Epidemiological aspects of travel related illness.
Explore the source record for details and available documents.
Communicable Diseases↗
Biomedical subjects
E Walker
Publications and source records attributed to E Walker.
In situ hybridization demonstrates the stability of mRNA in post-mortem rat tissues.
In situ hybridization was used to detect messenger RNA (mRNA) in a variety of rat tissues which were fixed in formalin either immediately after death or after a 24 h period of storage at 5 degrees C. A synthetic polydeoxythymidine [poly d(T)] oligonucleotide probe was used to demonstrate polyadenylated [poly (A)] mRNA in the small intestine, pancreas, liver, cerebellum, and pituitary. Of these tissues, only the liver showed a small reproducible reduction in hybridization signal following delayed fixation. Synthetic oligonucleotide probes complementary to albumin and pro-opiomelanocortin (POMC) mRNAs were hybridized to liver and pituitary, respectively. There was no significant reduction in hybridization signal in post-mortem tissues. The results suggest that some mRNAs may be remarkably stable under certain post-mortem conditions and this should encourage the wider application of in situ hybridization techniques to post-mortem material.
Animals↗
Fumarylacetoacetase activity in cultured and non-cultured chorionic villus cells, and assay in two high-risk pregnancies.
We describe further development of the fumarylacetoacetase (FAA) assay for the prenatal diagnosis of tyrosinaemia type 1 using chorionic villus sampling (CVS). We have established a reference range for FAA activity in cultured villus cells and have confirmed previously reported data on the FAA activity in uncultured chorionic villus cells. This should allow confirmation of results using CVS, without the need for further invasive procedures. We report the FAA enzyme stability at -70 degrees C, +4 degrees C, and at room temperature, and we have shown no obvious difference in enzyme activity with gestational age. We have analysed cultured and non-cultured CVS activity of FAA in two pregnancies at risk of tyrosinaemia type 1. In both, the fetus was designated unaffected, and these results were confirmed postnatally.
Cells, Cultured↗
The effect of alpha-1-adrenoreceptor agonist and antagonist administration on human upper gastrointestinal transit and motility.
To explore the role of alpha-1-adrenoreceptor-mediated pathways on human upper gut motor function in vivo, we studied the effects of the alpha-1-agonist phenylephrine and the alpha-1-antagonist thymoxamine on oro-caecal transit and antroduodenal motor activity. Transit was measured using a standard exhaled-breath hydrogen method, and motility was measured by intraluminal manometry. Oro-caecal transit was unaffected by 80 mg thymoxamine [median 63 min (range 35-164 min) vs. control, 65 min (range 30-155 min), P greater than 0.1]. However, phenylephrine (2.4 micrograms/kg/min) consistently delayed oro-caecal transit time to 103 min (50-215 min), P greater than 0.005. Co-administration of thymoxamine abolished this phenylephrine-induced delay. The mean amplitude of antral postprandial contractions was reduced by phenylephrine from 29 (13-37) to 10 (3-13) mmHg (P less than 0.02). In contrast, neither the pattern nor the mean inter-contraction interval was altered. Responses to phenylephrine in the duodenum were similar to those in the antrum, with reduction in amplitude from 12 (3-18) to 6 (5-13) mmHg without alteration in the pattern or interval between contractions. Nutrient transit through the upper gut can thus be inhibited via activation of an alpha-1-adrenoreceptor-mediated pathway. Failure of alpha-1-antagonist administration to alter oro-caecal transit suggests that this pathway is not tonically active, and it is therefore unlikely to play a major role in nutrient passage under normal circumstances.
Adrenergic alpha-Agonists↗
Primary cutaneous plasmacytoma: the use of in situ hybridization to detect monoclonal immunoglobulin light-chain mRNA.
A case of primary cutaneous plasmacytoma in a 16-year-old male is described. The neoplastic nature of the plasma cell infiltrate has been clearly established by the demonstration of monoclonal kappa immunoglobulin light-chain mRNA using in situ hybridization with biotin-labelled oligonucleotide probes applied to routine tissue sections.
Adolescent↗
Assessment of nutrition care provided to patients with diabetes in primary-care clinics.
Explore the source record for details and available documents.
Diabetes Mellitus↗
Cell populations synthesizing cartilage proteoglycan core protein in the early chick limb bud.
Cartilage specific macromolecules are known to be synthesized in the mesenchyme of the embryonic chick limb bud, especially in areas of prechondrogenic condensations (Shinomura et al, 1984). Even though the mesenchyme seems homogeneous according to histological criteria, studies in the past have suggested the presence of different cell populations with different chondrogenic potential (Solursh et al, 1982; Swalla et al, 1984). In this study we have investigated by means of flow cytometry, the synthesis of proteoglycan core protein during early development of the chick limb bud in order to identify the different chondrocyte progenitor cells. We were able to identify by virtue of different size and density a cell population which synthesizes core protein extensively at stage 24 and stage 25 of development. This cell population synthesizes core protein predominantly at the proximal half of the limb bud at stage 24. However at stage 25 the same population synthesizes core protein predominantly at the distal half of the limb bud. These observations indicate that the distal half of stage 25 limb bud is mostly homogeneous with prechondrogenic cells and is in agreement with in vitro experiments that show high chondrogenic potential of the mesenchymal cells from this stage.
Aggrecans↗
Adhesion characteristics of human interleukin 2-activated natural killer cells.
Culture of human monocyte-depleted peripheral blood mononuclear cells with recombinant IL2 (rIL2) induced adherence to plastic by 24 hr and subsequent proliferation in a subpopulation of lymphocytes with phenotypic and functional characteristics of activated natural killer (NK) cells. Purified human NK cells activated in the presence of IL2 for 24 hr upregulated the expression of the CD11c (p150.95) and CD11a antigen but not other cellular adhesion molecules (CAM). After further incubation with IL2, NK cells displayed upregulation of all of the antigens in the CD11/CD18 family of CAM. The process of adhesion was strictly dependent on culture in the presence of IL2, divalent cations, and active cellular metabolism. Adhesion also was dependent on expression of CAM on the cell surface, since monoclonal antibodies to CAM inhibited adhesion of activated NK cells to varying degrees (from 50 to 80%). An antibody (LeuM5) to the CD11c antigen (p150.95) gave the highest level of inhibition, and anti-CD11a (LFA-1) also was inhibitory, while anti-CD56 (NKH1) or anti-CD11b did not interfere with adhesion to plastic. Anti-CD11c was also the most effective in initiating the detachment of adherent-phase NK cells. Antibodies to CD18 or CD2 antigen also inhibited binding of NK cells to plastic. The blocking effects of anti-CD2 and anti-CD11a were additive in this system. On the surface of plastic-adherent and motile NK cells, all CAM except the CD56 antigen had a polar or bipolar distribution, as determined by staining with anti-CAM antibodies. Surface antigens CD11b, CD11c, CD2, and CD18 on nonadherent NK cells were clustered at the cellular poles by both immunofluorescence and immunogold electron microscopy, whereas CD11a (LFA-1) and CD56 antigens were distributed diffusely. CAM, especially CD11c, were also detected in cytoplasmic granules by immunostaining in IL2-activated NK cells. Thus, CAM may be stored in granules, allowing for their rapid transfer to the cell membrane in response to activation. Our results indicate that CAM are upregulated in IL2-activated NK cells and that some of these molecules (e.g., CD11c) play an important role in the development of plastic adherence by a subpopulation of these cells.
Antibodies, Monoclonal↗
Twin studies of psychopathology: why do the concordance rates vary?
Many current discussions of hereditary factors in psychopathology focus on twin studies as the primary source of evidence supporting the importance of genetic determinants. In summarizing the results of these studies, authors often derive estimates of concordance rates by collapsing across studies and presenting mean or median rates. This practice implicitly assumes that the concordance rates yielded by different studies represent equally reliable estimates of the population mean. The present study evaluates the validity of this assumption. Reports of twin studies of schizophrenia and affective disorder were reviewed. A meta-analysis was conducted to examine the influence of methodological factors on concordance rates. Analyses indicated that both sample-selection and zygosity-determination procedure are systematically associated with concordance rates. For schizophrenia, MZ concordance rates are significantly lower when samples are selected from a twin register as opposed to a psychiatric facility. Lower MZ concordance rates are also yielded by studies that employ laboratory procedures to determine zygosity. Implications of the findings for future research are discussed.
Affective Disorders, Psychotic↗
Non-isotopic in situ hybridization with digoxigenin and alkaline phosphatase labelled oligodeoxynucleotide probes. Applications in pituitary gland.
We report the application of digoxigenin labelled oligonucleotide probes for the detection of hormonal messenger RNAs (mRNAs) in human pituitary adenomas. Positive signal for the appropriate mRNA was detected in tumours associated with Cushing's disease, acromegaly and hyperprolactinaemia, where immunoreactivity for adrenocorticotrophin (ACTH) growth hormone and prolactin had also been confirmed. In addition, we report the detection of proopiomelanocortin (POMC) mRNA in the rat pituitary gland using an oligodeoxynucleotide probe directly linked to alkaline phosphatase.
Adenoma↗
Pituitary macroadenomas associated with hyperprolactinaemia: immunocytochemical and in-situ hybridization studies.
OBJECTIVE: We have assessed whether in-situ hybridization for prolactin messenger RNA (mRNA) provides additional information for the classification of pituitary macroadenomas associated with hyperprolactinaemia. DESIGN: In-situ hybridization for PRL mRNA was performed on surgical biopsies of pituitary adenomas and the results correlated with serum PRL levels and PRL immunoreactivity. PATIENTS: Twenty-one patients (11 men, 10 women) were included; five had normal serum PRL levels, 11 mild hyperprolactinaemia (less than 3000 mU/l) and five marked hyperprolactinaemia (greater than 3000 mU/l). MEASUREMENTS: Immunocytochemistry for PRL and in-situ hybridization for PRL mRNA were performed on surgical biopsies. RESULTS: Immunoreactivity for PRL was detected in tumours from all patients with serum PRL greater than 3000 mU/l and in one of 11 patients with mild hyperprolactinaemia. Positive signal for PRL mRNA was detected in four of five immunopositive cases studied, in a further two cases with mild hyperprolactinaemia, and in one tumour associated with normal serum PRL level. CONCLUSIONS: In-situ hybridization provides evidence of PRL gene activation in the absence of immunoreactivity for prolactin. This may reflect low levels of hormone storage or defective translation of the mRNA.
Adenoma↗
Single-dose tumor necrosis factor protection against endotoxin-induced shock and tissue injury in rats.
Tumor necrosis factor (TNF), a macrophage product released in response to endotoxin and other stimuli, has been shown to be a central mediator of endotoxin or septic shock. However, its highly conserved and wide-ranging physiological effects suggest that it may also be an essential cytokine in the host defense against acute bacterial infection or sepsis. A single nontoxic dose of human recombinant TNF administered intravenously 24 h prior to a lethal infusion of Escherichia coli lipopolysaccharide (LPS) completely prevented acute LPS-induced hypotension, ameliorated tissue injury in the lungs and liver, and improved survival in male Fisher 344 rats. The protective effects of TNF were dose dependent and required a 24-h pretreatment interval. After the infusion of LPS, animals in both groups (TNF-treated animals and saline-pretreated controls) initially appeared acutely ill and had a similar severe metabolic acidosis, indicating that TNF did not inactivate or prevent the toxic effects of LPS. Twelve hours after the administration of TNF, the gene for manganous superoxide dismutase, a mitochondrial enzyme which scavenges toxic reactive oxygen species and is induced during conditions which generate a free radical stress, was expressed in liver tissue, suggesting that the induction of manganous superoxide dismutase may be an important in vivo protective mechanism against cellular injury during lethal endotoxemia.
Animals↗
In vivo NMR spectroscopy of lithium-7 in humans.
The pharmacokinetics of lithium uptake was measured by 7Li NMR spectroscopy at 24.83 MHz in vivo in the brain and muscle of a normal subject and a patient suffering from bipolar affective disorder, using a modified General Electric Signa clinical magnetic resonance imaging system. Comparison was made to standard phantoms to estimate Li concentrations. The levels of Li in brain and muscle were similar, were typically less than the level in serum, and generally tracked the level in serum. The Li level at steady state in the brain of a patient suffering from schizoaffective disorder was measured over a 7-month period. Substantial variation was seen, which showed some correlation with serum level. Serum level peaked about 2 h after a single 300-mg dose at steady state, and muscle level, immediately thereafter. Brain level peaked considerably later at 4 h. Localized in vivo 7Li NMR spectroscopy was demonstrated by acquisition of a 125-cm3 DRESS slice from the occipital region in less than 7 min.
Adult↗
Prediction of adult-onset schizophrenia from childhood home movies of the patients.
In a preliminary study of developmental precursors of schizophrenia, home movies of adult-onset schizophrenic patients and their healthy siblings filmed during their childhood were viewed by judges who were blind to the psychiatric outcome of the subjects. The films began with the infancy of all subjects and extended through at least the first 5 years of their lives. Although none of the subjects had any psychiatric disorder in childhood, the preschizophrenic children were reliably identified by the viewers. This represents the first demonstration that preschizophrenic subjects can be distinguished from sibling control subjects within the first 8 years of life by observing their behavior.
Adult↗
Adrenal failure in fulminant meningococcal septicaemia: a clinical reality.
Current teaching is that adrenal failure is not a feature of meningococcal sepsis, and that cortisol levels are generally elevated. A case of fulminant meningococcal septicaemia in a 14-year-old boy is described. This patient had low/borderline cortisol levels, which normalised within some days.
Adolescent↗
Lyme disease: a review.
In the last decade, Lyme borreliosis has emerged as a complex new infection whose distribution is worldwide. The multisystem disorder, which primarily affects the skin, joints, heart and nervous system at different stages, is caused by the tick-borne spirochaete Borrelia burgdorferi. After the first weeks of infection almost all patients have a positive antibody response to the spirochaete and serological determinations are currently the most practical laboratory aid in diagnosis. Treatment with appropriate antibiotics is usually curative.
Diagnosis, Differential↗
Biology, cytogenetics, and sensitivity to immunological effector cells of new head and neck squamous cell carcinoma lines.
Twenty-one head and neck squamous cell carcinoma (HNSCC) cell lines were established from 89 fresh tumor specimens in order to study the biology of HNSCC lines, establish tumors in nude mice, and evaluate the sensitivity to immunological effector cells of these tumors in vitro and in vivo in nude mice. The lines were established from explants using differential trypsinization and culture for 2 to 20 mo. The explants were derived from 11 different sites. Three pairs of lines were derived from both the primary tumor and metastatic lymph nodes in the same patients. All cultures grew as either compact or diffuse adherent monolayers, and they had a median doubling time of 86 h (range, 33 to 531 h). DNA fingerprinting confirmed that the HNSCC lines were individual isolates. Thirteen of 14 lines tested induced tumors in athymic mice. The histology of each line growing in nude mice was similar to that of the original tumor tissue. Immunocytochemistry showed keratin production in all lines tested. Aneuploidy (36 to 87 chromosomes) was present in all 16 lines studied; the median chromosome number for lines derived from primary tumors was 70, whereas for lines originating from metastatic or recurrent tumors, it was 54. Karyotypic analysis showed deletion of the short arm of chromosome 3 (3p-) in 12 of 16 cell lines and trisomy 6 in 12 of 16 lines. In addition, translocations between chromosomes 9 and 11 or 9 and 12 were each present in five of 16 lines tested. The HNSCC lines were resistant to lysis by natural killer cells, but were efficiently lysed by lymphokine-activated killer cells in 4-h 51Cr release assays. These new lines have allowed us to establish a model of local adoptive immunotherapy of HNSCC in tumor-bearing nude mice, and they provide a resource for future studies of the biology of HNSCC.
Adult↗
Differentiation-inducing effect of recombinant human tumor necrosis factor alpha and gamma-interferon in vitro on blast cells from patients with acute myeloid leukemia and myeloid blast crisis of chronic myeloid leukemia.
Tumor necrosis factor alpha (TNF-alpha) and gamma-interferon (IFN-gamma) have been shown to suppress clonogenic growth in cultures containing blast cells obtained from patients with acute myeloid leukemia. We report that recombinant human TNF-alpha and IFN-gamma are also able to induce functional and morphological maturation in fresh myeloid leukemic cells in vitro. Assessing suspension cultures containing cells from patients with acute myeloid leukemia (11 patients) or myeloid blast crisis of chronic myeloid leukemia (5 patients), it was found that recombinant human TNF-alpha and IFN-gamma significantly enhanced the number of cells reducing nitroblue tetrazolium, as compared to control cultures containing no cytokine (P less than 0.001 and P less than 0.001, respectively). Cells from responders showed alterations characteristic of monocyte/macrophage differentiation, adherence to plastic surfaces, development of positive staining for alpha-naphthyl acetate esterase, typical morphology, and expression of cell surface antigens detected by the monoclonal antibodies Mo-1, Mo-2, and My-4. Both cytokines decreased the number of viable cells, the number of blast cells, and the number of cluster-forming units in suspension culture, suggesting inhibitory actions on the growth capacity of leukemic cells. Compared to the maximum effects of either factor alone, the combination of recombinant human TNF-alpha and IFN-gamma significantly increased the extent of growth inhibition and cell adherence but did not result in further increases in nitroblue tetrazolium reduction. The presence of Auer rods in IFN-gamma or TNF-alpha differentiation-induced macrophages with cells from a patient with M5 acute myeloid leukemia demonstrates that these cytokines can induce differentiation of a leukemic clone in primary cells from patients with leukemia.
Adolescent↗