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Biomedical subjects

S Adler

Publications and source records attributed to S Adler.

At least 19 recordsLinked to original sources

T7-induced DNA polymerase. Characterization of associated exonuclease activities and resolution into biologically active subunits.

Bacteriophage T7-induced DNA polymerase has been isolated by a procedure suitable for large scale use and which yields near homogeneous enzyme. In addition to previously described DNA polymerase activity and 3' to 5' exonucleolytic activity on single stranded DNA (Grippo, P., and Richardson, C. C. (1971) J. Biol. Chem. 246, 6867-6873), the enzyme also possesses a highly active exonuclease which hydrolyzes duplex substrates with 3' to 5' directionality. The native polymerase has been dissociated using 6 M guanidine HCl and resolved into biologically active subunits: T7 gene 5 protein and Escherichia coli thioredoxin. The phage-specified subunit obtained by this procedure is deficient in DNA polymerase and double strand exonuclease activities, with deficiencies in these activities being apparent at the level of a single turnover. However, it possesses near normal levels of a single strand hydrolytic activity which is identical to that associated with the native polymerase with respect to substrate specificity and suppression of hydrolysis by low levels of deoxyribonucleoside 5'-triphosphates. Thioredoxin forms a molecular complex with the T7 gene 5 protein, and addition of the host protein restores restores DNA polymerase and double strand exonuclease activities to near normal levels.

DNA-Directed DNA Polymerase

The paradoxial movement of the mediastinum. A diagnostic sign of foreign-body aspiration during childhood.

The paradoxical movement of the mediastinum, in relation to the respiratory cycle, is a valuable fluoroscopie sign in the evaluation of partial obstruction of air-flow through the trachea or larynx. Its recognition in the presence of the normal chest radiograms together with the clinical history of aspiration, is of importance in the diagnosis of a foreign body located above the tracheal bifurcation. The pathophysiology and the radiographic manifestations of this phenomenon are described. Various etiologies are discussed in which this sign is also seen. The experience with 18 pediatric patients is presented and 3 cases are outlined in details.

Airway Obstruction

Life-threatening metabolic alkalosis in a comatose patient.

A 63-year-old man with obstructive pulmonary disease developed severe metablic alkalosis and coma while receiving steroid therapy and nasogastric suction. Treatment, which included the acute induction of hypercarbia and the simultaneous administration of acetazolamide and saline, restored acid-base balance within 24 hours. This combined approach eliminated the need to infuse hydrochloric acid.

Acetazolamide

An extrarenal role for parathyroid hormone in the disposal of acute acid loads in rats and dogs.

Acid infusion studies were performed in nephrectomized rats and dogs with either intact parathyroid glands (intact) or after thyroparathyroidectomy (thyroparathyroidectomized [TPTX]) to determine the role of parathyroid hormone (PTH) in extrarenal disposal and buffering of acutely administered acid. 29 intact rats given 5 mM/kg HCl and 6 intact dogs given 7 mM/kg HCl developed severe metabolic acidosis but all survived. However, each of 12 TPTX rats and 4 TPTX dogs given the same acid loads died. Intact rats and dogs buffered 39 and 50% of administered acid extracellularly, respectively, whereas extracellular buffering of administered acid was 97 and 78% in TPTX rats and dogs, respectively. 17 TPTX rats and 6 TPTX dogs given synthetic PTH 2 h before acid infusion survived. The blood bicarbonate and extracellular buffering in these animals, measured 2 h after acid infusion, was similar to intact animals. Changes in liver, heart, and skeletal muscle pH determined from [(14)C]5,5-dimethyl-2,4 oxazolidinedione distribution seemed insufficient to account for the increased cell buffering of PTH-replaced animals. Indeed, muscle pH in TPTX dogs given PTH and acid was only 0.06 pH units lower than in control dogs given no acid, suggesting that another tissue, presumably bone, was the target for PTH-mediated increased cell buffering. This conclusion was supported by the observation that PTH did not alter the pH of intact rat diaphragms in vitro. These results indicate that PTH is necessary for the optimal buffering of large, acute acid loads presumably by increasing bone buffering.

Acidosis

Effect of early plasmapheresis and immunosuppressive therapy on natural history of anti-glomerular basement membrane glomerulonephritis: report of a 22-month follow-up.

A patient with anti-glomerular basement membrane (GBM)-mediated necrotizing and proliferative glomerulonephritis with crescents was treated with plasmapheresis, cyclophosphamide, and steroids. Treatment resulted in decreased circulating anti-GBM antibody and prompt improvement of renal function that remained stable for 15 months after all treatment was discontinued. Renal biopsies were performed initially, at seven and 17 months. Immunofluorescent examination showed that anti-GBM antibody continued to be present on GBMs although light and electron microscopic findings demonstrated a transformation to a form of sclerosing glomerulonephritis. To our knowledge, this patient's course is the first demonstration that early treatment with plasmapheresis and immunosuppressions may transform the histologic findings in anti-GBM-induced rapidly progressive glomerulonephritis, thereby altering the natural history of this disease.

Adrenal Cortex Hormones

Intervening polyadenylate sequences in RNA transcripts of vesicular stomatitis virus.

Purified and partially resolved vesicular stomatitis virus (VSV) messenger RNA has been annealed to the VSV genomic RNA and visualized in the electron microscope under conditions in which duplex regions have a wider image width than single-stranded RNA. The locations of the intercistronic boundaries between the messages have been mapped on the VSV genome. The contour of the double-stranded regions is occasionally interrupted by looped-out single-stranded RNA. The loops are comprised of post transcriptionally synthesized polyadenylate. Most of these structures are found at the intercistronic boundaries and covalently bridge adjacent message sequences. In this paper, we discuss the possible significance of these loops.

Chromosome Mapping

Metabolic acidosis after hyperalimentation with casein hydrolysate. Occurrence in a starved patient.

A 29-year-old woman with short bowel syndrome and prolonged starvation developed hyperchloremic metabolic acidosis after initiation of hyoeralimentation with a casein hydrolysate solution. The acidosis was not due to bicarbonate loss but was associated with diminished ability of the kidney to increase urinary acid excretion, particularly titratable acidity. Supplemental parenteral bicarbonate administration was necessary for two weeks until urinary acid excretion rose to normal.

Acidosis

Correction of hyperkalemia by bicarbonate despite constant blood pH.

Patients having hyperkalemia often are given bicarbonate to raise blood pH and shift extracellular potassium into cells. Blood pH in many hyperkalemic patients, however, is compensated. To determine whether bicarbonate, independent of its pH action, affects plasma potassium, 14 hyperkalemic patients were treated with bicarbonate in 5% dextrose. In five patients (changed pH group), blood pH rose at least 0.08, while in nine (constant pH group), it changed less than 0.04. In the first group, pH rose 0.12, bicarbonate rose 5.9 mEq/liter, and plasma potassium fell 1.6 mEq/liter, and plasma potassium fell 1.4 mEq/liter. The correlation between changes in plasma potassium and bicarbonate was identical in the two groups and independent of urinary potassium excretion. Four additional patients, who were treated with 5% dextrose alone, did not significantly lower their plasma potassium, although subsequent treatment with bicarbonate in 5% dextrose lowered their plasma potassium. Thus, bicarbonate lowers plasma potassium, independent of its effect on blood pH, and despite a risk of volume overload, should be used to treat hyperkalemia in compensated acid-base disorders, even in the presence of renal failure, provided the plasma bicarbonate concentration is decreased.

Adult

Potassium and intracellular pH.

Recent work has clarified some of the complex interrelationships between cell pH and potassium. These studies have been limited by the techniques available for accurately measuring cell pH. At present it is obvious that intracellular pH is a major regulator of the cellular potassium concentration, but the precise relationship between these two is still uncertain. It has become increasingly clear, however, that no simple relationship exists between the intracellular to extracellular hydrogen ion and potassium ion ratios. Many experiments do demonstrate that the extracellular metabolic alkalosis of potassium depletion is accompanied by a decrease in skeletal muscle pH in rat, rabbit, and probably dog. The response of cardiac and renal tubular cell pH to potassium depletion is less clear, although most evidence indicates that there is also a reduction in the pH of these tissues. This effect on cell pH appears to be independent of chloride. By contrast, hyperkalemia seems to raise muscle cell pH at the same time it induces an extracellular metabolic acidosis. The metabolic and physiologic consequences of potassium-induced alterations in cell pH have yet to be fully elucidated.

Acid-Base Equilibrium

[Obesity in childhood, seen by the pediatrician (author's transl)].

Presently, obesity is beginning more and more in early childhood. This is one of negative factors of civilization. Author describes biochemical properties and the sequelae of obesity (high morbidity and mortality). The role of psychic resp. educational factors is stressed. A program of a fasting cure in a childrens clinic is dealt with.

Adipose Tissue

[Cerebrospinal fluid protein electrophoresis in non-inflammatory central nervous system diseases].

Cerebrospinal fluids (CSF) (N = 365) from patients with non-inflammatory diseases of the central nervous system were analyzed for protein distribution by agar gel microelectrophoresis. After subdivision into diagnostically well defined groups, these patients were compared with 79 normal controls. Most of the diseases investigated were found to follow the "plasma-type" pattern. In some of them the deviations from normal were so extensive that a CSF-protein pattern similar to the "acute-phase reaction" in the serum occurred. Moreover, the following characteristics were found: a considerable increase in total protein and the gamma-globulin fractions in neurinomas; a reproducible increase in the alpha1-globulins in metastases of the central nervous system; and a statistically significant difference of CSF protein findings between male and female patients with protrusion of lumbar intervertebral discs.

Albumins