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Biomedical subjects

J Martin

Publications and source records attributed to J Martin.

At least 109 records · Page 6Linked to original sources
PubMed2002

The colonic response to genotoxic carcinogens in the rat: regulation by dietary fibre.

The apoptotic response to DNA damage appears to be an innate biological mechanism for protection against tumourigenesis. It is possible that agents that protect against colorectal cancer act by enhancing the apoptotic deletion of cells suffering DNA damage, with consequent removal of those with tumourigenic mutations. We examined the acute apoptotic response to genotoxic carcinogens ("AARGC") in colonic epithelium and the possibility that dietary fibres of different fermentability might regulate AARGC. To fully define the time-course and nature of AARGC in response to the carcinogen azoxymethane (AOM), a single injection of AOM (10 mg/kg) was given to rats and apoptosis monitored in the colon by light microscopy and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling staining over a 72 h period. Having defined the site and time of maximum response, two groups of eight rats were fed diets containing 10% wheat bran fibre (WB; fermentable) or 10% methylcellulose (MC; poorly fermentable) for 4 weeks. Colonic AARGC was compared by light microscopy; lumenal short chain fatty acids (SCFAs) and pH were measured as indicators of the fermentative environment. AOM-induced AARGC was maximal at 8 h and greater in distal compared with proximal colon. Apoptotic cells were situated predominantly in the lower half of the crypt, with the median at position 9 indicating involvement of daughter as well as stem cells. There was no "second wave" of apoptosis within 72 h as follows irradiation in small intestine. Distal colonic AARGC in rats fed WB was twice that in rats fed MC (P < 0.01). Compared with MC, WB significantly lowered lumenal pH and increased all SCFAs including butyrate, while proliferation did not differ between the fibres. Certainly, dietary fibres can regulate AARGC and further studies are warranted to determine if this biological effect is the way in which dietary factors regulate tumourigenesis. Lumenal generation of butyrate may enhance AARGC as butyrate is proapoptotic in vitro.

Animals↗
PubMed2002

Extramedullary myeloid cell tumours localised to the mediastinum: a rare clinicopathological entity with unique karyotypic features.

Extramedullary myeloid cell tumour (EMMT) localised to the mediastinum is a rare manifestation of acute myeloid leukaemia, forming less than 4% of all cases of EMMT. In contrast to other types of EMMT, cytogenetic characteristics of this rare entity are relatively unknown. This report describes a patient with EMMT who had evidence of superior vena cava syndrome and normal peripheral blood counts at diagnosis. The results from an initial biopsy specimen were consistent with a diagnosis of mediastinal large B cell lymphoma. A diagnosis of acute myeloid leukaemia was made three months after initial diagnosis by bone marrow examination. Review of the initial biopsy specimen showed strong positivity for myeloperoxidase, revealing that the patient had been initially misdiagnosed as having large B cell lymphoma. Cytogenetic studies revealed a near triploid and near tetraploid karyotype with structural abnormalities in 12 and three metaphases, respectively. Review of the literature showed that a near tetraploid or triploid karyotype is found in most of the reported cases of mediastinal EMMT. Thus, the presence of a near triploid/tetraploid karyotype and mediastinal EMMT may represent a specific subset of EMMT. The biological relevance of this observation is discussed.

Acute Disease↗
PubMed2002

Light symptoms following a high-dose intentional L-thyroxine ingestion treated with cholestyramine.

Adult exposure to L-thyroxine has a wide range of presentations: most adults either do not develop symptoms or only become minimally symptomatic. Appropriate treatments after exposure to L-thyroxine have yet to be established. A 26-year-old woman with a suicidal intention was witnessed to ingest approximately 50 L-thyroxine tablets, each containing 0.1 mg L-thyroxine (total dose 5 mg). Cholestyramine was administered (4 g every 8 h p.o.). Vital signs were monitored every 6 h and the hormone levels (L-thyroxine and thyroid-stimulating hormone) every 24 h. The thyroxine levels increased, and the thyroid-stimulating hormone levels decreased, with a normalization of the L-thyroxine level on postingestion day 6. Hypertension, dysrhythmias, and delusions did not appear in our patient. Only distal tremor and diaphoresis appeared on day 1 after ingestion. Cholestyramine has been used in cases of iatrogenic hyperthyroidism, in patients with Graves' disease, and in patients with digoxin intoxications, with good responses in all cases and a low incidence of side effects. This case illustrates the potential utility of cholestyramine to treat L-thyroxine intoxications.

Adult↗
PubMed2002

Efficacy of acupuncture in asthma: systematic review and meta-analysis of published data from 11 randomised controlled trials.

Contradictory results from randomised controlled trials of acupuncture in asthma suggest both a beneficial and detrimental effect. The authors conducted a formal systematic review and meta-analysis of all randomised clinical trials in the published literature that have compared acupuncture at real and placebo points in asthma patients. The authors searched for trials published in the period 1970-2000. Trials had to measure at least one of the following objective outcomes: peak expiratory flow rate, forced expiratory volume in one second (FEV1) and forced vital capacity. Estimates of the standarised mean difference, between acupuncture and placebo were computed for each trial and combined to estimate the overall effect. Hetereogeneity was investigated in terms of the characteristics of the individual studies. Twelve trials met the inclusion criteria but data from one could not be obtained. Individual patient data were available in only three. Standardised differences between means ranging from 0.071 to 0.133, in favour of acupuncture, were obtained. The overall effect was not conventionally significant and it corresponds to an approximate difference in FEV1 means of 1.7. After exploring hetereogenenity, it was found that studies where bronchoconstriction was induced during the experiment showed a conventionally significant effect. This meta-analysis did not find evidence of an effect of acupuncture in reducing asthma. However, the meta-analysis was limited by shortcomings of the individual trials, in terms of sample size, missing information, adjustment of baseline characteristics and a possible bias against acupuncture introduced by the use of placebo points that may not be completely inactive. There was a suggestion of preferential publication of trials in favour of acupuncture. There is an obvious need to conduct a full-scale randomised clinical trial addressing these limitations and the prognostic value of the aetiology of the disease.

Acupuncture Therapy↗
PubMed2002

Complications following endovascular abdominal aortic aneurysm repair.

There is a growing population of patients who have undergone endovascular abdominal aortic aneurysm repair (EVAR) and thus there is an increasing likelihood that radiologists who are unfamiliar with this technique and its complications will have to report radiological investigations on one of these patients. The purpose of this review is to describe and illustrate the normal and abnormal radiological appearances after EVAR on plain radiography, ultrasound and CT.

Aorta, Abdominal↗
PubMed2002

Bovine enterovirus as an oncolytic virus: foetal calf serum facilitates its infection of human cells.

Many viruses have been investigated for their oncolytic properties and potential use as therapeutic agents for cancer treatment. Most of these replication-competent viruses are human pathogens. We investigated the oncolytic properties of an animal virus which is non pathogenic for both its natural host and humans. Bovine enterovirus has previously been shown to exhibit a very wide tissue tropism for cell types in vitro. We compare the ability of bovine enterovirus to replicate in and to cause cytopathic effect in freshly isolated human monocytes and monocyte derived macrophages with the monocyte-like U937 tumour cell line. We also include the adherent ZR-75-1 human breast cancer cell line. We have also carried out infections of bovine enterovirus in the presence and in the absence of serum of bovine origin. Our study shows that the virus will replicate in and produce cytopathic effect in the U937 and ZR-75-1 cell types to the same extent as the cells (BHK-21) in which the virus is routinely propagated. We believe bovine enterovirus to be a worthwhile candidate for further study as an anti-tumour agent.

Animals↗
PubMed2002

A performance evaluation of commercial fibrinogen reference preparations and assays for Clauss and PT-derived fibrinogen.

The wide availability of fibrinogen estimations based on the prothrombin time (PT-Fg) has caused concern about the variability and clinical utility of fibrinogen assays. In a multi-centre study, we investigated fibrinogen assays using various reagents and analysers. Clauss assays generally gave good agreement, although one reagent gave 15-30% higher values in DIC and thrombolysis. Two commercial reference preparations had much lower potencies than the manufacturers declared, and plasma turbidity influenced parallelism in some Clauss assays. PT-Fg assays gave higher values than Clauss and showed calibrant dependent effects, the degree of disparity correlating with calibrant and test sample turbidity. Analyser and thromboplastin dependent differences were noted. The relationship between Clauss and PT-Fg assays was sigmoid, and the plateau of maximal PT-Fg differed by about 2 g/l between reagents. ELISA and immunonephelometric assays correlated well, but with a high degree of scatter. Antigen levels were higher than Clauss, but slightly lower than PT-Fg assays, which appeared to be influenced by degraded fibrinogen. Clauss assays are generally reproducible between centres, analysers and reagents, but PT-Fg assays are not reliable in clinical settings.

Blood Coagulation Tests↗
PubMed2002

[The Baikal scullcap (Scutellaria baicalensis Georgi)--a potential source of new drugs].

The scullcap (Scutellaria baicalensis Georgi) is a medicinal plant of traditional Chinese medicine and the drug--Scutellariae radix--is, because of its antioxidant, antiviral, antibacterial, antiinflammatory, antiallergic, and sedative properties, the subject of intensive development. This paper reports the results of pharmacological-toxicological studies of this drug and its flavonids approximately from the year 1990 till the year 2001. The results confirm the validity of traditional use and at the same time indicate that some flavonoids have more utilizable therapeutic effects. Mainly baicalein seems to be a prospective medicine for the treatment of some kinds of cancer.

Animals↗
PubMed2002

Acute myeloid leukemia presenting as splenic rupture.

We describe a rare case of acute myeloid leukemia presenting primarily as an acute abdomen due to spontaneous splenic rupture in a 19 years male patient. He was treated with splenectomy after failure of conservative management for splenic preservation but later succumbed to an intracerebral haemorrhage.

Abdomen, Acute↗
PubMed2001

Invasive melanoma in Cdk4-targeted mice.

Many human tumors harbor mutations that result in deregulation of Cdk4 activity. Most of these mutations involve overexpression of D-type cyclins and inactivation of INK4 inhibitors. In addition, a mutation in the Cdk4 protein has been described in patients with familial melanoma (Wolfel, T., Hauer, M., Schneider, J., Serrano, M., Wolfel, C., et al. (1995) Science 269, 1281-1284; Zuo, L., Weger, J., Yang, Q., Goldstein, A. M., Tucker, M. A., et al. (1996) Nat. Genet. 12, 97-99). This mutation, R24C, renders the Cdk4 protein insensitive to inhibition by INK4 proteins including p16(INK4a), a major candidate for the melanoma susceptibility locus. Here we show that knock-in mice expressing a Cdk4 R24C allele are highly susceptible to melanoma development after specific carcinogenic treatments. These tumors do not have mutations in the p19(ARF)/p53 pathway, suggesting a specific involvement of the p16(INK4a)/Cdk4/Rb pathway in melanoma development. Moreover, by using targeted mice deficient for other INK4 inhibitors, we show that deletion of p18(INK4c) but not of p15(INK4b) confers proliferative advantage to melanocytic tumor growth. These results provide an experimental scenario to study the role of Cdk4 regulation in melanoma and to develop novel therapeutic approaches to control melanoma progression.

Animals↗
PubMed2001

Energy saving in flight formation.

Many species of large bird fly together in formation, perhaps because flight power demands and energy expenditure can be reduced when the birds fly at an optimal spacing, or because orientation is improved by communication within groups. We have measured heart rates as an estimate of energy expenditure in imprinted great white pelicans (Pelecanus onocrotalus) trained to fly in 'V' formation, and show that these birds save a significant amount of energy by flying in formation. This advantage is probably a principal reason for the evolution of flight formation in large birds that migrate in groups.

Animals↗
PubMed2001

Activity analysis of English Premiership rugby football union refereeing.

Little is known about the physiological demands placed on officials during sporting activities. The purpose of this study was to ascertain the movement activities of referees during English Premiership rugby football union matches, and to determine the frequency and duration of these activities. Nine referees who were ranked in the top 20 referees in England were videotaped during a total of 19 matches. During playback of the videotapes, a single observer coded the referees' activities into one of six distinct categories (standing, walking forwards, walking backwards, jogging, running and sprinting) using a computerized video editing system (Observer Video-Pro). The referees were timed over a 20 m distance for the modes of locomotory activity, and the average velocity of the referee for each activity was used to calculate the total distance covered in each mode of activity during matches. The total distance covered during a match was (chi +/- SD) 8581 +/- 668 m. The mean percentage of total playing time spent in each activity was: standing still, 37.0 +/- 11.0%; walking forward, 29.5 +/- 7.2%; walking backward, 9.9 +/- 3.2%; jogging, 12.8 +/- 3.2%; running, 9.8 +/- 2.3%; and sprinting, 1.0 +/- 0.4%. There were a total of 672 transitions between modes of activity during a match. The results of this study suggest that refereeing top English rugby football union matches is physically demanding. Although the major physiological load is placed on the oxygen transport system, frequent sprint bouts and the associated requirements for acceleration and deceleration impose additional metabolic demands on referees. This information may be used in the design of physical training programmes to optimize performance in referees.

Adult↗
PubMed2001

[Danger of malaria self-treatment. Acute neurologic toxicity of mefloquine and its combination with pyrimethamine-sulfadoxine].

BACKGROUND: Mefloquine and pyrimethamine-sulfadoxine combination are recommended, as is quinine, for self-administered malaria prophylaxis. Patients should be carefully informed about appropriate use of this therapeutic scheme and advised on the importance of strict compliance to avoid overdose. CASE REPORT: We report the case of a patient who did not follow the prescribed dosage and who developed acute neurological disorders after overdosing. The patient developed seizures attributable to the sulfadoxine-pyrimethamine combination and mefloquine encephalopathy. DISCUSSION: Sulfadoxine-pyrimethamine-related seizures are exceptional and result from an overdose of pyrimethamine. The neurotoxicity of mefloquine is well-known and is particularly frequent at curative dosage. Toxic encephalopathy is a serious neurological manifestation which is slowly reversible depending on individual predisposition. Anti-malaria prophylaxis requires concerted efforts on the part of the traveler and the prescribing physician. Self-administration schemes can be both most useful and dangerous due to expected benefits and potential risks.

Adult↗
PubMed2001

Chaperonins--keeping a lid on folding proteins.

Two classes of chaperonins are known in all groups of organisms to participate in the folding of newly synthesized proteins. Whereas bacterial type I chaperonins use a reversibly binding cofactor to temporarily sequester folding substrate proteins within the cylindrical chaperonin cavity, type II chaperonins in archaea and the eukaryotic cytosol appear to have evolved a built-in lid for this purpose. Not entirely surprisingly, this has consequences for the folding modes of the two types of chaperonins.

Chaperonins↗
PubMed2001

Measurement of the high energy two-body deuteron photodisintegration differential cross section.

The first measurements of the d(gamma,p)n differential cross section at forward angles and photon energies above 4 GeV were performed at the Thomas Jefferson National Accelerator Facility (JLab). The results indicate evidence of an angular dependent scaling threshold. Results at straight theta(cm) = 37 degrees are consistent with the constituent counting rules for E(gamma) greater, similar 4 GeV, while those at 70 degrees are consistent with the constituent counting rules for E(gamma) greater, similar 1.5 GeV.

Journal Article↗
PubMed2001

Definition of an optimal cytotoxic T lymphocyte epitope in the latently expressed Kaposi's sarcoma-associated herpesvirus kaposin protein.

Cytotoxic T lymphocytes (CTL) recognize and kill virus-infected cells and contribute to immunologic control of viral replication. For many herpesviruses (e.g., Epstein-Barr and cytomegalovirus), virus-specific CTL responses can be readily detected in infected persons, but CTL responses against Kaposi's sarcoma-associated herpesvirus (KSHV) appear to be weak and remain poorly characterized. Using a human leukocyte antigen (HLA) binding motif-based epitope prediction algorithm, we identified 37 HLA-A*0201 binding peptides from 8 KSHV open-reading frames (ORFs). After in vitro stimulation of peripheral blood mononuclear cells from KSHV-infected persons, CTL responses against 1 peptide in the KSHV kaposin protein (ORF K12) were detected in 2 HLA-A*0201-positive subjects. The optimal CTL epitope was identified by HLA restriction analysis and peptide titration assays. These data describe a latent phase viral gene product targeted by CTL that may be relevant for KSHV immunopathogenesis.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Oligonucleotide microarray expression analysis of genes whose expression is correlated with tumorigenic and non-tumorigenic phenotype of HeLa x human fibroblast hybrid cells.

In order to understand the differences and similarities between tumorigenic and non-tumorigenic HeLaxhuman fibroblast hybrids, gene expression profiles were examined with synthetic oligonucleotide arrays containing nearly 7000 gene probe sets. We used two pairs of genetically related hybrids, each pair representing individual clones of non-tumorigenic and tumorigenic segregant hybrids, respectively. Analysis of six possible comparisons, utilizing two algorithms, identified 204 genes with differential expression. The greater number of differentially expressed genes was observed when non-tumorigenic hybrids were compared with tumorigenic segregants. Fifteen and 14 genes, respectively, were consistently found to be differentially expressed in non-tumorigenic and tumorigenic cells. Among those 29 differentially expressed genes, three (intestinal alkaline phosphatase, caveolin-1, and solute carrier family2, member3) have been reported previously to be associated with the tumorigenic phenotype, using the same hybrid pairs. In addition, among the genes previously detected by differential display, 78% of them exhibited more than 5-fold change, demonstrating a high consistency between the two methods of differential gene expression. These findings suggest that synthetic oligonucleotide arrays are a powerful and highly reproducible tool to identify those genes whose expression is associated with certain phenotypes.

Algorithms↗