Search PubMed⌕ Search

Biomedical subjects

M Stewart

Publications and source records attributed to M Stewart.

At least 415 records · Page 23Linked to original sources

Unusual stability of the Methanospirillum hungatei sheath.

The proteinaceous sheath of Methanospirillum hungatei was isolated by lysing cells in 50 mM dithiothreitol, separating the sheath from other cellular material by discontinuous sucrose density centrifugation, and removing the "cell spacers" with dilute NaOH. The isolated sheath material consisted of hollow tubes which had a highly ordered surface array. The stability of the sheath to treatment with denaturants and to enzymatic digestion was examined by a turbidimetric assay in conjunction with electron microscopy and optical or electron diffraction. The sheath was resistant to a range of proteases and also was not digested by peptidoglycan-degrading enzymes, a lipase, a cellulase, a glucosidase, or Rhozyme (a mixture of galactosidases, acetylglucosaminidase, acetylgalactosaminidase, fucosidase, and mannosidases). In addition to being unaffected by common salts, thiol-reducing agents, and EDTA, the layer was resistant to powerful denaturants such as 6 M urea, 6 M guanidinium hydrochloride, 10 M LiSCN, cyanogen bromide, sodium periodate, and 1% sodium dodecyl sulfate. Strong bases, boiling 3 N HCl, and performic acid did attack the sheath; in these cases, the array was systematically disassembled in a progressive manner, which was followed by electron microscopy. The layer was slightly modified by N-bromosuccinimide in urea, but the array remained intact. The stability of the sheath was remarkable, not only as compared to other bacterial surface arrays, but also as compared to proteins generally, and possibly indicated the presence of covalent cross-links between protein subunits.

Amino Acids↗

Why teetotallers abstain.

Drinking practices and attitudes to alcohol among the members of a Southampton church were investigated by questionnaire (602 subjects) and by interviews (126 subjects). Teetotallers were older than drinkers, and included a higher proportion of women. They perceived their childhood upbringing and the teaching of the Bible as the main factors influencing them to abstain. Both teetotallism and alcoholism were more common among relatives of teetotallers than among relatives of social drinkers.

Alcohol Drinking↗

Studies on the regulation of hemopoiesis.

Normal hemopoietic cell differentiation and proliferation is critically dependent upon marrow stromal elements. Long-term liquid culture of marrow provides a model for the study of stromal function. We evaluated the effects of radiation and 5-fluorouracil (5-FU) on various aspects of long-term murine hemopoietic cell growth and stromal function. Exposure of C57BL/6J murine adherent cells from long-term marrow cultures to varying doses of irradiation (0-1000 rad) in vitro resulted in the elaboration of growth factors stimulating granulocyte, macrophage, megakaryocyte, mixed megakaryocyte-granulocyte macrophage, and blast colonies. This increased production of growth factors appears to be related to the ablation of normal granulocyte production in the culture system since addition of normal stroma to irradiated stroma blocks growth factor production. Two cell types appear to be mediating stromal factor production and support of liquid culture hemopoiesis: a macrophagelike cell and an alkaline-phosphatase-positive epithelioid cell. Exposure of these two cell types to pokeweed mitogen results in marked enhancement of growth factor production. Furthermore, a cell line isolated from normal murine stroma produced an activity capable of acting at an early hemopoietic stem cell level and of inducing secondary marrow cell lines. The establishment of cultures from 5-FU-treated animals revealed that chemotherapy-depleted marrow was capable of establishing adequate stromal function and that the residual surviving stem cells had a higher than normal proliferative rate. In addition, the function of granulocytes derived from this post-5-FU marrow was normal. Thus, it appears that both chemotherapy and radiation exposure of marrow results in an enhanced capacity of stromal elements to produce growth factors and support hemopoiesis and that post-5-FU marrow represents an enriched source of high proliferative potential bone marrow stem cells.

Animals↗

Bone marrow adherent cell hemopoietic growth factor production.

These data suggest that two types of radioresistant adherent stromal cells are adequate for maintenance of long term hemopoiesis in the Dexter culture system. One cell type appears to be a typical adherent macrophage while the other is an alkaline phosphatase positive epitheloid cell possibly representative of the adventitial reticular cell of the bone marrow. These two cell types seem to be clearly defined by the in-vivo irradiation studies and less clearly defined in the in-vitro irradiation experiments. These data do not exclude other cell types as playing important roles in modulating hemopoiesis but do suggest that these major types are probably playing important roles in maintaining stem cells in long term liquid cultures. In addition, data suggests that the epitheloid cell directly nurtures hemopoietic cells on its surface while the macrophages may serve a separate function. A number of growth factors are produced by these two cell types which appear to include CSF-1, a granulocyte CSA separate from CSF-1 and a megakaryocyte CSA separate from both the GM-CSA and CSF-1 (Table 5). Thus the present data suggest that there are at least three (formula; see text) separate hemopoietic growth factors produced. The FDC-P1 activity produced by irradiated stroma would appear most likely to be GM-CSA-II. The fact that lectins enhanced production of these activities is intriguing but the cell type on which the lectins are acting has not as yet been defined. It appears that lithium also acts upon adherent marrow stromal cells to induce production of myeloid regulatory growth factors. Lithium appears to stimulate both normal and irradiated stroma to produce hemopoietic maintenance and growth factors and the present data suggests that factors active on pre IL-3 cells, HPP-CFC, CFU-D, CFU-meg, and CFU-S are all induced from these stromal cells by lithium. Whether the lithium induced factors and the factors derived from irradiated stroma represent a number of different growth factors or one or two critical regulatory molecules is at present unclear. The synergistic activity derived from the TC-1 cell line is of particular interest in this regard. This CSF-1 dependent activity is capable of acting on a very primitive stem cell to induce impressive proliferation and differentiation. In addition an activity in TC-1 conditioned media which may be synergistic activity appears capable of inducing adherent marrow cell lines which then can subsequently produce more of the same factor, a classic autocrine system.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The use of ECT in children: case report.

A case is presented in which electroconvulsive therapy (ECT) was successfully used to treat childhood depression. In addition, the literature of ECT use in childhood disorders is briefly reviewed. It is proposed that ECT is a valid therapy for children only in depression, mania, or acute schizophreniform psychoses, refractory to pharmacotherapy.

Age Factors↗

Penetrating injuries of the neck.

A review of 271 patients with penetrating wounds of the neck is presented. A policy of selective conservative management appears totally justified in view of the low mortality and morbidity in this series. Particular attention has been paid to the presentation and surgical approach to the injured vertebral artery.

Adolescent↗

Crystalline sheets of tropomyosin.

In the presence of spermine tropomyosin forms sheets having two-dimensional crystallinity and tactoids. The most common form of sheet has cmm symmetry with a = 80 nm and b = 5 nm. The structure of this sheet has been solved in projection to a nominal resolution of 1.5 nm by combining data from electron diffraction and electron microscopy. Analysis of this pattern and that of rarely observed sheets having p2 symmetry (a = 40 nm, b = 5 nm and gamma = 80 degrees) indicated that the cmm structure was formed by superposition of two p2 sheets. The tropomyosin molecules in each p2 sheet were arranged in rows directed along the p2 (0,1) lattice lines, with all the molecules in one row having the same polarity and lying antiparallel to the molecules in adjacent rows. These rows associated in pairs, possibly by the supercoiling of the molecules in one row about those in the neighbouring row.

Crystallization↗

Length of myosin rod and its proteolytic fragments determined by electron microscopy.

The mean length of rabbit myosin chymotryptic rod in electron micrographs of unidirectionally shadowed preparations was 154 nm. Tryptic light meromyosin prepared from this rod had a mean length of 86 nm whereas long and short S2 measured 62 and 43 nm, respectively. The combined length of light meromyosin and long S2 appeared to be less than that of rod, which indicated that possibly some material was lost on digestion. Molecular lengths agreed with sedimentation equilibrium Mr values but were lower than those indicated by gel electrophoresis.

Animals↗

Bileaflet, tilting disc and porcine aortic valve substitutes: in vivo hydrodynamic characteristics.

The St. Jude valve is a new bileaflet disc cardiac valve prosthesis designed to avoid some of the hemodynamic drawbacks of other prostheses. The in vivo flow characteristics of the St. Jude aortic valve (42 patients) were studied and compared with those of three other commonly used aortic prostheses. Björk-Shiley (12 patients), Hancock (27 patients) and Carpentier-Edwards (15 patients). The studies, performed 24 to 48 hours after surgery, included measurements at rest and during augmentation of valve flow by infusion of isoproterenol. The mean performance index for valves of all sizes is higher for the St. Jude than for either porcine valve, both at rest and during isoproterenol infusion (p less than 0.05). Utilizing data both at rest and with isoproterenol, the relation of valve flow and mean systolic gradient for each size of St. Jude valve (19 to 25 mm) indicates the occurrence of small increases in gradient (5.3 to 8.2 mm Hg) as valve flow increases, ranging from 161 to 436 ml/systolic X min. A direct comparison of valve flow and gradient data for all size 25 and 23 mm prostheses at rest indicates a tendency for a lower mean systolic gradient in both mechanical valves than in either porcine valve (p = 0.07). With isoproterenol augmentation of valve flow in 25 mm valves, the gradient is less (p less than 0.05), and the effective orifice area and performance index are larger (p less than 0.05) for the St. Jude than for either porcine valve.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Patient characteristics which are related to the doctor-patient interaction.

Audiotapes were made of 140 visits to the offices of family physicians by patients with acute or chronic problems. The tapes were analysed using Bales Interaction Process Analysis to identify interviews which were patient-centred: interviews in which the physician was supportive and encouraged the patient to express himself and in which the patient did express himself and offer suggestions. Instructions about medication were also classified. Four patient factors--age, sex, marital status, level of education--were noted and the relationship between these factors and the nature of the doctor-patient interaction was assessed. Physicians were more likely to ask elderly patients about their drug-taking in the past, but showed less positive rapport towards them. Older patients were more likely to express antagonistic feelings. Female patients expressed feelings while male patients more often presented facts. The physicians actively encouraged such behaviour by expressing themselves more openly with female patients and asking them for expression of feelings. Patients of different educational levels experienced different interviews; the physicians were more likely to appeal to the intellect of a university-educated patient by justifying the drug regimen while offering emotional support to patients with a lower level of education.

Adolescent↗

alpha-Hydroxylation of nitrogen-15 labelled N-nitrosamines by isolated hepatocytes.

The principal pathway of nitrosamine metabolism has long been considered to be alpha-hydroxylation. For N-nitrosodialkylamines, this hypothesis requires that a molecule of molecular nitrogen be released for every molecule of nitrosamine that is alpha-hydroxylated. Thus, the quantitative determination of nitrogen formation should provide a measure of the importance of this pathway. This method was applied earlier to the doubly-labelled nitrogen-15 compounds, N-nitrosodimethylamine (NDMA), N-nitrosomethylphenylamine (NMPhA) and N-methyl-N-nitrosourea (MNU), using both a 9 000 X g supernatant fraction of liver and the intact animal as metabolic systems. The in-vitro results were quite different from those obtained in vivo. The majority of the NDMA (67%) and the MNU (88%) were converted to nitrogen in vivo, while NMPhA gave considerably less nitrogen (52%). These results differed by a factor of approximately two from those obtained in vitro (NDMA, 33%; NMPhA, 18.8% and MNU, 96%). Since such differences may be a result of the loss of cellular architecture, we have extended the work to include isolated hepatocytes. It had been shown previously that isolated hepatocytes constitute a practical alternative to in-vivo systems, even though the correlation with in-vivo metabolism appears to depend on the substrate analysed. The values obtained using this system (NDMA, 47%; NMPhA, 23%; and MNU 105%) reconfirm that metabolism may be substrate dependent. As in our previous studies, no mixed nitrogen (15N14N) or labelled nitrogen oxides were found. The data are all consistent with the hypothesis that at least one demethylase for each of the nitrosamine substrates is associated with a cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Vasoactivity of cerebrospinal fluid from patients with brain swelling.

The triggering mechanisms of diffuse cerebral swelling are poorly understood. The findings in this study are in keeping with the hypothesis that chemicals released by brain trauma into the CSF promote vasodilatation. Other proposals have included brainstem stimulation with increased cerebral blood flow and defective autoregulation. A number of factors may be operative.

Animals↗

Nuclear magnetic resonance evidence for a flexible region at the C-terminus of alpha-tropomyosin.

The 1H nuclear magnetic resonance spectrum of alpha-tropomyosin contains a number of sharp peaks indicative of the presence of small regions of high flexibility in the molecule. Removal of 9 to 11 residues from the C-terminus by digestion with carboxypeptidase A causes a marked decline in the intensity of these peaks. The difference is consistent with at least the C-terminal four residues of the sequence (-Met-Thr-Ser-Ile) being highly mobile. The conformation of the C-terminus is thus radically different from the alpha-helical coiled-coil from which the bulk of the molecule is constructed.

Carboxypeptidases↗

Ciliary but not saltatory movements are inhibited by vanadate microinjected into living cultured cells.

To test the idea that saltatory organelle movements of nonmuscle cells might be driven by microtubule-dynein interactions, we microinjected vanadate into several different types of cultured cell. Solutions of sodium metavanadate made up in a simple buffered salt solution were pressure microinjected into fully spread cells in an open-topped culture chamber placed on the stage of an inverted microscope. The cells were observed by oil-immersion phase-contrast optics and results were recorded on movie film. Vanadate, at 10(-5)-10(-2) M, microinjected into cultured chick embryo fibroblasts, failed to inhibit organelle movements. To test the effectiveness of vanadate's inhibitory action under living cell conditions, ciliated epithelial cells were microinjected. In these cells even the smallest microinjection of 5 X 10(-5) M vanadate caused an immediate cessation of ciliary beating. Moreover, in cells that were well spread it was found that whereas vanadate, at 5 X 10(-5)-5 X 10(-3) M, inhibited ciliary motion, it failed to inhibit organelle saltations in the same cell. To determine whether vanadate would inhibit a living actin-myosin system, myocardial cells were also microinjected. Following microinjection of 5 X 10(-5) and 5 X 10(-4) M vanadate a temporary tonic contraction (which also occurred following microinjection of buffer alone) was followed by regular beating. Taken together these results demonstrate that in living cell systems microtubule-dynein interactions are as sensitive to vanadate inhibition as they are in demembranated model systems, and that a working actin-myosin system in a living muscle cell does not share this great sensitivity. In light of the pronounced differential inhibitory effects of vanadate on the movements of cilia and organelles, our results suggest that saltatory organelle movements in chick embryo fibroblasts and rabbit oviduct epithelial cells are unlikely to be brought about by microtubule-dynein interactions.

Adenosine Triphosphatases↗

Dientamoeba fragilis, a protozoan parasite in adult members of a semicommunal group.

Dientamoeba fragilis is an intestinal protozoan parasite associated with gastrointestinal symptoms. This study was undertaken in a semicommunal group reported to have a high prevalence of this parasite. Stools were collected from 81 adult group members. Intestinal parasites were observed in stool specimens of 45 (56%) of the 81 adults; D. fragilis was found in 33 (41%) subjects. This paper describes the clinical findings and treatment of 26 adults with D. fragilis alone or with a commensal. Gastrointestinal symptoms were observed in 22 (85%) of infected subjects; abdominal pain and excessive flatus were significantly more common in this group. diiohydroxyquin 650 mg three times a day for 20 days eliminated the parasite in 10 (83%) of the 12 treated, although three subjects required a second course of therapy. Parasitic infection should be considered in patients with vague gastrointestinal symptoms, especially those living in endemic areas, in close proximity, or with a history of foreign travel.

Adolescent↗