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Biomedical subjects

J Friedman

Publications and source records attributed to J Friedman.

At least 145 records · Page 8Linked to original sources
PubMed1990

Ca antagonist verapamil and tumor promoter 12-O-tetradecanoylphorbol-13- acetate (TPA) induce chromosomal aberrations in human lymphocytes.

Lymphocytes from 8 healthy donors were cultured for 3 days in the presence of phytohemagglutinin. Addition of the Ca antagonist verapamil or the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) increased chromosomal aberrations in comparison with control cultures. The effects of TPA and verapamil were additive. Although the Ca ionophore A23187 had no effect per se, it did abolish the effect of verapamil. Five patients with supraventricular tachycardia were treated clinically with verapamil for 1 week. Their lymphocytes were cultured for 3 days in vitro in the presence of phytohemagglutinin. These lymphocytes showed higher chromosomal aberrations in comparison with lymphocytes isolated from the patients before treatment. The clinical significance is still unclear. We suggest that calcium ions may be necessary for the intactness of chromosomes of human lymphocytes and presumably of other cells.

Chromosome Aberrations↗
PubMed1990

Thyroid carcinoma metastatic to the medial rectus muscle.

Isolated extraocular muscle metastasis is rare and is unreported for thyroid carcinoma. The authors describe a 72-year old man who presented with pain, redness, and proptosis of the right eye. Orbital computed tomography showed a large fusiform soft tissue mass along the medial aspect of the right orbit, involving the medial rectus. Orbital exploration disclosed a mass within the medial rectus muscle sheath involving the muscle belly. Histopathologic examination including electron microscopy, revealed metastatic thyroid carcinoma. Systemic treatment with radioactive iodine was recommended and refused by the patient. One year later, he died of complications from his metastatic disease.

Adenocarcinoma↗
PubMed1990

Syntax comprehension deficits in Parkinson's disease.

The comprehension of 100 different spoken English sentences was studied in 39 patients with mild to moderate Parkinson's disease (PD) using the Rhode Island Test of Language Structure. Eight of the PD patients were mildly demented, and the remaining 31 showed no cognitive deficits. Seven of the eight mildly demented patients had high comprehension error rates for sentences that had moderately complex syntax. The error rates of 28 of the 31 other, nondemented patients were low, similar to those of normal control subjects. The difference between the error rates of the demented and nondemented patients was significant (p less than .02, two-tailed t-test). The data argue against some current "modular" theories that segregate linguistic from other cognitive behavior. The destruction by PD of the midbrain regions that stimulate the frontal cortex may be responsible for both cognitive and syntactic comprehension deficits.

Aged↗
PubMed1990

Changes in steady-state levels of mRNAs coding for type IV collagen, laminin and fibronectin following capillary basement membrane thickening in human adult onset diabetes.

The development of capillary basement membrane thickening has been linked to microvascular changes known to occur in tissues of patients with type II diabetes. Previous evidence has suggested that capillary basement membrane thickening is due to increased basement membrane synthesis. In this study, skin samples from 8 diabetic patients with confirmed capillary basement membrane thickening and 7 non-diabetic controls were used to assess steady state levels of mRNAs coding for several basement components including pro alpha 1(IV) collagen, laminin and fibronectin. Total RNA was extracted from abdominal skin samples and levels of mRNAs coding for the basement membrane components laminin, fibronectin and pro alpha 1(IV) collagen, a fibrillar collagenous protein, pro alpha 1(I) collagen and an intracellular polypeptide, gamma-actin, were determined by dot blot hybridization analysis. While there were no changes of steady state levels of pro alpha 1(I) collagen mRNA and laminin mRNA, a significant reduction was noted in the quantitative recovery of mRNA levels for pro alpha 1(IV) collagen, gamma-actin and fibronectin in total RNA isolated from the skin of diabetic patients. This reduction in levels of mRNAs coding for basement membrane components contrasts with pathological confirmation of an accumulation of endothelial capillary basement membrane in skin from diabetic patients and suggests that basement membrane thickening arises more as a consequence of reduced basement membrane degradation than elevated synthesis of basement membrane components.

Aged↗
PubMed1990

Identification of a specific domain in the beta-adrenergic receptor required for phorbol ester-induced inhibition of catecholamine-stimulated adenylyl cyclase.

The molecular basis for the effects of 4 beta-phorbol 12-myristate 13-acetate (PMA) on adenylyl cyclase activation was examined using site-directed mutants of the hamster beta-adrenergic receptor (beta AR) expressed in L cells. Phorbol ester activation of protein kinase C (PKC) in L cells transfected with wild-type beta AR caused at least three discernible effects on adenylyl cyclase activity, each with an EC50 of 20 to 50 nM, (i) a 2-3-fold increase in the Kact for epinephrine stimulation, (ii) a 2-3-fold increase in the maximal level (Vmax) of hormonal stimulation, and (iii) a decrease in the Gi-mediated inhibition of forskolin stimulation. Deletion from the beta AR of amino acid residues 259-262, which removes one of the two consensus sites for phosphorylation by PKC, eliminated (greater than 90%) the PMA-induced increase in the Kact, whereas the PMA-induced increase in the Vmax and loss of Gi-mediated inhibition were not affected by the deletion. Neither deletion of the other PKC consensus site in the beta AR (residues 343-348) nor truncation of the Ser/Thr-rich C-terminal domain (residues 354-418) affected the PMA-induced changes in adenylyl cyclase. The effects of PMA on Gi-mediated inhibition and the Vmax closely mimicked the action of islet-activating protein, consistent with a direct effect of PMA-activated PKC on Gi. In contrast, the effects on the Kact appear to be receptor specific. These results demonstrate that the consensus site for phosphorylation by PKC, found in the third intracellular loop of the beta AR, is required for the PMA-induced increase in the Kact for epinephrine stimulation. Use of L cells transfected with D(259-262)beta AR allowed the characterization of the postreceptor effects of PMA without interference from receptor-level effects.

Adenylate Cyclase Toxin↗
PubMed1990

Quantitative analysis of tomographic stress thallium-201 myocardial scintigrams: a multicenter trial.

The accuracy of the previously developed and validated Cedars-Sinai Medical Center (CSMC) computer program for quantitative analysis of thallium-201 (201TI) stress myocardial tomograms was assessed in a multicenter trial consisting of 242 patients with coronary angiography and 76 with a low likelihood (LL) of coronary artery disease (CAD) involving various cameras, computers, and operators. The program utilized gender-matched normal limits developed from 35 LL patients at CSMC. The multicenter results as compared to those of 168 patients from CSMC were not significantly different with respect to the overall sensitivities (94% versus 95%) and specificities (44% versus 56%) for identification of CAD and normalcy rates which were determined in LL patients (82% for both) and with respect to identification of individual diseased arteries. The results indicate that our method for quantifying tomographic 201TI stress scintigrams utilizing standard normal limits can be applied at other institutions by different operators, using a variety of cameras and computers, with similar accuracy to that currently obtained at our institution.

Coronary Disease↗
PubMed1989

Comparison of technetium 99m methoxy isobutyl isonitrile and thallium 201 for evaluation of coronary artery disease by planar and tomographic methods.

To compare stress/rest technetium 99m methoxy isobutyl isonitrile (Tc-MIBI) with stress redistribution thallium 201(T1-201) myocardial perfusion imaging, 36 patients were studied by single photon emission computerized tomography (SPECT) and planar methods. For SPECT, overall sensitivities for identification of patients with coronary artery disease were 93% (14/15) by Tc-MIBI and 80% (12/15) by TI-201 (p = NS). For planar methods, overall sensitivities were 73% (11/15) by both TI-201 and Tc-MIBI. Overall specificity was 75% (3/4 patients with normal coronary arteries) for both tracers with SPECT and Tc-MIBI by planar imaging and was 50% for planar TI-201 (p = NS). The normalcy rates for overall identification of coronary artery disease were determined in 17 patients with a low likelihood of disease. For SPECT, normalcy rates were 100% by Tc-MIBI and 77% by TI-201 (p = NS). For planar, they were 94% by Tc-MIBI and 88% by TI-201 (p = NS). Vessel sensitivities in the 35 stenosed coronary arteries (greater than or equal to 50% stenosis) for SPECT were 87% by Tc-MIBI and 77% by TI-201 (p = NS). For planar, the vessel sensitivities were 60% by Tc-MIBI and 54% by TI-201 (p = NS). For both tracers, the SPECT vessel sensitivities were significantly higher (p less than 0.005) than planar vessel sensitivities. The vessel specificities in 22 coronary vessels with less than 50% stenosis were 86% by SPECT Tc-MIBI and TI-201, 80% by planar Tc-MIBI and 73% by planar TI-201 (p = NS, SPECT vs planar, Tc-MIBI vs TI-201). Regarding myocardial segmental agreement, for the presence of stress defects the agreement was 91% for the 720 SPECT segments and 95% for the 540 planar segments. For severity of stress defects based on semiquantitative visual scoring, the exact agreement was 87% for SPECT and 80% for planar. For the pattern of reversibility in myocardial segments with stress defects, the agreement was 97% for SPECT and 91% for planar. This study demonstrated that Tc-MIBI and TI-201 correlate well on both planar and SPECT images with respect to the identification of patients with coronary artery disease, identification of disease in individual coronary arteries, the presence and severity of perfusion defects, and the assessment of defect reversibility. Furthermore, SPECT Tc-MIBI was shown to be superior to planar Tc-MIBI for the identification of individual diseased vessels.

Adult↗
PubMed1989

Abortifacient potential for the epigeal parts of Peganum harmala.

The effect of methanol and acetone extracts of the epigeal parts of Peganum harmala, a common medicinal plant among Bedouins in Israel, was studied on several parameters of reproduction in female rats. The methanol extract at a dose of 2.5 g/kg/day, offered in food or in drinking suspension for 30 days, significantly prolonged diestrus by 1.0 day. The methanol extracts at doses of 2.0, 2.5 and 3.5 g/kg/day appeared to produce a dose-dependent significant decrease in litter size. No change in the physical and nutritional status of the animals and no adverse toxicological effects were observed.

Abortifacient Agents↗
PubMed1989

Quantitative single photon emission computed thallium-201 tomography for detection and localization of coronary artery disease: optimization and prospective validation of a new technique.

One hundred eight-three men underwent stress-redistribution thallium-201 myocardial perfusion tomography. After evaluation of various preprocessing filters in a phantom study, the Butterworth filter with a frequency cutoff of 0.2 cycles/pixel, order 5 (which provided optimal filter power) was used in the back projection algorithm of the patient studies. All short-axis and apical portions of vertical long-axis images were quantified by dividing each myocardial slice into 60 equal sectors and displaying the maximal count per sector as a linear profile. In a pilot group consisting of 20 normal men (less than 5% likelihood of coronary artery disease) and 25 men with coronary artery disease (greater than or equal to 50% coronary stenosis by angiography), profiles representing the lowest observed value below the mean normal profiles provided the best threshold for defining normal limits. Abnormal portions of the patient profiles were plotted on a two-dimensional polar map. The polar map was divided into 102 sectors, and sectors with a probability of greater than or equal to 80% for disease of each one of the three major coronary arteries were clustered to represent specific coronary artery territories. Receiver operating characteristic curve analysis for defect size showed that the optimal threshold for defining a definite perfusion defect was 12% for the left anterior descending and left circumflex and 8% for the right coronary artery territories. These criteria were prospectively applied to an additional 92 patients with angiographic coronary artery disease, 18 patients with normal coronary arteriograms and 28 patients with less than 5% likelihood of coronary disease. Sensitivity, specificity (in patients with normal coronary arteriograms) and normalcy rate (in patients with less than 5% likelihood of coronary artery disease) for overall detection of coronary disease were 96%, 56% and 86%, respectively. Sensitivity and specificity for identification of individual diseased vessels were, respectively, 78% and 85% for the left anterior descending, 79% and 60% for the left circumflex and 81% and 71% for the right coronary artery. These results were not significantly different from those of the pilot group. An optimized quantitative method for interpretation of stress thallium-201 myocardial perfusion tomography has been developed. Prospective application of this method indicates that the technique is accurate for the overall detection of coronary artery disease and identification of disease in individual arteries.

Coronary Circulation↗
PubMed1989

Cell-free heterologous desensitization of adenylyl cyclase in S49 lymphoma cell membranes mediated by cAMP-dependent protein kinase.

We have examined the cell-free heterologous desensitization of adenylyl cyclase in plasma membrane preparations from S49 wild-type (WT) and kin- cells (which lack cAMP-dependent protein kinase) incubated with purified catalytic subunit of cAMP-dependent protein kinase (cA.PKc). cA.PKc caused a rapid (t1/2 = 40 s) decrease in the hormone responsiveness of adenylyl cyclase in the WT membrane preparations that mimicked the intact cell heterologous desensitization; that is, there was an increase in the Kact for both epinephrine and prostaglandin E1 (PGE1) stimulations of adenylyl cyclase induced at the receptor level because neither forskolin- nor NaF-stimulated activity was affected. The desensitization was independent of agonist occupancy of the receptor, and the effects were blocked both by the active fragment (amino acids 5-22) of the specific inhibitor of cA.PK and by p[NH]ppA. cA.PKc treatment of kin- membranes resulted in a heterologous desensitization that resembled the effects of WT adenylyl cyclase, with the exception that forskolin-stimulated activity was also reproducibly decreased by 24%. cA.PKc had no effect on WT membranes isolated from cells that had previously undergone maximal heterologous desensitization during treatment with 10 microM forskolin. In contrast, cA.PKc-induced heterologous desensitization of kin- membranes was additive with the epinephrine-induced homologous desensitization of intact cells. Cell-free desensitizations were reversed by incubation of membranes with cA.PKc and ADP, conditions that drive the kinase reaction backward. The similarities of our cell-free cA.PKc-mediated heterologous desensitization of adenylyl cyclase with the intact cell desensitization support our hypothesis that heterologous desensitization of the WT lymphoma cells is mediated by cA.PK via a mechanism independent of homologous desensitization.

Adenosine Diphosphate↗
PubMed1989

Informed consent in the practice of acupuncture.

Early records reveal a parental, beneficent attitude, but an uncommunicative approach to the patient. The Nuremberg trials of 1946 demonstrated the need for ultimate responsibility of the physician, and for a well-informed, consenting patient in experimental procedures (Nuremberg Code of 1947). A later report, the Belmont Report (1975) emphasized the difference between therapeutic research and research unrelated to improving the patient's state of health. Acupuncture has the status of an experimental modality, and requires the informed consent discussion and signature on the form by the patient for each procedure.

Acupuncture Therapy↗
PubMed1989

Identification of a specific site required for rapid heterologous desensitization of the beta-adrenergic receptor by cAMP-dependent protein kinase.

The molecular basis for heterologous desensitization of the beta-adrenergic receptor (beta AR) was investigated by site-directed mutagenesis of the beta AR protein. Rapid heterologous desensitization of agonist-stimulated adenylyl cyclase activity was observed when L cells expressing the wild-type beta AR were incubated with 50 nM epinephrine. This desensitization response could be mimicked in a cell-free system by incubation with cAMP-dependent protein kinase (cA.PK). Deletion of amino acid residues 259-262 from the beta AR, removing one of the two consensus sequences in the receptor for phosphorylation by cA.PK, abolished the ability of the receptor to undergo rapid heterologous desensitization. In contrast, deletion of the other cA.PK consensus sequence (residues 343-348) or truncation of the Ser/Thr-rich C-terminal tail of the beta AR (deletion of residues 354-418) did not affect this heterologous desensitization process. These results suggest that the action of cA.PK on amino acid residue(s) contained within the sequence 259-262 of the beta AR is required for rapid heterologous desensitization of the receptor in response to agonists.

Adenylyl Cyclases↗
PubMed1989

"Upward creep" of the heart: a frequent source of false-positive reversible defects during thallium-201 stress-redistribution SPECT.

A new cause of artifactual 201Tl defects on single photon emission computed tomography (SPECT) termed "upward creep" of the heart is described. In 102 consecutive patients undergoing 201Tl SPECT, 30 (29%) demonstrated upward creep defined by an upward movement of the heart of greater than or equal to 2 pixels during acquisition. In 45 consecutive patients with a less than 5% likelihood of coronary artery disease, 17 (38%) had upward creep. Of these nine had reversible 201Tl defects localized to the inferior and basal inferoseptal walls, while none of the 28 without upward creep had defects. The 17 low likelihood patients with upward creep had longer exercise duration and higher peak heart rate than those without upward creep. In five additional low likelihood patients with upward creep in whom imaging was immediately repeated, the upward creep pattern disappeared on the repeated images. After we changed our test protocol to begin imaging 15 min postexercise, only five (14%) of 36 low likelihood patients tested demonstrated upward creep. Upward creep is probably related to a transient increase in mean total lung volume early following exhaustive exercise, resulting in a mean lower position of the diaphragm (and thus the heart) at the beginning of imaging. The frequency of this source of false-positive 201Tl studies can be reduced by delaying SPECT acquisition until 15 min postexercise.

Adult↗
PubMed1988

Sialic acid content in mouse myeloma cells and derived B-cell hybridomas with different metastatic potentials.

In a previous work we have reported on the metastatic capacities of mouse myeloma cells (NSO) and of two hybridomas derived from them. The present study was designed to examine the sialic acid content of these cell types, their attachment to glass and their capping in the presence of wheat germ agglutinin (WGA). The results showed no significant differences in sialic acid content between NSO and Hybridoma A (Hy A) cells which are non and low metastatic, respectively, whereas Hybridoma B (Hy B), which is highly metastatic, contained 1.4-1.6-fold higher sialic acid compared to the other two cell types. NSO cells exhibited a high, Hy A a moderate and Hy B a negligible attachment to glass. Capping experiments showed a low response of NSO cells, a moderate response of Hy A and a high response of Hy B in the presence of WGA. The results are discussed with regard to the metastatic potential of these cell types taking into consideration the properties cell surface sialic acid is known to endow to cells, determining various aspects of their behaviour.

Animals↗
PubMed1988

Mental stress and the induction of silent myocardial ischemia in patients with coronary artery disease.

To assess the causal relation between acute mental stress and myocardial ischemia, we evaluated cardiac function in selected patients during a series of mental tasks (arithmetic, the Stroop color--word task, simulated public speaking, and reading) and compared the responses with those induced by exercise. Thirty-nine patients with coronary artery disease and 12 controls were studied by radionuclide ventriculography. Of the patients with coronary artery disease, 23 (59 percent) had wall-motion abnormalities during periods of mental stress and 14 (36 percent) had a fall in ejection fraction of more than 5 percentage points. Ischemia induced by mental stress was symptomatically "silent" in 19 of the 23 patients with wall-motion abnormalities (83 percent) and occurred at lower heart rates than exercise-induced ischemia (P less than 0.05). In contrast, we observed comparable elevations in arterial pressure during ischemia induced by mental stress and ischemia induced by exercise. A personally relevant, emotionally arousing speaking task induced more frequent and greater regional wall-motion abnormalities than did less specific cognitive tasks causing mental stress (P less than 0.05). The magnitude of cardiac dysfunction induced by the speaking task was similar to that induced by exercise. Personally relevant mental stress may be an important precipitant of myocardial ischemia--often silent--in patients with coronary artery disease. Further examination of the pathophysiologic mechanisms responsible for myocardial ischemia induced by mental stress could have important implications for the treatment of transient myocardial ischemia.

Adult↗
PubMed1988

Pachyonychia congenita.

Pachyonychia congenita is a rare hereditary disorder characterized mainly by nail hypertrophy and dyskeratoses of skin and mucous membranes. A thorough literature survey since its first description in 1904 up to 1985 revealed 168 cases of pachyonychia congenita. There were no indications of any sex or ethnic group predilection. Based on this survey the following classification is suggested: type I (56.2% of cases), hyperkeratosis of nails, palmoplantar keratosis, follicular keratosis, and oral leukokeratosis; type II (24.9% of cases), clinical findings of type I plus bullae of palms and soles, palmar and plantar hyperhidrosis, natal or neonatal teeth, and steatocystoma multiplex; type III (11.7% of cases), clinical findings of types I and II plus angular cheilosis, corneal dyskeratosis, and cataracts; and type IV (7.2% of cases), clinical findings of types I, II, and III plus laryngeal lesions, hoarseness, mental retardation, hair anomalies, and alopecia.

Humans↗