Artemisinin-derived sesquiterpene lactones as potential antitumour compounds: cytotoxic action against bone marrow and tumour cells

Epidemiologic and public health researchers frequently include several dependent variables, repeated assessments, or subgroup analyses in their investigations. These factors result in multiple tests of statistical significance and may produce type 1 experimental errors. This study examined the type 1 error rate in a sample of public health and epidemiologic research. A total of 173 articles chosen at random from 1996 issues of the American Journal of Public Health and the American Journal of Epidemiology were examined to determine the incidence of type 1 errors. Three different methods of computing type 1 error rates were used: experiment-wise error rate, error rate per experiment, and percent error rate. The results indicate a type 1 error rate substantially higher than the traditionally assumed level of 5% (p < 0.05). No practical or statistically significant difference was found between type 1 error rates across the two journals. Methods to determine and correct type 1 errors should be reported in epidemiologic and public health research investigations that include multiple statistical tests.     

Somatization in general practice

Patients with unexplained physical symptoms are very common in primary care. Some patients attribute these symptoms to physical disease (somatizing patients). Somatization can be a symptom of psychiatric disorder, which is found in 1/4 to 1/3 of the patients in a primary care setting. This form of somatization makes diagnosing difficult and is the main reason why psychiatric disorders are underdiagnosed. Simple techniques for diagnosing and treating somatizing patients are available to general practitioners. However, to improve diagnostic sensitivity and treatment, further teaching and development in primary care settings are necessary.     

Protein oxidative damage in a transgenic mouse model of familial amyotrophic lateral sclerosis

The Gly93-->Ala mutation in the Cu,Zn superoxide dismutase (Cu,Zn-SOD) gene (SOD1) found in some familial amyotrophic lateral sclerosis (FALS) patients has been shown to result in an aberrant increase in hydroxyl radical production by the mutant enzyme that may cause oxidative injury to spinal motor neurons. In the present study, we analyzed the extent of oxidative injury to lumbar and cervical spinal cord proteins in transgenic FALS mice that overexpress the SOD1 mutation [TgN(SOD1-G93A)G1H] in comparison with nontransgenic mice. Total protein oxidation was examined by spectrophotometric measurement of tissue protein carbonyl content by the dinitrophenylhydrazine (DNPH) assay. Four ages were investigated: 30 (pre-motor neuron pathology and clinical disease), 60 (after initiation of pathology, but pre-disease), 100 (approximately 50% loss of motor neurons and function), and 120 (near complete hindlimb paralysis) days. Protein carbonyl content in 30-day-old TgN(SOD1-G93A)G1H mice was twice as high as the level found in age-matched nontransgenic mice. However, at 60 and 100 days of age, the levels were the same. Then, between 100 and 120 days of age, the levels in the TgN(SOD1-G93A)G1H mice increased dramatically (557%) compared with either the nontransgenic mice or transgenic animals that overexpress the wild-type human Cu,Zn-SOD [TgN(SOD1)N29]. The 100-120-day increase in spinal cord protein carbonyl levels was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoretic separation and western blot immunoassay, which enabled the identification of heavily oxidized individual proteins using a monoclonal antibody against DNPH-derivatized proteins. One of the more heavily oxidized protein bands (14 kDa) was identified by immunoprecipitation as largely Cu,Zn-SOD. Western blot comparison of the extent of Cu,Zn-SOD protein carbonylation revealed that the level in spinal cord samples from 120-day-old TgN(SOD1-G93A)G1H mice was significantly higher than that found in age-matched nontransgenic or TgN(SOD1)N29 mice. These results suggest that the increased hydroxyl radical production associated with the G93A SOD1 mutation and/or lipid peroxidation-derived radical species (peroxyl or alkoxyl) causes extensive protein oxidative injury and that the Cu,Zn-SOD itself is a key target, which may compromise its antioxidant function.     

A novel endonuclease from kinetoplastid hemoflagellated protozoan parasite Leishmania

A nuclease activity has been purified from the nuclei-kinetoplast fraction of Leishmania. This enzyme, termed endonuclease M (Endo M), is shown by electrophoresis in a denaturing polyacrylamide gel to be associated with a single polypeptide of molecular mass 52 kDa. Physical analysis of the enzyme indicates that it has a sedimentation coefficient S20,w of 4.5S, a Stoke's radius of 32.5 A, and a native molecular mass of 53 kDa. The final Mono Q purified Endo M possesses both DNase and RNase activities. It acts as an endonuclease by introducing random single-stranded nicks into the supercoiled DNA molecules, that often leads to its linearization due to nicking at the opposite strands, and subsequent degradation of the DNA with further incubation. Single-stranded DNA is twice preferred to double-stranded DNA as substrate. Single-stranded RNA is also degraded rapidly and is competitive as a substrate with single-stranded DNA. RNA:DNA hybrids, however, are largely resistant to the Endo M digestion.     

The production of Mullerian inhibiting substance by the fetal, neonatal and adult rat

The obligate aerobic yeast Rhodoturula gracilis was found to take up the alditols D-glucitol, D-mannitol, ribitol, xylitol, D-arabinitol, L-arabinitol and erythritol by means of a constitutive mobile membrane carrier. This uptake involved active transport, that is, it was dependent on the supply of metabolic energy, leading to the accumulation of alditols inside the cells. The accumulation ratio (intracellular concentration to extracellular concentration, Si/SO) was much lower for alditols than for monosaccharides. As for monosaccharides, this ratio decreased with increasing extracellular concentration, even to values below 1. The kinetic data showed that the carrier system for alditols was identical to that for monosaccharides, though it had a much lower affinity and maximum velocity for alditols. Hence the uptake of alditols was blocked in the presence of monosaccharides. Only ribitol and L-arabinitol were catabolized following enzyme induction. The other alditols were not broken down.     

Measurement of intracompartmental pressure: a comparison of the slit catheter, side-ported needle, and simple needle

An experimental model of acute compartment syndrome involving the anterolateral compartment of the hindlimb in dogs was used to compare three methods of measurement of intracompartmental pressure: the simple-needle technique, use of the slit catheter, and use of the side-ported needle. No statistical difference was found between the values obtained with the slit catheter and those obtained with the side-ported needle; the mean difference was 1.4 millimeters of mercury throughout the range of compartment pressures that were measured. The side-ported needle appeared to be as accurate as the slit catheter for the measurement of compartment pressures (p = 0.355, 1-beta = 0.9). The values obtained with use of the simple needle were consistently higher than those obtained with the other two methods (p < 0.001): an average of 18.3 millimeters of mercury higher than the values measured with the slit catheter and 19.3 millimeters of mercury higher than those measured with the side-ported needle. Clinically, the side-ported needle or the slit catheter can be used to obtain accurate measurements of compartment pressure. Use of the simple 18-gauge needle is not recommended for this purpose.     

Detection of serum antibodies to Chlamydia trachomatis in patients with chlamydial and nonchlamydial pelvic inflammatory disease by the IPAzyme Chlamydia and enzyme immunoassay

A novel serological test, IPAzyme Chlamydia (Savyon Diagnostics Ltd., Beer Sheva, Israel), was compared with an enzyme immunoassay (EIA) for the ability to detect serum immunoglobulin G and A antibodies in the diagnosis of acute chlamydial pelvic inflammatory disease. In comparison with cell culture, which is the "gold standard," IPAzyme Chlamydia and EIA exhibited sensitivities of 63 and 68% and specificities of 76 and 87%, respectively. Thus, IPAzyme Chlamydia offers no advantages over the EIA, and neither serological test can be recommended for the diagnosis of acute Chlamydia trachomatis infection. So far, conventional cell culture remains the most reliable diagnostic test for chlamydial pelvic inflammatory disease.