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Biomedical subjects

S Brenner

Publications and source records attributed to S Brenner.

At least 289 records · Page 16Linked to original sources

Social acceptability of methylphenidate and behavior modification for treating attention deficit hyperactivity disorder.

The social acceptability of methylphenidate, behavior modification, and methylphenidate plus behavior modification was evaluated. Fifty mothers of children with attention deficit hyperactivity disorder (ADHD) and 50 control mothers, along with 21 children with ADHD and 20 control children, read a case vignette of an 8-year-old boy with ADHD and descriptions of the three treatment conditions. Subjects then rated the acceptability of each treatment. The mothers of children with ADHD were reassessed 3.5 months later, after experience with interventions for their children. Both ADHD and control families rated behavior modification as the most acceptable, methylphenidate as least acceptable, and the combined condition intermediate between the other two. At follow-up, there was a significant improvement in the acceptability of methylphenidate and the combined condition. The increased acceptability of methylphenidate at follow-up was related to increases in parents' knowledge about ADHD but not to the significant improvements that occurred in the children's hyperactive behavior.

Adult↗

The human genome: the nature of the enterprise.

The development of methods of cloning and sequencing DNA has liberated genetics from the constraints of breeding experiments, and all organisms are now accessible to genetical analysis by the new methods. The analysis of the human genome is likely to produce a revolution in biomedical science, and it is argued that high priority should be given to gene identification. The strategy advocated is one which identifies the expressed genes and pursues mapping in parallel.

Genome, Human↗

Effect of ionization on microbial air pollution in the dental clinic.

The use of spray-producing instruments in the dental clinic continuously creates a potentially harmful contamination of the room environment. In the present study a 13.5-kV corona discharge ionizing generator was used in order to investigate the effect of ions on the microbial air pollution of the dental clinic. Samples of microbial air population were collected in 9-cm-diameter plates containing either Bacto-Brain Heart Infusion Agar or Bacto-Mitis Salivarius Agar and exposed to different time periods in various locations of an active dental clinic. Microbial air levels in the dental clinic were significantly reduced with the generator (by 40-50%). The data suggest that the ionizing generator can be used to reduce the microbial air pollution within the dental clinic, thus reducing the environmental hazard of infections to the staff.

Air Ionization↗

Psoriasis related to angiotensin-converting enzyme inhibitors.

Two mechanisms have been proposed for the pathogenesis of eruptions induced by angiotensin-converting enzyme (ACE) inhibitors: (1) an allergic, immune-mediated reaction and (2) a pharmacologic, dose-dependent response. Two cases of palmoplantar psoriasis are presented, which can be attributed to the induction (case 1) and exacerbation (case 2) of ACE inhibitors. The first patient developed his eruption 2 months after he had received captopril, probably as a result of an allergic immunologic mechanism. This has been based mainly on circumstantial evidence and is further strengthened by the positive result of the mast cell degranulation test. The second patient developed an atenolol-induced, mild plantar psoriasis. She experienced a dramatic flare-up of her psoriatic lesions shortly after she had received an ACE inhibitor. It is suggested that her reaction occurred as a result of the enalapril-induced augmentation of kinin levels in the skin. These 2 patients represent deductive and unusual examples of the two different mechanisms that are responsible for the cutaneous complications of ACE inhibitors.

Aged↗

Prevalence of respiratory conditions among schoolchildren exposed to different levels of air pollutants in the Haifa Bay area, Israel.

During spring 1984, 2334 second and 2000 fifth-grade schoolchildren living in three Haifa Bay areas on the eastern Mediterranean coast with different levels of air pollution were studied. The parents of these children filled out American Thoracic Society and National Heart and Lung Institute health questionnaires, and the children performed the following pulmonary function tests (PFT); FVC, FEV1, FEV1/FEV, PEF, FEF50, and FEF75. A trend of higher prevalence of most reported respiratory symptoms was found for schoolchildren growing up in the medium and high pollution areas as compared with the low pollution area. Part of the reported respiratory diseases were significantly more common among children from the high pollution area. Models fitted for the respiratory conditions that differed significantly among the three areas of residence also included background variables that could be responsible for these differences. Relative risk values, which were calculated from the logistic models, were in the range of 1.38 for sputum with cold and 1.81 for sputum without cold for children from the high pollution area as compared with 1.00 for children from the low pollution area. All the measured values of PFT were within the normal range. There was no consistent trend of reduced pulmonary function that characterized any residential area.

Air Pollutants↗

A possible case of drug-induced familial pemphigus.

Two sisters developed pemphigus vulgaris and pemphigus erythematosus within 3 years. The diagnosis was confirmed by clinical, histologic and immunofluorescent antibody studies. One of the sisters experienced a common cold before the pemphigus developed and displayed a positive macrophage migration inhibition (MIF) test to a combination drug compounded of paracetamol, caffeine, chlorpheniramine maleate and phenylephrine HCl, which she had received 2 weeks prior to the appearance of the cutaneous lesions. It is suggested that her pemphigus was triggered by the drug. Although the patient had a strong genetic and familial predisposition to pemphigus, her clinical symptoms did not become evident until they were activated through an exogenous factor, namely, the causative drug. This case offers an example of a possible interaction between endogenous, genetic factors, and exogenous, triggering factors in the development of full-blown disease.

Acetaminophen↗

Cutaneous horn.

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Carcinoma, Squamous Cell↗

Model for signal sequence recognition from amino-acid sequence of 54K subunit of signal recognition particle.

Protein targeting to the endoplasmic reticulum in mammalian cells is catalysed by signal recognition particle (SRP). Cross-linking experiments have shown that the subunit of relative molecular mass 54,000 (Mr 54K; SRP54) interacts directly with signal sequences as they emerge from the ribosome. Here we present the sequence of a complementary DNA clone of SRP54 which predicts a protein that contains a putative GTP-binding domain and an unusually methionine-rich domain. The properties of this latter domain suggest that it contains the signal sequence binding site. A previously uncharacterized Escherichia coli protein has strong homology to both domains. Closely homologous GTP-binding domains are also found in the alpha-subunit of the SRP receptor (SR alpha, docking protein) in the endoplasmic reticulum membrane and in a second E. coli protein, ftsY, which resembles SR alpha. Recent work has shown that SR alpha is a GTP-binding protein and that GTP is required for the release of SRP from the signal sequence and the ribosome on targeting to the endoplasmic reticulum membrane. We propose that SRP54 and SR alpha use GTP in sequential steps of the targeting reaction and that essential features of such a pathway are conserved from bacteria to mammals.

Amino Acid Sequence↗

Paramyosin gene (unc-15) of Caenorhabditis elegans. Molecular cloning, nucleotide sequence and models for thick filament structure.

Paramyosin is a major structural component of thick filaments isolated from many invertebrate muscles. The Caenorhabditis elegans paramyosin gene (unc-15) was identified by screening with specific antibodies an "exon-expression" library containing lacZ/nematode gene fusions. Short probes recovered from the library were used to identify bacteriophage lambda and cosmid clones that encompass the entire paramyosin (unc-15) gene. From these clones, numerous subclones containing epitopes reacting with anti-paramyosin sera were obtained, providing strong evidence that the initial cloned fragment was, in fact, derived from the structural gene for paramyosin. The complete nucleotide sequence of a 12 x 10(3) base-pair region spanning the gene was obtained. The gene is composed of ten short exons encoding a protein of 866 [corrected] amino acid residues. Paramyosin is highly similar to residues 267 to 1089 of myosin heavy chain rods. For most of its length, paramyosin appears to form an alpha-helical coiled-coil and shows the expected heptad repeat of hydrophobic amino acid residues and the 28-residue repeat of charged amino acids characteristic of myosin heavy chain rods. However, paramyosin differs from myosin in having non-helical extensions at both the N and C termini and an additional "skip" residue that interrupts the 28-residue repeat. The distribution of charges along the length of the paramyosin rod is also significantly different from that of myosin heavy chain rods. Potential charge-mediated interactions between paramyosin rods and between paramyosin and myosin rods were calculated using a model successfully applied previously to the analysis of the myosin rod sequences. Myosin rods aligned in parallel show optimal charge-charge interactions at multiples of 98 residue staggers (i.e. at axial displacements of multiples of 143 A). Paramyosin rods, in contrast, appear to interact optimally at parallel staggers of 493 residues (i.e. at axial displacements of 720 A) but show only weak interaction peaks at 98 or 296 residues. Similar calculations suggest optimal interactions between paramyosin molecules and myosin rods and in their anti-parallel alignments. The implications of these results for the structure of the bare zone and the assembly of nematode thick filaments are discussed.

Animals↗

Myosin heavy chain gene amplification as a suppressor mutation in Caenorhabditis elegans.

In the nematode, Caenorhabditis elegans, the body wall muscles contain paramyosin and two different types of myosin heavy chain, MHC A and MHC B. In mutants that do not express MHC B or that express defective paramyosin, muscle structure is disrupted and movement is impaired. Second site mutations in the sup-3 locus partially reverse these defects and are correlated with a 2- to 3-fold increase in the accumulation of the MHC A isoform. The sup-3 mutations occur at a high frequency (10(-4] after ethyl methanesulfonate (EMS) mutagenesis. This is comparable to the average EMS-induced mutation rate per gene in C. elegans. In this paper we show that the sup-3 mutation is an amplification of the structural gene for the MHC A protein, myo-3. We employed genomic Southern hybridization with MHC gene-specific probes in order to measure the copy number of the myo-3 gene relative to that of the MHC B gene, unc-54. We have identified the putative amplification junctions for these sup-3 alleles using a set of cosmid clones which encompass myo-3 region. Although it has been suggested that gene amplification plays an important role in evolution, there are few known cases of gene amplification in the germ line cells of multicellular organisms. The results shown here provide a clear example of a heritable gene amplification event that occurs at a high frequency in the germ line. Similar events may thus represent the initial event in the evolution of new function and in the formation of multigene families.

Animals↗

DNA fingerprinting by sampled sequencing.

We describe a method for characterizing DNA segments that combines limited sequencing with size separation of restriction fragments. As part of a multistep procedure, 5' overhangs of unknown sequence are generated by cleavage with a class IIS restriction enzyme. After labeling of these ends by using dideoxynucleotides tagged with distinctive fluorescent dyes, the restriction fragments are analyzed by polyacrylamide gel electrophoresis and detection of fluorescent emissions using a commercially available DNA sequencer. The nucleotide-specific fluorescent signatures permit determination of the terminal sequence for each labeled end. The set of labeled fragments, characterized by both size and terminal sequence, constitutes a fingerprint that can be used to compare DNA segments for overlap or relatedness. The inclusion of terminal sequence data dramatically increases the information content of the fingerprint, making comparisons more reliable and efficient than those based upon size alone.

Bacteriophage phi X 174↗

The molecular evolution of genes and proteins: a tale of two serines.

The advent of techniques for cloning and rapidly sequencing DNA has produced an explosive increase of sequence information for nucleic acids and their inferred proteins. Careful study of this large store of data might give us new insights into the relations between the linear sequences of genes and their functions embodied in the three-dimensional structure of proteins, and also illuminate the origin and evolution of the structural complexity of present-day proteins. Here I argue from such a study that the active site sequences of enzymes that have analogous essential serine residues lie in fact on two lines of descent from an ancient ancestral enzyme which had a cysteine instead of serine in its active site. This is based on the assumption that the two codon types which define the separate lines of descent and which have different bases in two positions could not interconvert by single mutations.

Amino Acid Sequence↗