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Biomedical subjects

S Davies

Publications and source records attributed to S Davies.

At least 307 records · Page 17Linked to original sources
PubMed1988

The effects of pH and various salts upon the activity of a series of superoxide dismutases.

The CuZn superoxide dismutases (SODs) from ox, sheep, pig and yeast were investigated by pulse radiolysis in order to evaluate the role of electrostatic interactions between O2.- and SOD proteins in the mechanism of action of the SOD enzymes. The protein net charge in this series varies, as evaluated by the protein pI values spanning over a large range of pH: 8.0 (sheep), 6.5 (pig), 5.2 (ox) and 4.6 (yeast). The amino acid sequences are largely conserved, with the three mammalian proteins being highly homologous and the yeast protein having some distinct variations in the region surrounding the active site. At pH 8.0 the activities of the SODs from various sources are similar, though the minor differences observed suggest that in the highly homologous mammalian series the most acidic protein is the most enzymically efficient one. The pH-dependences of the various activities in the pH range 7-12 are similar, and the related curves are best fitted by two pK values, which are approx. 9.2 and 11.0 for the mammalian enzymes and 9.1 and 11.4 for the yeast enzyme. The activities of the proteins at I 0.1 are decreased by approx. 20% when compared with the activity at I 0.02 at pH 8.5, whereas at pH above 10 the pH-dependence of the activity approaches that determined at I 0.02 and at pH 11.9 the activity is essentially independent of ionic strength. The dependence upon ionic strength also depends on the salt used, with perchlorate being more effective than phosphate or borate or Mops and still effective at pH above 10.5, where the effect of other salts becomes negligible. The dual and concerted dependence of the activities of different SODs on pH and salt concentration is explained with the encounter of O2.- with the active-site copper being governed by the protonation of two positively charged groups in the vicinity of the active site. The gradient between these localized charges and the rest of the protein may explain the different activities of the mammalian proteins at lower pH. On the basis of the sequence variation of the SODs examined it is not possible to definitely identify these groups. Likely candidates are conserved basic amino acid side chains in the vicinity (less than or equal to 1.2 nm) of the active site, i.e. Lys-134 and Arg-141, but co-ordination of OH- in the first copper co-ordination sphere may be an additional factor accounting for the higher pK.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Characteristics of the membrane of the stereocilia and cell apex in cochlear hair cells.

Freeze-fracture has been used to examine the membrane of the cell apex and of the stereocilia in cochlear hair cells. The apical (non-stereociliary) membrane of inner hair cells (IHCs) exhibited a lower density of intramembrane particles (IMP) than that of the outer hair cells (OHCs) but in both cell types the apical membrane responded to the effects of filipin. The distribution of IMP and of filipin-induced membrane deformations was uniform over the apical membranes in both IHC and OHC, thus, providing no evidence for local membrane differentiation on the non-stereociliary part of the hair cell apex. The stereociliary membranes of IHC and of OHC differed not only in the density of IMP, but also in their responses to filipin and to tomatin. IHC stereocilia responded intensely to both agents. OHC stereocilia showed a significantly lower density of filipin-induced lesions and appeared almost unaffected by tomatin. This suggests that the OHC stereocilial membrane may be structurally specialized. The membrane at the apical end of stereocilia appeared to be differentiated from the membrane of the stereociliary shaft. The tip region was free of the usual IMP and showed no filipin-induced lesions. The differentiation at the apical end was also apparent in samples which have been rapidly frozen without prior chemical fixation or cryoprotection, showing that the particle-free area was not an artefact induced by glutaraldehyde fixation. Close examination of the membrane at the apical-most tip of the stereocilium revealed the presence of a small number of large particles of 10.5-11.0 nm diameter. The occurrence of membrane differentiation localized to the tip of the stereocilium may be consistent with the suggestion that transduction channels in hair cells are situated at this point.

Animals↗
PubMed1988

Prospective study of lower respiratory tract infections in an extended-care nursing home program: potential role of oral ciprofloxacin.

PURPOSE: Infections of the lower respiratory tract pose an important problem in nursing homes. Despite the magnitude of this problem, few, if any, antibiotic studies have been targeted specifically at nursing home-acquired bronchopulmonary infections. Following the establishment of a teaching Extended-Care Nursing Home Program, which facilitated the early diagnosis and therapy of bronchopulmonary infections, a comparative trial of oral ciprofloxacin and intramuscular cefamandole was initiated in elderly patients with lower respiratory tract infections. In addition to assessing the relative efficacy and safety of ciprofloxacin and cefamandole, our goals were to identify problems and pitfalls associated with conducting clinical research in this nursing home setting, evaluate selected clinical and laboratory features of lower respiratory tract infection in this patient population, and measure outcomes in all study groups. PATIENTS AND METHODS: During a 20-month period, 40 patients with pneumonia and 20 patients with acute bronchitis were enrolled in this randomized study. Sixty-three patients with pneumonia who were ineligible for the randomized study were also followed prospectively. The mean age of the 111 participants (123 cases) was 80.8 years; all patients had at least one chronic medical condition. RESULTS: Although Streptococcus pneumoniae was the single most common isolate, gram-negative bacteria were cultured from 81 percent of the cases that yielded pathogens from a satisfactory sputum specimen. The in-hospital mortality rate was strikingly low (6.5 percent), and a large majority of patients in all study groups were discharged safely back to their nursing homes well within the Diagnosis-Related Group length of stay. CONCLUSION: Ciprofloxacin appeared to be as safe and effective as cefamandole in this nursing home program; however, additional studies are needed to determine its role in the treatment of elderly patients with bronchopulmonary infections.

Administration, Oral↗
PubMed1988

Effect of blood culture media on the in vitro recovery of Mycoplasma hominis.

Despite the prevalence of Mycoplasma hominis few cases of septicaemia due to this organism have been reported. The ability of various blood culture media to sustain the growth of an inoculum of M. hominis was therefore studied. Of the media tested, an 'in-house' Hartley's digest broth with 0.1% glucose was the most efficient. The investigation also demonstrated that growth of M. hominis is adversely affected by the concentration of liquoid (sodium polyanetholsulphonate) present in blood culture media.

Adolescent↗
PubMed1988

The Barthel ADL Index: a reliability study.

The Barthel Index is a valid measure of disability. In this study we investigated the reliability of four different methods of obtaining the score in 25 patients: self-report, asking a trained nurse who had worked with the patient for at least one shift, and separate testing by two skilled observers within 72 hours of admission. Analysis of total (summed) scores revealed a close correlation between all four methods: a difference of 4/20 points was likely to reflect a genuine difference. In individual items, most disagreement was minor and involved the definition of middle grades. Asking an informed nurse or relative was as reliable as testing, and is quicker.

Activities of Daily Living↗
PubMed1987

Co-localization of neuropeptide tyrosine and somatostatin immunoreactivity in neurons of individual subfields of the rat hippocampal region.

The co-localization of neuropeptide tyrosine (NPY) and somatostatin (SOM) in rat hippocampal cells was studied in double labelling experiments using a combination of antibodies against the two peptides on the same tissue section. The individual hippocampal subfields show large variations in the relative number of NPY- and SOM-immunoreactive (-i) neurons. While the entorhinal area is far richer in SOM as compared to NPY-i cells, NPY-i cells predominate in all subfields (e.g. regio superior, regio inferior) of Ammon's horn. Co-localization of both peptides in single neurons was highest in regio inferior and in the area dentata and lowest in the retrohippocampal structures. In the dorsal hippocampus, the number of SOM-i cells containing NPY-i was higher than the number of NPY-i cells containing SOM-i. This pattern was reversed in the retrohippocampal region. At ventral levels the incidence of colocalization of NPY- and SOM-i in single cells increased in all hippocampal subfields.

Animals↗
PubMed1987

A novel imino-acid carrier in the enterocyte basolateral membrane.

Basolateral membrane vesicles prepared from rat small intestinal epithelial cells were used to study the sodium-independent transport of L-proline. The uptake of L-proline was unaffected by the presence of sodium and showed saturation kinetics (Kt = 0.5 mM and Vmax = 23.3 pmol/mg protein per s). Competition experiments indicated that other amino acids had an affinity for the carrier system with L-leucine greater than L-alanine greater than sarcosine greater than glycine greater than L-lysine greater than OH-proline greater than taurine greater than beta-alanine greater than D-alanine greater than D-proline greater than L-serine greater than phenylalanine greater than valine greater than D-serine greater than phenylalanine greater than valine greater than D-serine greater than MeAIB greater than methionine greater than threonine. This pathway does not resemble those previously described either in the brush-border membrane of intestinal epithelial cells or the plasma membrane of other cell types. The lack of effect of methionine and threonine indicate that proline is not using the L-type system, while the very low affinity for MeAIB and the Na+ independence suggest that this is a novel system for imino acids. The relatively high capacity of this system and its low Kt, which is almost identical to the proline system in the brush-border membrane, strongly suggest that this is an important pathway in the final step for proline absorption by the small intestine.

Amino Acid Transport Systems, Neutral↗
PubMed1987

The relationship between radiation-induced DNA double-strand breaks and cell kill in hamster V79 fibroblasts irradiated with 250 kVp X-rays, 2.3 MeV neutrons or 238Pu alpha-particles.

Using the neutral filter elution technique, the induction of DNA double-strand breaks (dsb) has been measured in 250 kVp X-irradiated V79-379A Chinese hamster cells irradiated under air or nitrogen. The dose-effect curves for induced dsb were curvilinear, mirroring cell survival curves, such that there was an approximately linear relationship between induced dsb and lethal lesions (-In (cell survival)) which was independent of oxygen. With cells irradiated with 2.3 MeV neutrons or 238Pu alpha-particles the correlations between lethal events and dsb, although also approximately linear, do not match those for X-rays. With neutrons there is approximately a 2.5-fold reduction in the level of dsb induction per lethal event. Thus either the apparently linear relationships found are spurious, and there is no general correlation between induced dsb and lethal effect, or there are qualitative differences between neutron, alpha-particle and X-ray induced dsb that give them differing probabilities of cell kill.

Alpha Particles↗
PubMed1987

Comparative in-vitro activity of five fluoroquinolones against mycobacteria.

Fifty distinct strains of mycobacteria were investigated to determine their in-vitro susceptibility to five new fluoroquinolones (norfloxacin, pefloxacin, ofloxacin, enoxacin and ciprofloxacin). Ofloxacin and ciprofloxacin were found to be the most active, with minimum inhibitory concentrations (MIC) of 1.25 mg/l or less to all strains of Mycobacterium tuberculosis, M. bovis, M. xenopi, M. kansasii and BCG tested. All agents showed little activity against M. malmoense and M. avium-intracellulare complex with MIC values of greater than 2.5 mg/l.

Anti-Bacterial Agents↗
PubMed1987

Preparation of the mammalian organ of Corti for scanning electron microscopy.

The effect of various standard tissue preparation procedures for scanning microscopy on the morphology of the mammalian organ of Corti has been examined. Comparison was made of (i) different fixatives: glutaraldehyde (GA) alone, osmium (Os) alone, GA and Os together and GA followed by Os; (ii) freeze-drying (FD) versus critical point-drying (CPD); (iii) ligand binding of osmium with thiocarbohydrazide (TOTO procedure) versus sputter coating to provide a conductive coat. Results were assessed in terms of known structural parameters in fresh tissue. It is shown: (i) that double fixation, either GA, Os together or GA followed by Os, consistently produced less tissue distortion than either fixative alone, (ii) that FD produced less shrinkage of the tissue than CPD, and (iii) that the TOTO procedure appeared to rigidify the tissue and enhanced preservation of the morphology.

Animals↗
PubMed1986

Origin of the neuropeptide Y innervation of the rat retrohippocampal region.

Using the method of retrograde tracing of Fast Blue in combination with immunohistochemistry, the origins of the retrohippocampal neuropeptide Y (NPY) innervation was studied in the rat brain. The findings suggest that two NPY-immunoreactive (NPY-i) afferent systems, one intrinsic and the other of extrinsic origin give rise to the massive NPY innervation of the retrohippocampal region, including the entorhinal area (EA). The intrinsic projections originate from multipolar and fusiform cells situated primarily in layers IV through VI of the medial and lateral EA, as well as from a small number of NPY-i basket cells situated in layer II. Other NPY-i afferents originate from cortical neurons with long association projections located in the deep layers of the perirhinal area and in the piriform cortex, as well as from cells situated throughout the rostrocaudal extent of the endopiriform nucleus, in the lateral nucleus of amygdala and in the nucleus locus coeruleus.

Amidines↗
PubMed1986

A monoclonal antibody recognizes a phosphorylated epitope shared by proteins of the cell nucleus and the erythrocyte membrane skeleton.

Monoclonal antibody 3C5 recognizes a family of proteins in the nuclei of cultured cells [(1985) Eur. J. Cell Biol. 38, 344]. This antibody has now been shown to recognize equivalent proteins in liver nuclei and in the Triton-insoluble fraction of tissue extracts. In human erythrocytes the antibody recognized a single protein, present in the membrane skeleton fraction and with the molecular mass and extraction properties of beta-spectrin. The epitope recognized by 3C5 was destroyed by alkaline phosphatase. We conclude that this antibody recognizes a phosphorylation site shared by nuclear proteins and a protein of the erythrocyte membrane skeleton, probably beta-spectrin.

Alkaline Phosphatase↗
PubMed1986

Neuropeptide Y innervation of the hippocampal region in the rat and monkey brain.

Using antibodies to neuropeptide Y (NPY) in combination with immunohistochemical techniques we have studied the distribution of cell bodies and nerve terminals containing NPY immunoreactivity (-i) in the hippocampal region of rats and monkeys (cynomolgus). In colchicine-pretreated rats a large number of NPY-positive cells are present in all areas of the hippocampal region. The NPY-i cells range in size from small (diameter across soma: 10-15 micron) to large (approximately 20 micron). Most of the NPY-i cells are situated in the hilus, in the subgranular zone of the area dentata, and in the stratum oriens of Ammon's horn. A majority of these are polymorphic cells but cells of different morphology are present in these layers as well. These include small spheroid cells and dentate pyramidal basket cells that are distinct from the polymorphic cells in the subgranular zone. The subicular complex (e.g., the subiculum, pre-, and parasubiculum) and the entorhinal area contain fewer NPY-i cells than the rest of the hippocampal region. In the dorsal parts of the pre- and parasubiculum numerous small cells are scattered throughout all layers, while in the entorhinal area the NPY-stained cells are situated primarily in the deep layers (V and VI). In the ventral part of the lateral entorhinal area large multipolar and bitufted cells are found in layers II-VI. In the untreated monkey brain NPY-positive cells are found in the hilus of the area dentata and in the deep (IV through VI) layers of both the medial and lateral entorhinal area. Fewer NPY-stained cells are present in the subicular complex and in the entorhinal area. In the monkey as well as in the rat, NPY-stained cells are present in the angular bundle and in the alveus. A dense network of NPY-i fibers innervates the entire hippocampal region in both the rat and the monkey. The hippocampal NPY-i preterminal processes are present primarily in stratum moleculare of Ammon's horn and in the outer one-third of this layer in the area dentata. The NPY-positive innervation of the dentate molecular layer is far more prominent in the monkey than in the rat brain. Numerous NPY-stained fibers are scattered in other areas as well. In all retrohippocampal structures, and in particular the entorhinal area, the NPY-i fibers form a massive network that innervates all layers to about the same extent, with the exception of the molecular layer, which is more densely innervated than the other layers.

Animals↗