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Biomedical subjects

J Stein

Publications and source records attributed to J Stein.

At least 379 records · Page 21Linked to original sources
PubMed1986

The role of beta blocking agents as adjunct therapy to membrane stabilizing drugs in malignant ventricular arrhythmia.

Antiarrhythmic drugs are often either partially or totally ineffective for the suppression of ventricular arrhythmias in a given patient. Drug combinations afford an additional therapeutic option. We report the role of beta-blocking agents as adjunct therapy to membrane stabilizing drugs in the management of patients with malignant ventricular arrhythmias. The study group included 54 patients who were evaluated by 24-hour ambulatory monitoring and symptom-limited exercise testing. Patients underwent control studies without antiarrhythmic drugs, were evaluated on membrane stabilizing drugs and beta blocking agents separately, and were then tested on combination therapy. The combination of a beta-blocking agent and a membrane stabilizing drug abolished ventricular tachycardia and couplets in 83% and 86% of exercise tests in patients with this arrhythmia present during therapy with membrane drugs alone (p less than 0.01). The addition of a beta blocker to a membrane drug, as evaluated by ambulatory monitoring, resulted in an abolition of ventricular tachycardia and couplets in 43% and 20% of studies (p less than 0.05). Ventricular premature beat frequency was reduced by more than 50% in 65% of exercise tests and in 52% of monitoring studies (p less than 0.05). In this population, beta-blocking agents failed to reduce ventricular arrhythmias when used alone. Thus the addition of a beta blocker to a membrane stabilizing drug significantly enhances the suppression of ventricular arrhythmia, especially when assessed by exercise testing. This results from synergistic drug effects of the combination rather than from the effect of the individual drugs.

Adrenergic beta-Antagonists↗
PubMed1986

Human histone gene organization. Identification of a histone gene polymorphism prevalent in a black population.

Analysis of the restriction enzyme digests of total genomic DNAs from a broad spectrum of human cell lines and from individuals with different genetic backgrounds, by hybridization with a series of cloned human histone sequences, indicated restriction site polymorphisms (RSPs) for two adjacent human histone genes which reside on chromosome 1. In most cell lines and individuals examined we observed a single 2.05 kb H4 histone HindIII fragment and a 7.0 kb H3 histone HindIII fragment. In contrast, the polymorphisms were manifested as a 2.15 kb H4 HindIII fragment and a 9.1 kb H3 HindIII fragment. From population studies, we were able to show that there is no linkage disequilibrium between these two polymorphic restriction sites. Nor was there any apparent correlation between the presence of the H3/H4 histone polymorphisms and maintenance of the transformed karyotype, passage in culture, transformation or tumor progression. These chromosome 1 H3 and H4 histone gene polymorphisms are common in the American Black population and, in our survey of individuals, were not found in the American Caucasian population. Among the American Blacks studied, the frequency of the H3 HindIII(-) allele is 43% and of the H4 HindIII(-) allele 30%. In limited family studies, we were unable to detect recombination between these two physically linked alleles.

Black People↗
PubMed1986

Mexiletine and tocainide: does response to one predict response to the other?

Mexiletine and tocainide were administered to 79 patients to determine whether the response to one of these drugs would predict the effect of the other. In 57 patients, the two agents were evaluated noninvasively with monitoring and exercise testing, and efficacy was judged by the suppression of spontaneous ventricular arrhythmia. In the remaining 22 patients, electrophysiologic testing was performed and efficacy was defined as the inability to induce more than two repetitive ventricular premature beats. An equal number of patients responded to mexiletine and tocainide (38 versus 39%). However, in only 42 patients (53%) were the results concordant. There was no difference in concordance when the results were analyzed by method of drug evaluation, left ventricular ejection fraction or etiology of presenting arrhythmia. It is concluded that mexiletine and tocainide have different clinical effects and must be evaluated individually.

Adult↗
PubMed1986

Involvement of the 5'-leader sequence in coupling the stability of a human H3 histone mRNA with DNA replication.

Two lines of evidence derived from fusion gene constructs indicate that sequences residing in the 5'-nontranslated region of a cell cycle-dependent human H3 histone mRNA are involved in the selective destabilization that occurs when DNA synthesis is terminated. The experimental approach was to construct chimeric genes in which fragments of the mRNA coding regions of the H3 histone gene were fused with fragments of genes not expressed in a cell cycle-dependent manner. After transfection in HeLa S3 cells with the recombinant plasmids, levels of fusion mRNAs were determined by S1 nuclease analysis prior to and following DNA synthesis inhibition. When the first 20 nucleotides of an H3 histone mRNA leader were replaced with 89 nucleotides of the leader from a Drosophila heat-shock (hsp70) mRNA, the fusion transcript remained stable during inhibition of DNA synthesis, in contrast to the rapid destabilization of the endogenous histone mRNA in these cells. In a reciprocal experiment, a histone-globin fusion gene was constructed that produced a transcript with the initial 20 nucleotides of the H3 histone mRNA substituted for the human beta-globin mRNA leader. In HeLa cells treated with inhibitors of DNA synthesis and/or protein synthesis, cellular levels of this histone-globin fusion mRNA appeared to be regulated in a manner similar to endogenous histone mRNA levels. These results suggest that the first 20 nucleotides of the leader are sufficient to couple histone mRNA stability with DNA replication.

Animals↗
PubMed1986

Cell cycle-dependent expression of a stable episomal human histone gene in a mouse cell.

We have constructed a recombinant plasmid that includes a cell cycle-dependent human H4 histone gene with 650 base pairs of 5' and 900 base pairs of 3' flanking sequences and the 69% transforming fragment of bovine papilloma virus. When transfected into C127 mouse cells, this plasmid is maintained as a stable episome with approximately 20 copies per cell. Micrococcal nuclease digestion indicates that the episomal human histone gene is packaged as chromatin. The human H4 histone transcript is initiated at the correct 5' start site and undergoes selective destabilization when DNA synthesis is inhibited. When C127 cells containing the episomal H4 histone gene are synchronized, the human H4 histone mRNA levels are regulated coordinately with DNA replication and parallel those of transcripts from the murine chromosomal H4 histone genes. Our results suggest that the regulatory sequences and/or regulatory molecules associated with murine and human histone genes are compatible. The human histone gene-bovine papillomavirus episome is therefore a viable system for studying cell cycle-regulated histone gene expression under conditions where control is not influenced at the site of chromosomal integration by cis-acting elements of genes normally not contiguous.

Animals↗
PubMed1986

Enhancer-facilitated expression of prokaryotic and eukaryotic genes using human histone gene 5' regulatory sequences.

We examined the structural and functional properties of a human H3 histone gene promoter. The complete nucleotide sequence of an H3 structural gene and 515 nucleotides of 5' and 100 nucleotides of 3' flanking sequences were determined. The upstream region of this cell cycle dependent H3 histone gene, designated pST519, contains consensus sequences typical of genes transcribed by RNA polymerase II. To address promoter function directly, we determined the capability of the 5' flanking sequences to direct the transcription of two genes which are not functionally or structurally related. Fusion genes were constructed using the 5' flanking sequences of this human H3 histone gene and either human beta-globin or bacterial chloramphenicol acetyltransferase (CAT) coding sequences. Both of these fusion genes were expressed when transfected into HeLa cells. Under control of the pST519 histone gene promoter, a beta-globin mRNA transcript was initiated at the appropriate H3 (bp) enhancer, inserted upstream from the histone promoter in both fusion constructs, increased levels of beta-globin and CAT expression. Expression of the pST519 H3 histone gene in COS cells in the absence of the SV40 72-bp enhancer confirmed that the sequences required for promoting transcription reside within the 750-bp 5' flanking sequences and that the exogenous enhancer facilitates, but is not a prerequisite for, transcription. Enhancer-facilitated expression of a cell cycle dependent human H4 histone gene was also observed following transfection into mouse L cells and indicates that the regulatory sequences of human histone genes and transcription factors of mouse cells are compatible.

Acetyltransferases↗
PubMed1986

[Significance of C-reactive protein in pediatric diagnosis].

The present review summarizes the results of C-reactive protein determinations in the serum of 9100 infants and children and gives a survey on data presented in the literature. Quantitative estimations of CRP are a useful screening method for the evaluation of infections and the activity of inflammatory processes in chronic diseases. In a variety of diseases CRP correlates well with erythrocyte sedimentation rate. CRP is, however, superior to ESR in showing faster dynamics and being uninfluenced by anemia, nephrotic syndrome or renal insufficiency. Marked elevations of CRP concentration may help to differentiate between viral and bacterial infections. It can be concluded that the determination of CRP in the serum must be added to the list of standard investigations in acutely and chronically ill infants and children.

Arthritis, Juvenile↗
PubMed1985

Effect of monocular occlusion on visuomotor perception and reading in dyslexic children.

101 (68%) of 148 dyslexic children had unstable vergence eye movement control (unfixed reference) in the Dunlop synoptophore test. These children tended to make visual rather than phonemic errors when reading and writing; the opposite was true for those with stable control (fixed reference). The 148 dyslexic children were given plano spectacles to wear for 6 months when reading and writing and were randomised to receive either spectacles that had the left lens occluded or untreated ones. The trial was double blind. Conversion from unfixed to fixed reference occurred in 51% of the children who wore occluded spectacles, compared with 24% of those who wore plain spectacles. In the former group increase in reading ability improved by almost 6 months relative to change in age, whereas in those who wore plain spectacles and whose reference did not become fixed reading ability regressed by 0.4 months. The children with unfixed reference who did not benefit from occlusion were those who made not only visual but also phonemic and sequencing errors. Monocular occlusion may thus help one-sixth of dyslexic children to develop reliable vergence control and thereby to read.

Child↗
PubMed1985

Coordinate regulation of histone mRNAs during growth and differentiation of rat myoblasts.

To determine whether histone genes are coordinately regulated, histone mRNA concentrations were measured in exponentially growing L6 myoblasts, S-phase synchronized myoblasts and in differentiating myoblasts. The levels of various histone mRNA subspecies declined rapidly and coordinately once myoblasts were given the signal to differentiate. mRNA levels were reduced on average to 1-5% of the amount observed in exponentially growing cells by 48 h after the signal to differentiate. The reductions occurred in concert with the cessation of DNA synthesis as the cells differentiated. Inhibition of DNA synthesis by treating myoblasts with Ara-C or hydroxyurea resulted in a histone mRNA half-life of 10-13 min for each of the histones examined. One example of non-coordinate regulation was observed however among the H4 mRNA subspecies in S-phase synchronized cells. The levels of two major subspecies of H4 mRNA increased coordinately in S-phase compared to levels observed in cells growing exponentially. A third subspecies of H4 mRNA on the other hand was found to decline by 50%. These studies suggest that the majority of histone mRNA subspecies are under coordinate control, although one exception has been noted among the subspecies of histone H4.

Animals↗
PubMed1985

Enhancer-facilitated expression of a human H4 histone gene.

Cultured mammalian cells were transfected with a recombinant human H4 histone gene. S1 nuclease mapping of cellular RNAs from transfected cells revealed: (i) correct initiation of transcription at the cap site, with some transcripts originating from other sites in the 5' flanking region of this H4 gene; (ii) cis-linkage of an SV-40 transcriptional enhancer element upstream of the H4 5'-flanking region resulted in about a 50-fold increase in the level of correctly initiated H4 mRNA and (iii) in a heterologous murine system stability of human H4 mRNAs was apparently sensitive to inhibition of DNA-synthesis by hydroxyurea. Our results suggest that certain sequences required for the initiation of a human H4 histone gene transcript reside within the 210 nucleotides immediately upstream from the cap site and that the level of expression is influenced by the introduction of an enhancer element.

Animals↗
PubMed1985

Flow cytometric analysis of DNA replication during the differentiation of 3T3-L1 preadipocytes.

We have employed a flow cytometric method of monitoring DNA synthesis in order to study the stimulation of DNA replication during the induction of adipocyte differentiation in the preadipocyte cell line 3T3-L1. When confluent monolayers of this cell line are treated with a mixture of methyl isobutyl xanthine, dexamethasone, and insulin (MDI), they undergo at least one round of cell division, which is followed by the de novo synthesis of many enzymes that are involved in the formation of lipid. If the MDI-treated cells are incubated in iododeoxyuridine (IdUrd)- or bromodeoxyuridine (BrdUrd)-containing medium and subsequently stained with antibodies specific for these base analogues and with propidium iodide (PI), the kinetics of the induction of replication can be monitored. No differences in the patterns of IdUrd incorporation versus PI staining were observed between exponentially growing 3T3-L1 cells and those that had been stimulated to replicate DNA with MDI. In addition, we developed a flow cytometric (FCM) method for staining fatty acid synthetase and localizing the antigen in the G1 phase. We have thus demonstrated the feasibility of this methodology for correlating by FCM the production of enzymes such as fatty acid synthetase with IdUrd and BrUrd incorporation. The technique should permit studies of the inhibition of differentiation of adipocytes by halogenated pyrimidines.

Adipose Tissue↗
PubMed1985

Subcellular localization of histone messenger RNAs on cytoskeleton-associated free polysomes in HeLa S3 cells.

We have examined the subcellular distribution of histone mRNA-containing polysomes in HeLa S3 cells to assess the possible relationship between localization of histone mRNAs and the regulation of cellular histone mRNA levels. The distribution of histone mRNAs on free and membrane bound polysomes was examined as well as the association of histone mRNA-containing polysomes with the cytoskeleton. The subcellular localization of histone mRNAs was compared with that of HLA-B7 mRNAs which encode a cell surface antigen. Histone mRNAs were localized predominantly on the free polysomes, whereas the HLA-B7 mRNA was found almost exclusively on membrane bound polysomes. However, both species of mRNA were found associated with the cytoskeleton. Interruption of DNA synthesis by hydroxyurea treatment resulted in a rapid and selective destabilization of histone mRNAs in each subcellular fraction; in contrast, the stability of HLA-B7 mRNA appeared unaffected. The results presented confirm that histone mRNAs are predominantly located on non-membrane bound polysomes and suggest that these polysomes are associated with the cytoskeletal framework.

Cycloheximide↗
PubMed1985

A unique subspecies of histone H4 mRNA from rat myoblasts contains poly(A).

Fractionation of rat L6 myoblast histone H4 mRNA into its three component subspecies revealed that one of the major subspecies (H4-1) contained poly(A). The unique poly(A)+ H4 mRNA makes up about 8% of the total polysomal H4 mRNA population detected. Unlike the poly(A)- histone mRNAs, whose levels are reduced by greater than 95% when myoblasts differentiate into myotubes, the poly(A)+ subspecies is reduced by only 70%. The poly(A)+ H4 mRNA from myotubes incubated with actinomycin D decays with a half-life of 37-42 min, which is similar to that obtained for the poly(A)- H4 mRNAs in myoblasts. Both the poly(A)+ and poly(A)- subspecies decay at an increased rate after inhibition of DNA synthesis. In myoblasts the poly(A)+ H4 mRNA exists almost exclusively in the polysomal compartment (greater than 95%) with little (less than 5%) in the free ribonucleoprotein (mRNA-protein or mRNP) complex compartment of the cell. Poly(A)- histone H4 mRNA subspecies, on the other hand, are distributed with approximately 80% in the polysomal compartment and 20% in the free mRNP complex compartment. The unique poly(A)+ H4 mRNA is unusual, not only in that it contains poly(A) but also in its behavior compared to poly(A)- H4 mRNAs during terminal differentiation.

Animals↗
PubMed1985

A human histone H4 gene exhibits cell cycle-dependent changes in chromatin structure that correlate with its expression.

By use of synchronized human HeLa S3 cells, a site sensitive to both DNase I and nuclease S1 was identified 50-150 base pairs upstream of the ATG codon of a cell cycle-dependent histone H4 gene. This site expanded to include a broad region of approximately equal to 300 base pairs sensitive to DNase I throughout S phase and then narrowed again to the original site after the completion of DNA replication. The level of nuclease S1 sensitivity was greatest during early S phase, when the gene is replicated and its transcription rate is maximal. The chromatin structure of the human beta-globin gene, which is not expressed in HeLa cells, was also analyzed throughout the cell cycle, and in no case was a sub-band seen as a result of DNase I or nuclease S1 digestion, nor were there any changes in nuclease sensitivity correlated with its replication. Thus the cell cycle-dependent chromatin alterations in this histone H4 gene appear to be due to the coupled replication and expression of this gene rather than simply its replication. These results suggest that histone genes, as compared with developmentally regulated genes, exhibit an "intermediate" level of regulation whereby the gene is never in a completely inactive conformation, but changes in chromatin structure occur as a function of the cell cycle and expression.

Base Sequence↗
PubMed1985

Lactate infusions in obsessive-compulsive disorder.

Panic attacks followed sodium lactate infusions in one of seven patients with obsessive-compulsive disorder and 26 of 48 patients with panic disorder or agoraphobia with panic attacks. This suggests that lactate-induced panic is specific to the latter groups.

Adult↗