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Biomedical subjects

M F Cox

Publications and source records attributed to M F Cox.

At least 19 recordsLinked to original sources
PubMed2001

Synthesis and evaluation of cryptolepine analogues for their potential as new antimalarial agents.

The indoloquinoline alkaloid cryptolepine 1 has potent in vitro antiplasmodial activity, but it is also a DNA intercalator with cytotoxic properties. We have shown that the antiplasmodial mechanism of 1 is likely to be due, at least in part, to a chloroquine-like action that does not depend on intercalation into DNA. A number of substituted analogues of 1 have been prepared that have potent activities against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum and also have in common with chloroquine the inhibition of beta-hematin formation in a cell-free system. Several compounds also displayed activity against Plasmodium berghei in mice, the most potent being 2,7-dibromocryptolepine 8, which suppressed parasitemia by 89% as compared to untreated infected controls at a dose of 12.5 mg kg(-1) day(-1) ip. No correlation was observed between in vitro cytotoxicity and the effect of compounds on the melting point of DNA (DeltaT(m) value) or toxicity in the mouse-malaria model.

Alkaloids↗
PubMed1992

Human papillomavirus type 16 DNA in oral white sponge nevus.

White sponge nevus (WSN) is a benign hereditary lesion of the mucous membranes. DNA extracted from a biopsy specimen of oral WSN was assayed for the presence of DNA sequences homologous to human papillomavirus (HPV) types 1, 2, 4, 6, 11, 13, 16, and 18 by Southern blot hybridization. Only HPV-16 homologous DNA sequences were detected at a copy number of approximately 200 to 250 genome copies per diploid cell. The viral DNA sequences did not appear to be integrated into the host cell chromosome. The finding of HPV-16 in an inherited lesion such as WSN indicates that caution must be exercised in ascribing a causal association in relation to the demonstration of HPV in other mucosal disorders.

DNA, Viral↗
PubMed1992

Production and characterization of antibodies to platelet-activating factor.

Antibodies directed against platelet-activating factor (PAF) have been raised in rabbits immunized with a novel platelet-activating factor analogue-conjugate. An analogue of PAF with a carbon double bond at the terminal end of the alkyl chain was subjected to ozonolysis and converted to the aldehyde. The aldehyde was coupled to thyroglobulin by reductive alkylation and rabbits were immunized via either intramuscular or intradermal routes in complete Freund's adjuvant. The antibodies are specific for PAF with a preference for the optically active (R)-enantiomer. There appears to be a requirement for antibody binding of an alkyl chain of up to 18 Carbon atoms at C1, and an acetyl group in the C2 position. The ability of a number of structural analogues to inhibit binding of tracer to the antibody is related to the biological activity of the analogue, and therefore may reflect the structural domains that are critical for PAF to interact with its receptor.

Animals↗
PubMed1991

Viruses in the aetiology of oral carcinoma? Examination of the evidence.

This paper examines the evidence for an aetiological role for viruses in the development of oral carcinoma. Several viruses have been sought in oral cancer and evidence found for some, particularly herpes simplex and human papillomavirus. However, the evidence also suggests that these viruses are ubiquitous agents and a number of criteria must be met before these potentially oncogenic agents can reliably be implicated in human carcinogenesis. In contrast, there is no evidence that viruses such as adenovirus, Epstein-Barr virus, and retroviruses play any role in oral carcinogenesis.

Humans↗
PubMed1989

Detection of human papillomavirus genes in human oral tissue biopsies and cultures by polymerase chain reaction.

We have used the polymerase chain reaction to detect DNA sequences related to human papillomavirus type 16, by simultaneous priming with oligonucleotides from the E6 and L1/L2 open reading frames of the HPV16 genome. The HPV16-related sequence is present at low levels in normal oral tissue, in addition to biopsies and cell cultures from patients with benign and malignant disease. Ultimate analysis of the amplified sequences from the E6(120bp) and L1/L2(173bp) regions of HPV16 was achieved by gel electrophoresis and comparative nucleotide sequencing. The oral carcinoma biopsies and tissue cultures contained DNA sequences which were identical to the E6 region of HPV16, but only rarely contained sequences closely related to the L1/L2 region. The PCR technology should permit the detection, identification and cloning of latent viruses from extremely small tissue biopsies.

Base Sequence↗
PubMed1988

Papillomaviruses: the current status in relation to oral disease.

Human papillomaviruses of different types are associated with a variety of benign oral lesions and may be associated with some premalignant and malignant oral lesions. However, since it is now clear that a variant of human papillomavirus 16 is harbored by normal oral mucosa, as well as by premalignant and malignant lesions, such associations may not necessarily always be causal. The rapid progress of recent research in this field is reviewed, with particular reference to oral disease, and the current status is discussed.

Animals↗
PubMed1987

HPV 16 DNA in normal and malignant cervical epithelium: implications for the aetiology and behaviour of cervical neoplasia.

Southern blot hybridisation showed that cervical cancer biopsy specimens from 31 of 47 (66%, 95% confidence interval [CI] 52-80%) patients contained HPV 16 homologous DNA sequences, with evidence of integration of viral genome into host cell chromosomes in 7. Normal ectocervical biopsies from 9 of 26 (35%, 95% CI 16-53%) control women contained HPV 16 DNA, and none showed evidence of integration. HPV 16 DNA positivity did not correlate with marital or sexual history, parity, use of oral contraceptives, or smoking habits in cases or controls, or with outcome of treatment in cases. HPV 16 DNA positivity was found less frequently with age less than 40 years old than with age greater than 40 in both cases (p less than 0.05) and controls (p less than 0.01). After age-adjustment there was no significant difference between cases and controls in frequency with which HPV 16 DNA was found. These data suggest that the association between HPV 16 and cervical neoplasia is age-mediated and that the presence of the viral genome may not always warrant intervention.

Adenocarcinoma↗
PubMed1987

Detection of human papillomavirus DNA in biopsies of human oral tissue.

We have employed molecular probes produced from DNA fragments of human papillomavirus, cloned into prokaryotic vectors, to detect virus nucleic acid sequences in extracts of human oral tissues. The study was conducted with duplicate coded snap-frozen tissue biopsies from which frozen sections had been taken to accurately assess the pathology of each particular sample. The results show that a large proportion of the oral biopsies contained DNA which hybridized to the viral DNA probes, even under conditions of high stringency. The presence of virus did not correlate with neoplasia in the tissues examined, but HPV like sequences were found in a high proportion (80%) of biopsies taken from areas of keratosis and lichen planus and also in 41 to 46% of normal and tumour tissues.

Biopsy↗
PubMed1987

Nucleic acid probes in the study of latent viral disease.

Despite the apparent complexities of vocabulary and techniques involved in nucleic acid hybridization, these methods should become important new weapons in the pathologist's armoury. The particular strengths lie in the analysis of genes whose protein products defy detection either because they are absent (due, for example, to cellular controls as found in viral latency), to a point mutation, or to gene deletion (as is often the case with cellular oncogenes). However, the mere application of this technology will not solve all diagnostic problems. One must be aware, particularly in applying in situ hybridization to a new system, of the artefactual binding of the probes, and suitable control and duplicate experiments should be performed. In addition, it is vital to verify the identity of the probes and the specificity of the reaction by filter hybridization. The latter procedure may seem unwieldy, but is, in fact, no more complex than the recommended procedures for immunohistochemistry, as discussed by Matthews (this symposium). Sadly, for both hybridization and immunological detection, operator inexperience has often prevented such checks of specificity and as a result many spurious results populate the scientific literature, for example a recent controversy over the detection of Human T cell Lymphotrophic Virus Type 1 in multiple sclerosis patients. With careful application, however, these techniques will permit the detection of viral molecules under conditions where traditional electron microscopy/histology have failed, and may reveal possible viral aetiologies for a range of hitherto non-viral diseases.

Autoradiography↗
PubMed1986

Eosinophilic myositis and muscular sarcocystosis in the carcasses of slaughtered cattle and lambs.

Fifty-three bovine and 7 ovine carcasses condemned for having eosinophilic myositis were evaluated. Four (7.3%) of the bovine carcasses had a few, large local lesions in skeletal muscles (category A), and 49 (92.7%) of the bovine carcasses and 7 (100%) of the ovine carcasses had multiple, small, disseminated lesions in tongue, esophagus, heart, diaphragm, or skeletal muscles (category B). Tissue from carcasses of category B were evaluated for bacteria, viruses, selenium, and pathologic changes. Pathogenic bacteria and viruses were not isolated and selenium concentrations were normal. In category B, all carcasses had granulomas; of the 49 bovine carcasses and 7 ovine carcasses, 38 (77.6%) and 7 (100%), respectively, had one or more granulomas with opened dead sarcocysts. The data indicated that opened sarcocysts killed the host myocyte and adjacent myocytes and stroma, thereby initiating granuloma formation.

Animals↗
PubMed1981

Laryngeal diphtheria and papillomatosis in feedlot cattle.

In a random sample of 30,444 larynges from slaughtered beef cattle, 441 (1.4%) had chronic diphtheria and 1,345 (4.4%) had papillomatosis. Both types of lesions were centered in mucous membranes over the vocal processes and medial angles of the arytenoid cartilages. Since they are found in the same anatomical locations as laryngeal contact ulcers, we hypothesize that ulcers are primary and diphtheria and papillomatosis are secondary.

Animals↗
PubMed1981

Osteochondrosis in feedlot cattle.

Beginning in summer 1977 and continuing through four consecutive seasons, we examined lame limb joints from 106 partially fattened cattle and 28,235 pairs of occipital condyles from fully fattened cattle for osteochondrosis. Of the 106 lame cattle, nine (8.5%) had characteristic lesions, usually in their stifle joints, and of the 28,235 atlanto-occipital joints, 1063 (3.8%) had lesions on their condyles. Slices of affected articular cartilage and subjacent bone were studied radiographically and histologically. Radiographs showed subchondral defects and epiphyseal "cyst-like" lesions, and histologic sections showed disarrayed and degenerated chondrocytes. Splits occurred along osteochondral junctions or in adjacent cartilage or bone. Some bone trabeculae had been replaced by fibrous tissue that, in some areas, extended deep into epiphyses.

Animals↗
PubMed1980

Laryngeal contact ulcers in feedlot cattle.

Of 30,444 larynges from fattened cattle at three companies, 3,985 (13.1%) had contact ulcers or ulcer scars in the mucous membranes over the vocal processes and medial angles of the arytenoid cartilages. The incidence was higher in cattle fed during fall than in cattle fed during other seasons. We hypothesize: 1. that some feedlot cattle develop acute mucositis from mixed infections with species of Pasteurella, Haemophilus, Mycoplasma, and viruses in the nose, pharynx, and larynx; 2. that reflex coughing and swallowing accelerate the rate of larynx closure; and 3. that the closures erode the swollen membrane over the vocal processes and medial angles of the arytenoid cartilages and thus produce primary contact ulcers.

Animals↗
PubMed1980

Limb arthropathies and periarticular injuries in feedlot cattle.

Beginning summer 1977 and continuing through 4 consecutive seasons, we examined samples of at least 25, and a total of 106, lame limbs or joints from slaughtered beef cattle. Of this number about 64 (60%) were articular and 42 (40%) periarticular lesions. Fifty-three were caused by trauma and 9 by osteochondrosis. Stifle joints (40) and digital joints (19) were the most frequently affected articulations, and the humerus and femur were the most frequently fractured bones. Twenty joints, mostly stifles, had fibrinous arthritis, and Mycoplasma spp. were isolated from 11.

Animals↗
PubMed1975

Transformation of elemental mercury by bacteria.

The fate and impact of elemental mercury in closed bacterial cultures were examined. The quantity of elemental mercury oxidized by bacteria ranged from small amounts for Pseudomonas aeruginosa, P. fluorescens, Escherichia coli, and Citrobacter to essentially all of the added elemental mercury for Bacillus subtilis and B. megaterium. The percentage of the total mercury in the system associated with bacterial cells ranged from 18.6 to 43.2%. Growth of the two Pseudomonas species was inhibited by elemental mercury, whereas growth of the other cultures was not distinguishable from that in mercury-free controls. No methylmercury was formed by the six cultures within 48 h.

Bacillus megaterium↗