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Biomedical subjects

S H Smith

Publications and source records attributed to S H Smith.

At least 37 records · Page 2Linked to original sources
PubMed1994

CD40 ligand (CD40L) expression and B cell function in agammaglobulinemia with normal or elevated levels of IgM (HIM). Comparison of X-linked, autosomal recessive, and non-X-linked forms of the disease, and obligate carriers.

Hyper-IgM syndrome is a rare immunodeficiency characterized by low or absent IgG, IgA, and IgE with normal or elevated levels of IgM. It can occur as an acquired or familial disorder with either X-linked or autosomal modes of inheritance. The X-linked form (HIGM1) is a result of mutations in the CD40 ligand (CD40L) gene, but the defect in non-X-linked forms of the disease (HIM) has not been determined. We show here that CD40L expression on activated T cells from non-X-linked patients can be detected by CD40Fc, 5c8 Mab, and anti-TRAP, whereas activated T cells from HIGM1 patients either had no detectable CD40L (Type I), or stained with anti-TRAP but not CD40Fc or 5c8 (Type II). Activated T cells from obligate carriers varied from low to normal expression of CD40L. B cells from HIGM1 and non-X-linked HIM patients proliferated in response to CD40L. Costimulation of B cells from HIGM1, from sporadic HIM, or from non-X-linked HIM patients with CD40L plus IL-2 resulted in some IgM production, but no significant IgG or IgA. Costimulation with CD40L plus IL-10 resulted in significant IgG and/or IgA secretion by B cells from some HIGM1 patients, but consistently failed to stimulate IgG or IgA secretion by B cells from non-X-linked patients. In addition, costimulation with CD40L and IL-4 failed to induce IgE secretion by B cells from one non-X-linked HIM patient, and induced a weak response in another. These results suggest that patients with non-X-linked forms of HIM may have an intrinsic B cell defect preventing heavy chain switching, which is not related to expression of CD40L.

Adolescent↗
PubMed1994

The surface structure of Leptotrichia buccalis.

Leptotrichia buccalis shows a mosaic of surface structure on its outer membrane consisting of curved ridges 35 mm high and 22 nm apart, and erect on that surface. Fimbriae (common pili) are not present and nor is an S layer. The flap-like ridges consist of strings of macromolecules radiating from the cell surface. This ridge structure is not soluble in any of the usual chaotropes and can only be released when the outer membrane has been damaged or dispersed by extracting envelope preparations with 0.5% SDS at room temperature. The ridge is then found to be attached firmly to the peptidoglycan sacculus, which may be the point of origin of the structure. When so prepared the macromolecules forming the ridge can be removed from the sacculus by treatment with 6 M guanidine HCl, and SDS-PAGE analysis of the extract reveals a 210-kDa polypeptide as a major component and a 15-kDa minor component. The latter is probably a peptidoglycan-associated protein and much of it remains with the sacculus. Each string forming the ridge is of a volume consistent with being made of three elongated 210-kDa molecules, which are united in series by strong hydrophobic association and laterally with neighboring strings by slightly weaker forces. We confirm that L. buccalis causes haemagglutination and the bacteria are known to attach to various tissue cells. Human group A red blood corpuscles remove both of the proteins from solution, which supports the hypothesis that the ridges are adhesin structures. It is likely but not proven that the 210-kDa molecule is the adhesin.

Bacterial Adhesion↗
PubMed1994

SAS, a gene amplified in human sarcomas, encodes a new member of the transmembrane 4 superfamily of proteins.

Amplification of 12q13-14 occurs in a subset of human sarcomas including malignant fibrous histiocytoma and liposarcoma. This chromosomal region has previously been found to include a number of growth-related genes including the GLI proto-oncogene and the p53-associated protein, MDM2. We now report the characterization of SAS (sarcoma amplified sequence), a novel transcript found in this region. Sequence analysis demonstrates that SAS is a novel member of a transmembrane protein family (transmembrane 4 superfamily or TM4SF) thought to be involved in growth-related cellular processes. This observation adds a TM4SF protein to the cluster of genes at 12q13-14 frequently amplified in human sarcomas.

Amino Acid Sequence↗
PubMed1993

Interleukin 6 is not required for antigen-specific antibody responses by human B cells.

Interleukin-6 (IL-6) is a late-acting differentiation factor for human B cells activated by polyclonal mitogens such as pokeweed mitogen (PWM) and Staphylococcus aureus Cowan strain I, but its role in specific antibody responses has not been established. We show here that IL-6 has no consistent effect on specific antibody responses by tonsillar mononuclear cells (TMC) stimulated with influenza virus. A blocking IL-6 antibody also had no effect on antibody production, suggesting that endogenous IL-6 production was not required. In control experiments, this antibody inhibited PWM-stimulated immunoglobulin secretion and proliferation of the IL-6-dependent B cell line B9. A requirement for IL-6 in responses of unfractionated TMC may have been disguised by the presence of T cells. To overcome this problem, we investigated the effect of IL-6 on specific antibody production by T-depleted B cells stimulated with antigen in the presence of IL-2, which is a T cell replacing factor (TRF) for human B cells. Specific antibody production was restored by IL-2, but not IL-6. Neither IL-6 nor anti-IL-6 antibody had any consistent effect on specific antibody production by purified B cells stimulated with antigen and TRF. These experiments show that IL-6 does not have a significant role in antigen (influenza virus)-specific antibody responses by human B lymphocytes.

Antibodies, Viral↗
PubMed1993

Uremic pericarditis in chronic renal failure: nursing implications.

Cardiovascular complications are the leading cause of death in patients with chronic renal failure. Pericardial disease is among the first recognized manifestations of uremia. This article explores the pathophysiology of uremic pericarditis, assessment of chronic renal failure patients at risk for developing pericarditis, and major complications of pericarditis. Current treatment modalities and nursing care for the patient with uremic pericarditis are included.

Electrocardiography↗
PubMed1992

SAS amplification in soft tissue sarcomas.

Gene amplification is an important mechanism of increased gene expression in a number of human solid tumors. We have recently identified and cloned sequences from a novel DNA amplification unit in malignant fibrous histiocytoma. The amplified sequences are derived from chromosome 12q13-14 and encode a gene designated SAS (sarcoma amplified sequence). In the present study, a series of soft tissue sarcomas was studied to characterize further the phenomenon of SAS amplification. Seven of 22 (32%) malignant fibrous histiocytomas and three liposarcomas contained SAS amplification. Strikingly, all of the tumors with SAS amplification occurred in central sites (i.e., in the abdominal or inguinal regions) rather than in the extremities (i.e., in the arms of legs). These observations demonstrate that SAS amplification occurs with a significant frequency in mesenchymal tumors and is particularly associated with abdominal disease.

Adult↗
PubMed1992

Regioselectivity of the insertion reactions of some aromatic diazo compound complexes with cyclomaltoheptaose.

Pyrolysis of solid complexes of aromatic diazo compounds with cyclomaltoheptaose (beta-cyclodextrin) yields either derivatives via insertion of carbene into hydroxyl groups. The distribution of the 2-, 3-, and 6-O-isomers indicates that the regioselectivity is moderate. The guest geometry is not as important as its size in determining the ratios of regioisomers. The origins of the regioselectivity are discussed.

Carbohydrate Conformation↗
PubMed1992

CD19 regulation of human B cell responses. B cell proliferation and antibody secretion are inhibited or enhanced by ligation of the CD19 surface glycoprotein depending on the stimulating signal used.

The regulation of human B cell proliferation and differentiation by the CD19 surface glycoprotein was investigated. As expected, proliferation induced by costimulation with anti-IgM plus IL-4 or IL-2, or with G28.8 antibody plus IL-4 was inhibited by antibody ligation of CD19. In contrast, proliferation of tonsillar B cells to mitogenic doses of PMA (5 ng/ml) or to EBV were enhanced, and proliferation of B cell lines to BCGF(low) was unaffected. Similarly, specific antibody responses by tonsillar B cells to influenza virus, and Ig secretion by the CESS lymphoblastoid cell line in response to IL-6 were inhibited, whereas polyclonal Ig production in response to EBV was enhanced. These results show that human B cell responses may be inhibited or enhanced by CD19 depending on the stimulating signal used. The difference in response to CD19 ligation did not depend on whether proliferation or differentiation was being measured, or whether stimulation was by surface Ig. In experiments using PMA as a T cell independent mitogen, it was found that ligation of CD19 inhibited proliferation of B cells costimulated with low doses of PMA plus G28.5 (CD40) antibody, but enhanced the response to higher (mitogenic) doses with or without costimulation with G28.5. The change from inhibition to enhancement occurred over a very small increase in PMA dose (0.5-1.0 ng/ml) that corresponded exactly to the lowest dose required for mitogenic activity. Finally, we showed that CD19 ligation inhibited the increase in surface expression of CD23, but not IgM, induced by IL-4, showing that CD19 ligation can have opposed effects on different responses to the same signal. Together our results suggest that CD19 activation of human B cells interacts with other signaling events to enhance or inhibit the subsequent response.

Antibody Formation↗
PubMed1992

Immunogenicity of inactivated influenza vaccine in residential homes for elderly people.

One hundred and seventy residents of 11 Leicester City Council homes for the elderly, with a total of 515 beds, were studied during a 30-week period from September 1988 to March 1989 to determine the use of influenza vaccine, the levels of influenza antibody, the incidence of influenza, and the protection afforded by vaccination. The study group of 133 women and 37 men had a mean age of 85 years and 59% had one or more chronic medical conditions. The immunization rates by home for the 170 symptomatic residents ranged from 8% to 90% (mean 45%). Seventy-one sera, 36 from vaccinated and 35 from non-vaccinated residents were collected between 1 December 1988 and 24 March 1989 and were assayed for antibody to A/Taiwan/1/86 (H1N1), A Sichuan/2/87 (H3N2) and B/Beijing/1/87. Analysis revealed no statistically significant differences between the antibody profiles of vaccinated and unvaccinated subjects. Six influenza A and 6 influenza B infections were confirmed among the 170 subjects with upper respiratory tract infections. Influenza vaccination was not associated with significant levels of protection against influenza A or B. Studies of the haemagglutinins of the vaccine strains and influenza isolates during 1988/89 showed that they were closely related.

Aged↗
PubMed1992

Wearable air supply for pneumatic artificial hearts and ventricular assist devices.

An experimental wearable air supply for pneumatic artificial hearts and ventricular assist devices has been built and tested. The unit eliminates the need for tethering to a large, stationery driver. The miniaturized air supply is designed for ambulatory patients with implanted pulsatile pneumatic total artificial hearts (TAH) or pneumatic left-ventricular assist devices (LVAD), to permit mobility in clinical and home settings. The device has major short-term utility as a supply for pneumatic TAH or VAD bridges in patients awaiting heart transplants. The system design for the wearable driver includes a novel, fast rotary compressor, driven by a brushless direct current (DC) motor to supply air to the ventricle through an electromagnetically actuated directional valve, all controlled by a microcomputer. Stroke volume from 0 to 200 cc; pulse rate from 60 to 160 bpm, and duty cycle from 33% to 50% are selected on a keyboard, and the selected or measured parameters can be shown on a liquid crystal display. For control of delivery from a single ventricular assist device, stroke volume is controlled by variation of compressor speed. In the wearable air supply for a TAH, a single compressor drives both ventricles alternately through a double-acting directional valve. Air volume delivered to the left ventricle is adjusted by variation of compressor speed, and air volume to the right ventricle by variation of ejection time. The effect on blood flow rate of the lower impedance to the right ventricle is compensated by provision of a two-stage compressor, in which a single stage drives the right ventricle, and both stages connected in parallel drive the left ventricle. The overall dimensions of the prototype air supply for driving either a TAH or LVAD are 4.5 by 7.8 by 4.5 inches, including an emergency battery with a duration of 15 to 30 min depending on load. The weight is presently 5.5 lb, but this will be reduced in a production design and for a dedicated LVAD air supply. The size and weight of a separately worn, rechargeable battery pack depend on the load and desired duration of operation.

Electric Power Supplies↗
PubMed1992

The S-layer of Caulobacter crescentus: three-dimensional image reconstruction and structure analysis by electron microscopy.

The regular surface protein structure (S-layer) of Caulobacter crescentus was analyzed by electron microscopy and three-dimensional image reconstruction to a resolution of 2 nm. Projections showed that the S-layer is an array of ring structures, each composed of six subunits that are arranged on a lattice with p6 symmetry. Three-dimensional reconstructions showed that the ring subunits were approximately rod-shaped structures and were perpendicular to the plane of the array, with a linker arm emanating from approximately the middle of the rod, accounting for the connections between the rings. The calculated subunit mass was ca. 100 kDa, very close to the size of RsaA (the protein known to be at least the predominant species in the S-layer) predicted from the DNA sequence of the rsaA gene. The core region of the rings creates an open pore 2.5 to 3.5 nm in diameter. The size of the gaps between the neighboring unit cells is in the same range, suggesting a uniform porosity predicted to exclude molecules larger than ca. 17 kDa. Attempts to remove membrane material from S-layer preparations with detergents revealed that the structure spontaneously rearranged into a mirror-image double layer. Negative-stain and thin-section electron microscopy examination of colonies of C. crescentus strains with a mutation in a surface molecule involved in the attachment of the S-layer showed that shed RsaA protein organized into large sheets. The sheets in turn organized into stacks that tended to accumulate near the upper surface of the colony. Image reconstruction indicated that these sheets were also precise mirror-image double layers, and thickness measurements obtained from thin sections were consistent with this finding. The sheets were absent when these mutant strains were grown without calcium, supporting other data that calcium is involved in attachment of the S-layer to a surface molecule and perhaps in subunit-subunit interactions. We propose that when the membrane is removed from S-layer fragments by detergents or the attachment-related surface molecule is absent, the attachment sites of the S-layer align precisely to form a double layer via a calcium interaction.

Bacterial Outer Membrane Proteins↗
PubMed1992

Isolation and comparison of the paracrystalline surface layer proteins of freshwater caulobacters.

Several methods for isolation of the paracrystalline surface (S) layer protein (RsaA) of Caulobacter crescentus CB15A were evaluated. Treatment of cells with HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid) buffer at pH 2 was the most effective means of selectively removing RsaA from cells, and after neutralization, the protein was capable of reassembling into a paracrystalline structure. Ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid treatment could also be used to extract RsaA and yielded protein capable of reassembly. The success of the methods was likely related to disruption of calcium-mediated bonding; calcium was required for recrystallization, while magnesium and strontium ions were ineffective. Antibody was raised against purified RsaA and, along with the S-layer extraction techniques, was used to evaluate 42 strains of caulobacters isolated from a variety of aquatic and wastewater treatment locations. A single characteristic protein could be isolated from the 35 strains that produced an S layer; with one exception, no proteins were extracted from strains that had no S layer. The presumed S-layer proteins ranged in size from 100 to 193 kDa. All of these proteins specifically reacted with anti-RsaA serum by Western immunoblot analysis. In strain CB15A, a specific S-layer-associated oligosaccharide has been proposed to be involved in a calcium-mediated attachment of the S layer to the cell surface. This molecule was detected by Western immunoblotting with a specific antiserum and on polyacrylamide gels stained for polysaccharides. A comparable band was found in all S-layer-producing strains and for most, S-layer-associated oligosaccharide-specific antibody reacted with them in Western analysis. Overall, in freshwater caulobacters at least portions of their S-layer structures appear to be strongly conserved entities, as well as the means of attachment to the cell surface.

Bacterial Proteins↗
PubMed1991

The role of interleukin 4 in specific antibody responses by human B cells.

This study was designed to investigate the requirement for interleukin 4 (IL-4) in specific antibody responses by human lymphocytes. Addition of IL-4 to antigen (influenza virus)-stimulated cultures of tonsillar mononuclear cells was found to suppress specific antibody production significantly at doses as low as 10 units/ml. Specific immunoglobulin (IgG), IgA, and IgM antibodies were all equally inhibited by IL-4. Inhibition of the antibody response with IL-4 was completely abrogated by an IL-4 blocking antibody showing that the effect was specific for IL-4. It was also found that anti-IL-4 did not inhibit specific antibody production, showing that IL-4 was not required for responses to antigen. In contrast, significant inhibition was obtained with anti-Tac, indicating an important role for IL-2. In the absence of T helper cells antibody responses to influenza virus were completely restored with T cell replacing factor [TRF; IL-2 or low-molecular-weight B cell growth factor (BCGFlow)], but not with IL-4. In fact, IL-4 significantly suppressed the antibody response obtained when either IL-2 or BCGFlow was used as a TRF. Addition of IL-4 at different times after in vitro stimulation with antigen and IL-2 showed that the inhibitory activity of IL-4 was maximal during the first 3 days of culture and was lost by day 4. IL-4 therefore seems to inhibit an early activation event (possibly dependent on IL-2 or BCGFlow), or B cell proliferation essential for specific responses to antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1991

The impact of varying degrees of iron nutriture on several functional consequences of iron deficiency in rats.

The impact of varying severities of iron-deficiency anemia on fasting blood glucose, plasma triiodothyronine, heart norepinephrine concentrations and resting oxygen consumption were evaluated. Male weanling Sprague-Dawley rats were assigned to one of six dietary groups (4, 6, 11, 16, 23 or 40 mg Fe/kg diet) for 6 wk. Hemoglobin, liver iron and transferrin saturation were significantly lower in the 4 and 6 mg Fe/kg diet groups relative to the other groups and were indicative of anemia, low tissue iron stores and impaired erythropoiesis. Fasting blood glucose and heart norepinephrine concentrations were significantly higher and lower, respectively, in the 4 and 6 mg Fe/kg diet groups than the three highest dietary Fe groups. Although fasting blood glucose was significantly inversely correlated (r = -0.89, P = 0.0001) with hemoglobin concentration; a significant quadratic relationship (R 2 = 0.70, P = 0.0001) existed between hemoglobin and heart norepinephrine concentration. Differences in plasma triiodothyronine concentrations and resting oxygen consumption were not significant among the groups. Thus, base on hemoglobin concentration as an index of the severity of iron deficiency, these findings demonstrate that certain physiological manifestations of iron deficiency occur at even moderate-to-mild degrees of anemia.

Anemia, Hypochromic↗
PubMed1991

PIS and DRGs: coding inaccuracies and their consequences for resource management.

Accurate information is important for the successful implementation of the Resource Management Initiative and the NHS White Paper. A review of 153 joint replacements performed in a three-month period in Leicester showed that 24 per cent of 139 procedures for which medical notes were available had been given incorrect Diagnosis-Related Groupings (DRGs). Of these, 64 per cent could be ascribed to errors in allocating OPCS-3 codes and 36 per cent to errors in converting OPCS-3 codes to DRGs by computer. It is of concern that inaccurate information may in future be used to allocate resources. The resource implications of assiduous quality control of recording, coding and computing is pointed out, and it is suggested that improved classification systems should be assessed for use in the NHS.

Diagnosis-Related Groups↗
PubMed1991

Relationship between pyridinoline concentration and thermal stability of bovine intramuscular collagen.

Semimembranosus muscle samples were obtained from 49 Holstein beef animals representing different USDA maturities. Intramuscular collagen (IMC) was isolated in the frozen state and evaluated for heat-labile collagen solubility (% Sol), thermal shrinkage temperature (Ts), enthalpy (Hs) changes, and mature crosslink (pyridinoline) content. These measures were obtained to elucidate a relationship between pyridinoline content of IMC and beef maturity level and to relate IMC thermal stability (% Sol, Ts, and Hs) to pyridinoline content. With increasing maturity, % Sol decreased (P less than .01) and Ts increased (P less than .01), whereas Hs showed no change (P greater than .05). Thus, IMC melted at increasing temperatures, but the amount of energy required to induce this endothermic change remained constant throughout maturation. The pyridinoline content of IMC increased (P less than .01) linearly with maturity, indicating that this heat-stable, mature crosslink enhances thermal stability of IMC as beef muscle matures. Significant correlations between pyridinoline content and maturity (r = .56; P less than .001) and Ts (r = .34; P less than .05) support this contention.

Amino Acids↗
PubMed1991

Activation of human B cells through the CD19 surface antigen results in homotypic adhesion by LFA-1-dependent and -independent mechanisms.

Addition of CD19 monoclonal antibodies (mAb) to highly purified tonsillar B cells resulted in homotypic adhesion and the formation of cell clusters. This response was completely blocked by antibody to LFA-1, indicating an LFA-1-dependent adhesion mechanism. In contrast, aggregate formation by B cells activated with phorbol myristate acetate (PMA) was only partially inhibited by anti-LFA-1 antibody, and those formed in response to PMA plus CD19 antibody were not inhibited at all, suggesting aggregation of activated B cells stimulated with CD19 antibody was LFA-1 independent. This was confirmed with B-cell lines. The pre-B-cell line Nalm-6 formed aggregates in response to CD19 antibody which were not inhibited with anti-LFA-1. In addition, CD19 antibody induced aggregate formation by an Epstein-Barr virus (EBV)-transformed B-cell line derived from an LFA-1-deficient donor. These results suggest that different adhesion molecules may operate at different stages of B-cell activation, and that CD19 may be important in cell-cell interactions involved in regulation of antibody responses.

Antibodies, Monoclonal↗