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Biomedical subjects

J Hall

Publications and source records attributed to J Hall.

At least 325 records · Page 18Linked to original sources

Findings in newborns of cocaine-abusing mothers.

Cocaine has recently been shown to affect the outcome of pregnancy when taken by pregnant women. The authors measured fetal concentrations of cocaine and benzoylecgonine and reviewed autopsy and historical data for 62 successive infants who died at less than two days of age and were seen at the Los Angeles County Office of the Chief Medical Examiner-Coroner. Of 43 infants without an obvious cause of death at autopsy, cocaine or benzoylecgonine or both were present in 40%. None of the parameters studied predicted which infants would show cocaine or benzoylecgonine. We conclude that cocaine and benzoylecgonine concentrations should be measured on all infants who die at less than two days of age when the cause of death is not evident at gross autopsy.

Autopsy↗

[The age-related dynamics of the activity of the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase in different organs of rats].

Concentrations of O6-alkylguanine-DNA alkyltransferase (AT) which repairs a procarcinogenic DNA adduct O6-alkylguanine formed following exposure to carcinogenic N-nitroso compounds were measured in the liver, kidney and peripheral blood leukocytes of male L10 rats aged 1, 4, 14, 22 and 36 months. In the liver, peak AT level was observed at the age of 14 and 22 months. No age-related differences were established for kidney and leukocytes. The highest concentration of AT was registered in the kidney while the lowest--in leukocytes. The study revealed stoichiometric transfer of O6-methylguanine methyl group to cysteine residue of AT. No positive correlation was established between individual tissue AT levels in different animals. The highest level of total protein and the lowest concentration of DNA were observed in the liver and kidney of 14-22 month-old rats. The data obtained provide an explanation for relative resistance of 1-2 year-old rats to hepatotropic nitrosamine and suggest that the level of AT in a given tissue is not predictive of its activity in other tissues.

Aging↗

Eukaryotic and prokaryotic signal peptides direct secretion of a bacterial endoglucanase by mammalian cells.

It is well established that hydrophobic signal sequences direct proteins into or across the endoplasmic reticulum membrane in eukaryotes and cell membranes in prokaryotes. Although it is recognized that eukaryote proteins are efficiently secreted by bacterial systems, the export of bacterial proteins by eukaryotes has received little attention. To investigate membrane translocation of bacterial proteins by mammalian cells, the secretion of a bacterial endoglucanase (endoglucanase E) from stably transfected Chinese hamster ovary cells has been examined. We report that a functional endoglucanase is secreted when fused to prokaryote or eukaryote signal peptides. Furthermore, the endoglucanase was post-translationally modified before secretion. Data presented in this paper suggest that secretion of bacterial proteins by eukaryote cells may be a general phenomenon and infer that there are no specific requirements with respect to the origin of the signal sequences.

Animals↗

Modulation of O6-methylguanine-DNA methyltransferase in rat and hamster liver after treatment with dimethylnitrosamine.

Distinct species differences exist between BDIV rats and Syrian Golden hamsters in the repair of methylated DNA lesions, after single exposures to dimethylnitrosamine (DMN). The promutagenic lesions O6-methylguanine (O6-MeG) and O4-methylthymidine were actively repaired in rat liver; in contrast, in hamster liver the levels of O6-MeG remained relatively stable while O4-methylthymidine levels were reduced. Species differences in the levels of two enzymes involved in the repair of DNA alkylation damage were also noted. An increase in the methylpurine-DNA glycosylase levels was seen in both species following DMN exposure; however, significant species differences in the inactivation and subsequent time course of recovery of the "suicide protein" O6-MeG-DNA methyltransferase were observed. In the rat a rapid recovery of activity began within 24 h of DMN exposure (20 mg/kg) and an approximately 3-fold induction in enzyme levels was observed at 96 h. In hamster liver, in which the constitutive level of expression of this enzyme is similar, no activity was detectable up to 96 h after treatment (25 mg/kg DMN). Only in animals in the lowest treatment group (2.5 mg/kg DMN) was a significant recovery seen, 264 h after treatment. The data presented suggest that the schedule of DMN treatment, in particular the time between doses of the carcinogen and the regeneration of the O6-MeG-DNA methyltransferase, would evoke different carcinogenic responses in hamster and rat liver following chronic exposure to alkylating agents.

Animals↗

Spatial separation of protein domains is not necessary for catalytic activity or substrate binding in a xylanase.

Xylanase A (XYLA) from Pseudomonas fluorescens subspecies cellulosa shows sequence conservation with two endoglucanases from the same organism. The conserved sequence in XYLA, consisting of the N-terminal 234 residues, is not essential for catalytic activity. Full-length XYLA and a fusion enzyme, consisting of the N-terminal 100 residues of XYLA linked to mature alkaline phosphatase, bound tightly to crystalline cellulose (Avicel), but not to xylan. The capacity of truncated derivatives of the xylanase to bind polysaccharides was investigated. XYLA lacking the first 13 N-terminal amino acids did not bind to cellulose. However, a catalytically active XYLA derivative (XYLA'), in which residues 100-234 were deleted, bound tightly to Avicel. Substrate specificity, cellulose-binding capacity, specific activity and Km for xylan hydrolysis were evaluated for each of the xylanases. No differences in any of these parameters were detected for the two enzymes. It is concluded that XYLA contains a cellulose-binding domain consisting of the N-terminal 100 residues which is distinct from the active site. Spatial separation of the catalytic and cellulose-binding domains is not essential for the enzyme to function normally.

Alkaline Phosphatase↗

Counting the costs of mammography screening: first year results from the Sydney study.

Population-based mammography screening is a highly specialized service which aims to improve the early detection of breast cancer. This is achieved through the installation of a dedicated mix of medical technology and professional skills. It is therefore a resource-intensive activity so the benefits foregone by deploying these resources for mammography screening ought to be determined to investigate the relative efficiency of such a commitment. This paper describes the costing methodology used in the evaluation of the Sydney Breast X-ray Programme and presents the health service costs for the first 12 months of operation. In the first year when attendance was under 5000 it cost $118.93 to screen a woman, $13,817 to detect a cancer and $18,720 to detect an impalpable cancer. However, costs are expected to fall in subsequent years as attendance reaches capacity level. The first screening round will detect prevalent cancers; costs will change with subsequent screening rounds as incident cancers are detected. We are cautious in extrapolating the costs of a national programme from these results. However, on the basis of our data and disregarding treatment costs, a national programme which screened 70% of all Australian women over the age of 45 years every two years would add between $60 million and $100 million to the national health bill each year.

Aged↗

Walking frames.

Explore the source record for details and available documents.

Equipment Design↗

What every doctor should know about economics. Part 2. The benefits of economic appraisal.

In this article we have discussed a number of aspects of economic appraisal. Economic evaluation considers both costs and benefits. Cost-benefit analysis requires the evaluation of health in dollar terms but allows the comparison of health programmes with other programmes or the evaluation of one project alone. Because of the problems that are associated with placing a monetary value on life and health, cost-benefit analysis has not been used in the health field as extensively as has cost-effectiveness analysis. Cost-effectiveness analysis is used to compare alternative programmes with the same health goal. The importance of quality as well as length of life as health outcomes has led to the development of cost-utility analysis. Finally, a good economic evaluation of health care requires the collaboration of clinicians and health economists.

Cost-Benefit Analysis↗

Active site amino acid sequence of the bovine O6-methylguanine-DNA methyltransferase.

An O6-methylguanine-DNA methyltransferase has been partially purified from calf thymus by conventional biochemical techniques. The enzyme was specifically radioactively labelled at the cysteine residue of the active site and further purified by attachment to a solid support. Following digestion with trypsin, a radioactive peptide containing the active site region of the protein was purified by size fractionation, ion exchange chromatography and reverse phase HPLC. The technique yielded an essentially homogeneous oligopeptide which was subjected to amino acid sequencing. The sequence adjacent to the acceptor cysteine residue of the bovine protein exhibits striking homology to the C-terminal methyl acceptor site of the E. coli Ada protein and the proposed acceptor sites of the E. coli Ogt and the B. subtilis Dat1 proteins.

Amino Acid Sequence↗

Impaired renal function due to raised intraabdominal pressure.

A 19-year-old male developed renal failure after a laparotomy for liver trauma (urinary output of 30 ml/h, plasma creatinine 220 mumol/l). Surgical decompression of the abdomen was performed without any attempt at correcting the underlying pathology. This reduced the intraabdominal pressure (IAP) from 40 to 24 cm H2O and resulted in a massive diuresis (530 ml/h). Twenty-four hours later the plasma creatinine peaked at 280 mumol/l and then returned to within the normal range. This case report confirms that there is a direct relationship between IAP and renal function.

Acute Kidney Injury↗

Endoglucanase E, produced at high level in Escherichia coli as a lacZ' fusion protein, is part of the Clostridium thermocellum cellulosome.

The Clostridium thermocellum celE gene was expressed at high level in Escherichia coli TG1 when placed under the transcriptional and translational control of lacZ' in pUC18; in the presence of a multicopy plasmid (pNM52) containing the lacIq gene, expression of full-length and truncated forms of celE was regulated by isopropyl-beta-D-thiogalactopyranoside. Catalytically active endoglucanase E (EGE) produced by E. coli was subject to proteolytic processing. The main protein species produced from full-length and truncated forms of celE was around 40 kDa in size and had an N-terminal amino acid sequence corresponding to that derived for mature EGE from the nucleotide sequence; in addition, larger species of about 75 kDa, presumably corresponding to full-size EGE, were produced by E. coli containing the full-length celE gene. Even after removal of the signal peptide sequence, EGE produced by E. coli was secreted into the periplasm. Up to 157 bp could be deleted from the 5' end of the celE gene without affecting the catalytic activity of EGE produced by E. coli. A polypeptide of Mr 86 kDa, immunoreactive with anti-EGE antiserum, was demonstrated in the high-molecular-weight, cellulose-binding multiprotein aggregate recoverable from C. thermocellum culture supernatant.

Amino Acid Sequence↗