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Biomedical subjects

J Mather

Publications and source records attributed to J Mather.

At least 37 records · Page 2Linked to original sources

Retinal and preretinal localisation of epidermal growth factor, transforming growth factor alpha, and their receptor in proliferative diabetic retinopathy.

A number of growth factors have been implicated in the development and perpetuation of preretinal fibrovascular membranes in patients with proliferative diabetic retinopathy (PDR). The aim of this study was to determine the potential role of epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and their receptor (EGF-R) in PDR development. Immunostaining for EGF, TGF-alpha, and EGF-R was compared between normal retina, PDR retina, and PDR preretinal membranes. Weak staining for EGF and EGF-R was observed throughout the neural retina from non-diabetic eyes while weak to moderate staining for TGF-alpha was observed in the ganglion cell layer and the inner and outer nuclear layers. In contrast, intense staining for EGF and TGF-alpha and moderate staining for EGF-R were observed throughout the PDR retina. Immunoreactivity for EGF, TGF-alpha, and EGF-R was seen in the majority of the 11 excised membranes studied and, though variable, was generally greater than that observed in normal retinas. These results suggest an autocrine/paracrine role for EGF, TGF-alpha, and EGF-R in PDR.

Diabetic Retinopathy↗

Quantitative two-site enzyme-linked immunosorbent assays for inhibin A, activin A and activin B.

We have developed three specific enzyme-linked immunosorbent assay (ELISA) formats which quantitate inhibin A in conditioned media and serum. The assays are sensitive in a range 0.078-5.0 ng/ml and have been characterized in terms of cross-reactivity to inhibin related proteins. The CK:CK assay format recognizes inhibin A, inhibin B and inhibin-related molecules, while the 9A9:CK assay format recognizes inhibin A and inhibin A precursors, but not free alpha-subunit. The 11B5:CK assay appears to recognize only mature 32 kDa inhibin A. Additionally, we have developed separate, specific ELISA formats which quantitate activin A and activin B. The assays have a range of 0.2-50 ng/ml and 0.4-50 ng/ml for activin A and recombinant activin B, respectively. These assays are presently being used to examine the concentration of inhibin A, activin A and activin B in clinical serum samples.

Activins↗

Pharmacokinetic profile of recombinant human (rh) inhibin A and activin A in the immature rat. II. Tissue distribution of [125I]rh-inhibin A and [125I]rh-activin A in immature female and male rats.

The tissue distribution of recombinant human inhibin A (rh-inhibin A) and rh-activin A was determined in immature female Sprague Dawley-derived rats after iv administration of radiolabeled proteins. [125I]rh-Inhibin A and [125I]rh-activin A diverge in their distribution to tissues of the immature female rat as examined histologically (whole body autoradiography and thin section analysis) and by computing the percent dose and tissue to blood ratios for individual tissues. [125I]rh-inhibin A accumulated in the spleen, adrenal, bone marrow, and ovary after iv injection. Iodinated rh-inhibin A was also found in the anterior and posterior pituitary. [125I]rh-activin A was found in the ovary and pituitary after iv injection. Little specific binding was found in the spleen or adrenal. The bone marrow accumulated some [125I]rh-activin A which was competed by rh-activin A. The primary route of excretion for radioactivity was the kidney, with the label appearing in the bladder by 10 min after iv injection. Not only do rh-inhibin A and rh-activin A have different pharmacokinetics, but fewer tissues accumulate radioactive rh-activin A than rh-inhibin A.

Activins↗

In vitro ligand binding of 125I-recombinant human activin A to the female rat brain.

Activin has been localized within cells and terminals in the brain. However, little is known about the site of action of this hormone within the brain. In the present study in vitro ligand autoradiography was used to determine the distribution of high affinity binding sites for 125I-rh activin A in rat brain. The highest density of binding sites were concentrated in the amygdala and other forebrain limbic structures. Binding was saturable in selected amygdala nuclei with an apparent Kd of approximately 0.2 nM. 125I-rh activin A binds specifically in regions known to contain terminals immunoreactive for this hormone, and also at sites distinct from the location of activin A containing neuronal terminals (e.g. the ventral limbic system).

Activins↗

Characterization of recombinant human factor VIII.

Recently, complete human factor VIII DNA clones have been obtained and subsequently expressed in baby hamster kidney cells (Wood, W. I., Capon, D. J., Simonsen, C. C., Eaton, D. L., Gitschier, J., Keyt, B., Seeburg, P. H., Smith, D. H., Hollingshead, P., Wion, K. L., Delwart, E., Tuddenham, E. G. D., Vehar, G. A., and Lawn, R. M. (1984) Nature 312, 330-337). The recombinant factor VIII (rVIII) protein secreted from these cells has now been purified allowing its structural analysis and comparison to plasma-derived factor VIII (pdVIII). Analysis of purified rVIII by sodium dodecyl sulfate-polyacrylamide gel electrophoresis shows that it consists of multiple polypeptides with relative mobilities (Mr) ranging from 80,000-210,000. The same pattern of polypeptides is also observed for pdVIII resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The proteins associated with rVIII are recognized by pdVIII antibodies in a Western blot. When rVIII and pdVIII are subjected to isoelectric focusing they are resolved into a similar pattern of protein bands. Thrombin, factor Xa, and activated protein C, which modulate factor VIII activity by proteolysis, process rVIII in the same manner they do pdVIII. As is the case for pdVIII, thrombin activation of rVIII coagulant activity correlates with the generation of subunits with Mr of 73,000, 50,000 and 43,000. These subunits appear to form a metal-(perhaps Ca2+) linked complex. EDTA inactivates thrombin-activated rVIII and pdVIII, with the activity being regenerated after the addition of a molar excess of MnCl2. The results suggest that rVIII is structurally and functionally very similar to pdVIII.

Animals↗

Construction and characterization of an active factor VIII variant lacking the central one-third of the molecule.

The primary structure of factor VIII consists of 2332 amino acids that exhibit 3 distinct structural domains, including a triplicated region (A domains), a unique region of 909 amino acids (B domain), and a carboxy-terminal duplicated region (C domains), that are arranged in the order A1-A2-B-A3-C1-C2. The B domain (residues 741-1648) of factor VIII is lost when factor VIII is activated by thrombin, which proteolytically processes factor VIII to active subunits of Mr 50,000 (domain A1), 43,000 (domain A2), and 73,000 (domains A3-C1-C2). To determine if the B domain is required for factor VIII coagulant activity, a variant was constructed by using recombinant DNA techniques in which residues 797-1562 were eliminated. This shortened the B domain from 909 to 142 amino acids. This variant factor VIIIdes-797-1652 was expressed in mammalian cells and was found to be functional. The factor VIIIdes-797-1562 protein was purified and shown to be processed by thrombin in the same manner as full-length factor VIII. The factor VIIIdes-797-1562 variant also bound to von Willebrand factor (vWF) immobilized on Sepharose. These results indicate that most of the highly glycosylated B domain of factor VIII is not required for the expression of factor VIII coagulant activity and its interaction with vWF.

Amino Acid Sequence↗

Identification and possible function of pro-opiomelanocortin-derived peptides in the testis.

Using antibodies against peptides derived from different portions of the POMC molecule, immunocytochemical evidence suggests that this precursor and/or the peptides present within it are localized in testicular Leydig cells of at least five species. There is no evidence for the localization of these peptides or their precursor in any other cell type in this organ. Examination of testicular extracts by gel filtration, SDS-PAGE, and RP-HPLC indicate that the testis contains low concentrations of POMC-derived peptides relative to brain. Further analysis indicates that POMC is processed to alpha-MSH and beta-endorphin similar to its processing in intermediate pituitary lobe and brain. The relative mobilities of immunoreactive alpha-MSH and beta-endorphin on RP-HPLC columns indicate that they are in the unacetylated state as in brain and in contrast to the acetylated forms in the intermediate pituitary lobe. The potential for Leydig cells to synthesize POMC and its peptides was suggested by the demonstration of POMC-like mRNA in total testis and Leydig cell cultures. The size of the POMC-like mRNA is approximately 150 base pairs shorter than anterior or intermediate pituitary POMC mRNA. POMC-like mRNA activity has also been localized to Leydig cells in sections of testes using in situ hybridization. Immunostainable beta-endorphin and other POMC-derived peptides are present in testicular Leydig cells during fetal life and following puberty at times when testosterone secretion is maximal. The accumulation of immunostainable POMC-derived peptides in Leydig cells is dramatically increased by LH and hCG. A variety of observations suggests that testicular cells can respond to POMC-derived peptides. ACTH and the MSHs stimulate growth and cAMP accumulation in Sertoli cells. By contrast, studies using antagonists suggested that beta-endorphin and/or another testicular opioid inhibit Sertoli cell proliferation and ABP secretion. These observations are consistent with the postulate that different portions of the POMC molecule may have opposite effects on Sertoli cell function and suggest a mechanism by which Leydig cells could modulate Sertoli cell activity. Intratesticular administration of opiate antagonists inhibits testosterone secretion both in vivo and in vitro. These observations suggest that Leydig cell-derived beta-endorphin may facilitate testosterone secretion either directly or indirectly. The finding of POMC and its derivative peptides in testis, ovary, adrenal, and placenta suggests that all steroid hormone-secreting organs in mammals may utilize this peptidergic system.

Adrenocorticotropic Hormone↗

Status of geriatric medicine in the United States.

Geriatrics has experienced a gradual and cyclical evolution in the United States. A considerable amount of attention has recently been focused on the status of geriatric medicine and the issue of specialty recognition. Numerous organizations within established medicine have developed position documents and are in the process of re-examining their status. In the United Kingdom, physicians can now be designated as having a special interest in geriatric medicine, and Canada is proceeding with the development of a certificate of special competence in geriatric medicine under the auspices of the Division of Medicine, Royal College of Physicians and Surgeons. This paper presents hypotheses to account for the lack of organization status in geriatrics, and arguments are examined regarding the need for specialty recognition. There is general consensus that geriatrics has an identifiable body of knowledge and skills and that there is need for a cadre of academic geriatricians and educators in geriatrics for students and residents. However, specialty recognition introduces conflict within established specialties that consider care of the elderly crucial to their existence. The options for special recognition, including a certificate of special competence, are described with their advantages and disadvantages. Substantial arguments favor some form of specialty recognition.

Aged↗

Method for the removal of selected cells from cytological smear preparations for transmission electron microscopy.

The method described depends on fixing additional cytology smear preparations with glutaraldehyde to be used, if needed. Removal of cells from the slide makes use of partially polymerised resins in the usual way but a paper marker is used to localise the area in the resin block which contains the cells to be examined. Slides are placed in a freezing cabinet to facilitate easy separation of the resin block.

Cell Separation↗

Demonstration of papilloma virus particles in cervical and vaginal scrape material: a report of 10 cases.

The finding of virus particles by transmission electron microscopy (TEM) in fixed cervical and vaginal scrape material and their identification as papilloma viruses by negative staining is described. The colposcopic, cytological, and histological appearances in a group of 10 patients in whom virus particles were seen are discussed and the possibly considered of an association between papilloma virus infection and the development of cervical intraepithelial neoplasia (CIN) and multifocal intraepithelial neoplasia of the female lower genital tract.

Adolescent↗

Mouth lesions in iron-deficient anemia: relationship to Candida albicans in saliva and to impairment of lymphocyte transformation.

The atrophic glossitis and angular chilosis in patients with iron-deficient anemia are associated with infection of the mouth by Candida albicans. Saliva from these patients contained more Candida and supported the growth of Candida better than did saliva from a control group. The possibility that growth of Candida may be due to impaired lymphocyte function was investigated by measuring transformation of lymphocytes stimulated with phytohemagglutinin. Transformation was depressed in iron-deficient subjects and returned to normal after correction of their iron status. The lymphocyte count in the peripheral blood was also depressed and corrected by additional iron. Impaired lymphocyte function did not explain the mouth lesions and growth of Candida in saliva since lymphocyte transformation was equally depressed in patients with and without mouth lesions. A local factor, such as an effect of lack of iron on the resident vacterial flora of the mouth, may be important.

Adolescent↗

Does crew resource management training work?

INTRODUCTION: Effective crew resource management (CRM) may play a major role in decreasing the number of accidents and increasing overall safety of air medical programs. The purpose of the study was to compare the responses of crew members, in a variety of situations, who received CRM training and those who did not. The numerical results of the responses were used to evaluate the effectiveness of CRM in increasing crew awareness and promoting team concepts. METHOD: During a 12-month period, crew members of randomly selected air medical programs (fixed- and rotor-wing) were surveyed by questionnaire. Participants were asked if they had received CRM, effective communication, and team-building training. The next 15 questions pertained to crew interaction/communication in everyday and emergent situations and were scored on a Likert scale (1 = strongly agree and 5 = strongly disagree). A lower total score indicated a greater understanding of team awareness and effective communication. RESULTS: The mean score of crew members who received the three identified areas of training (initial CRM, team-building, effective communications) (37.96, SD +/- 7.67) was found to be significantly lower than the mean score of those who had received none of the training (44.13, SD +/- 5.0) and P < .05. CONCLUSION: Based on the results, CRM training increases crew awareness and promotes team concepts in both everyday and emergent situations.

Air Ambulances↗

Scheduled inspection of electromedical equipment. Planning and assessment.

Scheduled inspections help ensure the safety and efficacy of medical equipment. To ensure the regular checking of all items we developed a practical and realizable protocol consisting of basic safety and functional tests. Non-productive time spent searching for equipment was reduced enlisting the help of ward staff. Record keeping was simplified using monthly checklists detailing the tests to be performed. Clear labels distinguished items checked and the ward was informed about missing items. The effectiveness of the programme was assessed by auditing the number of items due for inspection, the average time per inspection, the number of faults found, and the incidence of breakdown repairs. The average inspection time per item was reduced to half an hour and the number of items due for inspection to below 10%. The programme was effective in fault detection (7% of items checked) and the incidence of breakdown repairs decreased from 75 to 53%.

Biomedical Engineering↗