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Biomedical subjects

A Mayer

Publications and source records attributed to A Mayer.

At least 127 records · Page 7Linked to original sources
PubMed1995

[Quality assurance, audit and quality control of radiotherapy at radiology departments in Hungary].

The first quality assurance, audit and control system in the Hungarian "'health" care industry" is described for the medical specialty of radiotherapy. The prerequisites of the elaboration of the programme were an exact knowledge of the current Hungarian infrastructural and staffing conditions, and the radiotherapeutic activities. The recommendations cover the 5 medical universities including the national institute (the Debrecen, Pécs, Semmelweis, Szent-Györgyk Albert Medical Universities, and Haynal Imre University of Health Sciences) and the 5 regional oncological centres in hospitals (Jósa András, Markusovszky, Petz Aladár, Szentpéteri kapu and Uzsoki Hospitals). The departmental functions (patient care, teaching-education, research work and scientific organizing activity) and the structure (organization, infrastructure, staffing conditions, etc.) are described first, followed by the therapeutic principles and clinical process (patient referral and selection, decision-making, priorities in therapy initiation, treatment preparation and execution, etc.). The informal daily/weekly quality assurance programme long applied in the routine patient care has been formalized and supplemented with a weekly audit conference. In the course of the medical audit, all relevant clinical data are reviewed and scored by an internal or an external expert (not participating directly in the treatment process), e.g. for the adequacy of the medical decision preparative process, conformation to the institutional treatment protocol, equipment selection, treatment planning, simulation and portal film, etc. If a major deviation is detected, an immediate correction is initiated; minor deviations need analysis and then preventive and correcting action. As concern the audit of the other activities of the departments, the important indicators and their minimally desirable level are defined. The final goal of the implementation of this programme is high-precision radiotherapy with the best achievable treatment result.

Dose-Response Relationship, Radiation↗
PubMed1995

MOM22 is a receptor for mitochondrial targeting sequences and cooperates with MOM19.

Recognition of targeting signals is a crucial step in protein sorting within the cell. So far, only a few components capable of deciphering targeting signals have been identified, and insights into the chemical nature of the interaction between the signals and their receptors are scarce. Using highly purified mitochondrial outer membrane vesicles, we demonstrate that MOM22 and MOM19, components of the protein import complex of the outer membrane, bind preproteins at the mitochondrial surface in a reversible fashion. Interaction specifically and directly occurs with the N-terminal presequence and is abolished after inactivation of either MOM22 or MOM19. Binding is salt sensitive, suggesting that recognition involves electrostatic forces between the positive charges of the presequence and the acidic cytosolic domain of MOM22. MOM19 and MOM22 can be cross-linked with high efficiency. We propose that the two proteins form a complex which functions as the presequence receptor at the mitochondrial surface and facilitates the movement of preproteins into the translocation pore.

Animals↗
PubMed1995

Sensitization to apomorphine-induced rotational behavior in 6-OHDA-lesioned rats: effects of NMDA antagonists on drug response.

The development of drug-induced behavioral sensitization is thought to underlie many of the motor complications that accompany chronic L-DOPA treatment of patients with Parkinson's disease. As the development of sensitization to some dopaminergic behaviors has been linked to alterations in NMDA neurotransmission in animal models, we sought to determine whether or not NMDA antagonists can block the development of sensitization to rotational effects of dopamine agonists in rodents with unilateral nigrostriatal lesions. Rats with unilateral 6-hydroxydopamine lesions received either a single dose or eight daily doses of apomorphine, each dose preceded by the NMDA antagonists MK-801 or CPP. Three days after the last apomorphine dose, the circling behavior produced by the D1 agonist SKF 38393 was measured. A single dose of MK-801 (0.1 mg/kg) prevented the subsequent response to SKF 38393 but neither repeated treatment with MK-801 (0.1 or 0.3 mg/kg) nor CPP (0.1 mg/kg) preceding apomorphine prevented the subsequent response to SKF 38393 or attenuated the response in comparison to a control group. Each of the chronic treatment groups exhibited an increase in rotational effects of apomorphine despite MK-801 or CPP pretreatment. These data suggest behavioral sensitization in unilateral nigrostriatally lesioned rats chronically treated with apomorphine is not dependent upon stimulation of NMDA receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1995

Translocation of apocytochrome c across the outer membrane of mitochondria.

Apocytochrome c follows a unique pathway into mitochondria. Import does not require the general protein translocation machinery, protease-sensitive components of the outer membrane, or a membrane potential across the inner membrane. We investigated the membrane binding and translocation steps of the import reaction using purified outer membrane vesicles (OMV) from Neurospora crassa mitochondria. OMV specifically bound, but did not import apocytochrome c. If, however, specific antibodies were enclosed inside OMV, apocytochrome c was accumulated in soluble form in the lumen. Import was reversible, since apocytochrome c became accessible to external protease after release from the antibodies. Thus, OMV are competent of translocating apocytochrome c into their lumen, but lack a binding partner which traps the apoprotein. In intact mitochondria, cytochrome c heme lyase (CCHL), a peripheral protein of the inner membrane, serves such a function by stably associating with apocytochrome c in a complex which is detectable by co-immunoprecipitation. We suggest a model for the import mechanism of apocytochrome c in which the apoprotein specifically associates with and reversibly passes across the outer membrane. Translocation is rendered unidirectional by stable association with CCHL which serves as a "trans side receptor." Finally, heme is attached by CCHL and the holoprotein folds into its native structure.

Apoproteins↗
PubMed1995

'Sheltered disruption' of Neurospora crassa MOM22, an essential component of the mitochondrial protein import complex.

MOM22 is a component of the protein import complex of the mitochondrial outer membrane of Neurospora crassa. Using the newly developed procedure of 'sheltered disruption', we created a heterokaryotic strain harboring two nuclei, one with a null allele of the mom-22 gene and the other with a wild-type allele. Homokaryons bearing the mom-22 disruption could not be isolated, suggesting that mom-22 is an essential gene. The mutant nucleus can be forced to predominate in the heterokaryon through the use of specific nutritional and inhibitor resistance markers. Cultivation of the heterokaryon under conditions favoring the mutant nucleus resulted in selective depletion of MOM22. MOM22-depleted cells did not grow and contained mitochondria with an altered morphology and protein composition. Protein import into isolated, MOM22-depleted mitochondria was abolished for most precursor proteins destined for all subcompartments. In contrast, precursors of MOM19, MOM22 and MOM72 became inserted normally into the outer membrane, defining a novel MOM22-independent import pathway which remained intact in mutant mitochondria. Furthermore, the specific binding of the ADP/ATP carrier to the outer membrane was unaffected, but subsequent transport across the outer membrane did not occur. Our data show that MOM22 is an essential component of Neurospora cells specifically required for the biogenesis of mitochondria.

Biological Transport↗
PubMed1995

Mitochondrial protein import: reversible binding of the presequence at the trans side of the outer membrane drives partial translocation and unfolding.

The mechanism of translocation of matrix-targeted, cleavable preproteins across the mitochondrial outer membrane was studied using purified outer membrane vesicles. The N-terminal presequence interacts in a sequential and reversible fashion with two specific binding sites. The first one is provided by protease-sensitive receptors on the surface of the membrane (cis site); the second one is located at the inner face of the outer membrane (trans site). Binding to the trans site drives translocation of the N-terminal portion of the preprotein and, at the same time, unfolding of its mature part. We suggest that the outer membrane protein import machinery forms a translocation channel that permits reversible sliding of preproteins and prevents their lateral aggregation in the membrane. Although translocation can be initiated by the outer membrane, its completion requires coupling to the energetic system of the inner membrane. Our data assign an essential role to the presequence, not only for efficient targeting, but also for the translocation step.

Binding Sites↗
PubMed1995

Holding on to success: a case study in mental health care reform.

This article analyzes the changes experienced by a mental health care organization in response to environmental threats and fluctuating expectations. On a general, more theoretical level, the article demonstrates how processes of environmental selection as well as organizational adaptation shape organizational forms. On a concrete, applied level, those administrative practices are articulated that can help ensure that reform efforts are successful. Administrators also must be aware of the inertial forces operating upon stable organizational forms and work to ensure that the organization remains vital and open to change.

Community Mental Health Centers↗
PubMed1995

Transcription of the Y chromosomal gene, Sry, in adult mouse brain.

The Y chromosomal gene Sry encodes a putative transcription factor which appears to serve as a master switch initiating testicular development. Here we show that this gene is transcribed in hypothalamus, midbrain, and testis of adult male but not adult female mice. In contrast to its circular transcripts in adult testis, those in brain are linear and may be translated. We propose that Sry exerts a role in the regulation of sex differentiation of the mammalian nervous system.

Animals↗
PubMed1995

Effects of carbamazepine on membrane properties of rat sensory spinal ganglion cells in vitro.

The present study aimed to examine effects of the antiepileptic drug carbamazepine (CBZ) on membrane properties. Therefore, effects of CBZ on voltage-dependent ion channels were investigated in rat sensory spinal ganglion cells in primary cultures. (i) Membrane potentials and action potentials were recorded by sharp microelectrodes: CBZ reduced neuronal excitability without changing the resting membrane potential, and suppressed tetrodotoxin (TTX)-resistant components of action potentials which were blocked by cobalt and hence were interpreted as Ca2+ spikes. The rising phase and peak amplitude of TTX-sensitive components of action potentials, however, were hardly altered. (ii) Voltage-dependent inward and outward currents were elicited in the whole-cell configuration of the patch clamp technique. CBZ reduced (presumably L-type) Ca2+ currents. In some cells Ca2+ currents partly recovered during washing with control saline. The effects on Na+ and K+ currents were not uniform and often insignificant. The present study indicates that CBZ has calcium-antagonistic properties.

Action Potentials↗
PubMed1995

Dual human immunodeficiency virus type 1 infection and recombination in a dually exposed transfusion recipient. The Transfusion Safety Study Group.

We studied a case in which a 2-month-old premature infant was concurrently transfused with packed erythrocytes from two different human immunodeficiency virus type 1 (HIV-1)-seropositive donors in late 1984. The two donors also each singly infected a second infant. Inspection of sequences from portions of the HIV-1 genomes in each of the two donors showed a close relationship to the strain in their respective singly exposed recipients. Inspection of sequences from the dually exposed recipient provided evidence of an individual simultaneously infected with two distinct HIV-1 strains, as well as recombination of the two strains in vivo.

Amino Acid Sequence↗
PubMed1995

[Latero-cervical thyroid tissue and congenital hypothyroidism revealed in adult age].

It is generally admitted that in front of tissues of thyroid origin found in latero-cervical position, the clinician should look for the presence of an occult thyroid carcinoma. This position is therefore against the diagnosis of lateral aberrant thyroids or benign metastatic thyroidosis that have been evocated in the past. We present the case of a 59 yr old woman in whom the diagnosis of benign latero-cervical mass of thyroid origin was made in association of an undiagnosed congenital hypothyroidism due to an ectopic thyroid gland in a sub-lingual position. This observation as well as recent published observations are in contrast with the current medical practices which should be discussed according to the location of the cervical mass and to precise histopathological features.

Age Factors↗
PubMed1994

Purification and characterization of a novel species of ubiquitin-carrier protein, E2, that is involved in degradation of non-"N-end rule" protein substrates.

Ubiquitin-carrier proteins (E2s, ubiquitin-conjugating enzymes, UBCs) participate in proteolysis by catalyzing transfer of activated ubiquitin to the protein substrates, which are bound to specific ubiquitin-protein ligases (E3s). Yeast UBC2 (RAD6) and the mammalian E2(14kDa) bind to the ligase that recognizes and is involved in the degradation of certain free amino-terminal substrates ("N-end rule" substrates). As such proteins are rather scarce, the role of these E2s in general proteolysis is probably limited. Here, we report the purification and characterization of a novel 18-kDa species of E2 from rabbit reticulocytes. Unlike most members of the E2 family, this enzyme does not adsorb to anion exchange resin in neutral pH, and it is purified from the unadsorbed material (Fraction 1). Thus, it is designated E2-F1. Like all members of the E2 family, it generates a thiol ester with ubiquitin that serves as an intermediate in the conjugation reaction. Sequence analysis revealed a significant homology to many known species of E2s. The enzyme generates multiply ubiquitinated proteins in the presence of an E3 that has not been characterized yet. Most importantly, the ubiquitination via this E2 leads to the degradation of certain non-"N-end rule" substrates such as glyceraldehyde-3-phosphate dehydrogenase (Val at the NH2 terminus) and to the ubiquitination and degradation of certain N-alpha-acetylated proteins such as histone H2A, actin, and alpha-crystallin. The enzyme is also involved in the conjugation and degradation of the tumor suppressor protein p53.

Amino Acid Sequence↗
PubMed1994

Fatty acids and other compounds with nematicidal activity from cultures of Basidiomycetes.

In a screening for nematicidal activities in cultures of Basidiomycetes, cultures of Pleurotus pulmonarius and Hericium coralloides exhibited toxic effects towards the saprophytic nematode Caenorhabditis elegans. Subsequently S-coriolic acid (1), linoleic acid (2), p-anisaldehyde (3), p-anisyl alcohol (4), 1-(4-methoxyphenyl)-1,2-propanediol (5), and 2-hydroxy-(4'-methoxy)-propiophenone (6) were isolated from submerged cultures of P. pulmonarius. All compounds showed nematicidal activities towards C. elegans. The most active compounds were 1 and 2 with LD50 values between 5 and 10 ppm. Compounds 1, 4, and 5 have not been previously isolated from higher fungi, 6 is a new natural product. From cultures of H. coralloides, which exhibited both repellant and nematicidal effects, a nematicidal fatty acid mixture was obtained, containing linoleic acid, oleic acid, and palmitic acid as its main components.

Animals↗
PubMed1994

Identification of human immunodeficiency virus type 1 envelope genes recombinant between subtypes B and F in two epidemiologically linked individuals from Brazil.

Sequence analysis of a human immunodeficiency virus type 1 env gene PCR amplified from a Brazilian woman's peripheral blood mononuclear cell DNA (sample RJIO1) showed that it was likely to have been derived from a double recombination event between human immunodeficiency virus type 1 subtypes B and F. The major portion of the gp120 coding sequence belonged to the B lineage, but a segment of the C2 to V3 region (approximately 135 nucleotides) clearly associated with sequences of the F lineage. The subtype F-like segment had 15 noncontiguous signature nucleotides in common with Brazilian subtype F sequences that were not found, or were rare, in subtype B sequences. In contrast, this same segment had only 3 signature nucleotides shared with subtype B sequences and not present in the Brazilian subtype F sequences. Phylogenetic analysis, amino acid signature pattern analysis, and the pattern of synonymous mutations all supported the hypothesis of a recombinational origin of the RJIO1 sequence. Related recombinant genes were also detected in peripheral blood mononuclear cell DNA obtained from the woman's recent sexual partner, indicating that the recombination event probably occurred at some previous time in the chain of virus transmission. Divergent viral sequences in the V3 region were found in the male sexual partner, while a relatively homogeneous viral population was detected in the woman, consistent with her recent infection.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Comparison of in vivo plasma and peripheral blood mononuclear cell HIV-1 quasi-species to short-term tissue culture isolates: an analysis of tat and C2-V3 env regions.

OBJECTIVE: To determine whether the HIV-1 genomes that grow out in vitro from peripheral blood mononuclear cells (PBMC) better represent the in vivo quasi-species present in plasma or PBMC. RESULTS: For one patient (9606), PBMC culture represented more accurately the plasma rather than the in vivo PBMC quasi-species distribution, because a large number of tat-defective proviruses present in PBMC in vivo were not detected in plasma nor in the PBMC cultures. For a second patient (9605), PBMC culture was representative of both in vivo PBMC and plasma tat sequences, but selection of C2-V3 env sequences was observed in PBMC cultures compared with sequences present in both plasma and PBMC in vivo. This selection consisted of the absence in vitro of genomes with certain amino-acid substitutions at or near conserved glycosylation sites of the C2 region at positions 276 and 289. Site 276 has been reported to be important for viral infectivity, and these substitutions may therefore have affected infectivity. In the third patient (10095), selection of both tat and C2-V3 sequences was observed in culture as compared to plasma and PBMC in vivo. In contrast to the first two patients, this third patient contained V3 sequences in vivo that were predicted to impart syncytium induction and enhanced replication capacity. It was these sequences that grew out preferentially in vitro. CONCLUSION: This study suggests that short-term PBMC culture is representative of HIV-1 genomes present in PBMC and plasma in vivo to the degree that they are infectious.

Amino Acid Sequence↗