Biomedical subjects
Publications and source records attributed to M Fletcher.
A model system to study food container leakage was developed. The model system allows the independent investigation of the effect of physical factors such as vacuum and contents viscosity, and microbial factors on the leakage process. The design, construction and operation of the container leakage model system is described.
Elevated levels of human chorionic gonadotrophin are associated with primary testicular tumours and usually indicate the presence of trophoblastic elements. Human chorionic gonadotrophin can also be secreted by extragonadal tumours which may metastasize to the testes. A patient is described presenting with a testicular tumour secreting human chorionic gonadotrophin which later proved to be a metastasis from a pancreatic adenocarcinoma. Up to 70% of malignant pancreatic tumours can secrete human chorionic gonadotrophin.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used and therapeutically effective groups of drugs in the Western world. However, gastrointestinal problems constitute all too frequently reported unwanted effects of NSAIDs; their effects on the gastric (and intestinal) mucosa are, therefore, well documented. A review of the evidence suggests that NSAID-induced gastric damage occurs as a result of a dual insult, by NSAID-mediated direct (and indirect) acidic damage followed almost simultaneously by the deleterious (systemic) effect of prostaglandin inhibition. A number of strategies have been used in the management of NSAID-induced gastric damage; however, not all have been entirely successful. Nonetheless, a number of approaches have met with a considerable amount of success, including direct gastroprotection, enhancement of mucosal defence mechanisms and, perhaps most encouragingly, the development of newer NSAIDs which display not only considerable clinical efficacy but a reduced gastrointestinal adverse event profile.
A survey of schistosomiasis mansoni infection was conducted in an area of northwestern Ethiopia which has been targeted for an irrigation project. The proximity of settlements to water-bodies infested with Biomphalaria pfeifferi, and used extensively for bathing and domestic purposes, indicated that the potential for transmission is high. Snails shedding S. mansoni cercariae were found in two localities. Stool specimens from a total of 7517 persons were examined, including specimens from 4915 children age 7-14 years in 29 localities, as well as from the total population of four of the more heavily infected localities. The 10-14 year age group had the highest transmission potential, in terms of prevalence (overall 25%), intensity of infection, and absolute numbers of infected individuals, suggesting that screening and chemotherapy would be most cost-effective in that age group.
A serological study of antibodies to Ehrlichia risticii was carried out on 10 species of wild and domestic mammals found on or near 21 horse farms in an area of the USA in which Potomac horse fever is endemic. No antibodies were found in 133 peridomestic rodents (Norway rats and house mice), nor in 108 wild rodents (white-footed mice and meadow voles) captured on farms. Three of the six domestic animal species examined, cats, pigs and a goat, showed serological evidence of exposure to E risticii. Seropositive animals were detected on three of the 21 premises. The eight seropositive cats (of 48 cats tested) were on two farms, and the three seropositive pigs (of 14 tested) were all on one farm which lay some 3 km from where the one seropositive goat (of three tested) was found. None of the 79 dogs, 75 cattle and seven sheep tested had antibodies to E risticii. The significance of these findings is discussed in the light of current understanding of the transmission of Potomac horse fever and of the epidemiology of other related ehrlichial diseases.
The polymers involved in the adhesion of Pseudomonas fluorescens H2S to solid surfaces were investigated to determine whether differences between cell surface adhesives and biofilm matrix polymers could be detected. Two optical techniques, i.e., interference reflection microscopy (IRM) and light section microscopy (LSM), were used to compare the responses of the two types of polymer to treatment with electrolytes, dimethyl sulfoxide (DMSO), and Tween 20. To evaluate initial adhesive polymers, P. fluorescens H2S cells were allowed to attach to glass cover slip surfaces and were immediately examined with IRM, and their response to chemical solutions was tested. With IRM, changes in cell-substratum separation distance between 0 and ca. 100 nm are detectable as changes in relative light intensity of the image; a contraction of the polymer would be detected as a darkening of the image, whereas expansion would appear as image brightening. To evaluate the intercellular polymer matrix in biofilms, 3-day-old biofilms were exposed to similar solutions, and the resultant change in biofilm thickness was measured with LSM, which measures film thicknesses between 10 and 1,000 microns. The initial adhesive and biofilm polymers were similar in that both appeared to contract when treated with electrolytes and to expand when treated with Tween 20. However, with DMSO treatment, the initial adhesive polymer appeared to contract, whereas there was no change in thickness of the biofilm polymer. These results indicate that both polymers bear acidic groups and thus act electrostatically with cations and are able to enter into hydrophobic interactions.(ABSTRACT TRUNCATED AT 250 WORDS)
Sites of close contact between gliding Cytophaga sp. strain U67 cells and glass were examined by interference reflection microscopy. Site patterns changed during translocation and moved relative to the substratum, in contrast to previous interference reflection microscopy observations of fibroblast and amoeboid motility. Sinistral rotation around the long axis of the cell was coupled with gliding, except when curved cells traversed curvilinear pathways. Close contact was temporary, since cells flipped up off the substratum on one pole, pivoted, or were displaced laterally in collisions. Other members of the order Cytophagales and Myxococcus sp. demonstrated similar patterns of close association with substrata.
We analyzed the metacarpophalangeal pattern profile (MCPP) on 18 male individuals from 16 families with fragile X--fra (X), or Martin-Bell--syndrome and calculated a mean syndrome profile. Fourteen of 18 individuals with fra (X) syndrome had significant positive correlations which indicated clinical homogeneity. Discriminant analysis of individuals with fra (X) syndrome compared with a sample of normal individuals produced a correct classification rate of 88% based on a function of 3 MCPP variables that may provide a useful tool in screening individuals for the fra (X) syndrome. Discriminant and correlation analyses of individuals with Sotos sequence and individuals with fra (X) syndrome did not identify MCPP similarities. Therefore, there was no MCPP evidence in our study of patients with Sotos sequence and fra (X) chromosome expression.
The influence of Na+, Ca2+, La3+, and Fe3+ on the adhesion of Pseudomonas fluorescens H2 and H2S was investigated with interference reflection microscopy (IRM). IRM is a light microscopy technique which allows (i) visualization of the adhesive sites of living bacteria as they attach to a glass cover slip surface and (ii) evaluation of the bacterium-glass surface separation distance within a range of 0 to ca. 100 nm. The addition of each cation caused changes in IRM images consistent with a decrease in the separation distance, and minimum effective concentrations were as follows: Na+, 1 mM; Ca2+, 1 mM; La3+, 50 microM; and Fe3+, 50 microM. With strain H2, the effects of Na+, Ca2+, and La3+ were fully reversible in that the separation distance increased again when the electrolyte was replaced with distilled water. However, with strain H2S, a spontaneous mutant of H2 with increased attachment ability, only the effect of Na+ was fully reversible, and the effects of Ca2+ and La3+ were only partially reversible or irreversible. The effect of Fe3+ was irreversible with both strains, but this may be related not only to the electrolytic nature of Fe3+ but also to the decrease in solution pH to 3.5 caused by its addition. It is proposed that the electrolytes caused a decrease in separation distance by neutralizing negative charges on bacterial surface polymers and that the different effects obtained with the two strains are related to their different adhesion abilities.
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The attachment of four species of bacteria to solid surfaces was investigated to determine whether the attachment of one species of bacterium could be influenced by the presence of other attaching or attached species. Three types of experiment were done: attachment of bacteria from suspensions containing two species (termed "simultaneous attachment") was compared to attachment of each species in pure culture, the attachment of one species of bacterium to surfaces already colonized by a second species (termed "sequential attachment") was compared to attachment of the bacteria to clean, uncolonized surfaces, and bacteria were allowed to attach to a surface already colonized by a second strain, and their effect on the stabilization of adhesion of the initial colonizing strain was determined. The bacteria were Acinetobacter calcoaceticus, a Staphylococcus sp., a coryneform (isolates from a canning factory), and Staphylococcus aureus. The surfaces were tin plate, glass, and nylon. The attachment of each species was either increased, decreased or not affected by the simultaneous or sequential attachment of another species. The results depended upon the species combination, the surface composition, and the sequence of attachment. The detachment of a primary colonizing species was either increased, decreased or not affected by the subsequent attachment of a second species, depending on the species combination and surface. The results demonstrate that bacterial attachment to a surface can be influenced by the composition of the attaching population and can differ considerably from the attachment of the component species in pure culture.(ABSTRACT TRUNCATED AT 250 WORDS)
Essential mixed cryoglobulinemia (EMC) is infrequently recognized in this country. We report studies performed in six patients with EMC evaluated by us over the last 6 years. Purpura was present in three patients and glomerulonephritis in all. Two patients had chronic hepatitis B infection. Positive cryoglobulins and C1q binding, hypocomplementemia (especially low C4), positive rheumatoid factor titer, and negative anti-DNA antibodies were characteristic laboratory findings. The cryoprecipitate had strongly positive rheumatoid factor activity and contained a monoclonal IgM, kappa type in one of the two patients evaluated. The predominant lesion by renal biopsy was mesangiocapillary glomerulonephritis type I; electron microscopy revealed typical fibrillar structures in four cases. The above-mentioned features help distinguish EMC from other forms of glomerulonephritis.
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This review covers significant developments in the understanding of the biochemistry and clinical pharmacology of Interleukin-2 (IL-2) that were achieved from 1984 through September 1986. These include developments in the molecular biology of IL-2 and its receptors. Human IL-2 was cloned and sequenced by Taniguchi et al. in 1983. The gene for human IL-2 is located on the long arm of chromosome 4. The secondary structure of the gene is predominantly alpha helix. The mature gene product is a 133 amino acid glycoprotein with a molecular weight of 15,420 Daltons. The IL-2 receptor was revealed to be a glycoprotein of 272 amino acids. The mature receptor has a molecular weight of 55,000 Daltons. A more precise understanding of the mechanism of action IL-2, in particular its role in the induction of the IL-2 receptor, and aspects of the control of IL-2 production was also achieved. Metabolic and morphologic studies have revealed that activation of the T-cell antigen receptor renders the cells responsive to IL-2, but does not move them through the cell cycle. Rather, it appears that IL-2 stimulates G1 progression to S phase ie. blastic transformation. During this progression the cellular proto-oncogene c-myb is induced transiently to 6 to 7 times basal levels. The role of IL-2 as a growth factor for several subsets of T cells has been confirmed, and a new role as a growth factor for B cells was defined. Most importantly, IL-2 was shown to be directly mitogenic for and to expand subpopulations of peripheral blood cells, termed lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). A number of pathologies of IL-2 production or activity have been defined, including Hodgkin's disease, graft versus host disease, systemic lupus erythematosus, lepromatous leprosy, acquired immune deficiency syndrome, and adult T cell leukemia. Murine and human in vivo studies reviewed here have revealed significant parameters of the therapeutic potential as well as the toxicity of this growth factor. Finally, the modulation of IL-2 receptors on human PBL's by thymosin fraction 5 and thymosin alpha 1 suggests that it might be possible to up-regulate IL-2 receptor expression in certain disease states and thus increase the efficacy of IL-2.
Primary deficiency of the C4 binding protein (C4bp) was present in a patient with disease clinically resembling Behçet's disease. Her father and her sister were also deficient. This protein, as a cofactor for factor I, interferes with the assembly of, and accelerates the decay of, the classical C3 convertase. Thus, the deficiency favours C3 conversion by classical pathway activation. In addition to genital and oral ulceration, cutaneous vasculitis and synovitis, our patient had relapses complicated by angioedema, atypical for Behçet's disease. It is not clear whether her total disease, or only the complicating angioedema, was a consequence of the C4bp deficiency.
Data on routine humidifier settings used in respiratory support for newborn babies were obtained from 242 neonatal units in the British Isles. For each of the most commonly used humidifiers inspired gas humidity was measured under routine clinical conditions with an electronic hygrometer. Most endotracheally intubated babies breathe inspired gas of well below physiological humidity (44 mg H2O/l) and many below the minimum recommended for adults by the British Standards Institution (33 mg H2O/l). Inadequate humidification could contribute to several complications of artificial ventilation in newborn babies by inhibiting mucociliary clearance.
A retrospective study in Vancouver was designed to evaluate parents' perceptions of support received after the death of a child up to 5 years old. The families were contacted with the help of health care professionals and the news media. A standardized questionnaire was used in a personal interview or occasionally by mail. The contact with health care professionals after the child's death was frequently considered by the 61 families not to have been helpful: 80% of the families judged the information or counselling they had received to be inadequate, and over 50% had received none; many listed comments and behaviour that they considered harmful. The families desired both full medical information and grief support; what forms such support could take are suggested.