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A M Daniel

Publications and source records attributed to A M Daniel.

At least 19 recordsLinked to original sources
PubMed1996

Sequences within the early and late promoters of archetype JC virus restrict viral DNA replication and infectivity.

Two forms of JC virus (JCV) have been isolated from its human host, an archetype found in kidney tissue and urine of nonimmunocompromised individuals and a rearranged type detected in lymphocytes and brain tissue of patients with and without progressive multifocal leukoencephalopathy. To investigate the hypothesis that alterations to the archetype transcriptional control region yield rearranged forms of the virus exhibiting new tissue tropic and pathogenic potentials, attempts were made to propagate archetype JCV in human renal and glial cell cultures. Although rearranged forms of JCV multiplied in these cells, archetype JCV failed to do so. Through the use of chimeric and mutant viral genomes, and a cell line that constitutively expresses viral T protein, we demonstrated that archetype's inactivity relative to that of rearranged forms was due to differences in the promoter-enhancer and not in the protein coding regions or origin of DNA replication. Additional analyses revealed that the absence of a large tandem duplication and the presence of a 23- and a 66-base pair sequence in the archetype transcriptional control region were responsible for this restricted lytic behavior. We discuss the possibility that deletion and duplication events within the archetype promoter-enhancer might yield more active viral variants via the loss of a negative, or the creation of a positive, transcriptional control signal(s).

Adult↗
PubMed1993

Transcription initiation sites of prototype and variant JC virus early and late messenger RNAs.

The locations of the authentic viral transcription initiation sites utilized during the course of a JCV(Mad1) infection of primary human fetal glial (PHFG) cells have been identified using the S1 nuclease and primer extension techniques. Early viral mRNA start sites were located 20 to 30 nucleotides (positions 89-92 and 5115-5125) downstream from the two TATA elements present within the promoter-enhancer region of the JCV(Mad1) strain. Absence of the distal TATA element, as seen in the JCV(Mad4) promoter-enhancer, resulted in the alteration of the position and intensity of these sites. Several start sites were observed for late viral mRNAs; two sites were located 25 and 35 nucleotides (positions 191-192 and 200-203) downstream from a potential surrogate TATA signal. To determine whether the presence of constitutively expressed JCV large T protein would alter the pattern of transcription initiation, RNA isolated from JCV(Mad1)-infected POJ cells was analyzed. Although the positions of the early and late viral mRNA start sites were similar to those observed in JCV(Mad1)-infected PHFG cells, they were detected earlier in the course of the infection.

Bacteriophage M13↗
PubMed1985

Carbohydrate metabolism and the hemodynamic response to shock.

To investigate the temporal relationship of changes in carbohydrate metabolism to changes in the hemodynamic stability of the dog in protracted hemorrhagic shock, 30 animals were studied. Blood pressure was maintained at 60 mm Hg for 12 hr during which hemodynamic and metabolic parameters were studied. In early shock cardiac output was decreased and peripheral resistance increased. After 2 hr cardiac output began to increase and peripheral resistance began a progressive decline despite the continuing hypotensive state. Hemodynamic decompensation was essentially complete at 5 hr. There was early and marked mobilization of carbohydrate stores. Muscle glycogen was rapidly mobilized over a 5-hr period. Serum glucose and blood lactate levels rose and remained elevated for 8 hr. Amino acid degradation remained at high levels throughout the experimental period. Hemodynamic decompensation began well before significant depletion of carbohydrate stores and was complete well before the relative exhaustion of the available reserves.

Amino Acids↗
PubMed1983

Fatty acid supply and organ phospholipid turnover in two canine shock models.

Serum free fatty acid (FFA) flux is decreased in shock. The question arose whether the limited availability of FFA would result in a fuel deficit in organs containing no stored lipid and also in the slower turnover of organ phospholipids. The fasting dog's lung, stomach, heart, and liver contained little or no triglyceride, while skeletal muscle, diaphragm, and occasionally intestine had large lipid stores. The replacement rate of lipid fuels and the turnover rate of the fatty acyl moieties of phospholipids were determined by radioactive tracer methods in several organs of dogs in shock due to controlled cardiac tamponade or hemorrhage and their respective controls. In the normotensive controls one-third of the FFA available was directly oxidized; the rest was temporarily incorporated into phospholipids and triglycerides. This incorporation represents replacement of lipid fuels in the organs. Both shock models caused a similar decrease in the total FFA flux and a similar pattern of redistribution among organs. Organs other than heart, lung, and diaphragm replenished their lipid stores slowly in shock. This could cause a fuel deficit in liver and stomach, neither of which have large triglyceride stores. FFA incorporation into phospholipids was slower than esterification into triglycerides in all organs except diaphragm and skeletal muscle both in shock and in normotension. The rate of phospholipid turnover decreased significantly in shock in liver, intestine, and stomach, but increased in heart and lung. Thus liver and stomach are the organs most likely to be affected by the decreased availability of FFA in shock.

Animals↗
PubMed1983

Metabolism of prolonged shock.

Dogs in shock due to controlled cardiac tamponade for 4 or 12 h were studied to determine which of the metabolic changes characteristic of early shock persisted if the shock state was prolonged. Moderate hyperglycemia and severe lactacidemia were present in the first few hours but the levels returned to near normal values by the end of 12 h. The entry rate of lactic acid into the circulation as well as the rate of glycogenolysis was high in the first 4 h but decreased thereafter even though skeletal muscle glycogen stores were not exhausted. In early but not in late shock glycogen accumulated in the heart. Glucose entry and exit rates were significantly elevated in early shock only. Increased protein utilization and decreased fatty acid mobilization persisted throughout the experimental period. Both in early and late shock the incorporation of labeled free fatty acid into tissue lipids was decreased in most organs. In the diaphragm free fatty acid incorporation only decreased in late shock. In the heart and lung, incorporation was higher than normal in the early stages but was at control levels after 12 h of shock.

Ammonia↗
PubMed1982

Exogenous amino acids as fuel in shock.

It has been suggested that in shock branched-chain amino acids are preferentially oxidized resulting in continued proteolysis and stimulated gluconeogenesis. To determine if exogenous amino acids could be used as fuel in shock, dogs rendered hypotensive by controlled cardiac tamponade and normotensive controls were infused with amino acid mixtures and individual amino acids. When Nephramine, a mixture rich in branched-chain amino acids, was infused, plasma alpha-amino nitrogen levels rose but urea output did not increase in either the control state or in shock, suggesting that these amino acids were not rapidly deaminated to serve as fuels. Travasol, which in addition contained large amounts of alanine and glycine, tripled urea output in the controls and doubled it in shock. The limit of urea production was reached in both groups at 35 mumoles urea/minute/kg. In the Travasol-infused animals plasma alpha-amino nitrogen levels were maintained in normotension but rose sharply in shock. When glycine alone was infused into five dogs in shock urea production rate was 30.6 + 2.1 mumoles/minute/kg; with alanine the same value was 22.5 + 2.2 mumoles/minute/kg. In both cases plasma alpha-amino nitrogen levels were high, suggesting that transport of these amino acids into the cell was slow in shock. In four dogs in shock glycine-14C was added to the glycine infusate as a tracer. At radioactive equilibrium 28% of the label infused appeared in CO2; another 22% appeared in glucose. It is concluded that of all the amino acids tested only glycine and alanine are deaminated rapidly enough to serve as exogenous fuels in shock.

Alanine↗
PubMed1981

Binding of the chloroplast coupling factor CF to lipid vesicles.

The binding of the chloroplast coupling factor CF to lipid vesicles was analyzed by gel filtration. CF can be bound to vesicles made of chloroplast lipids but not of lecithin. The presence in the vesicle walls of a proteolipid subunit of the hydrophobic component of the coupling factor increases the binding of CF. The apparent binding constant and the maximum protein/lipid ratio are calculated. The Ca2+-ATPase activity of bound CF is markedly lower than that of dissolved CF. It is confirmed that the proteolipid is a N,N'-dicyclohexylcarbodiimide sensitive proton channel. The binding of CF on proteolipid vesicles decreases their proton permeability.

Calcium-Transporting ATPases↗
PubMed1980

[Contribution of epidural infiltration in the treatment of acute ischemia in the lower inoperable limbs (author's transl)].

Epidural infiltration easily causes without surgical intervention, paralysis of the sympathetic nervous system and analgesia. In this way, spasm and vasoconstriction are inhibited and the use of collateral vessels which are still permeable is facilitated. The antalgesic position of the dropped foot, which is a cause of oedema and hemodynamic disconfort, is eliminated. Out of 17 patients showing an acute ischemia of the lower limbs treated by this method, seven were cured, 3 of whom already having trophic disorders, 7 underwent local amputations and 3 had leg and thigh level amputations. Six months later 10 of these patients were doing well. The best therapeutic conditions of this treatment are non-atheromatous arteritis: angiospasm, toxic or inflammatory acute ischemia and Buerger's disease. On the other hand, the results are mediocre with atheromatous arteritis.

Acute Disease↗
PubMed1979

The role of stress hormones in the catabolic metabolism of shock.

The role of catecholamines in shock metabolism in dogs was studied by comparing the metabolism of shock due to cardiac tamponade, shock with catecholamine depletion from prior reserpine adminstration and metabolism in the normal dog with continuous epinephrine infusion. It was concluded that the high serum concentrations of catecholamines in shock probably cause the increased blood lactate, initial hyperglycemia and, possibly, the poor free fatty acid oxidation seen in shock, but do not cause the increased protein catabolism of shock. With the simultaneous infusion of glucagon, cortisol and epinephrine in physiologic dosages, catabolic metabolism similar to that observed in shock was established in the normal dog. Lactacidemia, hyperglycemia, poor ability to oxidize free fatty acid and massive protein breakdown were observed. The decreased metabolic rate and diminished fatty acid mobilization of shock were not duplicated in those in the normal group and are probably a function of hypoperfusion. The importance of these observations is that impaired use of fat and increased protein breakdown, as seen in shock and trauma, are mediated by hormonal changes. It follows that there may be the opportunity to reverse or modify this catabolism by hormonal manipulation in the surgical patient.

Animals↗
PubMed1978

Protein and fat utilization in shock.

A previous study demonstrated that in the dog, shock, regardless of its etiology, resulted in increased oxidative utilization of substrates which form lactate and pyruvate as intermediary metabolites. The study implied a concomitant decrease in free fatty acid oxidation, as the oxidative pathway of the latter does not involve the lactate-pyruvate step. To test this hypothesis, free fatty acid metabolism was investigated by infusing carbon-14 labelled fatty acid in 12 normal dogs, in nine animals in shock due to controlled cardiac tamponade, and in six animals with endotoxin shock. The shock state was characterized by significant (p less than 0.05) decrease both in arterial fatty acid concentration and in free fatty acid turnover. In addition, both the rate of free fatty acid oxidation and the percentage of the total CO2 derived from free fatty acid oxidation were significantly (p less than 0.05) diminished. In contrast, urea production rates were higher in shock, and the calculated maximum contribution of protein oxidation to total CO2 production rose from 23% in the control animals to 50% in the test groups.

Animals↗
PubMed1978

The anatomic and metabolic source of lactate in shock.

The size of the lactate pool in canine shock was measured directly by determining the lactate concentration of various organs. All organs tested, except skeletal muscle, had lactate concentrations similar to those of arterial blood. Skeletal muscles had much higher concentrations of lactate than did arterial blood. When 14C-labeled glucose was infused intravenously, it was concluded from the relative specific activities of glucose and lactate in blood that about one-third of lactic acid originates from blood glucose in shock. Only skeletal muscle had lower lactate specific activity than did blood. This is a possible indication that skeletal muscle is the site of production of lactate. Low glucose specific activity in muscle indicates massive glycogen breakdown, which probably serves as a metabolic precursor of lactate. Lactate production from amino acids produced by proteolysis could also play a role.

Amino Acids↗
PubMed1976

Lactate metabolism in the dog during shock from hemorrhage, cardiac tamponade or endotoxin.

The elevated arterial lactate concentration in shock was investigated by measuring lactate production and clearance rate using a constant infusion of 14C-labeled lactate. In addition, the pathways of lactate metabolism were characterized by determining the percentage of lactate under-going oxidation and the percentage of the total carbon dioxide production which was derived from lactate. These measurements were performed on 16 normal dogs and on 23 dogs in a state of shock. Shock was induced by hemorrhage in ten, by controlled cardiac tamponade in seven and by endotoxin injection in six. In all of the dogs in a state of shock, there was a statistically significant increase in both the arterial lactate concentration and lactate turnover, while the lactate clearance decreased significantly. The percentage of the arterial lactate which underwent oxidation remained normal. The percentage of the total carbon dioxide production which was derived from lactate increased significantly, p less than 0.05, from 4.7 per cent in the normal dogs to 22.7 per cent in the dogs in a state of shock. Since both oxygen uptake and carbon dioxide production remain unchanged in shock, these data are consistent with an increased metabolism of substrates which from pyruvate and lactate as intermediary metabolites, that is, carbohydrates and certain amino acids, with a concomitant decrease in the metabolism of substrates which do not form pyruvate, that is, free fatty acids. In both the normal and shocked dogs, the arterial lactate concentration rose as the lactate production rate increased. Therefore, the elevated arterial lactate in shock was due to an increase in the lactate production and not to a lack of oxygen.

Animals↗