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Biomedical subjects

M Linder

Publications and source records attributed to M Linder.

At least 73 records · Page 4Linked to original sources

Identification of functionally important amino acids in the cellulose-binding domain of Trichoderma reesei cellobiohydrolase I.

Cellobiohydrolase I (CBHI) of Trichoderma reesei has two functional domains, a catalytic core domain and a cellulose binding domain (CBD). The structure of the CBD reveals two distinct faces, one of which is flat and the other rough. Several other fungal cellulolytic enzymes have similar two-domain structures, in which the CBDs show a conserved primary structure. Here we have evaluated the contributions of conserved amino acids in CBHI CBD to its binding to cellulose. Binding isotherms were determined for a set of six synthetic analogues in which conserved amino acids were substituted. Two-dimensional NMR spectroscopy was used to assess the structural effects of the substitutions by comparing chemical shifts, coupling constants, and NOEs of the backbone protons between the wild-type CBD and the analogues. In general, the structural effects of the substitutions were minor, although in some cases decreased binding could clearly be ascribed to conformational perturbations. We found that at least two tyrosine residues and a glutamine residue on the flat face were essential for tight binding of the CBD to cellulose. A change on the rough face had only a small effect on the binding and it is unlikely that this face interacts with cellulose directly.

Adsorption↗

The methyltransferase inhibitor Neplanocin A interferes with influenza virus replication by a mechanism different from that of 3-deazaadenosine.

Neplanocin A (NeplA) and 3-deazaadenosine (3DA-Ado) are both inhibitors of methyltransferases, and both interfere with influenza virus replication. Their modes of action, however, are different. In chicken embryo cells NeplA inhibits only in media depleted of or low in methionine, while 3DA-Ado acts independently of the concentration of methionine. While homocysteine partially reverses the effect of NeplA, it strongly potentiates the effect of 3DA-Ado. While NeplA inhibits the synthesis of all viral proteins to nearly the same extent, 3DA-Ado interferes only with the production of late proteins (Fischer et al. (1990) Virology 177, 523-531). In NeplA-pretreated cells there is an extreme accumulation of S-adenosylhomocysteine, independent of the concentration of methionine in the medium, although NeplA inhibits influenza virus replication only in methionine-depleted medium. Therefore an accumulation of this intermediate by NeplA cannot account for the inhibitory effect, as has been implicated in the inhibition of the replication of other viruses. Our results indicate that at least two different methyltransferases are involved in influenza virus replication.

Adenosine↗

Playing chicken with people: the occupational safety and health consequences of throughput über alles.

The political-economic and legal analysis of regulation in this article argues that the speed of work on disassembly lines in poultry processing plants, the fastest growing factory employment in the United States, is de facto regulated not by the Occupational Safety and Health Administration, the agency charged with protecting workers, but, perversely, by the U.S. Department of Agriculture. In arrogating to itself the power to set line speeds in connection with its inspection of processed carcasses, the Department of Agriculture has one-sidedly promoted chicken oligopolies' interests by accommodating their drive to produce as much product as quickly and cheaply as possible (throughput über alles) and especially without regard to the incidence of repetitive stress disorders associated with high-speed machine-paced manual production. In contrast, the Occupational Safety and Health Administration has failed either to assert its statutory authority over this vital determinant of workers' well-being or to persuade any administrative or judicial tribunal that it possesses such authority. Consequently, the article concludes, the health and safety of 200,000 low-paid and largely unorganized, female, and non-white workers continue to be held hostage to the self-valorization needs of capital and the state's cheap food policy.

Animals↗

Determination of beta-lactam residues in milk using perfusive-particle liquid chromatography combined with ultrasonic nebulization electrospray mass spectrometry.

The introduced electrospray (ESP) technique combined with quadrupole mass spectrometry (MS) was applied for the trace residue detection (10 ppb) of commonly administered beta-lactam antibiotics in bovine milk. Because of the widespread use of penicillin G, ampicillin, amoxicillin, cephapirin, cloxacillin, and ceftiofur in veterinary medicine, these six popular drugs were chosen to develop a fast and reliable microcolumn liquid chromatographic (micro-LC) separation method for residue-containing milk extracts. Furthermore, the analytes were selected to test the chromatographic behavior of a novel stationary phase, a perfusive-particle column packed with derivatized porous polystyrene divinylbenzene. The effects of mobile phase additives on separation and ESP ionization efficiency were investigated. The ionization of the eluted analytes took place either in a conventional ESP interface with a capillary shield allowing flow rates up to 40 microL/min or in the latest model of the ultrasonic nebulization ESP interface. The perfusive-particle column, although not optimized for the separation of small molecules, exhibited sufficient resolution of the antibiotics for its routine usage, especially when considering the remarkable time-saving advantage compared with ordinary reversed phase micro-LC columns. The application of the novel ultrasonic nebulization interface lowered detection limits and improved the stability of the signals over a much wider flow rate range than possible for ionization with the ESP system equipped with the conventional needle.

Animals↗

Structural elements in glycoprotein 70 from polytropic Friend mink cell focus-inducing virus and glycoprotein 71 from ecotropic Friend murine leukemia virus, as defined by disulfide-bonding pattern and limited proteolysis.

The disulfide-bonding pattern of glycoprotein 70 (gp70), the surface glycoprotein (SU) encoded by the envelope gene of polytropic Friend milk cell focus-inducing virus, was elucidated and compared with that of glycoprotein 71 (gp71), the corresponding glycoprotein of the ecotropic Friend murine leukemia virus, which had previously been determined (M. Linder, D. Linder, J. Hahnen, H.-H. Schott, and Stirm, Eur. J. Biochem. 203:65-73, 1992). In the carboxy-terminal constant domain, in which these glycoproteins have about 97% sequence homology, the location of the four disulfide bonds was found to be analogous. In the amino-terminal differential domain, with about 37% sequence homology, 8 of the 12 cysteine residues of the ecotropic SU are conserved in the polytropic SU. In this domain, a similar clustering of disulfide bonds was detected, which led to the identification of three distinct disulfide-bonded regions in both glycoproteins. However, because of deletions and sequence deviations, the glycoproteins must have significantly different three-dimensional structures in these regions. Since the receptor-binding functions of both glycoproteins have been attributed to their amino-terminal domains and since each binds to a different receptor, these disulfide-bonded structures are likely candidates for receptor-binding functions. Limited proteolysis of both glycoproteins with various endoproteinases led to the identification of preferential proteolytic sites between disulfide-bonded regions, at the beginning of the hypervariable proline-rich region, and between differential and constant domains, further confirming the structural organization of the folded glycoproteins.

Amino Acid Sequence↗

Human alpha 1-antichymotrypsin of pancreatic origin carries blood group determinants.

alpha 1-Antichymotrypsin was detected as a minor but normal component of pancreatic juice and found, with the aid of monoclonal antibodies and lectins, to differ from serum alpha 1-antichymotrypsin with respect to its carbohydrate moiety. alpha 1-Antichymotrypsin carries blood group determinants, as is typical for glycoproteins of pancreatic origin.

Antibodies, Monoclonal↗

Localization of the intrachain disulfide bonds of the envelope glycoprotein 71 from Friend murine leukemia virus.

Envelope glycoprotein 71 from Friend murine leukemia virus was purified to homogeneity by reversed-phase HPLC. It could be shown that all 20 cysteine residues of the molecule are linked by disulfide bonds. After complete tryptic digestion, peptides containing cystine were identified by comparison of the reversed-phase HPLC profile of the digest with that of a reduced aliquot which had been subjected to affinity chromatography on thiol-Sepharose. The locations of the 10 disulfide bonds were determined by isolation, further digestion and analysis of peptides containing cystine. The first cysteine residue of the sequence (Cys46) was shown to be coupled to the sixth (Cys98), leading to a large loop containing four additional cysteine residues. Computer model building and energy calculations led to the assignment of Cys72 to Cys87 and Cys73 to Cys83. The following four cysteine residues of the sequence also constitute a structural unit, with Cys121 bonded to Cys141 and Cys133 to Cys146, and the last two cysteine residues in the amino-terminal domain of glycoprotein 71 form a small loop (Cys178 to Cys184). The first two cysteine residues of the carboxy-terminal domain produce a very small hydrophobic loop (Cys312-Cys315). Cys361 is bound to Cys373, Cys342 to Cys396 and Cys403 to Cys416. A model for the folding pattern of the viral glycoprotein is proposed.

Amino Acid Sequence↗

Drug testing in the workplace. What primary care physicians need to know.

As drug testing in the workplace becomes more common, primary care physicians need to be more informed about social and technical issues involved. How are laboratory results of urinalysis interpreted? What are the primary care physician's responsibilities to the patients being tested and their employers? In this article, Drs Everett and Linder discuss current drug testing procedures, guidelines, and interpretation of results.

Ethics, Medical↗

Comparison of copper binding components in dog serum with those in other species.

The copper content of dog serum and its distribution to copper binding proteins was compared with that of rat and mouse. Total serum Cu concentrations of dogs and mice were one third those of the rat. Plasma ceruloplasmin, determined by azide-inhibitable oxidase activity with two substrates, was 8-fold less in the dog and 9- to 20-fold less in the mouse than in the rat, and, in both dogs and mice, there was 70-75% less ceruloplasmin Cu, determined by atomic absorption after gel filtration. In the dog, the largest proportion of total and exchangeable serum Cu was with the transcuprein fraction. Only one third as much Cu was with albumin in the dog (and mouse) versus the rat, and this was released much more readily through dialysis. In dogs and mice, the exchangeable (nonceruloplasmin) serum copper pool was half the size of that in rats and humans. Especially in the mouse (but also in rats and dogs), a small proportion of the exchangeable pool appeared bound to ferroxidase II. We conclude that the dog may rely more on transcuprein and low molecular weight complexes and less on albumin and ceruloplasmin for transport of copper to cells.

Adult↗

[Extrapyramidal movement disorders after "Isostar Cocktail"].

Two children developed extrapyramidal symptoms after taking an electrolyte drink. There was a good response to Biperidon (Akineton). Only exact investigations showed that both children had accidentally been poisoned by a neuroleptic drug which was added to the electrolyte mixture.

Adolescent↗

[Psychiatric aspects of psychomotor epilepsy].

Historical myths about inevitable behavioural and cognitive consequences of epileptic disorders still provide patients and their families with unfounded fears leading to self-fulfilling prophecies of psychosocial and mental deterioration. Psychomotor attacks are subjectively experienced disruptions in the continuity of life and self-perception which it will be difficult to integrate into the organization of daily life. These facts must be kept in mind when epileptic patients present psychological problems. The most common features of neuropsychological and psychosocial problems are discussed and the importance of combining optimal antiepileptic medication with psychotherapy is underlined. Coexisting epileptic and psychogenic symptoms being difficult to disentangle patients presenting both may be exposed to unfortunate alternating therapeutic strategies by ambitendent therapists. Careful observation without overt attention combined with assisting the patient in obtaining more autonomy and self management appear to be the best policy to stop psychogenic fits.

Anticonvulsants↗

Experience with routine applications of liquid chromatography-mass spectrometry in the pharmaceutical industry.

The combination of liquid chromatography and mass spectrometry (LC-MS) has been established to complement gas chromatography (GC)-MS in the analysis of non-volatile and labile drugs in complex materials. The possibilities of LC-MS in the pharmaceutical industry for the analysis of drug substances and dosage forms, metabolism studies and the elucidation of the structures of materials of biological origin are discussed. Instrumental requirements, limitations and applications of LC-MS are considered and experiences with LC-MS in routine applications are reported. Preliminary results obtained with thermospray LC-MS are compared with those using a direct liquid inlet interface.

Animals↗

Transport of glutathione by intestinal brush border membrane vesicles.

Intestinal brush border membranes prepared from pig jejunum were shown to transport intact reduced glutathione into an osmotically responsive intravesicular space. At early incubation time (under 1 min.) GSH was poorly hydrolysed in its free amino acids. Primarily glutathione uptake was obtained against a concentration gradient (vesicle greater than medium) and was stimulated by Na+.

Animals↗

[Value of sonography, computed tomography and angiography in adrenal diagnosis].

Between 1979 and 1982, 47 patients with pathological process of the adrenals were surgically treated after preceding thorough non-evasive angiographic diagnosis (6 phaeochromocytomas, 20 adrenal adenomas, 8 adrenal hyperplasias, 5 adrenal carcinomas, 5 adrenal cysts and 3 adrenal metastases). The most consistently accurate results were obtained via adrenal phlebography with an accuracy of 94%. This was followed by non-evasive computed tomography (87%). Compared with the data given in literature, hormone determination in the adrenal venous blood was less favourable (79%). Selective adrenal arteriography, which was used less often, yielded correct results in 83% of the cases, whereas the number of accurate diagnoses achieved via sonography was lowest with 54%.

Adenoma↗

Effect of meningomyelocele closure on the intracranial pulse pressure.

Intracranial pressure (ICP) was monitored in a 12-year-old child before and after closure of a large, skin-covered meningomyelocele. Significant cerebrospinal fluid pulse pressure augmentation was observed over a spectrum of pressures following sac closure. Linear regression analysis was done to define pulse pressure-ICP relationships before and after surgery, and a significant increase in the regression slope was noted postoperatively. It is suggested that the unoperated meningomyelocele defect served as a shock absorber to dampen the intracranial pulse pressure. Meningomyelocele closure removes this shock absorber effect, resulting in pulse pressure augmentation.

Blood Pressure↗

[Primary brain tumors in psychiatry].

At the University Psychiatric Clinic in Basle, 14 primary brain tumours were diagnosed in a patient population of 12,530 in the course of 10 years. The rate of primary brain tumours in hospitalized psychiatric patients is thus one in 1,000. Primary brain tumours occurred 20 times more frequently in psychiatric patients than in a normal population, in whom the rate is one in 20,000. The classic brain tumour triad frequently occurs late and is found in less than 50% of patients. In 50 to 60 percent, brain tumour is associated with mental changes, mainly confusional states and psychoorganic syndrome. There is no typical pathopsychology of brain tumours, and that is why the possibility must always be ruled out. On the basis of these remarks, concrete recommendations are made for daily practice.

Adult↗