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Biomedical subjects

P Delaney

Publications and source records attributed to P Delaney.

At least 19 recordsLinked to original sources
PubMed1996

Liver function and morphology after resuscitation from severe hemorrhagic shock with hemoglobin solutions or autologous blood.

OBJECTIVE: To test the effects of three hemoglobin solutions on liver function and hepatic morphology after resuscitation from severe hemorrhagic shock. DESIGN: Prospective study. SETTING: Laboratory. SUBJECTS: Thirty-three beagle dogs. INTERVENTION: Hemorrhagic shock was induced in anesthetized dogs by removal of blood at a rate of 2 mL/kg/min until systolic blood pressure (BP) reached 50 mm Hg. BP was maintained at this level 2 hrs by further withdrawing 5 to 10 mL aliquots whenever BP increased > 50 mm Hg. Resuscitation was then initiated with autologous whole blood (n = 7), 4% pyridoxalated-hemoglobin-polyoxyethylene conjugate (4% PHP [n = 6]), 8% pyridoxalated-hemoglobin-polyoxyethylene conjugate (8% PHP [n = 9], or 8% stroma-free hemoglobin (n = 7). Four dogs were managed identically but were not resuscitated. Gross necropsy and histologic examination of the liver were performed on all dogs after 7 days, or earlier if death occurred. MEASUREMENTS AND MAIN RESULTS: In vitro interferences of PHP and stroma-free hemoglobin with liver function tests were determined and recommendations for interpretation of results from blood samples containing PHP and stroma-free hemoglobin were made. Blood was collected before, during, and after resuscitation from hemorrhagic shock. The dogs were then awakened and survivors were monitored daily with blood sampling until they were killed and necropsy was performed. After 7 days, the survival rate following hemorrhagic shock was 100% for whole blood and 4% PHP, 86% for stroma-free hemoglobin, and 33% for 8% PHP. Of the resuscitated dogs not surviving 7 days, all but one died within 27 hrs from coagulopathy. All dogs not resuscitated died within 1.75 hrs after 2 hrs of shock. Bilirubin, alkaline phosphatase, and lactic dehydrogenase concentrations could not be measured due to interferences of stroma-free hemoglobin and PHP. Aspartate (AST) and alanine (ALT) aminotransferase concentrations could be measured after dilution to overcome the interferences. Significant increases in AST and ALT values in all groups 24 hrs after resuscitation were attributed to hypoxic hepatocellular damage associated with the severity of the shock model rather than to the resuscitation fluid. Liver histology showed no changes attributed to toxic damage of hepatocytes in dogs resuscitated with stroma-free hemoglobin or PHP. However, changes, were less severe in dogs resuscitated with 4% PHP than in other groups. CONCLUSION: Morphologic studies at necropsy and liver function tests in dogs receiving hemoglobin solutions, compared with autologous blood, support the conclusion that the PHP and stroma-free hemoglobin solutions tested did not produce hepatic toxicity when used as resuscitation fluids in this model of severe shock.

Acute Disease↗
PubMed1994

The interleukin-1-stimulated protein kinase that phosphorylates heat shock protein hsp27 is activated by MAP kinase.

In KB cells, interleukin-1 (IL-1), epidermal growth factor and phorbol ester transiently activated both MAP kinase and a serine kinase which phosphorylated the heat shock protein hsp27. Extracts made from IL-1-stimulated KB cells phosphorylated recombinant hsp27, in vitro, on serine residues 78 and 82 which are contained within Arg-X-X-Ser motifs similar to those phosphorylated by the ribosomal protein S6 kinases. Upon size exclusion chromatography, however, hsp27 kinase eluted as a single peak of activity at 50-60 kDa, clearly separated from ribosomal protein S6 kinases. Treatment of partially purified hsp27 kinase with protein phosphatase-2a reduced its activity by 80%. De-phosphorylated hsp27 kinase could be approximately 50% reactivated by a factor present in IL-1-treated cell extracts in the presence of ATP. This factor co-eluted with MAP kinase after partial purification by DEAE-cellulose, phenyl Sepharose, and size exclusion chromatography. Purified sea star p44mpk and recombinant ERK2 MAP kinases were also capable of re-activating hsp27 kinase to a similar extent. These data suggest that hsp27 kinase is downstream from, and probably a direct target of MAP kinase.

Amino Acid Sequence↗
PubMed1994

Mutations of Ki-ras and p53 genes in colorectal cancer and their prognostic significance.

The series of genetic changes leading to malignancy in colorectal cancer is well reported. This includes mutational activation of the proto-oncogene Ki-ras and mutation/deletion of the p53 tumour suppressor gene. The frequency of these mutations was investigated in a panel of 52 colorectal cancer patients using a combination of immunocytochemistry and non-radioactive, digoxigenin-labelled in situ hybridisation. Sixty two per cent (32 of 52) of the study population were positive for p53 overexpression and 36% (19 of 52) positive for Ki-ras mutation. Twenty seven per cent (14 of 52) of the patients expressed both mutations. Mutation of either the p53 or the Ki-ras gene did not correlate with Dukes's stage, tumour differentiation or 5 year survival rate of the patients. Most of the rectal carcinoma specimens (11 of 15) showed p53 over-expression but the significance of this was not supported statistically. Thus detection of molecular changes is becoming more amenable to incorporation into routine histological carcinoma assessment because of the advent of non-radioactive labelling in in situ hybridisation and antibodies suitable for paraffin wax embedded specimens. The significance of these mutations in disease prognosis, however, remains questionable.

Colonic Neoplasms↗
PubMed1988

Expression of ventricular-type myosin light chain messenger RNA in spontaneously hypertensive rat atria.

Using cloned DNA probes specific for two isoforms of cardiac myosin light chains (MLCs), nonphosphorylatable MLC1 and phosphorylatable, regulatory MLC2, we have observed that the MLC1 messenger RNA of ventricular type does not appear in detectable amounts in atrial cells of either normotensive Wistar-Kyoto rat strain (WKY) or spontaneously hypertensive rat strain (SHR). The messenger RNA of regulatory isoform of ventricular MLC2, on the other hand, is found in threefold excess in atria of SHR relative to that of age-matched WKY. The increased level of MLC2 messenger RNA is present even in 6-week-old SHR atria where there is no established overloading of the heart. Thus, it appears that the increased expression of the regulatory MLC2 gene in SHR atrial cells is a predetermined event, which, most likely, participates in functional adaptation of the myocardium in response to pressure overload and subsequent hypertrophy.

Animals↗
PubMed1986

Heart myosin light chain 2 gene. Nucleotide sequence of full length cDNA and expression in normal and hypertensive rat.

We have isolated and characterized a cDNA recombinant plasmid (pRLC429) specific for the rat heart myosin light chain 2 (MLC2). The cDNA insert consists of 446 base pairs, including a 72-base pair segment of the 3'-untranslated region. Additional 5'-sequence, not present in plasmid pRLC429, was obtained by primer extension of the cDNA. The extended cDNA sequence combined with the plasmid pRLC429 sequence provided the codon information for the entire MLC2 polypeptide and partial sequences for the 3'- and 5'-noncoding regions of MLC2 mRNA. The predicted amino acid sequence for rat heart MLC2 showed a high homology with the sequences available for the chicken (83%) and human heart (80%) MLC2s. However, the homology between rat heart MLC2 and its counterpart in rat skeletal muscle is relatively low (67%). On the basis of the nuclease S1 protection assay with uniformly labeled single-stranded pRLC429 DNA, subcloned into M13mp18 phage vector, we conclude that the rat atrial muscle also contains MLC2 of the ventricular type. In an attempt to ascertain whether structural variants of MLC2 are expressed in hypertrophic heart muscle, we examined the RNAs from spontaneously hypertensive rat where there is a natural progression of hypertrophy associated with an increase in blood pressure. The RNA isolated from 7-, 13-, and 18-week-old spontaneously hypertensive rat hearts protected the same length DNA against S1 nuclease as was observed with RNAs from the age-matched normal rat hearts, suggesting that there is a single MLC2 gene transcript expressed in both the normal and hypertrophic heart muscle cells.

Amino Acid Sequence↗
PubMed1986

Temporary workers in Canada: a multifaceted program.

"This article highlights important developments in the character of temporary worker flows to Canada between 1973 and 1985 through the use of unpublished data and new measures for analyzing this data. The number of employment authorizations are converted to person years to indicate the overall labor market impact of temporary worker flows and this measure is employed in an analysis of unpublished data from Employment and Immigration Canada. The analysis reveals that a significant and growing proportion of employment authorizations are exempted from governmental procedures which link the admission of temporary workers to the Canadian labor market." Reasons for these exemptions and policy implications are discussed

Americas↗
PubMed1985

Increased levels of myosin mRNAs in spontaneously hypertensive rat heart.

RNAs isolated from normal and spontaneously hypertensive (SHR) rat heart tissues were examined by direct hybridization assay using cloned DNA probes containing chicken cardiac myosin light chain and heavy chain specific cDNA sequences. In 7 weeks old SHR heart, the level of mRNA hybridizable to these probes is the same as in normal rat heart. However, at 18 weeks of age, when hypertrophy in SHR is well established as a consequence of age-related increase in blood pressure and cardiac mass, there is an increase in SHR mRNA levels consistent with the increase in the corresponding proteins. Thus, the increase in mRNAs for major myofibrillar proteins and the onset of hypertrophic state in SHR appear to occur simultaneously.

Age Factors↗
PubMed1983

Gouty neuropathy.

A patient with gout had a peripheral neuropathy that improved with the lowering of the serum uric acid level. He had a relapse when hyperuricemia recurred, suggesting that the hyperuricemia of gout may produce a treatable form of peripheral neuropathy.

Gout↗
PubMed1983

Solitary metastasis to the medulla oblongata.

Of 40 reported cases of solitary brain stem metastasis, only two patients had medullary lesions. We have presented a third case, suggesting that this infrequent occurrence may be due to the mid-brain and pons having a more abundant blood supply, with increased potential for metastatic deposits, and being larger targets for metastases than the medulla.

Adenocarcinoma↗