Apparent first-order kinetics in the transformation of 1,1,1-trichloroethane in groundwater following a transient release

A transient release of 1,1,1-trichloroethane (TCA) to an otherwise uncontaminated aquifer at a manufacturing facility presented a useful opportunity to validate the results of previous laboratory and field studies on TCA transformation in groundwater. Abiotic TCA transformation to 1,1-dichloroethylene (DCE) and acetic acid at the site exhibited first-order kinetics with half-life of 2.9 years 15 degrees C. Degradation effects were seen to overwhelm chemical retardation effects on the DCE/TCA concentration ratio in groundwater. The kinetic data was sufficient to date the release to within one week of when it actually occurred. A kinetic approach may be applicable to dating the releases on other contaminated sites where a single transient release is indicated. The transformation of dissolved TCA in groundwater with a half-life of several years can be expected at many contaminated sites.     

A role for Edman degradation in proteome studies

Advances in protein database design and the software used to access the sequence data has led to progress in using protein attributes such as amino acid composition and peptide masses to identify proteins separated by two-dimensional electrophoresis. However, Edman degradation remains the principal technique for protein identification and it presents a significant bottleneck in the progress towards rapid protein identification. Simple modifications to the sequencing hardware, which automate the delivery of protein spots into the sequencer, and parallel sequencing of the protein spots represent a significant advance in the use of Edman degradation to rapidly generate the powerful protein attribute, an N-terminal sequence tag.     

Non-diuretic-based antihypertensive therapy and potassium homeostasis in elderly patients

Aging and hypertension are associated with a progressive decline in renal blood flow and renal function. As a result, physicians planning therapeutic strategies to control blood pressure need to consider these changes and how they relate to potassium homeostasis, particularly in elderly patients. Commonly used antihypertensive drugs such as beta-blockers, angiotensin converting enzyme inhibitors and potassium-sparing diuretics need to be used with increasing caution in patients with declining renal function. This is especially important in patients with diabetes who may also have type IV renal tubular acidosis, and in patients given concomitant therapy with non-steroidal anti-inflammatory drugs. Other therapies such as calcium channel blockers, particularly those that gate atrioventricular nodal conduction, also need to be used with care in people with significant renal insufficiency and hyperkalemia, as this clinical scenario may result in a greater risk of complete heart block.     

Expansion in bioreactors of human progenitor populations from cord blood and mobilized peripheral blood

Umbilical cord blood (UCB) and mobilized peripheral blood (MPB) provide an alternate source to bone marrow for transplantation. Expansion in vitro of stem/progenitor cell populations from these sources may provide adult-sized grafts otherwise not attainable because of the limited cell numbers available in the case of UCB or because of numerous rounds of apheresis required for sufficient MPB cells. We asked whether continuous perfusion culture could be employed in ex vivo expansion to produce clinically relevant numbers of stem/progenitor cells from these sources. To evaluate MPB, 1-10 million leukocytes, from patients who had received either granulocyte colony-stimulating factor (G-CSF) or cyclophosphamide and granulocyte-macrophage colony-stimulating factor (GM-CSF), were inoculated into bioreactors, with or without irradiated, allogeneic stroma. The growth factor combination in the perfusion medium consisted of interleukin-3 (IL-3), stem cell factor (SCF), GM-CSF and erythropoietin (Epo). Under the best conditions tested, total cell numbers, granulocyte-macrophage colony-forming units (CFU-GM), and long-term culture-initiating cell (LTC-IC) populations were expanded by about 50-, 80-, and 20-fold, respectively, over 14 days. At low cell inocula (1 million), the presence of stroma enhanced the expansion of total cells and CFU-GM but not of LTC-IC. When SCF was not included in the medium, both total cells and CFU-GM expanded to a much lesser extent, but again the expansion of LTC-IC was not affected. At the higher cell inoculum (10 million), expansions of total cells and CFU-GM were equivalent with or without stroma. To evaluate UCB, cells were placed into bioreactors with or without irradiated, allogeneic stroma, and the bioreactors were perfused with medium containing the four standard growth factors. After 6-14 days, in several independent experiments, 20-24 million cells were harvested from bioreactors perfused with SCF-containing medium, irrespective of the presence or absence of preformed stroma. Similarly, in reactors perfused with SCF-containing medium (with or without stroma), an average 40- to 60-fold expansion of CFU-GM was obtained, yielding an average of 1.5-1.8 x 10(5) CFU-GM per reactor. Harvested cells were thus up to 40-fold enriched in CFU-GM in comparison to the inoculum. In the absence of SCF, cell expansions averaged 1.5- to 2-fold, and CFU-GM were expanded only 10- to 14-fold by day 14. As before, the presence of preformed stroma did not affect either cell or CFU-GM yields, provided the cell inoculum was at least 4.5 million cells.(ABSTRACT TRUNCATED AT 400 WORDS)     

Analysis of the roles of antilipopolysaccharide and anti-cholera toxin immunoglobulin A (IgA) antibodies in protection against Vibrio cholerae and cholera toxin by use of monoclonal IgA antibodies in vivo

Secretory immunoglobulin A (IgA) antibodies (sIgA) directed against cholera toxin (CT) and surface components of Vibrio cholerae are associated with protection against cholera, but the relative importance of specific sIgAs in protection is unknown. A monoclonal IgA directed against the V. cholerae lipopolysaccharide (LPS), secreted into the intestines of neonatal mice bearing hybridoma tumors, was previously shown to provide protection against a lethal oral dose of 10(7) V. cholerae cells. We show here that a single oral dose of 5 to 50 micrograms of the monoclonal anti-LPS IgA, given within 2 h before V. cholerae challenge, protected neonatal mice against challenge. In contrast, an oral dose of 80 micrograms of monoclonal IgA directed against CT B subunit (CTB) failed to protect against V. cholerae challenge. A total of 80 micrograms of monoclonal anti-CTB IgA given orally protected neonatal mice from a lethal (5-micrograms) oral dose of CT. Secretion of the same anti-CTB IgA antibodies into the intestines of mice bearing IgA hybridoma backpack tumors, however, failed to protect against lethal oral doses of either CT (5 micrograms) or V. cholerae (10(7) cells). Furthermore, monoclonal anti-CTB IgA, either delivered orally or secreted onto mucosal surfaces in mice bearing hybridoma tumors, did not significantly enhance protection over that provided by oral anti-LPS IgA alone. These results demonstrate that anti-LPS sIgA is much more effective than anti-CT IgA in prevention of V. cholerae-induced diarrheal disease.     

Cell death, axonal damage, and cell birth in the immature rat brain following induction of hydrocephalus

We hypothesized that hydrocephalus can cause death of brain cells and that generation of new brain cells might compensate for the cell loss. Hydrocephalus was induced in 3-week-old rats by injection of kaolin into the cisterna magna. The brains were studied 1 to 4 weeks later by histochemical, immunochemical, and ultrastructural methods. The ventricles enlarged progressively. Some axons in the corpus callosum were injured as early as 1 week, but axonal damage was not prevalent until 4 weeks when ventriculomegaly became severe. Dying cells detected by DNA end labeling and often identified as oligodendrocytes by electron microscopy were evident in white matter. Late-stage hydrocephalus was associated with a significant increase in the quantity of dying cells. Hydrocephalus was associated with increased Ki67 labeling and bromodeoxyuridine incorporation in the subependymal zone. Reactive changes were identified among astrocytes, oligodendroglia, and microglia. We conclude that hydrocephalus causes, in addition to axonal injury, gradual cell death in the cerebrum, particularly the white matter. The brain response includes production of new glial cells, but whether the new cells play any beneficial role remains unknown.     

Premature introduction of progestin-only contraceptive methods during lactation

INTRODUCTIONS: Cochlear implants are used for the rehabilitation of bilaterally deaf patients. Due to the improvements in speech processing they might be also useful for patients with residual hearing and some speech understanding. METHODS: Pre- and postoperative speech understanding scores in 26 patients receiving implants were evaluated in a retrospective study. RESULTS: The preoperative pure-tone threshold in the implanted ear was between 80 and 115 dB in the frequency range of 500 to 2000 Hz. On the contralateral side the mean threshold was 10 dB better. The mean score for the number test was 11.3%, for the monosyllables below 5%. Postoperatively speech understanding improved significantly up to 97% for numbers and 48% for monosyllables (tested with the Freiburger Speech Test). Cochlear implantation also benefits patients with residual hearing and some speech understanding with hearing aids under optimum conditions. The speech understanding scores must be below certain limits. General selection criteria cannot yet be specified. The individual decision must be based upon several criteria, especially the speech understanding scores in quiet and noise under optimum conditions. A prospective study is needed to develop generally applicable criteria.     

Diazepam alters caffeine-induced effects on beta-endorphin levels in specific rat brain regions

The present study was conducted to evaluate the effects of caffeine and the benzodiazepine agonist diazepam, and a combination of both on beta-endorphin (beta-EN) levels in specific rat brain regions. Male Sprague-Dawley rats (150-200 g) adapted to a 12-hour light: 12-hour dark illumination cycle were used in this study. Caffeine (10 mg/kg), diazepam (2 mg/kg) or a combination of caffeine (10 mg/kg) and diazepam (2 mg/kg) were administered intraperitoneally to rats at 11:00 hr. Control animals were injected with saline. Animals were sacrificed by decapitation 1 h after injection, the brains were immediately removed; the cortex, hippocampus, hypothalamus and midbrain were dissected and their B-EN levels measured by radioimmunoassay. Caffeine administration significantly increased B-EN levels in the cortex. Similarly, administration of diazepam alone resulted in a significant increase of B-EN levels in cortex. However, concurrent administration of diazepam and caffeine resulted in higher increase of B-EN levels in cortex. No significant changes in B-EN levels were detected in hippocampus and midbrain after administration of either caffeine or diazepam alone. On the other hand, when diazepam and caffeine were concurrently administered a significant increase of B-EN levels were observed in the midbrain. Moreover, administration of diazepam alone resulted in a significant increase of B-EN levels in hypothalamus. This increase was still observed following concurrent administration of diazepam and caffeine. These results clearly indicate that diazepam alters caffeine-induced effects on B-EN in specific rat brain regions.     

Arterial reactivity is enhanced in genetic males taking high dose estrogens

OBJECTIVES: We sought to assess whether high dose estrogen treatment is associated with enhanced arterial reactivity in genetic males. BACKGROUND: Although estrogens have been shown to enhance arterial reactivity in women, and are thereby thought to confer cardiovascular benefit, the vascular effects of long-term estrogen therapy in genetic males is unknown. METHODS: We studied the arterial physiology of 30 genetic males--15 male to female transsexuals receiving long-term high dose estrogen therapy and 15 healthy male control subjects matched for age, smoking history and vessel size. Using external vascular ultrasound, brachial artery diameter was measured at rest, after flow increase (causing endothelium-dependent dilation [EDD]) and after nitroglycerin (GTN), an endothelium-independent dilator. Blood pressure, cholesterol and testosterone levels were also measured in each subject. RESULTS: Total testosterone and free testosterone index levels were lower in the transsexuals compared with the control subjects (p < 0.001). In contrast, EDD was significantly higher in the transsexuals than in the control males (mean [+/-SD] 7.1 +/- 3.1% vs. 3.2 +/- 2.8%, p = 0.001), as was the GTN response (21.2 +/- 6.7% vs. 14.6 +/- 3.3%, p = 0.002). Total and high density lipoprotein cholesterol, blood pressure levels and baseline vessel size were similar in the two groups. On multivariate analysis, enhanced EDD was associated independently with estrogen therapy (p = 0.02) and with low total cholesterol (p = 0.04). An enhanced GTN response was also significantly associated with estrogen therapy (p = 0.03). CONCLUSIONS: Long-term treatment with high dose estrogens is associated with enhanced arterial reactivity in genetic males, which may be due to the effects of estrogen excess or androgen deprivation, or both.