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Biomedical subjects

M Conrad

Publications and source records attributed to M Conrad.

At least 73 records · Page 4Linked to original sources
PubMed1989

Role of maternal depression in perceptions of child maladjustment.

We investigated (a) the relation of maternal depression to perceptions of externalizing and internalizing disorders in children and (b) quality of communication in a mother-child interaction task as a function of maternal depression and perceptions of the child. 64 children of unipolar or bipolar mothers, chronic medically ill or normal mothers were studied; clinical diagnoses, children's reports, and teachers' ratings served as objective criteria of children's maladjustment. Maternal depression defined by current symptomatology on the Beck Depression Inventory and by psychiatric status was not associated with misperceptions of psychopathology. Maternal depression interacted with children's actual behaviors to predict mothers' perceptions: nondepressed mothers were less accurate reporters of problems in children than were depressed mothers. Depressed mothers who perceived maladjustment in their disturbed children made more negative comments in interactions that did nondepressed mothers of disturbed children. The apparent mutual impact of mothers' and children's maladjustment requires fuller exploration in offspring studies.

Adolescent↗
PubMed1989

DNA and spermidine provide a switch mechanism to regulate the activity of restriction enzyme Nae I.

Sequence-specific DNA-protein interactions are basic to DNA function. To better understand these interactions, we studied the effect of position on cleavage of DNA by the type II restriction enzyme (EC 3.1.21.4) Nae I. We discovered two classes of Nae I restriction sites: sites susceptible and sites resistant to cleavage. Kinetic analysis showed that Nae I was activated by DNA containing cleavable Nae I sites to rapidly cleave resistant Nae I sites by a noncompetitive mechanism with a Km for substrate DNA of about 2 nM and a KA for activating DNA of about 6 nM; activation increased catalysis but not substrate binding. Deletion mutagenesis in vitro showed that sequences flanking the Nae I recognition site were responsible for the differences between activating and nonactivating Nae I sites. The polyamine spermidine had a dramatic effect on the interaction of Nae I with DNA; in the presence of 1 mM spermidine, resistant sites were cleaved rapidly and cleavable DNA inhibited cleavage. The direct regulation of enzymatic activity by DNA sequences in trans, and the modulation of this regulation by a polyamine that is sensitive to the cell cycle, provides a regulatory switch mechanism. The implications of this switch for biological control functions are discussed.

Base Sequence↗
PubMed1989

Excision repair of O6-methylguanine synthesized at the rat H-ras N-methyl-N-nitrosourea activation site and introduced into Escherichia coli.

O6-methylguanine (O6-methylG) is believed to be the premutagenic lesion responsible for mutational activation of the H-ras proto-oncogene in rats treated with N-methyl-N-nitrosourea (MNU). Research on the repair of O6-methylG has primarily focused on the methyltransferases. Potentially, other repair proteins may be involved in repair of O6-methylG. We have investigated the effect of Escherichia coli UvrABC excision repair on O6-methylG synthesized at the rat H-ras MNU activation site in a partial rat H-ras sequence constructed in an M13mp vector. An oligonucleotide self-selection technique was used to identify progeny phage containing DNA replicated from the O6-methylG-containing strand. We found that excision repair can help protect against mutation by O6-methylG at the rat H-ras MNU activation site.

Base Sequence↗
PubMed1988

Maturation of the immune response: a computational model.

Experimental studies of the effect on antibody affinity of antigen dose and time after immunization show that average affinity increases progressively with time after immunization, and that this increase is greater at lower doses of antigen. In this paper we describe a polyclonal computer model of the immune system that yields all the essential phenomena of affinity maturation, including dose-dependency. Our main findings are (1) the dose-dependency relationship is not produced when typical assumptions regarding B-cell populations and binding reactions are employed, and (2) it is possible to reproduce this dependency by assuming two classes of lymphocytes: generalists and specialists. Generalists have a low threshold for response and produce antibody of low effectiveness, whereas specialists have a high threshold for response, and produce highly effective antibody. We make an analogy between the generalists and a pioneer species in ecological succession, and suggest how the generalists may contribute to a more effective defense against real infections.

Antibody Affinity↗
PubMed1988

Unexpected dystocia secondary to a fetal sacrococcygeal teratoma: a successful outcome.

Sacrococcygeal teratoma is a rare cause of dystocia. With recent advances in perinatal care, particularly the increasing use of maternal ultrasound, it is unlikely that unexpected dystocia secondary to this tumor will be seen by many physicians. Recent reports of this type of dystocia are rare and infant mortality secondary to it is high. However, if and when encountered, such dystocia need not imply a bad prognosis for either mother or infant. This is a report of successful management of one case as well as a presentation of recently reported cases and recommendations for management.

Adult↗
PubMed1986

Induction of deletion and insertion mutations by 9-aminoacridine. An in vitro model.

The ability of 9-aminoacridine to induce mutagenic lesions during DNA replication in vitro was investigated. The ampicillinase gene of pBR322 was replicated in vitro in the presence of 9-aminoacridine. Transfection of the replicated DNA into Escherichia coli gave Amps mutants. Determination of the base changes in 76 of these mutants indicated that the spectrum of mutations induced by 9-aminoacridine was consistent with its action in vivo. Both large (407-base) and small (1- and 2-base) deletions were induced at repetitive sequences. The frequency of deletion mutations depended on the identity of the base deleted and sequences surrounding the deletions. The characteristics of the frameshift mutations induced were consistent with the interactions of 9-aminoacridine with DNA. These results establish that 9-aminoacridine can induce frameshift mutations during the replication process and provide an in vitro model of frameshift induction for mechanistic studies.

Aminacrine↗
PubMed1986

O6-methylguanine mutation and repair is nonuniform. Selection for DNA most interactive with O6-methylguanine.

Mutations were induced in the ampicillinase gene of a bacteriophage f1/pBR322 chimera both by incorporation of O6-methyl-dGTP opposite T during DNA replication in vitro and by site-directed mutagenesis using O6-methylguanine-containing oligonucleotides. After passage of the DNA through Escherichia coli, analysis of 151 O6-methyl-dGTP-induced mutations indicated a significantly greater number of unmutated mutation sites than expected, whereas the mutated sites generally fit a Poisson distribution. The unmutated sites are assumed to be caused by the inability of some sequences to tolerate the presence of a tetrahedral methyl group within the confines of a Watson-Crick helix (Toorchen, D., and Topal, M.D. (1983) Carcinogenesis 4, 1591-1597). A consensus of the DNA sequences surrounding unmutated mutation sites was derived. The consensus sequence had significant similarity to the region of the rat Harvey ras oncogene containing the N-methyl-N-nitrosourea activated site for transformation (Zarbl, H., Sukumar, S., Arthur, A. V., Dionisio, M.-Z., and Barbacid, M. (1985) Nature 315, 382-385). We propose that direct alkylation at O6 of a guanine present within the consensus sequence may produce a DNA conformation less subject to repair. Mutation by O6-methylguanine-containing oligonucleotides demonstrated that repair of the O6-methylguanine lesions varied at least 3-4-fold with position of the lesion.

Alkylation↗
PubMed1986

DNA structural variability as a factor in gene expression and evolution.

Redundant DNA can buffer sequence dependent structural deviations from an ideal double helix. Buffering serves a mechanistic function by reducing extraneous conformational effects which could interfere with readout or which would impose energetic constraints on evolution. It also serves an evolutionary function by allowing for gradual variations in conformation-dependent regulation of gene expression. Such gradualism is critical for the rate of evolution. The buffer structure concept provides a new interpretation for repetitive DNA and for exons and introns.

Base Sequence↗
PubMed1985

Neuron generator potentials evoked by intracellular injection of cyclic nucleotides and mechanical distension.

Depolarization of neuron membrane was shown to occur during cAMP injection by means of both iontophoresis and pressure. Distension of the neuron by means of blowing with large volumes of solution without cAMP can produce reversible responses. The time course can be made similar to that of the cAMP effect and the responses can be repeated many times in the same neuron. The effect of cAMP can be differentiated from the mechanical response by injecting small volumes of concentrated solutions. The delay in this depolarization response to cAMP is only 0.1-0.3 s. The calculated time of diffusion from the electrode tip to the membrane is about 10 times greater. The similarity of cAMP and mechanical responses and the short delay of the cAMP effect suggests that a cAMP effect may be mediated by mechanical signals in the cytoskeleton.

Animals↗
PubMed1985

Evolve III: a discrete events model of an evolutionary ecosystem.

Evolve III is a discrete events model of an evolutionary ecosystem. The model includes three levels of organization: population, organism and genetic structure. Each of these components was modeled independently, so that selective replacement of subsystems can be used to create families of models capable of testing alternative hypotheses about the real system. To demonstrate the use of the model we describe an experiment on the relationship between adaptability of populations and the variability of the environment. Populations cultured in a constant environment usually dominated those cultured in a variable environment when both were placed in a variable environment at an early stage of development, whereas the opposite is the case at later stages of development. This agrees with experiments on laboratory microcosms and lends credence to the potential predictive value of the model.

Biological Evolution↗