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Biomedical subjects

R Mark

Publications and source records attributed to R Mark.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1989

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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

Histopathologic factors conducive to experimental ventricular tachycardia.

Ventricular tachyarrhythmia is the leading cause of sudden cardiac death. Determination of the substrates conducive to the initiation of this arrhythmia remains an important clinical goal. The purpose of this study was to correlate histopathologic findings, specifically: pattern (heterogeneous versus homogeneous infarct morphology), distribution (viable epicardial and/or endocardial rim), and infarct size, with susceptibility to the initiation of sustained ventricular tachycardia employing programmed electrical stimulation in two canine models of experimental myocardial infarction. Twenty-one adult dogs were randomly divided into two groups: 12 dogs underwent two-stage, 2-hour occlusion of the proximal left anterior descending coronary artery and nine animals underwent permanent, complete occlusion of the left anterior descending coronary artery with latex embolization. With programmed ventricular pacing with two premature ventricular extrastimuli, initiation of ventricular tachycardia was attempted, open chest, two weeks after infarction. 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 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). Nonuniform infarcts were more conducive to the initiation of sustained ventricular tachycardia than were homogeneous infarcts (p = 0.025). The presence of a large, nonuniform infarct correlated best with inducibility (p = 0.0002). Thus in these experimental models, specific infarct morphologies correlate significantly with susceptibility to inducible sustained ventricular tachyarrhythmias.

Animals↗
PubMed1984

The course of axons of retinal ganglion cells within the optic nerve and tract of the chick (Gallus gallus).

Small laser lesions placed in the posthatch chicken retina resulted in axotomy and then death of all ganglion cells located in a sector peripheral to the primary damage. With the use of silver techniques, the patterns of degenerating retinal fibers in the optic nerve, chiasm, and optic tract were examined. In the proximal part of the optic nerve, radial retinal lesions resulted in a sheet of degenerating axons along the rostrocaudal extent of the nerve. The position of degenerating axons was related to the site of their entry in the optic nerve head with an overlapping distribution of degenerating fibers entering the optic nerve head from equivalent points from the temporal and nasal sides. In the optic chiasm, the distribution of fibers was similar to that seen in the proximal part of the optic nerve. In the optic tract there was a similar mixing of fibers from opposite sides of the retina. The ventral, nasal and temporal retinal fibers lay in the superficial part of the tract whereas the fibers from the nasal and temporal dorsal retina ran in the deeper, medial aspect of the tract. The central-to-peripheral axes of the retina were mapped along the rostrocaudal axis of the tract. As the tract approached the tectum degenerating fibers from single retinal lesions did not always remain together. In the case of a lesion in the ventral nasal retina, degenerating fibers split into two bundles located at opposite ends of the tract only to reunite at their terminal regional at the caudal pole of the tectum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

An atlas of the primary visual projections in the brain of the chick Gallus gallus.

The localisation of the primary visual centres in the chick mesencephalon and diencephalon was determined by autoradiographic anterograde transport and degeneration techniques. Strong visual projections were found in the tectum, lateral anterior thalamic nucleus, lateroventral geniculate nucleus, superficial synencephalic nucleus, external nucleus, ectomammillary nucleus, tectal grey, dorsolateral anterior thalamus, rostrolateral part, and the pretectal optic area. Weaker retinal projections were found in the ventrolateral thalamus, two subregions of the dorsolateral anterior thalamus, lateral part, diffuse pretectal nucleus, dorsolateral anterior thalamus, magnocellular part, and the hypothalamus. An atlas of the retinal projections was constructed from sections.

Animals↗
PubMed1984

Topography of primary visual centres in the brain of the chick, Gallus gallus.

In a previous paper (Ehrlich and Mark, '83b) the primary visual centres of the chick were described. In this paper patterns of retinotopy are examined by means of silver degeneration and autoradiographic techniques following discrete laser lesions of the retina. Well-defined and complete retinotopic maps are found in each of the following visual centres: tectum, lateral anterior thalamus, lateroventral geniculate nucleus, superficial synencephalic nucleus, ectomammillary nucleus, and tectal grey. In the dorsolateral anterior thalamus, pars lateralis, and external nucleus there is some evidence of a retinotopic innervation, yet not as well defined as those nuclei mentioned previously. Retinotopic maps were not observed in other retinorecipient regions. These include the ventrolateral thalamus, dorsolateral anterior thalamus, magnocellular part and rostrolateral part, pretectal optic area, and diffuse pretectal nucleus. Within the lateroventral geniculate, lateral anterior thalamus, superficial synencephalic nuclei, and the tectal grey, the ventral to dorsal retinal axis is mapped along the rostrocaudal axis, the reverse of the orientation seen in the tectum, which may have implications for explanations of how retinotopic maps are formed. The poor retinotopy n dorsolateral anterior thalamus, lateral part, is discussed with respect to the view that it may be the avian homologue of the mammalian lateral geniculate nucleus.

Animals↗
PubMed1984

Adsorption of plasma from tumor-bearing hosts over protein A--containing nonviable Staphylococcus aureus Cowan I: possible mechanism of antitumor reactions.

Adsorption of autologous plasma over nonviable Staphylococcus aureus Cowan I (SAC) followed by reinfusion of the plasma causes regression of (a) chemically induced rat mammary adenocarcinomas (MA), and (b) canine transmissible venereal tumors (TVT) and spontaneously occurring dog tumors. Animal data are more impressive than that from trials in humans. Nine of 41 patients receiving perfusions of adsorbed plasma showed some partial objective response. Eight of these nine patients received multiple perfusions over a period of time. Twenty-one of 41 patients showed subjective responses. Adsorption of autologous plasma over non-protein A--containing S. aureus Wood 46 caused regression of MA. Adsorption of normal rat plasma with SAC, and infusion of this adsorbed plasma into mammary tumor--bearing rats, caused regression of MA. Intravenous infusion of purified protein A alone caused regression of both rat MA and canine TVT. Superimposed on this observation is the finding that, during plasma adsorption, bacterial moieties leach from SAC. It is possible that the immunostimulation observed in plasma-perfused hosts is due to the removal of plasma blocking agents on one hand, and introduction of the bacterial agents on the other.

Adenocarcinoma↗