Canine postradiation plasma glucose variations

One of the observations of endotoxic or septic shock in canines is the report of concurrent hypoglycemia. Canines exposed to supralethal gamma radiation also develop acute systemic hypotension. This study was performed in order to determine if hypoglycemia develops in the canine concurrent with radiation-induced hypotension. Systemic arterial mean blood pressure (MBP) was measured via femoral arterial catheter. Blood for plasma glucose determinations was obtained from the systemic arterial circulation at the level of the abdominal aorta and from the hepatic portal vein. Plasma glucose levels were determined on a Beckman Glucose Analyzer which employs the enzymatic reaction of β-D-glucose and oxygen. Glucose levels and MBP were monitored for one hour before and for one hour after exposure to 100 Gy, whole-body, gamma radiation or sham radiation for the control animals. Concurrent with postradiation hypotension, we measured a significant decrease in plasma glucose levels in both the systemic arterial circulation and in the hepatic portal vein. Arterial glucose levels in the sham radiated animals showed a slight rise two minutes after sham radiation, falling back to pretreatment, base line levels four minutes later and remaining at that level for the remainder of the hour. Arterial levels in the radiated animals showed a sharp decline two minutes postradiation, falling even further to twenty percent below preradiation levels by one hour postradiation. Venous blood glucose levels in sham radiated animals showed an initial increase and a gradual decrease to five percent below pretreatment base line levels; while glucose levels in radiated animals showed an immediate postradiation decrease continuing to twenty percent below preradiation levels by one hour postradiation. These findings suggest impaired hepatic gluconeogenesis, resulting in postradiation hypoglycemia.     

Effect of Lipid Structure on the Capacity of Myelin Basic Protein to Alter Vesicle Properties: Potent Effects of Aliphatic Aldehydes in Promoting Basic Protein-Induced Vesicle Aggregation

The capacity of myelin basic protein or of poly-L-lysine to promote leakage of carboxyfluorescein from vesicles or the aggregation of vesicles was studied. The vesicles were composed of phosphatidylcholine as the sole or major lipid component. Addition of 10% sphingomyelin, 10% phosphatidylglycerol, 10% egg or bovine brain phosphatidylethanolamine, or 30% dodecanal had relatively little effect on the extent of carboxyfluorescein release in the presence of either myelin basic protein or poly-L-lysine. In contrast with these results, the extent of vesicle aggregation was very sensitive to lipid composition. Addition of 10% phosphatidylglycerol induced more aggregation than the other phospholipids tested. Admixing 10% of a partially degraded sample of bovine brain phosphatidylethanolamine also led to a large amount of aggregation induced by the myelin basic protein. This latter aggregation appeared more specific for the basic protein, as it occurred to a much smaller extent with poly-L-lysine. In general, the effects of the myelin basic protein on either carboxyfluorescein release or vesicle aggregation were similar to, although somewhat greater than, that of poly-L-lysine. The aggregation of vesicles containing degradation products of phosphatidylethanolamine can be ascribed largely to the presence of aliphatic aldehydes. The effect of aliphatic aldehydes was specific in that the aliphatic alcohol, hexadecanol, or the short-chain aldehydes, acetaldehyde or butyraldehyde, did not promote myelin basic protein-induced vesicle aggregation. In addition, poly-L-lysine was less effective than the basic protein in aggregating vesicles containing aliphatic aldehydes. (ABSTRACT TRUNCATED AT 250 WORDS)     

Concentrations of Homovanillic Acid and 5-Hydroxyindoleacetic Acid in Cerebrospinal Fluid from Human Infants in the Perinatal Period

To assess maturation of central serotonin and catecholamine pathways at birth, we measured lumbar CSF homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), stable acid metabolites of dopamine and serotonin, using HPLC with electrochemical detection. CSFs from 57 neonates (38 premature and 19 at term) and 13 infants 1-6 months old were studied. HVA levels increased with maturity (p less than 0.05; ANOVA), whereas 5-HIAA levels were similar in all these subjects. HVA/5-HIAA ratios increased markedly from 1 +/- 0.12 in the most premature neonates to 1.98 +/- 0.17 in the older infants (p less than 0.01; t test). There were no sex differences for these values.     

Isolation, stages of differentiation, and long term maintenance of adult rat myocytes

Although a variety of techniques have been developed to isolate myocytes from adult hearts, the long term viability of such cells has only recently been investigated. In addition, relatively little is known about the stages of differentiation such cells proceed through following isolation. In the present study myocytes were isolated using two techniques, one involving retrograde perfusion via the aorta, and the other involving mechanical "shearing." In addition, several modifications were made to minimize the trauma normal associated with isolating myocytes from adult hearts. Both techniques yielded a high percentage of rod-shaped, quiescent myocytes, although myocytes isolated using the "shearing" method were less likely to remain viable for more than 24 hours. With both techniques those cells which remained viable for more than 24 hours proceeded through an identical pattern of differentiation leading to stable, attached cells which remained viable for up to four weeks. These results demonstrate that with the appropriate isolation techniques it is possible to maintain adult myocardial cells in culture for lengthy periods of time.     

Metastatic phenotype of human prostate tumor cells in athymic nude mice: Alteration by exposure to ethyl methanesulfonate and “reversion” by 5-azacytidine

Summary The human prostate tumor subline 1-LN-PC-3-1A (1-LN) is reproducibly metastatic in adult athymic nude mice. Cells surviving a brief in vitro exposure to ethyl methanesulfonate (EMS) exhibited a profound decrease in capacity for experimental lung metastasis in nude mice. Thirty days after EMS treatment, 1×10⁶ uncloned EMS-treated 1-LN cells (1-LN-EMS-10) were injected IV into groups of 6 to 8-week-old male athymic nude mice (BALB/cAnBOM). A median of 8.5 colonies/lung was observed among 20 1-LN-EMS-10-injected mice, which was significantly different from the median of 51 colonies/lung produced among 14 1-LN-injected mice (P=0.0002). This altered phenotype remained stable during 150 days of continuous culture. However, the 1-LN-EMS-10 cells were tumorigenic in 10/10 nude mice injected SC. Single lung tumor colonies recovered from 1-LN-EMS-10-injected mice and reinjected IV into nude mice produced medians of 32–63 colonies/lung. The altered metastatic phenotype resulting from treatment of 1-LN with EMS was reversed by exposure to a noncytotoxic dose of 5-azacytidine, but unaffected by a second exposure to EMS. Collectively these data demonstrate that the metastatic phenotype of these human tumor cells in athymic nude mice can be heritably altered by in vitro exposure to EMS and 5-azacytidine. Analysis of the mechanisms underlying these phenotypic changes may provide insight into parts of the complex process of tumor cell evolution.     

Effect of methylation of histidine-48 on some enzymatic and pharmacological activities of snake venom phospholipases A2

The effects on some pharmacological and enzymatic properties were determined following methylation of histidine at the enzymatic active site of the basic relatively toxic $\text{Naja}$$\text{nigricollis}$ and the acidic relatively non-toxic $\text{Naja}$$\text{naja}$$\text{atra}$ phospholipases A₂. Following methylation a very low residual enzymatic activity (0.4 -- 1% of control) was accompanied by a parallel loss in intraventricular lethality, anticoagulant potency, direct hemolytic action and ability to block directly and indirectly evoked contractions of the mouse phrenic nerve-diaphragm preparation. Since methylation does not impair the enzyme's ability to bind monomeric of micellar substrates or Ca²⁺, the results suggest that the pharmacologicallly active region of the molecule is different from the micellular substrate binding site but strongly influenced by the invariant histidine-48 located at the enzymatic active site.