Kinetic analysis of biochemical differentiation in Dictyostelium discoideum

The metabolic network leading to accumulation of cellulose, trehalose, and mucopolysaccharide during development of Dictyostelium discoideum was simulated on a computer. The program consists of a metabolic map, the measured specific activity of the enzymes involved at each stage in development, and the substrate and inhibitor affinities. The Km values of four enzymes, amylase, UDP-galactose polysaccharide transferase, UDP-galactose epimerase, and cellulose synthetase, were determined for this study. At each iteration (1 min) during the period simulated (1500 min), the in vivo activity was calculated for each enzyme using Michaelis-Menten equations and new values for metabolites and end products were generated. The computed values for the concentration of both metabolites and polysaccharides were in close agreement with the measured values at all stages of development. We conclude that the in vitro measured values correlate well with the measured in vivo rates when treated in this manner. The program was modified to simulate the alterations in carbohydrate metabolism which might be expected in mutant strains with reduced activity of various enzymes. Trehalose was found to overaccumulate when either the peak value of the developmentally controlled increase in the specific activity of UDPGlc pyrophosphorylase was reduced. Trehalose accumulation was decreased in simulations of mutants lacking glycogen phosphorylase or glycogen synthetase. The interaction of these metabolic pathways is discussed.     

Hepatitis among plasma fractionation workers. An industry-wide study

An industry-wide survey of plasm fractionation facilities in the United States was conducted during 1973-74. Hepatitis was reported among the workers with varying degrees of plasma contact at all plant sites. For each of fourteen facilities in this investigation, field inspections disclosed: (1) numerous overt instances of employee-product contact: (2) inconsistent methodologic approaches at virtually all stages of the plasma fractionation process; (3) at low level of management and employee awareness regarding the potential bio-hazard identified; and (4) disparate examples of hepatitis surveillance and prophylaxis. Our data suggests that there is a high risk of hepatitis among plasma fractionation workers and, as such, much more attention needs to be focused on the reduction of health hazards within this industry.     

Disruption of cellular translational control by a viral truncated eukaryotic translation initiation factor 2alpha kinase homolog

Phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha) is a common cellular mechanism to limit protein synthesis in stress conditions. Baculovirus PK2, which resembles the C-terminal half of a protein kinase domain, was found to inhibit both human and yeast eIF2alpha kinases. Insect cells infected with wild-type, but not pk2-deleted, baculovirus exhibited reduced eIF2alpha phosphorylation and increased translational activity. The negative regulatory effect of human protein kinase RNA-regulated (PKR), an eIF2alpha kinase, on virus production was counteracted by PK2, indicating that baculoviruses have evolved a unique strategy for disrupting a host stress response. PK2 was found in complex with PKR and blocked kinase autophosphorylation in vivo, suggesting a mechanism of kinase inhibition mediated by interaction between truncated and intact kinase domains.     

Neurite outgrowth stimulated by L1 requires calcium influx into neurons but is not associated with changes in steady state levels of calcium in growth cones

L1, NCAM and N-cadherin are cell adhesion molecules (CAMs), present on neuronal growth cones, which promote cell-contact dependent axonal growth by activating a second messenger pathway in neurons that requires calcium influx through L- and N-type calcium channels. In the present study we show that two of these CAMs, (L1 and N-cadherin) can stimulate neurite regeneration from axotomised adult dorsal root ganglion (DRG) neurons cultured in vitro and that this response can be fully inhibited by agents that block or negate the effect of calcium influx into the neurons. However although the response required calcium influx into neurons, it was not associated with an increase in the steady state levels of calcium in neuronal growth cones. These results suggest that small localised changes, or increases in the rate of calcium cycling, in growth cones and/or filopodia, are more important for regulating axonal growth than changes in the steady-state level of calcium.     

Acetohexamide hypoglycemia: treatment by peritoneal dialysis

Acetohexamide hypoglycemia in a patient with renal failure has been successfully treated by peritoneal dialysis. Peritoneal dialysis was done in such a patient, and specimens of serum were collected to measure levels of acetohexamide and its main active metabolite, hydroxyhexamide. During dialysis, hypoglycemia was corrected. After 17 1/2 hours of dialysis, serum acetohexamide level was essentially unchanged. Serum hydroxyhexamide level had decreased at a slower rate than the rate of decrease previously measured in a uremic patient not on dialysis. Although peritoneal dialysis may correct the hypoglycemia, the data suggest that acetohexamide and hydroxyhexamide are not dialyzable. Due to these problems this drug should not be used in patients with chronic renal failure. The drug of choice to control hyperglycemia in patients with renal insufficiency is insulin. If for any reason insulin cannot be used, tolbutamide is the oral hypoglycemic agent of choice.     

Plasma secretin and pancreatic bicarbonate response to exogenous secretin in man

Saccadic and smooth eye movements are controlled by separate mechanisms within the nervous system. We describe a patient with familial ataxia, considered to be a form of olivopontocerebellar degeneration, who is incapable of generating reflex or voluntary saccades. She can, however, move her eyes smoothly to the normal limits of lateral gaze, even when her head is prevented from moving. Latency before onset of movement is prolonged, and the velocity of movement is abnormally slow. We postulate that the degenerative process may have affected selectively those cells of the ventral paramedian pontine tegmentum responsible for the generation of saccades; and the the prolonged latency from presentation of a visual stimulus to the onset of movement is related to an inability to generate burst discharges needed to overcome the viscoelastic properties of the orbital tissues.     

Laparoscopic adrenalectomy for nonmalignant disease: improved safety, morbidity, and cost-effectiveness

The genetic diversity displayed by Plasmodiumfalciparum field isolates, the occurrence of variant forms of the parasite at different frequencies in different geographic areas, and the complexity of the infections represent major obstacles for the development of effective malaria control measures. However, since most of the existing studies have been performed in regions where P. falciparum transmission is high, little is known about the diversity and complexity of parasite populations circulating in areas of low malaria endemicity. We investigated the extent of genetic polymorphism in P. falciparum field isolates from Honduras, a region where its transmission is low and seasonal. Allelic diversity was analyzed in the highly polymorphic parasite genes encoding the merozoite surface proteins- (MSP-1) and -2 (MSP-2) and the glutamate-rich protein (GLURP) by the polymerase chain reaction. Gene polymorphism was also assessed in the EB200 region derived from the highly size polymorphic Pf332 gene. Limited size polymorphism was detected in all genes analyzed, with four and three variants for the MSP-1 and MSP-2 alleles, respectively, and two size variants for the GLURP and Pf332 genes. Moreover, based on the studied genetic markers, most infections consisted of only a few genetically distinct parasite clones. These results suggest that the P. falciparum parasite populations circulating in this region are genetically homogeneous and point to an association between the extent of parasite genetic diversity and the intensity of malaria transmission.     

Common pediatric esophageal disorders

Esophageal disorders in children can result in significant morbidity. The most common esophageal disorder seen in children is gastroesophageal reflux. Other common disorders affecting the esophagus include peptic esophageal strictures, esophageal atresia with or without tracheoesophageal fistula, caustic and foreign body ingestions, achalasia, and cricopharyngeal achalasia. We discuss what is currently known about these common pediatric esophageal disorders with regard to pathophysiology, clinical presentation, and diagnostic and treatment strategies.