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Biomedical subjects

J M Davies

Publications and source records attributed to J M Davies.

At least 19 recordsLinked to original sources
PubMed1992

Potassium transport into plant vacuoles energized directly by a proton-pumping inorganic pyrophosphatase.

Potassium is accumulated in plant vacuoles against an inside-positive membrane potential. The mechanism facilitating energized K+ transport has remained obscure. However, electrogenic activity of the inorganic pyrophosphatase (H(+)-PPase) at the vacuolar membrane is dependent on cytoplasmic K+, raising the possibility that the enzyme translocates K+ into the vacuole. Membrane currents generated by the H(+)-PPase were measured (using a patch clamp technique) in intact vacuoles isolated from Beta vulgaris storage tissue. A significant orthophosphate-dependent outward current mediated by the enzyme in reverse mode is evoked only when potassium is present at the vacuolar face of the tonoplast, suggesting that potassium is a translocated ion. Furthermore, current-voltage analysis of the effects of extravacuolar potassium and pH on the reversal potential of the H(+)-PPase-generated current points to direct translocation of K+ and H+ by the enzyme. Thus the H(+)-PPase represents a distinct class of eukaryote translocase and could facilitate vacuolar K+ accumulation in vivo.

Biological Transport, Active↗
PubMed1992

Endolymphatic delivery of IL2 in patients with melanoma and lymphoma.

UNLABELLED: During this phase I/II study, enodolymphatic cannulae were placed in the iliac lymphatics under general anaesthesia. IL2 was then infused via this route at escalating doses until the highest tolerated dose was achieved; then, continuous infusion was maintained for 2 to 3 weeks. Seven patients with advanced cancer (3 lymphoma, 4 melanoma), resistant to all other modalities of treatment received such therapy. Most patients tolerated 4 to 5 x 10(6) u/day of IL2 for 2 to 3 weeks with less toxicity as compared to the equivalent dosage given intravenously. No severe perioperative morbidity was experienced. One melanoma patient had a minor clinical response. Changes in circulating lymphocyte numbers and cytotoxicity demonstrated a systemic effect of endolymphatic IL2 therapy. CONCLUSIONS: The endolymphatic administration of IL2 is associated with less toxicity than the intravenous route but still achieves a systemic effect; a lower tumour burden may prove more responsive to this therapy.

Adult↗
PubMed1992

Accident analysis of large-scale technological disasters applied to an anaesthetic complication.

The occurrence of serious accidents in complex industrial systems such as at Three Mile Island and Bhopal has prompted development of new models of causation and investigation of disasters. These analytical models have potential relevance in anaesthesia. We therefore applied one of the previously described systems to the investigation of an anaesthetic accident. The model chosen describes two kinds of failures, both of which must be sought. The first group, active failures, consists of mistakes made by practitioners in the provision of care. The second group, latent failures, represents flaws in the administrative and productive system. The model emphasizes the search for latent failures and shows that prevention of active failures alone is insufficient to avoid further accidents if latent failures persist unchanged. These key features and the utility of this model are illustrated by application to a case of aspiration of gastric contents. While four active failures were recognized, an equal number of latent failures also became apparent. The identification of both types of failures permitted the formulation of recommendations to avoid further occurrences. Thus this model of accident causation can provide a useful mechanism to investigate and possibly prevent anaesthetic accidents.

Accidents↗
PubMed1992

Mimicry between HTLV-I and myelin basic protein: no response in HTLV-I-associated myelopathy patients.

The reactivity to a peptide from the HTLV-I polyprotein (FKLPGLNSR) and a similar sequence from myelin basic protein (MBP) (FKLGGRDSR) was examined in relation to the proposal that mimicry of MBP by HTLV-I could be involved in autoimmune responses in HTLV-I-associated myelopathy (HAM). It was found that rabbit antibodies raised against the HTLV-I peptide recognised both peptides, with a titre of 1/10240 to the HTLV-I peptide and 1/5220 to the MBP peptide. Human sera from HAM patients and a HTLV-I carrier without HAM showed slightly higher responses to the HTLV-I peptide compared to the responses from uninfected human sera. HAM patients had greater responses to the HTLV-I peptide than to the similar MBP peptide and an unrelated bovine MBP peptide. There was no recognition of the peptides by peripheral blood lymphocytes from HAM patients or a HTLV-I carrier without HAM. It was concluded that although cross-reactivity was demonstrated in rabbits and the HTLV-I peptide was recognised by sera from HAM patients, the epitope does not appear to evoke a mimicking response to the similar region in MBP. Hence it is not likely to be involved in the pathogenesis of HAM through molecular mimicry.

Amino Acid Sequence↗
PubMed1992

Vacuolar H(+)-translocating pyrophosphatases: a new category of ion translocase.

The membrane surrounding the central vacuole of plant cells contains an H(+)-translocating ATPase (H(+)-ATPase) and an H(+)-translocating inorganic pyrophosphatase (H(+)-PPase). Both enzymes are abundant and ubiquitous in plants but the H(+)-PPase is unusual in its exclusive use of inorganic pyrophosphate (PPi) as an energy source. The lack of sequence identity between the vacuolar H(+)-PPase and any other characterized ion pump implies a different evolutionary origin for this translocase. The existence of the vacuolar H(+)-PPase, in conjunction with increasing recognition of PPi as a key metabolite in plant systems, necessitates reconsideration of ATP as the primary energy source for membrane transport in plant cells.

Amino Acid Sequence↗
PubMed1992

The ethics of cardiopulmonary resuscitation. I. Background to decision making.

Futile cardiopulmonary resuscitation (CPR) may prevent humane care of the dying child and deprive parents of the opportunity to express their love, grief, and dedication at a critical moment, while appropriate and successful CPR may restore intact their child. Attempted resuscitation of corpses or children with terminal illness indicates inadequate knowledge, discrimination, and decision making. CPR is a medical procedure applicable to certain medical problems; weighing up the risks and benefits in each individual case is a medical function that is constrained by the law and must take full note of patient and family preferences, but cannot be governed by them and should not be over-ruled by laws based on complex but different cases. Time limits on occasions may curtail the full process of consultation and decision making. Applications of skills and resources in the right time and place requires understanding of the medical logistics and study of the potential for good outcome.

Cardiopulmonary Resuscitation↗
PubMed1992

The ethics of cardiopulmonary resuscitation. II. Medical logistics and the potential for good response.

Mismatches between provision of paediatric cardiopulmonary resuscitation (CPR) and potential to benefit are examined. Deficiencies are most likely to occur in peripheral maternity units but futile CPR is more common in emergency departments where the child is unknown. Decision making in individual cases is best retained by the medical profession for the sake of the child and family. American style intervention by the legislature is likely to dissipate scarce resources and perhaps harm infants not capable of benefiting.

Cardiopulmonary Resuscitation↗
PubMed1992

Neutrophil chemotaxis and adhesion in preterm babies.

To investigate the increased susceptibility to infection of very immature preterm neonates, neutrophil chemotaxis, Mac-1 adhesion receptor expression, and adherence to human umbilical vein endothelial cell monolayers (HUVE) were examined in neonates born at less than or equal to 32 weeks' gestation. Chemotaxis of neutrophils from well preterm neonates towards casein or zymosan activated serum (ZAS) was reduced (mean SE) being for casein 88.6 (3.8) microns; ZAS 76.2 (4.3) microns compared with adults (casein 117.8 (1.4) microns; ZAS 112.1 (1.4) microns), but similar to term neonate neutrophils (casein 92.7 (4.5) microns; ZAS 75.9 (3.1) microns). Stimulated Mac-1 expression showed a similar pattern: reduced on preterm neutrophils compared with adults, but similar to term neonates. Preterm and term neonate neutrophils were both hyperadherent to HUVE when unstimulated, but showed an equally impaired ability to increase adhesion following stimulation. Casein stimulated chemotaxis and stimulated Mac-1 expression 'matured' towards adult levels of performance four weeks after preterm birth. The increased incidence of sepsis in immature preterm infants is not due to greater defects of neutrophil migration.

Caseins↗
PubMed1992

Combination of GM-CSF and cytosine in myelodysplasia results in improved neutrophil function.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was given concurrently with low-dose cytosine arabinoside for 3 weeks to patients with myelodysplasia. Neutrophil activation as evidenced by increased chemiluminescence and reduced surface expression of CD16 was consistently seen during therapy. An attendant fall in chemotaxis was also observed. These effects occurred even when neutrophil counts did not rise significantly at lower doses of GM-CSF. Although no improvement in anaemia or thrombocytopenia was observed, the neutrophil counts became normal during therapy without significant expansion of marrow cellularity or colony-forming ability. No major toxicities were observed, even at higher dosages of GM-CSF.

Antigens, CD↗
PubMed1992

Changes in plasma FcRIII demonstrate increasing receptor production during late pregnancy and after preterm birth.

We have previously described reduced expression of the Fc gamma receptor type III on the cell membrane (M-FcRIII) of neutrophils from very preterm neonates. To investigate the mechanism underlying this reduced receptor expression, we have measured neutrophil-derived soluble FcRIII (S-FcRIII) in the plasma of fetuses and neonates from 19 wk gestation. S-FcRIII in fetal plasma and in preterm neonates born before 32 wk gestation was consistently low [mean 13.6 +/- 1.2% (mean adult S-FcRIII = 100%, range 30-240%)]. In utero, S-FcRIII starts to rise from 33 wk and increases more than 4-fold to reach adult levels by term. S-FcRIII measured sequentially in preterm infants born as early as 24 wk of gestation showed a rapid postnatal increase to reach adult levels within 3 wk of birth. The changes in S-FcRIII paralleled changes in M-FcRIII expression on the cell surface. These observations point to a reduced rate of FcRIII production by fetal neutrophils as opposed to an increase in receptor release. The parallel increase in S-FcRIII and M-FcRIII suggests that there may be a programmed activation of FcRIII synthesis within individual cells late in the 3rd trimester of fetal development. In addition, FcRIII production may be switched on early by preterm birth.

Cell Membrane↗
PubMed1992

Peanut agglutinin (lectin from Arachis hypogaea) binding to hemopoietic cells: an immunophenotypic study using a biotin streptavidin technique.

The lectin peanut agglutinin (PNA) was used to study the surface carbohydrate expression of galactose beta 1, 3, N-acetylgalactosamine by normal and malignant hemopoietic cells. Immunostaining was performed using biotinylated PNA and a streptavidin-alkaline phosphatase staining technique on 78 patients. The study was undertaken to enlarge on previous reports of lectin binding to cells of hemopoietic origin and to establish the potential role of biotinylated PNA as a component of an immunotoxin for in vitro purging of bone marrow in patients with multiple myeloma. In normals only monocytes, macrophages, centroblasts and plasma cells showed reactivity. Of the hematological malignancies, all cases of multiple myeloma were positive and non-Hodgkin's lymphoma cases with a large cell component had positive centroblasts. Two of 5 cases of acute myelomonocytic leukemia, one case of chronic myelomonocytic leukemia and one case of pleomorphic T cell non-Hodgkin's lymphoma showed PNA positive neoplastic cells. The reactivity of biotinylated PNA with centroblasts and plasma cells suggests that it may be of potential value when linked to a streptavidin-ricin conjugate in the in vitro purging of bone marrow of patients with multiple myeloma prior to autologous bone marrow transplantation.

Bacterial Proteins↗
PubMed1992

A method for clinical purging of myeloma bone marrow using peanut agglutinin as an anti-plasma cell agent, in combination with CD19 monoclonal antibody.

Previous studies have shown that the lectin peanut agglutinin (PNA) binds bone marrow plasma cells in the majority of patients with myeloma and does not bind to normal haemopoietic progenitors. This lectin has been used in combination with anti-CD19 monoclonal antibody (moAb) in a system for purging myeloma bone marrow. This has now been scaled up for application to ex vivo treatment of large volumes of bone marrow suitable for autologous bone marrow transplantation. Four bone marrow harvests from patients with myeloma containing 9.5 +/- 4.9% plasma cells were depleted of erythrocytes and mature granulocytes by Ficoll separation using the Haemonetics V50 cell separator. The mononuclear fraction was then purged with magnetic beads coated with PNA and anti-CD19 moAb. The system proved highly efficient with removal of all detectable plasma cells and CD19+ cells. Average mononuclear cell recovery following purging was 71% of the concentrated marrow with 78% yield of CFU-GM. Normal progenitor recovery related to patients' weight is predicted to be adequate for haemopoietic reconstitution following ablative chemoradiotherapy. This system is therefore feasible for large-scale clinical purging.

Adult↗
PubMed1991

Continuing medical education undertaken by general practitioners using the rural registrar scheme.

OBJECTIVE: To evaluate the first full year of operation of the rural registrar scheme by comparing the educational activities undertaken by the participating rural general practitioners with those undertaken in the previous year. DESIGN: Retrospective questionnaire survey mailed to all participants. SETTING: Continuing medical education (CME) for rural general practitioners (GPs) in South Australia. PARTICIPANTS: All 25 GPs who used the scheme from July 1989 to June 1990 were included in the study. All were from solo or two person practices in rural South Australia. One had gone abroad and could not be contacted, and 23 of the remaining 24 responded. INTERVENTIONS: A competent locum was supplied at no cost to the GP, so that the GP could leave the practice to undertake CME. MAIN OUTCOME MEASURES: GPs were asked to outline CME activities for two consecutive years, to rate the educational value of each activity, and to note whether skill or knowledge acquisition was most relevant. RESULTS: The rural registrar scheme increased the amount of time that rural GPs spent on CME. The range of topics studied increased considerably. CONCLUSIONS: The provision of a satisfactory locum service has enabled rural GPs to participate in a wide range of CME activities, which reflect the diversity of general practice. Most participants preferred individual, experiential study programmes to more structured CME programmes.

Clinical Competence↗