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Biomedical subjects

M Hall

Publications and source records attributed to M Hall.

At least 37 records · Page 2Linked to original sources

Association of human papillomavirus and colon neoplasms.

Human papillomavirus has been shown to be associated with squamous carcinomas. We evaluated benign and malignant colon tissues for the presence of human papillomavirus infection to determine if a similar relationship exists between human papillomavirus and colon neoplasms. Colon tissues were screened using an immunohistochemical technique to detect human papillomavirus antigen. In situ DNA hybridization was then performed on those tissues that yielded positive results by immunohistochemistry. Groups were compared using chi 2 analysis. Human papillomavirus antigen was present in 23% of normal colon specimens, 60% of benign tumors, and 97% of carcinomas. Human papilloma viral genome was demonstrated in 27% of benign tumors and in nearly 43% of all carcinomas tested. These data indicate that human papillomavirus infects the columnar mucosa of the colon, and that an association exists between human papillomavirus and colon neoplasia.

Adenoma

Effects of 1-ethynylpyrene and related inhibitors of P450 isozymes upon benzo[a]pyrene metabolism by liver microsomes.

The effects of three aryl acetylenes, 1-ethynylpyrene (EP), 2-ethynylnaphthalene (EN) and 3-ethynylperylene (EPE), upon the metabolism of benzo[a]pyrene (BaP) by microsomes isolated from rat liver were investigated. These aryl acetylenes all inhibited the total metabolism of BaP. Formation of BaP 7,8-dihydrodiol and BaP tetrol products by microsomal preparations from rats that had been pretreated with 3-methylcholanthrene (3MC) were preferentially inhibited. The effects of EP upon the metabolism of BaP 7,8-dihydrodiol by microsomes from rat liver were also studied. This aryl acetylene strongly inhibited the formation of BaP tetrols from BaP 7,8-dihydrodiol by liver microsomes both from untreated rats and from rats pretreated with 3MC, but enhanced the conversion of the BaP dihydrodiol into other metabolites.

Animals

Sequence similarity between alpha 2-macroglobulin from the horseshoe crab, Limulus polyphemus, and proteins of the alpha 2-macroglobulin family from mammals.

1. Purified alpha 2-macroglobulin (alpha 2M) from the American horseshoe crab, Limulus polyphemus was cleaved with trypsin and 20 of the tryptic peptides were sequenced and compared with the sequences of human alpha 2M, rat alpha 1M, alpha 2M, and alpha 1-inhibitor 3, and human complement proteins C3 and C4. 2. Ten of the peptides (233 residues), including that containing the thiol ester site, could be aligned unambiguously with stretches in mammalian alpha 2M, with a degree of identity greater than 30%. 3. The 12-residue thiol ester-containing peptide of Limulus alpha 2M showed 67% identity with the same stretch of human alpha 2M.

Amino Acid Sequence

An outbreak of Salmonella saint-paul infection associated with beansprouts.

In March 1988, there was an outbreak of infection by a strain of Salmonella saint-paul with a distinctive antigenic marker. A total of 143 reports were received between 1 March and 7 June. Preliminary investigations suggested that raw beansprouts were a possible source of infection and a case-control study confirmed the association. S. saint-paul of the epidemic type was isolated from samples of beansprouts on retail sale in different cities in the United Kingdom and from mung bean seeds on the premises of the producer who was most strongly associated with cases. In addition, Salmonella virchow PT34 was isolated from samples of raw beansprouts and was subsequently associated with seven cases of infection. Four other serotypes of salmonella were also isolated from beansprouts. On 8 April the public were advised to boil beansprouts for 15 seconds before consumption, and the premises of the one producer associated with many cases were closed. As a result of these actions there was a significant decrease in the number of infections with S. saint-paul.

Adolescent

Tissue distribution of DNA adducts in CDF1 mice fed 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ).

Male and female CDF1 mice were administered a single oral dose of 3 mumol of the food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) or 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and killed 24 h later. DNA was isolated from the livers, lungs, kidneys, colon and forestomach and analysed by 32P-postlabelling for the presence of IQ and MeIQ adducts. Several adduct-enrichment procedures were investigated, including ATP-deficient labelling conditions, butanol extraction and nuclease P1 digestion, and only the ATP-deficient procedure was found to produce the same adduct pattern on polyethyleneimine--cellulose TLC as the standard procedure. Up to nine adduct spots were detected in liver DNA from IQ-treated mice, two of which were not detected in other tissues. The levels of binding in both male and female mice were in the order liver greater than kidney greater than colon greater than forestomach greater than lung. Analysis of DNA from MeIQ-treated mice revealed the presence of up to seven adducts, one of which was detected in liver but not in other tissues. The relative order of DNA binding was kidney greater than liver greater than or equal to colon greater than forestomach greater than lung. As dietary feeding of IQ induces liver, lung and forestomach tumours, and MeIQ induces liver and forestomach tumours in this mouse strain, these binding levels do not correlate with the susceptibility of the organs to carcinogenesis induced by these compounds; the results may indicate the importance of additional factors in determining organ specificity of carcinogenicity.

Animals

Systemic lupus erythematosus presenting as pneumococcal septicaemia and septic arthritis.

A 50 year old woman presented with pneumococcal septicaemia, septic arthritis, and a lobar pneumonia and was subsequently diagnosed as having systemic lupus erythematosus. The blood film and splenic 99mTc sulphur colloid uptake were normal, although selective functional hyposplenism was shown by the impaired clearance of immunoglobulin coated erythrocytes. Systemic lupus erythematosus presenting with fulminating pneumococcal sepsis in the presence of selective defects in spleen function is previously unreported.

Arthritis, Infectious

Vesicoureteral reflux in children: endoscopic treatment.

Endoscopic correction of vesicoureteral reflux in children has been increasingly used in the last years with encouraging results. During a 4-year period 152 children were treated by endoscopic injection of Teflon. A follow-up, ranging from 3 months to 5 years, was available for 173 refluxing ureters. For primary reflux, correction was observed after a single injection in 87% of the cases and in 93% after a second injection in some failures. In duplication, the technique is somewhat more difficult but the results quite satisfactory with 58% success after one injection, increasing to 74% after a second injection. The limitations of these techniques are underlined, the major concern being the safety of the injectable Teflon particles, eliciting a foreign-body granulomatous reaction with the potential hazard of distant migration. So far no long-term morbidity and complications have been observed with the use of Teflon to correct reflux. Extensive pathological study in 7 children submitted to ureteral reimplantation for failure of endoscopic correction showed a typical encapsulated granulomatous reaction below the intramural ureter, but particles of Teflon were noted in only one hypogastric ganglion when the Teflon was injected outside of the bladder. There is a need for finding an ideal substance for endoscopic injection, preferably prepared from the patient's own tissue allowing simple and safe correction of vesicoureteral reflux in children.

Child, Preschool

A practical mouthstick for early intervention with quadriparetic patients.

There are few commercially available mouthsticks with bite plates that are easy to use by quadriparetic patients. The purpose was to design a practical, economical single-arch mouthstick for use in early rehabilitation. The mouthpiece designed was constructed out of self-curing acrylic. It adapted well to the existing dentition, hence giving a stable base. The mouthstick was easily fabricated, using limited materials and resources, and resulted in an appliance which was comfortable, required minimal training and allowed for independent use by the patient.

Equipment Design

Does heparin improve survival in experimental porcine gram-negative septic shock?

To evaluate the effects of heparin on gram-negative septic shock, immature piglets were subjected to fecal Escherichia coli peritonitis. One group of animals received a continuous infusion of heparin 25 units/kg/hr, while the control animals were given an equivalent volume of lactated Ringer's solution. Heparin-treated animals (n = 5) had a mean survival time (+/- SEM) of 18.8 +/- 2.2 hr vs. 11.9 +/- 2.8 (P less than 0.05) in controls (n = 5). Animals receiving heparin tended to have improved hemodynamic profiles and less leukopenia than controls.

Animals

Amino acid sequence around the thiolester of alpha 2-macroglobulin from plasma of the crayfish, Pacifastacus leniusculus.

Alpha 2-Macroglobulin (alpha 2 M) was isolated from plasma of the freshwater crayfish, Pacifastacus leniusculus, using ultracentrifugation, ion-exchange chromatography and gel filtration techniques. The Pacifastacus alpha 2 M molecule (P alpha 2 M) was radio-actively labeled in the thiol ester structure with iodo [14C]acetic acid in the presence of methylamine. After reduction and carboxymethylation of the protein, it was digested with trypsin. A 14C-labeled tryptic peptide was sequenced and contained an amino acid sequence very similar to other known thiol ester sequences from human alpha 2 M and related proteins. The N-terminal sequence of P alpha 2 M was related to that recently determined for lobster alpha 2 M [(1987) J. Biol. Chem. 262, 14606-14611].

Amino Acid Sequence

Hypothesis: reduced renal mass with glomerular hyperfiltration, a cause of renal hyperechogenicity in children.

A group of 10 pediatric patients had renal hyperechogenicity and reduced renal mass. The authors wish to suggest a relationship between renal hyperechogenicity and glomerular hyperfiltration according to Brenner's theory on the progressive nature of kidney disease. Reduced renal mass was related to multicystic dysplastic kidney (3 cases) nephrectomy (3 cases) and to reflux nephropathy (4 cases). The hyperechogenicity was diffuse in 6 cases with the preservation of cortico-medullary differentiation and was localized in all four cases of reflux nephropathy producing a "pseudotumoral" appearance. Hyperfiltration was confirmed by isotope studies in all 3 cases where it was performed. This condition together with secondary glomerulosclerosis could explain hyperechogenicity. The predictive value of such patterns are still unclear; yet such findings should lead to appropriate radiolocal, functional, clinical and dietary measures.

Child

Glutathione transferase catalyzed conjugation of benzo[a]pyrene 7,8-diol 9,10-epoxide with glutathione in human skin.

Glutathione transferase (GST) activity towards racemic as well as the resolved enantiomers of 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a] pyrene (anti-BPDE) and 1-chloro-2,4-dinitrobenzene (CDNB) was measured in post-microsomal supernatants (PMS) obtained from eight human skin samples. All preparations showed significant activity towards anti-BPDE and an almost exclusive preference for the more tumourigenic (+)-enantiomer. The specific activity towards (+)-anti-BPDE varied about five-fold between different PMS (range 147-781 pmol/min per mg protein) whereas the variation in specific activities towards CDNB was about two-fold (range 30-71 nmol/min per mg protein). The activities obtained with PMS at saturating concentrations of racemic anti-BPDE were about half of the activity towards the (+)-enantiomer indicating that (-)-anti-BPDE competitively inhibits conjugation of the (+)-form. No correlation was evident between the activities towards (+)-anti-BPDE and CDNB implying that different classes of GST isoenzymes participated in the two different reactions. Immunoblot analysis revealed the presence of Class Alpha and Pi isoenzymes whereas Class Mu isoenzymes seemed to be absent in the human skin samples analyzed. Quantitatively, the Class Pi isoenzyme(s) predominated in all skin samples and the amount of enzyme was about 1-3 micrograms GST Pi/mg PMS protein. The almost exclusive conjugation of (+)-anti-BPDE by PMS and previous results with GST Pi enzymes from human placenta suggested that this type of enzymes catalysed the conjugation reaction. The five-fold variation in specific activity towards (+)-anti-BPDE observed among the different PMS may be explained by individual differences in GST Pi content or by the presence of endogenous modifiers of GST activity towards the diol-epoxide.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide

Prospective management of neonates with pelviureteric junction stenosis. Therapeutic strategy based on 99m Tc-DPTA studies.

A prospective therapeutic strategy based on separate glomerular filtration rate (SGFR) was evaluated in 14 prenatally detected asymptomatic neonates, suspected of having pelviureteric junction obstruction. The patients with low SGFR were referred for pyeloplasty with the hope to improve the renal function. A marked improvement occurred in only one patient, although the drainage function (furosemide test) did improve in all cases. A conservative attitude was adopted for those children with normal SGFR. In 6 of them, a progressive increase of SGFR was noted, related to the normal maturation of the function, followed by a stabilization in the normal range. In 1 patient, a sudden decrease of SGFR was observed around 1 year and the patient was shifted into the surgical group. In this patient, an initial partial response of the kidney to a furosemide injection changed into a persistent non-response, whereas in the other non-operated patients, partial or good response was always recorded, although the responses were essentially variable on successive tests. On the basis of these data, the protocol was slightly modified, the patients with persistent non-response to furosemide after 6 months of life being shifted to the surgical group.

Clinical Protocols

Relative contribution of various forms of cytochrome P450 to the metabolism of benzo[a]pyrene by human liver microsomes.

A variety of cytochromes P450 have been implicated in the hepatic metabolism of benzo[a]pyrene (BP), including forms that are constitutively expressed and those that are highly inducible. In the present study the metabolism of BP to organic solvent-soluble derivatives by eight forms of cytochrome P450 isolated from rat liver and by a series of 11 human liver microsomal samples was investigated. The relative contribution of specific P450 forms to the human hepatic metabolism was evaluated. A 4-fold variation in formation of total organic solvent-soluble BP metabolites was observed, as well as differences in the regio- and stereoselectivity of this metabolism between the three individuals studied. The levels of expression of cytochromes P450 from five gene sub-families, as determined by Western blot analysis, did not show any correlation with the rate of BP metabolism to organic solvent-soluble derivatives in these livers. No reduction in metabolism was observed in three livers in which either the debrisoquine P450 (P450IID1) was not expressed or bufuralol 1-hydroxylase activity was low. Of six different antibodies to forms of rat liver P450 tested, only those to P450s MC1a (P450IA2), MC1b (P450IA1) and UT1 (P450IIA1) consistently inhibited BP metabolism. This inhibition was generally limited and rarely exceeded 30%. An antibody to cytochrome P450 PB3a (P450IIB1) did, however, inhibit the formation of metabolites at the 4,5- and 9,10-positions of BP by microsomal fractions of livers from one individual who had been receiving the drug phenytoin. These data indicate that several forms of P450 in human liver are involved in the metabolism of BP and that both constitutively expressed as well as inducible forms are important in its disposition in man.

Adult

Purification and characterization of an alpha 2-macroglobulin-like proteinase inhibitor from plasma of the crayfish Pacifastacus leniusculus.

An alpha 2-macroglobulin (alpha 2M)-like proteinase inhibitor from plasma of the crayfish Pacifastacus leniusculus was purified to apparent homogeneity by acid precipitation, hydrophobic interaction chromatography, affinity chromatography on concanavalin A-Sepharose and anion-exchange chromatography. The subunit Mr is about 190,000. Pore-size-limit electrophoresis proved the native protein to be a dimer. The purified protein resembled vertebrate alpha 2 Ms in that it protected trypsin from inhibition by soyabean trypsin inhibitor, and in its sensitivity to methylamine treatment. Methylamine also prevented the protein from being autolytically cleaved into Mr 60,000 and 140,000 fragments when subjected to heat treatment. The amino acid composition showed similarities with both human alpha 2 M and an alpha 2 M-like protein from the arthropod Limulus polyphemus. These data indicate that this Pacifastacus alpha 2M-like protein (P alpha 2M) may be a distantly related homologue of vertebrate alpha 2Ms.

Amino Acids