Abnormal plasma levels of polyunsaturated fatty acid in autosomal dominant retinitis pigmentosa.
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Docosahexaenoic Acids↗
Biomedical subjects
R E Anderson
Publications and source records attributed to R E Anderson.
Effect of light history on rod outer-segment membrane composition in the rat.
Albino rats were born and raised through 12 weeks of age in 12L:12D regimes of 5, 300- or 800-lx illuminance. Upon killing, the animals' retinas were examined for the following: (1) rhodopsin of whole retina and isolated rod outer-segment membrane; (2) retinal morphology, including outer segment length and outer nuclear layer area; and (3) outer-segment membrane lipid biochemistry. The three groups of animals show significant differences with respect to one another for nearly every parameter measured. Rod outer-segment membranes of rats raised in dim cyclic light (5 lx) have high rhodopsin packing densities, high levels of polyunsaturated fatty acids, and low cholesterol levels in comparison with animals raised in brighter illuminances (300- or 800 lx). The mole ratio of phospholipid to rhodopsin in the outer-segment membrane of rats raised in 5-lx cyclic light is only 43% of that of rats raised in 800-lx cyclic light. The difference between these two groups of animals for docosahexaenoic acid is greater than three times, with dim light-reared animals showing higher levels. These rats (5 lx-reared) have less cholesterol in their photoreceptor outer segments, 6.6 mol% compared with 19.7 mol% for animals from the 800-lx regime. In all cases, rats from the intermediate rearing illuminance (300 lx) exhibit intermediate membrane composition values. It is likely that these differences in membrane composition illustrate a profound effect of light history on photoreceptor function.
Animals↗
Effect of light history on retinal antioxidants and light damage susceptibility in the rat.
Albino rats were born and raised to 12 weeks of age in 12L:12D light regimes of 5, 300 or 800 lx. Upon killing, the activities of the following glutathione enzymes were measured in the neuroretina: (1) glutathione peroxidase; (2) glutathione-S-transferase; and (3) glutathione reductase. Also measured were vitamin E, ascorbic acid, and the levels of oxidized and reduced glutathione. Animals raised in 800-lx cyclic light have a significant increase in the retinal activities of the three glutathione enzymes over activities measured in animals raised in the two dimmer regimes. The retinal level of vitamin E, measured per nmol of lipid phosphorus, is directly and significantly correlated with rearing illuminance (P less than 0.05). The same is true of retinal ascorbic acid, which shows a 30% increase in the 800-lx-reared rats over the level of those raised in the intermediate light regime (300 lx). Some of the animals from each group were exposed to 2000 lx for 24 hr to determine if correlations existed between the levels of retinal antioxidants listed above and susceptibility to light damage. Animals raised in 5-lx cyclic light lost almost all of their photoreceptors as a result of the exposure. Rats raised in 300-lx cyclic light lost a small but significant number (ca. 20%), while those raised in 800 lx sustained no light damage. Electroretinographic evaluation supports these morphometrical findings.
Animals↗
Ectopic pregnancy in unrepaired distal tubal remnant after contralateral tubal anastomosis.
A case is described in which, after a tubal sterilization procedure and subsequent unilateral tubal anastomosis, an ectopic gestation occurred in the contralateral, unrepaired, distal tubal segment. On the basis of this case and related evidence, the authors suggest that in cases in which only a unilateral tubal anastomosis is possible, strong consideration should be given to removal of the contralateral, unrepaired, distal tubal remnant.
Adult↗
Focal cerebral ischemia: pathophysiologic mechanisms and rationale for future avenues of treatment.
Although approximately 500,000 patients suffer from a stroke each year in the United States, treatment of these patients to date has consisted primarily of prevention, supportive measures, and rehabilitation. The modification of experimental cerebral infarction by new pharmacologic agents, along with encouraging results from the restoration of blood flow to areas of focal ischemia in both laboratory and clinical trials, suggests that a more aggressive approach might be considered in selected patients with acute stroke.
Anticoagulants↗
Autopsy-related initiatives in the United States: current status and suggestions for the future.
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Academies and Institutes↗
Methods for determination of lipid peroxidation in biological samples.
Interest in the pathological consequences of lipid peroxidation has led to the development of a number of analytical approaches to the quantitation of products. However, the various analytical methodologies employed often do not measure the same chemical classes of products, and apparent discrepencies have been observed, particularly in studies of lipid peroxidation in biological systems. This review provides a brief discussion of some of the strengths and weakness of methods currently used for the determination of lipid peroxidation in biological tissues.
Animals↗
Regional cerebral blood flow and focal cortical perfusion: a comparative study of 133Xe, 85Kr, and umbelliferone as diffusible indicators.
We report that regional CBF determined by the initial slope technique using 133Xe and 85Kr in cats and rabbits can be significantly influenced by the size of the field of measurement. The clearance curves of umbelliferone, a lipid-soluble intracellular pH fluorescent indicator, from a visually avascular 80-micron field were used to cross-correlate rCBF with focal cortical perfusion. Our findings indicate that in the cat, as the gamma or beta detector's field of volume was reduced, regional CBF (rCBF) measured by intraarterially injected 133Xe or 85Kr decreased in value by 33% and 28%, respectively, and the slope of the rCBF-PaCO2 response curve became less steep by 56% and 45%, respectively. Umbelliferone, measuring a much smaller volume of tissue, showed a lower normocapnic flow and a more oblique PaCO2 response curve. In the rabbits studied, the normocarbic rCBFs and the rCBF-PaCO2 response curves measured with the three techniques corresponded to those measured in the cat. These results suggest that large field/volume measurements assess a measure of flow that is a weighted average of several distinct flow compartments and that these compartments differ in their response to changes in PaCO2.
Animals↗
In vivo studies on intracellular pH, focal flow, and vessel diameter in the cat cerebral cortex: effects of altered CO2 and electrical stimulation.
The time course of changes in cortical tissue pH (pHi) and blood flow during cortical seizures in halothane-anesthetized cats was examined. The clearance of the molecular form of umbelliferone (Um) was used to estimate focal cortical blood flow (CBFu), whereas the ratio of the molecular to the ionic form of the molecule was used to concurrently calculate the local pHi. Resting pHi and flow in normocarbic animals was 7.116 +/- 0.008 and 46 +/- 8 ml/100 g/min, respectively. Respiratory induced alterations of PaCO2 over a range of 20-60 torr revealed a correlated change in pHi from 7.39 +/- 0.05 to 7.01 +/- 0.03 and a monotonic increase in the rate of Um clearance (slope 0.89 +/- 0.13 ml/100 g/min/torr). Focal electrical stimulation of the cortex resulted in a rapid vasodilation (50% dilation = 1-3 s) of pial arterioles and venules and an increase in Um clearance. pHi showed no significant change until around 10 s. The maximum fall in pHi occurred by 30-60 s (6.85 +/- 0.054). Longer intervals of stimulation (10 min) resulted in no further decline in pHi, but upon cessation of stimulation. pHi remained acidotic for poststimulation periods up to 10 min, with a mild but statistically significant acidosis being observed at 20 min. The absolute decline in pH observed following stimulation appeared to be closely regulated, as comparable levels following stimulation were observed during hypocarbia and hypercarbia. These observations thus suggest that pHi regulation during intense cortical activation may be considered in three phases: following the onset of activity, an initial acute regulation of pHi at control levels; an intracellular acidosis of around 6.8, which is closely regulated and which can be readily reversed upon termination of stimulation; and during continued stimulation, a change in state where in spite of no further change in pHi, the ability of the cortex to return to control pHi appears to be significantly impaired.
Animals↗
Activity of phthalocyanine photosensitizers against human glioblastoma in vitro.
In vitro studies utilizing an established human glioblastoma cell line (U87MG) were undertaken to compare the light absorption spectra and photocytotoxicity characteristics of hematoporphyrin derivative (HpD), metal-free phthalocyanine tetrasulfonate (PcS), and aluminum phthalocyanine tetrasulfonate (AlPcS). The peak absorption wavelengths for the compounds studied were: HpD = 630 nm, PcS = 630 nm, AlPcS = 677 nm. Seven different concentrations of each compound (0 to 20 micrograms/ml) were subjected to five different energy levels (40 to 640 joules/cm2) of broad band light (wavelength = 650 +/- 40 nm). Control experiments employing each drug alone and photoactivation alone were also performed. HpD showed a consistent dose-dependent photoactivated cytotoxicity with an abrupt decrease in cell survival when energies of 160 joules/cm2 or more were administered and a drug concentration dependency that resulted in a progressive decline in cell survival beginning at 1.0 microgram/ml. The metal-free PcS had a 10 times greater absorption of light at 675 nm, but only a very weak cytotoxic effect, which occurred at concentrations in excess of 10.0 micrograms/ml and energy levels greater than 320 joules/cm2. AlPcS, however, displayed a 100-fold increase in light absorption at 675 nm when compared to HpD. This was coupled with a decrease in cell survival similar to the HpD curves, but with a much steeper slope of percentage cell kill at lower drug concentrations and energy dosages. The control studies did not result in any appreciable cytotoxic effect. The data suggest that AlPcS holds promise as a second generation photosensitizer in the photodynamic treatment of human gliomas.
Brain Neoplasms↗
The San Francisco Men's Health Study: III. Reduction in human immunodeficiency virus transmission among homosexual/bisexual men, 1982-86.
The prevalence and incidence of infection by the human immunodeficiency virus (HIV) has been under study in a cohort of 1,034 single men recruited by area probability sampling from a six kilometer square area of San Francisco where the epidemic of acquired immunodeficiency syndrome (AIDS) has been most severe. Prevalence of infection among homosexual/bisexual study subjects increased from an estimated 22.8 per cent during the last half of 1982 to 48.6 per cent during the period July through December 1984. During three subsequent six-month periods, prevalence remained stable at approximately 50 per cent. Annual infection rates, measured by seroconversion among seronegative study subjects, decreased from an estimated 18.4 per cent per year from 1982 to 1984, to 5.4 and 3.1 per cent during the first and second halves of 1985, and to 4.2 per cent during the first six months of 1986. These declines were associated with reductions of 60 per cent or more in the prevalence of high-risk sexual practices associated with both acquiring and disseminating infection by the human immunodeficiency virus.
Acquired Immunodeficiency Syndrome↗
Treatment of experimental focal cerebral ischemia with mannitol. Assessment by intracellular brain pH, cortical blood flow, and electroencephalography.
Intracellular brain pH, cortical blood flow (CBF), and electrocorticograms were recorded in regions of severe and moderate ischemia in 10 control rabbits and 10 rabbits given mannitol, 1 gm/kg, after occlusion of a major branch of the middle cerebral artery. Pooling the data from all 20 animals, preocclusion CBF was 46.4 +/- 3.6 ml/100 gm/min and intracellular brain pH was 7.01 +/- 0.04 (means +/- standard error of the means). Although mannitol administration mildly improved CBF in regions of severe ischemia, this increase was not sufficient to prevent metabolic deterioration as assessed by brain pH. However, in regions of moderate ischemia, CBF improved significantly with mannitol and the gradual decline in brain pH observed in control animals was prevented. For example, in the treated moderate ischemia sites 4-hour postocclusion CBF and pH values were 31.8 ml/100 gm/min and 6.89 +/- 0.09, respectively, as compared to control values of 14.3 ml/100 gm/min and 6.75 +/- 0.06. These results suggest that mannitol may be of benefit in stabilizing regions of moderate, but not severe, ischemia after vessel occlusion.
Animals↗
Effect of dihydropyridines and diphenylalkylamines on pentylenetetrazol-induced seizures and cerebral blood flow in cats.
Nimodipine, a dihydropyridine that interacts with a Ca++ channel-associated binding site, when delivered (30 to 150 micrograms/kg) intra-arterially (ia) to enflurane-anesthetized cats, produced a dose-dependent suppression of seizures evoked by pentylenetetrazol. A comparable suppression was produced by clonazepam (1 to 30 micrograms/kg, ia). Phenytoin was maximally effective only at nearly lethal doses (90 mg/kg, ia). Verapamil, a diphenylalkylamine that interacts with a separate Ca++ channel-associated site, at the maximum nonlethal dose (6 mg/kg, ia) resulted in a mild facilitation of seizure activity. The drug vehicle used in these studies (50% polyethylene glycol-400) had no effect when given alone. Regional cerebral blood flow (rCBF) as measured by the clearance of xenon-133 was markedly elevated immediately after the onset of seizure activity (89 +/- 3 to 168 +/- 4 ml/100 gm/min). Concurrent with their resolution of the seizure activity, both nimodipine and clonazepam reduced rCBF to near preseizure levels and preserved the rCBF response to hypercarbia which would otherwise have been abolished following prolonged seizure activity. Moreover, the effect of nimodipine on rCBF and seizures occurred without any prominent alterations in mean arterial blood pressure as compared to preseizure levels. These data support the proposition that a dihydropyridine Ca++ channel binding site may play a role in modulating paroxysmal neuronal activity, and suggest that this class of agents may reflect a novel group of antiepileptic drugs.
Animals↗
Cause of death. Proper completion of the death certificate.
Mortality statistics derived from death certificates are the only continuously collected, population-based, disease-related information available in most parts of the world, including the United States. For this reason, every effort must be made to ensure that the most specific, accurate, and complete information regarding cause of death is registered on death certificates. This article discusses identification of the underlying and immediate causes of death, the mechanism and manner of death, and completion of the medical certification section of the death certificate. Examples are given to illustrate the appropriate sequencing of casual information and the selection of the proper underlying causes of death.
Cause of Death↗
Murine autoimmune oophoritis, epididymoorchitis, and gastritis induced by day 3 thymectomy. Immunopathology.
(C57BL/6 X A/J) F1, (SWR/J X A/J) F1 and BALB/cBy mice, thymectomized on Day 3 (D3TX) or Day 7 (D7TX) or sham thymectomized (STX), were studied for immunopathologic changes in the ovary, testis, and gastric wall. In 95% of B6AF1, 100% of SWRAF1, and 35% of BALB/cBy mice ovarian disease developed, with onset at 5-6 weeks of age. Ovarian disease was not found in D7TX or STX mice. In D3TX mice, it was associated with mononuclear infiltration and ovarian follicle destruction, leading to atrophy. Epididymovasitis was detected in 70-90% of SWRAF1, 50% of B6AF1, and 64% of BALB/cBy mice after D3TX; whereas orchitis occurred in about 20% of SWRAF1 and B6AF1 mice. In some mice epididymovasitis also developed after D7TX, but not after STX. In contrast to the negative immunohistochemical findings in diseased ovaries, typical immune complex-like deposits of mouse IgG were detected by immunofluorescence along the basement membrane of epididymal ducts and seminiferous tubules. However, maximum incidence of epididymitis preceded immune complex detection. Gastritis developed in both female (57%) and male (50%) BALB/cBy mice after D3TX, occasionally after D7TX, but not after STX. Gastric mucosa was hypertrophic with dilated glands and heavy lymphocytic infiltrations throughout all gastric layers. BALB/cBy mice with gastritis usually did not have disease in the gonads, and vice versa. This study, therefore, confirms and extends the findings of Nishizuka and colleagues.
Animals↗
The effects of cyclophosphamide and irradiation singly and in combination upon SaI growth in A/J mice.
The effects of various doses of cyclophosphamide and low-dose (15 rads) radiation upon the size of tumors caused by 10(4) Sarcoma I (SaI) cells was determined. In intact A/Jax (A/J) recipients, the effect of the two agents singly and in combination was found to be dependent especially upon the dosage of cyclophosphamide and the time of its administration in relation to tumor inoculation. In cell transfer experiments to adult thymectomized, lethally irradiated, bone-marrow-restored (ATxXBM) mice, the effects of cyclophosphamide and irradiation appeared to be either overlapping (low dosages of cyclophosphamide) or additive (dosages of cyclophosphamide greater than or equal to 50 mg/kg), suggesting that the two agents exert their influence in dissimilar fashion, perhaps by injuring different cell types with the same basic function. The most pronounced conjoint effects are seen when low dosages of cyclophosphamide are given 3 days after the adoptive transfer of spleen cells from mice pretreated with low-dose irradiation. The implications of this observation with respect to immunotherapy are discussed.
Animals↗
Murine autoimmune oophoritis, epididymoorchitis, and gastritis induced by day 3 thymectomy. Autoantibodies.
In adult mice thymectomized at age 3 days (D3TX), increased incidences and/or levels of organ-specific antibodies to oocytes and/or zona pellucida, to testicular cell-sperm-differentiation antigens (TSDA), and to gastric parietal cells were detected, and these correlated significantly with oophoritis, orchitis (not epididymovasitis), and gastritis, respectively. The autoantibodies occurred in mice with the corresponding endogenous antigens. Thus, anti-oocyte/zona antibodies were detected in female, anti-TSDA antibodies in male, and anti-parietal cell antibodies in both sexes. Anti-oocyte/zona antibodies were first detected at age 5-6 weeks and were absent by 25 weeks. Serum antizona antibodies, but not anti-oocyte antibodies, inhibited mouse fertilization in vitro. In contrast, antibodies to sperm acrosome and antibodies to sperm surface did not correlate with testicular or epididymal disease. Moreover, both male and female mice had increased levels of anti-sperm surface antibodies, indicating that the sperm antigens detected may not be organ-specific. In addition, sera from 5-10% of D3TX mice reacted with a wide spectrum of epididymal and testicular antigens with defined cellular locations but of yet unknown specificity. Although the incidence of antibodies to cytoskeletal antigens was not significantly elevated after D3TX, anti-nuclear antibodies were more frequently detected in (SWR/J X A/J) F1 (SWRAF1) and (C57 BL/6J X A/J) F1 (B6AF1) mice after D3TX.
Animals↗
A core curriculum in graduate medical education in pathology.
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Certification↗