Argon-40-argon-39 dating of apollo sample 15555.

An age of 3.33+/-0.05x10(9) years was obtained for Apollo 15 sample 15555 by argon40-argon-39 dating. The age of rock 15555, a basalt from the rim of Hadley Rille, establishes an upper limit to the age of the rille. The basalt flows filling the Hadley Rille section of the Imbrium basin postdate the formation of the basin-as measured by the Apollo 14 samples of the Fra Mauro formation-by at least 500x10(6) years. Therefore, the mare basalts cannot be simple impact melts but rather must result from some igneous activity on the moon.

Iodine-129/xenon-129 age of magnetite from the orgueil meteorite.

Magnetite from the Orgueil C1 chondrite is only 2.0 +/- 2.4 million years older by the iodine-xenon method than the next oldest meteorite, the Karoonda C4 chondrite. This age ties the primitive C1 chondrites to the extensive iodine-xenon chronology of normal chrondrites. If Karoonda and Orgueil magnetite formed from similar material, then the age difference is an upper limit to the formation time of these meteorites-and by customary extension, the solar system. Condensation, chondrule formation, accretion, and metamorphism of the Karoonda parent body all seem to have been completed within a few million years.

Isotopic analysis of rare gases from stepwise heating of lunar fines and rocks.

Highlights of a first effort in sorting out rare gases in lunar material are solar wind rare gases in abundance; variable (20)Ne/(22)Ne but constant (21)Ne/ (22)Ne ratios in fractions of the trapped neon; cosmogenic rare gases similar to those found in meteorites, except for copious (131)Xe in one rock but not in another; at Tranquillity Base a rock 4.1 x 10(9) years old which reached the surface 35 to 65 million years ago, amid soil whose particles have typically been within a meter of the surface for 10(9) years or more.

Differential regulation of retinoblastoma tumor suppressor protein by G(1) cyclin-dependent kinase complexes in vivo.

The retinoblastoma tumor suppressor protein (pRB) negatively regulates early-G(1) cell cycle progression, in part, by sequestering E2F transcription factors and repressing E2F-responsive genes. Although pRB is phosphorylated on up to 16 cyclin-dependent kinase (Cdk) sites by multiple G(1) cyclin-Cdk complexes, the active form(s) of pRB in vivo remains unknown. pRB is present as an unphosphorylated protein in G(0) quiescent cells and becomes hypophosphorylated (approximately 2 mol of PO(4) to 1 mol of pRB) in early G(1) and hyperphosphorylated (approximately 10 mol of PO(4) to 1 mol of pRB) in late G(1) phase. Here, we report that hypophosphorylated pRB, present in early G(1), represents the biologically active form of pRB in vivo that is assembled with E2Fs and E1A but that both unphosphorylated pRB in G(0) and hyperphosphorylated pRB in late G(1) fail to become assembled with E2Fs and E1A. Furthermore, using transducible dominant-negative TAT fusion proteins that differentially target cyclin D-Cdk4 or cyclin D-Cdk6 (cyclin D-Cdk4/6) and cyclin E-Cdk2 complexes, namely, TAT-p16 and TAT-dominant-negative Cdk2, respectively, we found that, in vivo, cyclin D-Cdk4/6 complexes hypophosphorylate pRB in early G(1) and that cyclin E-Cdk2 complexes inactivate pRB by hyperphosphorylation in late G(1). Moreover, we found that cycling human tumor cells expressing deregulated cyclin D-Cdk4/6 complexes, due to deletion of the p16(INK4a) gene, contained hypophosphorylated pRB that was bound to E2Fs in early G(1) and that E2F-responsive genes, including those for dihydrofolate reductase and cyclin E, were transcriptionally repressed. Thus, we conclude that, physiologically, pRB is differentially regulated by G(1) cyclin-Cdk complexes.

p73.

The discovery of p73 as a family member of p53 has instigated a number of studies in search of its function, regulation, and involvement in tumorigenesis. p73 has been identified as a transcription factor that can regulate p53-dependent transcriptional targets. Similarly to p53, p73 can induce apoptosis in response to various stimuli, including certain types of DNA damage. This evidence suggests that p73 may act as a tumor suppressor with overlapping functions of p53. While mutations of p73 appear rare in human tumors, some leukemias have shown silencing of the gene by hypermethylation. Thus, introduction of p73 into tumor cells possessing inactive p53 may provide a valuable therapeutic approach.

Anoxia-induced changes in extracellular K+ and pH in mammalian central white matter.

In gray matter (GM), anoxia induces prominent extracellular ionic changes that are important in understanding the pathophysiology of this insult. White matter (WM) is also injured by anoxia but the accompanying changes in extracellular ions have not been studied. To provide such information, the time course and magnitude of anoxia-induced changes in extracellular K+ concentration ([K+]o) and extracellular pH (pHo) were measured in the isolated rat optic nerve, a representative central WM tract, using ion-selective microelectrodes. Anoxia produced less extreme changes in [K+]o and pHo in WM than are known to occur in GM; in WM during anoxia, the average maximum [K+]o was 14 +/- 2.9 mM (bath [K+]o = 3 mM) and the average maximum acid shift was 0.31 +/- 0.07 pH unit. The extracellular space volume rapidly decreased by approximately 20% during anoxia. Excitability of the rat optic nerve, monitored as the amplitude of the supramaximal compound action potential, was lost in close temporal association with the increase in [K+]o. Increasing the bath glucose concentration from 10 to 20 mM resulted in a much larger acid shift during anoxia (0.58 +/- 0.08 pH unit) and a smaller average increase in [K]o (9.2 +/- 2.6 mM). The increased extracellular glucose concentration presumably provided more substrate for anaerobic metabolism, resulting in more extracellular lactate accumulation (although not directly measured) and a greater acid shift. Enhanced anaerobic metabolism during anoxia would provide energy for operation of ion pumps, including the sodium pump, that would result in smaller changes in [K+]o. These effects were probably responsible for the observation that the optic nerve showed significantly less damage after 60 min of anoxia in the presence of 20 mM glucose compared to 10 mM glucose. Under normoxic conditions, increasing bath K+ concentration to 30 mM (i.e., well beyond the level shown to occur with anoxia) for 60 min caused abrupt loss of excitability during the period of application but minimal change in the amplitude of the compound action potential following the period of exposure. The anoxia-induced increase in [K+]o, therefore, was not itself directly responsible for irreversible loss of optic nerve function. These observations indicate that major qualitative differences exist between mammalian GM and WM with regard to anoxia-induced extracellular ionic changes.

Anoxic injury of CNS white matter: protective effect of ketamine.

Gray and white matter of the mammalian CNS are both damaged by anoxia. Anoxic injury in gray matter is mediated in part by excessive accumulation of excitotoxins like glutamate. Drugs such as ketamine, a dissociative anesthetic known to block glutamate (NMDA) receptors, reduce hypoxic neuronal injury in gray matter. In this study we used the isolated rat optic nerve preparation to determine if ketamine influences recovery after anoxia in a nonsynaptic system, ie, CNS white matter. Optic nerves from adult rats were exposed to a standard 60-minute period of anoxia. Ketamine (1 mM) improved recovery of the compound action potential (CAP) after anoxia. Since glutamate and aspartate (up to 10 mM) had no effect on CAP amplitude in the optic nerve, the effect of ketamine is probably not mediated by NMDA receptor blockade. These observations indicate that ketamine is able to protect CNS white matter, as well as gray matter, from anoxic injury.

Biological methods for cell-cycle synchronization of mammalian cells.

Understanding the molecular and biochemical basis of cellular growth and division involves the investigation of regulatory events that most often occur in a cell-cycle phase-dependent fashion. Studies examining cell-cycle regulatory mechanisms and progression invariably require cell-cycle synchronization of cell populations. Thus, many methods have been established to synchronize cells at specific phases of the cell cycle. Several of the common methods involve pharmacological agents, which act at various points throughout the cell cycle. Because of adverse cellular perturbations resulting from many of the synchronizing drugs used, other synchrony methods that involve less perturbation of biological systems, such as serum deprivation, contact inhibition, and centrifugal elutriation have a significant advantage. The advantages and disadvantages of these cell synchronization methods are discussed in this review.

Postoperative necrotizing fasciitis in children.

Necrotizing fasciitis is a rapidly progressive soft tissue infection, involving the skin, subcutaneous tissue, and superficial fascia. It is a rare but life-threatening complication in the postoperative patient. In the last 7 years, we have treated four children in whom necrotizing fasciitis developed after appendectomy for ruptured appendix, bilateral inguinal herniorrhaphy, or gastrostomy closure. These four patients and seven well-described children from the literature with necrotizing fasciitis following surgery form the basis of this review. The ages ranged from six days to 15 years (mean 4.5 years). There were eight boys and three girls. There were five clean, five clean-contaminated, and one contaminated surgical procedures. No patient had evidence of malignancy or diabetes. Two of our four patients had evidence of failure to thrive. Only one patient had an intraabdominal abscess. In ten, the infection started in the abdominal wall; in one, the infection started in the chest wall. In our four patients, three had neutropenia and fever, four had tachycardia, and two had wound crepitation and radiographic evidence of subcutaneous gas. Cultures of all ten wounds were positive for bacteria; six were positive for more than one organism. Blood culture results were positive in five of five patients who died and in only two of five patients who survived. All survivors had wide surgical debridement and were treated with broad-spectrum antibiotics. The mortality rate was 45% in the whole series.(ABSTRACT TRUNCATED AT 250 WORDS)

Toward an implantable artificial heart. Experimental and clinical experience at The Pennsylvania State University.

The number of patients who would be candidates for replacement of their failing native heart with an artificial device increases every year. A multidisciplinary group at The Pennsylvania State University is working toward the development of a reliable, totally implantable artificial heart. Initial work resulted in a pneumatic total artificial heart that has performed well in animal implants and has been used clinically in three patients as a temporary bridge to cardiac transplantation. Although pneumatic total artificial hearts have demonstrated utility as temporary mechanical circulatory support devices, attempts at permanent implantation by other groups have been fraught with complications. Because of the suboptimal performance of the pneumatic devices used for permanent implantation, the authors' groups at Penn State is developing n electric motor-driven total artificial heart with encouraging results in calf implants. This artificial heart of the future will use a transcutaneous energy transmission system that will obviate the need for percutaneous lines. Thus, the patient will be provided with as near a normal life-style as possible. At present the technology is at hand to implant an electric blood pump system that should provide a reasonable life-style and function reliably with minimal care. Ongoing cooperative experimental efforts will help to provide the answers necessary to make this system ready for clinical use.

Intravascular plastic catheters. How they potentiate tumor necrosis factor release and exacerbate complications associated with sepsis.

We tested the hypothesis that long-term intravascular cannulation exacerbates the harmful effects of an infectious challenge. Four groups of rats were initially studied: rats without intravascular catheters or infection (group 1), rats without catheters with a polymicrobial infection (group 2), rats with catheters but no infection (group 3), and rats with catheters and infection (group 4). Infected animals had an increased mortality and generated a significantly increased tumor necrosis factor response compared with noninfected animals. Animals with catheters and infection generated far less cardiac output than animals from the other three groups. No histologic changes differentiated the four groups. Therefore, the presence of a sterile intravascular catheter significantly increases cardiac dysfunction and mortality rates in rats with chronic bacteremia. These results suggest that intravascular plastic catheters potentiate the destructive cascade of events produced by the host in response to bacteremia.

Current status of permanent total artificial hearts.

Pneumatic total artificial heats, although demonstrating utility as temporary mechanical circulatory support devices, have not demonstrated a great deal of promise as permanent cardiac replacements. The increasing number of patients who would be candidates for total heart replacement suggests a large role for a permanent implantable total artificial heart. To that end, the Pennsylvania State University is developing an electric motor-driven total artificial heart; the results with implants in calves are encouraging. In this device, a roller-screw mechanism is used to translate the rotation of a brushless direct-current motor into rectilinear motion of a pusher-plate assembly, which in turn empties the blood sacs. The total artificial heart of the future will function under automatic control without percutaneous leads, and this should provide the patient with a nearly normal life-style. Although further experimental efforts are necessary to prepare the device for clinical trials, the technology to provide a safe and reliable electric blood-pump system is at hand.

Strut fracture and disc embolization in Björk-Shiley mitral valve prostheses: diagnosis and management.

Mechanical failure of the Björk-Shiley tilting disc prosthesis is a rare but catastrophic complication of the valve. Several previously reported cases of major strut fracture with disc embolization led to improvements in the structure of the prosthesis. A case of minor strut fracture in the improved convexoconcave model of the Björk-Shiley mitral valve prosthesis is described. The literature on mechanical failures in the Björk-Shiley mitral valve prosthesis is reviewed, and recommendations for recognition and management of this problem are made.

Mortality of coronary artery bypass grafting before and after the advent of angioplasty.

In an effort to determine whether the population of patients undergoing isolated coronary artery bypass grafting and the outcome of these operations have changed, we analyzed the records of two patient populations from our institution. Interventional cardiology techniques (angioplasty, thrombolysis) were not used at our institution before 1982. The records of 736 patients (group 1) who underwent isolated coronary artery bypass grafting from January 1975 to July 1981 were reviewed and compared with a group of 603 patients (group 2) who underwent operation from July 1985 to December 1987. The techniques of operation and myocardial preservation were virtually identical during the two periods. During the group 2 analysis period, 343 angioplasty procedures were performed. The patients in group 2 were significantly older, had increased preoperative New York Heart Association classification, had sustained more previous myocardial infarctions, and had more associated morbid medical conditions. There was a threefold increase in patients seen for reoperative revascularization procedures and a fourfold increase in emergency operations. Overall mortality, although not significantly different, did increase slightly from 2.69% in group 1 to 3.83% in group 2. Mortality after elective procedures remained essentially unchanged (2.05% for group 1 and 1.90% for group 2).

Carbonic anhydrase activity develops postnatally in the rat optic nerve.

We examined the appearance of carbonic anhydrase (CA) activity in rat optic nerves (RONs) 5-77 postnatal days of age and correlated the appearance of enzyme activity with structural and physiological alterations. CA activity was nearly absent before 10 days of age and appeared in this CNS white matter tract with a developmental time-course similar to that of oligodendrogliogenesis and myelinogenesis. When oligodendrocytes and myelin were depleted in the RON by treatment with a mitotic inhibitor, CA activity was markedly reduced. These observations support the hypothesis that CA is contained primarily in oligodendrocytes and myelin. Neural activity in the RON caused changes in extracellular pH (pHo) and the character of these pHo responses was very age dependent; older nerves exhibited much larger acid shifts than neonatal nerves. The development of CA activity may be a factor contributing to this physiological alteration.

A torsional strength comparison of vascularized and nonvascularized bone grafts.

Comparisons of torsional strength are made on the ulnae from the forelegs of short haired hounds where a nonvascularized graft was performed on one leg and a vascularized graft performed on the other. By using the forelegs of a dog as the experimental model and microsurgical techniques, a vascularized bone segment was used to graft a five centimeter nonunion in one leg and at the same time a conventional bone graft was performed on a similar nonunion in the other leg. Similar segments of rib bone were used for each graft. Torsional strength data are shown for nine experimental animals. A successful method for mounting the bones for testing of torsional strength in a torsion machine is given. In each case for which the bones healed properly, the vascularized bone graft proved to be significantly stronger in torsion.

Compartmentation and kinetics of urea cycle enzymes in porcine enterocytes.

We have recently reported the synthesis of urea from ammonia, glutamine and arginine in enterocytes of postweaning pigs. The present study was conducted to determine the compartmentation and kinetics of urea cycle enzymes in these cells. Carbamoyl phosphate synthase I (CPS I) and ornithine carbamoyltransferase (OCT) were located exclusively in mitochondria, whereas argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL) were found in the cytosol. Arginase isozymes were present in both the cytosol and mitochondria of enterocytes, and differed in their sensitivity to heat inactivation. Except for OCT, Vmax values of urea cycle enzymes were much lower in enterocytes than in the liver of pigs, and vice versa for their Km values. Because of a low rate of ureagenesis in enterocytes compared with the liver, intestinal urea cycle enzymes may function primarily to synthesize citrulline. The co-localization of CPS I and OCT and a high activity of OCT in enterocyte mitochondria favors the intestinal synthesis of citrulline from ammonia, HCO3- and ornithine. Low activities of cytosolic ASS and ASL minimize the conversion of citrulline into arginine and therefore, the recycling of citrulline into ornithine via arginase in postweaning-pig enterocytes. These kinetic properties of intestinal urea cycle enzymes maximize the net synthesis of citrulline from glutamine and explain the release of large amounts of citrulline by the pig small intestine. The two compartmentally separated arginase isozymes in enterocytes may play an important role in regulating the intestinal metabolism of proline, nitric oxide and polyamines.

"Would I be able to ... "? Teaching clients to assess the availability of their community living life style preferences.

A three-phase program was developed to involve six institutionalized adults with mild mental retardation in their transition to community living. In Phase I, subjects were interviewed to determine their community living life style preferences and were found to be reliable and skillful in stating their preferences. In Phase II, the subjects' 10 strongest preferences were identified. In Phase III, they were taught to obtain preference availability information from group home representatives and report these findings to their social worker. A simultaneous replication design across two component skills, questioning and reporting, revealed that both increased after training and generalized to community group homes. The 5 subjects available for follow-up maintained their posttraining performance. Implications of these results in extending choice and decision-making technology were discussed.

A biomechanical comparison of vascularized and conventional autogenous bone grafts.

Vascularized and conventional autogenous rib grafts were used to reconstruct 6-cm ulnar defects in the forelegs of the nine dogs. Each dog served as its own control. Biomechanical torsional testing of the grafted ulnas showed that vascularized grafts were 234 percent stronger than the conventional grafts. Bone toughness (energy absorbed) was 483 percent greater in the vascularized grafts, and elastic modulus and proportional limits were 263 and 246 percent greater, respectively. We conclude that vascularized bone grafts are significantly stronger than conventional autogenous bone grafts after 3 months of healing in the dog ulna model.

Gas chromatographic determination of p-chloroaniline in a chlorhexidine digluconate-containing alcohol foam surgical scrub product.

A gas chromatographic (GC) method with flame ionization detection was developed to separate and quantitate p-chloroaniline (PCA) from other components in a chlorhexidine digluconate (CHG)-containing alcohol foam surgical scrub product. A simple sample preparation method was developed in which 1-butanol was used to dissolve the foam and precipitate the CHG, which otherwise would interfere with the GC analysis. The method was validated with respect to linear dynamic range, precision, accuracy, selectivity, limit of detection, and limit of quantitation.