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Biomedical subjects

S Goldstein

Publications and source records attributed to S Goldstein.

At least 541 records · Page 30Linked to original sources

Local intranasal immunotherapy for ragweed allergic rhinitis. II. Immunologic response.

Local nasal immunotherapy (LNIT) was administered in a double-blind study to 67 subjects. Twenty-three received an unmodified ragweed extract (RW), 24 received a glutaraldehyde polymer of ragweed extract (PRW), and 21 received placebo. Serum ragweed-specific IgE (S-IgE), ragweed-specific nasal secretory (NS-) IgE, secretory IgA (SIgA) and IgG, and NS-albumin were measured. RW therapy caused a significant increase in ragweed-specific S-IgE (p less than 0.005) and NS-SIgA (p less than 0.05). PRW therapy caused a significant rise in ragweed-specific NS-SIgA (p less than 0.001). NS-IgE (p less than 0.05), and NS-IgG (p less than 0.01). Ragweed-specific S-IgG was not affected by any of the treatments. There was no consistent correlation between NS-antibody levels and symptom/medication scores.

Administration, Intranasal↗

Electrocardiogram computer analysis. practical value of the IBM Bonner-2 (V2 MO) program.

One thousand ECGs were selected from those taken from an adult population and analyzed by three cardiologists to assess the performance of the IBM Bonner-2 (V2 MO) program. The sample included 200 ECGs with 248 myocardial infarctions, 200 with conduction abnormalities, 100 with ventricular hypertrophy, 300 normals and 200 with electronic pacemakers. In the MI group, there was a total sensitivity of the program with respect to the readers of 88% (218/248) with 19 (8%) program errors and 90% (248/275) specificity. In 53 ECGs with two MI statements, the sensitivity was 89% (47/53). The sensitivity in conduction abnormalities was 93.4% (183/196) with 98.7% specificity (800/810). The sensitivity in LVH was 90% (74/81) and in RVH 83% (5/6). Among the normals, the specificity was 98.6% (289/293). The sensitivity to PVCs was 84% (56/67), to atrial fibrillation 87% (48/55), to SVCs 58.6% (17/29) and to electronic pacemakers 65% (127/196). Recognizing the limitations of this type of analysis, this study indicates that the V2 MO version compares favorably with the earlier versions of the same program and is a valuable aid in ECG interpretation with rapid acceptance by physicians.

Arrhythmias, Cardiac↗

Status of mitochondria in living human fibroblasts during growth and senescence in vitro: use of the laser dye rhodamine 123.

Rhodamine 123, a fluorescent laser dye that is selectively taken up into mitochondria of living cells, was used to examine mitochondrial morphology in early-passage (young), late-passage (old), and progeric human fibroblasts. Mitochondria were readily visualized in all cell types during growth (mid-log) and confluent stages. In all cell strains at confluence, mitochondria became shorter, more randomly aligned, and developed a higher proportion of bead-like forms. Treatment of cells for six days with Tevenel, a chloramphenicol analog that inhibits mitochondrial protein synthesis, brought about a marked depletion of mitochondria and a diffuse background fluorescence. Cyanide produced a rapid release of preloaded mitochondrial fluorescence followed by detachment and killing of cells. Colcemid caused a random coiling and fragmentation of mitochondria particularly in the confluent stage. No gross differences were discernible in mitochondria of the three cell strains in mid-log and confluent states or after these treatments. Butanol-extractable fluorescence after loading with rhodamine 123 was lower in all cell strains in confluent compared to mid-log stages. At confluence all three cell strains had similar rhodamine contents at zero-time and after washout up to 24 h. At the mid-log stage, young cells contained more rhodamine initially and lost it more rapidly than old or progeria cells, in that order. The data indicate no gross derangement in the morphology or number of mitochondria in old and progeria fibroblasts but there is a reduction of protonmotive force evident in these cells at the mid-log stage that may be growth limiting.

Cell Division↗

Plasma lipids in kidney transplanted children and adolescents: influence of pubertal development, dietary intake and steroid therapy.

Plasma triglycerides and/or cholesterol were significantly increased in twenty-four of thirty kidney transplanted children and adolescents with stable renal function, at least one year after the last rejection crisis who received low dose prednisone therapy. The cholesterol increment was related to both low density and high density lipoproteins. However, similar to findings in adult allograft recipients, these increases were very variable: six subjects had normal levels, eight had increased triglycerides, five increased triglycerides and cholesterol, and eleven increased cholesterol. No influence of renal function was found in this series of patients all of whom had plasma creatinine below 160 mumol/l. Subjects who had achieved sexual development had lower cholesterol values. An insignificant difference was observed between patients receiving daily and alternate-day steroid therapy, but a significant negative correlation was found between plasma triglycerides and fractional urinary excretion of 17 OH corticosteroids in the first 6 h after an oral dose of prednisone. Finally, no correlation was found between energy intake and triglycerides; but a significant correlation was observed between protein intake and plasma cholesterol. In conclusion, some patients show a high level of triglycerides and/or cholesterol after renal transplantation, possibly due to a different individual response to steroid therapy.

Adolescent↗

Tryptic modification of human serum low-density lipoprotein leads to altered rates of turnover and intravascular transformation in the guinea pig.

The metabolism of human serum low-density lipoprotein (LDL) and its trypsin-treated counterpart have been compared in the guinea pig in vivo. Removal of surface-exposed protein from the lipoprotein particle in this way resulted in significant modification of its metabolism in guinea pigs in vivo. Limited trypsinisation of LDL permitted removal of 20-25% of its protein moiety; trypsinised LDL was deficient in lysine and arginine residues (25-30% of each removed). The modified particle retained its basic structural features, such as internal molecular architecture, but displayed an elevated net negative surface charge and diminished immunological reactivity. Following intravascular injection of iodinated LDL (131I) and trypsinised LDL (125I) into the same animal, the two lipoproteins displayed biexponential decays; the rate constants for the plasma turnover of LDL and trypsinised LDL were significantly different (P less than 0.05), trypsinised LDL exhibiting a slower disappearance from the circulation. Density-gradient ultracentrifugation revealed marked elevation in the modal densities of both LDL and trypsinised LDL upon metabolism in vivo, although the rate of increase was greater for trypsinised LDL than LDL in each case (average increment 0.022 g/ml and 0.014 g/ml at 24 h respectively). The diminished plasma clearance of trypsinised LDL as compared to the native human and guinea pig LDL indicates that sites required for the cellular recognition and uptake of the LDL particle reside in its surface-exposed, trypsin-accessible protein. Furthermore, such protein appears to play a central role in regulating the intravascular processes by which the lipid content of LDL is diminished, and by which it is transformed to a particle of higher density.

Animals↗

Functional mitral stenosis in patients with massive mitral annular calcification.

Mitral insufficiency with mitral annular calcification occurring predominantly in elderly females has been described. We studied six patients with mitral diastolic obstruction associated with mitral annular calcification without stenosis of the mitral leaflets. Three were males and three were females, aged 43-77 years. All had significant diastolic gradients across the mitral valve (mean gradient 16 mm Hg) recorded at catheterization. Two patients had aortic and three had mitral valve replacement. No patient had retraction of the mitral leaflets, diffuse thickening or fusion of the commissures at surgery or pathologic examination. Three patients had severe mitral insufficiency, one associated with voluminous prolapsing mitral leaflets and one as a result of ruptured chordae tendineae. The left ventricle was dilated in three patients, two with mitral regurgitation and one with mixed aortic valve disease. Active mitral annular motion is a normal event and is necessary for normal valvular function; severe calcification of the ring interferes with its normal diastolic relaxation and this alone may explain the holodiastolic mitral gradient found in these patients.

Acute Disease↗

Characteristics of the resuscitated out-of-hospital cardiac arrest victim with coronary heart disease.

The clinical entry characteristics and medical history of 142 resuscitated out-of-hospital cardiac arrest victims with coronary heart disease were studied in order to identify factors that affect their long-term survival. The cardiac arrest event was classified as being secondary to an acute myocardial infarction (AMI) in 44% (62 of 142), an ischemic event (IE) in 34% (49 of 142) and a primary arrhythmic event (PAE) in 22% (31 of 142). The majority of patients in all groups had a history of angina pectoris. Twenty-seven percent of the AMI, 55% of the IE, and 71% of the PAE patients had a history of infarction. Ten percent of the AMI, 31% of the IE, and 55% of the PAE had used digitalis before their cardiac arrest. Cardiac arrest was the first cardiac event in 35% of the AMI, 16% of the IE and 6% of the PAE patients. One year after arrest, 89% of the AMI, 80% of the IE and 71% of the PAE were alive (p less than 0.01). Covariate analysis for more than 40 variables indicates that a high-risk group included 22% (31 of 142) of the cardiac arrest victims had 1- and 2-year survival rates of 71% and 55%, respectively, and was characterized as having used digitalis before arrest, experiencing blood urea nitrogen elevation and pulmonary congestion during the hospitalization for the event, and classification of the cardiac arrest event as a PAE. A low-risk group comprised 78% (111 of 142) of the survivors and had 1- and 2-year survival rates of 85% and 69%, respectively. These data indicate that cardiac arrest due to coronary heart disease is secondary to several mechanisms related to subsequent survival.

Acute Disease↗

Decreased sensitivity of old and progeric human fibroblasts to a preparation of factors with insulinlike activity.

To determine whether old cells have a reduced response to a preparation of factors from human plasma with insulinlike activity (ILA), we analyzed the response to ILA of early and late passage human fibroblasts from young, old, and progeric donors in the acute stimulation of [3H]2-deoxy-D-glucose (2dG) uptake and the delayed stimulation of [3H]thymidine (TdR) incorporation into DNA. The ILA concentration required to produce equivalent, relative stimulation of TdR incorporation was increased two- to three-fold in late passage cells and cells from old and progeric donors (P less than 0.01). 50 and 95% of maximal stimulation (ILA50, ILA95) was achieved by 0.26 +/- 0.07 and 1.38 +/- 0.13 ng insulin equivalents/ml (mean +/- SD) respectively, in cells from young adults at early passage. Corresponding values were 0.54 +/- 0.05 and 2.90 +/- 0.25 in cells from old donors; greater than 0.9 +/- 0.1 and greater than 3.1 +/- 0.1 in cells from a 9-yr-old progeric donor; and 0.4 +/- 0.05 and 1.1 +/- 0.04 in cells from normal children (9-13 yr). For two cell strains from young adults, ILA50 and ILA95 were 0.30 +/- 0.02 and 1.0 +/- 0.3 ng eq/ml at 30% of their in vitro lifespan completed (%LC) and these values increased at rates of 0.005 ng eq/ml per %LC and 0.04 ng eq/ml per %LC, respectively. The mean stimulation of 2dG uptake ratio (ILA/control) decreased from early to late passage from 2.1 +/- 0.6 to 1.3 +/- 0.1 in young adult donors (P less than 0.05), but there were no significant differences between young and old donors at either early or late passage. The mean stimulation ratio in progeric cells (1.2 +/- 0.2) did not change with in vitro passage, but was significantly lower than that of age-matched normal cells (2.1 +/- 0.8, P less than 0.001). In progeria cells, the reduced stimulation of 2dG uptake upon addition of ILA was due to an increased basal rate of uptake (0.19 +/- 0.01 pmol [3H]2dG/min per mg protein vs. 0.13 +/- 0.01 in age-matched normal cells), and not to a decline in the maximal rate of uptake (0.26 +/- 0.01 vs. 0.27 +/- 0.02, respectively). Similar results were found for in vitro aging in cells from an old donor.

Adolescent↗

Echocardiographic changes in the thickness of porcine valves with time.

To assess the ability of M-mode echocardiography to detect the incidence and frequency of porcine xenograft valve thickening, echocardiograms were obtained in 147 mitral and aortic porcine xenograft valves implanted in 131 patients. The patients were divided into an early group in whom the echocardiograms were performed within two months of valve replacement, and intermediate group studied two to 48 months after surgery, and a late group 48 months or longer after surgery. The porcine cusp echoes were visualized with proper gain settings, enlarged, and then recorded on a strip chart. The mean thickness of both the mitral and the aortic cusps was measured with the valve in the coapted position. The mean thickness of the porcine mitral valve increased from 1.23 +/- 0.12 in the early group to 2.3 mm +/- 0.19 in the late group (P less than .02). Aortic valve thickness increased from 0.91 mm +/- 0.07 in the early group to 2.1 mm +/- 0.37 (P less than .05) in the late group. A significant change in valve thickness was not observed in the intermediate group. In the late group of valves, 21/82 (27 percent) had a thickness greater than 3 mm. Nine of these valves (43 percent) have required replacement because of clinical dysfunction. Only 1.6 percent (1/61) of the valves in the late group with a thickness of less than 3 mm had or developed severe porcine valve insufficiency (P less than 0.001). In all ten instances, the echocardiographic assessment of valve thickness was validated on gross examination of the valve removed at surgery. This study indicates that the thickness of both mitral and aortic porcine valves can be measured by M-mode echocardiography. Valve thickness increases after 48 months and those valves with thickening of 3 mm or more are at a higher risk of developing clinical evidence of valve dysfunction.

Aortic Valve↗

A density gradient ultracentrifugal procedure for the isolation of the major lipoprotein classes from human serum.

A density gradient ultracentrifugal procedure is described for the rapid and reproducible isolation of the major lipoprotein classes, VLDL, LDL, HDL2, and HDL3, from human serum. A step gradient is constructed from four NaCl/KBr solutions varying in density from 1.006 to 1.24 g/ml and from 3 ml of serum adjusted to d 1.21 g/ml. Separation is achieved after a single ultracentrifugation for some 56 x 10(7) gavg min at 15 degrees C in a swinging bucket rotor, at which time the lipoproteins band isopycnically and albumin and other serum proteins are sedimented. Densitometric scanning of gradients revealed a lipoprotein mass profile distinguished by four absorption maxima which fell within the hydrated density ranges of VLDL (d less than 1.016 g/ml), LDL (1.028-1.050 g/ml), HDL2 (1.066-1.100 g/ml), and HDL3 (1.100-1.153 g/ml). Fractionation of gradients on the basis of band distribution, followed by chemical, physical, and immunological analyses of the four principal fractions (i.e., bands) provided data on their electrophoretic mobility, chemical composition, morphology and size distribution, immunological reactivity and apolipoprotein content, thereby confirming their identities as VLDL, LDL, HDL2, and HDL3. The validity of this separation was supported by the quantitative distribution of apo B and apo A-I as assessed by radial immunodiffusion. Lipoprotein quantitation based on chemical analysis of gradient fractions was compared with that by analytical ultracentrifugation for a group of normolipidemic males; results concorded well, giving a similar HDL2:HDL3 ratio (0.35-0.36). Our procedure thus provides a simple and precise manner in which to assess the lipoprotein and apolipoprotein profile of human serum quantitatively and qualitatively.

Adult↗

The use of the multiplicity survey to identify migrants.

New approaches must be developed and tested to meet the needs for current data on population movement. One such approach is the survey with multiplicity (social networks). It allows respondents to report events (in this case, migration) that occurred to specified relatives living elsewhere. In order to test the value of the approach on a limited, exploratory basis, a two-stage research design was employed. A sample of persons resident in Cranston, Rhode Island who had changed address in the three years preceding the survey, was first identified and information was gathered in Round I on their mobility and on their relatives living in the State. In turn, these relatives (Round II) were asked about the mobility of their parents, siblings, and children. (The responses from Round II should have included the migrants in Round I.) Evaluation of the accuracy of Round II responses in comparison to those obtained in Round I was undertaken in terms of kin relationships, recency of move, and type of move. The results indicate that respondents had a low awareness of their relatives' movements, that moves of females were more likely to be reported than those of males, that recent moves were more frequently cited and that moves between communities were more likely to be reported than intracity mobility.

Adult↗

Motile flagellum with a "3 + 0" ultrastructure.

The male gamete of the parasitic protozoan Diplauxis hatti has a flagellum consisting of three doublet microtubules. This flagellum exhibits a helicoidal waveform in which bends propagate toward the tip with a frequency of about 1.5 hertz. It is the simplest motile eukaryotic flagellum yet described.

Animals↗

Retesting the commitment theory of cellular aging.

The commitment theory of human fibroblast aging predicts that 55 percent of cells will be nondividing at the middle to late stages of the replicative lifespan; in the present study, however, fewer than 10 percent were nondividing. The fact that no immortal diploid cells have yet been reported is also at odds with the theory. Available data on the variable life-span of clones and mass cultures, the dependence of longevity on population size, and the predominance of certain cell types at termination of a culture are compatible with simpler theories, which support the idea that the limited replicative life-span of diploid fibroblasts is a valid model for organismic aging.

Cell Differentiation↗

Fidelity of protein synthesis does not decline during aging of cultured human fibroblasts.

To ascertain whether the fidelity of protein synthesis declines during cellular aging in vitro, we have developed a cell-free protein synthesizing system from cultured human fibroblasts which actively incorporates phenylalanine into acid-insoluble material upon addition of poly (U). The accuracy of poly (U)-directed protein synthesis was determined by comparing the ratio of leucine to phenylalanine incorporation in extracts of early- and late-passage fibroblasts derived from normal persons and from subjects with two genetic disorders of premature aging, progeria, and Werner syndrome. The results show no decline in translational fidelity at late passage or in prematurely aging cells, and thus fail to support the error catastrophe theory of cellular aging.

Cell Survival↗

A comparative dielectric study of human serum low density lipoprotein before and after partial digestion by trypsin.

The relative permittivity of aqueous solutions of human serum low density lipoprotein (LDL) and partially trypsin digested lipoprotein (T-LDL) has been determined for various concentrations at 20 degrees C over the frequency range 0.15-100 MHz. Comparison of the dielectric dispersion curves for the digested lipoprotein with those for the native preparation revealed a larger low-frequency dielectric increment, which may be attributed to an increase in the number of counterions moving over the surface of the molecule. An explanation of this observation is an elevation of 70% in the net negative charge on the surface of the trypsin-treated particle as compared to its native counterpart.

Electrochemistry↗