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Biomedical subjects

E Meyer

Publications and source records attributed to E Meyer.

At least 163 records · Page 9Linked to original sources
PubMed1992

The differential expression of the G surface antigen alleles in Paramecium primaurelia heterozygous cells correlates to macronuclear DNA rearrangement.

The Paramecium primaurelia cell surface is covered with a high molecular weight protein called the surface antigen. Several genes encode alternative surface antigens, but only one is expressed at a time. In addition, each of these genes shows a high degree of allelic polymorphism. Paramecium primaurelia strains 156 and 168 have different alleles of the G antigen gene whose respective antigens can be distinguished in vivo using specific antibodies. An interallelic exclusion phenomenon has been previously described: 94% of the 156/168 heterozygotes express only the 156 allele of the G gene; 6% express both the 156 and the 168 alleles. The phenotype of the heterozygotes is determined at the time of macronuclear differentiation. We have investigated the molecular basis for the different heterozygous phenotypes. Both mRNAs are always produced, and the 156 mRNA is always more abundant than the 168 mRNA. The relative amounts of these messages, however, vary greatly between different heterozygotes and parallel their phenotype. Pushing the analysis further, we show that the copy number of each allele in the macronucleus correlates with the relative amounts of the mRNAs. However, allelic dosage alone is not sufficient to explain the variations of the mRNA ratio. The G antigen gene is located near a telomere in the macronucleus. We show that the distance between the 156G gene and the telomere is different in homozygotes and heterozygotes. It also varies among heterozygotes and is correlated with the mRNA ratio. Thus, we have identified two different parameters, both linked to the genome rearrangements occurring during macronuclear differentiation, that correlate with the relative expression of the two alleles. Two hypotheses concerning the influence of the telomere position on the expression of the gene are discussed.

Alleles↗
PubMed1992

Internal water molecules and H-bonding in biological macromolecules: a review of structural features with functional implications.

Conserved structural patterns of internal water molecules and/or H-bond chains were observed and are here correlated in this review, which then describes two functional properties: equilibration of hydrostatic pressure and proton transport. Available evidence in support of these hypotheses is presented, together with suggested experiments to test them. High-resolution crystal structures of a variety of proteins were studied with interactive computer graphics. Conserved H-bonding linkages may be used as a paradigm for a rationalization of proton transport in membranes. The concept of the "proton wire," which links buried active-site amino acids with the surface of the protein raises the more general question of the functional role of the various molecular components.

Amino Acid Sequence↗
PubMed1992

Identification of anti-CD3 antibodies that do not modulate antigen but induce mitogenesis and block the mixed lymphocyte reaction.

Using a panel of anti-CD3-TCR monoclonal antibodies (OKT3 A-E), it appears possible to separate the ability to cause surface antigen modulation from inhibition of MLR or induction of mitosis. OKT3D, an antibody that recognizes the CD3 antigen at a site that can be differentiated from the epitopes recognized by other members of this panel by competition binding, does not cause antigen modulation when incubated with human T cells for up to 3 days. Despite this, OKT3D is mitogenic and is capable of blocking MLR. Two different isotypes were produced from the OKT3D clone, IgG1 and IgG2b. The IgG2b isotype of OKT3D blocked MLR even in individuals unable to respond mitogenically to this antibody. Use of members of this panel may now permit dissection of the types of signals delivered by the CD3-TCR complex inducing mitosis, receptor modulation, and other T-cell responses.

Animals↗
PubMed1992

Anatomical mapping of functional activation in stereotactic coordinate space.

Numerous applications have been reported for the stereotactic mapping of focal changes in cerebral blood flow during sensory and cognitive activation as measured with positron emission tomography (PET) subtraction images. Since these images lack significant anatomical information, analysis of these kinds of data has been restricted to an automated search for peaks in the PET subtraction dataset and localization of the peak coordinates within a standardized stereotactic atlas. This method is designed to identify isolated foci with dimensions smaller than the image resolution. Details of activation patterns that may extend over finite distances, following the underlying anatomical structures, will not be apparent. We describe the combined mapping into stereotactic coordinate space of magnetic resonance imaging (MRI) and PET information from each of a set of subjects such that the major features of the activation pattern, particularly extended tracts of increased blood flow, can be immediately assessed within their true anatomical context as opposed to that presumed using a standard atlas alone. Near areas of high anatomical variability, e.g., central sulcus, or of sharp curvature, e.g., frontal and temporal poles, this information can be essential to the localization of a focus to the correct gyrus or for the rejection of extracerebral peaks. It also allows for the removal from further analysis of data from cognitively-normal subjects with abnormal anatomy such as enlarged ventricles. In patients with neuropathology, e.g., Alzheimer's disease, arteriovenous malformation, stroke, or neoplasm, the use of correlated MRI is mandatory for correct localization of functional activation.

Adult↗
PubMed1992

Density of perfused capillaries in living human brain during functional activation.

Recent evidence has indicated that functional activation of cerebral cortex is accompanied by increases of blood flow and glucose consumption but not oxygen consumption. No explanation has been advanced for this change of the flow-metabolism couple. We formulated the hypothesis that oxygen delivery to brain tissue is diffusion-limited by the enormous hemoglobin binding, and rate-limiting for the oxygen consumption of the tissue. One prediction of this hypothesis is very low oxygen tensions in the tissue. A second prediction is the inability of oxygen consumption to increase during functional activation in the absence of recruitment of capillaries for the oxygen diffusion capacity. We designed a study to test the latter prediction by calculating the density of functioning capillaries during vibrotactile stimulation of the parietal cortex. We defined functioning capillaries as capillaries that transport glucose and therefore calculated the capillary density from the glucose diffusion capacity (K1) of the cerebral capillaries. We confirmed the presence of a partial flow-CMRglc couple (2:1) during the functional activation. Oxygen consumption did not change despite an increase of capillary density in proportion to the change of blood flow.

Brain↗
PubMed1992

Pharmacokinetics and drug interactions of etretinate and acitretin.

Acitretin, the metabolite of etretinate, is eliminated far more rapidly from the human body than is etretinate. It had therefore been suggested that only a short period of contraception would be required after the cessation of long-term therapy with acitretin. However, recent studies have demonstrated the presence of etretinate in the plasma of patients who were treated with acitretin. In this article we provide results from a study in our center and discuss earlier data in light of the recently discovered metabolic pathways for acitretin. Reesterification of acitretin to etretinate, however, results in a loss of the metabolic advantages of acitretin. Because of this situation the recommended contraception period after acitretin therapy has been lengthened to 2 years.

Acitretin↗
PubMed1992

Oxygen consumption of the living human brain measured after a single inhalation of positron emitting oxygen.

We measured the rate of washout of 15O-labeled water generated from labeled oxygen accumulated in brain after bolus [15O]O2 inhalation, and compared the washout with that of labeled water measured with H215O. Contrary to the original expectation, the radioactive water generated from labeled oxygen failed to leave the brain tissue at the rate predicted by exogenous water. Therefore, the use of a separately measured value for exogenous water clearance led to an error in the calculation of oxygen consumption. A new method presented in this paper eliminated the error by yielding oxygen consumption in a single oxygen study. We used time-weighted integration to estimate three parameters, including the unidirectional clearance from blood to brain (KO2(1)), the fractional clearance of the distribution volume in brain (kO2(2)), and the vascular volume correction (VO). We showed that the clearance of oxygen from blood to brain can be estimated with acceptable precision by this new approach, and that the new method yields a reliable measure of oxygen consumption.

Administration, Inhalation↗
PubMed1992

Induction of specific macronuclear developmental mutations by microinjection of a cloned telomeric gene in Paramecium primaurelia.

In Paramecium, the differentiation of a highly polyploid macronucleus from a diploid nucleus is accompanied by an extensive reorganization of the genome, involving reduction in chromosome size and formation of new telomeres at heterogeneous, but reproducible, positions. The results presented here, as well as work by others, indicate that telomere addition regions are not strictly determined by the micronuclear sequence, but are at least partially controlled by the old macronucleus. It is shown that microinjecting a high copy number of a plasmid containing the G surface antigen gene into the macronucleus of wild-type cells specifically modifies the processing of the G gene-bearing micronuclear chromosome at the following autogamy. Telomeric repeats are added upstream of the gene, rather than at their wild-type position 5 kb downstream of its 3' end, resulting in the deletion of the gene from the new macronucleus. This macronuclear mutation is unstable at the following autogamy, giving rise to many different telomere addition regions in different postautogamous clones. However, after several successive autogamies, cell lines can be obtained in which the telomeres reproducibly form in the same region. In crosses with wild-type cells, these macronuclear mutations show cytoplasmic inheritance; the micronuclei of the mutants are shown to be fully functional. The implications for the mechanism of choice of telomere addition sites are discussed.

Animals↗
PubMed1992

The distribution of cis- and trans-acitretin in human epidermis.

The concentrations of trans-acitretin and its principal metabolite, cis-acitretin, were measured by h.p.l.c. after single and multiple dosing (50 mg orally for 13 days) in plasma, blister fluid and epidermal samples from four healthy male volunteers. Within-day epidermal concentrations of trans-acitretin exceeded those of the cis-form which were at the limit of assay sensitivity. No accumulation of trans-acitretin was observed in plasma or blister fluid but AUC values for the drug in blister roof cells tended to be higher after multiple dosing.

Acitretin↗
PubMed1992

Sensitivity of different areas of the flexor aspect of the human forearm to corticosteroid-induced skin blanching.

The intensity of corticosteroid-induced blanching has been found to vary at different areas of the flexor aspect of the human forearm. A retrospective analysis of 38,880 observations of skin blanching in 56 volunteers was conducted to assess the sensitivity of forearm skin to betamethasone 17-valerate. The mid-forearm appears to be more sensitive to the blanching response than do the areas close to the wrist or elbow. These results indicate that each preparation under evaluation should be applied to several sites along the forearm when using the human skin blanching assay in order to obtain an accurate comparative assessment of corticosteroid release from topical delivery vehicles.

Administration, Topical↗
PubMed1992

Connective tissue of the orbital cavity in retinal detachment: an ultrastructural study.

The connective tissue from Tenon's capsule of 7 patients who underwent surgery for retinal detachment was studied ultrastructurally. Five patients were 58-70 years old, and 2 were young adults. The Tenon capsules of 6 children and of 2 aged patients without retinal problems were used as controls. In young controls the Tenon capsule was composed mainly of round, smooth collagen fibrils and a few elastic fibers. The collagen fibrils varied in size from 70 to 110 nm. In the aged patients with retinal detachment, the collagen fibrils showed marked variation of size and also abnormalities of shape in 4 out of 5 cases. The diameter of collagen fibrils varied from 32 to 160 nm, and the elastic fibers were fewer as compared with controls. The possibility arises that age-related structural changes of the orbital connective tissue could predispose to retinal detachment.

Adult↗
PubMed1992

Language localization with activation positron emission tomography scanning.

We report the first instance of the use of 3-dimensional magnetic resonance imaging anatomically correlated to positron emission tomography (PET) scanning to identify language areas in a patient with an arteriovenous malformation (AVM) in the posterior speech region. The patient was a 24-year-old right-handed woman with an angiographically proven AVM (3-4 cm) in the left mid-posterior second temporal convolution in whom a left intracarotid injection of sodium Amytal produced significant language disruption. A baseline PET cerebral blood flow study identified the AVM, and an activation PET scan performed during the reading and speaking of simple words showed increased activity in the left parastriate cortex (the second visual area), in the left posterior third frontal convolution (Broca's area), and in the left inferior and midtemporal gyri (Wernicke's area). Increased activity was also noted in the right and left transverse temporal (Heschl's) gyri, in the left precentral gyrus, in the left medial superior frontal gyrus (the supplementary motor area), and in the right cerebellum. We conclude that activation PET scanning is useful in the preoperative assessment of patients who harbor cerebral AVMs in classically described speech regions.

Adult↗
PubMed1992

[Neonatal isoimmune thrombocytopenia by anti-GP IIb/IIIa].

Neonatal alloimmune thrombocytopenic purpura is caused by maternal platelet-specific alloantibodies which react on fetal platelets with the corresponding antigen. We describe a 30-year-old female patient with type I Glanzmann thrombasthenia who developed an isoantibody against the platelet GP IIb/IIIa complex before or during pregnancy. The platelet count in the male newborn was 35 x 10(9)/l, but there were no signs of cerebral hemorrhage. Following infusion of 2 g/day i.v. IgG on 3 consecutive days, platelet counts rose to normal values. An isoantibody reacting with the GP IIb/IIIa complex of all platelet donors tested was found in the maternal serum using the MAIPA assay. Thus, immune-mediated neonatal thrombocytopenia may be caused by platelet isoantibodies against GP IIb/IIIa as well as by platelet-specific alloantibodies and by maternal autoantibodies.

Adult↗
PubMed1992

[Digitization of conventional x-ray films].

The diagnostic value of a digitization system for analogue films based on a charge-coupled-device (CCD) scanner with adjustable resolution of 2.5 or 5 lp/mm was assessed. Some 110 skeletal radiographs, 50 contrast studies, including 25 of patients with Crohn's disease, and 70 abdominal plain films before and after successful lithotripsy for renal stones were digitized. Receiver operating characteristic (ROC) studies showed improved detection of cortical and trabecular defects with contrast-optimized digitized films. Edge enhancement algorithms yielded no additional information. Inflammatory lesions of Crohn's disease were detected equally well by conventional films and digitized images. A statistically significant improvement (p less than 0.05) in the recognition of disintegration after lithotripsy was found for the processed digitized images. On the basis of this initial investigation, the digitization system tested appears to be useful for diagnostic purposes, especially when contrast resolution plays an important part, as with stone fragmentation or cortical defects.

Bone Neoplasms↗
PubMed1992

Immunohistochemical staining techniques of intraocular tumors.

The peroxidase-antiperoxidase staining technique for the antigens S-100, neuron-specific enolase, and alpha 1-antichymotrypsin (alpha 1ACT) was applied to 57 intraocular tumors: 46 malignant melanomas of the uvea, seven retinoblastomas, and four tumors metastasizing to the eye. The staining characteristics of the different intraocular tumors were compared. Staining for S-100 in a fine-needle aspiration biopsy sample taken from a malignant melanoma of the choroid before enucleation of the globe was attempted. The positive staining of a few cells thus obtained suggested that this technique may be helpful in the diagnosis of melanomas. The alpha 1ACT stain used in this study has not been used previously in ophthalmology to our knowledge. We found 60% of malignant melanomas of the choroid stained positively. Another finding was the staining of the retinal pigment epithelium with alpha 1ACT in 30% of eyes with malignant melanoma of the uvea.

Eye Neoplasms↗
PubMed1992

Tenon's capsule: ultrastructure of collagen fibrils in normals and infantile esotropia.

No detailed information about the ultrastructure of Tenon's capsule has been published. The purpose of the present study was to compare the ultrastructural features of collagen fibrils from Tenon's capsule in a nonstrabismic control group (seven children) to those in an infantile esotropic group (10 children). Small biopsy specimens from Tenon's capsule were taken during various operations to be examined by electron microscopy. On electron microscopy, the capsule was found to be composed of groups of collagen fibrils arranged irregularly in different orientations, forming a three-dimensional network that provides tissue resistance to stress. The cross-sectioned collagen fibrils were studied by an image analyzer. In both study groups, all fibrils had a round, regular contour. In the esotropic group, the Tenon's collagen fibrils were thicker, as reflected by their significantly greater mean diameter: 101 +/- 5 nm (mean +/- standard deviation) compared to 86 +/- 5 nm in the control group. Also, significantly greater heterogeneity was found in the collagen fibril thickness of each individual in the esotropic group compared to the control group. Moreover, the mean number of collagen fibrils per unit area was significantly higher in the esotropic group: 98 +/- 13 fibrils per 10(6) nm2 compared to 73 +/- 5 fibrils per 10(6) nm2 in the control group. These ultrastructural changes may be stress-induced secondary alterations of the Tenon's collagen fibrils resulting from prolonged deviation of the eye in infantile esotropia. The significantly denser collagen fibrils may cause a decrease in the elasticity of Tenon's capsule in infantile esotropia.

Biopsy↗
PubMed1992

[An irritating cough in dialysis patients. A rare differential diagnosis].

Soft tissue calcification is a well-known complication in chronic dialysis patients. These calcifications are mainly located around the large joints. Calcification of the visceral organs also occurs in these patients, even though this fact is far less known. These visceral calcifications are mostly diagnosed post mortem as they tend to be discrete and asymptomatic. In this article, we report on a chronic dialysis patient in whom extensive pulmonary calcifications occurred, leading to clinical symptoms.

Adult↗