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Biomedical subjects

S Jackson

Publications and source records attributed to S Jackson.

At least 217 records · Page 12Linked to original sources

Mucosal immunity in the female genital tract: relevance to vaccination efforts against the human immunodeficiency virus.

The development of vaccines that induce specific immune responses in the genital tract secretions would have far-reaching implications for the prevention of AIDS and other sexually transmitted diseases. Most of the currently studied vaccines utilize systemic routes of immunization that are of limited value for the prevention of mucosa-contracted diseases. The relative contribution of antigen-sensitized cells and IgA-committed lymphocytes from IgA inductive sites (e.g., Peyer's patches and rectal tonsils) to remote or adjacent effector sites (e.g., salivary glands and female genital tract) as manifested by the appearance of corresponding secretory antibodies has not been studied in humans despite its unquestionable practical importance. Exploitation of immunization routes that are effective for induction of mucosal immune responses and reflect our current knowledge of the origin of antibodies and of specific antibody-forming cells in mucosal tissues is likely to reduce the incidence of many infectious diseases including AIDS.

AIDS Vaccines↗

A diabetic day in the outback.

Isolated communities present particular problems for patients with chronic conditions. This article studies information gained from a 'diabetic day' held in our community, the aim of which was to assess our present standard of care and to provide our diabetic community with much easier access to specialised health care workers.

Administration, Oral↗

Acute fatty liver of pregnancy and long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency.

The pathogenesis of acute fatty liver of pregnancy is unknown, but similarities in the clinical presentation and the histological appearance of the liver with those found in children with metabolic defects in the intramitochondrial beta-oxidation pathway of the liver suggest that a disturbance in hepatic fatty acid oxidation may play a role. We report a woman with acute fatty liver of pregnancy who gave birth to a seemingly normal full-term infant who was seen at 4 mo of age with hypoglycemia, coma and profound hepatic steatosis. The infant had a defect in fatty acid oxidation, long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency, and the mother proved to be heterozygous for this metabolic condition. We hypothesize that the interaction of an affected fetus with a female heterozygous for this defect in fatty acid oxidation in the late third trimester accounts for some cases of acute fatty liver of pregnancy.

3-Hydroxyacyl CoA Dehydrogenases↗

Episiotomy: does it have to hurt so much afterwards?

Episiotomy is one of the commonest surgical procedures in the UK. Many women suffer pain for several days sometimes weeks afterwards and dyspareunia may be a problem. Absorbable suture materials appear to be preferable to non-absorbable ones. Infiltrating the perineum with normal saline before suturing may help reduce postpartum perineal pain. Omitting sutures just below the skin surface may cause less pain. More research is needed. The skill of the operator seems to be a factor. Midwives need to evaluate their practice in repairing the perineum

Clinical Nursing Research↗

Shared idiotypes in mesangial deposits in IgA nephropathy are not disease-specific.

The antigenic specificity of the mesangial IgA in IgA nephropathy (IgAN) remains unknown. Because shared antigenic specificities may be reflected in the usage of shared idiotypes, we prepared five monoclonal anti-idiotypic antibodies (MoAbs) specific for the mesangial IgA eluted from the kidney of an IgAN patient. All five MoAbs reacted with the same idiotype, which proved to be of a public nature. Although the idiotype could be identified in the mesangial deposits of the majority of IgAN patients studied, it was not specific for the disease because it was also found in the glomerular deposits of other types of glomerulonephritis. The idiotype was also expressed in polyethylene glycol precipitates of sera and in pokeweed mitogen-induced plasma cells from both IgAN patients and healthy controls. The conclusion that no disease-specific idiotypes are present in the renal eluate was further supported by the failure to produce polyclonal anti-idiotypic antibodies by immunizing a rabbit with the eluted mesangial IgA. Our results support the concept that mesangial IgA deposits in IgAN are of a polyclonal nature.

Antibodies, Monoclonal↗

Theory to practice: developing a Rogerian-based assessment tool.

Nursing models are invaluable in the direction they provide for nursing practice, education and research. The growth and development of the nursing profession is enhanced when its practice is guided by nursing theory. Rogers' Science of Unitary Human Beings is appealing to nursing because of its open-systems perspective and focus on holistic and individualistic care. Rogers' model is utilized to develop a nursing assessment tool that may be used in a variety of situations. The Rogerian-based assessment tool is used to gather data from a postpartum mother experiencing the challenges of her first newborn. Problems incurred while developing and utilizing the tool are discussed. Rogers' model is shown to be practical and effective in this case study.

Adult↗

Elevated serum alpha fetoprotein and normal liquor alpha fetoprotein values in association with an abdominal pregnancy.

A case report is described in which abdominal pregnancy was misdiagnosed by ultrasound scanning as a pregnancy within a horn of a bicornuate uterus. Two serum alpha fetoprotein (SAFP) results were greatly elevated and an amniocentesis was performed, the liquor alpha fetoprotein (LAFP) and karyotype were normal. Elective Caesarean section was performed at 38 weeks for a persistent transverse lie and an abdominal pregnancy was found. The outcome was excellent for both the mother and child. This is the first reported case of amniocentesis and measurement of LAFP in an abdominal pregnancy and confirms abdominal pregnancy as a rare cause of an elevated SAFP.

Adult↗

Met-enkephalin secretion from mixed cultures of hypothalamic neurons and astrocytes.

Release of the endogenous opioid pentapeptide, met-enkephalin, from primary cultures of dissociated fetal rat hypothalamic cells was studied using an assay system which could both measure and differentiate between free met-enkephalin and the larger enkephalin-containing peptides (ECPs), which are the processing intermediates of the enkephalin precursor. The cultures were maintained in fully defined, serum-free medium and contained both neurons and astrocytes. Free met-enkephalin was secreted from the cultures in significant quantities in response to nonspecific depolarisation with 56 mM potassium, by a mechanism dependent upon extracellular calcium. Under basal conditions, barely detectable amounts of free peptide were released, whereas ECPs were secreted in significant quantities which were not reduced by the removal of extracellular calcium. As the period of culture increased, so did the quantitative importance of this constitutive ECP secretion, relative to the stimulated release of free peptide. Treatment of the cultures with the cytotoxic agent, cytosine arabinoside, attenuated this temporal increase of ECP secretion, whilst leaving the stimulated release of free met-enkephalin relatively unaffected. This suggested that the met-enkephalin secretion seen within the cultures reflected the presence of at least two distinct enkephalinergic cell types and that the change in the nature of the secreted enkephalin was at least in part, due to the proliferation of one of these cell populations. These results are consistent with secretion of met-enkephalin from both neurons and astrocytes within these cultures. We propose that the neurons secreted essentially fully processed peptide in a regulated manner, whilst the mitotic glial cells constitutively secreted non- or partially processed precursor peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antiplatelet efficacy and specificity of DMP728, a novel platelet GPIIb/IIIa receptor antagonist.

The present study was undertaken to define the platelet GPIIb/IIIa affinity and specificity of DMP728, the cyclic [(D-2-aminobutyrate-N-methyl-L-arginyl-glycyl-L-aspartyl)-3-aminomethyl- benzoic acid] methane sulfonate. DMP728 demonstrated similar potency (IC50 = 0.046 +/- 0.002 microM) in inhibiting human platelet aggregation induced by various agonists or combination of agonists as assessed either by light transmittance aggregometry or impedance techniques. Similarly, DMP728 inhibited (IC50 = 2.3 +/- 0.8 nM) with equipotency in inhibiting 125I-fibrinogen binding to human gel-purified platelets regardless of the agonist used. In purified human GPIIb/IIIa ELISA, DMP728 demonstrated a competitive high affinity binding (Ki = 0.4 nM). Additionally, a high binding affinity (Kd = 0.1 nM) of 3H-DMP728 was demonstrated in human platelets. Furthermore, a platelet deaggregatory efficacy was shown. DMP728 demonstrated a high degree of specificity for platelet GPIIb/IIIa (alpha 2/beta 3) as compared to other integrins on endothelial cells (vitronectin receptors), platelets GPIb/1X, alpha v/beta 3, and other integrins on leukocytes or nonintegrin-related systems. In conclusion, DMP728 is a novel antiplatelet agent with high affinity and specificity for platelet GPIIb/IIIa.

Animals↗

Endothelin binding to receptors and endothelin production by human thyroid follicular cells: effects of transforming growth factor-beta and thyrotropin.

Measurable endothelin (ET) was found in serum-free medium of cultured primary thyroid cells derived from human thyroid tissues after 3 days incubation at levels ranging from undetectable to 35 fmol/100,000 cells. Out of 12 thyroid glands studied, 2 responded to transforming growth factor-beta (TGF-beta) treatment with increased ET secretion into medium. Detailed study of cells derived from one of these thyroids showed TGF-beta at 1 ng/ml stimulated ET secretion from 13.7 to 33.3 fmol/100,000 cells after 3 days incubation. Although TSH alone did not significantly modulate ET release into medium, TSH enhanced the stimulatory effect of TGF-beta. A combination of TSH at 1 mU/ml and TGF-beta at 1 ng/ml stimulated ET secretion to 63.8 fmol/100,000 cells after 3 days incubation. Immunostaining studies demonstrated the presence of intracellular immunoreactive ET, largely localized in perinuclear regions, which was greatly stimulated by TSH but not by TGF-beta. These observations suggest that TSH may stimulate only ET synthesis, whereas TGF-beta may stimulate both synthesis and secretion. Binding of [125I]ET-1 to receptor on thyroid cells was dose-dependently stimulated by TGF-beta (0-10 ng/ml) pretreatment for 3 days. Scatchard analysis of competitive binding data from TGF-beta (1 ng/ml)-treated cells indicated that increased binding was the result of increased receptor number and not increased receptor affinity. TSH (0-10 mU/ml), though not as potent as TGF-beta, also dose-dependently stimulated ET binding. Treatment of thyrocytes with 1 mU/ml TSH for 3 days did not significantly affect ET receptor number or binding affinity. These results illuminate aspects of a possible autocrine regulation of ET in the thyroid gland.

Adenoma↗

Transforming growth factor-beta inhibits the production of IgG, IgM, and IgA in human lymphocyte cultures.

Transforming growth factor beta (TGF beta) has potent immunoregulatory effects acting on both T and B cells. It strongly inhibits secretion of IgG and IgM in human and murine B cell cultures, but has been shown to have an enhancing effect on IgA production in the mouse. We have studied the effect of TGF beta on the production of IgA in human lymphocyte cultures. The addition of TGF beta to pokeweed-stimulated peripheral blood lymphocytes resulted in a suppression of IgA production of both subclasses, similar in magnitude to the suppression of IgG and IgM production. Membrane IgA expression was not increased by culturing tonsillar lymphocytes with TGF beta. In conclusion, we find no evidence for a selective enhancing effect of TGF beta on IgA synthesis in humans, in contrast to the findings reported in mice.

Adult↗

The sequence of the flavoprotein subunit of bovine heart succinate dehydrogenase.

The cDNA sequence of the flavoprotein subunit of bovine heart succinate dehydrogenase is reported. This is the first complete eukaryotic sequence of the flavoprotein subunit to be characterized, and it encodes a 665-amino acid protein that consists of a presequence and a 621-residue mature protein. The deduced bovine sequence shows homology to the corresponding peptides of prokaryotic succinate dehydrogenase and the related fumarate reductases; in particular, there is good overall homology (48%) to the flavoprotein subunit of Escherichia coli succinate dehydrogenase. The conserved sequences comprising the active site and those involved in FAD binding are also found in the bovine protein. The active site of the bovine polypeptide contains a cysteine that confers sensitivity of the enzyme to sulfhydryl reagents; this cysteine is only present in some sequences and thus provides a discriminatory biochemical marker. A putative flavoprotein subunit of human placental succinate dehydrogenase (partial sequence) that lacks this critical cysteine (Malcovati, M., Marchetti, T., Zanelli, T., and Tenchini, M. L. (1991) in Flavins and Flavoproteins 1990 (Curti, B., Ronchi, S., and Zanetti, G., eds) pp. 727-730, Walter de Gruyter & Co., Berlin) has only 16% homology to the bovine heart flavoprotein subunit. However, we show that the enzyme from human placenta is as sensitive to N-ethylmaleimide as that from bovine tissues. In addition, a transcript in human placenta and muscle hybridizes to the bovine heart flavoprotein cDNA and is the same size as that in bovine tissues.

Amino Acid Sequence↗

The measurement of carnitine and acyl-carnitines: application to the investigation of patients with suspected inherited disorders of mitochondrial fatty acid oxidation.

We describe an improved radio-enzymatic method for the measurement of carnitine, short-chain acyl-carnitine and long-chain acyl-carnitine in plasma and tissue. An internal standard, hexadecanoyl-[CH3-3H]-carnitine was synthesised and used to improve the determination of long-chain acyl-carnitine. The between and within batch precisions were 10.4 and 7%, respectively. Control data for neonates, infants, children and adults in the fed and fasted state are documented. In addition we confirm the hypocarnitinaemia associated with pregnancy. Patients with medium-chain acyl-CoA dehydrogenase deficiency were studied during episodes of hypoglycaemia. In both fasted controls and patients there were high concentrations of short-chain acyl-carnitine, however in the latter group there were also low concentrations of free carnitine. We suggest that the monitoring of plasma carnitine and its derivatives is a useful adjunct to the investigation of children suspected to suffer from inherited disorders of mitochondrial beta-oxidation. We also describe a sample preparation procedure suitable for high performance liquid chromatographic analysis of specific acyl-carnitines from urine, plasma and tissue homogenates. The recoveries of acetyl-carnitine, octanoyl-carnitine and hexadecanoyl carnitine from urine were 101.5, 95 and 91% and from plasma 99.5, 91.5 and 85.5%, respectively. Acyl-carnitines (C2-C16) were analysed as their p-bromophenacyl derivatives by reverse-phase high performance liquid chromatography using a ternary gradient of acetonitrile/water/triethylamine phosphate. We report ten patients who excreted octanoyl-carnitine, hexanoyl-carnitine and in some cases a small amount of decanoyl-carnitine. In most of these cases suberylglycine and dicarboxylic acids were also detected by GC/MS. We had access to cultured fibroblasts from five of these patients and were able to demonstrate medium-chain acyl-CoA dehydrogenase deficiency by direct enzyme assay.

Aging↗

The complex CD44 transcriptional unit; alternative splicing of three internal exons generates the epithelial form of CD44.

We have utilized the polymerase chain reaction (PCR) to isolate a 3.5 kilobase pair (kb) genomic fragment that encodes the additional extracellular domain unique to the epithelial isoform of CD44 (CD44E). Nucleotide sequence was determined for this complete region and sequence comparison to our previously determined CD44R1 and CD44R2 cDNA sequences revealed the R region to be comprised of three exons of 102 bp, 90 bp, and 204 bp. Northern blot analysis of CD44 expressing cell lines confirmed the presence of CD44R1 transcripts and indicates that the epithelial domain may be inserted through alternative splicing into all CD44 transcript classes. Southern blot analysis of the CD44E genomic fragments is consistent with a single copy per human haploid genome. The data presented here further supports our model of the human CD44 transcriptional unit as a single gene complex that utilizes an invariant 5' initiation site, alternative internal and 3' end splicing, and multiple poly (A) sites to generate through RNA processing a diverse number of human CD44 isoforms.

Amino Acid Sequence↗