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Biomedical subjects

M J McKay

Publications and source records attributed to M J McKay.

At least 37 records · Page 2Linked to original sources
PubMed1990

Malignant fibrous histiocytoma developing in bone 44 years after shrapnel trauma.

Tumors induced by foreign bodies are uncommon in humans, but they are a relatively common occurrence in some experimental animals. The development of sarcoma in association with metallic foreign bodies has rarely been reported. The development of a malignant fibrous histiocytoma in a 65-year-old man 44 years after shrapnel fragments lodged in his left arm is described. The literature regarding metallic foreign body-induced cancer in humans is reviewed.

Aged↗
PubMed1990

Persisting cyclical uterine bleeding in patients treated with radical radiation therapy and hormonal replacement for carcinoma of the cervix.

Radical radiation therapy used for carcinoma of the cervix will ablate ovarian function. Since January 1986, our policy has been to administer oral combination oestrogen-progesterone replacement hormonal therapy to all premenopausal patients undergoing radical radiation with or without synchronous chemotherapy, for invasive cervix cancer. Five out of 22 (23%) such patients unexpectedly experienced between one and four episodes of cyclical per vaginal bleeding after the completion of radiation therapy. Bleeding episodes occurred in the absence of persistent tumor or radiation reaction, and suggest persisting endometrial response to exogenous hormonal stimulation. Uterine activity was temporarily retained in these five patients despite a minimal endometrial surface dose of between 4800 and 6490 cGy. The limited number of cycles before bleeding spontaneously ceased may represent the slow death of endometrial cells subsequent to radiation or radiochemotherapy treatment, and has not previously been described. In view of the paucity of data on the radiosensitivity of normal endometrium, we have carefully examined these patients who appear to have retained endometrial sensitivity to hormonal stimuli after radical radiation-chemotherapy for uterine cervix cancer.

Adult↗
PubMed1990

Pulmonary blastoma.

Pulmonary blastoma (PB) is the least common malignant pulmonary neoplasm, with less than 100 reported cases. This tumour occurs up to three times more commonly in males. There exists an age peak in the third and fourth decades, although approximately one quarter of cases occur in children, often in association with congenital lung disease. Although the clinical features of PB are not specific, the histopathological appearance is distinctive, showing an admixture of both epithelial and mesenchymal (sarcomatous) elements. Historically, surgery has been the most commonly used modality for localized disease: however, useful data on local control rates are lacking. Extrathoracic metastases are the major cause of treatment failure in PB, with chemotherapy having little impact in this disease. The role of radiation therapy in the management of PB has not been established, however, early radioresponsiveness was demonstrated in the palliative treatment of soft tissue and bone metastases in the case presented: radiation therapy should be considered in the management of this disease.

Adult↗
PubMed1990

The American 'Patterns of Care' Study: a model for the assessment of the quality of patient care in radiation oncology.

There are well documented manpower and equipment deficiencies in the specialty of Radiation Oncology in Australia. These deficiencies persist despite numerous reports over the last decade detailing their existence. The Patterns of Care Study (PCS) from the United States of America (USA) is a unique, comprehensive review of Radiation Oncology services in that country. It has clearly demonstrated that substantial benefits not only in survival but also in reduced treatment morbidity accrue when a full range of modern techniques and equipment is used. The present paper is a review of the PCS: this study has immense implications for patient care in particular and cancer services in general, in Australia. There seems little point in continuing to fund cancer research in the hope of gains in survival rates while continuing to ignore the fact that gains of a similar magnitude can be obtained by the maximum use of current knowledge and the provision of modern equipment.

Australia↗
PubMed1989

Basaloid-squamous carcinoma of the hypopharynx.

Basaloid-squamous carcinoma, a variant of squamous cell carcinoma, has only recently been described as arising in the pharynx. The cardinal histopathologic feature, as its name suggests, is a biphasic cellular pattern of basaloid and squamous components in an intimate relationship. Major differential diagnoses include adenoid cystic, squamous, adenosquamous, and sarcomatoid carcinomas. Although the number of reported cases is small, basaloid-squamous carcinoma appears biologically virulent, with a propensity to aggressive local behavior and early regional and distant metastasis, and subsequent poor survival. The authors add a further case of basaloid-squamous carcinoma to the world literature.

Carcinoma, Basosquamous↗
PubMed1989

Treatment of hepatic cavernous haemangioma with radiation therapy: case report and literature review.

Cavernous haemangiomas are the most common benign tumours of the liver, most of which are found incidentally during abdominal imaging, laparotomy or autopsy. A patient with a large, symptomatic lesion, which responded well to radiation therapy, is described. In view of the fact that a large proportion of these vascular malformations are unresectable and response to radiation therapy is well documented, the latter modality should be considered for symptomatic lesions.

Adult↗
PubMed1988

On the yield of new information from the selective requesting of post mortem examinations in oncology patients.

Traditionally, a high rate of post mortem (PM) examinations has been advocated, primarily for the quality control of clinical diagnosis. In days of increasing scrutiny of medical costs, the role of the 'routine' requesting of any investigation must be questioned, and we report here the results of a policy to request post mortem examinations selectively when there was a reasonable expectation that it would yield new information. Between 21/3/82 and 12/2/86 there were 1356 deaths in patients registered with the Department of Radiation Oncology, Westmead Hospital. During this period, 100 PM examinations were performed. The overall post mortem rate is thus 6.7%, but for patients dying whilst under our direct care it is 23%. The cause of death was changed in 9% of cases following PM examination. The ante mortem assessment of the remission status of irradiated volumes was confirmed in 69% but was not recorded in the post mortem report in 22%, in spite of the medical record being available to the pathologist. Minor modifications were made by PM examination to the establishment of primary tumor site, sites of metastatic disease, histological diagnosis and other significant pathological states. The autopsy is an expensive investigation: we conclude that the low yield of relevant new information in this selective series is a powerful argument against the traditional routine request. Indeed the yield of new information in cases when the histological tumour type was known was even lower. The necessity for a problem-orientated approach is apparent from the data on the remission status of treated sites.

Adult↗
PubMed1987

Characterization of meprin, a membrane-bound metalloendopeptidase from mouse kidney.

Meprin is an intrinsic protein of the brush border, a specialized plasma membrane, of the mouse kidney. It is a metalloendopeptidase that contains 1 mol of zinc and 3 mol of calcium per mol of the 85,000-Mr subunit. The enzyme is isolated, and active, as a tetramer. The behaviour of the enzyme on SDS/polyacrylamide gels in the presence and absence of beta-mercaptoethanol indicates that the subunits are of the same Mr (approx. 85,000) and held together by intersubunit S--S bridges. Eight S-carboxymethyl-L-cysteine residues were detected after reduction of the enzyme with beta-mercaptoethanol and carboxymethylation with iodoacetate. The enzyme is a glycoprotein and contains approx. 18% carbohydrate. Most of the carbohydrate is removed by endoglycosidase F, indicating that the sugar residues are N-linked. The isoelectric point of the enzyme is between pH 4 and 5, and the purified protein yields a pattern of evenly spaced bands in this range on isoelectric focusing. The peptide-bond specificity of the enzyme has been determined by using the oxidized B-chain of insulin as substrate. In all, 15 peptide degradation products were separated by h.p.l.c. and analysed for their amino acid content and N-terminal amino acid residue. The prevalent peptide-bond cleavages were between Gly20 and Glu21, Phe24 and Phe25 and between Phe25 and Tyr26. Other sites of cleavage were Leu6-Cysteic acid7, Ala14-Leu15, His10-Leu11, Leu17-Val18, Gly8-Ser9, Leu15-Tyr16, His5-Leu6. These results indicate that meprin has a preference for peptide bonds that are flanked by hydrophobic or neutral amino acid residues, but hydrolysis is not limited to these bonds. The ability of meprin to hydrolyse peptide bonds between small neutral and negatively charged amino acid residues distinguishes it from several other metalloendopeptidases.

Amino Acids↗
PubMed1985

Deficiency of a mouse kidney metalloendopeptidase activity: immunological demonstration of an altered gene product.

Meprin, an 85,000 molecular weight metalloendopeptidase is a major component of the kidney brush border membrane in mice. Some inbred mouse strains exhibit low levels of meprin activity. These strains were characterized by little, if any, protein in brush border preparations corresponding to the native enzyme. However, material exhibiting partial identity to meprin was identified by Ouchterlony immunodiffusion. Immunoblots of brush border proteins confirmed that this immunoreactive material was present but of higher molecular weight than the native enzyme. The implication of these data is that the structural gene for meprin is expressed, albeit incorrectly, in the low-meprin strains.

Amino Acids, Sulfur↗
PubMed1984

Glutathione disulfide inactivates, destabilizes, and enhances proteolytic susceptibility of fructose-1,6-bisphosphate aldolase.

Disulfides (glutathione disulfide, cystine, cystamine) caused a first-order inactivation of rabbit-muscle fructose-1,6-bisphosphate aldolase at pH values of 7.4 and above. Inactivation by glutathione disulfide was partially reversed by reducing agents, but the enzyme became irreversibly inactivated with time. The disulfide-inactivated aldolase had a lower transition temperature and enthalpy of denaturation than the native enzyme. In addition, the disulfide-inactivated enzyme was extensively degraded by proteinases, whereas the native enzyme was resistant. Mixed disulfides were formed; a maximum ratio of 4-5 mol of glutathione/mol of the aldolase tetramer was found. The number of titratable--SH groups on aldolase decreased by 16 (out of 32 total on the control enzyme) after inactivation by glutathione disulfide, indicating that other oxidation reactions in addition to those resulting in mixed disulfides occurred. The substrate, fructose 1,6-bisphosphate, prevented inactivation of aldolase by glutathione disulfide, the formation of glutathione-enzyme mixed disulfides, thermodynamic destabilization of the enzyme, and a decrease of--SH groups on the enzyme. These data indicate that covalent modification of aldolase by biological disulfides is important in modulating enzyme stability and vulnerability to proteinases as well as enzyme activity and that the substrate protects against modification by disulfides.

Animals↗
PubMed1984

Inactivation of fructose-1,6-bisphosphate aldolase by cathepsin L. Stimulation by ATP.

Cathepsin L was capable of destroying rabbit muscle aldolase (D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase, EC 4.1.2.13) activity towards the substrate fructose 1,6-bisphosphate. The rate of loss of activity towards this substrate was stimulated (approx. 2-fold) by physiological concentrations of ATP and to a lesser degree by GTP, CTP, UTP, ADP and cyclic AMP, while PPi and Pi decreased the rate of inactivation. Other proteinases (cathepsin B, cathepsin D, trypsin and chymotrypsin) also decreased aldolase activity toward fructose 1,6-bisphosphate more rapidly in the presence of ATP and more slowly in the presence of Pi. Cathepsin L, at higher concentrations, was capable of inactivating aldolase activity towards fructose 1-phosphate and extensively degrading the enzyme; these reactions were not affected by ATP and Pi. The thermostability of aldolase was also unaffected by these ligands. ATP and Pi had no effect on the rates of hydrolysis of other proteins (hemoglobin, bovine serum albumin, casein and azocasein) by cathepsin L. These data indicate that the effects of ATP and Pi are due to interactions of these ligands with aldolase that make the enzyme more vulnerable to limited but not extensive proteolysis; these ligands do not directly affect cathepsin L activity.

Adenosine Triphosphate↗
PubMed1983

Changes in proteinase and peptidase activities during reticulocyte maturation.

The ability of rabbit reticulocytes to degrade puromycin-peptides and aminoethylcysteine-induced aberrant polypeptides decreased during cellular maturation. Cell-free studies indicate that the fall in proteolytic activity is not a consequence of accumulation of proteinase inhibitors or the conversion of all of the abnormal protein into undegradable forms. A decrease in peptidase activity using seven dipeptides and one tripeptide as substrates was also found to accompany reticulocyte maturation. Addition of the aminopeptidase B inhibitor bestatin to reticulocyte extracts did not inhibit the conversion of acid-precipitable puromycin-peptides to acid-soluble products; bestatin did induce the accumulation of very low molecular weight material (possibly di- or tripeptides) within the acid soluble fraction.

Animals↗