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Biomedical subjects

H R Smith

Publications and source records attributed to H R Smith.

At least 199 records · Page 11Linked to original sources
PubMed1985

Analysis of B-cell subpopulations. I. Relationships among splenic xid, Ly 1+, and Lyb 5+ B cells.

The phenotypic and functional relationships among the various B-cell subsets is of importance for better understanding studies of the immune system. In this report, the realm of B cells encompassed by Lyb 5, Ly 1, and xid has been examined through the use of the alloantiserum anti-Lyb 5, the unique functional properties of Ly 1+ B cells, and the spontaneous autoantibody producing congenic xid mice, NZB.xid. By functional and phenotypic analysis, we have shown that (i) Lyb 5- B cells and B cells of xid mice are largely, but not completely, overlapping; (ii) xid spleen cells contain a population which is Lyb 5+; (iii) Ly 1+ B cells fall largely in the Lyb 5+ compartment; and (iv) the autoantibody-producing Ly 1+ B cells are predominantly Lyb 5+.

Animals↗
PubMed1985

Expression of cloned plasmid regions encoding colonization factor antigen I (CFA/I) in Escherichia coli.

Molecular cloning from a plasmid encoding colonization factor antigen I (CFA/I) and heat-stable enterotoxin isolated two regions, 1 and 2, that are required for the production of CFA/I fimbriae. The level of CFA/I synthesis measured by ELISA was similar in an Escherichia coli K12 strain carrying regions 1 and 2 cloned separately on compatible plasmid vectors to that in the same strain containing the parental plasmid. The structural gene for the CFA/I fimbrial subunit was within region 1. This region directed production in E. coli minicells of at least six independent polypeptides, of which the fimbrial subunit and at least three others appeared to be synthesized as precursor molecules that underwent processing. Cloned DNA containing CFA/I region 2 specified three polypeptides in minicells. Attempts to reduce the size of the cloned region 1 resulted in a derivative plasmid that carried the CFA/I structural gene but did not complement a region-2 recombinant plasmid to restore production of CFA/I fimbriae.

Antigens, Bacterial↗
PubMed1985

Cloning of genes determining the production of vero cytotoxin by Escherichia coli.

Sequences encoding the production of a cytotoxin (VT) active on Vero cells were cloned in Escherichia coli K12 from a VT-determining phage that originated in E. coli strain H19 of serotype O26.H11. Subcloning resulted in the identification of a 2.5 kb fragment that still coded for VT production. Mutagenesis with transposon Tn1000 was used to map VT sequences and a 0.75 kb probe was developed. In colony hybridization tests with strains isolated from patients with haemolytic uraemic syndrome or diarrhoea, this probe derived from the H19 VT genes detected only some of the VT+ strains belonging to serogroup 0157. A VT+ strain, E32511, serotype 0157.H-, which was negative in colony hybridization was the source of another VT-determining phage from which VT sequences were cloned. Southern hybridization of the VT genes from E32511 with the H19 probe was negative under stringent conditions but there was weak homology under conditions of low stringency. These results indicate that there are differences in the VT genes of pathogenic E. coli.

Bacterial Toxins↗
PubMed1985

Studies of the pathogenesis of angioimmunoblastic lymphadenopathy.

We studied the immune functions of two patients with angioimmunoblastic lymphadenopathy (AILD) in an attempt to determine whether the B cells were primarily hyperactive or, rather, if T cell abnormalities might underlie the B cell hyperactivity observed in these patients. We found that the B cells of the AILD patients did not proliferate spontaneously, nor were they induced to proliferate excessively by fresh normal T cells. In contrast, AILD T cells induced both autologous and allogeneic B cells to proliferate and to differentiate into Ig secreting cells. Spontaneous culture supernates of T cells obtained from each patient induced substantial proliferation of B cells (B cell-activating activity) as well as proliferation in a standard costimulatory assay (B cell growth factor activity). The culture supernate of a T cell line, which was established from one patient, showed both activities. The T cell line supernate also induced Ig production by staphylococcal A Cowan-activated B cells. None of these properties of AILD T cells was found among 10 normal controls. The addition of AILD T cells to autologous or allogeneic B cells in the presence of pokeweed mitogen (PWM) led to marked suppression of both proliferation and Ig production. This was true even in the presence of fresh normal T cells. Pretreatment studies showed that suppressor cells were induced by the interaction of AILD T cells with PWM-activated B cells. The present study suggests that the B cell hyperactivity observed in AILD patients might in part be due to excessive T cell effects on B cells. In addition, our results may help clarify the paradoxical impaired responsiveness to in vitro stimulation with PWM by active B cells from patients with autoimmune diseases.

Antibodies, Monoclonal↗
PubMed1985

Modulation of c-myb transcription in autoimmune disease by cyclophosphamide.

This study explores the relationship between autoimmunity and the myb proto-oncogene, a gene important for T cell development. The lpr/lpr mice had very large amounts of myb RNA in the lymph node (LN) cells; but unexpectedly, they had abnormally low levels of myb RNA in the thymus, an organ normally rich in myb RNA. Mice with the gld/gld genotype had high myb RNA levels in peripheral LN, similar to lpr/lpr mice, but had normal thymic myb RNA levels. Both lpr/lpr and gld/gld mice and an AILD patient with lymphadenopathy and high myb RNA in peripheral blood cells were treated with cyclophosphamide (CY). In all cases, the CY eliminated the lymphadenopathy and corrected the abnormal myb expression. However, there were significant differences in the clinical and cellular responses to this drug. A single large dose of CY led to marked regression of the lymphadenopathy of gld/gld mice and long-term amelioration of their autoimmune syndrome. In contrast, similar treatment of lpr/lpr mice failed to alter either the lymphadenopathy or the disease process. Consistent with these clinical findings, LN myb was normalized in gld/gld mice by a single injection of CY, whereas there was no effect on myb expression in lpr/lpr mice. The AILD patient reacted much like the gld/gld mice in that myb RNA levels in the peripheral blood, and bone marrow returned to normal after only three doses of CY. The lymphadenopathy and high levels of LN myb mRNA of the lpr/lpr mice could be normalized; this occurred only after long-term treatment with CY. These events were accompanied by an increase in thymic myb mRNA from low levels. These studies have combined a molecular probe with CY therapy to provide insights into the cellular bases for lymphoproliferative autoimmune diseases.

Animals↗
PubMed1984

Autoimmunity and increased c-myb transcription.

A single recessive gene, lpr, induces an autoimmune-lymphoproliferative syndrome in several strains of mice. The lymphoid organs of lpr/lpr mice contained cells with increased amounts of myb RNA, which codes for a protein found in the nucleus. A similar human lymphoproliferative disorder also had an increase in c-myb expression. Mouse T cells induced by mitogens to proliferate did not express large amounts of myb RNA, indicating that marked myb expression is not a general feature of lymphocyte activation and proliferation.

Animals↗
PubMed1984

Nonhemorrhagic venous infarction of the spinal cord.

A 71-year-old man experienced gradually progressive leg weakness, urinary retention, and mild loss of sensation in dermatomes T8 through T12 bilaterally. After 5 to 6 weeks of illness, he developed flaccid paraplegia and sensory loss below T8. He died 16 weeks after onset of neurological symptoms. Neuropathologically, there was widespread, subtotal necrosis of the spinal cord, largely of nonhemorrhagic character, from T8 downward. Dorsal and anterior median spinal veins were occluded by a partially organized thrombus. Comparison of this case with 19 previously recorded examples of venous infarction of the spinal cord (8 hemorrhagic, 7 nonhemorrhagic, and 4 embolic) suggests major differences in clinical presentation, rate of progression, and length of survival among the three groups.

Aged↗
PubMed1984

Cyclophosphamide-induced changes in the MRL-lpr/lpr mouse: effects upon cellular composition, immune function, and disease.

MRL-lpr/lpr mice develop massive lymphadenopathy with excessive proliferation of T cells and associated immune abnormalities. To examine whether to not the disease process is intrinsic and irreversible, an immunomodulatory drug, cyclophosphamide, was administered to 16-week-old, sick MRL-lpr/lpr mice. Analysis of lymph node cells by flow cytometry from injected and control MRL-lpr/lpr mice indicated that cyclophosphamide had a marked effect upon the lymphoid cellular composition. Whereas control lymph nodes had a very large number of abnormal dull Ly 1+ T cells and very few other cells, the cyclophosphamide-injected mice had normal T and B cells. The immune responses to a T-cell-dependent antigen, sheep red blood cells, and a T-cell mitogen, concanavalin A, were normalized in cyclophosphamide-injected mice as compared to controls. In addition, injected mice had prolonged survival, decreased arthritis, markedly reduced adenopathy and splenomegaly, improved renal histology, and significantly diminished autoantibody levels. This study suggests that the disease and associated immune abnormalities of MRL-lpr/lpr mice are reversible by selective elimination of the abnormal dull Ly 1+ T cells.

Animals↗
PubMed1984

NIH conference. Systemic lupus erythematosus: insights from animal models.

Systemic lupus erythematosus is a multisystem, antibody-mediated, autoimmune disorder that occurs spontaneously in humans and mice. Genetic factors appear to play an important predisposing role in the disorder: The presence of certain genes may produce a generalized immune abnormality, whereas others may lead to specific autoantibodies. Environmental triggers increase autoantibody production and augment the expression of illness. Bacterial and viral illnesses can provide stimulation by activating macrophages and T cells that, in turn, stimulate B cells. In the absence of normal control mechanisms, the stimulatory process is not suppressed, and excessive stem cell proliferation results in abnormal B-cell proliferation. A trigger for the disease is the signaling of the proliferating B cells to differentiate into antibody-forming cells. Most autoantibody-producing B cells can be eliminated from mice with lupus erythematosus by virtue of the presence of the gene, xid. In addition, administration of an analog of arachidonic acid is an effective treatment for murine lupus erythematosus.

Animals↗
PubMed1984

Computergraphics and biocommunication: a report on the impact.

This report is based on a survey conducted to determine the impact of computergraphics on biocommunication departments. Data and comments were received from 24 departmental directors and 45 computergraphics artists/operators. Reported are: impacts on productivity, turnaround times, staffing, and workloads; comments related to implementation of the technology; and advice concerning factors that affect job satisfaction for artists/operators. From the report emerges a picture of technology that, if properly implemented, can provide an exciting cost-effective tool for the biocommunicator.

Academic Medical Centers↗
PubMed1983

Expression of plasmids coding for colonization factor antigen II (CFA/II) and enterotoxin production in Escherichia coli.

Two plasmids transferred from enterotoxigenic Escherichia coli (ETEC) of serotype O6. H16 and biotypes A and C coded for mannose-resistant haemagglutination (MRHA) and production of heat-stable enterotoxin (ST) and heat-labile enterotoxin (LT). Both plasmids were nonautotransferring being mobilized most efficiently by the R plasmid R100-1. They were similar in their genetic properties being incompatible with each other and plasmids of the Inc group FI. The wild-type strains produced the colonization factor antigen II (CFA/II) which was made up of different coli surface antigens (CS). The biotype A strains produced CS1 and CS3 while the biotype C strains produced CS2 and CS3. These three antigens have the ability to cause MRHA. When plasmids coding for MRHA were transferred to K12 strains, the degree of haemagglutination was markedly reduced and only CS3 was produced. When both plasmids were transferred back into biotype A strains, good MRHA was restored and the strains produced CS1 and CS3. In a biotype C strain CS2 and CS3 were formed. The production of the antigens was compared by enzyme-linked immunosorbent assay (ELISA). The strains were also examined by electron microscopy where it was found that CS1 and CS2 were fimbrial antigens while CS3 was not.

Antigens, Bacterial↗
PubMed1983

Plasmids that code for production of colonization factor antigen II and enterotoxin production in strains of Escherichia coli.

Similar plasmids that code for production of colonization factor antigen II and enterotoxins were mobilized into Escherichia coli K-12 from strains of E. coli O6.H16 biotype B or C that expressed colonization factor antigen II components CS2 and CS3. Further transfer experiments demonstrated that there was production of CS2 and CS3 in an O6.H16 biotype C strain, but there was expression of only CS3 in other serogroups and in E. coli K-12.

Antigens, Bacterial↗