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Biomedical subjects

M Davey

Publications and source records attributed to M Davey.

At least 37 records · Page 2Linked to original sources
PubMed1997

Lepidopteran peptides of the allatostatin superfamily.

Peptides of the allatostatin superfamily with the C-terminal amino acid sequence -YXFGL-NH2 have been isolated and identified from the lepidopterans, the codling moth, Cydia pomonella (Tortricidae) and the bollworm, Helicoverpa armigera (Noctuidae). The peptides, designated cydiastatins and helicostatins respectively, were monitored during purification with radioimmunoassays based on the callatostatins of the blowfly Calliphora vomitoria. The eight peptides from each of the two species appear to form an homologous series with four identical and three that differ by a single amino acid. This study demonstrates the ubiquitous nature of this family of peptides in insects.

Amino Acid Sequence↗
PubMed1996

Selective depletion of myelin-reactive T cells with the anti-OX-40 antibody ameliorates autoimmune encephalomyelitis.

The OX-40 protein was selectively upregulated on encephalitogenic myelin basic protein (MBP)-specific T cells at the site of inflammation during the onset of experimental autoimmune encephalomyelitis (EAE). An OX-40 immunotoxin was used to target and eliminate MBP-specific T cells within the central nervous system without affecting peripheral T cells. When injected in vivo, the OX-40 immunotoxin bound exclusively to myelin-reactive T cells isolated from the CNS, which resulted in amelioration of EAE. Expression of the human OX-40 antigen was also found in peripheral blood of patients with acute graft-versus-host disease and the synovia of patients with rheumatoid arthritis during active disease. The unique expression of the OX-40 molecule may provide a novel therapeutic strategy for eliminating autoreactive CD4+T cells that does not require prior knowledge of the pathogenic autoantigen.

Animals↗
PubMed1995

Phase I trial of 2B1, a bispecific monoclonal antibody targeting c-erbB-2 and Fc gamma RIII.

2B1 is a bispecific murine monoclonal antibody (BsMAb) with specificity for the c-erbB-2 and Fc gamma RIII extracellular domains. This BsMAb promotes the targeted lysis of malignant cells overexpressing the c-erbB-2 gene product of the HER2/neu proto-oncogene by human natural killer cells and mononuclear phagocytes expressing the Fc gamma RIII A isoform. In a Phase I clinical trial of 2B1, 15 patients with c-erbB-2-overexpressing tumors were treated with 1 h i.v. infusions of 2B1 on days 1, 4, 5, 6, 7, and 8 of a single course of treatment. Three patients were treated with daily doses of 1.0 mg/m2, while six patients each were treated with 2.5 mg/m2 and 5.0 mg/m2, respectively. The principal non-dose-limiting transient toxicities were fevers, rigors, nausea, vomiting, and leukopenia. Thrombocytopenia was dose limiting at the 5.0 mg/m2 dose level in two patients who had received extensive prior myelosuppressive chemotherapy. Murine antibody was detectable in serum following 2B1 administration, and its bispecific binding properties were retained. The pharmacokinetics of this murine antibody were variable and best described by nonlinear kinetics with an average t 1/2 of 20 h. Murine antibody bound extensively to all neutrophils and to a proportion of monocytes and lymphocytes. The initial 2B1 treatment induced more than 100-fold increases in circulating levels of tumor necrosis factor-alpha, interleukin 6, and interleukin 8 and lesser rises in granulocyte-monocyte colony-stimulating factor and IFN-gamma. Brisk human anti-mouse antibody responses were induced in 14 of 15 patients. Several minor clinical responses were observed, with reductions in the thickness of chest wall disease in one patient with disseminated breast cancer. Resolution of pleural effusions and ascites, respectively, were noted in two patients with metastatic colon cancer, and one of two liver metastases resolved in a patient with metastatic colon cancer. Treatment with 2B1 BsMAb has potent immunological consequences. The maximum tolerated dose and Phase II daily dose for patients with extensive prior myelosuppressive chemotherapy was 2.5 mg/m2. Continued dose escalation is required to identify the maximally tolerated dose for patients who have been less heavily pretreated.

Adult↗
PubMed1994

Substitution of the amino acid at position 102 with polar and aromatic residues influences substrate specificity of lactate dehydrogenase.

The Gln residue at amino acid position 102 of Bacillus stearothermophilus lactate dehydrogenase was replaced with Ser, Thr, Tyr, or Phe to investigate the effect on substrate recognition. The Q102S and Q102T mutant enzymes were found to have a broader range of substrate specificity (measured by kcat/Km) than the wild-type enzyme. However, it is evident that either Ser or Thr at position 102 are of a size able to accommodate a wide variety of substrates in the active site and substrate specificity appears to rely largely on size discrimination in these mutants. The Q102F and Q102Y mutant enzymes have low catalytic efficiency and do not show this relaxed substrate specificity. However, their activities are restored by the presence of an aromatic substrate. All of the enzymes have a very low catalytic efficiency with branched chain aliphatic substrates.

Amino Acid Sequence↗
PubMed1993

A study of the characteristics and needs of people transferred from acute hospitals to nursing homes.

OBJECTIVES: To describe the categories of people being approved for admission to nursing homes; to consider whether any alternatives would have been more appropriate; and to outline the care needed for each category. PARTICIPANTS AND SETTING: Patients in acute-care facilities in metropolitan Perth for whom a request had been made for nursing home admission. DESIGN: Patients were interviewed (by R B L and M D) and records in the acute hospital were examined. A second interview of those patients still available was conducted after their transfer to the nursing home. RESULTS: Nursing care was considered necessary for 123 of the 201 people seen in the acute hospitals; domestic care in a standard hostel for 24 people; care in a special dementia unit (SDU) hostel for 26 people; and care in a psychiatric institution for 16 people. Twelve others had various specific needs. Several different categories were identified in the group needing nursing care. CONCLUSIONS: Applicants for nursing home admission do not form a homogeneous group; there are several categories with different needs. SDU hostels should be added to the available facilities. In addition to undertaking the assessment of nursing home applicants, personnel from geriatric services should be encouraged to become involved in their continuing care.

Aged↗
PubMed1992

A method for rapid analysis of peripheral blood mononuclear leukocyte cytokine mRNA.

Interleukins, hematopoietic growth factors, and adhesion molecules mediate multiple components of the inflammatory response. Conventional methods for purification of cytokine-producing cells are time consuming and can, therefore, depending on the conditions of cell purification and the nature of the mRNA being purified, result in both over- and underestimates of mRNA content. Therefore, it has been difficult to quantify such factors in ways that are unambiguously reflective of in vivo cytokine production. We describe herein a method for such rapid preparation of peripheral blood mononuclear leukocytes (PBML) that amounts of cytokine mRNA derived from these cells, apart from readily quantifiable losses during RNA preparation, will be reflective of quantities in vivo. Small quantities (10(5) of normal PBML were isolated by density centrifugation of heparinized blood for 1.25 min in a capillary tube. Poly(A)+ RNA isolated by oligo(dT)-cellulose column chromatography was sufficient to reverse transcribe both antigen-specific T-cell-receptor beta-chain mRNA and interleukin 6 (IL-6) mRNA and subsequently amplify the cDNA with Taq polymerase in reverse transcription-polymerase chain reactions (RT-PCR). Although IL-6 mRNA was not present in normal PBML, PBML incubated in culture medium for only 3 h contained approximately one molecule per cell. Because of its rapidity this technique will permit quantification of cytokine mRNA in the steady state and in clinical setting of inflammation. Because the method requires only a small quantity of blood it can be applied to clinical research studies involving children.

Base Sequence↗
PubMed1991

The analysis of underivatized oligosaccharides by matrix-assisted laser desorption mass spectrometry.

Matrix Assisted Laser Desorption Mass Spectrometry is shown to provide a rapid and sensitive technique for the analysis of underivatized oligosaccharides. Typical sample loading is 1 pmol and analysis time is around 5 minutes. Through the use of an internal standard, mass measurements are generally accurate to within 0.5 Da. The technique is particularly useful for the analysis of oligosaccharide mixtures released from glycoproteins.

Carbohydrate Conformation↗
PubMed1987

Mechanism of alpha blockade for blood pressure control.

The realization that a generalized increase in peripheral vascular resistance was the fundamental hemodynamic abnormality in essential hypertension and that the maintenance of arteriolar tone depended on the continuity of the adrenergic nervous system led to the alpha-adrenoceptor inhibitors being the first substances to receive serious consideration as antihypertensive agents. An agent that inhibited the effect of the adrenergic transmitter at the neuroeffector junction was anticipated to be ideal in inhibiting adrenergic vasoconductor tone. The clinical expectations for these compounds in the treatment of arterial hypertension, however, were not fulfilled. Although they lowered blood pressure, the effect was accompanied by unacceptable side effects such as tachycardia, and tolerance rapidly developed. The realization that transmitter norepinephrine modulates its own release through a prejunctionally located, alpha-adrenoceptor operated control mechanism explained several paradoxical phenomena and suggested exciting therapeutic possibilities. Most important, it provided a plausible if not compelling explanation for the clinical failure of the classic alpha-adrenoceptor inhibitors as antihypertensive agents. Characterization of the prejunctional and postjunctional effects of alpha agonists and antagonists led to the conclusion that prejunctional and postjunctional alpha adrenoceptors differed in receptor structure and led to the identification of prazosin as the first virtually specific alpha-adrenoceptor inhibitor. This was a crucially important step in the development of specific agents to combat adrenergic predominance in essential hypertension. Antihypertensive drugs like prazosin and doxazosin preserve feedback control of transmitter norepinephrine release, and consequently cause minimal reflex activation. They represent an alternative choice for therapy in all grades of hypertension with virtually no contra indicatons to their use.

Adrenergic alpha-Antagonists↗
PubMed1986

Serum enzyme concentrations in untreated acute myeloid leukaemia.

Serum concentrations of lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBD), phosphohexose isomerase (PHI), leucine aminopeptidase (LAP), beta-glucuronidase (beta-gluc) and angiotensin-converting enzyme (ACE), were measured in 107 cases of untreated acute myeloid leukaemia which were classified by morphological, immunological and cytochemical criteria. The results show that serum LDH was increased in most cases, irrespective of leukaemic subtype, serum PHI and LAP were significantly higher in monocytic variants and serum beta-gluc and ACE levels were generally within normal limits. In addition, significant (p less than 0.05) relationships were found between serum LDH, PHI, LAP and beta-gluc concentrations and the numbers of circulating leucocytes.

Glucose-6-Phosphate Isomerase↗
PubMed1984

Precapillary vessels: effects of the sympathetic nervous system and of catecholamines.

The study of receptor-operated control mechanisms involved in adrenergic transmission in the blood vessel wall has substantially advanced the understanding of the factors involved in the maintenance of arteriolar tone. As a result of this work, alpha-adrenoreceptors have been divided into two major subtypes termed alpha 1- and alpha 2-adrenoreceptors. Initially, the term alpha 1 was proposed as a synonym for the postjunctional alpha-adrenoreceptor. There is now a large body of evidence for the existence of postjunctional alpha-adrenoreceptors mediating the contraction of vascular smooth muscles that are resistant to blockade by the alpha 1-adrenoreceptor antagonist prazosin, but are blocked by alpha 2-antagonists and can be activated by selective alpha 2-agonists but not by selective alpha 1-agonists. The physiological significance of postjunctional alpha 2-adrenoreceptors is discussed in respect to factors such as their role in blood pressure control and of whether they are innervated or not, and the differences in contractile responses and in the postreceptor mechanisms involved in stimulation-contraction coupling following activation of each receptor subtype are reviewed. Although the situation is complex, on balance the data are compatible with the view that alpha 2-adrenoreceptor-mediated responses in vascular smooth muscle are more dependent on the physiological environment than are responses mediated by alpha 1-adrenoceptors. Thus, although postjunctional alpha 2-adrenoreceptors can be involved in sympathetic nerve transmission, they appear largely to fulfill a humoral role in vascular smooth muscle closely allied to the prevailing conditions, whereas alpha 1-adrenoreceptors are primarily involved in sympathetic neurotransmission, independent of local environmental conditions.

Adrenergic alpha-Agonists↗