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D Davies

Publications and source records attributed to D Davies.

At least 19 recordsLinked to original sources
PubMed1992

Eosinophil chemotactic peptide sequences in rat alpha-CGRP. Activation of a novel trophic action by neutral endopeptidase 24.11.

Rat alpha- and alpha-CGRP are substrates for endopeptidase 24.11 in vitro. Cleavage of both peptides occurs at several points, including an unusual substrate recognition site to the amino side of ala36. In alpha-CGRP this resulted in the early formation of val32-gly-ser-glu35, a sequence previously reported to be a component of the eosinophil chemotactic factor of anaphylaxis (ECF-A). The biological activity of this peptide fragment was confirmed by bioassay. Chemotactic activity in other hydrolysis fragments of both alpha- and beta-CGRP was observed. Both alpha- and beta-CGRP could thus serve as precursors to different eosinophil chemotactic peptide fragments. A novel function of endopeptidase 24.11 may be to modify rather than to terminate the biological activity of CGRP peptides.

Amino Acid Sequence↗
PubMed1992

Endopeptidase-24.11 cleaves a chemotactic factor from alpha-calcitonin gene-related peptide.

The sequence of rat alpha-calcitonin gene-related peptide (CGRP-alpha) contains the tetrapeptide eosinophil granulocyte chemotactic factor Val32-Gly-Ser-Glu35. Peptide fragments formed following hydrolysis of rat CGRP-alpha in vitro by endopeptidase-24.11 were identified. The tetrapeptide fragment was generated following cleavage at a substrate recognition site unusual for this enzyme (-Glu-Ala-). Chemotactic activity of rat CGRP-alpha was increased following hydrolysis. Furthermore, rat CGRP-beta, which lacks the tetrapeptide sequence and is completely devoid of chemotactic activity, displayed low but measurable activity after hydrolysis. Val-Gly-Ser-Glu was identified as the principle fragment with chemotactic activity in rat CGRP-alpha. The results show that the chemotactic activity of the neuropeptide rat CGRP-alpha towards eosinophil polymorphonuclear leukocytes is increased following its hydrolysis in vitro by endopeptidase 24.11 through the formation of a previously identified eosinophil chemotactic tetrapeptide.

Amino Acid Sequence↗
PubMed1992

Complications following fast neutron therapy for head and neck cancer.

Serious complications resulting from the use of fast neutrons to treat head and neck malignancies are reported in 38 patients. The average interval between treatment and onset of complications was 5.5 years. Significant airways obstruction, requiring a tracheostomy, occurred in two patients, and a gastrostomy or pharyngostomy was performed for intractable dysphagia in six. Eight patients developed osteoradionecrosis: carotid artery rupture occurred in three patients following surgery for residual or recurrent disease. Our experience suggests that complications following fast neutron therapy for head and neck tumours are more severe, more common and occur after a longer time interval than those seen following conventional radiotherapy. Subsequent surgery in the irradiated area is compromised by severely impaired wound healing. When radical surgery is necessary for residual or recurrent disease the entire volume of irradiated tissue must be removed if healing is to be achieved.

Airway Obstruction↗
PubMed1992

Investigations into the mechanism by which sulfated polysaccharides inhibit HIV infection in vitro.

Sulfated polysaccharides have been shown to inhibit human immunodeficiency virus (HIV) infection in vitro. Dextrin sulfate, fucoidan, and dextran sulfate fail to neutralize virions directly, but interact with target cells to inhibit virus entry. Ionic interactions of sulfated polyanions with oppositely charged cell surface components, including CD4, have been assumed to be the inhibitory mechanism. It is shown that the sulfated polysaccharides inhibit infection of both CD4+ and CD4- cell lines by HIV and also that they inhibit HTLV-1 and, to a lesser extent, the simian retrovirus, MPMV, which use receptors other than CD4. One binding site for radiolabeled fucoidan on the surface of human T cells is an 18 kD protein, but its significance is not yet clear.

Antiviral Agents↗
PubMed1992

Scrapie in the central nervous system: neuroanatomical spread of infection and Sinc control of pathogenesis.

Following bilateral intraocular (i.o.) infection of Sinc s7 mice with ME7 scrapie, sequential tissue pools were taken from retina, optic nerve, superior colliculus (SC), dorsal lateral geniculate nucleus (dLGN), visual cortex and cerebellum. The infectivity levels in these pools were estimated by intracerebral (i.c.) assay in C57BL/FaBtDk mice. Infectivity was first detected in retina at 35 days post-injection (as an increase above residual injected inoculum), SC at 56 days, dLGN at 77 days and in optic nerve, visual cortex and cerebellum at 98 days. Pathological lesions were shown to develop in the same sequence later in the incubation period. Comparison of sequential retina and SC assays in congenic mice, which differ only in the vicinity of the Sinc locus, revealed a difference in the initial detection and progression of i.o. infection of between 60 and 100 days, indicating that Sinc acts by delaying the initiation of replication. Higher levels of infectivity were found in retina and SC of mice infected with 79A scrapie, which destroys the photoreceptor layer in the retina, than with ME7 scrapie, which does not. Retrograde transport of infection was indicated by the levels of infectivity in the retina after i.c. infection with ME7 or 79A scrapie. These results indicate that scrapie spread within the central nervous system is restricted to neuroanatomical pathways, and that Sinc controls the initiation, but not the rate of replication.

Animals↗
PubMed1992

Pharmacokinetics of [14C]FCE 22891, a penem antibiotic, following oral administration to healthy volunteers.

FCE 22891 is a prodrug of the penem antibiotic FCE 22101 and is suitable for oral administration. The pharmacokinetics of FCE 22891 were investigated in four healthy male volunteers following the oral administration of 500 mg of [14C]FCE 22891. Levels of radioactivity in plasma were always higher and persisted for longer than those of FCE 22101. The time to the maximum concentration of radioactivity in plasma generally coincided with that of FCE 22101. The respective values for the maximum concentrations of radioactivity in plasma were, on average, 8.57 +/- 2.95 micrograms equivalent/ml and 2.97 +/- 2.05 micrograms/ml. Over a 5-day period, mean urinary and fecal recovery of radioactivity accounted for 53.2 and 41.0% of the dose, respectively. The average amount of FCE 22101 excreted in urine and feces corresponded to 9.0 and 1.6% of the dose, respectively. The urinary recovery of the open-ring metabolite P1 and of its 5-S epimer P2 accounted for about 6.5 and 1.2% of the dose, respectively. Other chromatographic peaks corresponding to nonidentified compounds accounted for about 14.0% (polar metabolite fraction; peak P), 3.7% (less polar fraction; peak X), and 15.4% (least polar fraction) of the dose. Elimination of radioactivity and FCE 22101 in urine was rapid. Intersubject variability in the kinetics of total radioactivity in plasma was far less than that observed for FCE 22101. The results of the present study support suggestions that presystemic metabolism of FCE 22101 and/or transformation of the prodrug to compounds other than FCE 22101 are the main cause of intersubject variability in the kinetics of FCE 22101 produced in plasma following oral administration of its prodrug.

Administration, Oral↗
PubMed1991

Anti-neutrophil cytoplasm antibodies in rheumatoid arthritis.

Anti-neutrophil cytoplasm antibodies (ANCA) occur occasionally in rheumatoid arthritis (RA), but their incidence and clinical significance have been unclear. In this study we have investigated 58 patients with RA. In 22 patients the disease was inactive and the remaining 36 with active disease were further subdivided into those without clinical evidence of vasculitis (26), those with cutaneous vasculitis (8) and those with systemic vasculitis (2). ANCA were demonstrated by indirect immunofluorescence in 10 of the 58 patients (17%). While both perinuclear (pANCA) and cytoplasmic (cANCA) staining were detected, pANCA were more common (70%). Neutrophil-specific anti-nuclear antibodies (ANNA) were demonstrated in a further eight sera (14%) and ANA were detected on Hep-2 cells in 30 of the 58 sera (52%). ELISAs for the detection of anti-myeloperoxidase and anti-elastase antibodies were then established. Five sera with pANCA and five that contained ANNA were negative for both anti-myeloperoxidase and anti-elastase antibodies, suggesting other as yet unidentified cytoplasmic antigens as the target molecules. However, anti-myeloperoxidase or anti-elastase antibodies were found in four sera that had homogeneous or speckled ANA on both Hep-2 cells and neutrophils. One serum contained both antibodies. The presence of ANCA detected by indirect immunofluorescence or of anti-myeloperoxidase or anti-elastase antibodies in these patients with RA was not associated with disease activity nor with the demonstration of cutaneous vasculitis or renal disease (P NS). A possible association with systemic vasculitis remains to be confirmed. There is an incomplete correlation between indirect immunofluorescence patterns and antibody specificity in ELISA systems.

Antibodies, Antinuclear↗
PubMed1991

Asbestos induced pericardial effusion and constrictive pericarditis.

The number of disorders attributable to asbestos exposure has increased gradually over the years. The latest to be recorded is pericardial effusion and constrictive pericarditis, and three cases are reported here. A man with bilateral pleural thickening and plaques developed acute pericarditis and an effusion and was treated by pericardiectomy. Two men died from constrictive pericarditis associated with bilateral pleural effusions and diffusion pleural thickening. The pericardium showed nonspecific fibrous thickening. All had been occupationally exposed to asbestos. In the fatal cases the lungs contained amphibole fibres, in keeping with a modest degree of occupational exposure. Asbestos produces progressive fibrosis of the pericardium that is similar to diffuse pleural thickening and may be fatal. Both conditions may develop after relatively short or light exposure.

Adult↗
PubMed1990

Use of zoospore concentrations and life cycle parameters in determining the population of anaerobic fungi in the rumen ecosystem.

An indirect approach to quantification of the fibrolytic anaerobic fungi in the rumen is described. A mathematical model of the life cycle of anaerobic fungi, based upon observations of the life histories and growth kinetics of these organisms in vitro and in vivo, is constructed and solved in the steady-state to determine the population of particle-attached (substrate-associated) fungal thalli from the concentration of free-swimming zoospores in rumen liquid. The values obtained are broadly consistent with ruminal observations and with observations on faecal populations, which assume that a significant proportion of fungi leaving the rumen (as cysts or spores) can ultimately be accounted for in the faeces.

Animals↗
PubMed1990

Nutritionally induced peripheral neuropathies.

The authors have presented a discussion of some of the more common nutritional deficiency syndromes. A discussion of the etiology, clinical manifestation, diagnosis, and prognosis has been provided. Special attention has been given to the relationship between nutritional deficiency and the development of peripheral neuropathies. When patients suffering from peripheral neuropathy present, the possibility of a nutritional deficiency should be considered. The diagnosis of a nutritional deficiency neuropathy is rarely established. This may not merely be the result of a low incidence of the problem. The prompt diagnosis and treatment may afford dramatic results. The more protracted the course for diagnosis, the less favorable the prognosis. It is often difficult to pinpoint the exact nutritional deficiency present. Various methods have been discussed in this article; however, often multiple deficiencies are present simultaneously. The treatment with pharmacologic supplementation is usually very innocuous. It often proves beneficial to administer pharmacologic supplementation for a short period. This will aid in the differential diagnosis. Often prescribing a patient large doses of the B-complex vitamins for a limited time will allow the physician to determine if a nutritional neuropathy is present. It should also be remembered that just because a patient is suffering from a peripheral neuropathy from a metabolic disease or secondary to medication, they may also be suffering from a nutritional deficiency simultaneously. We believe that the podiatric physician is well trained to extend comprehensive treatment of pedal manifestations of peripheral neuropathies. Podiatric physicians have a large armamentarium at their disposal to treat the pedal manifestations of the disease sufficiently. These treatments may be conservative or surgical in nature, as previously discussed. We hope that this discussion will increase the awareness of the physician to the various ramifications of nutritionally induced neuropathies as well as the provision of insight into the most efficacious means available for appropriate management.

Alcoholism↗