Apoptosis as a cause of death in measles virus-infected cells

To determine the mechanism of measles virus-induced cell death, we studied the infection of Vero cells and monocytic cell lines with wild-type (Chicago-1) and vaccine (Edmonston) strains of measles virus. DNA fragmentation indicative of apoptosis was apparent by flow cytometry, agarose gel electrophoresis, and electron microscopy. Within syncytia, DNA strand breaks were demonstrated by end labeling with terminal transferase and then by visualization.     

Angiotensin II regulates the expression of plasminogen activator inhibitor-1 in cultured endothelial cells. A potential link between the renin-angiotensin system and thrombosis

Plasminogen activator-inhibitor C-1 (PAI-1) plays a critical role in the regulation of fibrinolysis, serving as the primary inhibitor of tissue-type plasminogen activator. Elevated levels of PAI-1 are a risk factor for recurrent myocardial infarction, and locally increased PAI-1 expression has been described in atherosclerotic human arteries. Recent studies have shown that the administration of angiotensin converting enzyme inhibitors reduces the risk of recurrent myocardial infarction in selected patients. Since angiotensin II (Ang II) has been reported to induce PAI-1 production in cultured astrocytes, we have hypothesized that one mechanism that may contribute to the beneficial effect of angiotensin converting enzyme inhibitors is an effect on fibrinolytic balance. In the present study, we examined the interaction of Ang II with cultured bovine aortic endothelial cells (BAECs) and the effects of this peptide on the production of PAI-1. 125I-Ang II was found to bind to BAECs in a saturable and specific manner, with an apparent Kd of 1.4 nM and Bmax of 74 fmol per mg of protein. Exposure of BAECs to Ang II induced dose-dependent increases in PAI-1 antigen in the media and in PAI-1 mRNA levels. Induction of PAI-1 mRNA expression by Ang II was not inhibited by pretreating BAECs with either Dup 753 or [Sar1, Ile8]-Ang II, agents that are known to compete effectively for binding to the two major angiotensin receptor subtypes. These data indicate that Ang II regulates the expression of PAI-1 in cultured endothelial cells and that this response is mediated via a pharmacologically distinct form of the angiotensin receptor.     

SURFACE TENSION AND BUOYANCY DRIVEN INSTABILITIES IN A LAYER OF LIQUID TIN HEATED FROM BELOW

The linear theory of Pearson (1958) and Nield (1964) is modified here to study liquid tin and include the finite thermal resistances of the bounding layers of boron nitride, copper and air (∼10^-2 torr) in the experiments of Ginde et al. (1989). The magnitude of the ΔT_c across the layer of liquid tin required for the onset of convection depends on the ratios of the thermal conductivities and thicknesses of the supporting layers of boron nitride and copper to those of the tin.

According to our theory surface tension contributes more than buoyancy to the instability observed experimentally. The critical ΔT_c observed required for the onset of convection in the layer of tin, is up to 25% lower than that predicted, which shows the layer is less stable than the theory indicates. Thus the surface of the tin was uncontaminated, or a significantly larger observed critical ΔT_c would be expected.

The boundary condition on the thermal fluctuations at the base of the supporting layer of copper does not appear to be important in these experiments. However, the thermal resistance of the boron nitride would have to be assumed to be unrealistically large to obtain agreement within experimental error with the theory.     

Evaluation of a commercial process for collection and cooling of beef offals by a temperature function integration technique.

The hygienic adequacy of a commercial process for the collection and cooling of beef offals was assessed by a temperature function integration technique. The diverse operations for collection of offals were inspected. The rates of product movement through those operations, and the temperatures of products at the time of their being packed, were determined. From that information, four of the nine product types were selected for examination of their temperature histories during the assembly and cooling of the cartoned products. The products selected encompassed product at near-body and near-air-ambient temperatures at the time of packaging, product in the largest and smallest cartons used in the process, and product with relatively short and long residence times in an unchilled carton stack assembly area. Twenty-one temperature histories were collected for each of the products, and the possible proliferation of an indicator organism, Escherichia coli, calculated for each temperature history. The results were assessed against a temperature function integration criterion derived from studies of beef carcass and cartoned meat cooling processes. Products packaged at near-ambient temperature readily met with the criterion, but products packed at near-body temperatures did not comply. The latter non-compliance was extreme for product packaged in large cartons. However, the principal cause of non-compliance was identified as highly variable cooling conditions in the carton freezing facility. A brief survey of air speeds and temperatures within that facility indicated means by which product cooling could be better controlled.     

Computational dosimetry and treatment planning for boron neutron capture therapy

The longitudinal, expert, all data (LEAD) procedure has been employed as a criterion for the assessment of the procedural validity of diagnostic instruments. This study evaluated the procedure's concurrent, discriminant and predictive validity. Interview and questionnaire data obtained from 100 individuals in a substance abuse treatment program were used to assess current and lifetime substance use disorders and common comorbid disorders. An experienced, doctoral-level clinician formulated LEAD diagnoses for each patient, based on an initial interview, ongoing clinical contact and the results of the research assessment and all available clinical records. LEAD-derived substance use diagnoses showed good concurrent, discriminant and predictive validity. The validity of comorbid diagnoses obtained using the LEAD procedure was generally fair to good. Comparison with diagnoses based only on the clinician's unstructured initial interview showed that the availability of additional data enhanced diagnostic validity. Diagnoses derived by a research technician using the Structured Clinical Interview for DSM-III-R showed validity comparable to that of LEAD diagnoses. To enhance its diagnostic validity, applications of the LEAD standard should include a structured interview. Other variations in the application of the LEAD standard, including a longer evaluation period, may also enhance its performance as a diagnostic criterion measure.     

Assessment of bog-body tissue preservation by pyrolysis-gas chromatography/mass spectrometry

Flash pyrolysis-gas chromatography/mass spectrometry (py-GC/MS) was used to assess the quality and mechanism of protein preservation in the tissue of Iron Age bog bodies from Lindow, UK, and south-eastern Drenthe, The Netherlands. Abundant pyrolysis products of the fresh skin tissue, including 2,5-diketopiperazines of Pro-Gly, Pro-Ala, Pro-Val, Pro-Pro and Hyp, were readily assigned to specific amino acid or dipeptide moieties. Comparison of the pyrolysates of the bog-body tissues with that of modern samples revealed qualitative similarities suggesting good preservation of the collagen and non-collagenous proteins in the ancient tissues. Examination of the pyrolysates of samples of fresh calf skin, which had been treated with various vegetable tanning agents, clearly revealed markers of non-hydrolysable tannins including 1,2-benzenediol, 1,3-benzenediol and 1,2,3-benzenetriol, although chromatographic quality inevitably diminished with increasing functionalization of the compounds. Such markers were not detected in the pyrolysates of the bog-body tissues. Instead 4-isopropenylphenol, a characteristic pyrolysis product of Sphagnum moss, was detected in both solvent-extracted and base-treated samples of tissue. The presence of 4-isopropenylphenol in the pyrolysates of the bog-body tissues provides evidence that their preservation involves reactions of amino acids with sphagnum acid, and possibly other agents derived from the peat. The study constitutes the first chemical characterization of the pyrolysis products of modern and ancient collagen.     

Treatment with alendronate prevents fractures in women at highest risk: results from the Fracture Intervention Trial

BACKGROUND: The efficacy of antiresorptive therapy in preventing fractures in women at highest fracture risk, such as very elderly women or those with severe osteoporosis, is uncertain. PARTICIPANTS AND METHODS: Using data from a double-blind, randomized, placebo-controlled clinical trial that enrolled 2027 postmenopausal women aged 55 to 81 years with low femoral neck bone mineral density (BMD) and existing vertebral fractures, we examined the consistency of the effect of treatment with alendronate sodium in preventing fractures within a priori-specified risk subgroups defined at baseline by age, bone density, number of preexisting vertebral fractures, and history of postmenopausal fracture. The women were randomized to oral administration of alendronate or placebo and followed up for an average of 2.9 years. The initial dose of alendronate sodium was 5 mg/d; the dosage was increased from 5 to 10 mg/d at 24 months. New vertebral fractures, the primary end point of this arm of the trial, were defined by morphometry as a decrease of 20% and at least 4 mm in any vertebral height between baseline and a follow-up radiograph at 36 months. Incident clinical fractures, the secondary end point, included nonspine and clinical (symptomatic) vertebral fractures. All clinical fractures were confirmed with x-ray film reports or, in the case of clinical vertebral fractures, x-ray films. RESULTS: Overall, there was a 47% significant reduction in risk of new vertebral fractures in the alendronate group compared with the placebo group. The reduction in risk of new vertebral fracture was consistent across fracture risk categories including age (relative risk [RR], 0.49 in women < 75 years compared with 0.62 in those > or = 75 years), BMD (RR, 0.54 in women with a femoral neck BMD < 0.59 g/cm2 [median] compared with 0.53 in those with a BMD > or = 0.59 g/cm2), and number of preexisting vertebral fractures (RR, 0.58 in women with 1 vertebral fracture compared with 0.52 in those with > or = 2). The overall significant 28% reduction in risk of incident clinical fractures in the alendronate group compared with the placebo group was also observed within these subgroups. Compared with the number of lower-risk women, a similar or smaller number of high-risk women needed to be treated to prevent 1 fracture. For example, 8 women aged 75 years or older compared with 9 women younger than 75 years, or 4 women with 2 or more existing vertebral fractures compared with 16 women with 1 existing vertebral fracture, needed to be treated with alendronate for 5 years to prevent 1 new vertebral fracture. CONCLUSIONS: Alendronate effectively reduces fracture risk in postmenopausal women with vertebral fractures and low BMD, including those women at highest risk because of advanced age or severe osteoporosis. Since the risk reductions observed with alendronate treatment were consistent within fracture risk categories, more fractures were prevented by treating women at highest risk.