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Biomedical subjects

M Baron

Publications and source records attributed to M Baron.

At least 37 records · Page 2Linked to original sources
PubMed1991

Heterocyclic quinones. 17. A new in vivo active antineoplastic drug: 6,7-bis(1-aziridinyl)-4-[[3-(N,N-dimethylamino)propyl]amino]-5,8- quinazolinedione.

A series of heterocyclic quinones, 6-substituted and 6,7-disubstituted 4-(alkylamino)-5,8-quinazolinediones, have been synthesized in order to evaluate their in vitro cytotoxicity on L1210 leukemia cells. Among 14 derivatives that have been prepared and studied for the structure-activity relationship, the most potent cytotoxic compound on L1210 leukemia cells was the 6,7-bis(1-aziridinyl)-4-[[3-(N,N-dimethylamino)propyl]amino]-5,8- quinazolinedione (24). This compound has been tested with the use of a cell-image processor on MCF-7 human mammary and HBL human melanoma cell lines. The results show that compound 24 influences cell proliferation and blocks both cells lines in the S phase. In vivo antineoplastic activity of compound 24 has been demonstrated on a broad spectrum of murine experimental models, but it was found highly toxic and produced long-delayed deaths.

Animals↗
PubMed1991

Schizophrenia and affective disorder: are they genetically linked?

The relationship between schizophrenic 'spectrum' disorders and affective illness was studied in the nuclear families of 90 chronic schizophrenic probands. An increased risk of schizophrenia and related disorders was demonstrated among the first-degree relatives of probands with a family history of major affective disorders. Conversely, relatives of probands with a family history of schizophrenic 'spectrum' disorders were at a greater risk of affective illness (major depression) than relatives of probands with no family history. These results lend support to the notion that a subset of affective disorders is associated with the liability to schizophrenia.

Adult↗
PubMed1991

Factor analysis of responses to the WISC-R for gifted children.

Several researchers have focused on the question of whether the traditional two-factor interpretation of WISC--R scores proposed by Wechsler (1974) is appropriate in selecting students to be admitted to gifted programs. Some researchers have suggested that the two-factor solution (Verbal and Performance) of Karnes and K. E. Brown provides the appropriate model, while others have proposed an alternative model based on exploratory research with gifted and average students. The current study expands exploratory findings of S. W. Brown with Rood in 1982 and Yakimowski in 1987, using confirmatory factor analytical procedures. The confirmatory factor analyses for selected groups of gifted (n = 158) and average (n = 195) students (M = 9.6 yr.) indicate that the alternative three-factor solution model may be a better system for interpreting the pattern of WISC--R subtest scores of gifted students than the conventional Verbal and Performance solution.

Child↗
PubMed1991

Radionuclide esophageal transit studies in progressive systemic sclerosis: an analysis of longitudinal data.

Nineteen patients with progressive systemic sclerosis (PSS) were studied by radionuclide esophageal transit (ET) and followed longitudinally for 3 to 5 years. Results were expressed as percent retention at 20 s and 10 min. There was gradual deterioration of ET at both 20 s and 10 min. When results were grouped into quartiles, deterioration occurred in 58.5% of followup studies in patients who initially had potential to deteriorate regarding 20 s retention and in 48% of similar patients regarding 10 min retention.

Adult↗
PubMed1991

[Intestinal obstruction after Nissen's fundo-plication].

Nissen's fundal plication is acknowledged as the most effective procedure to suppress gastroesophageal reflux. It entails some morbidity (dysphagia, gas bloat syndrome), in which obstruction is the least frequently evoked but most severe risk. We report about 6 cases (4 children and 2 adults). The 4 children had been operated 3 times during the first few months of life, and their reflux was secondary to the cure of atresia of the esophagus in 2 cases, and caused severe apneas in 1 case, a former premature infant. In three cases, the obstruction was complicated within a few hours by intestinal ischemia causing death. In one case, the emergent insertion of a gastric tube allowed the decompression of the digestive tract and second surgery; the obstruction recurred 2 months later, with no postoperative complications. Two adults (aged 64 and 66) presented with gastric perforation 7 days and 9 months after fundal pliction; one of them died. These cases show how serious these obstructions are (4 deaths/6 cases). The emergent measure in such cases consists of inserting a gastric tube, although which may be impossible (1 case). The patients and their parents must be informed of this risk of complication and of its expressions. Prevention is based on a strictly submesocolic surgical approach, without any exposure of the small bowel.

Aged↗
PubMed1991

Genetics of manic depressive illness: current status and evolving concepts.

The bipolar affective spectrum is clinically heterogeneous and genetically complex. Current methods for assessment and analysis of familial traits with variable phenotypic expression and unclear mode of inheritance are reviewed. Recent evidence for a major gene localized on the X-chromosome is presented and other linkage findings are discussed. The limitations and prospects of psychiatric genetics are discussed in the light of recent advances in diagnostic nomenclature, statistical genetic techniques, and molecular biology. Methodological uncertainties notwithstanding, the powerful new techniques in genetic research portend well for unraveling the genetics of bipolar affective illness.

Bipolar Disorder↗
PubMed1990

Structure-function relationships in epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha).

The solution structures of the homologous growth factors human epidermal growth factor (hEGF) and human transforming growth factor-alpha (hTGF-alpha), as determined by high resolution NMR and various computational methods, are described. Knowledge of these structures and the sequences of other homologous proteins leads to predictions about growth factor residues which may be involved in the receptor/ligand interface. Recent experiments designed to check these predictions are described briefly. These involve site-specific mutagenesis, receptor binding assays and high resolution NMR studies.

Amino Acid Sequence↗
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↗
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↗