Reactions of 'bay-region' and non-'bay-region' diol-epoxides of benz(a)anthracene with DNA: evidence indicating that the major products are hydrocarbon-N2-guanine adducts

The rates of reaction and the products formed when two vicinaldiol-epoxides derived from benz(a)an-thracene, anti-BA-3, 4-dioI1, 2-oxide (t-3, r-4-dihydroxy-t-1, 2-oxy-l, 2, 3, 4-tetrahydrobenz(a)anthracene)^* and anti-BA-8, 9-diol 10, 11-oxide (r-8, t-9-dihydroxy-t-10,ll-oxy-8, 9, 10, ll-tetrahydro-benz(a)anthracene) reacted withDNA were studied in vitro and the results were compared withthose obtained in similar experiments using anti-BP-7, 8-diol9, 10-oxide (r-7, t-8-dihydroxy-t-9, 10-oxy-7, 8, 9, 10-tetrahydrobenzo(a)pyrene).The reactivities appeared to decrease in the order anti-BP-7,8-diol 9, 10-oxide > anti-BA-3, 4-diol 1, 2-oxide anti-BA-8,9-diol 10, 11-oxide. The diol-epoxides reacted to a similarextent with single- and with double-stranded DNA but reactionswith dGMP, at equivalent concentrations, were much slower thanwith DNA. With the diol-epoxides of benz(a)anthracene, two principaladducts were present in DNA hydrolysates and evidence was obtained,based on pK determinations before and after nitrous acid treatment,consistent with their being N²-guanine derivatives, analogousto the known DNA-reaction products of benzo(a)-pyrene 7, 8-diol9, 10-oxide.     

Neuroendocrinology and brain peptides

To date about thirty peptides--low-molecular-weight, single-chain amino acid compounds--are known to be distributed widely in the central nervous system within selective neuron pathways. These findings, combined with a large body of neuropharmacological, behavioral, and electrophysiological data, open new horizons in neurobiology, force a reexamination of old and accepted hypotheses, and hold important implications for the clinician. There is evidence that substance P and the opioid peptides play a major role in the pain pathway, particularly at the level of the spinal cord. Available evidence also implicates vasoactive intestinal polypeptide in the control of cerebral circulation, cholecystokinin in the regulation of appetite, and vasopressin and adrenocorticotropic hormone in memory. Many questions, however, remain. For most peptides there is little information on mechanisms of biosynthesis, release, interaction with receptors, and termination of biological effect. Another important question is the interaction of peptides with other neurotransmitters. The evidence that both "classic" neurotransmitters and peptides can be found in the same neuronal necessitates reformulation of Dale's "one neuron, one neurotransmitter" hypothesis. It may be that a single cell, while containing different classes of neurotransmitter, will contain only one member of any particular class. It is not too early to speculate on the role of the numerous and diverse peptides in neuronal tissue and on the implications of peptide abnormalities in a variety of neurological diseases. The answers to these and other questions pose a fascinating challenge to neurobiologist and clinician alike.     

Comparison of the efficacy, safety, and therapeutic usage of HA-1A and E5 in the treatment of gram-negative sepsis

Clinical trials have shown that the murine monoclonal antibody E5 and the human hybrid monoclonal antibody HA-1A increase survival of patients with gram-negative sepsis. However, significant reduction in mortality associated with E5's use was limited to patients who had not progressed to refractory shock. Patients treated with E5 compared to placebo receivers were also significantly more likely to experience resolution of organ failures. Significant reductions in morbidity and mortality associated with HA-1A's use were limited to patients with gram-negative bacteremia, and occurred even in patients with shock. Treatment with HA-1A also had a significant positive effect on resolution of the major complications of sepsis (shock, disseminated intravascular coagulation, acute renal failure, acute hepatic failure, or adult respiratory distress syndrome) in patients with documented gram-negative bacteremia. Both products appear to be safe, with generally mild, transient, and clinically insignificant adverse effects reported.     

Stroke rehabilitation - who benefits? A comparison of medical wards and rehabilitation units

This prospective, multicentre, population study, of all first-stroke survivors in one year referred for in-patient rehabilitation, compares the efficiency and effectiveness of functional recovery following ad hoc and routine rehabilitation of general medical wards with intensive and comprehensive rehabilitation of mixed disability geriatric/rehabilitation units. After controlling for potential confounding variables, no significant differences were recorded in terms of Barthel discharge function scores, effectiveness or efficiency of rehabilitation. Conventional rehabilitation in general medical wards of acute hospitals was 35% more efficient than comprehensive rehabilitation in geriatric/rehabilitation units (1.08 vs. 0.70, P < 0.001), this being due to unnecessarily long rehabilitation stays (44 vs. 70 days, P < 0.000). Contrary to other studies, geriatric/rehabilitation units did not significantly increase the discharge scores, did not accelerate the process of rehabilitation, and did not decrease the demand for extended-care beds.     

Blood lipid measurements. Variations and practical utility.

OBJECTIVE--To describe the magnitude and impact of the major biological and analytical sources of variation in serum lipid and lipoprotein levels on risk of coronary heart disease; to present a way to qualitatively estimate the total intraindividual variation; and to demonstrate how to determine the number of specimens required to estimate, with 95% confidence, the "true" underlying total cholesterol value in the serum of a patient. DATA SOURCES--Representative references on each source of variation were selected from more than 300 reviewed publications, most published within the past 5 years, to document current findings and concepts. Most articles reviewed were in English. STUDY SELECTIONS--Studies on biological sources of variation were selected using the following criteria: representative of published findings, clear statement of either significant or insignificant results, and acquisition of clinical and laboratory data under standardized conditions. Representative results for special populations such as women and children are reported when results differ from those of adult men. DATA EXTRACTION--References were selected based on acceptable experimental design and use of standardized laboratory lipid measurements. DATA SYNTHESIS--The lipid levels considered representative for a selected source of variation arose from quantitative measurements by a suitably standardized laboratory. Statistical analysis of data was examined to assure reliability. The proposed method of estimating the biological coefficient of variation must be considered to give qualitative results, because only two or three serial specimens are collected in most cases for the estimation. CONCLUSIONS--Concern has arisen about the magnitude, impact, and interpretation of preanalytical as well as analytical sources of variation on reported results of lipid measurements of an individual. Preanalytical sources of variation from behavioral, clinical, and sampling sources constitute about 60% of the total variation in a reported lipid measurement of an individual. A technique is presented to allow physicians to qualitatively estimate the intraindividual biological variation of a patient from the results of two or more specimens reported from a standardized laboratory and to determine whether additional specimens are needed to meet the National Cholesterol Education Program recommendation that the intraindividual serum total cholesterol coefficient of variation not exceed 5.0. A National Reference Method Network has been established to help solve analytical problems.     

Increased regulation. Do the benefits outweigh the costs?

A Florida attorney suggests that regulations designed to control costs, such as the new safe harbor rules, should determine whether the benefits to the public exceeds the cost.     

Implementation of an On-Line lsokinetic Analysis System

A cost effective and efficient means of obtaining torque, work, and power measurements for a large group of subjects was needed. As a solution to this problem, an Apple 111 microcomputer was interfaced to a Cybex II isokinetic dynamometer. This system provided instantaneous values for the three parameters listed above as well as additional options for filekeeping and data manipulation. Intraclass reliability coefficients for the parameters of torque, work, and power ranged from r = 0.991 to r = 0.999. It was concluded that a microcomputer support system is, in view of its time saving qualities and relative cost, an economical and efficient means of providing meaningful information for clinical analysis of patients. J Orthop Sports Phys Ther 1982;4(1):36-38.