Biomedical subjects

R Theiler

Publications and source records attributed to R Theiler.

At least 55 records · Page 3Linked to original sources

PubMed1994

Reduced vitamin A tolerance in a hyperlipidaemia patient with rapid destructive and hyperostotic osteoarthritis of the hip.

A 59-year-old patient suffering from hyperlipidaemia developed a chronic vitamin A intoxication syndrome after ingestion of 30000 IE retinol/daily over a period of six years. Functional disability of the right hip was caused by radiologically documented hyperostosis of the acetabular circumference. Finally, a prosthesis had to be implanted because of rapid destructive osteoarthritis of the right hip. Implications of vitamin A for rheumatological management are discussed.

Drug Tolerance↗

PubMed1994

Clinical, biochemical and imaging methods of assessing osteoarthritis and clinical trials with agents claiming 'chondromodulating' activity.

This paper reviews, in a first part, methods used for the clinical assessment of osteoarthritis (OA) with special reference, in a second part, to trials of drugs claimed to be chondromodulating agents. The agents examined include glycosaminoglycan-peptide complex (GP-C, Rumalon) and glycosaminoglycan-polysulfate (GAGPS, Arteparon), which both showed some beneficial clinical response. However, their effect on cartilage still remains controversial. The development of a functional hip and knee OA index in clinical assessment and the role of imaging methods and biochemical markers are discussed. In future clinical trials only validated OA indices such as the Lequesne or WOMAC index and the newly established ILAR guidelines for classifying and testing drugs in OA will be accepted for registration purposes. Imaging methods including magnetic resonance imaging (MRI) offer the capacity to provide more precise information concerning cartilage destruction in OA joints. In addition, the biochemical assessment of proteoglycan fragments, bone sialoprotein (BSP), cartilage oligometric matrix protein (COMP) and the balance between stromelysin and its inhibitor (TIMP) in synovial fluid would appear to offer potential applications for the determination of joint tissue damage in the early and later stages of OA. However, these biochemical markers have yet to be validated. It is clear that in the 1990s, for a drug to be designated as disease modifying in OA, it will require a more rigorous evaluation than was hitherto required.

Analgesics↗

PubMed1993

[Chronic vitamin A poisoning with musculoskeletal symptoms and morphological changes of the liver: a case report].

The case of a 69-year-old woman with a chronic vitamin A intoxication syndrome after self-administration of vitamin A is presented. The clinical picture included musculoskeletal disorders, headache and hepatomegaly. The diagnosis of chronic vitamin A intoxication was based on a history of excessive vitamin A ingestion, clinical chemistry and needle biopsy of the liver. Besides retinol and retinyl ester, the serum concentration of retinol-binding protein (RBP) should be determined. Whereas the serum retinol concentration in chronic vitamin A intoxication often does not correlate with toxicity, the ratio between retinol and RBP and the concentration of retinyl ester is more sensitive. Morphological alterations are associated with the cumulative dosage of ingested vitamin A, whereas the daily amount of vitamin A determines the latency until pathological changes occur. The hormone-like, retinoid-receptor mediated molecular mechanism of action seems to be responsible for the multisystemic manifestations in chronic vitamin A intoxication syndrome.

Aged↗

PubMed1993

[Diffuse idiopathic skeletal hyperostosis (DISH) and pseudo-coxarthritis following long-term etretinate therapy].

A 51-year old patient with congenital basal cell naevus syndrome was treated with etretinate (50-100 mg/daily) over a period of 5 years (cumulative dose 110 g). Clinically he developed a stiff back with pronounced disability of both hips. Radiologically, axial involvement of the spine with severe diffuse idiopathic skeletal hyperostosis especially of the lumbar spine, and ossifications of both hips were documented. Rheumatological implications of long-term therapy with etretinate are discussed.

Basal Cell Nevus Syndrome↗

PubMed1993

Predictive value of bronchoalveolar lavage in excluding a diagnosis of Pneumocystis carinii pneumonia during prophylaxis with aerosolized pentamidine.

We assessed the negative predictive value of bronchoalveolar lavage (BAL) for Pneumocystis carinii pneumonia (PCP) during prophylaxis with aerosolized pentamidine. On the basis of the assumption that undiagnosed and untreated PCP would progress and become clinically apparent, for 3 months we prospectively followed 34 consecutive cases in which BAL had not detected PCP. All patients were immunodeficient, had a symptomatic human immunodeficiency virus infection, and were evaluated for possible PCP during prophylaxis with aerosolized pentamidine. No transbronchial biopsies were performed. In 32 of 34 cases, a diagnosis of PCP could be excluded because of other definite diagnoses or improvement during the follow-up. Despite negative results of an examination of their BAL fluid, two patients received empirical treatment that was active against PCP; these patients were regarded as possibly having undiagnosed PCP. Thus, the negative predictive value of BAL alone was at least 94% (32 of 34 cases) in excluding a diagnosis of PCP during prophylaxis with aerosolized pentamidine.

AIDS-Related Opportunistic Infections↗

PubMed1991

Localization of chromatophore proteins of Rhodobacter sphaeroides. II. Topography of cytochrome c1 and the Rieske iron-sulfur protein as determined by proteolytic digestion of the outer and luminal membrane surfaces.

Proteinase K was used to degrade membrane proteins exposed at the outer (cytoplasmic) and inner (periplasmic) surface of sealed, uniformly oriented chromatophore vesicles of Rhodobacter sphaeroides. Exclusive and controlled digestion of the chromatophore interior was achieved after Ca(2+)-induced fusion with large unilamellar phosphatidylglycerol liposomes containing microencapsulated enzyme. Reaction center subunit H, which served as a marker for the outer surface, was degraded to a slightly smaller product in chromatophores. This protein remained intact after liposome-chromatophore fusion, suggesting that the intermixing of lipid bilayers proceeded without significant leakage of the aqueous vesicle contents. In contrast, while cytochrome c1 was not affected in chromatophores, 70-75% was degraded within 60 min after liposome-chromatophore fusion. These results support an arrangement in which the bulk of this protein, including the mesoheme component and active site residues, faces the periplasmic side of the membrane. Although current functional models for the cytochrome bc1 complex predict that the Rieske iron-sulfur center interacts with cytochrome c1 in the periplasm, the iron-sulfur protein resisted proteolytic attack in the liposome-chromatophore fusion products under conditions that caused extensive degradation of cytochrome c1. Two cleavage products of the iron-sulfur protein were observed after the digestion of chromatophores, suggesting both a heterogeneity in the population of this protein and the exposure of at least part of its molecular mass to the cytoplasm.

Bacterial Chromatophores↗

PubMed1991

Localization of chromatophore proteins of Rhodobacter sphaeroides. I. Rapid Ca(2+)-induced fusion of chromatophores with phosphatidylglycerol liposomes for proteinase delivery to the luminal membrane surface.

A protease delivery system was developed for the exclusive and controlled digestion of proteins exposed at the morphological inside (periplasmic surface) of Rhodobacter sphaeroides chromatophores. In this procedure, proteinase K is encapsulated within large unilamellar liposomes which are fused to the chromatophores in the presence of Ca2+ ions. The liposomes were prepared by a detergent dialysis procedure from native phosphatidylglycerol and found to undergo rapid bilayer fusion with purified chromatophore preparations above a threshold concentration of 12.5 mM CaCl2. The fusion process was complete within 10 min at 35 mM Ca2+ with about 80% of the pigment located in the fusion products. Electron micrographs of freeze-fracture replicas confirmed the intermixing of the lipid bilayers and the unilamellar structure of the fused membrane vesicles. The procedure did not affect the labile B800 chromophore of the B800-850 antenna complex, but reduced slightly the absorption due to the B875 core antenna. Emission from both light-harvesting complexes was increased in the fused membranes, suggesting a partial dissociation of photosynthetic units in the expanded bilayer. The results, together with those presented in the following paper (Theiler, R., and Niederman, R. A. (1991) J. Biol. Chem. 266, 23163-23168), demonstrate that this new method fulfills the stringent requirements for a successful delivery of macromolecules to the chromatophore interior.

Bacterial Chromatophores↗

PubMed1991

[The classification of atypical forms of neurofibromatosis].

Neurofibromatosis (NF) represents not an entity but a group of several forms which differ as to symptoms, prognosis and inheritance. In 1982 Riccardi suggested a classification into eight categories. Two of these--Von Recklinghausen NF-1 and bilateral acoustic NF-2- were defined in 1987 by a National Institutes of Health Consensus Development Conference. We describe 13 patients whose symptoms do not fit the diagnostic criteria for NF-1 and NF-2. 6 subjects can be classified as segmental NF-V. One of these patients was remarkable in having iris hamartomata, while his daughter was affected with NF-1. Another (female) patient in this group had areolar freckling, a finding not yet reported in NF patients. 4 cases belong to the late-onset NF-VII category, 3 of whom developed a neurofibrosarcoma. Two subjects are fist-degree relatives (mother and son). We are not aware of familial occurrence of NF-VII. Two further subjects were assigned to the variant form of NF, NF-IV. One patient had symptoms similar to NF-2 but the minimal diagnostic criteria were not fulfilled. Nevertheless, we consider his classification as NF-2 in view of a pattern of intracranial calcification repeatedly and exclusively found in NF-2. In general, assignment to a category of NF is important for appropriate patient management and genetic counselling. Classification of individual patients may be arbitrary at the time.

Adolescent↗

PubMed1991

Functional radiographic diagnosis of the lumbar spine. Flexion-extension and lateral bending.

Several attempts have been made to measure the segmental range of motion in the lumbar spine during flexion-extension with the purpose of gathering additional data for the diagnosis of instability. The previous studies were performed in vitro or in vivo during active motion. The aim of this study was to obtain normal values of passively performed segmental motions. Forty-one healthy adults were examined by means of functional radiographs during flexion-extension and lateral bending. A graphic construction method and a computer-assisted method were used to measure rotations. Comparing with recent in vivo studies, the values obtained for normal angles of rotation were predominately larger. This might be due to the passive examination used in the study. The graphic construction method and computer-assisted method techniques are equally reliable, but the computer-assisted method method yields other important kinematic data, such as translations. It is proposed that passive motion be applied during functional examination of patients with suspected instabilities. However, the large variation of rotational values between individuals in the normal population may limit the clinical usefulness of functional lumbar analysis using this parameter. Future studies should explore the clinical relevance of determining altered segmental mobility in low-back pain patients.

Adult↗

PubMed1991

Magnetic stimulation of motor cortex and motor roots for painless evaluation of central and proximal peripheral motor pathways. Normal values and clinical application in disorders of the lumbar spine.

Magnetic stimulation of the motor cortex, motor roots, and proximal nerve trunks was performed in 46 healthy adults and in 73 consecutive patients with disorders of the lumbar spine. In combination with neurography and F-wave recordings, the fractionated stimulation of the motor pathways allowed calculation of conduction times of the pyramidal tract fibers, of the motor roots (ie, caudal fibers), and of the motor fibers of the lumbosacral plexus. Normal values for motor conduction times to the quadriceps, anterior tibial, and extensor digitorum brevis muscles were established. Patients had clinical and radiologic diagnoses of spinal stenosis (n = 43) and nerve root compression syndromes (n = 30). Motor conduction times to lower limb muscles were significantly delayed (above mean normal value +/- 2 x SD) in 65% of the patients with spinal stenosis and 50% of the patients with nerve root compression syndromes. Conduction slowing could be localized within the motor root and caudal fiber segment of the motor pathways in 80% of the patients in whom F-waves could be recorded. This method can be used to verify, quantify, and locate lesions of the motor pathways in conditions such as compression of the spinal cord, the caudal fibers (spinal stenosis), or the motor root passing through the intervertebral canal.

Adult↗

PubMed1991

Conduction velocities of pyramidal tract fibres and lumbar motor nerve roots: normal values.

Measurements of spinal cord and individual lumbar nerve root lengths were performed in 20 dissected cadavers. These data were correlated with the pyramidal tract and motor root conduction times obtained in 53 healthy subjects using motor evoked potentials. The distance between motor cortex and the level of the anterior horn cells ranged from 50.2 +/- 3.0 cm (mean +/- standard deviation) for the L1 segment to 54.4 +/- 3.6 cm for the L5 segment. The length of the motor roots from their exit from the myelon to their exit from the intervertebral foramen ranged from 10.3 +/- 1.7 cm in the L1 root to 17.5 +/- 1.9 cm in the L5 root. The central motor conduction velocity calculated for the distance motor cortex - anterior horn cells of the L5 segment was 50.1 +/- 4.5 m/s. The proximal peripheral conduction velocity of the motor nerve root between its exit from the spinal cord and its exit from the intervertebral foramen was 75.9 +/- 29.0 m/s. The overall conduction velocities between motor cortex and exit of the nerve roots from the intervertebral foramen were 57.4 +/- 6.3 m/s for the L4 fibers to the quadriceps femoris and 57.3 +/- 6.1 m/s for the L5 fibers to the anterior tibial muscle.

Adult↗

PubMed1990

Chromatographic and protein chemical analysis of the ubiquinol-cytochrome c2 oxidoreductase isolated from Rhodobacter sphaeroides.

The ubiquinol-cytochrome c2 oxidoreductase (cytochrome bc1 complex) purified from chromatophores of Rhodobacter sphaeroides consists of four polypeptide subunits corresponding to cytochrome b, c1, and the Rieske iron-sulfur protein, as well as a 14-kDa polypeptide of unknown function, respectively. In contrast, the complex isolated from Rhodospirillum rubrum by the same procedure lacked a polypeptide corresponding to the 14-kDa subunit. Gel-permeation chromatography of the R. sphaeroides cytochrome bc1 complex in the presence of 200 mM NaCl removed the iron-sulfur protein, while the 14-kDa polypeptide remained tightly bound to the cytochromes; this is consistent with the possibility that the latter protein is an authentic component of the complex rather than an artifact of the isolation procedure. The individual polypeptides of the R. sphaeroides complex were purified to homogeneity by gel-permeation chromatography in the presence of 50% aqueous formic acid and their amino acid compositions determined. The 14-kDa polypeptide was found to be rich in charged and polar residues. Edman degradation analysis indicated that its N terminus is blocked and not rendered accessible by de-blocking procedures. Cyanogen bromide cleavage gave rise to a blocked N-terminal fragment as well as a C-terminal peptide comprising more than one-third of the protein. Gas-phase sequence analysis of this peptide established a sequence of 48 residues and identified a putative trans-membrane segment near the C terminus. The blocked N-terminal fragment was cleaved at tryptophan with BNPS-skatole. The resulting peptides, together with tryptic fragments derived from the intact protein, yielded additional sequence information; however, none of the sequences exhibited significant homologies to any known proteins. Tryptic fragments were also used to generate sequence information for cytochrome c1.

Amino Acid Sequence↗

PubMed1990

Motor-evoked potentials in patients with cervical spine disorders.

Measurements of motor-evoked potentials by means of fractionated magnetic stimulation of motor pathways to the upper limbs was performed as part of the clinical assessment in 268 patients with cervical spine disorders. Seventy-two percent of the 127 patients with degenerative changes of the cervical spine, 67% of the 55 patients with rheumatoid arthritis (RA), and 57% of the 51 patients with trauma of the cervical spine showed a pathologic delay of central motor latency (CML). The data suggest that this method has a high sensitivity and therefore is recommended in the diagnosis of cervical spine disorders in patients with suspected compression of neural structures.

Adolescent↗

PubMed1990

Magnetic transcranial brain stimulation: painless evaluation of central motor pathways. Normal values and clinical application in spinal cord diagnostics: upper extremities.

Painless transcranial magnetic stimulation has been performed on 53 healthy adults in order to obtain normal values of central motor pathway conduction times to cervical segments innervating upper limb muscles. Central motor latency was 5.1 msec when recording from the biceps brachii and 5.2 msec when recording from the abductor pollicis brevis or abductor digiti minimi muscles. The plexus motor latency as the conduction time between the cervical motor root and the proximal nerve trunks in the axillary region was 2.2 msec and 2.6 msec when recorded from the abductor pollicis brevis and abductor digiti minimi muscles, respectively. Conduction times higher than mean latency + 2 standard deviation may indicate a pathologic conduction slowing. Magnetic stimulation of the motor system is a new painless neurophysiologic technique enabling examination of the central motor pathways in awake subjects. With respect to spinal cord diagnostics, this method is useful in conditions such as compression of the spinal cord or of the motor root in the intervertebral foramen or canal.

Adult↗

PubMed1986

Effect of infrared and visible light on 2-azidoanthraquinone in the QA binding site of photosynthetic reaction centres. An unusual mode of activation of a photoaffinity label.

Quinone-depleted reaction centres of Rhodobacter sphaeroides were reconstituted with 2-azidoanthraquinone and irradiated with short (50 ms) pulses of intense infrared (lambda = 850 +/- 50 nm) or visible light (460 less than lambda less than 630 nm). The irradiations brought about the rapid degradation of the protein-bound photoaffinity label even though it does not absorb light in either spectral region. The decomposition of the label was accompanied by a covalent modification of subunit M and by a loss of photochemical activity of the reaction centre protein (as measured by the light-induced electron transfer onto the primary acceptor, QA). In the case of the photolysis with IR light, these effects were triggered by the reduction of the protein-bound quinone (QA) to the semiquinone (Q-A) in the process of primary charge separation. The resulting reactive species showed properties of both a semiquinone and a triplet nitrene. Efficiency and specificity of the covalent incorporation were markedly improved when visible rather than IR light was used for the photolysis, presumably, because the triplet nitrene resulting from the primary charge separation was further activated in a second light-dependent reaction. The results suggest that, in conventional photoaffinity labeling experiments, the efficiency and specificity of the covalent incorporation of an aryl azide photolabel into a target protein may be improved when the photolysis is carried out with a combination of UV and intense visible light, rather than with UV light alone.

Affinity Labels↗

PubMed1985

Complete amino acid sequence of the B875 light-harvesting protein of Rhodopseudomonas sphaeroides strain 2.4.1. Comparison with R26.1 carotenoidless-mutant strain.

The complete amino acid sequence was determined for the alpha- and beta-chains of the B875 light-harvesting protein purified from photosynthetic membranes of Rhodopseudomonas sphaeroides 2.4.1. The sequence of the B875-alpha-polypeptide was identical to that reported for the R26.1 carotenoidless mutant [(1985) Biochim. Biophys. Acta 806, 185-186] and contained 58 amino acid residues with a blocked methionine and a glutamic acid at the N- and C-termini, respectively. The B875-beta-polypeptide contained 48 amino acid residues with alanine and phenylalanine as respective N- and C-termini; although otherwise identical, the leucine at position 29 in the wild-type strain was replaced by proline in the mutant. This radical amino acid substitution occurred within the central hydrophobic domain of the beta-polypeptide chain and is thought to result in a weakening of the structure of the alpha/beta heterodimer since it was not possible to isolate the intact pigment-protein complex from the R26.1 mutant strain.

Amino Acid Sequence↗

PubMed1984

The light-harvesting polypeptides of Rhodopseudomonas sphaeroides R-26.1. I. Isolation, purification and sequence analyses.

Four low-molecular-mass polypeptides were isolated and purified from chromatophore membranes of Rhodopseudomonas sphaeroides blue-green mutant R-26.1 by a combination of gel filtration and ion-exchange chromatography in organic solvents. On dodecyl sulfate polyacrylamide gels, the purified polypeptides comigrate with bands LH-1, LH-2 and LH-3 known to be related to the antenna-pigment-protein complexes. The complete primary structures were elucidated by automated Edman degradation of the intact polypeptides and of overlapping C-terminal fragments obtained after chemical cleavage at tryptophan and methionine residues. The C-termini were verified by hydrazinolysis and, in one case where an overlapping C-terminal fragment could not be obtained, by digestion with carboxypeptidase A. The four polypeptides show a tripartite structure: i.e. a polar N-terminal region is separated from a polar C-terminal region by a segment of about 21 predominantly hydrophobic amino-acid residues. All hydrophobic segments contain a characteristic conservative histidine residue. The C-terminal region is reduced to only a few amino acids in the two polypeptides which together form band LH-3, i.e. LH-3A and LH-3B. Their extended N-terminal region is rich in charged residues and contains an additional conserved histidine residue close to the beginning of the hydrophobic segment. These properties place LH-3A and LH-3B into subgroup (beta-polypeptides: B 870-beta and B 850-beta, respectively). LH-1 and LH-2 appear to form another subgroup (alpha-polypeptides: B 870-alpha and B 850-alpha, respectively) as suggested during a search for conservative elements within their sequences (structural basis for classification). N-Terminal analyses carried out with intact antenna-pigment-protein complexes revealed the following: (i) LH-1 and LH-3 are associated with the B 870 complex in Rp. sphaeroides 24.1 (wild type), (ii) the same polypeptides are almost exclusively present in chromatophore membranes of Rp. sphaeroides R-26, a blue-green mutant which absorbs at 870 nm, (iii) LH-2 and LH-3B are the constituent polypeptides of the B 800-850 complex of Rp. sphaeroides 2.4.1 and of the spectrally altered B 850 complex isolated from the blue-green mutant R-26.1 which absorbs at 860 nm. This mutant contains LH-2 and LH-3B along with LH-1 and LH-3A and apparently is able to form both types of antenna complexes.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

PubMed1984

The light-harvesting polypeptides of Rhodopseudomonas sphaeroides R-26.1. II. Conformational analyses by attenuated total reflection infrared spectroscopy and the possible molecular structure of the hydrophobic domain of the B 850 complex.

Attenuated total reflection infrared spectroscopy were used to study the conformation of the purified light-harvesting polypeptides from Rhodopseudomonas sphaeroides R-26.1. B 870-alpha and B 850-beta are characterised by a high content of alpha-helix; B 850-alpha and B 870-beta, in contrast, contain extensive antiparallel chain-pleated sheet structure. The beta-structure is likely to be an artifact of the isolation because B 850-alpha assumes a predominantly alpha-helical conformation in the intact antenna complex. It is concluded that lipid-protein interactions play a crucial role in the stabilisation of the "native" alpha-helical fold of B 850-alpha and thus in the stabilisation of the entire antenna-pigment-protein complex. The results obtained concerning the "in situ" conformation of B 850-alpha and B 850-beta were used, together with the known primary structures and data available from the literature, to construct a rough molecular model of the hydrophobic domain of the elementary unit of the B 850 complex.

Bacterial Proteins↗