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Biomedical subjects

M McLaughlin

Publications and source records attributed to M McLaughlin.

At least 19 recordsLinked to original sources
PubMed1992

Which newborns in New York City are at risk for special education placement?

In this study of 162 third graders in New York City public schools, we found that slightly over half of the children in special education were males who had Medicaid coverage at birth and mothers with medical conditions or adverse health habits noted on the birth certificate; two thirds of the children with this combination of characteristics actually were placed in special education. These findings suggest that newborns at risk for later learning disabilities can be targeted to receive preventive interventions.

Birth Certificates↗
PubMed1991

Robustness of G proteins in Alzheimer's disease: an immunoblot study.

Many of the neurotransmitter systems that are altered in senile dementia of the Alzheimer type are known to mediate their effects via G proteins, yet the integrity of guanine nucleotide-binding proteins (G proteins) in Alzheimer's diseased brains has received minimal investigation. The aim of this study was to establish whether the level of G alpha subunits of five G proteins was altered in Alzheimer's disease. We used immunoblotting (Western blotting) to compare the amounts of Gi1, Gi2, GsH (heavy molecular weight), GsL (light molecular weight), and Go in the frontal cortex and hippocampus, two regions severely affected by the disease, and the cerebellum, which is less severely affected. The number of senile plaques was also quantified. We report that there was no significant difference in the level of these G alpha subunits between Alzheimer's diseased and age-matched postmortem brains. These results suggest that alterations in the amount of G protein alpha subunits are not a feature of Alzheimer's disease.

Alzheimer Disease↗
PubMed1991

Expression in non-lens tissues of an enzyme activity related to the 'lens-specific' protein, delta crystallin.

When chick embryo neutral retina (NR) cells are cultured for long periods in vitro, they undergo extensive transdifferentiation into lens and express the lens protein, delta crystallin. We now demonstrate that this process is accompanied by a change in the chromatin conformation of the delta-gene locus from DNAase1-resistant to DNAase1-sensitive in the nuclei of most cells. Transcripts hybridising to a delta probe are also much more prevalent among the in vitro transcription products from lens or transdifferentiated NR culture nuclei, as compared to nuclei from fresh NR tissue. Published evidence indicates that the chick delta 1 crystallin gene encodes the major structural protein of embryonic lens fibres, whereas the closely related delta 2 gene may encode the urea-cycle enzyme argininosuccinate lyase (ASL). Our present data lends further support to this view. Both immunodetectable delta-related protein(s) and ASL activity are present in fresh embryonic NR tissue, as well as in mouse and Rana liver, and in Rana lens. Our polyclonal anti-delta antibody also cross-reacts with a major constituent of commercial bovine ASL, of the same molecular size as chick delta crystallin. Immunoselection studies suggest that the ASL activity in chick embryonic NR is conferred mainly by the delta-related protein band. So-called 'ectopic' expression of delta crystallin in embryonic NR (and other tissues) may thus involve the delta 2/ASL gene, and could reflect some metabolic requirement for ASL activity.

Animals↗
PubMed1990

Basal and haloperidol-stimulated prolactin in neuroleptic-free men with schizophrenia defined by 11 diagnostic systems.

Forty-four male, neuroleptic-free, acutely psychotic patients with at least one diagnosis of schizophrenia among 11 diagnostic systems, and 28 healthy controls, underwent measurement of prolactin (PRL) concentrations before and after intravenous administration of haloperidol (0.5 mg). Basal PRL concentrations were lower in the patients with Research Diagnostic Criteria (RDC) DSM-III, Cloninger, and Taylor and Abrams schizophrenias than in controls. Compared with the controls, the PRL response to haloperidol was lower in the patients with schizophrenia defined by all diagnostic systems except those of Schneider and M. Bleuler. Neither basal nor stimulated PRL concentrations were correlated with positive symptoms, but basal PRL was correlated with the Brief Psychiatric Rating Scale (BPRS) depression-related subscore. This study lends further support for the presence of dopaminergic dysfunction in schizophrenia, and demonstrates the advantages and problems in the use of multidiagnostic psychopathological evaluation to categorize a disorder where there is major disagreement among diagnostic systems.

Acute Disease↗
PubMed1990

Effect of 2-amino-7-phosphonoheptanoic acid (APH) on seizure susceptibility in the prepubescent and mature rat.

There is now considerable evidence that the N-methyl-D-aspartic acid receptor is important in the genesis of seizures. One of the selective antagonist of the NMDA receptor is 2-amino-7-phosphonoheptanoic acid (APH). In this study we evaluated the effects of intracerebroventricular (i.c.v.) administration of APH on seizure susceptibility in both prepubescent and mature rats using the rapid kindling and flurothyl ether seizure models. Both the immature and mature animals receiving APH kindled at a significantly slower rate than control animals receiving phosphate-buffered saline. APH also demonstrated a significant anticonvulsant effect against flurothyl-induced seizures in both the immature and mature animals. This study supports prior work that selective NMDA receptor antagonists such as APH may have promise as potential antiepileptic agents.

2-Amino-5-phosphonovalerate↗
PubMed1990

Inhibitory influence of phosphate and arsenate on contraction of skinned skeletal and cardiac muscle.

It has been widely observed that Pi decreases maximum calcium-activated force (Fmax) and calcium sensitivity of skinned skeletal and cardiac muscle. However, whether a particular ionic species of Pi (i.e., H2PO4-) is responsible for these effects is controversial. To clarify this issue, we examined the influence of Pi and its structural analogue arsenate (Asi) on contraction of skinned rabbit psoas (fast twitch), soleus (slow twitch), and cardiac papillary muscle. Asi decreased Fmax of all three muscles types to a greater extent than Pi. Both Pi and Asi decreased calcium sensitivity of psoas and cardiac muscles, with Asi having the greater effect. The effect of the protonated form of Pi and Asi on Fmax was evaluated by measuring the response to 30 mM total Pi or Asi at pH 7.4, 7.0, 6.6, and 6.2. In psoas fibers we found that both Pi and Asi were more effective in decreasing Fmax as the pH was lowered (i.e., as the concentration of the diprotonated forms increased). On the contrary, soleus and cardiac fibers did not exhibit this behavior. These differences in the effects of Pi and Asi on Fmax in psoas vs. cardiac and soleus muscles may be related to differences in their myosin heavy chains other than the binding site for the gamma-phosphate of ATP which appears to be conserved for all myosins.

Animals↗
PubMed1989

Nuclear factors from expressing tissues interact in vitro with a rat alpha-2u globulin gene intron.

Members of the rat alpha 2u globulin gene family are expressed in a tissue-specific manner. Using a DNase I footprinting assay, we find that expressing tissues (liver, lachrymal, and salivary gland) contain nuclear proteins that interact specifically with two sites in the third intron of a cloned gene. These sequences are similar to a CCAAT-like sequence in the 5'-flanking region of the gene and the binding site for the transcription factor Sp1. Extracts of nonexpressing tissues (kidney, testis, brain, and spleen) do not show footprinting activity at these sites. Whereas hepatic expression of alpha 2u globulin is restricted to normal adult males, nuclear extracts of liver from all animals (adult and juvenile, male and female, intact and hypophysectomized) produce similar footprints. Footprints by extracts of lachrymal and salivary glands, tissues that express a subset of alpha 2u globulin genes distinct from the hepatic set, are also similar to the liver activity. The findings suggest that the third intron of an alpha 2u globulin gene contains sites that interact with tissue-specific factors to establish the potential for hormonal and developmental control of expression.

Alpha-Globulins↗
PubMed1988

A high-efficiency vector for expression of foreign genes in myeloma cells.

We have constructed a high-efficiency vector for expression of genes of interest in myeloma cells. This vector is comprised of regulatory sequences from immunoglobulin (Ig) genes, including the heavy-chain enhancer, a kappa light-chain promoter and splice site, and the polyadenylation signal downstream from the kappa constant region. The expression capacity of this vector was assayed in J558L myeloma cells using human tissue plasminogen activator as a reporter gene. Stable transfectants were analyzed for protein, RNA, DNA copy number and transcription rate. Expression was compared to that of intact, transfected Ig genes and to endogenous Ig. Tissue plasminogen activator cloned into this vector was found to be expressed as efficiently as intact, transfected Ig genes, producing 1-2% of total cellular mRNA from a single copy of the gene. RNA levels and transcription rates relative to those of endogenous Ig genes were found to be about 25% and 38%, respectively. Because of its high efficiency, potential for gene amplification, and various scale-up advantages of myeloma cells, this vector-host system may yield levels of desired proteins than currently available systems.

Animals↗
PubMed1988

Regulation of mutator activities in maize.

We discuss the properties of the Mutator (Mu) transposable element family of maize. We report the cloning of bz2-mu1, a mutable allele containing a 1.4-kb Mu element, using a combination of transposon tagging and tests for differential hybridization to northern and Southern blots. We report the sequence of this allele and the Mu element insertion, and propose a model for the structure of the Bz2 locus. We discuss the relationship between increased DNA modification of Mu elements and loss of somatic instability at bz2-mu1. To further explore this aspect of regulation of Mutator, we have used gene-specific probes to determine the level of modification at this locus in active and inactive Mutator lines. We have also utilized CsCl density gradients to estimate the overall level of DNA modification in active and inactive lines; we find that Mu elements in active lines are hypomethylated relative to other maize nuclear DNAs examined, and that in inactive lines the level of modification in Mu elements is similar to the genome as a whole. Utilizing gamma-irradiation, we have demonstrated that inactive lines can be reactivated; this reactivation is first noted as restitution of the spotted kernel phenotype characteristic of bz2-mu1 in active Mutator lines. Hybridization analysis of DNA from reactivated plants demonstrates that the Mu elements in general, and specifically the Mu element at bz2-mu1, have the lower level of DNA modification characteristic of active lines. These results are discussed in terms of the role and timing of DNA modification in regulating Mutator activities.

Base Sequence↗
PubMed1988

Live virus vaccines in human immunodeficiency virus-infected children: a retrospective survey.

Live virus vaccines can cause serious adverse reactions when administered to immunocompromised patients. Because children infected with human immunodeficiency virus (HIV) may be immunosuppressed, immunization of these children with live virus vaccines is a potential problem. A retrospective survey was conducted by the New York City Department of Health, with consultation from the Centers for Disease Control, to evaluate the frequency of serious adverse events following receipt of live vaccines among children with HIV infection receiving pediatric care in New York City and New Jersey. Outpatient records of 319 children being cared for by 16 participating physicians were reviewed. Of the 319 charts, 221 (69%) contained vaccination histories. Perinatal transmission of HIV infection was suspected for 208 (94%) of the 221 cases and infection via transfusion for the remaining 13 (6%). Of the 221 for whom immunization histories were available, 180 (81%) had received at least one dose of live oral polio vaccine and 70 (32%) had received measles, mumps, and rubella vaccine. There were 120 children for whom a temporal relationship between immunization and onset of symptoms of immunodeficiency could be seen; 46/120 had received at least one dose of oral polio vaccine and 23/45 had received measles, mumps, and rubella vaccine after onset of symptoms. Although follow-up of this population has been limited, there were no reports of serious adverse events such as typical or atypical measles, paralytic poliomyelitis, or aseptic meningitis in the month following vaccination.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1987

Cloning of a mutable bz2 allele of maize by transposon tagging and differential hybridization.

Sequences of Bronze2 (Bz2), a maize gene which is required for the synthesis of the purple pigment anthocyanin, have been cloned by combining the techniques of transposon tagging and differential hybridization. First, a mutable bz2 allele (bz2-mu1) was recovered from a Mutator line. The mutation was assumed to result from an insertion of the transposable element Mutator (Mu), which is found in 10-60 copies in Mutator lines. A library was prepared using DNA isolated from bz2-mul, and a small bank of Mu-specific candidate clones was selected. Because much is known about the genetic requirements for the synthesis of anthocyanin in different tissues, we were able to identify the bz2 clone based on its hybridization to RNA isolated from different bz2 mutants. Only one clone hybridized to RNA isolated from the husks of purple (Bz2, B, Pl) plants but not to RNA isolated from the husks of green (an-bz2-6923, b, pl) plants. Further confirmation was provided by the hybridization pattern of the clone on blots containing DNA from other bz2 mutants. We present a restriction map of the clone, indicating the location and orientation of the 1.4-kbp Mu insert. We identify the transcribed region, the direction of transcription and the location of the 1.4-kbp Mu insert in an independently isolated mutant, bz2-mu2.

Alleles↗
PubMed1987

Bipolar affective disorder in Down's syndrome.

Recent literature reports suggest that the presence of Down's syndrome precludes the development of mania. A case of bipolar affective illness in a man with Down's syndrome is presented.

Adult↗
PubMed1986

Synthesis of congeners and prodrugs of the benzene maleimide photoadduct mitindomide as potential antitumor agents. 2.

Potential prodrugs of the highly insoluble, diimide antitumor agent mitindomide (1b) were synthesized by several different methods. The condensation reaction between mitindomide and formaldehyde cleanly gave the stable bis(hydroxymethyl) compound 7a, which was partially soluble in water (ca. 0.8%) and showed improved activity in the P-388 screen. When this compound was treated with secondary amines, good yields of Mannich bases could be isolated. The compound from N-methylpiperazine (7b) had excellent properties and is a candidate for clinical trials. Condensation with other aldehydes gave either no reaction or compounds with poor activity. A water-soluble ester was prepared from 7a and succinic anhydride, but had reduced potency and activity. Oxidation of the double bond of 1a with ozone gave an inactive diacid, whereas the dihydro compound was as active as the olefin. When other aromatics (anisole, p-xylene, mesitylene) were photolyzed with maleimide, the resulting photoproducts were found to be inactive. Diimides from other ring system were synthesized from the corresponding anhydrides and found to be inactive. However, the bis(hydroxymethyl) derivative of one of these (12a) was active in the P-388 screen.

Antineoplastic Agents↗
PubMed1986

Outpatient metrizamide myelography: prospective evaluation of safety and cost effectiveness.

A group of 228 consecutive patients undergoing metrizamide myelography was prospectively evaluated for postprocedure symptoms. The observed prevalence of these symptoms concurs with previously reported inpatient studies, with the most common sequelae being exacerbation or onset of spine or extremity pain, headache, nausea, and paresthesia. Limitation of administered dose of metrizamide in lumbar myelography may slightly reduce the occurrence of common symptoms, but withdrawal of contrast medium at the completion of examination had no impact on their occurrence. There was a higher occurrence of paresthesia in cervical myelography, but otherwise there was no significant difference in symptoms between cervical and lumbar studies. Outpatient metrizamide myelography can be performed with relative safety with the potential for significant cost savings.

Adolescent↗
PubMed1985

Effects of delta-aminolaevulinic acid on contractile activity in the isolated small intestine of the rabbit. Role of adrenergic receptors.

The porphyrin precursor, delta-aminolaevulinic acid (ALA) at concentrations of 0.23-7.6 mM caused dose-dependent inhibition of spontaneous contractions in isolated preparations of rabbit small intestine, suspended in Ringer-Locke solution. Contractions which returned after inhibition from 3.8 and 7.6mM ALA showed increased amplitude and from 7.6 mM ALA a reduction in rate. Pretreatment with prazosin (10(-7) M) significantly reduced the duration of inhibition exerted by 3.8 and 7.6 mM ALA and also the amplitude of contractions returning after this inhibition. Pretreatment with yohimbine (10(-6) M) and propranolol (7 X 10(-6) M) had no significant effects. Blocking of the release of noradrenaline in preparations by incubation with 6-hydroxydopamine (10(-3) M) or guanethidine (1.5 X 10(-5) M) did not prevent the inhibitory effects of ALA. The alpha 1 agonist, cirazoline (10(-5) M), inhibited contractile activity. This effect was blocked by prazosin (10(-7) M). The alpha 2 agonist, guanoxabenz (10(-5) M) had no detectable effect, in the presence of prazosin, to block any residual alpha 1 actions. It is concluded that alpha 1 receptors mediate inhibitory effects in this preparation and that ALA appears to have direct effects upon these receptors.

Aminolevulinic Acid↗