Inhibition of glyoxylate conversion to oxalate in cultured human cells by the carbonyl-scavenging drug, aminoguanidine

Calcium oxalate is the most frequent cause of kidney stones, and is responsible for the damage to kidneys and other organs observed in inherited disorders of oxalate metabolism. Most oxalate produced in the body is derived from its metabolic precursor, glyoxylate. Thus, any means of scavenging glyoxylate to a non-toxic product, thereby diverting it away from oxalate synthesis, has considerable therapeutic implications. Here we show that aminoguanidine, a compound with a proven safety record and used for many years to prevent long-term complications of diabetes, binds glyoxylate covalently and reduces its conversion to oxalate by human liver- and lymphocyte-derived cell lines by >90%. We propose that scavenging glyoxylate with aminoguanidine or its congeners may provide a means of reducing oxalate production in vivo, and advocate the tissue culture system described here as a convenient means for testing such agents in vitro. A serendipitous finding to emerge from our study was the abiotic and strongly pH-dependent formation of oxalate from ascorbate, which has implications for the contribution of ascorbate to urine oxalate excretion

Risk factors for atherosclerosis - can they be used to identify the patient with multisystem atherosclerosis?

Risk factors are often used in preventive care programmes to identify the patient at particular risk for developing atherosclerosis. Risk factors for atherosclerosis have also been shown to be linked to the presence of the disease at a given time, a fact that may be helpful when screening for additional atherosclerotic disease in the known arteriopath. Risk factors .were recorded in 471 patients admi"ed to hospital with symptoms of atherosclerosis. In patients admi"ed primarily with peripheral vascular disease, risk factors linked to the presence of additional coronary artery disease were a family history of ischaemic heart disease (odds ratio = 2,6), the presence of carotid artery disease (odds ratio = 1,9) and high fasting serum triglyceride levels (P < 0,04). Grouping these factors together usin.g logistic regression, ischaemic heart disease could be predicted with a sensitivity of 72% and a specificity of 43%. Patients admitted with carotid artery disease were more likely to have ischaemic heart disease in the presence of peripheral vascular disease (odds ratio = 1,9) and a raised serum cholesterol level (P < 0,02), while female gender (odds ratio = 2,9) and an increase in age (P< 0,001) were linked to an increased prevalence of concomitant atherosclerosis in patients admmed with acute myocardial infarction or for elective coronary artery bypass surgery. Using an age cut-off point, additional atherosclerosis could be predicted with a sensitivity of 32% and a specificity of 88% in these patients

KPNB1 (karyopherin (importin) beta 1)

Review on KPNB1 (karyopherin (importin) beta 1), with data on DNA, on the protein encoded, and where the gene is implicated

Plasma sarcosine does not distinguish early and advanced stages of prostate cancer

Introduction. Diagnosis of prostate cancer by prostate specific antigen (PSA) is error-prone and cannot distinguish benign prostatic hyperplasia (BPH) from malignant disease, nor identify aggressive and indolent types. Methods. We determined serum sarcosine (N-methylglycine) in 328 cancer patients by gas chromatography (GC)/mass spectroscopy (MS) and searched for correlations with early (stage T1/T2) and advanced (stage T3/T4) disease. Results. Serum sarcosine of male control patients ranged from 1.7 µmol/l to 4.8 µmol/l. In prostate cancer patients, sarcosine ranged from 2.8 µmol/l to 20.1 µmol/l. Expressed as the sarcosine/alanine ratio, serum control values were 9.4±5.5x10-3 (mean±SD) compared with 21.6±9.0; 28.5±16.6; 22.7±7.7 and 22.2±11.0 for patients diagnosed with T1, T2, T3 and T4 prostate tumours, respectively. The small differences between T1, T2, T3 and T4 patients were not statistically significant (p=0.51). However, the conventional PSA marker significantly correlated with T stage in these patients (r=0.63;

The Globular Cluster Systems in the Coma Ellipticals. II: Metallicity Distribution and Radial Structure in NGC 4874, and Implications for Galaxy Formation

Deep HST/WFPC2 (V,I) photometry is used to investigate the globular cluster system (GCS) in NGC 4874, the central cD galaxy of the Coma cluster. The luminosity function of the clusters displays its normal Gaussian-like shape and turnover level. Other features of the system are surprising: the GCS is (a) spatially extended, with core radius r_c = 22 kpc, (b) entirely metal-poor (a narrow, unimodal metallicity distribution with mean [Fe/H] = -1.5), and (c) modestly populated, with specific frequency S_N = 3.7 +- 0.5. We suggest on the basis of some simple models that as much as half of this galaxy might have accreted from low-mass satellites, but no single one of the three classic modes of galaxy formation (accretion, disk mergers, in situ formation) can supply a fully satisfactory formation picture. Even when they are used in combination, strong challenges to these models remain. The principal anomaly in this GCS is essentially the complete lack of metal-rich clusters. If these were present in normal (M87-like) numbers in addition to the metal-poor ones that are already there, then the GCS in total would more closely resemble what we see in many other giant E galaxies.Comment: 27 pp. with 9 Figures. Astrophys.J. 533, in press (April 10, 2000

Impact of a Prohibitive Versus Restrictive Tobacco Policy on Liver Transplant Candidate Outcomes

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150602/1/lt25497_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150602/2/lt25497.pd

Arsenic in Soils and Forages from Poultry Litter-Amended Pastures

In regions of concentrated poultry production, poultry litter (PL) that contains significant quantities of trace elements is commonly surface-applied to pastures at high levels over multiple years. This study examined the effect of long-term applications of PL on soil concentrations of arsenic (As), copper (Cu), Zinc (Zn), and the uptake of these elements by bermuda grass grown on Cecil (well-drained) and Sedgefield (somewhat poorly-drained) soils. The results showed that concentrations of As, Cu, and Zn in soils that had received surface-applied PL over a 14-year period were significantly greater than untreated soil at 0–2.5 and 2.5–7.5 cm depths. However, the levels were well below the USEPA loading limits established for municipal biosolids. Arsenic fractionation showed that concentrations of all As fractions were significantly greater in PL-amended soils compared to untreated soils at 0–2.5 and 2.5–7.5 cm depths. The residual fraction was the predominant form of As in all soils. The water-soluble and NaHCO3-associated As were only 2% of the total As. Significant differences were found in concentrations of these trace elements and phosphorus (P) in forage from PL-amended soils compared to that in untreated plots. The concentrations of Cu, Zn, As, and P were significantly greater in forage from Sedgefield amended soil compared to Cecil soil, but were in all cases below levels of environmental concern