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Biomedical subjects

M Cox

Publications and source records attributed to M Cox.

At least 91 records · Page 5Linked to original sources

Solution structure of the POU-specific DNA-binding domain of Oct-1.

The transcription factor Oct-1 belongs to a family containing a POU DNA-binding domain. This bipartite domain is composed of a POU-specific domain (POUs) and a POU-homeodomain (POUhd) connected by a flexible linker. The left half of the optimal POU binding site, the octamer ATGCAAAT, is recognized by POUs and the right half by POUhd. We have determined the solution structure of POUs by nuclear magnetic resonance. It consists of four alpha-helices connected by short loops. Helices I and IV are in a parallel coiled-coil arrangement. The folding topology appears to be similar to that of the bacteriophage lambda-repressor and 434 repressor. For the well defined parts of the protein (residues 1-71), the average root-mean square deviation for the backbone atoms is 0.9 A. Based on the observed selective exchange broadening in the (15N,1H)-HMQC (heteronuclear multiple quantum coherence) spectrum of the POUs-DNA complex we conclude that DNA-binding is mediated by helix III. We propose a model for the POU-DNA complex in which both recognition helices from the two subdomains have adjacent positions in the major groove.

Amino Acid Sequence↗

Human herpes simplex-1 and papillomavirus type 16 homologous DNA sequences in normal, potentially malignant and malignant oral mucosa.

We have tested a range of normal, potentially malignant and malignant oral mucosal biopsies tissues by Southern blot hybridisation analysis for the simultaneous presence of HSV-1 and HPV type 16 DNA sequences, both of which have been implicated as risk factors in oral carcinogenesis. The results show that: (1) 2/4 patients with lichen planus, 2/4 patients with non-specific keratosis, 1/8 patients with oral carcinoma and 3/5 biopsy specimens of normal oral mucosa contained DNA sequences homologous to the HSV-1, Bam HI-G fragment. (2) HPV-16 homologous DNA sequences were detected in 3/4 patients with lichen planus, 4/4 non-specific keratosis, 4/8 oral carcinomas and in 3/5 biopsy specimens of normal oral mucosa. (3) Overall, only 5 patient biopsy specimens were positive for both HSV-1 and HPV-16 homologous DNA sequences; 2 lichen planus, 2 non-specific keratosis and 1 normal. The data cannot exclude a "hit and run" oncogenic mechanism for HSV but suggest that if HSV-1 and HPV-16 play a synergistic role in the development of oral cancer this may be an early event. Indeed, the data suggest HSV might be more frequently found in potentially malignant lesions than in carcinoma.

Adolescent↗

Zinc supplementation in very-low-birth-weight infants.

Inadequate zinc intake may lead to poor growth and developmental outcome in very-low-birth-weight (VLBW; < 1,500 g) infants. Fifty-two infants (mean birth weight, 1,117 +/- 287 g; mean gestational age, 29 +/- 2.9 weeks) were randomly allocated to two groups. SUPP infants received a regular term formula plus zinc supplements (4.4 mg/L; final content, 11 mg/L); PLAC infants received the same formula plus placebo (final content, 6.7 mg/L). Infants started their formula at 1,853 +/- 109 g and consumed the formula for 6 months. All subjects were evaluated at 3, 6, 9, and 12 +/- 0.75 months corrected-for-gestational-age. At each evaluation, weight, length, and head circumference were measured, a Griffiths developmental assessment was performed, and a blood sample was taken. Higher plasma zinc levels (p < 0.05) were found in the SUPP group at 1 and 3 months, and improved linear growth velocity was found in the SUPP group over the study period for the whole group as well as for girls alone. Maximum motor development scores were higher (p = 0.018) in the SUPP (98 +/- 10) than the PLAC (90 +/- 8) group, indicating that increased zinc intake in early infancy may be beneficial to VLBW infants.

Double-Blind Method↗

Enzymatic reactions of Clostridium difficile in aerobic and anaerobic environments with the RapID-ANA II identification system.

The RapID-ANA II anaerobic identification system (Innovative Diagnostic Systems, Inc., Atlanta, Ga.) was used to determine whether the incubation environment affects enzyme detection. Twenty strains of Clostridium difficile were tested in aerobic, anaerobic, and low-CO2 anaerobic incubation environments. The percentages of enzymes detected in reactions with the following substrates were noted in the three incubation environments: phenylalanine-beta-naphthylamide, aerobic, 0%; anaerobic, 35%; low-CO2 anaerobic, 35%; arginine-beta-naphthylamide, aerobic, 5%; anaerobic, 55%; low-CO2 anaerobic, 75%; pyrrolidonyl-beta-naphthylamide, aerobic, 5%; anaerobic, 65%; low-CO2 anaerobic, 65%. When the aerobic incubation environment was compared with either the anaerobic or the low-CO2 anaerobic incubation environments, the results were statistically different with respect to enzyme detection in reactions with the substrates listed above. The results for the anaerobic and low-CO2 anaerobic environments were not statistically different. The study was repeated twice. Statistical comparisons between the three environments were consistent with the results presented above, with the following exceptions. The aerobic and the anaerobic environments were not different in a reaction with phenylalanine-beta-naphthylamide in one of the runs, and there was no significant difference between the three environments in a reaction with arginine-beta-naphthylamide in another run. These results suggest that some of the enzymes used in the identification of clinical anaerobes appear to be inactive in an environment containing oxygen.

Aerobiosis↗

Evaluation of the obstetric significance of some pelvic characters in an 18th century British sample of known parity status.

The excavations at Christ Church, Spitalfields (1984-86) produced a sample of 968 human skeletons which were interred between 1729 and 1859. Of these, 387 were recovered in association with coffin plates stating name, age at death, and date of death. There are 138 adult females in the named sample and the obstetric histories of 94 have been reconstructed from historical documentation. Such variables as birth spacing, number of children, and age at first and last births are known for the majority of this sample. Any individual about whose history there is any doubt has been excluded from the analysis. A middle-class group, they were largely of high nutritional status and, by the standards of the day, lived in sanitary and comfortable conditions. Both males and females have a mean age at death of 56 years. The presence or absence, the typology, the severity, the width and the length of the preauricular sulcus, the presence or absence and the number of pits on the dorsal aspect of the pubic body, sulci along the anterior sacrum adjacent to the auricular facet, and the extension of the pubic tubercle were evaluated in relation to the obstetric histories of these females. Statistical analysis has demonstrated a relationship between the presence of pubic tubercle extension and parity status and between the degree of extension and the number of children borne (P < .02). Statistically there is no significant relationship (P > .05) between either the preauricular sulcus or pubic pitting and parity status. Sacral scarring is significantly associated (P < .05) with parity status, but as it was evident in only eight females it has little practical application. Sample sizes are small, and it must be considered that statistical evaluation of larger samples might detect associations between variables not demonstrated here. There is no significant relationship between any of the cortical variants under consideration and age at death.

Adult↗

Improved technique for polytetrafluoroethylene bypass grafting: long-term results using anastomotic vein patches.

Results of peripheral arterial bypass using polytetrafluoroethylene grafts have remained poor in comparison with those using saphenous vein grafts, particularly for anastomoses to tibial and peroneal vessels. A simple modification to the conventional operative technique, involving the incorporation of a vein patch into the distal anastomosis, has enabled considerable improvement. Five-year patency rates of 71 per cent for popliteal and 54 per cent for infrapopliteal grafts have been achieved in a series of 256 patients operated on between 1982 and 1989.

Aged↗

Evidence that inhibitor(s) are formed which may interfere with the growth of revertant colonies in the Ames Salmonella and the E. coli tryptophan reverse mutation assays when strictly anaerobic conditions are used.

Spontaneous and chemically induced revertant colonies were not observed on plates when a strictly anaerobic environment and anaerobically prepared media were used to perform the Ames histidine reversion assay with each of eight different Salmonella strains. A similar effect was observed when the E. coli tryptophan reverse mutation assay was performed under strictly anaerobic conditions. We provide evidence here that under anaerobic conditions growth inhibitor(s) are formed by the S. typhimurium and E. coli bacteria when the limited histidine and tryptophan, respectively, are depleted from the medium. The inhibitor(s) are nonspecific and inhibit the growth not only of prototrophic bacteria but also of the inhibitor-producing bacteria as measured by neutralized supernatants of growth-limiting minimal liquid cultures. Inhibitor(s) are also formed in stationary phase cultures of Salmonella and E. coli in minimal liquid medium supplemented with excess histidine and tryptophan, respectively. These results suggest that inhibitor formation under anaerobic conditions is a physiological phenomenon which interferes with at least two reverse mutation assays. Whether or not it also interferes with the reverse mutagenesis process remains to be determined.

Anaerobiosis↗

Spontaneous cessation of umbilical blood flow in the acardiac fetus of a twin pregnancy.

The acardiac fetus is a rare entity found only in monozygotic multiple pregnancy. Although the acardiac fetus is non-viable, the perinatal mortality rate for the normal fetus may be as high as 50 per cent, and is usually associated with fetal heart failure and hydrops fetalis, or as the result of prematurity. In this communication, we describe a case of spontaneous cessation of blood flow to an acardiac fetus and discuss the management of this condition with special reference to optimizing the outcome for the normal fetus.

Abnormalities, Severe Teratoid↗

Development of a high performance zinc-62/copper-62 radionuclide generator for positron emission tomography.

Clinical utilisation of positron emission tomography could be enhanced by the availability of short-lived radionuclides derived from generator systems. The zinc-62/copper-62 combination is one such system which could be used as a source for a number of copper-62 radiopharmaceuticals. We have developed and optimised a high activity (5.6 GBq, 150 mCi) zinc-62/copper-62 generator to provide 62Cu in a form that is suitable for direct labelling of pyruvaldehyde-bis-(N4-methylthiosemicarbazone)-copper(II), Cu(PTSM). The distribution coefficients of Zn(II) and Cu(II) between anion-exchange resin and various hydrochloric acid/organic solvent mixtures were measured. Based on these measurements a generator eluent of 0.3 M HCl/40% ethanol provided 62Cu in greater than 90% yield in a 3-ml volume. A very low 62Zn breakthrough of less than 3 x 10(-7)% was achieved. Copper-PTSM was successfully labelled with the no-carrier-added 62Cu eluent directly from the generator with 94% radiochemical yield.

Copper↗

Truancy and illegal drug use, and knowledge of HIV infection in 932 14-16-year-old adolescents.

In a sample of 932 4th & 5th year comprehensive school adolescents, 41% had truanted in the current term. The truants, compared with their non-truanting peers, had three times the level of solvent misuse (14% compared with 4%), thrice the soft drug misuse (19% compared with 6%), and four times the involvement with hard drugs (9% compared with 2%). Truants were significantly more involved with other problematic behaviour and were found to score higher on all negative social indices, including parents who smoked. Despite the sample's relatively accurate knowledge about drugs and HIV infection, truants scored less well on these and other HIV-related issues. An extrapolation of the results indicates a significant number of adolescents at risk demanding urgent policy initiatives.

Acquired Immunodeficiency Syndrome↗

Raised resting energy expenditure in Parkinson's disease and its relationship to muscle rigidity.

1. Resting energy expenditure was measured, by indirect calorimetry, in 12 patients with Parkinson's disease and in eight healthy age-matched control subjects. In the patients with Parkinson's disease measurements were made in both the untreated state and after an injection of the dopamine agonist apomorphine (treated state). In each state muscle rigidity was recorded. 2. Resting energy expenditure was higher in patients with Parkinson's disease in both the treated and untreated states than in the control subjects. Of the patients with Parkinson's disease, seven showed no difference in resting energy expenditure between the two treatment states, whereas four showed markedly increased resting energy expenditure in the untreated state. The change in resting energy expenditure in the untreated state, as compared with the treated state, was significantly related to the development of muscle rigidity in the untreated state. 3. In Parkinson's disease, even in optimally treated patients, resting energy expenditure is raised and this may contribute to the weight loss seen in this disease. Severe muscle rigidity occurring during untreated periods results in a further increase in resting energy expenditure.

Apomorphine↗

Prepregnancy counselling: experience from 1,075 cases.

OBJECTIVE: To assess the activity of a prepregnancy counselling clinic in terms of investigations, counselling, treatment and subsequent pregnancy outcome. DESIGN: Review of 1,075 couples attending over a nine year period. SETTING: University Hospital offering a tertiary referral service for fetal medicine. SUBJECTS: Couples referred to the clinic from a variety of sources. MAIN OUTCOME MEASURES: Categories of referral, value of diagnostic tests, and subsequent pregnancy outcome. RESULTS: The main categories of referral were: previous miscarriage (44.4%); previous fetal abnormality (19.6%); chronic maternal disease (22.3%); and others (13.7%). Routine investigations produced a low yield of abnormality (1%), in contrast to investigations selected for specific reasons (12%). Subsequent pregnancy outcome, which was unaltered in either the previous miscarriage or fetal abnormality groups, did improve in the chronic maternal disease group. CONCLUSIONS: This study does not prove the value of prepregnancy counselling. However, it does illustrate the importance of making an accurate assessment of previous problems and current health as a means of determining both maternal and fetal risks in a subsequent pregnancy, a process which seems to lead to an improved outcome within selected groups. The importance of continuity of care in all couples, especially when there has been a previous adverse pregnancy outcome is emphasized.

Abortion, Spontaneous↗

Aldosterone-mediated Na+ transport in renal epithelia: time-course of induction of a potential regulatory component of the conductive Na+ channel.

To correlate synthesis of aldosterone-induced proteins (AIPs) with the hormone's effect on transepithelial Na+ transport, protein synthesis in two model renal epithelia was examined during the natriferic response to aldosterone. Newly synthesized epithelial cell proteins were pulse-labelled with [35S]-methionine, separated by 2D-PAGE and detected by autoradiography. In both toad urinary bladder and A6 cells, a constellation of polypeptides which are a component of the renal epithelial conductive Na+ channel first appeared prior to, or concordant with, the increase in Na+ transport. The early synthesis of these proteins taken together with the fact that they appear to be the only aldosterone induced component of the multimeric Na+ channel, is compatible with the hypothesis that they are responsible for regulating Na+ channel activity during aldosterone-stimulated epithelial Na+ transport.

Aldosterone↗

Insulin and IGF1 receptors in a model renal epithelium: receptor localization and characterization.

Insulin and IGF1 stimulate transepithelial Na+ transport in the urinary bladder of the toad Bufo marinus, a model renal epithelium. The signal transduction mechanisms for the natriferic action are unknown. Ultrastructural techniques were used to localize both receptors and ligands in the epithelium. Electron microscopy using gold-labelled anti-insulin or anti-IGF1 receptor antibodies demonstrated the majority of the insulin receptors were associated with the basolateral membrane while IGF1 receptors were found on basolateral and apical membranes. Both insulin and IGF1 receptors were found in endosomes and on the membranes surrounding subapical granules. In intact tissues incubated with iodinated IGF1 or insulin, both ligands were associated with the basolateral membrane. IGF1 was internalized to a greater extent than insulin and only IGF1 accumulated in cell nuclei.

Animals↗

Diet, body size and micronutrient status in Parkinson's disease.

Nutritional status was assessed in a group of patients with Parkinson's disease. Weight loss since the onset of disease occurred in 52% of the patients and 22% had lost more than 12.8 kg. Although 67% of patients experienced eating difficulties of some kind, dietary intakes of protein and energy were not significantly lower than recommended intakes. Plasma levels of albumin (44.2 g/l vs 45.7 g/l), vitamin A (2.61 vs 2.94 mumol/l), vitamin E (22.0 vs 32.0 mumol/l), iron (15.3 vs 18.3 mumol/l) and zinc (14.2 vs 18.7 mumol/l) were significantly lower (P < 0.05) in the patients than in healthy controls. Levels of ferritin, total iron-binding capacity and copper were similar between groups. The potential significance of low levels of vitamin E and zinc are discussed in relation to oxidative stress in the pathogenesis of this disease.

Adult↗

Computer-assisted assignment of 2D 1H NMR spectra of proteins: basic algorithms and application to phoratoxin B.

A suite of computer programs (CLAIRE) is described which can be of assistance in the process of assigning 2D 1H NMR spectra of proteins. The programs embody a software implementation of the sequential assignment approach first developed by Wüthrich and co-workers (K. Wüthrich, G. Wider, G. Wagner and W. Braun (1982) J. Mol. Biol. 155, 311). After data-abstraction (peakpicking), the software can be used to detect patterns (spin systems), to find cross peaks between patterns in 2D NOE data sets and to generate assignments that are consistent with all available data and which satisfy a number of constraints imposed by the user. An interactive graphics program called CONPAT is used to control the entire assignment process as well as to provide the essential feedback from the experimental NMR spectra. The algorithms are described in detail and the approach is demonstrated on a set of spectra from the mistletoe protein phoratoxin B, a homolog of crambin. The results obtained compare well with those reported earlier based entirely on a manual assignment process.

Algorithms↗

Viruses and chronic disorders involving the human oral mucosa.

Viruses have been implicated in the etiology of several chronic disorders of the oral mucosa. Most of these associations have been with DNA viruses, particularly certain herpesviruses, which are associated, for example, with some cases of erythema multiforme and with hairy leukoplakia. Papillomaviruses are associated with various papillomatous lesions, focal epithelial hyperplasia, and possibly with some carcinomas. Viruses may possibly be associated with recurrent aphthae, Behçet's syndrome, and some dermatoses. The literature concerning these possible associations is reviewed. However, much more research needs to be done before the full story of viral associations with oral mucosal disorders can be written.

Burkitt Lymphoma↗