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Biomedical subjects

J Salisbury

Publications and source records attributed to J Salisbury.

At least 19 recordsLinked to original sources
PubMed2006

Microscopic polyarteritis presenting with skin necrosis in a patient with sickle-cell disease.

A 20-year-old Caribbean woman with sickle cell anaemia was admitted with a 4-day history of fever and a painful swollen right ankle. She rapidly developed skin necrosis. The differential diagnosis is discussed. This case illustrates the difficulty in identifying the cause of cutaneous necrosis in an acutely ill patient. In our patient, histopathology implicated a vasculitic process, which was subsequently identified as a manifestation of microscopic polyarteritis.

Adult↗
PubMed2005

PNP with Waldenström's macroglobulinaemia.

We describe a 65-year-old Caucasian man with Waldenstrom's macroglobulinaemia who developed paraneoplastic pemphigus (PNP) 3 years after his haematological diagnosis. This is a very rare malignancy that is associated with PNP. The evolution of PNP in this patient appears to exhibit the postulated immunological phenomenon of epitope spreading.

Aged↗
PubMed2003

Epstein-Barr virus-related post-transplant lymphoproliferative disorder with t(9;14)(p11-12;q32).

The immunoglobulin heavy chain gene locus on 14q32 is known to be involved in translocations that are associated with B-lymphoproliferative disorders, typically Burkitt lymphoma and B-cell acute lymphoblastic leukemia. Several cytogenetic abnormalities have been described in post-transplant lymphoproliferatve disease (PTLD), some of which include this locus. To our knowledge, we report the first case of translocation t(9;14)(p11-12;q32) in a PTLD that developed after orthoptic liver transplantation.

Biliary Atresia↗
PubMed2001

Functional and compositional studies of arteries stored in University of Wisconsin solution compared with Krebs-Bülbring buffer.

Endothelium-dependent and -independent vasorelaxation in ring segments of rabbit thoracic aorta is reduced and noradrenaline-induced vasoconstriction unaltered after prolonged storage in University of Wisconsin solution (UW) compared to arteries stored in extracellular-type solutions such as Krebs-Bülbring buffer (KBB). The aims of the present study were to determine whether angiotensin-II-induced vasoconstriction, alterations in myosin light chains, protein synthetic capacity, and subcellular structures are altered after 8 days of UW storage at 4 degrees C. The present study showed reduced contractility to angiotensin II, following 8 days of cold storage in UW, that was not reversed in the presence of a nitric oxide synthase inhibitor, N(G)-nitro-l-arginine methyl ester (100 microM). Measurements of contractile protein ratios in the same tissues after cold storage in UW or KBB did not show any significant alterations in smooth muscle myosin light chains or protein synthetic capacity (reflected by total RNA). It is concluded that reductions in vasoconstriction in UW-stored tissue are unlikely to be due to increased release of nitric oxide nor reduced availability of myosin light chains for phosphorylation and vasoconstriction.

Angiotensin II↗
PubMed2001

Characterisation of molecular alterations in microdissected archival gliomas.

Classification of gliomas according to their molecular characteristics may be important in future histopathological diagnosis. However, gliomas frequently display heterogeneity at the histological, biological and molecular level. In this study of archival diagnostic gliomas, precision microdissection was used to enrich samples in the most malignant cells or to investigate intratumoural histological heterogeneity. Analysis of tumour samples microdissected from the most aggressive regions, representative of the histopathological diagnosis, revealed PTEN mutations in 4/14 anaplastic astrocytomas, 4/13 glioblastomas and 1 gliosarcoma, but not in 19 low-grade gliomas. Using a novel PCR procedure and direct sequence analysis of the entire coding sequence, TP53 mutations were detected in 1/3 pilocytic astrocytomas, 3/13 astrocytomas, 4/14 anaplastic astrocytomas, 5/13 glioblastomas and 1 gliosarcoma. All but one of the tumours with TP53 mutation showed p53 immunopositivity, but 5 low-grade and 10 high-grade gliomas had p53 protein nuclear accumulation in the absence of detectable mutation. p53 status was unrelated to p21 expression. Neither PTEN nor TP53 mutations influenced the proliferative index or microvessel density of high-grade astrocytomas. Unusual findings include: TP53 mutation in a juvenile pilocytic astrocytoma; TP53 and PTEN mutations in a de novo glioblastoma, a gliosarcoma with identical mutations in gliomatous and sarcomatous components, and an infratentorial anaplastic astrocytoma with an earlier supratentorial grade II astrocytoma bearing the same TP53 mutation but not the PTEN mutation or loss of heterozygosity (LOH) of 10q23. Similarly, the transition to high-grade histology was associated with acquisition of PTEN mutations and 10q23.3 LOH in two de novo high-grade tumours with regions of low-grade histology.

Adolescent↗
PubMed2000

Comparative effects of acute ethanol dosage on liver and muscle protein metabolism.

Experiments were performed to address some outstanding issues and investigate possible mechanisms relating to the acute comparative effects of ethanol on liver and skeletal muscle protein metabolism. Ethanol (EtOH)-treated rats were injected (i.p.) with a bolus of EtOH (75 mmol/kg body weight) and sacrificed at 20 min, 1-, 2.5-, 6-, and 24-hr time points. Control rats were injected with saline (Con-Sal; 0.15 mmol/L NaCl). All 24-hr ethanol-treated animals were compared with saline-injected rats subjected to controlled feeding (i.e. pair-fed controls for 24 hr EtOH). At 24 hr, there was no measurable alcohol in the plasma, whereas high levels were seen from 20 min to 6 hr (up to 448 mg/dL). Plasma levels of albumin were reduced at initial time points, and activities of aspartate aminotransferase increased, but there was no histological evidence of overt tissue damage either in muscle or liver. Hepatic protein and RNA contents and indices of tissue (C(s) and k(s)) and whole-body (V(s)) protein synthesis were significantly increased in ethanol-dosed rats relative to saline-injected pair-fed controls at 24 hr. In the liver, four of the seven cytoplasmic proteases investigated (alanyl-, arginyl-, and pyroglutamyl-aminopeptidases and proline-endopeptidase) showed significant increases in activity at 24 hr relative to pair-fed controls; four of the six lysosomal proteases showed significant decreases in activity (dipeptidyl-aminopeptidase II and cathepsins B, L, and H). In skeletal muscle, k(s) fell progressively between 1 and 24 hr (-25 to -69%; P < 0.001), but no significant changes in skeletal muscle protease activities were seen at 24 hr. At 24 hr after ethanol dosage in vivo, there were no significant increases in protein carbonyl content in liver or skeletal muscle compared to pair-fed controls (muscle levels actually decreased slightly). However, using either rat or human tissue, both liver and muscle carbonyl increased in vitro in response to superoxide and hydroxyl radicals: muscle was more susceptible to carbonyl formation than liver and both tissues were more sensitive to hydroxyl compared to superoxide radicals. These results show divergent effects of acute ethanol treatment on liver and skeletal muscle protein metabolism, which may not be linked to in vivo free radical-mediated protein damage (as indicated by carbonyl formation), at least in the short term.

Acute-Phase Reaction↗
PubMed2000

Global water resources: vulnerability from climate change and population growth.

The future adequacy of freshwater resources is difficult to assess, owing to a complex and rapidly changing geography of water supply and use. Numerical experiments combining climate model outputs, water budgets, and socioeconomic information along digitized river networks demonstrate that (i) a large proportion of the world's population is currently experiencing water stress and (ii) rising water demands greatly outweigh greenhouse warming in defining the state of global water systems to 2025. Consideration of direct human impacts on global water supply remains a poorly articulated but potentially important facet of the larger global change question.

Agriculture↗
PubMed2000

Novel polymerase chain reaction approach for full-coding p53 mutation detection in microdissected archival tumors.

Evidence suggests that up to 25% of p53 mutations are outside of exons 5-8 and that insertions, deletions, and polymorphic sites in the p53 gene may play a significant role in the process of carcinogenesis. A novel polymerase chain reaction (PCR) approach for the analysis of the entire p53 coding and splice site regions from microdissected, formalin-fixed, paraffin-embedded tumor tissues has been developed which allows multiple genetic analyses to be performed from one primary amplification reaction. The method was initially evaluated using well-characterized cell lines. In addition to confirming the published p53 mutations for HT29, Molt 4, A431, and HN5, a 16 base pair (bp) duplication within intron 3 was detected in both the A431 and HT29 cell lines. Analysis of archival samples of ovarian cancer identified the same 16-bp duplication and coding region variations. In all samples, using GenBank submission U94788 as a reference, a C-insertion was detected at nucleotide positions 11818 and 11874 within intron 2. At nucleotide position 14168, within intron 7, a T-to-G base change was found. This novel PCR approach has the potential to reduce the amount of clinical material required by up to 95%, thus facilitating retrospective studies on archival tumor collections. Furthermore, a wider analysis of the p53 gene, including splice sites and intronic regions, may yield additional information regarding cancer predisposition, response to therapy, and progression.

Base Sequence↗
PubMed1999

Mutation in the PTEN/MMAC1 gene in archival low grade and high grade gliomas.

The PTEN gene, located on 10q23.3, has recently been described as a candidate tumour suppressor gene that may be important in the development of advanced cancers, including gliomas. We have investigated mutation in the PTEN gene by direct sequence analysis of PCR products amplified from samples microdissected from 19 low grade (WHO Grade I and II) and 27 high grade (WHO grade III and IV) archival, formalin-fixed, paraffin-embedded gliomas. Eleven genetic variants in ten tumours have been identified. Eight of these are DNA sequence changes that could affect the encoded protein and were present in 0/2 pilocytic astrocytomas, 0/2 oligoastrocytomas, 0/1 oligodendroglioma, 0/14 astrocytomas, 3/13 (23%) anaplastic astrocytomas and 5/14 (36%) glioblastomas. PTEN mutations were found exclusively in high grade gliomas; this finding was statistically significant. Only two of the PTEN genetic variants have been reported in other studies; two of the genetic changes are in codons in which mutations have not been found previously. The results of this study indicate that mutation in the PTEN gene is present only in histologically more aggressive gliomas, may be associated with the transition from low histological grade to anaplasia, but is absent from the majority of high grade gliomas.

Adolescent↗
PubMed1999

The joint vulval clinic: a review of the first three years.

This aim of this study was to undertake a retrospective analysis of the notes of all new patients who attended the joint vulval clinic between 1994 and 1997. One hundred and forty-five patients were seen, and data analysed for 133 (92%). The study identified the range of diagnoses seen; treatment modalities undertaken; and enabled comparisons to be made between our findings and those of other workers.

Journal Article↗
PubMed1999

Paradoxical cholinergic and purinergic vascular reactivity of rabbit thoracic aorta cold-stored in University of Wisconsin solution.

Endothelial dysfunction has been reported in donor blood vessels destined for organ transplantation following cold-storage preservation with University of Wisconsin solution (UW). This was investigated in the present work. Segments of rabbit thoracic aorta were mounted on isometric fine-wire myographs at 37 degrees C and gassed with 95% O2/5% CO2. Concentration-dependent vasodilatations to acetylcholine and adenosine-5'-triphosphate (ATP) were obtained in freshly-harvested rabbit aortic rings, with and without the endothelium, and after 8 days of cold-storage, at 4 degrees C, in either UW, Krebs-Bülbring buffer (KBB) or saline. The action of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) (100 microM) was evaluated upon the concentration-response curves to determine whether nitric oxide (NO) exerted any modulatory actions. Endothelium-dependent, NO-mediated responses to acetylcholine were unaltered after eight days of storage in UW, reduced after storage in KBB and absent after removal of the vascular endothelium, saline storage or after testing in the presence of L-NAME, suggesting improved NO-mediated endothelial function with the use of UW. Structural preservation was also confirmed using scanning electron microscopy. In contrast, endothelium-dependent responses to ATP were unchanged after eight days of storage in KBB but were reduced after storage in UW and saline, suggesting purinergic (ATP) endothelial dysfunction after storage in UW. L-NAME markedly reduced vasodilatation to ATP in freshly harvested rings and after eight days of storage in KBB. This reduction was statistically significant (P < 0.05, Student's two tailed, unpaired t-test) at -log (M) ATP concentrations of 5.5, 5.0, 4.5, 4.0 and 3.5. NO-dependent vasodilatation to ATP was not attenuated by L-NAME in UW-stored rings. Eight days' UW-storage of rabbit thoracic aortic rings appeared to have differential and paradoxical effects upon NO-dependent vasodilatation to acetylcholine and ATP. Morphological observations using electron microscopy suggested that UW preserved the vascular endothelium and this was verified by retained vascular reactivity of endothelium-dependent vasodilatations to acetylcholine. UW-storage however, significantly reduced endothelium-dependent relaxation to ATP thereby suggesting that P2Y-purinoceptors, which are located on the vascular endothelium, may be more susceptible to biodegradation than cholinergic receptors and may be responsible for endothelial dysfunction following transplantation.

Acetylcholine↗
PubMed1998

Cutaneous Rosai-Dorfman disease.

We report a patient with purely cutaneous Rosai-Dorfman disease (RDD) who presented with a solitary, asymptomatic plaque on the back of her left thigh, with characteristic, large histiocytoid cells exhibiting emperipolesis histologically. Cutaneous lesions occur in 27% of patients with lymph node involvement in RDD however purely cutaneous disease has only been reported on 18 previous occasions. The aetiology is unknown, although it is though to be a reactive disorder rather than neoplastic, possibly an immunological response to an infectious agent.

Adult↗
PubMed1997

Cold-storage of rabbit thoracic aorta in University of Wisconsin solution reduces endothelium-independent vasodilation.

Optimum preservation conditions for storage of donor livers and blood vessels are essential for successful transplantation. The blood vessels are used as vascular conduits to facilitate anastomosis of the liver to the recipient's systemic vasculature. Failure of some transplants has been ascribed to thrombosis of these vascular conduits possibly because of alterations in vascular reactivity owing to inadequate storage techniques. To restrict data variability previously associated with studies using a heterogeneous sample of vessels from man, this study investigated changes in vascular reactivity in segments of rabbit thoracic aorta from male, age-matched, New Zealand White rabbits stored at 4 degrees C in either University of Wisconsin solution (UW; Du Pont Pharmaceuticals, UK) or Krebs-Bülbring buffer (KB). Percent vasodilation to acetylcholine remained significantly greater in UW than in KB at -log (M) concentrations of 7.0 (UW = 47.05 +/- 4.26 compared with KB = 13.20 +/- 7.20%; P < 0.001), 6.5 (UW = 66.82 +/- 4.83 compared with KB = 26.60 +/- 9.48%; P < 0.01), and 6.0 (UW = 83.68 +/- 5.26 compared with KB = 31.20 +/- 9.83%; P < 0.001). This was not significantly different to relaxation in unstored arteries and suggested improved endothelial function and structure, confirmed by electron microscopy. Percent vasodilation to sodium nitroprusside was significantly lower in UW than in unstored (D0) arteries at -log (M) concentrations of 7.5 (D0 = 28.27 +/- 4.02 compared with UW = 15.21 +/- 1.82%; P < 0.01), 7.3 (D0 = 52.58 +/- 5.05 compared with UW = 29.23 +/- 1.94%; P < 0.01), 7.0 (D0 = 69.70 +/- 4.85 compared with UW = 49.72 +/- 2.49%; P < 0.05), and 6.4 (D0 = 93.16 +/- 2.93 compared with UW = 71.29 +/- 5.20%; P < 0.05). Percent vasodilation was also lower in UW- compared with KB-stored arteries at -log (M) sodium nitroprusside concentrations of 7.0 (UW = 49.72 +/- 2.49 compared with KB = 64.11 +/- 5.03%; P < 0.05) and 6.4 (UW = 71.29 +/- 5.20 compared with KB = 96.91 +/- 5.96; P < 0.05). Electron microscopy confirmed that this was not a result of degradation of smooth muscle structure. The nitric oxide synthase inhibitor L-NG-nitro-L-arginine methyl ester (100 microM) did not significantly modulate sodium nitroprusside-induced vasodilation in unstored arteries, when endothelial function was maximum, or in UW-stored arteries, suggesting that the reduced responses in UW-stored arteries were not because of increased synthesis of nitric oxide. This reduced relaxation to sodium nitroprusside was therefore nitric oxide-independent and not a result of competition between sodium nitroprusside and endothelial 'nitric oxide donation' for cGMP. In summary, cold-storage preservation with UW reduced endothelium-independent vascular relaxation by mechanisms other than competition with NO; this requires further evaluation.

Acetylcholine↗
PubMed1997

Studies on the time-course of ethanol's acute effects on skeletal muscle protein synthesis: comparison with acute changes in proteolytic activity.

A study of the effects of ethanol on skeletal muscle protein synthesis and protease activities was carried out in young male Wistar rats (150 g) for up to 24 hr after a single intraperitoneal dose of 75 mmol of ethanol/kg of body weight. At 20 min, the mean blood ethanol levels were 448 mg/dl. This level dropped steadily to zero through the following 24 hr. Compared with pair-fed controls, significant reductions in total protein, RNA, and DNA contents were seen only after 24 hr in all skeletal muscles studied: changes were more marked in the muscles containing large proportions of type II fibers. In plantaris muscle, the fractional rate of protein synthesis (ks, %/day) did not fall 20 min after dosage but was reduced after 1 hr by 23% (p < 0.001), and by 63% after 24 hr, compared with control saline-injected rats (p < 0.001). This effect was independent of dietary intake because, compared with the pair-fed group, the 24-hr ethanol-treated rats still showed a 52% decrease in fractional rates of protein synthesis (p < 0.001). Smaller reductions in ks were seen in soleus muscles in response to ethanol at 24 hr (-39%, p < 0.001). The activities of a variety of lysosomal and nonlysosomal proteases in plantaris muscle of 24-hr treated rats were not significantly affected by ethanol. Only alanyl- and tripeptidyl-aminopeptidase activities were reduced significantly (26%, p < 0.05 and 39%, p < 0.01, respectively). These results suggest that the muscle compositional changes seen over acute periods of ethanol toxicity are predominantly associated with impaired synthesis of protein and that the contribution of cellular proteolytic systems may be minimal. The effects of ethanol on skeletal muscle protein metabolism are greater in muscles containing a predominance of type II fibers than in those containing mainly type I fibers. Ethanol's effects on muscle may be influenced by hormonal changes after 24 hr, because protein synthesis is still compromised and free plasma T3 and corticosterone are altered at this time-point.

Alcoholism↗