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Biomedical subjects

M Baron

Publications and source records attributed to M Baron.

At least 145 records · Page 8Linked to original sources
PubMed1990

Structure of the fibronectin type 1 module.

The rapid accumulation of sequence data has provided insight into the evolution of proteins and led to the identification of 'mosaic proteins'. These proteins have evolved by duplication, insertion and deletion of a common pool of structural units or modules, yet their biological functions are diverse. They are involved in cell adhesion and migration, embryogenesis and the pathways of blood clotting, fibrinolysis and complement. The modular units are defined by 'consensus sequences' which often include conserved disulphide bonds. Despite the available sequence information, little is known of the tertiary structure of mosaic proteins. If, however, the 'consensus structure' of the modules were known, valuable structural information could be inferred about a wide variety of proteins and biological systems. An important mosaic protein is fibronectin, an extracellular matrix protein that consists of three types of module (see refs 3, 7 for reviews). Here we describe the structure of the fibronectin type 1 module which appears twelve times in fibronectin and is also found in factor XII and tissue plasminogen activator. The module was produced using a yeast expression system and the structure was determined in solution using 1H NMR. This methodology promises to be extremely powerful in the investigation of modules from a wide range of mosaic proteins.

Amino Acid Sequence↗
PubMed1990

Structure-function analysis of epidermal growth factor: site directed mutagenesis and nuclear magnetic resonance.

The role of leucine-47 in determining the structure and activity of human epidermal growth factor was examined using site-directed mutagenesis. Wild type protein and four variants in which Leu47 was replaced by valine, glutamate, aspartate and alanine were produced from yeast. 1H NMR experiments demonstrated that substitution of Leu47 had little effect on the protein structure. The observed reduction in receptor binding affinity caused by the substitutions could thus be attributed to perturbation of a residue directly involved in receptor interactions.

Binding, Competitive↗
PubMed1990

The fibromyalgia syndrome. Could you recognize and treat it?

Many of your patients may complain of innumerable "aches and pains." One possible diagnosis for these symptoms is the fibromyalgia syndrome, a common musculoskeletal condition. This article provides information to help you increase your ability to recognize, understand, and treat this condition.

Fibromyalgia↗
PubMed1990

Inflammation and cartilage metabolism in rheumatoid arthritis. Studies of the blood markers hyaluronic acid, orosomucoid, and keratan sulfate.

Single analyses of peripheral blood of rheumatoid arthritis (RA) patients showed a significant reduction in the mean value for keratan sulfate (KS) compared with that in control subjects, but the mean value for orosomucoid (OM) was elevated compared with that in control subjects. Some RA patients displayed highly elevated levels of hyaluronic acid (HA), while others exhibited normal levels. There was a significant inverse correlation between OM and KS content in RA patients, as well as a direct correlation between HA and OM. In longitudinal studies of RA patients, parallel changes in OM and HA and inverse changes between KS and OM or HA were commonly observed. Clinical analyses revealed that there was an inverse correlation between KS and morning stiffness, and direct correlations between the number of tender joints and HA, and between HA or the erythrocyte sedimentation rate and the number of joints with effusions. The reason(s) for the inverse correlation between KS and OM as an index of systemic inflammation remains to be established. Circulating HA represents an index of joint inflammation, for which a marker has not been previously available.

Adult↗
PubMed1990

The first EGF-like domain from human factor IX contains a high-affinity calcium binding site.

It has been suggested that epidermal growth factor-like (EGF-like) domains, containing conserved carboxylate residues, are responsible for the high-affinity calcium binding exhibited by a number of vitamin K-dependent plasma proteins involved in the control of the blood coagulation cascade. These include the procoagulant factors IX and X, and the anticoagulants protein C and protein S. To test this hypothesis we have expressed the first EGF-like domain from human factor IX (residues 46-84) using a yeast secretion system, and examined calcium binding to the domain. Using 1H-NMR to measure a calcium-dependent shift assigned to Tyr69 we have detected a high-affinity calcium binding site (Kd = 200-300 microM). We suggest that other EGF-like domains of this type may have similar calcium binding properties. In addition, we have completely assigned the aromatic region of the NMR spectrum by NOESY and COSY analysis, and have used these data to discuss the effect of calcium and pH on the conformation of the domain with reference to a model based on the structure of human EGF.

Amino Acid Sequence↗
PubMed1990

The impact of phenotypic variation on genetic analysis: application to X-linkage in manic-depressive illness.

Genetic linkage studies have opened new vistas for behavioral and psychiatric genetics. However, phenotypic diversity and diagnostic uncertainties can lead to spurious linkage findings. A method of analysis is proposed that takes these factors into account. When applied to manic-depressive disease, the results indicate that previous evidence for a major gene localized on the distal long arm of the X-chromosome cannot be ascribed to phenotypic uncertainties and misclassifications, i.e., a type I error. Although the lod score (the logarithm of odds) favoring linkage is reduced with the more restrictive clinical definitions of the phenotype, it remains significant nonetheless. Thus, the linkage finding is robust over a range of phenotypic patterns and presumed phenocopy frequencies. The results also suggest that the X-linked phenotype is a particularly severe form of manic depression characterized by early onset, high familial prevalence of the bipolar form, and high recurrence rate of major depression. These findings may have important implications for the design and interpretation of genetic linkage studies and for refining diagnostic techniques in mental disorders.

Adolescent↗
PubMed1990

Genetic linkage in mental illness. Limitations and prospects.

Advances in genetic linkage strategies, including techniques of molecular genetics, augur well for the discovery of disease-related genes in mental disorders. Recent studies showing linkage of chromosomal loci to bipolar affective illness and schizophrenia attest to the potential in the 'new genetics'. However, the failure to replicate some of the early findings has led to calls for re-evaluation of the methodology in psychiatric research. Problems in studying complex (psychiatric) disorders include diagnostic uncertainties, unclear mode of transmission, aetiological heterogeneity, cohort effects, and assortative mating. Knowing the potential pitfalls in linkage analysis of mental illness should avert spurious findings and will increase the prospects of success.

Genetic Linkage↗
PubMed1990

The purchase of specialized radiologic software: estimation of investment. Part II.

For the most part, specialized radiologic software addresses narrow vertical markets that are not large enough to attract the larger software firms. This can work to the benefit of the user, for smaller companies tend to be more flexible and are better able to respond to the user's needs and to tailor their product to meet specific requirements. However, because the companies are small and often relatively young, some do not have the stability associated with larger, well-established firms. As a result, it may be more risky to commit to one of their programs. Nevertheless, with appropriate cautions regarding the company and its product, with proper training of departmental personnel and with adequate safeguards to protect data, these programs can represent a secure and prudent investment.

Capital Expenditures↗
PubMed1989

Changes in glomus cell membrane properties in response to stimulants and depressants of carotid nerve discharge.

Intracellular recordings were made from glomus cells in the excised, intact or sliced (150-200 microns) carotid body. Carotid nerve discharge was also recorded from intact preparations. Slices were prepared for visual (Nomarski) control of microelectrode impalement. Resting potential (Em), input resistance (Ro) and voltage noise (Erms) were measured in control conditions and in response to several stimulants (interruption of flow, hypoxic and histotoxic [NaCN]anoxia, hypercapnia, asphyxia and acidity) and depressants (alkalinity, cooling) of the carotid nerve sensory discharge. Different glomus cells responded differently to the same stimulus but significant trends were found. The more common responses to zero flow and anoxia (hypoxic and histotoxic) were depolarization (64%) and decreases in Erms (63%) and Ro (71%). When extracellular pH was varied from 8.5 to 5.0, the preponderant responses were cell depolarization, and increases in noise and input resistance as pH decreased. Consequently, cell depolarization induced by zero flow and anoxia tended to be accompanied by reduced Ro, whereas that induced by acidity generally showed increased Ro. Changes in voltage noise usually followed variations in Ro. When nerve discharge frequency was plotted against delta Em or delta Erms there were positive correlations during acid stimulation. However, these correlations were complex (parabolic) during flow interruption and anoxia: an increase in discharge occurred in response to cell depolarization and to hyperpolarization. These results suggest that hypoxia and hypercapnic or acidic stimuli act on glomus cells by different mechanisms. This finding is consistent with evidence obtained by recording carotid nerve discharges in intact animals.

Animals↗
PubMed1989

The solution structures of epidermal growth factor and transforming growth factor alpha.

The structures of human epidermal growth factor (EGF) and human transforming growth factor alpha (TGF alpha) have been determined in solution using nuclear magnetic resonance techniques. The features of each structure are described and similarities and differences between them are discussed. The structures are combined with information from sequence homologies to produce a model of the receptor-recognition sites of EGF and TGF alpha, which can be tested in a site-directed mutagenesis programme. The model assists in explaining previous observations of sequence-activity relationships. The TGF alpha and EGF structures also serve as models for homologous modules in other extracellular proteins.

Amino Acid Sequence↗
PubMed1989

HLA-B27 testing in ankylosing spondylitis: an analysis of the pretesting assumptions.

Typing for histocompatibility antigen HLA-B27 has been suggested as a useful diagnostic test for ankylosing spondylitis (AS) in certain clinical situations. The appropriate use of any diagnostic test requires the clinician to estimate the likelihood of disease before the test is performed. One clinical situation in which B27 testing has been suggested to be useful is in the investigation of a patient with low back pain suggestive of AS but with normal sacroiliac radiographs. We analyze here the sequence of steps taken by the clinican in estimating the likelihood of AS. The assumptions that must be made to render B27 typing useful are calculated.

Back Pain↗
PubMed1989

Traumatic knee injuries: the accuracy of MRI compared with arthroscopy.

Forty-three knees in 43 patients were evaluated preoperatively with magnetic resonance imaging (MRI). Both menisci and cruciate ligaments subsequently were examined directly with arthroscopy. A grading scale was used to evaluate intrameniscal signal intensity and to predict the presence of meniscal tear using MR. Compared with arthroscopy, the sensitivity, specificity and accuracy of MRI were, respectively, 100%, 88% and 93% for tears of the medial meniscus; 72.7%, 93.7% and 88.4% for tears of the lateral meniscus; 100%, 96.7% and 97.7% for tears of the anterior cruciate ligament. There were no posterior cruciate ligament tears, and none were suggested from the images. Our results show that MRI is a valuable diagnostic aid in the management of traumatic knee injury.

Adolescent↗
PubMed1988

Isolation of proteoglycan-specific T lymphocytes from patients with ankylosing spondylitis.

Three T-cell lines and clones of the OKT4 phenotype have been isolated from the peripheral blood of three patients with ankylosing spondylitis. Antigen specificities of T cells were determined with purified protein derivative-(PPD) and cartilage-derived antigens, namely proteoglycans from human articular cartilage and intervertebral disc, bovine nasal cartilage, and rat chondrosarcoma and human type II collagen from cartilage. A cell line from one patient reacted with proteoglycans from human articular cartilage and human intervertebral disc, but the other two cell lines (each from a different patient) and four clones from one of the latter two lines proved to be highly specific for the human articular cartilage proteoglycan. From a study of four proteoglycan specific clones isolated from one patient, it is clear that removal of chondroitin sulfate had no effect on immunoreactivity but digestion of proteoglycan with pronase or alkali/sodium borohydride treatment abolished all reactivity. A OKT4-positive T-cell clone isolated from a healthy adult which was reactive to PPD was used to compare the antigen specificity of cells: this clone showed no reactivity to any of the other putative antigens listed above.

Adult↗
PubMed1988

Diurnal and circannual variation in platelet 3H-imipramine binding: comparative data on normal and affectively ill subjects.

Using a cross-sectional design, we examined the diurnal and circannual variation in platelet 3H-imipramine binding in 33 patients with bipolar affective disorder, 34 patients with unipolar affective disorder and 58 normal controls. There was no evidence for statistically significant diurnal or circannual variation in the binding parameters in any of the diagnostic categories.

Adult↗
PubMed1988

Risk factors in schizophrenia. Season of birth and family history.

The association between the familial risk for schizophrenia and season of birth was studied in 88 schizophrenic patients. An increased risk for schizophrenia and 'spectrum' disorders was demonstrated among the first-degree relatives of winter and spring-born schizophrenic patients. However, patients with a family history of schizophrenia and 'spectrum' disorders did not differ from patients with no family history with respect to season of birth. Season of birth was unrelated to the sex of the patient, birth order, age at onset, or clinical subtypes (paranoid vs non-paranoid, as defined by the RDC, and 'narrow' vs 'broad', as defined by Taylor & Abrams' 1975 criteria). The morbid-risk data support a 'stress-diathesis' hypothesis whereby environmental factors (in this case a seasonally varying viral insult may be implicated) interact with genetic vulnerability to increase the risk for schizophrenia.

Adult↗
PubMed1988

Molecular genetics and human disease. Implications for modern psychiatric research and practice.

Techniques of molecular genetics, including recombinant-DNA technology, are likely to have a key role in modern psychiatric research and practice. This article reviews some methods of DNA analysis and their applications to clinical science: specifically, how these methods can be used to localise, identify, isolate, and clone clinically important genes, and how this should enable us to elucidate the molecular pathology of most inherited (psychiatric) disorders. The implications of these developments for prevention and treatment of genetic disease are discussed.

Brain Chemistry↗