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Biomedical subjects

J Whittaker

Publications and source records attributed to J Whittaker.

At least 109 records · Page 6Linked to original sources
PubMed1981

Metabolism of somatostatin and its analogues by the liver.

The rate of degradation of 125I-labelled [Tyr11]somatostatin by isolated rat hepatocytes was similar to that of unlabelled somatostatin. Reaction was dependent upon cell concentration and temperature, being rapid at 37 degrees C and negligible at 0 degrees C. The apparent Km for the overall degradative process was approximately the same for degradation by hepatocytes and by partially-purified liver plasma membranes. Extracellular breakdown of somatostatin, by proteases released from cells into the incubation medium, represented less than 10% of the cell-associated degradation. Homogenization of hepatocytes resulted in a 10--20-fold increase in the degrading ability of the cells. After incubation of 125I-labelled [Tyr11]somatostatin and 125I-labelled [Tyr1]somatostatin with hepatocytes, 125I-labelled tyrosine was the major radioactive product identified in the incubation medium. The rate of release of 125I-labelled tyrosine from the labelled [Tyr1]analogue was approximately 11 times greater than from the labelled [Tyr11] analogue. 125I-labelled [Tyr11]somatostatin bound to the cells in a non-saturable manner and approx. 70% of the cell-associated radioactivity could be dissociated by dilute acid. The rate of degradation of somatostatin was unchanged by reagents that inhibit the internalisation and lysosomal degradation of polypeptides by cell suspensions but was reduced by reagents that inhibit sulphydryl-dependent proteases. It is proposed that plasma-membrane associated proteolysis, involving both endo- and exopeptidases may represent the predominant degradative pathway of somatostatin in vivo.

Animals↗
PubMed1981

Impaired insulin binding to isolated adipocytes in experimental diabetic ketoacidosis.

Insulin sensitivity in vivo and insulin binding in vitro to adipocytes have been studied in streptozotocin diabetic rats with ketoacidosis. Insulin sensitivity in vivo measured as the acute (20 min) fall in blood glucose in response to an insulin infusion of 1 U/kg body weight per hour correlated positively with arterial blood pH (r = 0.92, p less than 0.01: n - 38). At pH less than 6.9 there was no fall in blood glucose. For studies in insulin binding to adipocytes ketoacidotic animals were divided into a group with moderate ketoacidosis (pH greater than 7.0) and a second group with severe ketoacidosis (pH less than 6.9). Insulin binding to adipocytes was maximal in cells from both ketoacidotic and from normal rats at pH 7.6-7.8. Total binding was decreased in he diabetic rats (P less than 0.01) and this was more marked in the severely diabetic group (p less than 0.001) at all pHs studied. At pH 7.4, 125I-insulin binding was decreased in diabetics compared with normal rats (0.89 +/- 0.14 versus 2.0 +/- 0.24% with 2 x 10(5) cells/ml: n = 6;p less than 0.01) and also in the severe compared with the moderate ketoacidotic rats (0.5 +/- 0.08%/2 X 10(5) cells; n = 6, p less than 0.05). Equilibrium binding studies showed that there was a small decrease in apparent affinity in adipocytes from both groups of diabetics (KD = 2.8 +/#- 0.2 X 10-9 mol/l, n = 6 in moderate ketoacidosis; 2.5 +/- 0.3 X 10-9 mol/l, n = 6 in severe ketoacidosis) compared with control animals (KD = 1.8 +/- 0.15 X 10-9 mol/l, n = 6). Scatchard analysis revealed that there was also a decrease in receptor concentration which was greater in the severely ketoacidotic group. These findings may explain in part the insulin resistance of severe ketoacidosis.

Adipose Tissue↗
PubMed1981

A study of amyloid arthropathy in multiple myeloma.

Forty-three patients with classical multiple myeloma were studied to assess the prevalence and characteristics of amyloid arthropathy using clinical, radiological, and histological methods. Two patients were found to have amyloid arthropathy, and a third case is described in detail. Complement and cryoprecipitate analysis of the synovial fluid, and electronmicroscopy of the synovium, synovial debris and cartilage were undertaken in an attempt to shed further light onto the pathogenesis of what has hitherto been regarded as a rare complication of multiple myeloma. Complement components were not depressed and no evidence of specific light chain containing immune complexes was found in synovial fluid cryoprecipitates. Histochemical and electron microscopic localization of amyloid in perichondrocytic lacunae as well as in synovial fluid debris, synovium and the articular cartilage surface suggest the possibility that chondrocytes and synovial macrophages may share a role in processing immunoglobulin components as a prelude to the formation of amyloid fibrils. Amyloid arthropathy occurs in about 5 per cent of patients with multiple myeloma. The clinical picture can resemble rheumatoid arthritis with median nerve compression in the carpal tunnel and symmetrical arthritis of the wrists and small joints of the hands. Diagnosis can be established by examination of Congo red stained synovial fluid sediments under polarized light even in the absence of other clinical features of amyloidosis and when rectal biopsy is negative.

Aged↗
PubMed1980

Metastatic spermatocytic seminoma.

Spermatocytic seminoma is noted generally for its relative infrequency of regional or distant metastases. A case of metastatic spermatocytic seminoma is reported in which there was radiographic evidence of tumor recurrence within an irradiated area. The need for aggressive initial management and careful followup of patients with this entity is emphasized.

Dysgerminoma↗
PubMed1977

Is cerebral palsy a preventable disease?

The causes of cerebral palsy in 96 young patients were analyzed. Potentially avoidable situations including inappropriate obstetric management and inappropriate neonatal care occurred in 38%. There should be a shift in emphasis from the rehabilitation of cerebral palsy to its prevention by improving services for reproductive care. Prevention can be undertaken by 1) identification and referral of the mother with a high-risk pregnancy to a perinatal center for her confinement; 2) fetal monitoring and appropriate resuscitation at delivery; and 3) early transfer of compromised infants to a neonatal care unit under good supervision.

Abruptio Placentae↗
PubMedDate not supplied

A prospective study of psychosocial morbidity in adult bone marrow transplant recipients.

Forty recipients of bone marrow transplantation were recruited prospectively and assessed pretransplant, at 1 month postdischarge, and at 6 months postdischarge between 1989 and 1990. Assessments included a psychiatric interview, a variety of standardized questionnaires (Hospital Anxiety and Depression Scale, Mental Attitude to Cancer Scale, Psychosocial Adjustment to Illness Scale), and a standardized diagnostic interview. The influence of factors such as depression and anxiety upon length of stay, survival, psychosocial adjustment, and negative prognostic attitudes were examined. In contrast to other studies, little influence was found for psychiatric illness on physical outcome variables, but they did affect psychosocial outcome. The implications of these findings are discussed.

Adult↗
PubMedDate not supplied

Quality assurance/control issues. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: General definitions of quality assurance and quality control (QA/C) have existed in many forms for decades, and a new discipline guides their application to diverse industrial and recently medical processes without much fanfare. However, in the field of cervical cytology screening, the range of QA/C options has recently broadened and become controversial. With the advent of new systems of terminology, larger-scale laboratories and new technologies--plus strong governmental and legal pressures in some nations--the range of extremely difficult and sometimes expensive QA/C choices our community faces is greater than ever. CONSENSUS POSITION: At our conference, the basic definitions of QA/C posed little difficulty. Presentation of the range of methods in use today and of those based on new technologies where use is proposed or has just begun also was achieved with little or no dispute. However, there was lack of consensus on exactly how QA/C methods are to be assessed. Indeed, there was little consistency in the use of different outcome measures with which we can judge success or failure of specific QA/C options. In addition, the tension between pressure to adopt sometimes uncertain or expensive method enhancements and pressure to maintain affordability and the widest possible access for populations that most need cervical cytology screening is greater than ever. ONGOING ISSUES: More data are required that would enable assessment of QA/C options with the clearest possible understanding of cost/benefits and current or new assumptions of risk. Other task forces, such as medicolegal, cost/benefit and those devoted to new technologies, are our essential partners in meeting the challenges described above.

Centers for Medicare and Medicaid Services, U.S.↗
PubMedDate not supplied

Insulin receptor transmembrane signaling: evidence for an intermolecular oligomerization mechanism of activation.

To evaluate the mechanism of ligand activation of the insulin receptor we have generated mutant receptor cDNAs which encode proteins with oligopeptide linkers between the carboxy terminus of the extracellular domain and the transmembrane domain of the molecule. Mutant cDNAs encoding a rigid alpha helical insert (HIR NQDVD) or a flexible polyglycine insert (HIR G12) were expressed in CHO Kl cells. Both basal and insulin stimulated autophosphorylation in vitro and in vivo of the expressed receptors were indistinguishable from those of wild type receptor expressed in the same cells. These findings suggest that ligand binding can activate the insulin receptor by an intermolecular dimerization mechanism.

Amino Acid Sequence↗
PubMedDate not supplied

The interaction of DNA-targeted platinum phenanthridinium complexes with DNA in human cells.

DNA-targeted platinum phenanthridinium complexes were investigated in intact human cells and in tumour-bearing mice. The DNA sequence specificity of platinum phenanthridinium complexes was examined in intact human cells using a Taq DNA polymerase stop assay. It was found that the platinum phenanthridinium complexes had a similar sequence specificity to that of cisplatin. However, the rate at which DNA was damaged in intact human cells was 6-fold greater for the platinum phenanthridinium chloride complexes compared with cisplatin. These results are consistent with a DNA-targeting hypothesis where the attachment of an intercalating group to cisplatin places the platinum in close proximity to DNA and increases the rate of DNA platination. Platinum phenanthridinium iodide complexes were also tested, but damaged DNA at a rate similar to cisplatin. The platinum phenanthridinium complexes with shorter linker chain lengths damaged DNA more efficiently than the longer linker chain length complexes. The platinum phenanthridinium chloride complexes also showed significant anti-tumour activity in tumour-bearing (P388) mice.

Animals↗