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Biomedical subjects

K Jacobson

Publications and source records attributed to K Jacobson.

At least 37 records · Page 2Linked to original sources

Quality of life among patients post-myocardial infarction at baseline in the Survival and Ventricular Enlargement (SAVE) trial.

A quality of life ancillary study was incorporated into the Survival and Ventricular Enlargement (SAVE) trial of captopril versus placebo among patients who survived an acute myocardial infarction with compromised ventricular functioning, but no overt heart failure. Assessments included patient symptoms, health perceptions, emotional, cognitive, social and sexual levels of functioning, as well as potential covariates, such as life events and social support. The purpose of this study was to evaluate the psychometric properties of the quality of life measures in the SAVE at baseline, and provide a pre-randomization profile of the SAVE patients. One hundred and eighty-four patients participated in this aspect of the trial. Reliability alpha coefficients were adequate or better for all questionnaires, except for life events and sexual activities. Consistent with prior studies, the quality of life parameters were uncorrelated with ventricular ejection fraction. Despite experiencing a recent myocardial infarction with compromised ventricular functioning, patients at baseline generally neither appeared depressed nor focused on symptoms. The baseline findings support the inclusion of the quality of life ancillary study in the overall SAVE trial because of the independent contribution likely to be achieved in terms of evaluating both disease progression and treatment efficacy.

Adult

Arthroscopic treatment of anterolateral ankle impingement.

Fifty-five ankle arthroscopies performed for anterolateral ankle impingement between January 1987 and April 1992 were reviewed for functional outcome and patient satisfaction. There were 33 men and 22 women with an average age of 34 years (range 20-67). All patients reported a previous history of ankle injury, and 60% of the patients had at least one ankle sprain. At an average follow up of 2.6 years (range 1.0-4.5), 87% of the patients had good/excellent results, 98% were satisfied, and 84% returned to their previous sports.

Adult

Traction forces generated by locomoting keratocytes.

Traction forces produced by moving fibroblasts have been observed as distortions in flexible substrata including wrinkling of thin, silicone rubber films. Traction forces generated by fibroblast lamellae were thought to represent the forces required to move the cell forwards. However, traction forces could not be detected with faster moving cell types such as leukocytes and growth cones (Harris, A. K., D. Stopak, and P. Wild. 1981. Nature (Lond.). 290:249-251). We have developed a new assay in which traction forces produced by rapidly locomoting fish keratocytes can be detected by the two-dimensional displacements of small beads embedded in the plane of an elastic substratum. Traction forces were not detected at the rapidly extending front edge of the cell. Instead the largest traction forces were exerted perpendicular to the left and right cell margins. The maximum traction forces exerted by keratocytes were estimated to be approximately 2 x 10(-8) N. The pattern of traction forces can be related to the locomotion of a single keratocyte in terms of lamellar contractility and area of close cell-substratum contact.

Animals

Adhesion of peripheral blood lymphocytes of children with arthritis to human umbilical vein endothelial cells.

To determine whether adhesion of peripheral blood lymphocytes (PBL) of patients with juvenile rheumatoid arthritis (JRA) may be enhanced, adhesion of PBL of children with JRA, children with seronegative spondyloarthropathies (SSA), age-appropriate and adult controls, to human umbilical vein endothelial cells (HUVEC) was assessed in vitro. B and CD4 T lymphocytes in initial, adherent, and non-adherent cell fraction were identified by flow cytometry. B lymphocytes of all the younger subjects combined had a higher adherence to activated HUVEC compared with B lymphocytes of the adult donors. Except for greater adherence of HLA-DR+ CD4 T cells, lymphocytes of children with JRA showed no enhanced adhesion to either unactivated or activated HUVEC. The percentage of B cells adherent to activated HUVEC in each of the subject groups was 1.5-3.6-fold higher than adherent CD4 T lymphocytes. Surface analyses indicated higher percentages of CD49d (alpha 4)+ and CD29 (beta 1)+ CD4 T lymphocytes in adherent cells, but less of a differential in CD49 (alpha 4)+ and no difference in CD29 (beta 1)+ B lymphocytes. There were fewer Leu-8 (L-selectin)+ B and Leu-8+ CD4 T cells among adherent cells. The data suggest a greater adhesive capacity of B lymphocytes compared with CD4 T lymphocytes which is unrelated to disease, and the possibility that B lymphocytes may utilize adhesion molecules distinct from those of CD4 T lymphocytes. Only a small subset of T cells of patients with JRA may have an enhanced capacity for adhesion to endothelium.

Adolescent

Comparison of static and dynamic posturography in young and older normal people.

OBJECTIVE: To measure sway velocity during static and dynamic posturography in "normal" older people and to determine which tests best distinguish young from older subjects. SUBJECTS: A sample of 30 young (18-39 years) and 82 community-dwelling older (> 75 years) subjects who reported normal balance underwent a battery of balance tests. MEASUREMENTS: Velocity and frequency of sway, Tinetti gait and balance score, self-reported fear of falling and number of falls. RESULTS: Mean sway velocity and the ratio of high to low frequency sway velocity were significantly increased in older subjects compared with younger subjects for static and dynamic tests with eyes open and with eyes closed. Measures of anterior-posterior sway velocity during angular tilt of the platform with eyes closed best distinguished young from older subjects (almost three-fourths of older subjects had values greater than 2 standard deviations from the young normal mean). Older subjects who reported falls in the past year did not have a significantly higher sway velocity on static or dynamic tests compared with those who did not report falls. However, subjects who reported a fear of falling had significantly higher sway velocity on dynamic tests with eyes closed compared to those who did not report a fear of falling. CONCLUSIONS: On average, velocity of sway is higher in older subjects compared with younger subjects, and the difference between young and old is greater with dynamic posturography than with static posturography.

Accidental Falls

Familial vestibulopathy: a new dominantly inherited syndrome.

Three patients who presented with episodic vertigo followed by gait imbalance and oscillopsia had profound bilateral vestibular loss despite normal hearing. All had a parent with similar findings. The patients, their affected parent, and multiple other family members had a history of migraine headaches, although several of the latter had normal vestibular function. Acetazolamide stopped or markedly decreased the frequency of vertigo attacks in the three patients treated but had little effect on the chronic vestibular loss. This is the first report of a dominantly inherited bilateral vestibulopathy associated with normal hearing.

Acetazolamide

Principles of locomotion for simple-shaped cells.

Moving cells display a variety of shapes and modes of locomotion, but it is not clear how motility at the molecular level relates to the locomotion of a whole cell, a problem compounded in studies of cells with complex shapes. A striking feature of fish epidermal keratocyte locomotion is its apparent simplicity. Here we present a kinematic description of locomotion which is consistent with the semicircular shape and persistent 'gliding' motion of fish epidermal keratocytes. We propose that extension of the front and retraction of the rear of these cells occurs perpendicularly to the cell edge, and that a graded distribution of extension and retraction rates along the cell margin maintains cell shape and size during locomotion. Evidence for this description is provided by the predicted circumferential motion of lamellar features and the curvature of 'photo-marked' lines within specific molecular components of moving keratocytes. Our description relates the dynamics of molecular assemblies to the movement of a whole cell.

Animals

Protein lateral mobility as a reflection of membrane microstructure.

The lateral mobility of membrane lipids and proteins is presumed to play an important functional role in biomembranes. Photobleaching studies have shown that many proteins in the plasma membrane have diffusion coefficients at least an order of magnitude lower than those obtained when the same proteins are reconstituted in artificial bilayer membranes. Depending on the protein, it has been shown that either the cytoplasmic domain or the ectodomain is the key determinant of its lateral mobility. Single particle tracking microscopy, which allows the motions of single or small groups of membrane molecules to be followed, promises not only to reveal new features of membrane dynamics, but also to help explain longstanding puzzles presented by the photobleaching studies, particularly the so-called immobile fraction. The combination of the two complementary technologies should measurably enhance our understanding of membrane microstructure.

Cell Membrane

Phorbol ester has different effects on forskolin and beta-adrenergic-stimulated cAMP accumulation in mouse parotid acini.

Phorbol 12-myristate 13-acetate (TPA) augmented the effects of forskolin, and inhibited the effects of isoproterenol on cAMP accumulation in mouse parotid acini. Treatment of intact cells with the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (MIX), blocked TPA inhibition of isoproterenol but not forskolin-stimulated cAMP accumulation. TPA also caused the translocation of protein kinase C (PKC) from cytosol to membrane. Pre-treatment of parotid acini with TPA for 30 min enhanced the forskolin and isoproterenol-stimulated adenylate cyclase activity in isolated parotid membranes. Addition of purified PKC (pPKC) to parotid membranes mimicked the effects of TPA in increasing cAMP synthesis; the effects were blocked in the absence of calcium and phospholipid, and in the presence of the synthetic peptide (PKC 19-36). Purified PKC also mimicked the effects of TPA in augmenting forskolin and isoproterenol-stimulated adenylate cyclase activities in the cell-free system. Data suggest that the differential regulation of forskolin and isoproterenol-stimulated cAMP accumulation by TPA results from modification of enzymes that synthesize and degrade cAMP.

1-Methyl-3-isobutylxanthine

Gestalt relations and object perception: a developmental study.

We investigated whether adults and infants aged 3, 5, and 9 months perceive the unity and boundaries of visible objects in accord with the Gestalt relations of color and texture similarity, good continuation, or good form. Adults and infants were presented with simple but unfamiliar displays in which all three Gestalt relations specified either one object or two objects-perception of the objects was assessed by a verbal rating method in the adults and by a preferential looking method in the infants. The Gestalt relations appeared to influence the adults' perceptions strongly. However, the relations appeared to have no effect on the perceptions of 3-month-old infants and weak effects on the perceptions of 5-month-old and 9-month-old infants. The findings support the suggestion that developmental changes in object perception occur slowly. These changes, and the organizational phenomena to which Gestalt psychology called attention, may depend in part on the child's developing ability to recognize objects of particular kinds.

Adolescent

The dynamic structure of the pericellular matrix on living cells.

Although up to several microns thick, the pericellular matrix is an elusive structure due to its invisibility with phase contrast or DIC microscopy. This matrix, which is readily visualized by the exclusion of large particles such as fixed red blood cells is important in embryonic development and in maintenance of cartilage. While it is known that the pericellular matrix which surrounds chondrocytes and a variety of other cells consists primarily of proteoglycans and hyaluronan with the latter binding to cell surface receptors, the macromolecular organization is still speculative. The macromolecular organization previously could not be determined because of the collapse of the cell coat with conventional fixation and dehydration techniques. Until now, there has been no way to study the dynamic arrangement of hyaluronan with its aggregated proteoglycans on living cells. In this study, the arrangement and mobility of hyaluronan-aggrecan complexes were directly observed in the pericellular matrix of living cells isolated from bovine articular cartilage. The complexes were labeled with 30- to 40-nm colloidal gold conjugated to 5-D-4, an antibody to keratan sulfate, and visualized with video-enhanced light microscopy. From our observations of the motion of pericellular matrix macromolecules, we report that the chondrocyte pericellular matrix is a dynamic structure consisting of individual tethered molecular complexes which project outward from the cell surface. These complexes undergo restricted rotation or wobbling. When the cells were cultured with ascorbic acid, which promotes production of matrix components, the size of the cell coat and the position of the gold probes relative to the plasma membrane were not changed. However, the rapidity and extent of the tethered motion were reduced. Treatment with Streptomyces hyaluronidase removed the molecules that displayed the tethered motion. Addition of hyaluronan and aggrecan to hyaluronidase-treated cells yielded the same labeling pattern and tethered motion observed with native cell coats. To determine if aggrecan was responsible for the extended configuration of the complexes, only hyaluronan was added to the hyaluronidase-treated cells. The position and mobility of the hyaluronan was detected using biotinylated hyaluronan binding region (b-HABR) and gold streptavidin. The gold-labeled b-HABR was found only near the cell surface. Based on these observations, the hyaluronan-aggrecan complexes composing the cell coat are proposed to be extended in a brush-like configuration in an analogous manner to that previously described for high density, grafted polymers in good solvents.

Animals

Clinical efficacy of dirithromycin in pneumonia.

In a double-blind, double-dummy, multicentre study the efficacy and safety of dirithromycin 500 mg/day given orally once daily for 10-14 days were compared with those of erythromycin 1000 mg/day given orally four times daily for 10-14 days in patients with bacterial pneumonia. At 3-5 days post-therapy, 90 dirithromycin- and 83 erythromycin-treated patients were evaluable; the main reason for non-evaluability was failure to isolate the causative organism. Symptomatic responses were favourable in 94.5% of dirithromycin- and 100% of erythromycin-treated patients at post-therapy. At late post-therapy (2-3 weeks after completion of treatment), symptomatic responses were favourable in 98.7% of dirithromycin- and 94.8% of erythromycin-treated patients. At post-therapy, 63.3% of dirithromycin- and 50.6% of erythromycin-treated patients were unable to be evaluated bacteriologically, mainly due to Mycoplasma pneumoniae or Legionella pneumophila being assessed serologically. In the remaining evaluable patients treated with dirithromycin and erythromycin, bacteriological responses were favourable in 91.4% and 87.8%, respectively. At late post-therapy, favourable bacteriological responses occurred in 89.7% and 86.8%, respectively, of dirithromycin- and erythromycin-treated patients. Abdominal pain was the only treatment-emergent event to occur significantly more frequently in dirithromycin-treated patients.

Adult

Horizontal semicircular canal variant of benign positional vertigo.

We report the clinical features and results of quantitative eye-movement testing in 13 patients with episodic positional vertigo and nonfatiguing direction-changing horizontal positional nystagmus (beating to the right with the head turned to the right and beating to the left with the head turned to the left). The benign history and lack of associated neurologic findings support a peripheral localization of the lesion. This syndrome probably represents a horizontal semicircular canal variant of benign positional vertigo. Free-floating debris in one horizontal canal may explain many of the clinical and oculographic findings.

Adult

The fish epidermal keratocyte as a model system for the study of cell locomotion.

Keratocytes provide an excellent system for the study of locomotion because their simple shape allows the description of basic principles that govern their movement. The graded radial extension (GRE) model is a kinematic description of keratocyte locomotion which relates cell shape to movement. It predicts the circumferential motion of morphological features within the plane of the moving cell. The detection of circumferential motion allows the GRE model to be distinguished from the process of spreading and parallel extension. The circumferential motion of morphological features and the curvature of lines "photomarked" into macromolecular assemblies can be explained in terms of the regulation of actin filament dynamics. The GRE model can thus relate molecular scale events to the locomotion of a whole cell. The principles of the GRE model may operate in other cell types especially since different modes of locomotion appear to be part of the same phenomenon.

Animals

Spontaneous incorporation of the glycosyl-phosphatidylinositol-linked protein Thy-1 into cell membranes.

Thy-1 is a membrane protein that is attached to the plasma membrane by a glycosyl-phosphatidylinositol anchor. Purified rat brain Thy-1 could be reincorporated into the plasma membrane of murine Thy-1- cells directly from aqueous suspension and without the use of detergents. A peripheral staining pattern similar to that observed for endogenous Thy-1 was achieved. Treatment with phosphatidylinositol-specific phospholipase C removed nearly all antibody staining due to either endogenous or inserted Thy-1. Fluorescence recovery after photobleaching (FRAP) was used to compare the lateral mobility of endogenous and inserted Thy-1. Both forms exhibited large lateral diffusion coefficients, but with a substantial immobile fraction (approximately 50%) indicating that the immobile fraction was not due either to chemical differences between inserted and native Thy-1 or to some surface Thy-1 molecules having a protein anchor. However, the inserted Thy-1 failed to activate mouse T lymphocytes upon crosslinking as assayed by [3H]thymidine uptake. Since Thy-1 could be directly labeled with rhodamine, the effect of the size of the labeling ligand on the mobility obtained by the FRAP technique could be explored. Rhodamine-conjugated MRC-OX7 monoclonal antibody or its fragments [R-F(ab)2 or R-Fab] were compared with rhodamine as labels for Thy-1. The measured diffusion coefficients were 1.6 x 10(-9), 2.0 x 10(-9), and 3.2 x 10(-9) cm2/sec for Thy-1 labeled with R-F(ab)2, R-Fab, and rhodamine, respectively; mobile fractions were all in the 40-50% range. Thus, the size of the ligand affects the lateral mobility of this labeled membrane protein to a measurable extent.

Animals

Origins of knowledge.

Experiments with young infants provide evidence for early-developing capacities to represent physical objects and to reason about object motion. Early physical reasoning accords with 2 constraints at the center of mature physical conceptions: continuity and solidity. It fails to accord with 2 constraints that may be peripheral to mature conceptions: gravity and inertia. These experiments suggest that cognition develops concurrently with perception and action and that development leads to the enrichment of conceptions around an unchanging core. The experiments challenge claims that cognition develops on a foundation of perceptual or motor experience, that initial conceptions are inappropriate to the world, and that initial conceptions are abandoned or radically changed with the growth of knowledge.

Cognition