography experience. Implications for dissemination of counseling interventions in health care organizations are discussed.

Aged↗
PubMed1999

Placebo-controlled trial of 13-cis-retinoic acid activity on retinoic acid receptor-beta expression in a population at high risk: implications for chemoprevention of lung cancer.

PURPOSE: To establish the incidence of abnormalities in the expression of retinoic acid receptor-beta (RARbeta) in bronchial cells and determine the capacity of 13-cis-retinoic acid (13-CRA) to correct such abnormalities. PATIENTS AND METHODS: One hundred eighty-eight smokers had a medical indication for bronchoscopy and were studied with bronchial brushings. Bronchial brushing samples were obtained for cytology analysis and for molecular analysis. After RNA was extracted, RARbeta sequences were amplified by reverse transcriptase polymerase chain reaction and Southern blots were performed to assess RARbeta expression. Forty-four eligible individuals with diminished RARbeta expression consented to double-blind randomization to receive a placebo or 13-CRA 30 mg orally daily for 6 months. A second bronchoscopy was performed at the end of the treatment period. An analysis of variance was used to analyze changes in RARbeta expression before and after treatment. RESULTS: The 6-month treatment course was completed by 27 patients, and results were obtained for a total of 18 patients (eight patients treated with 13-CRA and ten treated with the placebo). In the placebo group, there was no difference between the results of RARbeta expression before and after treatment (P =.43). In the 13-CRA group, there was an upregulation of RARbeta expression at the end of 13-CRA treatment (P =.001). Cytologic changes were uncommon. Toxicities were primarily of grade 1. Palatal brushings were compared with bronchial brushings in 40 smokers. A perfect correlation of the results of RARbeta expression was obtained from 27 patients. CONCLUSION: RARbeta expression is frequently decreased in the bronchial epithelium of smokers and is upregulated at the end of 13-CRA treatment. These results support undertaking a phase III chemoprevention trial of 13-CRA treatment for lung cancer.

Analysis of Variance↗
PubMed1999

Livestock nutrient management concerns: regulatory and legislative overview.

A greater focus on manure nutrient disposition from concentrated animal-feeding operations has developed from environmentalists, concerned citizens, and regulatory agencies. The establishment and enforcement of manure nutrient regulations will alter the future of livestock production. Proposed legislation and strategies may provide a false sense of security regarding environmental preservation or restoration and may impose monitoring and record keeping on the livestock operators. Existing regulations and proposed regulations and strategies are presented. Implications of legislation and proposed strategies, policies, and regulations are discussed. Livestock operations will need to comply with regulations to remain in business and to minimize environmental liability.

Agriculture↗
PubMed1999

Effects of dietary nitrogen manipulation on ammonia volatilization from manure from Holstein heifers.

Decomposition of livestock manure produces gaseous ammonia. Dietary manipulation is one means to reduce N in manure and ammonia volatilization. The effects of dietary crude protein concentration on N intake, N and urinary urea-N excretion, and ammonia volatilization were measured. Eight Holstein heifers (body weight = 260 to 488 kg) were fed a total mixed ration containing either 9.6 or 11.0% crude protein in a crossover design. Oatlage and concentrate were fed at 77:23 (dry matter basis), and soybean meal was used to alter total dietary crude protein. Seven-day adjustment periods preceded 5-d collection periods. Indwelling urinary catheters were inserted 2 d prior to the collection periods. Daily feces and acidified urine were collected, stirred, and subsampled for total Kjeldahl N, urinary urea N, dry matter, P, K, and ash. Urine collection tubes were split during period 2 to allow for collection of unacidified samples for urea N and total N determinations. Unacidified urine and fecal samples were combined (1:1.3) for collection of volatilized ammonia. Remaining slurries were extracted for total and urea N. Increased dietary crude protein concentration increased N intake, N excretion, urea-N excretion, and N excreted in the urine by the heifers. Dietary manipulation of N intake by reduction of 14.0% (dry matter basis) resulted in a 28.1% decrease in ammonia emission and decreases in the urea N, total N, and percentage N excreted in the urine of 29.6, 19.8, and 7.4%, respectively. Ammonia volatilization was dependent on N quantity and form in the urine.

Ammonia↗
PubMed1999

New assay for measuring binding of platelet glycoprotein IIb/IIIa to unpurified von Willebrand factor.

Among the numerous variants of vWD, no patient with an abnormal vWF binding to GPIIb/IIIa has been described to date. To search for such potential variants, we developed a two-site assay for measuring the binding of purified GPIIb/IIIa to vWF in biological fluids and we used it to study a large series of plasmas from various types of von Willebrand disease (vWD) and recombinant vWF (rvWF). vWF in plasma or rvWF in culture medium was immobilized onto anti-vWF monoclonal antibodies (MoAb)-coated wells of microtiter plates. After incubation with either unlabeled GPIIb/IIIa and a 125I-anti-GPIIb/IIIa MoAb or 125I-GPIIb/IIIa, binding curves and binding isotherms were respectively established. Normal pool plasma and wild-type rvWF were used as reference samples. We tested plasmas from 85 normal subjects, 115 patients with different types of vWD (64 type 1, 2 type 3, 9 type 2A, 4 type 2M, 16 type 2B, 15 type 2N, 3 type IID and 2 acquired forms) and 50 patients with various bleeding disorders. Four mutated rvWF with 2A (Glu875Lys and Pro885Ser) or 2B (Dupl.Met540 and Val551Phe) substitutions and one rvWF mutated in the RGD domain of the C-terminal part of vWF-subunit (Asp1746Gly) were also studied. Among the various samples tested, only rvWF Asp1746Gly had no affinity for GPIIb/IIIa. In contrast, GPIIb/IIIa similarly bound to the other vWF, independently of the proteic environment, the factor VIII level, the degree of multimerization or the mutation of vWF. Our results indicate that subjects with an abnormal vWF binding to GPIIb/IIIa are probably rare and difficult to target for a specific screening.

Biological Assay↗
PubMed1999

Estimation of the von Willebrand factor-cleaving protease in plasma using monoclonal antibodies to vWF.

A protease present in plasma cleaves von Willebrand factor (vWF) at the peptide bond 842Tyr-843Met of the mature subunit. To quantify this vWF-cleaving protease activity in plasma we have developed a simple method based on the estimation by IRMA of the degradation of a constant amount of wild type recombinant vWF used as substrate, by serial dilutions of test plasma used as protease provider. vWFAg was estimated by two-site IRMA using as first coating antibody a monoclonal antibody (MoAb) whose epitope is localized on the C-terminal side of the cleavage site, and as second labeled antibody a pool of MoAbs specific for the N-terminal side. Because the proteolytic process leads to the progressive separation of the C- and N-terminal portions of the vWF subunit such an IRMA also shows a progressive apparent loss of vWFAg. In contrast, the levels of vWFAg estimated after proteolysis by regular IRMA remained essentially constant. Results obtained with this new method were compared with the analysis by SDS-agarose gel electrophoresis of the multimeric pattern of proteolyzed WT-rvWF and no significant difference was noted testing a series of 28 plasmas. As compared with normal pooled plasma, 14 normal individuals and 13 patients with various types of vWD had normal levels of protease activity (44-178%) by both methods. The validity of the method was confirmed by showing a lack of detectable protease activity in a patient with chronic relapsing thrombotic thrombocytopenic purpura. In conclusion our method appears as a useful tool for the quantification of the vWF-cleaving protease activity in plasma. Its sensitivity and specificity are similar to those of SDS-gel electrophoresis. However, this new IRMA has the major advantages of being much simpler and faster, and open to most research laboratories in the field.

ADAM Proteins↗
PubMed1999

[Inhibition of thrombus formation by anti-Willebrand monoclonal antibodies in the guinea pig].

To experimentally evaluate the role of von Willebrand factor in thrombosis, a monoclonal antibody-712-, directed against the binding domain of von Willebrand factor to the platelet glycoprotein Ib and a control antibody D4H1, directed against the light chain of Factor VII C, were injected into guinea pigs. A model of experimental thrombosis induced by laser in guinea pig mesenteric arteries was used. The antibody 712 induced a dose-dependent reduction of the thrombus formation without affecting the bleeding time and the platelet number. Ex vivo, the ristocetin-induced platelet aggregation was inhibited by the antibody 712 in a dose-dependent manner while the adenosine diphosphate-induced platelet aggregation was not modified. In conclusion, this study showed that antibody-712- has a significant antithrombotic activity without inducing a hemorrhagic state, suggesting that the von Willebrand factor--glycoprotein Ib axis was a promising target for the strategy of a new antithrombotic therapy.

Animals↗
PubMed1998

Apoptosis of T lymphocytes in liver and/or small bowel allografts during tolerance induction.

BACKGROUND: Apoptosis of parenchymal cells has been described during allograft rejection. Immunologically privileged tissue in the mouse has been found to prevent rejection by initiating apoptosis of infiltrating lymphocytes. The aim of this study was to investigate whether apoptosis may play a role in T-cell regulation during rejection and subsequent tolerance induction after liver transplantation (LTx) and combined liver/small bowel transplantation (LSBTx). METHODS: LTx and LSBTx (Brown Norway-->Lewis) were performed without immunosuppression. Cell migration, activation, and apoptosis were investigated by means of sequential histology, immunohistochemistry, and the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling assay. Donor (Brown Norway) and third-party (Dark Agouti) cardiac allografts were transplanted into LSBTx recipients to determine specific tolerance. RESULTS: Transient acute cellular rejection occurred after LTx and LSBTx and was followed by specific tolerance. The kinetics of apoptosis were similar in liver allografts after LTx and LSBTx, but differed from the processes in small bowel allografts after LSBTx. Apoptosis of parenchymal cells in the grafted livers correlated directly with interleukin-2 receptor expression of the infiltrating T cells. During the late phase of rejection, a peak of apoptosis in the lymphocyte infiltrate was demonstrated, characterized as predominantly apoptotic CD8+ T lymphocytes. CONCLUSIONS: These results demonstrate that specific tolerance is achieved in both LTx and LSBTx after a transient rejection crisis. Apoptosis is involved in graft rejection and tolerance induction. Activation of T lymphocytes correlates with parenchymal cell apoptosis in the allograft. T-cell inactivation seems to result in apoptosis of cytotoxic T cells and tolerance, which appears to be unique to the liver allograft.

Animals↗
PubMed1998

Centrally applied NPY mimics immunoactivation induced by non-analgesic doses of met-enkephalin.

Neuropeptide Y (NPY) and endogenous opioids (EOPs) such as methionine-enkephalin (Met-enk) regulate similar physiological responses, but it is not known whether nociceptive and immune responses also show analogy after intracerebroventricular (i.c.v.) application. Dose-response studies show that Met-enk stimulates the blood granulocyte and splenic natural killer (NK) cell function of Lewis rats at a low dose (10(2) ng/kg, i.c.v.), whereas a high dose (10(5) ng/kg) causes suppression of innate immune functions associated with analgesia in the hot-plate test. At 15 min, 1 h and 24 h after i.c.v. application, both Met-enk (10(2) ng/kg) and NPY (1 ng/kg) produced similar effects: An initial suppression of innate immune function was followed by a long lasting stimulatory action on cell functions and serum interleukin-6 (sIL-6) levels. Thus, central NPY application resembles Met-enk-induced immunostimulation at doses not affecting nociception, suggesting an involvement of both peptides in shaping stress-induced immunomodulation of the non-analgetic form, possibly via activation of a common immunomodulatory effector mechanism.

Adjuvants, Immunologic↗