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Biomedical subjects

J C Craig

Publications and source records attributed to J C Craig.

194 records · Page 11Linked to original sources
PubMedDate not supplied

Valproic acid-induced alterations in growth and neurotrophic factor gene expression in murine embryos [corrected].

Although the teratogenicity of valproic acid (VPA) has been well established, the mechanism(s) by which this anticonvulsant drug induces malformations remains controversial. Using the combined molecular techniques of in situ-transcription (IST) and antisense RNA (aRNA) amplification we analyzed VPA-induced alterations in the gene expression for 10 genes within the neural tubes of embryos from two murine strains that have been shown to differ in their susceptibility to VPA-induce neural tube defects (NTD). Pregnant dams from both SWV (susceptible) and LM/Bc (resistant) strains were either treated with saline (control) or VPA (600 mg/kg) on gestational day (GD) 8:12 (day:hour). Neural tubes were isolated from control or VPA exposed embryos at three gestational time points, which represented the beginning (GD 8:18), middle (GD 9:00), and end (GD 9:12) of neural tube closure (NTC) in both of these murine strains. Using univariant statistics we demonstrated that in LM/Bc embryos with NTDs, the expression of bdnf, ngf, and trk, ngf-R were significantly elevated at all three time points, and the cytokine, cntf was significantly decreased at GD 9:00. In contrast, the major gene alterations observed in SWV embryos were a significant increase in tfgalpha and tgfbeta1-3 at GD 9:00. In an effort to better define the more intricate interactions between VPA exposure and the expression of these genes, we analyzed our data using Principal Component Analysis. The results from this analysis demonstrated that embryos from these two stains behaved differently, not only in response to a VPA exposure, but also under control conditions, which may explain the multifactorial nature of NTDs in these mice.

Analysis of Variance↗
PubMedDate not supplied

Dry-grind process for fuel ethanol by continuous fermentation and stripping.

Conversion of a high-solids saccharified corn mash to ethanol by continuous fermentation and stripping was successfully demonstrated in a pilot plant consuming 25 kg of corn per day. A mathematical model based on previous pilot plant results accurately predicts the specific growth rate obtained from these latest results. This model was incorporated into a simulation of a complete dry-grind corn-to-ethanol plant, and the cost of ethanol production was compared with that of a conventional process. The results indicate a savings of $0.03 per gallon of ethanol produced by the stripping process. The savings with stripping result from the capacity to ferment a more concentrated corn mash so there is less water to remove downstream.

Ethanol↗
PubMedDate not supplied

Continuous fermentation and stripping of ethanol.

Recycling the contents of a continuous fermentor through a stripping column is proposed as a means of reducing product inhibition and lowering the cost of fuel ethanol production. A 2-L fermentor and 10-cm packed column were continuously operated for 150 days without contamination. Some fouling of the packing with attached yeast cells was observed which partially blocked the column. Cell yield was lower than in a simple continuous fermentor. Complete conversion of 200 g/L glucose feed and 90% conversion of 600 g/L glucose feed were achieved. Data were analyzed by computerized process simulation. Cost analysis indicated that, with heat recovery to reduce heating and cooling costs, the continuous fermentor/stripper is possibly a lower-cost alternative to conventional fermentation and distillation.

Biotechnology↗
PubMedDate not supplied

Quantitative analysis of benzene by selected ion monitoring/gas chromatography/mass spectrometry.

A selected ion monitoring gas chromatographic/mass spectrometric method for the quantitative determination of benzene in air, breath, and blood was developed utilizing a headspace assay with benzene-d3 as an internal standard. Limits of detection for 2 ng/mL in blood and 0.1 ppb in a 5-L sample of air or breath were attained. The influence of contamination by background benzene on the analytical process was studied carefully. For cases where background contamination could not be adequately controlled, the assay was modified for the quantitative determination of labelled benzenes six mass units heavier than natural benzene (benzene-d6 or benzene-13C6). Use of the method for the analysis of natural benzene was illustrated for the measurement of background levels in urban smokers and nonsmokers.

Air↗
PubMedDate not supplied

A selected ion monitoring GC/MS assay for 3,4,4'-trichlorocarbanilide and its metabolites in biological fluids.

A selected ion monitoring gas chromatography/mass spectrometric method for the quantitative determination of 3,4,4'-trichlorocarbanilide (TCC) and its major metabolites (the 2'-hydroxy sulfate and the N- and N'-glucuronides) in human plasma and urine was developed using the deuterium-labelled compounds as internal standards. Limits of detection of 3 ng/mL in urine for the N-glucuronides and of 1.5 ng/mL in plasma for the 2'-hydroxy sulfate were attained. Use of the method was illustrated in a study in human subjects employing TCC-containing bar soaps.

Body Fluids↗
PubMedDate not supplied

Renal impairment and anaemia in a population-based study of older people.

BACKGROUND: Established renal failure is a known cause of anaemia. However, the association between more modest levels of renal impairment and anaemia is unclear. AIMS: The aim of the present study was to investigate the association between mild renal impairment and anaemia in the general population. METHODS: A population-based, cross-sectional study was conducted in the general community in an urban area of the Blue Mountains, just west of Sydney, Australia. The study included 3222 people aged > or =49 years (mean age 65 years). Serum creatinine and haemoglobin were measured using standard laboratory techniques. Creatinine clearance was estimated from serum creatinine, body weight, sex and age. RESULTS: Two hundred and seventy subjects (8.4%) had serum creatinine levels > or =125 micromol/L and estimated -creatinine clearances were <0.84 mL/s (50 mL/min) in 894 subjects (27.7%) and <0.50 mL/s (30 mL/min) in 120 subjects (3.7%). There was a strong association between reduced renal function and anaemia. Compared to those with serum creatinine <125 micromol/L, the age-adjusted relative risk (RR) of anaemia in women (haemoglobin <12.0 g/dL) with serum creatinine > or =125 micromol/L was 5.5 (95% confidence interval (CI) 2.9-10.7) and the RR of anaemia in men (haemoglobin < 13.0 g/dL) was 3.1 (95% CI 1.6-6.0). Estimated -creatinine clearance <50 mL/min was associated with a three-fold increased risk of anaemia in women and a five-fold increased risk in men. CONCLUSIONS: The results of the present study suggest that even modestly impaired renal function is associated with anaemia in older men and women. The possibility of renal impairment should be considered in the diagnosis and management of anaemia in people aged>50 years.

Age Factors↗
PubMedDate not supplied

Feasibility study of the early detection and treatment of renal disease by mass screening.

AIM: To determine whether mass screening for proteinuria may be worthwhile in the detection of early renal disease in Australians. METHODS: A feasibility study was conducted using systematic review, meta-analysis and cost-effectiveness methods. RESULTS: End-stage renal disease (ESRD) develops in about 1500 Australians each year. Of these, about 1000 are over 50 years of age (an incidence of about 200 per million, per year). Proteinuria, which is present in about 5% of the general population, confers an approximately 15-fold increased risk for ESRD. Twelve randomized trials of angiotensin-converting enzyme inhibitors (ACEi), in 1943 patients with varying degrees of renal impairment, hypertension and proteinuria, showed that the risk of developing ESRD can be reduced by about 30% over a 2- to 3-year period. In a general-practice-based screening model involving: (i) an opportunistic single dipstick test for protein, (ii) a confirming 24-h urine test for protein and (iii) commencement of ACEi in appropriate individuals, 20 000 people over 50 years of age would need to be screened to prevent one case of ESRD. To achieve this, approximately 100 people would need to be treated with ACEi for 2 to 3 years, and 1,000 would need to have a 24-h urine protein test (and of these, 700 would be false positives). Such a strategy may save health dollars but some critical research questions are still unanswered. What is an individual's risk of developing ESRD, given values for proteinuria, blood pressure and renal function? What is the benefit of ACEi in screen-detected cases, which are at low risk of ESRD? What psychological and physical harm is caused by screening, including the specific renal investigations and treatments that follow on from proteinuria detection? CONCLUSIONS: Given available data, screening middle-aged and older Australians for proteinuria and treating some with ACEi is, at best, a promising primary prevention strategy for preventing ESRD. However, a large population-based cohort study, with nested trial of ACEi, is still required to evaluate whether this model of screening for renal disease does more harm than good.

Aged↗
PubMedDate not supplied

Chlorpromazine metabolism in extracts of liver and small intestine from guinea pig and from man.

The metabolism of chlorpromazine by microsomes in vitro has been examined with extracts from normal liver and small intestinal mucosa of man and guinea pigs. A GC-MS approach has been utilized to measure primary metabolites generated by these extracts, including the S-oxide, N-oxide, 7-hydroxyl, desmethyl, and didesmethyl species. In short term incubations (less than 30 min), the measured metabolites accounted for at least 90% of the substrate utilized. Chlorpromazine metabolism differed strikingly both between species and between hepatic and intestinal tissues of the same species. Guinea pig hepatic microsomes were the most active of the preparations studied, producing relatively large amounts of N-oxide. By contrast, human hepatic microsomes produced the 7-hydroxyl metabolite predominantly, with minimal formation of N-oxide. Extracts of guinea pig intestinal mucosa formed the desmethyl and S-oxide products; an extract of duodenal mucosa from a healthy accident victim exhibited minimal metabolism of chlorpromazine. The kinetics of metabolite formation and studies with inhibitors of cytochrome P-450 suggested the involvement of multiple microsomal enzymes in chlorpromazine metabolism.

Adult↗