Biomedical subjects
M Brown
Publications and source records attributed to M Brown.
Inferior mesenteric vein cannulation for veno-venous bypass during liver transplantation: alternative access in difficult hilar dissection.
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Refinery kerosene contaminated by 210Po from a U mill processing facility.
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Managed care programs.
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Gynecologic surgery in the aged.
Aged women, those over 75 years, experience a high incidence of nearly all gynecologic neoplasms as well as associated chronic medical illnesses. In this study, 773 women underwent major surgery, while 711 underwent minor procedures. Fifty-two patients (3.5%) were 75 years of age or older. Forty-three of the 52 (83%) had a total of 119 associated medical complications. Eighty-nine surgical procedures were performed. A total of 17 postoperative complications occurred in 15 patients. Thirty-eight patients (73%) had no postoperative complications. One patient died because of infarction of the bowel diagnosed within 30 days of her primary surgical procedure. The aged patients in this study did well postoperatively with routine preoperative medical evaluation and postoperative care. Same-day admission and surgery did not increase morbidity. Aged patients can safely undergo major pelvic and abdominal surgery at a community medical center if one manages their associated medical conditions in a routine manner similar to that utilized in younger patients with similar problems. The associated medical complications and not age per se should be the deciding factor.
Dim view of headline writers.
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Neonatal hyperbilirubinemia at high altitude.
A previous retrospective study showed an increased frequency of neonatal hyperbilirubinemia at high altitude in Colorado. In a prospective study we found that 39% of newborns at 3100 m altitude vs 16% at 1600 m exhibited hyperbilirubinemia, defined as a day 3 serum bilirubin level of 205 mumol/L or higher. Increased bilirubin production at 3100 m vs 1600 m was shown by increased levels of corrected carboxyhemoglobin. This finding was supported by increased erythropoietin and bilirubin values in cord blood and increased hematocrit values at day 3 among infants at 3100 m vs 1600 m. The sustained elevation in bilirubin for breast-fed vs formula-fed infants at 1600 m was observed for both feeding types at 3100 m. The findings suggested that there is a hematologic response to decreased oxygen availability at high altitude, resulting in increased bilirubin production accompanied by delayed bilirubin clearance.
Extracellular proteases of Onchocerca.
Two important events in infection by Onchocerca parasites involve cutaneous tissue migration by larval stages. L3 larvae migrate from the blackfly bite site to subcutaneous locations for adult development, and microfilariae from subcutaneous nodules to distant regions of the skin and sometimes the eye. By analogy to other tissue-invasive helminth larvae, it has been proposed that migration of Onchocerca larvae through cutaneous tissue is facilitated by secretion of proteolytic enzymes. To test this hypothesis, neutral protease activity capable of degrading a model of cutaneous extracellular matrix was assayed using live L3 larvae of O. lienalis and microfilariae of O. cervicalis and O. cervipedis. Five hundred L3 larvae degraded most of the matrix within 24 hr of incubation. Substrate gel electrophoresis and other protease assays showed a 43-kDa serine elastase was secreted by O. lienalis L3 larvae. Larvae and adults of the free-living nematode, Caenorhobditis elegans, by contrast, did not secrete neutral proteases and large numbers of motile C. elegans juveniles and adults produced no degradation of the extracellular matrix. Expression of Onchocerca neutral protease activity was stage specific. No protease activity corresponding to that seen in L3 larvae was found in adult worms. Microfilariae of O. cervicalis and O. cervipedis produced both a serine and a metalloprotease, but the level of protease activity of these microfilariae was substantially lower than that of L3 larvae, and no significant protease activity was detected in extracts of O. lienalis microfilariae. Uterine microfilariae of O. cervicalis had different protease species than skin microfilariae, suggesting that changes in protease expression parallel other morphologic and biochemical changes in the development of skin microfilariae. The serine protease of L3 larvae probably plays an important parasitic function, facilitating L3 migration from the blackfly bite site to distant regions of the body where adults will develop and form nodules. The protease activity of microfilariae, while individually considerably less than that of L3 larvae, may still contribute to the tissue destruction seen with heavy skin densities of microfilariae.
pBR322-derived multicopy plasmids harboring large inserts are often dimers in Escherichia coli K-12.
pBR322-related plasmids that are 2.3 to 5.1 kb were found predominantly as monomers, while plasmids that are 7.7 to 15.2 kb were found predominantly as dimers in rec+ cells of Escherichia coli K-12.
Characterization of lambda class antibodies from the BALB/c memory response to a [glucosyl-alpha(1----3) glucosyl]-protein conjugate.
Both dextran B-1355 and nigerosyl-KLH (N-KLH) contain alpha(1----3) diglucosyl moieties and both induce lambda class serum antibodies which recognize the alpha(1----3) linkage. However, as shown here, some of the antibodies induced by the thymus-dependent form, N-KLH, have a distinct fine specificity. It is known that B-1355 induces antibodies which resemble the anti-alpha(1----3) myeloma proteins MOPC 104E and J558. The new fine specificity which does not resemble such antibodies is found in the serum of N-KLH primed mice challenged with N-KLH. The two fine specificity types are distinguished by their sensitivity to inhibition by nigerose in ELISA using B-1355 or N-BSA as bound antigen. Twelve hybridomas were produced from N-KLH primed mice boosted with either N-KLH or B-1355. Six of the 12 had the new fine specificity; only two out of the 12 expressed the IdX determinant commonly associated with the B-1355 response and neither of these possessed the new reactivity pattern. Comparative inhibition with the disaccharide nigerose and the tetrasaccharide nigerantetraose indicated that 11 out of the 12 hybridoma proteins have combining sites larger than a disaccharide. Southern and Northern blot analysis of eight hybridomas revealed that all expressed VH genes from the J558 family, but that at least two distinct VH genes from this family were used. The data support the hypothesis that immunization with an alpha(1----3) diglucosyl-protein conjugate alters the composition of the B cell pool capable of producing lambda class antibodies from that ordinarily observed following immunization with B-1355.
Electrical stimulation of quadriceps femoris in an elite weight lifter: a single subject experiment.
The response to treatment of high intensity neuromuscular electrical stimulation (NMES) to both quadriceps femoris muscles as an adjunct to ongoing weight training was evaluated using a single subject experimental design. For an elite weight lifter weekly maximal measurements of snatch (S), clean and jerk (CJ), and front squat (SQ) were obtained over 4 months during which the subject weight trained daily for 3 h. The 1st month, baseline data were collected. After baseline measurements, a 1-month period of high-intensity NMES was added to the subject's weight training. NMES was then withdrawn for 1 month and administered once more for 2 weeks. Three quadriceps femoris muscle biopsies were taken, two during the initial baseline period and one just before the end of the first stimulation period. The results showed a significant and clear relationship between performance gains and NMES administration and withdrawal. Steep gains for S, CJ, and SQ were seen after 2 weeks of stimulation, with front squat showing a 20-kg increase within the 1st week of both stimulation periods. Muscle biopsy showed an increased type I fiber area, decreased type IIa and IIb fiber area, and an increase of type II fibers after NMES. The results of this study support the use of high-dose NMES as an adjunct to weight training in elite lifters.
Resistance exercise effects on aging skeletal muscle in rats.
The purpose of this study was to determine whether a resistance exercise program could be initiated successfully at progressively older ages in rats. Forty female Sprague-Dawley rats, 7 to 10 in each age group (21, 24, 27, and 30 months, respectively), performed 60 manually resisted chin-ups (three sets of 10 repetitions each twice daily) for three months. Twenty controls, 5 in each age group, were followed for three months but not exercised. Before the experimental period began, the rats' left palmaris longus (PL) muscle was removed, weighed, frozen, sectioned, and stained. After the three-month period, the right PL muscle was removed and the same tissue preparation procedure was followed. Muscle fiber types I and II were identified on photomicrographs, and areas of each fiber type measured. No significant change in muscle wet weight or fiber size occurred in the controls. Significant increases (p less than .01) in type II muscle fiber area occurred for the 21-, 24-, and 30-month-old rats that exercised. No histological evidence of exercise-related harm was observed in tissues from exercised rats. Results indicate that resistance exercise can be introduced successfully to an aging or aged rat without doing harm. Studies are needed to determine whether similar results can be achieved for elderly humans.
Concentration-response relationships for salicylate-induced ototoxicity in normal volunteers.
1. Ototoxicity is a common and troublesome side-effect of high-dose aspirin treatment but there has been little previous study of the relationships between the degree of ototoxicity and the plasma concentrations of salicylate. 2. In order to investigate the relationships between aspirin dose, total and unbound plasma salicylate concentrations and ototoxicity, eight normal volunteers were dosed with aspirin 1.95, 3.25, 4.55 and 5.85 g day-1 for 1 week at each dose level, the doses being administered in random order and double-blind, 2 weeks apart. 3. Ototoxic effects measured were hearing loss in decibels (dB) over six frequencies and tinnitus intensity, estimated both by electronic matching and a fixed interval scale (FIS). Measurements were taken after steady-state concentrations of salicylate had been achieved. 4. Total and unbound plasma salicylate concentrations increased disproportionately with increasing daily doses of aspirin. The increase in the unbound salicylate was relatively greater since the percentage of salicylate unbound in plasma increased over the dose range investigated from a mean of 3.9% to 10.4%. 5. Hearing loss and tinnitus intensity increased progressively with the aspirin dosage and increasing concentrations of total and unbound plasma salicylate concentrations. These ototoxic symptoms were observed at lower concentrations of total salicylate than previously reported. 6. There was a linear relationship between hearing loss and unbound salicylate concentrations. 7. Further work is required to test the hypothesis that unbound plasma salicylate concentration is a better predictor of salicylate-induced ototoxicity than total plasma salicylate concentration.
Neuropeptide Y and neuropeptide Y18-36. Structural and biological characterization.
Neuropeptide Y (NPY), a 36-residue peptide amide, has been shown by numerous studies to be a potent vasoconstrictor. In order to gain an appreciation of the structural requirements for this action, we have previously synthesized a number of fragments of NPY. It had been shown that sequential deletions from the N-terminus resulted in peptides with decreasing hypertensive activity. In the present study we present data supporting the unexpected finding of two fragments, NPY17-36 and NPT18-36 with substantial hypotensive action in vivo. This action was dose dependent (data not shown) and was also observed to a lesser extent with NPY19-36 but not NPY16-36 or NPY20-36. It was, however, slower in onset and of longer duration than the hypertensive action of NPY. These differing kinetics of action may suggest that NPY and NPY18-36 act through different mechanisms. Structural studies using circular dichroism were performed. While NPY was found to assume an ordered helical structure in both aqueous buffer and trifluoroethanol (TFE), 30% TFE in aqueous buffer was required to induce substantial helicity for NPY18-36. This structural investigation suggests that both NPY and NPY18-36 assume an ordered conformation upon reaching the lipid rich receptor environment.
Detection of T cells in paraffin wax embedded tissue using antibodies against a peptide sequence from the CD3 antigen.
Rabbit polyclonal antibodies were raised against a proline rich, peptide sequence, comprising 13 amino acids, in the cytoplasmic domain of the CD3 epsilon chain. Immunoprecipitation experiments showed that this antibody preparation recognised the CD3 antigen on human T lymphoblasts. The antibody stained normal T cells strongly in tissue sections which had been fixed in formalin or Bouin's solution and embedded in paraffin wax. Its reactivity with T cell lymphoma, when evaluated on a series of 96 previously phenotyped cases, closely agreed with the results obtained on cryostat sections. These results indicate that the specific detection of T cells in routinely processed tissue biopsy specimens is now technically feasible on a wide scale in diagnostic laboratories using CD3 peptide antibodies, and they also suggest that in future the use of anti-peptide antibodies may detect other lineage specific antigenic markers in paraffin wax sections.
In the rat, interleukin-1 alpha and -beta stimulate adrenocorticotropin and catecholamine release.
Recombinant interleukin-1 alpha and -beta (Il-1 alpha and -beta) have been evaluated for their abilities to stimulate ACTH and catecholamine secretion in the intact adult male rat. Additionally, the role of adrenergic-dependent pathways in mediating Il-1-induced ACTH release has been assessed. The iv or intracerebroventricular injection of either Il-1 alpha or Il-1 beta caused dose-related increases in plasma ACTH, epinephrine, and norepinephrine levels. While at low iv doses (less than or equal to 10 ng), Il-1 beta was more effective than Il-1 alpha at releasing ACTH, no measurable differences were noted at higher doses. In contrast, Il-1 beta was significantly more active at all doses in elevating plasma ACTH levels after intracerebroventricular injection. Similarly, Il-1 alpha was more effective than Il-1 beta at stimulating epinephrine, but not norepinephrine, secretion after icv injection. Because of the ability of catecholamines to alter ACTH secretion, we then examined the role of adrenergic-dependent pathways as possible mediators of Il-1-induced ACTH secretion. Blockade of adrenergic receptors by the concomitant administration of prazosin and propanolol prevented the simultaneous actions of phenylephrine and isoproterenol on the corticotrophs, but did not significantly alter the effect of peripherally administered Il-1 alpha on ACTH release. These results suggest that both Il-1 alpha and Il-1 beta stimulate ACTH and catecholamine secretion in the rat. Despite the ability of the lymphokine to elevate plasma epinephrine and norepinephrine values, circulating catecholamines do not appear to represent essential modulators of ACTH release induced by acutely injected Il-1.
General anesthesia and fibrodysplasia ossificans progressiva.
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Axonal injury in the optic nerve: a model simulating diffuse axonal injury in the brain.
A new model of traumatic axonal injury has been developed by causing a single, rapid, controlled elongation (tensile strain) in the optic nerve of the albino guinea pig. Electron microscopy demonstrates axonal swelling, axolemmal blebs, and accumulation of organelles identical to those seen in human and experimental brain injury. Quantitative morphometric studies confirm that 17% of the optic nerve axons are injured without vascular disruption, and horseradish peroxidase (HRP) studies confirm alterations in rapid axoplasmic transport at the sites of injury. Since 95% to 98% of the optic nerve fibers are crossed, studies of the cell bodies and terminal fields of injured axons can be performed in this model. Glucose utilization was increased in the retina following injury, confirming electron microscopic changes of central chromatolysis in the ganglion cells and increased metabolic activity in reaction to axonal injury. Decreased activity at the superior colliculus was demonstrated by delayed HRP arrival after injury. The model is unique because it produces axonal damage that is morphologically identical to that seen in human brain injury and does so by delivering tissue strains of the same type and magnitude that cause axonal damage in the human. The model offers the possibility of improving the understanding of traumatic damage of central nervous system (CNS) axons because it creates reproducible axonal injury in a well-defined anatomical system that obviates many of the difficulties associated with studying the complex morphology of the brain.