Characterization of “plasma proteins” secreted by cultured rat macroglial cells

The brain is isolated behind a blood-tissue barrier that restricts the access of circulating proteins to neural cells. There is evidence that some of these proteins are synthesized within the central nervous system. The present study examines the synthesis and secretion of such proteins by cultured macroglial cells. Primary glial cultures were derived from cortical and subcortical regions of neonatal rat brains, and subsequent secondary cultures were enriched in type-1 astrocytes, type-2 astrocytes, or oligodendrocytes. Newly synthesized proteins were immunoprecipitated from the culture media using antisera directed against whole rat serum. All three types of glial cells secreted a range of plasma proteins. In general, type-1 astrocytes secreted more of these proteins than did type-2 astrocytes or oligodendrocytes, although the one-dimensional polyacrylamide gel electrophoresis (PAGE) profiles were specific for each cell type. Antisera directed against specific plasma proteins identified three of the most abundant proteins secreted by type-1 astrocytes as transferrin, α-2-macroglobulin, and ceruloplasmin. Northern blot analysis of cellular RNA confirmed that type-1 astrocytes contained transferrin mRNA, and that it was more abundant in cultures derived from subcortical regions than from cortical regions. In situ hybridization studies revealed that virtually all type-1 and type-2 astrocytes contained transferrin mRNA. Since the proteins identified in this study have been proposed to have a variety of neurotrophic roles in the central nervous system, these data further extend the range of possible functions that glial cells may serve in the CNS.     

High-Temperature Short-Time Heat Inactivation of HIV and Other Viruses in Human Blood Plasma

An ultra-short-time heating system was used to process blood plasma spiked with various viruses (HIV, vesicular stomatitis virus, encephalomyocarditis virus). Virus reduction and recovery of plasma proteins were measured at various temperatures from 65 to 85 degrees C. Processing at 77 degrees C and 0.006 s resulted in a high level of virus kill, including greater than or equal to 4.4 log10 HIV, while maintaining protein structure and activity essentially intact.     

Oral tolerance in EAE: reversal of tolerance by T helper cell cytokines

Oral administration of myelin basic protein (MBP) inhibits clinical and histopathological manifestations of experimental autoimmune encephalomyelitis (EAE), but only partially reduces serum anti-MBP antibody titers. We report here that orally administered MBP alters the isotypic distribution of anti-MBP antibody-forming cells (AFC) among various lymphoid tissues, with the most profound differences seen in mucosal tissues. We observed an isotype-selective reduction in anti-MBP IgA but not IgM AFC frequencies in Peyer's patches. The anti-MBP IgA AFC frequencies could be reconstituted by addition of interleukin 4 (IL-4) and interleukin 5 (IL-5). The cytokines did not appear to generate de novo responses since no increases in anti-MBP IgA AFC frequencies were observed in control cultures. These results indicate that decreased antibody production, as a result of oral antigen administration, can be reversed by exposure to the appropriate cytokines.     

Use of somatosensory evoked potentials to detect peripheral ischemia and potential injury resulting from positioning of the surgical patient: case reports and discussion.

BACKGROUND: Somatosensory evoked potentials (SSEPs) have long been recognized as an excellent tool for detecting neural and vascular compromise during vascular, neurosurgical and orthopedic procedures. SSEPs have the ability to localize, central versus peripheral, the area of compromise. Many surgeons use only lower-limb SSEP monitoring when performing lumbar spinal surgery. The upper extremities are usually not monitored during such procedures, and monitoring oxygen saturation does not detect neural compromise. PURPOSE: To report that the expanded use of SSEP monitoring during surgery can be beneficial in detecting peripheral ischemia or neural compromise resulting from positioning. STUDY DESIGN: Three case reviews of orthopedic spine surgeries where SSEP monitoring provided early warnings of vascular and neural compression. METHODS: The cases review three different lumbar procedures in which evidence of peripheral ischemia and nerve compression were detected by SSEP monitoring. RESULTS: By the use of upper- and lower-extremity monitoring during lumbar procedures, early detection of ischemia and nerve compression were noted intraoperatively. These changes prompted examination of the patient and repositioning to correct the ischemia or compression. The repositioning in these cases corrected the problem, and no lasting effects were found. CONCLUSIONS: Including SSEP monitoring of the bilateral upper extremities should be considered during lumbar spinal procedures. Such monitoring can be offered for a slightly increased expense and only minimal time delay to place the additional required electrodes by the technician. As a direct result of the early warning of the SSEP monitoring, we were able to avoid potential ischemic injuries and improve patient outcomes.     

Factors associated with prolonged prehospital delay of African Americans with acute myocardial infarction.

BACKGROUND: Delays in seeking treatment for signs and symptoms of acute myocardial infarction are longer for African Americans than for whites. OBJECTIVE: To determine factors associated with prolonged delay and the extent to which perceived racism influences prehospital delay in African Americans with acute myocardial infarction. METHODS: Sixty-one African Americans with acute myocardial infarction were interviewed within 1 month of hospital admission. Delay times were calculated on the basis of the interviews. Independent t tests and chi(2) tests were used to determine factors associated with prolonged delays. RESULTS: Median delay was 4.25 hours and did not differ significantly between women and men (4.42 vs 3.50 hours). Most patients (69%) experienced their initial signs and symptoms at home, often witnessed by family members or friends (70%). Delay was longer for insured patients than for uninsured patients (4.45 vs 0.50 hours). Single, widowed, or divorced patients had longer delay times than did married patients (5.33 vs 2.50 hours), and patients with diabetes delayed longer than did those without diabetes (7.29 vs 3.50 hours). Perceived racism did not differ significantly between patients who delayed seeking treatment and those who did not. CONCLUSIONS: Median delay times were substantially longer than the recommended time of less than 1 hour, reducing the benefit from reperfusion therapies. Education and counseling of patients and their families should be a major strategy in optimizing patients' outcomes and decreasing the time to definitive treatment.     

Subarachnoid injection as a complication of retrobulbar anesthesia

We studied eight cases of apparent subarachnoid injection of local anesthetic through the optic nerve sheath and subsequent spread to the parabrainstem cisterns and the contralateral optic nerve sheath. The patients all experienced bilateral decrease in vision and ophthalmoplegia, and variable degrees of central nervous system symptoms and respiratory depression. The complications occurred with a variety of local anesthetic agents and with sharp disposable needles in six of the eight cases. These cases demonstrated the spectrum of signs and symptoms that may follow optic nerve sheath injection of local anesthetic agents.     

Fixed-interval schedules for drug self-administration in the rat

The practicality of using second-order fixed-interval schedules in studies of heroin reinforcement with rats was examined. Optimum rates of responding were obtained with a dose of 0.03 mg/kg/infusion and an interval duration of 3 min. In addition, schedules consisting of a only a single interval were shown to be practical, leading to response rates comparable to those obtained with cocaine or food as reinforcer.The views expressed in this publication are those of the author and do not necessarily represent those of the Addiction Research Foundation     

Public health laws and implications for a national accreditation program: parallel roadways without intersection?

Public health law has been one of the leading contributors to the extension of life expectancy in the 20th century. Nonetheless, the legal infrastructure supporting public health law in the United States is underdeveloped and nonuniform. With national interest growing in public health agency accreditation, the individual legal approach taken by states may pose an obstacle to wholesale adoption of a proposed voluntary national model. This article describes the legal foundations supporting accreditation or assessment programs in states participating in the Multi-State Learning Collaborative, a project funded by the Robert Wood Johnson Foundation. The Turning Point Model State Public Health Act is recommended as one option to resolve the current impasse, assist in acceptance of a national accreditation model, and provide a common public health legal infrastructure.     

Long-term precision of 18F-fluoride PET skeletal kinetic studies in the assessment of bone metabolism.

(18)F-Fluoride PET allows noninvasive evaluation of regional bone metabolism and has the potential to become a useful tool for assessing patients with metabolic bone disease and evaluating novel drugs being developed for these diseases. The main PET parameter of interest, termed K(i), reflects regional bone metabolism. The aim of this study was to compare the long-term precision of (18)F-fluoride PET with that of biochemical markers of bone turnover assessed over 6 mo. METHODS: Sixteen postmenopausal women with osteoporosis or significant osteopenia and a mean age of 64 y underwent (18)F-fluoride PET of the lumbar spine and measurements of biochemical markers of bone formation (bone-specific alkaline phosphatase and osteocalcin) and bone resorption (urinary deoxypyridinoline) at baseline and 6 mo later. Four different methods for analyzing the (18)F-fluoride PET data were compared: a 4k 3-compartmental model using nonlinear regression analysis (K(i-4k)), a 3k 3-compartmental model using nonlinear regression analysis (K(i-3k)), Patlak analysis (K(i-PAT)), and standardized uptake values. RESULTS: With the exception of a small but significant decrease in K(i-3k) at 6 mo, there were no significant differences between the baseline and 6-mo values for the PET parameters or biochemical markers. The long-term precision, expressed as the coefficient of variation (with 95% confidence interval in parentheses), was 12.2% (9%-19%), 13.8% (10%-22%), 14.4% (11%-22%), and 26.6% (19%-40%) for K(i-3k), K(i-PAT), mean standardized uptake value, and K(i-4k), respectively. For comparison, the precision of the biochemical markers was 10% (7%-15%), 18% (13%-27%), and 14% (10%-21%) for bone-specific alkaline phosphatase, osteocalcin, and urinary deoxypyridinoline, respectively. Intraclass correlation between the baseline and 6-mo values ranged from 0.44 for K(i-4k) to 0.85 for K(i-3k). No significant correlation was found between the repeated mean standardized uptake value measurements. CONCLUSION: The precision and intraclass correlation observed for K(i-3k) and K(i-PAT) was equivalent to that observed for biochemical markers. This study provided initial data on the long-term precision of (18)F-fluoride PET measured at the lumbar spine, which will aid in the accurate interpretation of changes in regional bone metabolism in response to treatment.