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Biomedical subjects

B Jones

Publications and source records attributed to B Jones.

At least 325 records · Page 18Linked to original sources

Ritanserin, imipramine, and placebo in the treatment of dysthymic disorder.

Fifty outpatients with dysthymic disorder (DSM-III) were divided by double-blind randomized assignment into three groups given ritanserin, imipramine, and placebo, respectively. The trial was of 7 weeks' duration; by week 6, imipramine was clearly superior to placebo, whereas by week 7, both drugs caused significantly more improvement than the placebo. Although imipramine had slightly greater efficacy than ritanserin, it also had significantly more side effects. This was particularly evident in the higher dropout rate with imipramine. The efficacy and side effect profile of ritanserin makes it well tolerated and acceptable with dysthymic patients who, although they do not respond as quickly as patients with major depressive disorder, do show significant improvement, given sufficient time.

Adult↗

The utilization of quantitative trait loci in toxicogenetics.

With the increasing number of marker loci available in mouse, the traditional method of recombinant inbred strains can be extended to searches for quantitative trait loci (QTL) influencing continuously distributed phenotypes. These loci have effect sizes too small to be easily detectable by conventional single-locus techniques. Collective, several QTL may account for a substantial proportion of the phenotypic variability. Prospective advantages of location of QTL in toxicology-relevant phenotypes include opportunities for the study of mechanism, prospects of generating animal models by genotypic selection, study of the dynamics of gene interaction, and guiding the search for homologous genes in human beings.

Alleles↗

The tumoricidal potential of extracorporeal shock wave therapy.

A potential role of extracorporeal shock wave lithotripsy (E.S.W.L.), in the destruction of tumours has been proposed in recent literature. To examine further this potential, we have studied the effects of E.S.W.L. on the sarcoma-derived osteoblast-like cell line MG-63. An in-situ assay of cell viability was used to establish the cellular response to high energy shock wave therapy. A significant tumoricidal effect was confirmed when the cells were grown and tested in conventional monolayer phase. However cells grown in the three-dimensional matrix of alginate beads were significantly less vulnerable to extracorporeal shock wave therapy as earlier studies have suggested.

Cell Survival↗

Data about mortality.

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Data Interpretation, Statistical↗

Vagal reflexes referred from the upper aerodigestive tract: an infrequently recognized cause of common cardiorespiratory responses.

OBJECTIVE: To review the physiologic basis for normal and abnormal vagal reflexes arising from the pharynx, larynx, and esophagus, as well as the relevance of vagal reflexes to the pathogenesis of such clinically common cardiorespiratory responses as bradycardia, tachycardia, dysrhythmia, coronary angiospasm, bronchospasm, laryngospasm, prolonged apnea, and singultus (hiccups). DATA SOURCES: Pertinent articles and reviews were identified through a MEDLINE search (April 1966 to October 1991). Older studies and others not identified in the MEDLINE search were found through a manual search of the bibliographies of the retrieved articles. STUDY SELECTION: Experimental studies in both humans and animals, as well as case series and single case reports, were selected for evaluation and citation. In instances where a similar phenomenon was described in multiple independent reports, only studies that provided a novel finding or interpretation were cited. More authoritative book chapters and peer-reviewed summaries were also cited in support of commonly accepted principles. DATA EXTRACTION AND SYNTHESIS: Most of the clinical data are derived from case reports and small case series and are therefore anecdotal; equal weight was given to all such studies. Reports of conflicting observations or interpretations were clearly identified and were cited without exception. CONCLUSIONS: Stimulation of the upper aerodigestive tract can lead to clinically significant cardiorespiratory responses. Although the prevalence of and risk factors for such responses have not been established, we suggest that a pharyngeal, a laryngeal, or an esophageal source for abnormal cardiorespiratory responses be sought whenever a detailed clinical evaluation fails to reveal a cause, particularly when there are concurrent symptoms or signs of upper aerodigestive tract disease, such as dysphagia or gastroesophageal reflux.

Cardiovascular System↗

Heat-stable antigen is a costimulatory molecule for CD4 T cell growth.

Optimal induction of clonal expansion by normal CD4 T cells requires a ligand that can engage the T cell receptor as well as functionally defined costimulatory activity on the same antigen-presenting cell surface. While the presence of effective costimulation induces proliferation, T cell receptor ligation in its absence renders T cells inactive or anergic. The molecular basis of this costimulatory activity remains to be defined. Here we describe a monoclonal antibody that can block the costimulatory activity of splenic accessory cells. Treatment with this antibody not only blocks the proliferation of CD4 T cells to a T cell receptor ligand, but also induces T cell nonresponsiveness to subsequent stimulation. Sequence analysis of the antigen recognized by this antibody indicates that it recognizes a protein that is identical to heat-stable antigen. Gene transfer experiments directly demonstrate that this protein has costimulatory activity. Thus, heat-stable antigen meets the criteria for a costimulator of T cell clonal expansion.

Animals↗

Co-stimulation of murine CD4 T cell growth: cooperation between B7 and heat-stable antigen.

The B cell activation antigen B7/BB1 has been shown to co-stimulate growth of human T cells by binding the T cell molecule CD28. In mice, the heat-stable antigen (HSA) has also been shown to act as a co-stimulator for T cell growth. In this study, we have evaluated the contributions of B7 and HSA to the co-stimulatory activity of antigen-presenting cells (APC). Mouse B7 provides co-stimulatory activity for murine CD4 T cells in anti-CD3-induced proliferation. Human CTLA4Ig, a chimeric molecule comprising the extracellular region of CTLA-4 fused to an immunoglobulin C gamma fragment, binds to murine B7. We, therefore, use human CTLA4Ig and the hamster anti-HSA monoclonal antibody 20C9 to analyze the relative contributions of B7 and HSA to the co-stimulatory activity of murine spleen APC. Our data reveal that both murine B7 and HSA are expressed by dendritic cells and by low-density spleen B cells. Either CTLA4Ig alone or anti-HSA alone inhibited CD4 T cell proliferation to anti-CD3 by > 90%, while CTLA4Ig and anti-HSA together were far more efficient in inhibiting clonal expansion of CD4 T cells. These results demonstrate that functionally defined co-stimulation involves at least B7 and HSA and suggest that signals delivered by B7 and HSA synergize in promoting T cell growth.

Animals↗

Interaction of H-2Eb with an IAP retrotransposon in the A20/2J B cell lymphoma.

In the A20/2J BALB/c B cell lymphoma, Southern analysis revealed an insertion of approximately 6 kilobases of DNA into the first intron of one Ebd-allele. Two observations suggest that the rearrangement did not occur recently in the A20/2J subline. Firstly, normal and altered Ebd-alleles are present in equal numbers, and secondly, the LB 27.4 and LS 102.9 somatic cell hybrids formed at an earlier date both possess the rearrangement. Sequences of two cDNA clones, lambda Eb-7 and lambda Eb-125, selected from an A20/2J cDNA library prepared from poly [A+] RNA indicate that the rearranged Ebd-allele directs the synthesis of atypical Eb transcripts. The clones contain Eb sequence linked to a portion of retroviral-like intracisternal A-particle (IAP) genomic sequence, and they appear to be copies of mRNA produced by splicing between a 5' donor site in the retroviral transcript and the 3' acceptor site of the Eb gene's first intron. The longer lambda Eb-125 insert corresponds to RNA that initiated in the 5'-untranslated region of the Eb gene. The 3'-end of the first Eb exon joins to long terminal repeat sequence, and retroviral sequence extends up to the splice junction with the second Eb exon; 3' of the junction, the lambda Eb-125 sequence corresponds to that of a correctly spliced Eb transcript. It seems feasible that the cDNA clones represent hybrid RNA synthesized by read-through transcription of the Eb coding region and an IAP element inserted into the first intron of the rearranged Ebd-allele.

Animals↗

Hypomethylation of MHC class II Eb gene is associated with expression.

Methylation patterns in the major histocompatibility complex (MHC) class II Eb locus have been analyzed in cell lines representative of different cell types; in particular those with phenotypes found at various stages of B cell development. A series of variant B cell lymphoma lines which serves as a model in which to investigate mechanisms regulating class II gene expression in normal peripheral B cells has been examined. Eb methylation patterns have also been determined in various healthy mouse tissues. The pattern of methylation of the Eb locus varies between different cell lines and tissue types such that hypomethylation is associated with gene expression. There appears to be a methylation pattern which is permissive for class II gene expression and which is characteristic of a variety of cell lines, but is lost in cell lines representing terminally differentiated class II nonexpressing plasma cells. Another methylation pattern has been identified which is found in cloned cell lines selected for expression of very high levels of cell surface class II product. The patterns of methylation associated with MHC class II expression involve changes in methylation sites located within the first intron and several kilobase pairs 5' of the promoter, but no changes were observed in the 3' end of the locus. Moreover, the different methylation patterns do not map to the prominent CpG rich cluster located 5' of the Eb promoter and which remains completely methylated regardless of transcriptional status.

Animals↗

Confirmation of centromeric fusion in 7p/1q translocation associated with myelodysplastic syndrome.

Fluorescence in situ hybridization (FISH) using chromosome 1- and chromosome 7-specific centromeric alpha-satellite probes was performed on the bone marrow (BM) cells of a patient with myelodysplastic syndrome (MDS) who had been treated for lymphoma and whose BM karyotype was initially considered to be 46,XY,-7,+der(1)t(1;7)(p11;p11). FISH results suggested the presence of both chromosome 1 and chromosome 7 centromeres in the rearranged chromosome. Thus, the correct karyotype should be written as 46,XY,-7,+der(1;7)(q10;p10).

Adult↗