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Biomedical subjects

L Abrams

Publications and source records attributed to L Abrams.

At least 37 records · Page 2Linked to original sources

Insulin action and glucose metabolism in nondiabetic control and NIDDM subjects. Comparison using human skeletal muscle cell cultures.

Myoblasts from human skeletal muscle were isolated from needle biopsy samples of vastus lateralis and fused to differentiated multinucleated myotubes. Specific high-affinity insulin and insulin-like growth factor I (IGF-I) binding, glucose transporter proteins GLUT1 and GLUT4, glycogen synthase and pyruvate dehydrogenase proteins, and their specific mRNAs were identified in fused myotubes. Insulin and IGF-I stimulated 2-deoxyglucose uptake twofold with half-maximal stimulation by insulin at 0.98 +/- 0.12 nmol/l and maximal stimulation at 17.5 nmol/l. Acute insulin treatment (33 nmol/l) doubled glycogen synthase activity and glucose incorporation into glycogen while increasing pyruvate dehydrogenase approximately 30%. In cells cultured from NIDDM subjects, both basal (6.9 +/- 1.0 vs. 13.0 +/- 1.7 pmol.mg protein-1.min-1) and acute insulin-stimulated transport (13.5 +/- 2.0 vs. 22.4 +/- 1.3 pmol.mg protein-1.min-1) were significantly reduced compared with nondiabetic control subjects (both P < or = 0.005). GLUT1 protein content of total membranes from NIDDM subjects was decreased compared with control subjects, while GLUT4 levels were similar between groups. A significant correlation (r = 0.65, P < or = 0.05) was present when maximal rates of insulin-stimulated glucose transport in cell culture from subjects were compared with their corresponding in vivo glucose disposal determined by hyperinsulinemic glucose clamp. In summary, differentiated human skeletal muscle cultures exhibit biochemical and molecular features of insulin-stimulated glucose transport and intracellular enzyme activity comparable with the in vivo situation. Defective insulin-stimulated glucose transport persists in muscle cultures from NIDDM subjects and resembles the reduced insulin-mediated glucose uptake present in vivo. We conclude that this technique provides a relevant cellular model to study insulin action and glucose metabolism in normal subjects and determine the mechanisms of insulin resistance in NIDDM.

Adult↗

Hydroxyapatite ceramics for continuous delivery of heparin.

The goal of this investigation is to develop a ceramic system for delivering therapeutic amounts of heparin continuously from subcutaneous implants. Hydroxyapatite (HA) ceramic reservoirs were used for the continuous delivery of heparin in both in vitro and in vivo environments. Each reservoir was loaded with heparin. The open end was then sealed with a silastic medical adhesive and sterilized by ethylene oxide. A total of 15 capsules were used for conducting the in vitro experiments. Each capsule (control, sham, 1400, 2800, 4200 units heparin) was suspended in a vial containing 100 ml phosphate buffered saline (pH 7.4) at 37 degrees C. A one ml aliquot was withdrawn from each serum bottle at fixed intervals for three weeks, and assayed for heparin by the Sigma Heparin Clotting Assay. The largest amount of heparin was released from the capsule containing 4200 units of heparin and the smallest amount was released from the capsule containing 1400 units of heparin. Thirty Holtzman rats (140 +/- 15 g.) were used in the in vivo experiment. The rats were equally distributed into five groups (control, sham, 1400, 2800, and 4200 units of heparin). Animals in four of the five groups were implanted with HA capsules containing various amounts of heparin. Capillary tube clotting times were observed at regular intervals. Six days following implantation, the clotting times of the blood obtained from rats implanted with heparin-containing capsules was significantly higher (6.3 +/- 0.07 minutes) than the clotting times of blood obtained from shams and controls (4.3 +/- 0.03 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A world between realities: an exploration of therapeutic group culture and transitional phenomena in a long-term psychotherapy group.

In long-term, open-ended psychotherapy groups in which there are inevitable, yet potentially disruptive changes in membership, therapeutic group culture can become particularly important in sustaining a group's sense of cohesion. This article focuses on how transitional phenomena, as defined by D. W. Winnicott, and representational play serve as vehicles for establishing therapeutic group culture in a preadolescent girls' group. Applications of both transitional phenomena and therapeutic group culture to group stage development, as outlined by Garland, Jones, and Kolodny (1970), will also be explored.

Child↗

Activation of an intron enhancer within the keratin 18 gene by expression of c-fos and c-jun in undifferentiated F9 embryonal carcinoma cells.

The mouse forms of human keratins 18 and 8 (K18 and K8) are the first members of the large intermediate filament gene family to be expressed during embryogenesis. To identify potential regulatory elements of the human K18 gene, various recombinant constructions were expressed in cultured cells. An enhancer element was found in the first intron that functions on both the K18 and thymidine kinase promoters in differentiated cells. In F9 embryonal carcinoma cells, the level of expression was low in the presence or absence of the first intron. Cotransfection of F9 cells with K18 constructs that include the first intron and increasing amounts of an expression vector of c-jun results in a modest increase in the reporter gene expression. Cotransfection of the same construct with increasing amount of the mouse c-fos gene results in activation of the reporter gene by as much as 15-fold, with a near linear response to the amount of c-fos gene added. Site-specific mutagenesis of a putative AP-1 site within the intron abolishes trans-activation by c-fos in F9 cells. Furthermore, induction of c-fos in a derivative of F9 cells results in increased expression of the endogenous mouse form of K18. Cotransfection with c-jun or c-fos expression vectors had little effect on the expression of the K18 reporter construct in a parietal endodermal cell line already expressing the endogenous mouse gene. These results identify an enhancer within the first intron of K18 that may interact directly with c-jun and c-fos via a conserved AP-1-binding site. K18 expression in undifferentiated F9 cells may be limited by the low levels of c-jun and c-fos.

Animals↗

A new crystal form of ricin-OR.

Ricin-OR, an antitumor toxin, has been crystallized in space group P2 with cell parameters a = 8.77 nm, b = 4.64 nm, c = 7.64 nm and beta = 101 degrees. There is one molecule in the asymmetric unit and the solvent content is estimated to be 48% by volume. The crystals diffract to 0.25 nm resolution which is higher than that of the previously reported C2 crystal form which had a solvent content of 65%.

Antineoplastic Agents↗

Clinical application of a new glucose analyzer in the neonatal intensive care unit: comparison with other methods.

We evaluated the operation of the Yellow Springs Instrument Co. (YSI) glucose analyzer (model 23A) by clinical nurses for the measurement of blood glucose in the intensive care nursery. In vitro performance was determined with the use of aqueous standards; with a 2-point calibration of 0.0 and 200 mg/dl, a precision of better than 1.0% of each standard (25, 50, 100, 200 mg/dl) was achieved, and the linearity was excellent (Y = 0.99X - 0.49, r = 0.99). The YSI correlated well with a manual spectrophotometric glucose oxidase method (r = 0.99) and the Kodak Ektachem analyzer (r = 0.98) using human umbilical cord blood samples. Five trained clinical nurses performed all YSI and glucose reagent strip analyses, including all in vitro and patient samples. Four reagent strip methods were compared with the YSI from 104 neonatal heel-stick blood samples: Glucometer II with memory (r = 0.73), Glucostix (r = 0.74), Dextrostix (r = 0.70), and Chemstrip bG (r = 0.83). We conclude that clinical nurses can and do learn to use the YSI with excellent precision and that the YSI represents an improved method for measuring glucose concentrations in the newborn intensive care nursery.

Blood Chemical Analysis↗

Hemodynamic changes after nafcillin administration during coronary artery bypass surgery.

The hemodynamic response to nafcillin administration was studied in 45 patients with good left ventricular function and no known history of hypersensitivity to penicillin during coronary artery bypass grafting (CABG). Group I (15 patients) received 1 gram of nafcillin in 10 mL of saline as an intravenous (IV) bolus, group II (15 patients) received 1 gram of nafcillin in 50 mL of saline as a slow IV infusion over 15 minutes, and group III (15 patients) did not receive nafcillin. Hemodynamic variables and plasma histamine and catecholamine levels were measured before and after nafcillin administration, after 500 mg of CaCl2, and after 0.1 mg of phenylephrine. Bolus nafcillin administration produced profound hypotension secondary to vasodilatation with significant increases in cardiac index and decreases in systemic and pulmonary vascular resistances. Cardiac index increased from 3.15 +/- 0.3 L/min/m2 to 5.75 +/- 0.25 L/min/m2 (P less than 0.005) one minute after nafcillin administration, and remained at 5.1 +/- 0.35 L/min/m2 after administration of CaCl2 (P less than 0.005). All hemodynamic parameters returned toward control values after administration of 0.1 mg of phenylephrine, IV. Plasma epinephrine, norepinephrine, and histamine levels increased more than 100%. In group II, cardiac index increased, while systemic and pulmonary vascular resistances and mean arterial pressure decreased. However, these changes were less significant than those found in group I.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

1,25(OH)2D3 administration in moderate renal failure: a prospective double-blind trial.

This study represents the first randomized prospective, double-blind, placebo-controlled trial of the efficacy of 1,25(OH)2D3 on bone histology and serum biochemistry in patients with mild to moderate renal failure. Sixteen patients with chronic renal impairment (creatinine clearance 20 to 59 ml per min) received either 1,25(OH)2D3, at a dose of 0.25 to 0.5 microgram daily (eight patients), or placebo. Transiliac crest bone biopsies were performed before entrance into the study and after 12 months of experimental observation. None of the patients were symptomatic or had radiological evidence of bone disease. Of the thirteen patients who completed the study, initial serum 1,25(OH)2D levels were low in seven patients and parathyroid hormone levels were elevated in seven patients. Bone histology was abnormal in all patients. 1,25(OH)2D3 treatment was associated with a significant fall in serum phosphorus and alkaline phosphatase concentrations as well as with histological evidence of an amelioration of hyperparathyroid changes. In contrast to previous reports, no deterioration of renal function attributable to the treatment occurred, perhaps because a modest dose of 1,25(OH)2D3 was employed combined with meticulous monitoring. Further investigation is required to determine whether alternative therapeutic strategies (smaller doses or intermittent therapy) may avoid the potential for suppressing bone turnover to abnormally low levels in the long term.

Adult↗

Differential susceptibility of isolated mouse retinal neurons and photoreceptors to kainic acid toxicity. In vitro studies.

Dissociated cultures of mouse retinal neurons and photoreceptors in chemically defined medium were used to investigate the susceptibility of these cells to the neurotoxin kainic acid (KA). Cells isolated from the newborn mouse retina were initially insensitive to this toxin, and the cells that differentiated as rod photoreceptors retained this resistance throughout the culture period. However, amacrine neurons became increasingly sensitive to KA toxicity as they differentiated in culture; after the fifth day in vitro approximately 90% of these cells were killed by KA in a concentration- and time-dependent fashion. The neurons showed pronounced swelling within 10 min of treatment onset, and cell lysis and nuclear fragmentation were evident during the next few hours. KA-induced degeneration of these neurons was corroborated using the amacrine cell-specific monoclonal antibody HPC-1, as well as autoradiographic and biochemical determinations of the high affinity uptake for GABA. This inhibitory neurotransmitter was taken up by amacrine neurons but not by photoreceptor cells, and this uptake was completely abolished in KA-treated cultures. Similar results were obtained with the neuronal enzyme choline acetyltransferase. However, both photoreceptor survival and the expression of photoreceptor markers such as opsin and the retinoid-binding protein interphotoreceptor (IRBP) were similar in KA-treated and control cultures. Similarly, the high affinity uptake of glutamate, an excitatory amino acid which is predominantly taken up by photoreceptors, showed only modest changes in KA-treated cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗