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Biomedical subjects

B Jones

Publications and source records attributed to B Jones.

At least 19 recordsLinked to original sources

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

Alternative approaches to the analysis of binary and categorical repeated measurements.

The purpose of this paper is to describe, illustrate, and compare a number of different approaches to the analysis of repeated binary and categorical data. These approaches include empirical generalized least squares and generalized estimating equations, as well as traditional log-linear modeling methods. It is shown that the interpretation of the parameters in the various models depends critically on the type of model fitted. In particular, we contrast the population-averaged and subject-specific models. Two example data sets are used to illustrate the approaches, and throughout we concentrate on methods that can be easily implemented.

Clinical Trials as Topic

Iron absorption differs in piglets fed extrinsically and intrinsically 59Fe-labeled sow's milk.

Iron bioavailability from species-specific milk is assumed to be high for the offspring, possibly due to species-specific iron-binding proteins in the milk. To assess this bioavailability using radioisotopes, the validity of extrinsic labeling technique needs to be proven. Using the suckling piglet as an animal model, we have compared iron bioavailability from sow's milk labeled extrinsically and intrinsically. During intrinsic labeling transfer into milk of 59Fe given intramuscularly was slow and was found to be at maximum 14 h post-injection. Recovery of isotope in the milk was only 0.00014%. Extrinsic and intrinsic labels were distributed differently among milk fractions; intrinsic iron bound primarily to the fat fraction but the extrinsic iron bound primarily to the casein fraction. Iron retention from intrinsically labeled milk was considerably higher than from extrinsically labeled milk. These results show that the extrinsic tag method is not valid for studies on iron absorption from sow's milk and suggest that the situation may be the same for human milk.

Absorption

Neuropathic (Charcot) arthropathy of the spine after traumatic spinal paraplegia.

Neuropathic (Charcot) arthropathy of the spine is a relatively rare problem that, nonetheless, must be considered in the differential diagnosis of any patient with degeneration of one or more levels of the spine associated with diminished or absent protective sensation. This study presents 15 patients in whom Charcot arthropathy of the spine developed after traumatic paraplegia. Eight were successfully treated with surgical fusion, and the remaining seven were treated nonoperatively. By the use of combined anterior and posterior fusion with extensive debridement, autogenous grafting, and posterior instrumentation, successful fusion can be achieved in patients with Charcot arthropathy of the spine. However, the surgical technique is demanding, the rehabilitation must be carefully supervised, and the postoperative complication rate remains high. The possibility of developing secondary levels of arthropathy below a previously successful fusion must be considered.

Adult

Gastrointestinal tract in the immunocompromised host: opportunistic infections and other complications.

In the decade since the early 1980s, the increasing use of immunosuppressive therapy for cancer and autoimmune disease, as well as for organ transplantation, has combined with the acquired immunodeficiency syndrome epidemic to increase greatly the incidence of opportunistic infections and other complications of the gastrointestinal tract. Consequently, barium fluoroscopic and cross-sectional imaging studies tailored to address these problems are no longer uncommon. Although overlap exists, there are radiographic patterns that can direct the diagnosis to an opportunistic infection and sometimes to a specific pathogen. This article describes and illustrates the radiographic findings of gastrointestinal superinfection with Candida albicans, cytomegalovirus, Cryptosporidium spp, herpes simplex virus, Mycobacterium tuberculosis, M avium-intracellulare, and human immunodeficiency virus. Other gastrointestinal tract complications of immunosuppression are discussed, including graft-versus-host disease following bone marrow transplantation, typhlitis, and pseudomembranous colitis.

AIDS-Related Opportunistic Infections

Caustic ingestion injuries of the upper aerodigestive tract.

Few reports have described in detail the injuries that occur to the oral cavity, pharynx, and larynx following caustic ingestion. The role of dynamic radiographic studies to delineate the extent of damage has been minimized. In-depth radiographic analysis of such cases has not, to our knowledge, been previously reported. In order to examine the injuries and functional abnormalities of these sites following caustic ingestion, the records of The Johns Hopkins Swallowing Center were reviewed. Five patients were identified as having significant upper aerodigestive tract caustic injuries. All patients had dysphagia, epiglottis injuries, and incomplete laryngeal protection with aspiration. Four of five had sustained some degree of esophageal stenosis. Also noted were pharyngeal muscle dysfunction, nasopharyngeal regurgitation, tongue fixation, and hypopharyngeal stenosis. Roentgenographic findings are described and illustrated. The multidisciplinary approach to the management and rehabilitation of these patients is discussed.

Adult

Swallowing dysfunction in the postpolio syndrome: a cinefluorographic study.

Twenty patients with a remote history of poliomyelitis and recent or progressive dysphagia were evaluated with cinefluorography. Radiographic abnormalities were present in the pharynx in varying degrees in all but one of the patients. Findings included atrophy of the prevertebral soft tissues, unilateral or bilateral weakness of the tongue or soft palate, paresis or paralysis of the pharyngeal constrictor muscle, incomplete or absent epiglottic tilt, poor laryngeal elevation, poor laryngeal closure with laryngeal penetration, aspiration (often without a cough), and luminal narrowing at the cricopharyngeal level. Other structural lesions included a Zenker diverticulum in one patient, bilateral pharyngeal pouches in five, and a unilateral pouch in one. Additional structural lesions contributing to dysphagia were found in two other patients, including a focal stricture in the cervical esophagus in one patient and two stenotic rings in the distal esophagus in another. In four patients (one of whom had the Zenker diverticulum), the inferior constrictor muscle contracted forcibly above a prominent cricopharyngeus muscle, perhaps contributing to the formation of the diverticulum. It is important to examine postpolio patients with dysphagia carefully with dynamic imaging to assess the severity of decompensation and to detect other lesions that may be treatable. The information derived can be used to guide management.

Cineradiography