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S J Anderson

Publications and source records attributed to S J Anderson.

At least 109 records · Page 6Linked to original sources

Tandem linkage and unusual RNA splicing of the T-cell receptor beta-chain variable-region genes.

The variable-region (V) genes of the murine T-cell receptor beta chain exist largely as single-element subfamilies. The V beta 5 and V beta 8 genes belong to the only two known three-member V beta subfamilies. We present studies on the linkage of these six genes and show that the genomic organization is that of alternating V beta 5 and V beta 8 genes. Our analysis suggests that these genes were tandemly duplicated, the unit of duplication being a pair of V beta 5 and V beta 8 genes. This tandem organization permits transcripts to initiate from the promoter of an unrearranged V beta located upstream of the rearranged V beta gene. These transcripts can generate functional beta-chain gene messages by novel RNA splicing of the upstream leader exon to the V beta coding exon of the downstream rearranged gene. We extend the analysis of the T-cell receptor genomic organization to include 12 V beta genes and suggest that all V beta genes are closely linked on chromosome 6. In addition, we discuss the possible implications of the close linkage of the V beta genes on the development of the T-cell receptor beta-chain gene repertoire.

Amino Acid Sequence↗

Considerations in the use of echocardiography in epidemiology. The Framingham Study.

To quantify potential biases in the use of echocardiography in epidemiologic studies, we assessed the relationship of sex, age, vital capacity, body fatness, and overt cardiovascular disease to prevalence of acceptable echocardiograms in 6148 Framingham men and women aged 17 to 90 years. Echocardiograms adequate to assess left ventricular chamber dimensions and wall thickness, aortic root, and left atrial dimensions as well as mitral and aortic valves were obtained in 4947 (80%) of the 6148 subjects. The prevalence of acceptable echocardiograms ranged from less than 50% for those more than 80 years of age to more than 96% for subjects under 30 years of age. A significant learning curve was apparent, particularly in the older subjects (more than 60 years of age) for whom prevalence of acceptable echocardiograms rose from a minimum of 28% during the first 5 months of studies to a maximum of 74 to 81% during studies 2 years later. The likelihood of unacceptable echocardiograms was slightly greater in men. Obesity (in subjects younger than 60 years of age), lower vital capacity, and overt cardiovascular disease were associated with unacceptable echocardiograms, independent of age. Consideration of these biases should aid in the interpretation and planning of epidemiologic and other studies using echocardiography.

Adult↗

The spectrum of left ventricular hypertrophy in a general population sample: the Framingham Study.

To assess the prevalence, characteristics, and correlates of echocardiographically determined left ventricular hypertrophy (echo LVH) in a free-living population, 510 men and 855 women from the original Framingham cohort (age 59 to 90 years) were studied by M-mode echocardiography. Offspring and offspring spouses (1718 men and 1892 women; age 17 to 75 years) were similarly studied. The severity of echo LVH, as reflected by left ventricular mass indexed to body surface area, ranged from 101 g/m2 (women) and 132 g/m2 (men) to more than 400 g/m2. The prevalence of electrocardiographically assessed LVH increased proportionately with increased echocardiographic left ventricular mass. Women with echocardiographic left ventricular mass indexes exceeding 200 g/m2 were three to four times more likely to have electrocardiographic LVH than men with similar elevations of echocardiographic left ventricular mass index. The prevalence of echo LVH ranged from 6.6% in the younger (offspring study) women to 33% in the older (original cohort) women (8.6% and 23.7%, respectively, for men) and included a spectrum of forms--eccentric-dilated, eccentric-nondilated, concentric, and disproportionate septal thickness--which varied in prevalence in the various age-sex groups. Each of these forms of echo LVH was associated with higher systolic blood pressures at the time of echocardiographic examination and over the previous 30 years when compared with blood pressures of Framingham subjects without echo LVH.

Adult↗

Echocardiographic left ventricular mass and physical activity: quantification of the relation in spinal cord injured and apparently healthy active men.

To assess the relation of echocardiographic left ventricular (LV) mass to reported physical activity, 2 groups of subjects with widely different physical activity levels were evaluated: 50 men with spinal cord injuries and 166 apparently healthy, active men. Multivariate analysis revealed that reported physical activity was a significant independent predictor of LV mass index (LV mass/body surface area) in both injured patients and healthy, active subjects after controlling for age and blood pressure. The relation between LV mass index and physical activity (linear regression) was similar for both groups; LV mass index = 0.00321 (physical activity) + 82.8 and LV mass index = 0.00335 (physical activity) +88.4 for patients and healthy active subjects, respectively. These results suggest that physical activity as assessed by self-report is associated with echocardiographically detectable differences in LV mass in groups with widely divergent physical activity levels. In addition, for each of these groups 1,000 kcal/week of physical activity apparently results in a change of approximately 3 g/m2 in LV mass index. This information may have practical use for correction of LV mass for the effects of physical activity.

Adult↗

Spatial and temporal selectivity of the human motion detection system.

Measurements were made of spatial frequency, orientation and temporal frequency selectivity of the visual motion system. The results suggest: (1) There exists in the motion system mechanisms selective for spatial frequency. The preferred spatial frequency varies considerably and extends down to at least 0.06 c/deg. (2) At all spatial frequencies (from 0.1 to 10 c/deg) there exist detectors selective for orientation which vary in (directed) orientation tuning to encompass 360 degrees. (3) The bandwidth of both spatial frequency and orientation selectivity vary inversely with spatial frequency: the lower the spatial frequency, the broader the bandwidth. (4) There exist two classes of temporally tuned detectors, one lowpass (sustained) and one bandpass (transient), of preferred temporal frequency of 7-13 Hz (depending on spatial frequency).

Form Perception↗

Subcellular localization of glycoproteins encoded by the viral oncogene v-fms.

The McDonough strain of feline sarcoma virus encodes a polyprotein that is cotranslationally glycosylated and proteolytically cleaved to yield transforming glycoproteins specified by the viral oncogene v-fms. The major form of the glycoprotein (gp120fms) contains endoglycosidase H-sensitive, N-linked oligosaccharide chains lacking fucose and sialic acid, characteristic of glycoproteins in the endoplasmic reticulum. Kinetic and steady-state measurements showed that most gp120fms molecules were not converted to mature forms containing complex carbohydrate moieties. Fixed-cell immunofluorescence confirmed that the majority of v-fms-coded antigens were internally sequestered in transformed cells. Dual-antibody fluorescence performed with antibodies to intermediate filaments (IFs) showed that the IFs of transformed cells were rearranged, and their distribution coincided with that of v-fms-coded antigens. No specific disruption of actin cables was observed. The v-fms gene products cofractionated with IFs isolated from virus-transformed cells and reassociated with IFs self-assembled in vitro. A minor population of v-fms-coded molecules (gp140fms) acquired endoglycosidase H-resistant, N-linked oligosaccharide chains containing fucose and sialic acid residues, characteristic of molecules processed in the Golgi complex. Some gp140fms molecules were detected at the plasma membrane and were radiolabeled by lactoperoxidase-catalyzed iodination of live transformed cells. We suggest that v-fms-coded molecules are translated as integral transmembrane glycoproteins, most of which are inhibited in transport through the Golgi complex to the plasma membrane.

Animals↗

Prevalence of submitral (anular) calcium and its correlates in a general population-based sample (the Framingham Study).

To obtain epidemiologic information on submitral calcium, 2,069 subjects in the original Framingham Study cohort (mean age 70 +/- 7 years) and 3,625 of the offspring of the cohort and their spouses (mean age 44 +/- 10 years) with adequate echocardiograms were evaluated. Submitral calcium was detected in 162 (2.8%) of the 5,694 subjects; greater than 90% of the subjects with such calcium came from the 40% of the study group greater than 59 years of age. Women were more than twice as likely to have such calcium as men. Age in both sexes, systolic blood pressure in men, and obesity in women were significantly and independently associated with submitral calcium. There was a 12-fold excess of atrial fibrillation in subjects with (20 of 162, 12%) compared with those without (53 of 5,532, 1%) submitral calcium.

Adult↗

Prevalence and correlates of posterior extra echocardiographic spaces in a free-living population based sample (the Framingham study).

To obtain epidemiologic information on extra echocardiographic spaces immediately posterior to the left ventricular free wall, 2,028 subjects in the original Framingham cohort study (mean age 70 +/- 7 years) and 3,624 of the offspring of the cohort (and their spouses) (mean age 44 +/- 10 years) with adequate echocardiograms were evaluated. Extra echocardiographic spaces were detected in 370 (6.5%) of the 5,652 subjects. The prevalence ranged from less than 1% in subjects in the 20- to 30-year age decade to greater than 15% for those in their 80s. Extra echocardiographic spaces tended to be more common in subjects who were older, female, obese, more hypertensive, and who had higher blood sugar levels and higher low density lipoprotein cholesterol levels (measured 8 years earlier). The high prevalence of extra echocardiographic spaces and the independent association with age (cohort and offspring), obesity (cohort and male offspring), and ventricular septal hypertrophy (cohort and male offspring) is compatible with at least 2 hypotheses among others that should be tested: (1) Subepicardial fat may often masquerade as pericardial fluid producing a posterior extra echocardiographic space, especially in obese elderly subjects. (2) Small posterior extra echocardiographic spaces may often be early markers of subclinical hypertensive heart disease.

Adolescent↗

Sudden unexpected death during ambulatory electrocardiographic monitoring. The Framingham Study.

This report documents the clinical and electrocardiographic events of sudden unexpected death in a 52-year-old man without known heart disease during ambulatory electrocardiographic monitoring. This death occurred two and a half hours after detailed noninvasive testing, including treadmill exercise, that was unrevealing. The sequence of S-T change suggesting epicardial injury, multiform ventricular premature depolarizations, and frequent and early cycle ventricular premature depolarizations followed by ventricular tachycardia-flutter-fibrillation precipitated by an early cycle ventricular premature depolarization were documented. The delay in cardiopulmonary resuscitation in this witnessed cardiac arrest punctuates the need for widespread dissemination of the skills of cardiopulmonary resuscitation.

Death, Sudden↗

Generation of antigen-responsive B-cell line by somatic cell hybridization.

An antibody-secreting hybridoma specific for the fluorescein hapten has been fused with a nonsecreting pre-B-cell tumor line to yield an inducible antigen-binding hybrid with very little antibody secretion. Upon stimulation with fluoresceinated LPS (FL-LPS), the amount of specific antibody secreted by this hybrid increased up to five-fold. Although unhaptenated LPS alone induced a small response (two-fold increase), several lines of evidence suggested that the stimulation induced by the haptenated LPS involved an interaction with the fluorescein specific surface immunoglobulin receptor. However, since a variety of other antigens bearing the same hapten failed to induce a secretory response, a role for mitogenic focusing and/or B-cell subset triggering can also be envisaged. This is the first report of a monoclonal, antigen-specific and responsive hybrid, which can serve as a model for studying the differentiation of specific B lymphocytes into antibody-secreting cells.

Animals↗

Mutant feline sarcoma proviruses containing the viral oncogene (v-fes) and either feline or murine control elements.

The sequences required for transformation by the Gardner-Arnstein (GA) strain of feline sarcoma virus (GA-FeSV) were defined by site-directed, in vitro mutagenesis of molecularly cloned proviral DNA. Portions of the Ga-FeSV provirus, subcloned in the plasmid pBR322, were mutagenized by deletion or frameshift at XhoI restriction sites flanking the nucleotide sequences presumed to encode the GA-FeSV transforming polyprotein (P108(gag-fes)). The biological activity of subgenomic and reconstructed full-genome-length molecules was assayed by transfection and focus induction in NIH 3T3 cells. Both mutant and wild-type molecules containing the intact P108(gag-fes) coding region induced foci of transformed cells at efficiencies between 10(4) and 10(5) focus-forming units per pmol of DNA; a deletion mutant lacking 3'-terminal v-fes sequences was completely nontransforming in parallel assays. Representative subcloned foci of transformed NIH 3T3 cells synthesized P108(gag-fes) with associated in vitro protein kinase activity. Focus-forming viruses could be rescued from transformed subclones induced by full-length proviral DNA, but not from cells transformed by subgenomic DNA lacking a 3' long terminal repeat (LTR). It was concluded that: (i) nucleotide sequences encoding P108(gag-fes) and its associated kinase activity are responsible for transformation, (ii) the GA-FeSV 3' env and LTR sequences are not required for focus induction, and (iii) the 3' LTR is necessary for rescue of infectious FeSV RNA. A chimeric DNA containing the 5' LTR and P108(gag-fes) coding region of GA-FeSV joined to the 3' LTR of Moloney murine sarcoma virus was both transforming and rescuable at high efficiency. Restriction analysis showed that passaged stocks of rescued transforming virus contained Moloney murine sarcoma virus U3 sequences at both proviral DNA termini, consistent with generally accepted models for LTR formation during reverse transcription. Wild-type GA-FeSV and the chimeric virus (here designated as GAHT), each rescued from NIH 3T3 cells with the same amphotropic murine leukemia virus, yielded approximately equal numbers of foci when titrated on CCL 64 mink cells. By contrast, on mouse NIH 3T3 cells, the focus-forming titer of GAHT was 1 to 2 log higher than that of FeSV. The foci induced on NIH 3T3 cells by GAHT appeared earlier and were reproducibly larger than those induced by GA-FeSV. Differences in transforming activity on NIH 3T3 cells were also found using colony formation in agar, showing that the more rapid appearance and larger size of foci formed in liquid media were not due to virus spread. These data suggest that transcriptional control signals within the viral LTR regulate the levels of the transforming gene product in a species-specific manner.

Animals↗