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Biomedical subjects

S Goldstein

Publications and source records attributed to S Goldstein.

At least 469 records · Page 26Linked to original sources

Predictive survival models for resuscitated victims of out-of-hospital cardiac arrest with coronary heart disease.

Resuscitated victims of cardiac arrest with coronary heart disease represent a group of patients with an accelerated mortality rate. Among 227 such patients in our follow-up study, 20% had died at 1 year and 50% were dead in slightly over 3 years. Predictors of death were related to use of digitalis, elevated blood urea nitrogen, cerebral vascular accident, previous myocardial infarction, and age. In a subset of 103 patients in whom ambulatory electrocardiographic recordings were available within 3 months of the arrest event, the presence of complexity and high-frequency ventricular premature beats (VPBs) (greater than or equal to 25/hr) were added to the mortality predictors of digitalis and diuretic therapy and elevated blood urea nitrogen. An almost equal number of patients died suddenly and nonsuddenly. Predictors of sudden death were treatment with quinidine and paired VPBs. Occurrence of arrhythmias was an important addition to the previous mortality predictors related to left ventricular dysfunction.

Actuarial Analysis↗

Cancer in the elderly: basic science and clinical aspects.

The incidence of cancer increases progressively with age. Rearrangements of genomes have been found to accompany cellular aging. These factors, in concert with age-dependent alterations in immune function and host defense, may help to explain the increased risk of malignant disease in aged persons. The clinical presentation and natural history of neoplasia are also affected by aging. This conference reviews recent developments in these areas, examines the effects of drug use in the elderly and implications for management, and discusses current information on how age may influence the response of cancer to therapy.

Aged↗

Fibroblast growth factors in scleroderma.

Sera from patients with progressive systemic sclerosis (PSS), compared to normal sera, contained increased fibroblast growth promoting factor(s) (FGPF) for autologous and heterologous PSS skin fibroblasts and fibroblasts from normal donors. The relative stimulatory effect of FGPF was unaltered by dilution, mixing with normal serum, or media refeeding. The mean value of 42 PSS sera tested showed growth promoting activity significantly greater than the mean level of activity obtained with 42 sex matched normals (p less than 0.001). FGPF in sera from 25 patients with rheumatoid arthritis did not differ from normal controls. No correlation was seen between growth enhancement and patient age or medications. FGPF was present in serum plasma and is unlikely from platelets because serotonin and purified platelet factor produced no equivalent growth stimulation. FGPF was nondialysable, heat labile and insensitive to ribonuclease A. Disulphide bond integrity was required since 20 mM dithiothreitol destroyed activity. FGPF was excluded by an XM-50 filter after Sephadex G100 gel filtration.

Cell Division↗

Monoclonal antibodies to low density lipoprotein used for the study of low- and very-low-density lipoproteins, in "ELISA" and immunoprecipitation technics.

Seven monoclonal antibodies to low-density lipoprotein were studied by the ELISA for their reactivity with LDL or VLDL. Cotitration experiments showed that five of them are addressed to different antigenic epitopes. Two of the monoclonal antibodies were temperature independent whereas the others had a decreased binding activity at 37 degrees C compared to that obtained at 25 degrees C or 4 degrees C, suggesting the presence of antibodies directed to sequence or conformation epitopes, respectively. All antibodies reacted with both LDL and VLDL; four of them had a higher affinity for LDL and two others for VLDL. Immunoprecipitation of LDL and/or VLDL was observed upon immunodiffusion with certain pairs of antibodies. This may allow the use of pairs of monoclonal antibodies to LDL for the quantitative determination of apolipoprotein B in serum LDL and VLDL.

Antibodies, Monoclonal↗

Marital therapy for the elderly.

Little attention has been paid to marital therapy for the elderly in spite of its relevance to morale and emotional problems. Physical illness is of particular significance in altering the dynamics of the marital relationship. Retirement and financial problems, as well as changes in sexual activity and gender roles, are also important. However, radical changes in patterns of behaviour cannot be expected. Therapeutic techniques must be altered for this age group, and the therapist must be active, giving and concretely helpful. As with therapy for younger couples, children may need to be involved in the therapy sessions. Family physicians should be a main source of help for marital problems among the elderly. However, because problems related to countertransference must be faced, working with the elderly will not be for everyone.

Aged↗

Binding of 5-methoxypsoralen to human serum low density lipoproteins.

5-methoxypsoralen (5-MOP) binds to human serum low density lipoproteins (LDL) according to a two-step process. Scatchard analysis of the first step yields K = 1.4 X 10(5) M-1 and 4 binding sites. It involves the LDL apoprotein. The second step corresponds to a solubilization, in the lipidic core, of congruent to 45 molecules of 5MOP per LDL molecule. It is accompanied by a large blue shift of the 5MOP fluorescence. The ability of LDL to bind 5MOP and to carry it into various cells may explain some biological effects sometimes encountered during PUVA therapy.

5-Methoxypsoralen↗

Phorbol esters inhibit the binding of low-density lipoproteins (LDL) to U-937 monocytelike cells.

The present study demonstrates that U-937 monocytelike human cells possess specific LDL receptors. 125I-LDL binds at 4 degrees C on the cell surface. The bound molecules are releasable by heparin. The reaction requires Ca2+ and the binding sites are sensitive to proteolysis. Unlabeled LDL compete with 125I-LDL, whereas HDL are ineffective. At 37 degrees C, LDL are internalized and degraded by a chloroquine-sensitive pathway. Tumor-promoting phorbol esters inhibit the binding of 125I-LDL to its receptor on U-937 cells. This inhibition exhibits temperature, time, and concentration dependence. At 37 degrees C, inhibition is 50% at 5 X 10(-9) M of TPA. After removal of phorbol esters, treated cells recover their 125I-LDL-binding activity in 60 min. The inhibitory activities of various phorbol esters are proportional to their tumor-promoting activities. Inhibition appears to be due to a reduction in the number of available LDL receptors rather than a decrease in receptor affinity.

Cell Line↗

Intracerebral neutron brachytherapy for hemispheric glioblastoma multiforme. A pilot study.

The University of Kentucky Brain Tumor Study and Research Group has developed a new treatment protocol of interstitial brain brachytherapy using Californium-252 neutron source implantation in 1980. Only patients with malignant gliomas were eligible for this pilot study. Nine patients entered the Phase I trial of the protocol study between November 1980 and October 1981. According to the design of the protocol, all patients who had a verified histologic diagnosis of glioblastoma multiforme underwent postoperative intracerebral Cf-252 neutron source implantation, followed by 6 000 cGy of external photon beam irradiation. The purpose of this pilot study was to test the feasibility of interstitial Cf-252 neutron source implantation and only one implant afterloading applicator was used for brachytherapy. The implant applicator was placed in the center of tumor and the procedure was performed under CT guidance. In the assessment of the procedure, Karnofsky functional performance status, intellectual status, neurological examination, CT scans, and complications were used. All patients tolerated the procedure well and no serious complications were encountered. Despite the quality of these early treatments, there was some evidence of short-term benefit in duration of survival of the patients. We believe that further technical improvement to achieve an adequate isodose distribution to cover the tumor volume might result in longer duration improvement in survival.

Aged↗

CT and MR for brain tumor implant therapy using CF-252 neutrons.

Magnetic resonance (MR) imaging of the brain allows very effective localization of tumor in brain, visualization of brain reaction to tumor, peritumoral edema, as well as destruction of normal anatomy and spread of tumor. MR readily imaged the brain in multiple views allowing three dimensional (3D) evaluation and more precise localization of tumor in the depths of the brain. It also assessed the extent of tumor infiltration away from the primary site. In an ongoing study of Cf-252 neutron brachytherapy of hemispheric malignant gliomas of the brain, we have found that the extent of tumor and the planning of the placement of multiple applicators in the brain for implant therapy was facilitated by both CT and MR scanning, but MR allowed better 3D localization, assessment of response and follow-up of tumor response. MR gave additional and different types of information about the tumor than CT scanning based upon proton distribution which greatly aided planning of tumor implant therapy and understanding of patterns of tumor response and recurrence after therapy.

Adult↗

Genetic modifications during cellular aging.

We review evidence that biological aging is a genetic process related to development and cytodifferentiation and thus may involve alterations of DNA structure and gene expression. We conclude that although determined to a high degree aging also involves stochastic features which lead to progressive somatic cell diversification during the life span. These considerations may help to explain the unevenness of physiological decline and the clonal emergence of certain age-dependent diseases such as cancer.

Cell Differentiation↗

Right ventricular function evaluated by radionuclide angiography in acute myocardial infarction.

Radionuclide angiographic studies were performed in 26 patients with a first myocardial infarction, 11 with anterior and 15 with an inferior location. Right ventricular (RV) and left ventricular (LV) ejection fractions (EF) were determined. Mean LVEF in anterior infarctions (33.2 +/- 7.3) was lower than in inferior myocardial infarctions (59.9 +/- 10.2) (p less than 0.001). Mean RVEF in the anterior infarct group was 41.3 +/- 15.1 and in the inferior myocardial infarction group 33.7 +/- 12.8 (p = NS). RVEF was less than 40% in 11 of 15 (73%) with inferior and 7 of 11 (66%) with anterior myocardial infarction. The ratio of LVEF:RVEF was 0.84 +/- 0.19 in the anterior and 2.13 +/- 1.28 in the inferior myocardial infarction group (p less than 0.001). LVEF correlated with RVEF in patients with anterior infarcts (r = 0.77; p less than 0.05) but not in those with inferior myocardial infarction (r = 0.14). RV regional wall motion abnormalities were observed in the inferolateral zones in 10 of 15 (66%) with inferior and in none of the 11 patients with anterior myocardial infarctions (p less than 0.001). Inferoseptal wall motion abnormalities were observed in 3 of 15 (20%) with inferior and 6 of 11 (56%) with anterior myocardial infarctions (p = NS). RV dysfunction in the inferior infarctions is probably an expression of primary RV dysfunction rather than secondary to LV dysfunction. RV dysfunction was proportional to LV dysfunction in the anterior infarction group and was often accompanied by RV septal contraction abnormalities.

Aged↗

Sequential radionuclide angiographic assessment of left and right ventricular performance and quantitative thallium-201 scintigraphy following acute myocardial infarction.

Sequential changes in radionuclide angiographic measurement of left and right ventricular performance and quantitative thallium-201 scintigraphy were studied in 20 patients sustaining their first acute myocardial infarction (AMI). The studies were performed on the average 29.4 hours and 9.4 days after hospital admission. Anterior infarction had greater impairment of left ventricular (LV) performance in terms of ejection fraction and percentage of abnormal contraction area in addition to larger thallium-201 perfusion defects. At the time of the late study evidence of thallium-201 perfusion of infarcted area was seen in 14 of 20 patients, five of whom demonstrated improvement of regional wall motion. The remaining patients in the reperfused group and all of the patients in the nonperfused group failed to show evidence of LV functional improvement. This study indicates that reperfusion as measured by thallium-201 scintigraphy does occur spontaneously in 70% of patients with AMI and only in those patients with established reperfusion is there any potential for improvement in LV performance.

Coronary Circulation↗

High-voltage electron microscopy of human diploid fibroblasts during ageing in vitro. Morphometric analysis of mitochondria.

Since recent studies have suggested a diminished mitochondrial functional capacity in late-passage ('old') compared to early-passage ('young') normal fibroblasts and fibroblasts from the Hutchinson-Gilford (progeria) syndrome of premature ageing, we analysed whole-cell preparations on the high voltage electron microscope to look for mitochondrial and related defects. All strains examined showed considerable heterogeneity in cell size and intracellular morphology. Mitochondria were readily seen in all cells, predominantly as long slender rods with frequent branching, but occasional circular and saccular forms were also evident. Various parameters of mitochondrial mass including mean number, weight, and total length of mitochondria per cell weight tended to increase in old and progeria cells, but only the former attained statistical significance due to the heterogeneity and consequent variance. A significant finding was the decreased width of mitochondria in old and progeria cells. Cystic blebs were evident in mitochondria of some cells with an apparent increase in old and progeria fibroblasts. These blebs appeared to be due to weakening of the inner membrane, allowing dilatation of the outer membrane which otherwise appeared intact. The number of osmiophilic inclusions per cell weight, particularly lipofuscin granules and autophagic vacuoles, was significantly increased in old and progeria cells. In conclusion, despite some morphological changes, mitochondria of old and progeria cells maintain a structurally and bioenergetically adequate mass compatible with continued cellular viability.

Aging↗

Chimpanzee serum lipoproteins. Isolation, characterisation and comparative aspects of the low density lipoprotein and apolipoprotein-BH.

Evaluation of the serum lipoprotein profile in non-fasting, adult chimpanzees by analytical ultracentrifugation revealed a lower mean LDL level (269 mg/dl) than typical of man. The major molecular form(s) of low density lipoprotein (LDL) was then isolated in the density interval 1.024-1.050 g/ml by sequential ultracentrifugation. The physicochemical properties of chimpanzee LDL, including net surface charge as judged by electrophoresis, molecular size (220 A) by electron microscopy, and chemical composition closely resembled those of man. The antigenic structures of chimpanzee and human LDL were essentially indistinguishable, since immunodiffusion against antiserum to either the human or ape lipoprotein produced a precipitin reaction of complete identity between the two antigens. By micro-immunoprecipitation, the immunological cross-reactivity of LDL from the two species was in the range 85-97%, depending on the nature of the assay.

Amino Acids↗