Reactive oxygen species as causal agents in the neurotoxicity of the Alzheimer's disease-associated amyloid beta peptide.
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Alzheimer Disease↗
Biomedical subjects
R Mark
Publications and source records attributed to R Mark.
Alterations in brain protein kinase C after experimental brain injury.
Regional activities and levels of protein kinase C were measured after lateral fluid percussion brain injury in rats. At 5 min and 20 min after injury, neither cofactor-dependent nor -independent PKC activities in the cytosol and membrane fractions changed in the injured and contralateral cortices or in the ipsilateral hippocampus. Western blot analysis revealed decreases in the levels of cytosolic PKC alpha and PKC beta in the injured cortex after brain injury. In the same site, a significant increase in the levels of membrane PKC alpha and PKC beta was observed after injury. Although the level of PKC alpha did not change and that of PKC beta decreased in the cytosol of the ipsilateral hippocampus, these levels did not increase in the membrane fraction after injury. The levels of PKC gamma were generally unchanged in the cytosol and the membrane, except for its decrease in the cytosol of the hippocampus. There were no changes in the levels of any PKC isoform in either the cytosol or the membrane of the contralateral cortex after injury. The present results suggest a translocation of PKC alpha and PKC beta from the cytosol to the membrane in the injured cortex after brain injury. The observation that such a translocation occurs only in the brain regions that undergo substantial neuronal loss suggests that membrane PKC may play a role in neuronal damage after brain injury.
Animals↗
Measurement of wound healing by image analysis.
Chronic wound healing is a major health problem consuming more than $10 Billion/year. Noninvasive measurements of wounds are critical for evaluation of different therapies. In this paper, we present two image processing methods which can be used to compare the effects of different dressings on pig skin wounds. In the first part, the healing process is monitored by area measurements. Using thresholding the wound areas are calculated by pixel counting and corrected with perspective scaling. This technique showed good correlation with manual area measurements. In the second part, 3 D coordinates of the selected wound points are calculated using triangulation from a single colored image coordinates. Such a 3 dimensional image reconstruction from a single camera is made possible by projecting a structured light pattern onto the skin. In this study, a unique pattern consisting of colored dots is used. This color-coded pattern provides many advantages over widely used grid patterns: it is not necessary to see the whole image to recognize the points, since every dot can be identified correctly from its closest eight neighbors, eliminating occlusion problems. Our approach to structured light also mitigates the problem of motion in a subject, since all the coding information is contained in a single image.
Animals↗
Minor salivary gland tumors of the head and neck: treatment strategies and prognosis.
Between 1961 and 1985, 117 patients with malignant tumors of the minor salivary glands of the upper aerodigestive tract were treated with curative intent at the University of California, Los Angeles (UCLA). The length of follow-up ranged from 24-225 months, with a median of 38 months. The most common site of origin was the oral cavity (65 cases), and the most common histology was adenoid cystic carcinoma (69 cases). Tumor size, histology, and site were important prognostic factors. For oral cavity lesions, small tumors were well controlled with resection alone (25 of 26) or local excision, followed by irradiation (7 of 7). For advanced tumors arising from the paranasal sinuses and pharynx, the control rates were 43% (15 of 35) and 29% (5 of 17), respectively. Ninety-three percent (27 of 29) of patients with mucoepidermoid carcinoma had no evidence of disease at last follow-up versus 55% (38 of 69) of patients with adenoid cystic carcinoma and 56% (10 of 18) of those with adenocarcinoma. It appears that resection with good margin is adequate treatment for small lesions. Large, poorly differentiated tumors require a combined approach: surgery and radiation therapy.
Adolescent↗
A study of homologous chromosomes using a morphometric approach.
A previous study of 100 karyotyped metaphase cells has demonstrated the utility of a graphic arts tool in deriving chromosome measurements for relative length determination. In the present study we utilize this same approach to address the question: "What are the average differences in relative lengths between apparently normal homologous chromosomes?" Normal standards derived from this study will be useful for testing specific hypotheses involving heteromorphic differences between homologs. No such data on normal controls could readily be found in either An International System for Human Cytogenetic Nomenclature (1985) or elsewhere.
Chromosomes↗
A novel, convenient, and inexpensive approach for deriving ISCN (1985) relative lengths: validation by a morphometric study of 100 karyotyped metaphase cells.
The present study stemmed from a need for a rapid means of deriving reproducible chromosome measurements. An internal set of standards can serve as the basis for routine, easy, and reliable morphometric comparisons. In this study, a total of 100 karyotyped metaphases were analyzed using the Nestler Run-Mate, a computerized curvilinear measuring tool. The null hypothesis tested was that there are no significant differences between chromosomal relative-length values obtained via this previously untested approach and those cited in ISCN (1985). The results indicate that this new method is not only feasible and adequate but has advantage over the conventional approach, which requires the use of a projector and screen to measure chromosomes in unkaryotyped metaphase spreads; further, it is less expensive and easier than using computerized digitizing tablets, a conclusion supported by time-and-effort measurements. Immediately obvious applications include routine use in clinical cytogenetics laboratories, as well as for fractional length estimations in fluorescent in situ hybridization studies performed in research laboratories that do not have access to expensive automated instrumentation.
Chromosomes↗
Amino terminus of the interleukin-8 receptor is a major determinant of receptor subtype specificity.
Interleukin-8 (IL-8) is a key mediator in the migration of neutrophils from the circulation to the site of inflammation in the tissue. IL-8 is secreted by many cell types in response to proinflammatory stimuli such as interleukin 1, tumor necrosis factor, and lipopolysaccharide and is a potent chemoattractant and activator of neutrophils. Neutrophil activating peptide-2 (NAP-2) and melanoma growth-stimulatory activity (MGSA/GRO) are structurally and functionally related to IL-8 and, like IL-8, bind to specific G protein-coupled receptors on neutrophils. In the present study two closely related cloned IL-8 receptor subtypes are characterized by expression of the cDNA clones in monkey kidney cells (COS-7) or chinese hamster ovary cells and analysis of their ligand binding profiles. Both receptor subtypes bind 125I-labeled IL-8 with similar high affinity, however, the F3R receptor binds IL-8 exclusively, while the 4Ab receptor binds both IL-8 and MGSA/GRO with high affinity and NAP-2 with lesser affinity. Furthermore, we demonstrate with the use of intersubtype chimeric receptors that the specificity of ligand binding to both IL-8 receptor subtypes is dictated by the heterogeneous NH2-terminal domain. The F3R receptor is representative of a restricted IL-8 receptor subtype, and 4Ab represents a nonrestricted receptor subtype. It is proposed that these subtypes be named IL-8 receptors alpha and beta, respectively.
Amino Acid Sequence↗
Postoperative radiation therapy after radical prostatectomy for prostate carcinoma.
BACKGROUND: The role and benefit of adjuvant radiation therapy after radical prostatectomy is unclear. This role was evaluated in 58 patients who, after undergoing radical prostatectomy for prostate carcinoma, had local extension of disease beyond the prostate or positive surgical margins. Thirty-nine patients treated surgically alone were compared with 19 patients who received adjuvant postoperative radiation therapy. All patients were followed for at least 5 years, and 50 patients had 10-year follow-ups. RESULTS: At 10 years, the actuarial local failure rate was 31% for patients treated with prostatectomy alone versus 6% for the group receiving postoperative radiation therapy (P less than 0.05). The actuarial survival and metastasis-free survival were similar for both groups. When patients with involved lymph nodes were excluded from analysis, the addition of radiation therapy resulted in improved recurrence-free survival (91% versus 46% at 10 years, P = 0.04) and in a trend toward improved metastasis-free survival (91% versus 55%, P = 0.08). Complications occurred in similar frequencies in both groups. CONCLUSIONS: In patients with local disease extension or positive surgical margins after radical prostatectomy, adjuvant radiation therapy improved local control and was administered with acceptable side effects.
Adult↗
Sarcomas of the head and neck. Prognostic factors and treatment strategies.
The authors reviewed 164 cases of head and neck sarcoma from adult patients seen at the University of California, Los Angeles (UCLA), between 1955 and 1988. The median follow-up was 70 months. Multivariate analysis demonstrated that tumor grade, size, and surgical margin status were the most important independent prognostic factors. Thirty-one percent (27 of 85) of patients with high-grade lesions were free of disease versus 81% (44 of 55) with low-grade lesions at last follow-up. Sixty-seven percent (50 of 76) of patients with lesions smaller than 5 cm were free of disease versus 38% (33 of 88) with lesions larger than 5 cm. In 16 patients, low-grade lesions, measuring less than 5 cm and with negative margins histologically, were controlled with surgery alone. For the 94 patients whose primary tumors were treated at UCLA, local control was achieved in 52% (26 of 50) of patients treated with surgery alone and 90% (20 of 22) with combined therapy (surgery and radiation therapy [RT] with or without chemotherapy). Seventy-five percent (6 of 8) of patients with positive surgical margins treated with postoperative RT achieved local control versus 26% (5 of 19) of patients receiving no additional treatment. In conclusion, surgery alone appears to be adequate treatment for small, low-grade tumors and negative surgical margins. Patients with incomplete resection or high-grade tumors should receive aggressive treatment--surgery and RT.
Adult↗
Primary non-Hodgkin's lymphomas of the paranasal sinuses and nasal cavity. A report of 18 cases with stage IE disease.
During a 26-year period (1961-1987), a total of 18 patients with primary non-Hodgkin's lymphoma (NHL) of the paranasal sinuses and nasal cavity received radiation therapy at (University of California at Los Angeles) UCLA Medical Center. At the time of diagnosis and using the available diagnostic methods, none of these patients had clinically detectable disease beyond the paranasal sinuses. All 18 patients were staged IE by the Ann-Arbor system. When the patients were staged according to the AJC staging system from epithelial tumors, half presented with advanced T3-4 disease. Diffuse histiocytic lymphoma was the most common histology (eight cases) and maxillary sinus, the most common site of origin (11 cases). All nine T1-2 tumors received radiation therapy alone, while radiation and chemotherapy was used in seven of nine advanced T3-4 staged tumors. The mean follow-up was 71 months. At last follow-up, eight of nine T1-2 patients were rendered disease-free. In contrast, only four of nine T3-4 patients had long-term disease-free survival. Seventy-five percent of the failure occurred within 2 years. Radiation therapy alone achieves high local control in small tumors (T1-2), while large tumors (T3-4) require aggressive combined treatment, i.e., radiation and chemotherapy.
Adolescent↗
Electrophysiologic effects of left ventricular hypertrophy in the intact cat.
Electrophysiologic abnormalities have been described in isolated, hypertrophied left ventricular tissue removed from animals exposed to a chronic pressure load. However, changes in electrical properties of intact hypertrophied hearts have not been described. To study this question, 15 cats underwent supraventricular aortic banding and five underwent a sham procedure. After ten weeks, the animals were anesthetized and instrumented using paired transmural plunge electrodes and endocardial quadripolar pacing catheters. Measurement of pacing threshold, refractoriness, inducibility of ventricular arrhythmias (using programmed electrical stimulation), and vulnerability to ventricular fibrillation (ventricular fibrillation threshold) were made in both groups. Mean left ventricular mass was significantly greater in the banded compared with sham-operated animals (2.5 +/- 0.9 v 2.1 +/- 0.5 g/kg body weight; P less than .05). Pacing thresholds and refractory periods measured at multiple left and right ventricular sites were similar in both groups, and there was no difference in the extent of site-to-site differences in refractoriness (dispersion). Six banded but no sham animals had inducible ventricular tachycardia or fibrillation using programmed stimulation. Furthermore, left ventricular mass was significantly greater in animals with inducible arrhythmias compared with those noninducible (P less than .05). Ventricular fibrillation thresholds, measured in milliamperes (mA), in the banded animals were significantly lower in the left ventricle (13.5 +/- 1.3 mA) than in the right (21.7 +/- 3.2 mA; P less than .05) and was also lower than the thresholds obtained in either the left or right ventricle of the sham-operated animals (18.3 +/- 1.9 mA and 20.1 +/- 1.1 mA, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Impaired heart rate responses to cough and deep breathing in elderly patients with unexplained syncope.
To test the hypothesis that elderly patients with unexplained syncope have impaired autonomic control of heart rate, chronotropic responses to deep breathing and cough were studied in 12 elderly patients (85 +/- 4 years), 14 elderly control subjects (82 +/- 7 years) and 10 young subjects (26 +/- 5 years). There was no difference in resting RR interval between elderly patients with syncope and control subjects. However, the ratio of the maximum RR/minimum RR (an index of heart rate variability) during deep breathing was significantly lower in patients than in control subjects (p less than 0.005). In the minute following cough, there was no difference in initial reflex tachycardia, but subsequent rebound bradycardia was blunted in the elderly patients with syncope. The predominant impairment in elderly patients with unexplained syncope was the bradycardia component of the responses to deep breathing and cough, suggesting that these patients may have impaired parasympathetic modulation of heart rate. Although not likely to be the cause of syncope in these patients, these findings may reflect an underlying autonomic defect.
Aged↗
Effects of diethylstilbestrol on Propionibacterium acnes immunomodulation: inhibition of macrophage activation and antitumor activity.
Exposure of mice to diethylstilbestrol (DES) inhibited Propionibacterium acnes-induced antitumor activity in vivo against the B16F10 subcutaneous tumor. The inhibitory effect was associated with inhibition by DES of the characteristic P. acnes induced splenomegaly and changes in splenic and peritoneal macrophages (M phi) cell populations. The characteristic P. acnes induced reductions in M phi alkaline phosphodiesterase I (APD) ectoenzyme activity and in total RNA synthesis, proposed biochemical markers of tumoricidal M phi, were partially or completely reversed in DES-treated mice. As predicted from these in vivo and in vitro results, DES treatment significantly decreased P. acnes activation of M phi antitumor activity in vitro against B16F10 melanoma and Lewis lung carcinoma cells. These data suggest a macrophage activation defect may be involved in the reduced resistance that DES-treated animals exhibit to a variety of neoplastic and microbial challenges.
Animals↗
Histopathologic correlates of inducible ventricular tachycardia in two experimental canine models of myocardial infarction.
Ventricular tachyarrhythmias are the leading cause of sudden cardiac death. Determination of the substrates conducive to the initiation of ventricular tachyarrhythmias remains an important clinical goal. The purpose of this study was to correlate electrophysiologic and histopathologic parameters conducive to the initiation of sustained ventricular tachycardia using programmed electrical stimulation in two canine models of myocardial infarction. Histopathologic correlates included: infarct pattern (heterogeneous vs. homogeneous morphology), distribution (viable epicardial or endocardial rim), and size. Twenty-one adult dogs were randomly divided into two groups: (1) 12 dogs underwent two-stage, 2-hour occlusion of the proximal left anterior descending coronary artery (LAD); and (2) nine animals had permanent, complete occlusion of the LAD with latex embolization. Using programmed ventricular pacing with two premature ventricular extrastimuli, initiation of ventricular tachycardia was attempted at both 1 and 2 weeks after infarction with the chest closed and opened each time. Electrophysiologic evaluation of the infarct type correlated significantly with the histologic morphology of the infarction (p less than 0.001), the presence of a viable epicardial rim was an extremely important discriminating variable for ability to induce sustained ventricular tachycardia (p = 0.04). The presence of an endocardial rim was not significant (p = 1.0). Infarct size alone was only marginally related to ventricular tachycardia inducibility (p = 0.08). Non-uniform infarcts were more conducive to the initiation of sustained ventricular tachycardia than homogeneous infarcts (p = 0.025). The presence of a large, non-uniform infarct was the best overall discrimination variable for inducibility (p = 0.0002). Thus, in these experimental models, specific infarct morphologies correlate significantly with susceptibility to inducible sustained ventricular tachyarrhythmias.
Animals↗
Serial cardiac function tests in myocarditis.
Sixteen patients (mean age 27 years, range 16 to 39 years) with the diagnosis of myopericarditis established by strict clinical criteria were evaluated following recovery 0.7 to 4.0 years (mean 2.7 years) later. Evidence of an acute viral infection was present in 44%. During the acute illness, the major clinical manifestations consisted of pericarditis in 10 patients, acute myocardial infarction in 5, right ventricular dysfunction in 5, bundle branch or hemiblock in 4, ventricular arrhythmias in 3, congestive heart failure in 3 and cardiogenic shock and inappropriate sinus tachycardia in one patient each. Holter monitoring, echophonocardiography and radionuclide ventriculography results were abnormal in 57, 67 and 64% of patients respectively. At follow-up, these tests were abnormal in 67, 7 and 73%. Focal wall motion abnormalities were present in five. Seventy-five percent of patients had one or more abnormal tests at last follow-up. Although 8 patients had improved by a scoring system, 5 patients had an increase in the number of abnormal tests, including one who died. These findings indicate that persistent abnormalities following recovery from myopericarditis are not rare and support the hypothesis that the syndrome of dilated cardiomyopathy may be a sequel of myopericarditis.
Acute Disease↗
[The wedge test--a simple testing procedure for the fatigue strength of bonded joints].
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Chromium Alloys↗
Arrhythmia inducibility and ventricular vulnerability in a chronic feline infarction model.
Ventricular tachyarrhythmias are the cause of sudden cardiac death in ischemic heart disease. Reliable animal models are necessary to study techniques for identifying individuals at risk and to develop effective modes of therapy. The purpose of the present study was to evaluate the inducibility of ventricular tachyarrhythmias and vulnerability to ventricular fibrillation and to correlate these findings with changes in ventricular refractoriness in a chronic feline model. Twelve conditioned cats were randomly divided into two groups: group A, sham-operated controls (n = 5); or group B, permanent occlusion of the left anterior descending coronary artery (n = 7). Two weeks later, the following measurements were made: (1) assessment of refractory periods at several ventricular sites; (2) inducibility to ventricular tachyarrhythmias; and (3) determination of ventricular fibrillation threshold. After electrophysiologic testing, the animals were killed and the hearts were studied histologically. Ventricular fibrillation thresholds were significantly lower in group B compared with group A (13 +/- 3 vs 46 +/- 9 mA; p less than 0.01). One of the sham-operated controls had induction of nonsustained ventricular tachycardia, while six of the group B animals had reproducible, inducible ventricular tachyarrhythmias (p less than 0.01). There was a significant dispersion in effective refractory periods between normal and infarcted sites in group B (46 +/- 6 msec) not seen in group A (12 +/- 2 msec, p less than 0.01). The group A cats demonstrated minimal damage to the myocardium or cardiac architecture. Group B cats demonstrated extensive, transmural, homogeneous infarcts of approximately 30% of the anterior wall of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Nonarrhythmogenicity of therapeutic cryothermic lesions of the myocardium.
There is increasing interest in the application of surgical methods to the treatment of refractory ventricular tachyarrhythmias (VT). Cryothermic ablation is one of the more promising techniques. However, there is clinical concern that a cryothermic lesion may lead to later arrhythmias. Previous studies have shown that dogs with nonhomogeneous, transmural infarctions are susceptible to VT initiation using programmed electrical stimulation (PES). The purpose of this study was to compare the incidence of inducing VT in dogs with transepicardial cryothermic myocardial damage (Group A) versus dogs with nonhomogeneous transmural infarctions resulting from 2-hr occlusion of the left anterior descending coronary artery (LAD) and subsequent reperfusion (Group B). Twelve dogs in each group were studied 10-14 days later using PES with unipolar cathodal ventricular pacing and two ventricular extrastimuli. Initiation of VT was attempted from at least six normal intramyocardial sites in each dog along the distribution of the LAD and in close proximity (less than or equal to 1 cm) to areas of chronically cryoablated damaged tissue. All dogs survived the initial procedure. VT was not inducible in any dog in Group A. Histological as well as electrophysiological evaluation, including determination of regional excitability thresholds and refractory periods employing strength-interval curves, revealed that all of the Group A dogs had homogeneous transmural infarcts with variable subendocardial sparing. In conclusion (1) cryothermal injury produces homogeneous damage; and (2) the lesion produced is not arrhythmogenic at 7-14 days.
Animals↗