Biomedical subjects

A Marx

Publications and source records attributed to A Marx.

At least 199 records · Page 11Linked to original sources

PubMed1990

Estimate of the maximal daily dietary intake of butylated hydroxyanisole and butylated hydroxytoluene in The Netherlands.

The daily dietary intake of the phenolic antioxidants butylated hydroxyanisole (BHA) and/or butylated hydroxytoluene (BHT) was estimated using data obtained from a nationwide dietary record survey carried out in The Netherlands in 1987/1988. The estimates were based on the fat content of selected food categories and their respective maximum permitted levels of BHA and/or BHT. The results indicate that it is unlikely that the current acceptable daily intake for BHA (0-0.05 mg/kg body weight) is surpassed, even in individuals with an extremely high caloric intake, except in extreme cases in 1-6-year-olds. However, it cannot be excluded that the acceptable daily intake for BHT (FAO/WHO: 0-0.125 mg/kg; EEC: 0-0.05 mg/kg) is exceeded in all age and sex groups, but particularly in children aged 1-6 years.

Age Factors↗

PubMed1990

HAB-1, a new heteromyeloma for continuous production of human monoclonal antibodies.

To obtain suitable cell lines for the immortalisation of human lymphocytes, we constructed a heteromyeloma between the murine myeloma Ag8 and human lymphocytes from a highly malignant polymorphic, centroblastic B-cell lymphoma. The thioguanine-resistant and HAT-sensitive heteromyeloma HAB-1 neither secretes nor contains cytoplasmatic immunoglobulins, the cells being EBV negative but positively stained for HLA-BC and the human proliferation marker Ki-67. The karyotype consists of about 50 murine and 20 human chromosomes. The HAB-1 cells grow in suspension and have a doubling rate of about 25-30 h. In fusion experiments with spleen cells from stomach carcinoma patients HAB-1 cells show a 5-7 times higher fusion efficiency than murine Ag8 cells or another heteromyeloma SPM4-0 and give stable antibody producing products. The cell line will be made available to interested scientists.

Animals↗

PubMed1990

Structural studies of lipid A from Pseudomonas aeruginosa PAO1: occurrence of 4-amino-4-deoxyarabinose.

Lipid A derived from Pseudomonas aeruginosa PAO1 contains a biphosphorylated 1-6-linked glucosamine disaccharide backbone. The reducing glucosamine has an unsubstituted glycosidically linked phosphate at C-1. The nonreducing glucosamine has an ester-bound phosphate at C-4' which is nonstoichiometrically substituted with 4-amino-4-deoxyarabinose. Induction of 4-amino-4-deoxyarabinose was dependent on cultural conditions. No pyrophosphate groups were detected. Acyloxyacyl diesters are formed by esterification of the amide-bound 3-hydroxydodecanoic acid with dodecanoic acid and 2-hydroxydodecanoic acids in an approximate molar ratio of 2:1. Dodecanoic and 3-hydroxydecanoic acids are esterified to positions C-3 and C-3' in the sugar backbone. All hydroxyl groups of the glucosamine disaccharide except C-4 and C-6' are substituted. Lipopolysaccharide chemical analyses measured glucose, rhamnose, heptose, galactosamine, alanine, phosphate, and glucosamine. The proposed lipid A structure differs from previous models. There are significant differences in acyloxyacyl diesters, and the proposed model includes an aminopentose substituent.

Amino Sugars↗

PubMed1990

Characterization of a protein with an acetylcholine receptor epitope from myasthenia gravis-associated thymomas.

Immunohistochemical studies have shown that almost all thymomas of myasthenia gravis patients contain at least one protein sharing an antigenic determinant with the nicotinic acetylcholine receptor (AchR) of human muscle. We describe the characterization of this protein (p153) which has a molecular weight of 153 and an isoelectric point of 5.0. By treatment of p153 with endoglycosidases, no significant glycosylation has been detected. Immunologically, p153 crossreacts with monoclonal antibodies against the amino acid sequence 371-378 of the alpha-chain of the AchR. No cross-reactivity to the main immunogenic region of the AchR nor an alpha-bungarotoxin binding site are found. By Western blotting, p153 was generally neither detectable in normal tissues nor extrathymic tumors with the exception of paraganglioma and neuroblastoma. In conclusion, the structure of p153 is apparently unrelated to the AchR from muscle or the alpha-bungarotoxin binding proteins from thymoma. Since there is no evidence for an AchR expression in thymoma, the antigenic homology of p153 with the nicotinic AchR might be relevant for triggering an intrathymomatous autosensitization of maturing T cells and could be responsible for the high association of thymomas with myasthenia gravis.

Antibodies, Monoclonal↗

PubMed1990

[Significance of neuronal acetylcholine receptors as differentiation antigens in neuroblastomas and paragangliomas].

Using a panel of monoclonal antibodies to various epitopes of the alpha-, beta- and gamma-subunit of the muscle acetylcholine receptor (AchR), two different immunohistochemical reactivity patterns--corresponding to different neuronal AchRs--were identified in ganglia of the peripheral and central nervous system. The immunoreactivity pattern of neuroblastomas and paragangliomas was identical to the pattern found in the peripheral nervous system and has not been encountered in any other tumor type. Both the intensity of neuronal AchR immunoreactivity and the transcription of the neuronal AchR alpha-gene seem to correlated with a higher degree of neuroblastoma differentiation.

Antibodies, Monoclonal↗

PubMed1990

[Nicotinic acetylcholine receptors in tumors with rhabdomyomatous differentiation. Immunohistochemical amd molecular genetic demonstration].

The nicotinic acetylcholine receptors (AChRs) of the skeletal muscle consist of pentameric ion channels, each of which is composed of 4 kinds of subunits. During the development of the muscle a change from a fetal type (alpha beta alpha gamma delta) to an adult type (alpha beta alpha epsilon delta) of AChR is due to the replacement of the gamma-subunit with the epsilon-subunit. We investigated the expression and transcription of the AChRs in rhabdomyosarcomas (5 cases) and in nephroblastomas with rhabdomyomatous differentiation (2 cases) by immunohistochemistry using monoclonal antibodies to the alpha-, beta- and gamma-AChR-subunit, and by mRNA dot blot and in situ hybridization applying cDNA-probes of the alpha-, beta-, gamma-, delta- and epsilon-AChR-subunit. The results indicate an intratumorous coexpression of fetal and adult types of AChRs. The presence of gamma-subunits of fetal AChRs may serve as a novel selective marker of tumors with rhabdomyomatous differentiation.

Cell Differentiation↗

PubMed1990

[Surgical treatment of cholelithiasis and its complications. Comparison of 2 treatment periods].

We have realized a retrospective analysis of all cholecystectomies performed during two five-year periods (period I: 1970 to 1974, period II: 1984 to 1988) for stone disease. We were especially interested in the development concerning the type of intervention, the diagnostic procedures, the morbidity and mortality. Our analysis showed in the second period the substitution of the preoperative diagnostic procedure away from the cholangiography up to the ultrasound, a significant decrease of interventions, a marked decrease of surgically performed papillotomies and a reduction of mortality.

Ampulla of Vater↗

PubMed1990

[Value of extracorporeal piezoelectric lithotripsy in treatment of gallstone disease].

Alternative techniques were introduced in the last 20 years for the treatment of gallstones. Among these the extracorporeal shock wave lithotripsy followed by a systemic litholytic therapy represents undoubtedly the most attractive one. A group of two surgeons and two gastroenterologists has started to evaluate this treatment in April 1988, using a piezoceramic lithotryptic system (Piezolith 2300). From April 1988 to May 1989 we have treated 32 patients who fulfilled the selection criteria-symptomatic gallstone disease, 1-3 radiolucent concrements of less than 30 mm of diameter, functioning gallbladder. We noted only one pancreatitis as a complication of this treatment. The overall stonefree rate is 16% after two months, 32% after four months and 56% after six months, depending on the size and number of stones. A definitive evaluation and final conclusion will only be possible when the rate of late recurrences after this treatment will be known.

Adult↗

PubMed1989

Thyrotoxic periodic paralysis and the sodium/potassium pump.

The hypothesis of altered Na+/K+ transport in thyrotoxic periodic paralysis (TPP) was tested in an investigation of the K+ influx into erythrocytes from two patients with episodes of thyrotoxic muscle weakness. A patient with primary hypokalemic periodic paralysis (HPP) and three healthy volunteers served as controls. The TPP patients were of Oriental and Caucasian origin and differed in their clinical symptoms. For the Caucasian patient, the Na+ content of the erythrocytes was twice the control, for the Oriental patient it was normal. The K+ dependence of the ouabain-inhibitable K+ influx (the pump action) was also abnormal in the Caucasian patient, the flux being 70% of control at 2 mM [K+]e and normal at 4 mM [K+]e. The K+ influx was normal in the Oriental patient. By contrast, the K+ leak of the cells was normal in the Caucasian and was increased in the Oriental patient. The pump/leak ratio was thus reduced in both TPP patients. All parameters investigated were normal in the patient with primary HPP. It is concluded that the ion transport systems of muscle may be altered in TPP, but that the patho-mechanism might be different in the rare Caucasian cases and the rather more common Oriental cases.

Adolescent↗

PubMed1989

Primary cultures of human thymic epithelial tumors. Morphological and immunocytochemical characterization.

Primary cultures are introduced as a method for an immunocytochemical and functional characterization of epithelial cells (ECs) from human thymic epithelial tumors. Neoplastic ECs were obtained after enzymatic digestion of the tumor tissue with dispase. The ECs were kept in culture for up to 1.5 months. Over this period a progressive decline in their proliferation rate was observed. In all five cases studied, ECs showed a co-expression of keratin and vimentin intermediate filaments in vitro as well as strong expression of major histocompatibility complex (MHC)-class I antigens and a progressive loss of MHC-class II antigens. Acetylcholine receptor (AchR)-epitopes were detected immunohistochemically by using monoclonal antibodies (mAbs) to the cytoplasmic site of the alpha-chain if the AchR. Epitopes were found in three of five thymomas in vivo and to a varying degree in all five cases in vitro.

Antibodies, Monoclonal↗

PubMed1989

Proteins with epitopes of the acetylcholine receptor in epithelial cell cultures of thymomas in myasthenia gravis.

Thymomas from 12 patients with myasthenia gravis (MG) were investigated for the presence of epitopes of the alpha-subunit of the nicotinic acetylcholine receptor (AchR) using monoclonal antibodies (MAb) reacting against the AchR. In all but two of the tumors epitopes corresponding to antigenic determinants located on the cytoplasmic side of the AchR were identified. From eight thymomas cell lines were established that have been kept in culture for up to 6 months. The cultured cells expressed the same AchR-epitopes as did the primary tumors. During early passages the percentage of epithelial cells positive for the AchR epitopes approximately mirrored the percentage of positive cells in the original tumors. With passaging the relative number of positive cells usually declined but in some cultures an increase was observed. Three cell lines that showed extensive staining with an MAb against the AchR were radiolabeled to characterize the antigen. From protein extracts of these three cell lines proteins of 45 kd and 156 kd molecular weight (MW) were precipitated. These proteins are different from other proteins described in the context of both thymomas and MG. The negative reactivity with MAb against other epitopes of the alpha-subunit, especially against the main immunogenic region (MIR), speaks in favor of membrane-associated proteins of only limited crossreactivity to the AchR. A previous study found an almost exclusive occurrence of these AchR-epitopes in thymomas associated with MG, but not in other thymomas of similar histologic type. The expression of the proteins described here could therefore play a role in the triggering of the autoimmune process against the AchR of the motor, endplate in MG patients.

Adult↗

PubMed1989

Acetylcholine receptor epitope in proteins of myasthenia gravis-associated thymomas and non-thymic tissues.

Immunohistochemical studies have shown that almost all thymomas of myasthenia gravis (MG) patients contain proteins which share antigenic determinants with the nicotinic acetylcholine receptor (AChR) of human muscle. Here we describe one of the proteins (p153) which (1) is not part of a compound structure, (2) has a MW of 153 kd, (3) has an isoelectric point of 5.0, and (4) is probably free of sugar residues. The protein does not bind mAb to the main immunogenic region of the AChR and has no alpha-bungarotoxin (alpha-btx) binding site. p153 was not found in both normal tissues and a variety of tumours. However, the epitope defined by mAb155 also occurs in at least two other proteins (from muscle and TE671 cells) which have MW different from 153 kd and which are unrelated to AChR. Experiments presented elsewhere [Geuder et al., this volume] show that there are no proteins in thymomas which share an extensive molecular homology with the AChR. All these findings suggest that p153 is unrelated to the AChR. As p153 is the only protein demonstrated in thymomas which is significantly correlated with MG and which shares an antigenic determinant with AChR, p153 is a candidate protein determining the AChR-specificity of the autoimmune process in MG.

Antibodies, Monoclonal↗

PubMed1989

The gene of the alpha-subunit of the acetylcholine receptor: molecular organisation and transcription in myasthenia-associated thymomas.

DNA and RNA were isolated from 5 thymomas of Myasthenia Gravis (MG) patients, from normal tissues, and from the TE671 cell line (which expresses a muscle type acetylcholine receptor, AChR). The cDNA of the alpha-subunit of the AChR, a 159 bp BglII/BstEII fragment encoding the main immunogenic region (MIR) and a 88 bp EcoRV/TaqI fragment encoding the mAb155 binding site (a cytoplasmic epitope of AChR) served as probes. Hybridizations were performed under both high and low stringent conditions. Southern blot analysis of genomic DNA, restricted with EcoRI, HindIII and BamHI/HindIII, showed a normal pattern of restriction fragments in all tissues investigated. In particular, in thymomas there was no deletion of exon 4 which encodes the MIR. Dot and Northern blot analysis of total RNA and mRNA revealed transcription of the alpha-subunit AChR gene in TE671 cells and skeletal muscle but not in other tissues including thymomas. These results confirm former reports that there are no intact AChR in thymomas of MG patients. In addition we show here that there is also no truncated, MIR-deficient AChR or a protein with extensive molecular homology with the AChR in thymomas. These investigations support our idea that an AChR-unrelated protein might play a role in the pathogenesis of thymoma-associated MG [Marx et al., this volume].

Autoimmune Diseases↗

PubMed1989

Evaluation of prognostic features in thymic epithelial tumors.

Based on the original proposals of Müller-Hermelink [3,8] and the study of 95 tumor specimens from the files of our institute we have established a new concept for the classification of thymic epithelial tumors. Thymomas are related to the structural components of normal thymus and divided in medullary, mixed, predominantly cortical and cortical types. In addition a well-differentiated thymic carcinoma with partial loss of organotypic differentiation is characterized and distinguished from other carcinoma types with total lack of specific thymic features. Prognostic evaluation showed, that medullary and mixed thymomas are always benign tumors, whereas predominantly cortical thymomas, cortical thymomas and well-differentiated thymic carcinomas are low-grade malignant tumors with increasing invasiveness and even metastatic capacity. Moreover the proliferation rate of neoplastic epithelial cells in vitro, which was studied in 12 cases, correlated to the different tumor types and their growth behaviour in vivo.

Carcinoma↗

PubMed1989

[Reduction of renal reperfusion damage following warm ischemia by allopurinol and superoxide dismutase].

Preserved organs are damaged not only by the ischemic injury due to lack of oxygen. The reperfusion injury mediated by oxygen free radicals is an important factor in the postischemic organ failure. The prevention of free radical-induced reperfusion injury with allopurinol (AP) and superoxide dismutase (SOD) is shown in a warm ischemia kidney model. Rats were treated with allopurinol (40 mg/kg i.v.) one hour, or with SOD (20,000 IU/kg i.v.) one minute before reperfusion after a period of 35 minutes of warm ischemia. Allopurinol and SOD reduced significantly the postischemic kidney failure with a less important increase of creatinine. Creatinine levels on day three in the control group: 517 +/- 87 mumol/ml, in the SOD-group: 206 +/- 105 mumol/ml, and in the AP-group: 163 +/- 81 mumol/ml (anal. of variance: p = 0.0001). AP has a wide therapeutic range. We feel, that it is important to confirm the prevention of reperfusion injury by allopurinol prophylaxis clinically.

Allopurinol↗

PubMed1988

The membrane lipid and fatty acid composition of erythrocyte ghosts from three patients with paramyotonia congenita.

The membrane lipid and fatty acid composition of red blood cell ghosts from three paramyotonia patients was investigated. Cholesterol and total phospholipid contents were not different from the controls, but the sphingomyelin content was reduced, and this was compensated for by an increase in phosphatidylcholine. Thus, the molar ratios of phosphatidylcholine/sphingomyelin and phophatidylcholine/phosphatidylethanolamine were greater than normal. The saturated fatty acids in the total phospholipids were increased so that the ratio of saturated/unsaturated fatty acids was 1.4-1.6 versus 1.1-1.2 in the controls. The polyunsaturated fatty acids comprised only 22-26% of the fatty acids versus 31-32% in controls. The reduction in content of unsaturated fatty acids concerned all phospholipid classes in one patient and only the choline phospholipids in the tow other patients who were related to each other. The pattern of the fatty acids in the C2-position of the glycerophospholipids reflected the finding in the total phospholipids. Thus, an alteration of the activity of the acyl-CoA: 1-mono-acylphosphoglyceride-acyltransferase seems unlikely. The results support the notion of a generalized membrane defect in paramyotonia congenita, although the degree of abnormality in the fatty acid pattern was not correlated with the severity of the clinical symptoms.

Adult↗

PubMed1988

Structural relationship between the polyagglutinable antigen and the core polysaccharide of Pseudomonas aeruginosa.

It has been observed that each strain of the Pseudomonas aeruginosa species harbours the so-called polyagglutinable antigen (PA). Some strains may produce it in a form which is linked to the core moiety of lipopolysaccharide (LPS) and this type of PA can thus be detected by passive haemagglutination using the isolated LPS as coating antigen. Other strains synthesize PA exclusively in a free form, which is also coextractable with LPS, its presence can, however, be demonstrated by the haemagglutination inhibition test. From a polyagglutinable strain of P. aeruginosa an R-type LPS was isolated having the core-linked PA. This LPS preparation was highly immunogenic with regard to its PA moiety. The core-bound PA seems to exert an immunosuppression on the core region, hence, the polyagglutinable strains isolated from cystic fibrosis patients only engender anti-PA antibodies, whereas antibodies against both, side chain and core region of LPS, are not engendered. The mucoid exopolysaccharide also contains the PA which could possibly play an important role in the patient by protecting P. aeruginosa cells against anti-PA antibodies.

Antibodies, Bacterial↗

PubMed1988

Antigenicity and immunogenicity of the polyagglutinable antigen of Pseudomonas aeruginosa.

Pseudomonas aeruginosa strains isolated from cystic fibrosis patients agglutinate in antisera against anti-polyagglutinable antigen (PA). Anti-PA antibodies were formed in rabbits when immunization was carried out with bacteria possessing core-bound PA, independently of whether the strains were of S or R phenotype. For bacterial agglutination with anti-PA antibodies two prerequisites are essential: the bacterial cell must be of R phenotype and must possess the core-linked PA. In contrast, the PA in the isolated LPS's can be demonstrated in passive haemagglutination for both (S or R) phenotypes, provided the PA is core-linked. Two PA forms have been recognized, one found only in P. aeruginosa species, both in free and bound form. The other one is shared by all members of Pseudomonas genus but is present only in a free, unbound form.

Antigens, Bacterial↗