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Biomedical subjects

A Moll

Publications and source records attributed to A Moll.

At least 19 recordsLinked to original sources
PubMed2002

Predictors of treatment failure during highly active antiretroviral therapy (racing trial).

PURPOSE: To determine factors associated with virological failure during long-term treatment with the triple combination of saquinavir soft gel capsule, zalcitabine and zidovudine. METHOD: Open-label, prospective, multicentre study undertaken in private practices and the outpatient department of the Auguste-Viktoria-Hospital. A total of 95 patients with plasma HIV RNA > 5000 copies/ml who had received no more than 6 months pre-treatment with NRTIs and no prior PI therapy received saquinavir soft gel, zalcitabine and zidovudine for 52 weeks, before being randomly assigned to either remain on therapy or switch to nelfinavir, lamivudine and zidovudine for further 52 weeks. RESULTS: Combination therapy with saquinavir, zalcitabine and zidovudine was found to be effective and well tolerated, with virological response to therapy maintained for up to 2 years. In patients responding to therapy, switching to a novel triple regimen did not result in a virological or immunological worsening, but it did not confer an additional clinical benefit. Factors predictive of early treatment failure (virological failure within 16 weeks of treatment initiation) included high viral load and presence of RT mutations at baseline (OR: 0.30, 95% CI 0.11 0.83 and OR 0.13, 95% CI 0.03 0.52, respectively), with baseline viral load and the development of genotypic mutations on therapy being predictive of late treatment failure (16 52 weeks; OR: 0.15, 95% 0.05 0.46 and OR: 0.26, 95% CI < 0.001 1.16, respectively). Plasma saquinavir concentration < 50 mg/ml at 4 weeks was also found to be an independent risk factor for both early and late treatment failure (OR: 1.80, 95% CI 1.23 2.64 and OR: 1.16, 95% CI 0.84 1.60, respectively). CONCLUSIONS: While antiretroviral drug resistance appears to be a principal cause of treatment failure, other factors such as inadequate drug plasma concentrations also play a role.

Adult↗
PubMed2002

Treatment of HIV-associated wasting with recombinant human growth hormone: monitoring of body composition changes by bioelectrical impedance analysis (BIA).

INTRODUCTION: Recombinant human growth hormone (r-hGH) has demonstrated efficacy in treating HIV-associated wasting (HAW), however, HAW has become less prominent since the introduction of highly active antiretroviral therapy (HAART). Recent studies suggest that patients receiving HAART may still experience HAW. We investigated the nature of HAW and the efficacy of r-hGH in these patients. METHODS: We treated 27 HIV-positive patients receiving HAART who had either recent loss of >5% body weight or weight <90% lower limit of normal with 12 weeks of r-hGH (6 mg given either daily or every other day). Body composition changes were monitored using bioelectrical impedance analysis (BIA). RESULTS were assessed for all patients and for a subgroup meeting more stringent definitions of wasting (BIA phase angle a<5.6 degrees, n = 14). - RESULTS: Significant increases from baseline in weight and body cell mass (BCM) occurred in the full population (medians: 2.0 kg weight, 1.5 kg BCM). Patients with phase angle alpha<5.6 degrees also showed increases in weight and BCM (medians: 2.5 kg weight, 1.95 kg BCM), and 10 of 14 showed improvements in the ratio of extracellular mass (ECM) to BCM. At follow-up there was a trend towards loss of the weight and BCM gained on treatment. Treatment was well tolerated. CONCLUSION: Patients receiving HAART continue to experience wasting, and respond well to r-hGH therapy as monitored by BIA.

Adult↗
PubMed2001

Structure prediction of protein complexes by an NMR-based protein docking algorithm.

Protein docking algorithms can be used to study the driving forces and reaction mechanisms of docking processes. They are also able to speed up the lengthy process of experimental structure elucidation of protein complexes by proposing potential structures. In this paper, we are discussing a variant of the protein-protein docking problem, where the input consists of the tertiary structures of proteins A and B plus an unassigned one-dimensional 1H-NMR spectrum of the complex AB. We present a new scoring function for evaluating and ranking potential complex structures produced by a docking algorithm. The scoring function computes a 'theoretical' 1H-NMR spectrum for each tentative complex structure and subtracts the calculated spectrum from the experimental one. The absolute areas of the difference spectra are then used to rank the potential complex structures. In contrast to formerly published approaches (e.g. [Morelli et al. (2000) Biochemistry, 39, 2530-2537]) we do not use distance constraints (intermolecular NOE constraints). We have tested the approach with four protein complexes whose three-dimensional structures are stored in the PDB data bank (Bernstein et al., 1977) and whose 1H-NMR shift assignments are available from the BMRB database. The best result was obtained for an example, where all standard scoring functions failed completely. Here, our new scoring function achieved an almost perfect separation between good approximations of the true complex structure and false positives.

Algorithms↗
PubMed1996

[Conservative therapy of fecal incontinence].

Fecal incontinence is not diagnosis, but a symptom which can result from multiple causes. Therefore, therapy should attempt to treat the underlying disorder whenever possible. If this is not possible, therapy becomes symptom oriented. Besides drug treatment anal biofeedback training is the most important basis of medical therapy. Except for special situations surgery is indicated only if medical therapy has failed.

Biofeedback, Psychology↗
PubMed1995

Interhemispheric transfer in multiple sclerosis.

Interhemispheric transfer (IHT) was investigated in patients with multiple sclerosis (n = 20) and healthy control subjects (n = 23). On verbal dichotic listening and tachistoscopic reading tests, MS patients showed a pattern of left-sided suppression and/or right-sided enhancement, consistent with impairment of IHT. Patients with chronic-progressive MS were most affected. Clinical and empirical implications are noted.

Adult↗
PubMed1992

Depression in male and female subjects with complex partial seizures.

Eighty-four epileptic patients, with seizures originating in either the left or the right hemisphere, were evaluated to determine the relations between lateralization of epileptogenic foci, gender, and depression. Our data suggest that male subjects, but not female subjects, with left-sided foci may be particularly vulnerable to depression.

Adult↗
PubMed1989

Evidence for immunological differences between circulating and thyroid tissue-derived thyroglobulin in men.

The expression of six antigenic epitopes on plasma Tg and tissue-derived Tg was investigated using mouse mabs in immunoradiometric assays. The sensitivity of the assays ranged between 0.5 and 1.5 micrograms l-1. Plasma thyroglobulin of 15 normal individuals and 18 patients with metastatic, differentiated thyroid cancer was analysed. Whereas five monoclonals produced values comparable to the conventional RIA system, the monoclonal antibody Tg 158 did not detect any Tg in the normal individuals and only low levels in two of the cancer patients with the highest Tg levels. In contrast, dilutions of extracts of three different euthyroid goitre samples and three different samples of differentiated thyroid cancer revealed no difference in the antigenic expression of all six epitopes, including the Tg 158 epitope. Papain digestion of purified Tg resulted in a 76 kD fragment which showed immunoreactivity for Tg 158 as well as for Tg 11. No interference of the binding of Tg 158 by T3, T4 or DIT could be detected. We conclude that the monoclonal antibody Tg 158 detects an epitope which is present in thyroid tissue-derived Tg but not in circulating thyroglobulin. This antibody might be useful for the investigation of the secretory process of thyroglobulin from the thyrocytes into the circulation.

Antibodies, Monoclonal↗
PubMed1989

The metabolic causes of slow relaxation in fatigued human skeletal muscle.

1. The relationship between slowing of relaxation and changes of intracellular pH and phosphorous metabolites has been examined in human skeletal muscle during the development of fatigue and subsequent recovery. Results obtained with normal subjects have been compared with those from a subject with myophosphorylase deficiency (MPD) who produced no H+ from glycolysis during exercise and therefore afforded the opportunity of assessing the role of H+ in the slowing of relaxation. 2. Subjects fatigued the first dorsal interosseous muscle in a stepwise fashion under ischaemic conditions, with intervals between the fatiguing contractions during which the relaxation rate was measured from brief tetanic contractions and the muscle phosphorous metabolites and pH were measured by nuclear magnetic resonance spectroscopy. 3. After 21 s maximal voluntary contraction under ischaemic conditions, relaxation in the MPD subject slowed to approximately 50% of the rate in the fresh muscle at a time when the intramuscular pH had not changed. This demonstrates that there is a mechanism causing slowing of relaxation that is independent of H+ accumulation. 4. The normal subjects showed a slow recovery of relaxation compared to the MPD subject when the circulation was restored. The main difference in the intracellular metabolite concentrations between MPD and normal subjects at this time was that, for the latter, the pH remained low (around 6.5) for at least 60 s after the circulation was restored. The results suggest that the slow recovery is a consequence of continuing acidosis, i.e. the existence of a pH-dependent mechanism of slowing. 5. The existence of a pH-dependent mechanism was further indicated by the fact that for the normal subjects, for a similar intracellular concentration of phosphocreatine, relaxation of the recovering muscle was approximately half that of the fatiguing muscle. This was at a time when the pH of the recovering muscle was 0.3-0.4 units less than in the partially fatigued muscle. 6. The results show that in normal muscle there are at least two processes that lead to slow relaxation in fatigued muscle: one due to H+ accumulation, the other being independent of H+.

Adenosine Triphosphate↗
PubMed1988

Purification and characterization of eight class 5 outer membrane protein variants from a clone of Neisseria meningitidis serogroup A.

Methods published for the purification of P.II proteins from Neisseria gonorrhoea have been modified to allow the purification of class 5 proteins from Neisseria meningitidis serogroup A bacteria. The five class 5 protein electrophoretic variants detected within an epidemic in the Gambia (a, b, c, d, and e) and three other variants (f, g, and h) found within other isolates of the same clone in West Africa have been purified with yields of 6-28 mg. The NH2-terminal amino acid sequence for variant c differs from those of the other class 5 proteins, whereas the latter are very similar to the sequence predicted for two class 5 proteins from DNA analyses of serogroup C meningococci and determined for 8 P.II proteins from gonococci. Numerous other regulatory, chemical, and serological differences were found between the c protein and the other class 5 proteins such that we recommend that the class 5 proteins be subdivided into two subclasses. mAbs have been isolated that distinguish between these two protein subclasses and Western blotting with these antibodies enabled us to conclude that both protein subclasses were found in bacteria isolated from different epidemics and pandemics of the last 50 yr.

Amino Acid Sequence↗
PubMed1986

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and monoclonal antibodies as tools for the subgrouping of Escherichia coli lipopolysaccharide O18 and O23 antigens.

The lipopolysaccharide (LPS) of Escherichia coli O18 isolated from a wide variety of sources was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Four different LPS types, designated O18A, O18A1, O18B, and O18B1, were identified. Most O18 strains possess O18A, O18A1, or O18B LPS types, and these types are clonally associated. A reference test strain with the classical O18ab designation possessed O18B LPS, while two reference O18ac strains possessed O18A and O18A1 LPS, respectively. A panel of 15 anti-O18A B-cell hybridomas was isolated. Enzyme-linked immunosorbent assays revealed that some of the monoclonal antibodies produced by these cells recognize different epitopes. Four of these antibodies suffice to distinguish the four O18 types. Numerous strains whose LPS had been typed by SDS-PAGE were tested by agglutination with seven monoclonal antibodies whose specificities had been determined by enzyme-linked immunosorbent assays. The results indicated a perfect correlation between the two methods. Rabbit antisera raised against O18A bacteria agglutinated boiled bacteria of each of the O18 LPS types efficiently. The antisera were adsorbed with bacteria possessing each of the LPS types. The adsorbed sera only distinguished between two groups: O18A and O18A1 versus O18B and O18B1, as shown by agglutination assays and Western blotting. E. coli O4 and O23 and Serratia marcescens O8 antigens, which are reputed to cross-react with O18, were also analyzed. One O4, one O8, and four O23 strains were tested. All made an LPS which was distinguishable from O18 LPS types by SDS-PAGE. Each O23 strain synthesized a different LPS, and three of them synthesized only few short chains. Some of the monoclonal antibodies reacted with O4, O8, and O23A LPSs. The results are interpreted as indicating that numerous E. coli O serogroups will prove to be chemically heterogeneous and that future analyses of subgroup heterogeneity should be guided by results from SDS-PAGE and rely preferentially on monoclonal antibodies as opposed to rabbit hyperimmune sera.

Antibodies, Bacterial↗
PubMed1986

A reexamination of the O1 lipopolysaccharide antigen group of Escherichia coli.

A total of 64 Escherichia coli strains of the O1 serogroup were tested for the migration pattern of their lipopolysaccharides (LPS) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. O1:K1 and O1:K51 strains of the OMP5 outer membrane protein pattern possessed LPS with a doublet pattern (O1A1) or the lowermost band of the O1A1 doublet (O1A2). O1:K1 strains of the OMP9 pattern possessed LPS referred to as O1A, which corresponded to the uppermost band of the O1A1 doublet pattern. A few O1:K? strains possessed LPS of different migration patterns (O1B and O1C). O1A and O1A1 LPS were indistinguishable by chemical techniques, and both reacted with each of 10 different monoclonal antibodies tested. However, O1A1 had an additional epitope within the additional band in each doublet, as demonstrated by adsorption experiments with hyperimmune rabbit sera followed by Western blotting. Furthermore, purified polysaccharide from O1A bacteria was incapable of inhibition in enzyme-linked immunosorbent assays performed with O1A1 LPS as antigen and adsorbed, specific anti-O1A1 antibodies, whereas O1A1 polysaccharide inhibited this reaction. O1B and O1C LPS differed in all respects tested, including chemical composition, from O1A and O1A1 LPS.

Animals↗
PubMed1983

Evaluation of radiculopathies by segmental stimulation and somatosensory evoked potentials.

Thirty-six patients with suspected or myelographically proven radiculopathies were investigated with motor and sensory conductions, F-waves, needle electromyography, and somatosensory evoked potentials (SEPs). SEPs were elicited by cutaneous nerve stimulation representative of input from individual cervical and lumbosacral dorsal roots. A myelographic defect was present in 83% of 30 patients who had myelograms. Overall 78% of patients had one or more abnormal electrophysiologic tests, the needle EMG giving the best diagnostic yield (75%). F-waves and SEPs were abnormal in 43% and 57% of cases respectively. Motor deficit correlated best with abnormal EMGs, whilst abnormal SEPs occurred most frequently when sensory deficit predominated. Prolonged latency of the SEP occurred rarely, reduced amplitude or abnormal morphology being the most useful characteristics. SEPs evoked by cutaneous nerve stimulation are a useful addition to conventionally available electrophysiological methods of evaluating radiculopathies, especially in the absence of motor deficit.

Adult↗
PubMed1982

Mutants that overproduce TraTp, a plasmid-specified major outer membrane protein of Escherichia coli.

The isolation of a series of plasmid mutant derivatives that overproduce the traT outer membrane protein, TraTp, is described. Some of the mutants directed the synthesis of 10-fold more TraTp (200,000 copies/cell) than did the parental plasmid (20,000 copies/cell). The proteins specified by all mutant plasmids except one were correctly inserted into the outer membrane and exposed on the cell surface. The TraTp that was not correctly inserted did not mediate the expected levels of surface exclusion and serum resistance, suggesting that surface localization is a requirement of TraTp function. The overproduction of TraTp was deleterious to bacterial growth, particularly that of minicell mutants of E. coli K-12.

Bacterial Outer Membrane Proteins↗
PubMed1980

Plasmid-determined resistance to serum bactericidal activity: a major outer membrane protein, the traT gene product, is responsible for plasmid-specified serum resistance in Escherichia coli.

Resistance to the bactericidal activity of serum appears to be an important virulence property of invasive bacteria. The conjugative multiple-antibiotic-resistance plasmid R6-5 was found to confer upon Escherichia coli host bacteria increased resistance against rabbit serum. Gene-cloning techniques were used to localize the serum resistance determinant of R6-5 to a segment of the plasmid that encodes conjugal transfer functions, and a pACYC184 hybrid plasmid, designated pKT107, that contains this segment was constructed. The generation and analysis of deletion and insertion mutant derivatives of the pKT107 plasmid that no longer specify serum resistance permitted precise localization of the serum-resistance cistron on the R6-5 map and demonstrated that this locus is coincident with that of traT, one of the two surface exclusion genes of R6-5. Examination of the proteins synthesized in E. coli minicells of pKT107 and its serum-sensitive mutant derivative plasmids confirmed that the serum-resistance gene product of R6-5 is the traT protein and showed that this protein is a major structural component (about 21,000 copies per cell) of the bacterial outer membrane.

Bacterial Proteins↗
PubMed1977

[Creatine kinase isoenzyme MB and CK/GOT-ratio in the differential diagnosis of acute myocardial infarction (author's transl)].

In 56 patients with certain transmural myocardial infarction the reliability of myocard specific creatine kinase isoenzyme MB is compared with the usual estimation of creatine kinase activity in serum and the use of CK/GOT activity quotient. In measurements at different times CK-MB proves to be more reliable than other laboratory parameters: during the first 24 hours after hospital admission CK-MB indicates the infarct and correlates with ECG alterations in practically all cases. In 11 patients with CK-activity increase over 100 U/l of extracardial origin, myocardial involvement can be excluded by measuring CK-MB-activity. Formation of CK/GOT quotient shows erroneously an infarction in about half the cases.

Aspartate Aminotransferases↗
PubMed1976

[Unusual infectious diseases in a municipal hospital (author's transl)].

UNLABELLED: The most important criteria for differential diagnosis are presented with reference to case histories: Falciparum malaria: relapsing fever, hemolytic anemia, hepatosplenomegaly, leucopenia; Kala-azar: insidious course with fever, pancytopenia, macrocytic anemia, hepatosplenomegaly, enlargement of lymph nodes; echinococcosis: symptoms of a benign tumor with displacement. DIAGNOSIS: by identification of the pathogen in malaria and kala-azar, serologically in all three diseases and also radiologically in echinococcosis.

Adult↗