First, trap your enhancer.
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Journal Article↗
Biomedical subjects
M Freeman
Publications and source records attributed to M Freeman.
T cell responses to synthetic thyroid peroxidase peptides in autoimmune thyroid disease.
Sixteen peptides, representing four different extracellular regions of thyroid peroxidase (TPO) predicted to contain a high proportion of potential T cell epitopes, were synthesized to investigate which parts of this autoantigen may be targets for the T cell response in thyroid autoimmunity. Compared with 25 controls, peripheral blood T cells from 23-37% of 30 patients with Graves' disease or autoimmune hypothyroidism were stimulated significantly by three peptides, representing amino acids 415-432, 439-457 and 463-481 of the TPO sequence; T cells from individual patients were also stimulated by several other peptides. These results indicate that the T cell response to TPO is directed against several epitopes which may be recognized by different patients.
Amino Acid Sequence↗
Therapeutic use of storytelling for older children who are critically ill.
Like play, a story can be functional and therapeutic in the care of children dealing with chronic illnesses such as cancer, even when patients' courses prove terminal. Examples include both oral telling and reading of stories, picturebooks, novels and accounts of natural phenomena, as well as children;s recounting of desires and fantasies. The field of therapeutic stories offers unlimited opportunities for both practitioner and parent to learn better ways to support children's own inner processes of imagination and motivation, to strengthen and to provide comfort.
Adaptation, Psychological↗
Subcutaneous fluid infusions.
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Fluid Therapy↗
Decentralised responsibility--a way forward for 'homeland' mental health care?
A case study of mental health services in Mhala, a district of the Gazankulu homeland area in South Africa, is reported; it is argued that more comprehensive mental health care could be promoted by transferring certain basic mental health functions (repeat prescriptions for stable psychosis and epilepsy) from the single itinerant community psychiatric nurse to general health nurses in the 22 clinics in the district. This would improve access to and continuity of care, and through the new 'freedom' of the community psychiatric nurse, allow for the introduction of mental health functions that are presently neglected. Training to safe levels of competence is attainable, and the additional load on clinics would be very small.
Community Mental Health Services↗
Type I macrophage scavenger receptor contains alpha-helical and collagen-like coiled coils.
The macrophage scavenger receptor is a trimeric membrane glycoprotein with unusual ligand-binding properties which has been implicated in the development of atherosclerosis. The trimeric structure of the bovine type I scavenger receptor, deduced by complementary DNA cloning, contains three extracellular C-terminal cysteine-rich domains connected to the transmembrane domain by a long fibrous stalk. This stalk structure, composed of an alpha-helical coiled coil and a collagen-like triple helix, has not previously been observed in an integral membrane protein.
Amino Acid Sequence↗
Coiled-coil fibrous domains mediate ligand binding by macrophage scavenger receptor type II.
The macrophage scavenger receptor, which has been implicated in the pathogenesis of atherosclerosis, has an unusually broad binding specificity. Ligands include modified low-density lipoprotein and some polyanions (for example, poly(I) but not poly(C]. The scavenger receptor type I (ref. 3) has three principal extracellular domains that could participate in ligand binding: two fibrous coiled-coil domains (alpha-helical coiled-coil domain IV and collagen-like domain V), and the 110-amino-acid cysteine-rich C-terminal domain VI. We have cloned complementary DNAs encoding a second scavenger receptor which we have termed type II. This receptor is identical to the type I receptor, except that the cysteine-rich domain is replaced by a six-residue C terminus. Despite this truncation, the type II receptor mediates endocytosis of chemically modified low-density lipoprotein with high affinity and specificity, similar to that of the type I receptor. Therefore one or both of the extracellular fibrous domains are responsible for the unusual ligand-binding specificity of the receptor.
Amino Acid Sequence↗
Characterization of fully active biotinylated parathyroid hormone analogs. Application to fluorescence-activated cell sorting of parathyroid hormone receptor bearing cells.
[Nle8,18,Tyr34]bPTH-(1-34)amide (NlePTH) was biotinylated using sulfosuccinimidyl 6-(biotinamido)hexanoate, in dimethyl sulfoxide, and the multiple resulting peptides peaks were separated by reverse-phase high performance liquid chromatography. Their biological activities were compared with those of NlePTH, the parent compound, in radioreceptor and cAMP accumulation bioassays using rat osteosarcoma 17/2.8 cells; the earliest two eluting products, bioPTH 1 and 2, were equipotent, a third, bioPTH 3, was only 10% as potent, and the remaining, later eluting derivatives all were less than 0.1% as active. Competitive avidin binding assays using [3H]biotin suggested that bioPTH 1 and 2 had a single biotin congener per molecule, while bioPTH 3 contained two biotin residues. Upon Edman degradation, bioPTH 1 contained biotin on the lysine at position 13 of NlePTH; bioPTH 2's biotin was on the lysine at position 26 (or 27) and bioPTH 3 had biotins on lysines at both positions 13 and 26 (or 27). Avidin tagged with 125I, peroxidase, or fluorescein isothiocyanate was detected on bone-derived cells which had been incubated initially with bioPTH 2 (1, 10, and 100 nM) for 4 h, but not when NlePTH (1 microM) was added with bioPTH 2. A fluorescence-activated cell sorter detected a symmetrical shift in fluorescence of bone-derived cells incubated with 10 nM of bioPTH 2 and 10 micrograms/ml fluorescein isothiocyanate-avidin. Addition of a 30-fold molar excess of NlePTH, or omission of bioPTH 2, completely reversed this fluorescence shift, and no shift in fluorescence was seen with cells lacking PTH receptors. This fully active, high affinity biotinylated PTH-derivative should prove useful in the study of PTH receptor-bearing cells.
Animals↗
Functional analysis of intercellular adhesion molecule-1-expressing human thyroid cells.
We have tested the potential role of thyroid cell intercellular adhesion molecule-1 (ICAM-1) expression by in vitro assays of cell clustering and cytotoxicity. Increased ICAM-1 appeared within 24 h of thyroid cell stimulation with cytokines and was not inhibited by the antithyroid drug methimazole. Autologous and allogeneic lymphocyte-thyroid cell cluster formation, assessed by flow cytometry, was reduced by about one-third in the presence of a monoclonal antibody against ICAM-1, regardless of whether thyroid cells were expressing basal levels of ICAM-1 or had been stimulated with interferon-gamma. The cytotoxicity produced by interleukin 2-stimulated allogeneic lymphocytes was not consistently inhibited by anti-ICAM-1 antibody, but phytohemagglutinin-stimulated lymphocytes showed a reduction of 23%-28% in cytotoxicity against untreated or interferon-gamma stimulated thyroid cells when the anti-ICAM-1 monoclonal antibody was present. Finally, thyroid cells could be infected by rhinovirus, confirming the presence of fully functional ligand. These results show that ICAM-1 expression by thyroid cells may enhance immune cell recognition and play some role in cytotoxicity, features which could be important in the initiation or perpetuation of autoimmune thyroiditis.
Cell Adhesion↗
Automated laser-fluorescence sequencing.
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DNA↗
An ancient, highly conserved family of cysteine-rich protein domains revealed by cloning type I and type II murine macrophage scavenger receptors.
Scavenger receptors have been implicated in the development of atherosclerosis and other macrophage-associated functions. The bovine type I and type II scavenger receptors are multidomain transmembrane proteins that differ only by the presence in the type I receptor of an additional, extracellular cysteine-rich C-terminal domain. The isolation of type I and type II receptor cDNAs from a murine macrophage cell line, P388D1, establishes the presence of mRNAs encoding both receptor types in a single cell. Their sequences are highly similar to the bovine cDNAs. Receptor type-specific cDNA probes map to a common locus on murine chromosomes 8, suggesting that a single gene encodes both mRNAs. The type I-specific scavenger receptor cysteine-rich (SRCR) domain helps define a previously unrecognized family of remarkably well-conserved domains. Highly homologous SRCR domains (one, three, or four per polypeptide chain) are found in diverse secreted and cell-surface proteins from humans (e.g., CD5, complement factor I), mice (Ly-1), and sea urchins (speract receptor).
Amino Acid Sequence↗
Impact of childhood cancer on healthy school-age siblings.
One part of a study on the effects of childhood cancer on families focused on the emotional reactions of school-age siblings. The authors identify themes in the siblings' feelings taken from transcripts of interviews with them. Responses were categorized as experience of diagnosis and hospitalization; awareness of prognosis and mortality; need for information; continuing effect of disease or death on the well child; correct understanding of cancer; and hopes and desires for the future. The responses were grouped either in a sibling with a living child category or sibling with a deceased child category. From their analysis, the authors present implications for nurses' interactions with these children: children's need for information; their feelings of being displaced and unimportant; need for encouraging involvement in the life of the ill child. The authors also identify additional questions that could direct future nursing research.
Adult↗
Thyroid follicular cell function after non-lethal complement membrane attack.
Terminal complement complexes have been identified around thyroid follicles in Graves' disease and Hashimoto's thyroiditis, and the concentrations of such complexes are increased in the sera of these patients, suggesting a role for complement activation and membrane attack complexes (MAC) in autoimmune thyroiditis. This has been investigated further using cultured human and rat thyroid cells. Thyrocytes were resistant to lysis by homologous complement, in contrast to the effects of heterologous (rabbit) complement. The formation of non-lethal amounts of MAC, using reactive lysis or classical pathway activation, significantly reduced cAMP production by these cells in response to thyroid-stimulating hormone (TSH) (P less than 0.01); similar effects were seen with thyroid-stimulating antibodies. Thyroid cells were able to recover rapidly from complement attack after washing and incubation for 30 min. Non-lethal MAC formation also resulted in reactive oxygen metabolite production, detected by luminol-dependent chemiluminescence in three out of five thyroid cell preparations tested. Ionomycin, but not TSH, also stimulated reactive oxygen metabolite production. These results suggest that repeated or continuous sub-lethal complement attack on thyroid cells may exacerbate hypothyroidism in Hashimoto's thyroiditis, or partially counter the effects of thyroid-stimulating antibodies in Graves' disease. Furthermore, the production of reactive oxygen metabolites in these circumstances could increase the intra-thyroidal inflammatory response; oxygen radical scavenging by anti-thyroid drugs (which are concentrated by thyrocytes) may account in part for the amelioration of thyroiditis observed with such treatment.
Animals↗
Reversal and inhibition of cholera toxin-induced secretion in isolated rabbit ileum.
1. Cholera toxin (1 microgram/ml) abolished net fluid absorption by everted sacs of rabbit ileum, leading to net fluid secretion. This action occurred via the toxin-catalysed ADP ribosylation of the stimulatory GTP-binding protein Gs which is linked to adenylate cyclase. Nicotinamide (10 mM), a reaction product of ADP ribosylation, reversed cholera toxin-induced secretion, restoring absorption. Lower concentrations of nicotinamide induced partial reversal. 2. Nicotinamide (1 mM) blocked the secretory action of cholera toxin applied to ileal sacs. This inhibitory action was more effective in the presence of methionine (1 mM). 3. Other inhibitors of ADP ribosylation, benzamide and adenine, blocked the secretory action of cholera toxin. Hypoxanthine, an analogue and metabolite of adenine, was similarly effective. 4. Nicotinamide was not, however, effective in blocking or reversing the secretory action of theophylline (10 mM) or of heat-stable E. coli enterotoxin STa. This indicates that nicotinamide has a highly specific action against ADP ribosylating toxins. 5. It is proposed that nicotinamide reverses the secretory action of cholera toxin by reversing ADP ribosylation, simply by the law of mass action. This counters the established idea that the effects of cholera and other ADP-ribosylating toxins are irreversible under physiological conditions.
Adenine↗
Regulation of interleukin-6 release by human thyrocytes.
Autoimmune thyroiditis is characterized by lymphocytic accumulation within the thyroid which may be the result, in part, of immunomodulatory cytokine secretion by thyrocytes. We have tested human thyroid cell cultures (n = 9) for interleukin-6 (IL-6) release using two bioassays. IL-6 was detected in all culture supernatants under basal conditions and was increased by gamma-interferon, tumour necrosis factor and TSH in a dose-dependent manner. The bioactivity was confirmed as IL-6 by immunoblotting experiments and could not be accounted for by contamination of the thyroid cell cultures with fibroblasts, lymphocytes or monocytes. Circulating IL-6 levels were not raised in patients with Graves' hyperthyroidism. Exogenous recombinant IL-6 reduced cyclic AMP production in response to TSH when added to thyroid cell cultures. Since IL-6 plays a major role in B cell differentiation and T cell activation, release of IL-6 by thyrocytes may increase the intrathyroidal autoimmune response in Graves' disease and Hashimoto's thyroditis. Our results also suggest that IL-6 may modulate thyroid cell function.
Adenoma↗
Breast Cancer Screening Project in Northeast Florida.
The American Cancer Society--Duval Unit, in June, 1987, helped organize a community demonstration screening project involving all hospitals and institutions with mammography units in the area. A Northeast Florida Cooperative Breast Cancer Screening Group was formed comprised of physicians and administrators from each institution. A total of 1,200 women agreed to participate in the project and each underwent complete screening including education, instruction in self-examination, physical examination by a physician and mammography as indicated according to ACS guidelines. Of the study group, 1,032 women were eligible for mammography at a participating center, and 628 (61%) underwent a mammogram at no cost to them as instructed. Twenty four (4%) had definite abnormalities which led to biopsy and seven (1%) of them had malignant lesions. The medical community organized to provide breast cancer screening and follow-up with low-cost mammography.
Adult↗
Translocation to rat liver mitochondria of phosphatidate phosphohydrolase.
When a particle-free supernatant fraction from rat liver was incubated at 37 degrees C with mitochondria and oleate, some of the enzyme phosphatidate phosphohydrolase (PAP), initially present in the particle-free supernatant, was recovered, after the incubation, bound to mitochondria. This translocation of PAP from cytosol to mitochondria was stimulated by oleate or palmitate in a similar fashion to the stimulation of translocation of PAP to endoplasmic reticulum [Martin-Sanz, Hopewell & Brindley (1984) FEBS Lett. 175, 284-288]. Translocation of PAP from particle-free supernatant to a partially purified mitochondrial-outer-membrane preparation was also stimulated by oleate. More PAP was bound to a mitochondrial-outer-membrane fraction washed in 0.5 M-NaCl before resuspension in sucrose than to a sucrose-washed mitochondrial-outer-membrane preparation. In contrast, washing of microsomal membranes in 0.5 M-NaCl did not enhance the binding of PAP to these membranes. PAP also binds to phosphatidate-loaded mitochondria or microsomes (microsomal fractions). In the experimental system employed, more PAP bound to mitochondria loaded with phosphatidate than to microsomes loaded with phosphatidate. The results are discussed in relation to the role of mitochondrial phosphatidate in liver lipid metabolism.
Animals↗
Responses of left and right ventricular ejection fractions to aerobic and anaerobic phases of upright and supine exercise in normal subjects.
The effects of aerobic and anaerobic exercise on ventricular performance were studied in 13 normal subjects who underwent simultaneous pulmonary gas exchange evaluation and exercise radionuclide ventriculography in the supine and upright postures. Right and left ventricular ejection fraction was measured serially at 2-minute intervals during exercise. The anaerobic threshold occurred at 74% and 80% of maximum heart rate, respectively, during upright and supine exercise. Left and right ventricular ejection fractions rose from rest to the anaerobic threshold (p less than 0.01, p less than 0.01, respectively) and there was a further increase between the anaerobic threshold and maximum exercise (p less than 0.01, p less than 0.01, respectively). The rate of rise of ejection fraction beyond the anaerobic threshold was slightly blunted compared with the rise prior to attaining the anaerobic threshold. There was no significant difference in ventricular performance between supine and upright exercise. The data demonstrate that ventricular performance increases steadily during exercise and is not limited by the conversion of aerobic to anaerobic metabolism.
Adult↗