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Biomedical subjects

M Tyler

Publications and source records attributed to M Tyler.

At least 19 recordsLinked to original sources
PubMed2001

Impact of Celsior solution on hepatocellular, reperfusion and endothelial cell injury after liver transplantation.

BACKGROUND: Initially, preservation solutions were developed to maintain cell function of the transplanted organs. However, recently developed preservation solutions also contain a variety of substances to reduce the reperfusion injury. AIM: To study the effect of three different preservation solutions on the liver cell injury, endothelial cell function and reperfusion injury after liver transplantation. MATERIAL AND METHODS: Large White X Landrace pigs of either sex were subjected to orthotopic liver transplantation. Donor livers were flushed and stored in University of Wisconsin Solution, Eurocollins Solution or Celsior Solution for 3 hours. Blood samples were taken at various times post transplantation for assessment of aspartate aminotransferase, hyaluronic acid, malondialdehyde and Vitamin A levels. RESULTS: Serum aspartate aminotransferase levels were lower in the livers preserved in the Wisconsin solution. Plasma malondialdehyde levels were lower and serum Vitamin A levels were higher in the livers preserved in Celsior solution. Serum hyaluronic acid levels increased after liver transplantation but were similar with all three solutions. CONCLUSIONS: There was less hepato-cellular injury in the livers preserved in Wisconsin solution and less reperfusion injury with the Celsior solution. The endothelial cell injury was similar with all three solutions.

Animals↗
PubMed2001

Effect of early arterialization of the porcine liver allograft on reperfusion injury, hepatocellular injury, and endothelial cell dysfunction.

The conventional technique of liver transplantation involves the initial perfusion of the graft with portal blood. However, recent evidence suggests that initial arterialization of the graft may be better. The aim of this study is to evaluate the timing of arterialization on reperfusion injury, hepatocellular injury, and endothelial cell function after liver transplantation. Large white X Landrace pigs (n = 24) were subjected to orthotopic liver transplantation. The animals were randomly assigned to 4 groups, ranging from late arterialization (60 minutes after portal reperfusion) to early rearterialization (20 minutes before portal reperfusion). Aspartate aminotransferase levels continued to increase 4 hours posttransplantation in group 1 (late arterialization), but remained stable after 1 hour posttransplantation in group 4 (early rearterialization). Levels of malondialdehyde doubled in all groups after portal reperfusion with the exception of group 4, in which the liver received arterial blood before portal reperfusion. Vitamin A levels decreased in all groups after revascularization, but the decrease was more pronounced and prolonged in groups 1 and 2 (late arterialization) compared with groups 3 and 4 (early rearterialization). Hyaluronic acid levels continued to increase in all groups until 1 hour posttransplantation except in group 4, in which the level decreased from 20 minutes posttransplantation. Results of this study show that early rearterialization is associated with less hepatocellular damage, less reperfusion injury, and improved liver endothelial cell function. In conclusion, our results indicate that early rearterialization of the graft is beneficial to the transplanted liver.

Animals↗
PubMed2000

Assessment of the value of the vertebral heart scale in the radiographic diagnosis of cardiac disease in dogs.

In order to assess the influence of the vertebral heart scale (VHS) on the accuracy of the radiographic diagnosis of cardiac disease, thoracic radiographs of 50 dogs with proven cardiac disease, 26 with other thoracic diseases, and 50 with no clinical signs of cardiovascular or respiratory disease were mixed and examined by three independent, blinded observers chosen to represent a range of radiographic abilities. They first examined all the radiographs without making measurements of VHS and made a diagnosis. They then re-examined the radiographs, and measured VHS on both lateral and dorsoventral or ventrodorsal radiographs before again recording a diagnosis without reference to their original diagnoses. For all the observers, the dogs with cardiac disease had a higher mean VHS than the normal dogs. A VHS over 10.7 on the lateral radiograph was a moderately accurate sign of cardiac disease. The observers' accuracy of diagnosis did not change significantly as a result of using VHS as an adjunct to a subjective assessment of the radiographs.

Animals↗
PubMed1999

The changes in circulating hepatocyte growth factor after partial hepatectomy in the baboon.

There is no established model of regenerative liver resection in the baboon, and no study comparing the circulating hepatocyte growth factor (HGF) response with the DNA synthetic response after liver resection. A mean 20% partial hepatectomy (PH) was performed in 19 baboons and a sham operation comprising liver mobilisation only was performed in 20 baboons. Blood HGF levels were measured up to 5 days after either procedure, using the human HGF enzyme-linked immunosorbent assay (ELISA) kit (Otsuka, Japan). The white cell count (WCC), aspartate transaminase (AST) and bilirubin were also measured. Liver regeneration, reflected by an increase in DNA synthesis, was determined from serial liver biopsies in 23 baboons, using a tritiated thymidine assay of liver thymidine kinase (TK). Liver resection and WCC had a significant influence on circulating HGF levels. There was a linear relationship between WCC and circulating HGF levels, which was independent of PH. For a constant value of WCC, resection produced a peaking of HGF over time, with the maximal levels occurring between 2 and 3 days, compared with the linear response in HGF in sham-operated baboons. Liver damage, as reflected by AST levels, was found to have no significant influence on circulating HGF levels. The 20% PH produced a significant increase in liver TK, with maximum levels evident between 2 and 4 days. Accordingly in this baboon model of PH the increase in biologically active, circulating HGF preceded the increase in liver DNA synthesis over 5 days. This observation supports the role of HGF in hepatocyte proliferation and as an initiator of liver regeneration, and suggests that further investigation into the potential endocrine action of HGF could be studied in this established liver regenerative primate model.

Animals↗
PubMed1998

Protein identification with N and C-terminal sequence tags in proteome projects.

Genome sequences are available for increasing numbers of organisms. The proteomes (protein complement expressed by the genome) of many such organisms are being studied with two-dimensional (2D) gel electrophoresis. Here we have investigated the application of short N-terminal and C-terminal sequence tags to the identification of proteins separated on 2D gels. The theoretical N and C termini of 15, 519 proteins, representing all SWISS-PROT entries for the organisms Mycoplasma genitalium, Bacillus subtilis, Escherichia coli, Saccharomyces cerevisiae and human, were analysed. Sequence tags were found to be surprisingly specific, with N-terminal tags of four amino acid residues found to be unique for between 43% and 83% of proteins, and C-terminal tags of four amino acid residues unique for between 74% and 97% of proteins, depending on the species studied. Sequence tags of five amino acid residues were found to be even more specific. To utilise this specificity of sequence tags for protein identification, we created a world-wide web-accessible protein identification program, TagIdent (http://www.expasy.ch/www/tools.html), which matches sequence tags of up to six amino acid residues as well as estimated protein pI and mass against proteins in the SWISS-PROT database. We demonstrate the utility of this identification approach with sequence tags generated from 91 different E. coli proteins purified by 2D gel electrophoresis. Fifty-one proteins were unambiguously identified by virtue of their sequence tags and estimated pI and mass, and a further 11 proteins identified when sequence tags were combined with protein amino acid composition data. We conlcude that the TagIdent identification approach is best suited to the identification of proteins from prokaryotes whose complete genome sequences are available. The approach is less well suited to proteins from eukaryotes, as many eukaryotic proteins are not amenable to sequencing via Edman degradation, and tag protein identification cannot be unambiguous unless an organism's complete sequence is available.

Amino Acid Sequence↗
PubMed1998

'98 Escherichia coli SWISS-2DPAGE database update.

The combination of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), computer image analysis and several protein identification techniques allowed the Escherichia coli SWISS-2DPAGE database to be established. This is part of the ExPASy molecular biology server accessible through the WWW at the URL address http://www.expasy.ch/ch2d/ch2d-top.html . Here we report recent progress in the development of the E. coli SWISS-2DPAGE database. Proteins were separated with immobilized pH gradients in the first dimension and sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the second dimension. To increase the resolution of the separation and thus the number of identified proteins, a variety of wide and narrow range immobilized pH gradients were used in the first dimension. Micropreparative gels were electroblotted onto polyvinylidene difluoride membranes and spots were visualized by amido black staining. Protein identification techniques such as amino acid composition analysis, gel comparison and microsequencing were used, as well as a recently described Edman "sequence tag" approach. Some of the above identification techniques were coupled with database searching tools. Currently 231 polypeptides are identified on the E. coli SWISS-2DPAGE map: 64 have been identified by N-terminal microsequencing, 39 by amino acid composition, and 82 by sequence tag. Of 153 proteins putatively identified by gel comparison, 65 have been confirmed. Many proteins have been identified using more than one technique. Faster progress in the E. coli proteome project will now be possible with advances in biochemical methodology and with the completion of the entire E. coli genome.

Bacterial Proteins↗
PubMed1997

Candidal colonization and oral candidiasis in patients undergoing oral and pharyngeal radiation therapy.

OBJECTIVES: Radiotherapy-induced hyposalivation encourages oral candidal colonization that often leads to oral/pharyngeal candidiasis. The purpose of this study was to quantitate oral candidal colonization, assess signs, symptoms, and response to antifungal management, speciate Candida, and evaluate the influence of smoking and dentures. STUDY DESIGN: Forty-six patients undergoing radiation therapy for oral/pharyngeal squamous cell carcinoma were evaluated clinically and by Candidal cultures before, during, and after irradiation. RESULTS: All patients complained of progressive xerostomia. There was a significant increase in the prevalence of positive candidal cultures (P = < 0.0001): baseline 43%, completion of radiotherapy 62%, and follow-up timepoint 75%. Smoking and denture wearing were not statistically significant risk factors for increased candidal colonization (p = 0.085 and p = 0.420, respectively). Eight patients developed clinical candidiasis. Although five responded clinically to systemic antifungal medication, all follow-up cultures remained positive. Candida albicans was the predominant species at baseline and completion of radiation (85% and 68%, respectively). CONCLUSIONS: When salivary glands are included in the field of radiation, xerostomia occurs, causing progressive increases in oral Candida colonization. Because 17.4% developed clinical candidiasis during radiotherapy and the question of fungal resistance remains speculative, a recommendation for the prophylactic use of antifungal medication is unresolved.

Adult↗
PubMed1995

Ear reduction.

Four cases of ear reduction for congenital macrotia and ear asymmetry are presented. To minimize the visible scarring the technique of helical advancement was used. The indications for this uncommon procedure are discussed with a review of the literature. This simple technique has been effective in achieving the desired reduction, leaving the scar hidden in the eaves of the helix, and we endorse its wider use.

Adult↗
PubMed1995

Correlates of left-handedness in a large sample of schizophrenic patients.

Questionnaire data concerning hand preference from the parents of 686 schizophrenic patients were used to test predictions relevant to neurodevelopmental models of schizophrenia. In line with predictions, left-handed patients (n = 94) had a more frequent history of difficult birth, more childhood cognitive and behavioural abnormalities and more persistent auditory hallucinations than did right-handed patients.

Adolescent↗
PubMed1995

Regeneration after in situ flushing of partially hepatectomised rat livers.

The effect of various components of the transplant procedure upon the regenerative process in reduced liver grafts is not known. In this study, partially hepatectomised rat liver remnants were flushed with 5 ml of either Ringer's lactate, Euro Collins solution or University of Wisconsin solution at 4 degrees C and then 5 ml Ringer's lactate at 4 degrees C. After partial hepatectomy alone, the peak increase in thymidine kinase was measured at 24 hours (36,021 +/- 8,060 disintegrations per minute per milligram protein; the mitotic index was 25 +/- 7). In all the groups in which the remnant was flushed, peak thymidine kinase and mitotic index were measured at 48 hours. The pattern of ornithine decarboxylase activity was disorganised in all groups. Flushing of the liver remnant therefore delays the regenerative response by 24 hours. In large animals, including humans, regeneration appears to commence within the first 5 days after resection. A comparable delay doubling this time might coincide with the onset of rejection and further compromise liver function.

Animals↗
PubMed1994

The effect of administration of FK506 on delayed regeneration in flushed partially hepatectomized livers.

It has been shown previously that liver regeneration after partial hepatectomy in rats is delayed if the liver is subjected to either concurrent ischaemia, flushing with cold solution, or grafting. We have shown recently that treatment with CsA preoperatively overcomes the suppressive effect of flushing and returns the regenerative response to a normal time scale. The present study was designed to investigate whether administration of FK506 would also return the observed delayed regenerative response to normal. Long-Evans rats weighing 250-350 g were subjected to standard 68% partial hepatectomy. Group 1 had no further treatment; in group 2, the liver remnant was flushed with 10 ml cold (4 degrees C) Ringers lactate solution, and in group 3, FK506 (1 mg/kg/day) was administered by intramuscular injection for 3 days before the partial hepatectomy and flushing as in group 2; a final dose was given after completion of the procedures. Animals were killed in sets of 6 per group at 4, 24, 48, 72, and 96 hr after surgery and blood samples were taken for measurement of plasma aspartate amino-transferase. Liver biopsies were analyzed for measurement of thymidine kinase and ornithine decarboxylase activity and for counting of mitotic figures. While the highest recorded thymidine kinase activity occurred in group 1 at 24 hr, this was delayed to 48 hr in both group 2 and 3 and counts remained high up to 96 hr in group 3. Mitotic indices were only significantly elevated (compared with group 1 at 96 hr), while ornithine decarboxylase activity did not correlate with these changes being significantly lower than in groups 2 and 3 at 4 hr and in group 3 also at 24 hr. Plasma aspartate aminotransferase was also significantly higher in group 3. It is concluded that the administration of FK506 preoperatively to rats subjected to partial hepatectomy and flushing did not restore the delayed regenerative response to normal but enhanced the response (as measured by thymidine kinase but not by mitotic indices) which commenced at 48 hr and was still present at 96 hr.

Animals↗
PubMed1994

Does liver transplantation in the rat cause a regenerative response. The effect of arterialisation of the graft.

This study was conducted to determine the pattern of early regenerative response to orthotopic intact liver transplantation in the rat and to investigate whether the response differed in grafts with or without revascularisation of the arterial bed. Outbred male Long Evans (LE-LE allogeneic, non rejector) rats weighing 300-350g were subjected to orthotopic intact liver allograft using a "sleeve" anastomosis for the hepatic artery. Total warm ischaemia ranged from 19 to 34 minutes and no storage was employed. Comparison was made with a group of control rats which were subjected to 25 minutes total inflow occlusion and regeneration was measured with tissue thymidine kinase (TK) and mitotic figures. Samples were taken at 1, 2, 4, 7, 10 and 20 days post-operatively. Plasma aspartate aminotransferase (AAT) and light microscopy were used to evaluate hepatocyte necrosis. There was a brief sharp increase in TK and AAT in the first 24 hours after sham operation but no appearance of mitotic figures. A similar but more prolonged increase in TK occurred in the arterialized transplant group with the highest levels recorded on day 4. The level remained significantly elevated above pre-operative until 10 days and declined within 20 days. Mitotic figures appeared at 2 days, reached significance at 7 and 10 days and had disappeared by 20 days. The pattern of changes was accentuated in animals in which the artery was not reanastomosed and the increases in TK and AAT were still significant at 20 days. Whilst similar degrees of peri-portal cellular infiltrate occurred in both groups of rats, bile duct proliferation was most obvious in non-arterialized animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗
PubMed1993

A case for changing the way schizophrenia is conceptualised, using a questionnaire to relatives.

In view of dissatisfaction among philosophers and many doctors with the DSM III criteria for schizophrenia a new conceptualization is needed. Recent research results showing the complex influences on the development and functions of the brain suggest that the primary problem is a reduced capacity for information processing and not the more obvious symptoms of acute episodes. An analysis of a questionnaire to relatives (members of the National Schizophrenia Fellowship) has been used to illustrate how data from relatives can provide useful indicators of some of the factors such as possible metabolic abnormalities and immune system deficiencies which may contribute to this problem. It is suggested that a broad data-base is needed to study such contributory factors and point the way to forms of treatment which might make lower levels of maintenance neuroleptic medication possible.

Antipsychotic Agents↗