The lakes of Titan.

The surface of Saturn's haze-shrouded moon Titan has long been proposed to have oceans or lakes, on the basis of the stability of liquid methane at the surface. Initial visible and radar imaging failed to find any evidence of an ocean, although abundant evidence was found that flowing liquids have existed on the surface. Here we provide definitive evidence for the presence of lakes on the surface of Titan, obtained during the Cassini Radar flyby of Titan on 22 July 2006 (T16). The radar imaging polewards of 70 degrees north shows more than 75 circular to irregular radar-dark patches, in a region where liquid methane and ethane are expected to be abundant and stable on the surface. The radar-dark patches are interpreted as lakes on the basis of their very low radar reflectivity and morphological similarities to lakes, including associated channels and location in topographic depressions. Some of the lakes do not completely fill the depressions in which they lie, and apparently dry depressions are present. We interpret this to indicate that lakes are present in a number of states, including partly dry and liquid-filled. These northern-hemisphere lakes constitute the strongest evidence yet that a condensable-liquid hydrological cycle is active in Titan's surface and atmosphere, in which the lakes are filled through rainfall and/or intersection with the subsurface 'liquid methane' table.

Magellan: radar performance and data products.

The Magellan Venus orbiter carries only one scientific instrument: a 12.6-centimeter wavelength radar system shared among three data-taking modes. The synthetic-aperture mode images radar echoes from the Venus surface at a resolution of between 120 and 300 meters, depending on spacecraft altitude. In the altimetric mode, relative height measurement accuracies may approach 5 meters, depending on the terrain's roughness, although orbital uncertainties place a floor of about 50 meters on the absolute uncertainty. In areas of extremely rough topography, accuracy is limited by the inherent line-of-sight radar resolution of about 88 meters. The maximum elevation observed to date, corresponding to a planetary radius of 6062 kilometers, lies within Maxwell Mons. When used as a thermal emission radiometer, the system can determine surface emissivities to an absolute accuracy of about 0.02. Mosaicked and archival digital data products will be released in compact disk (CDROM) format.

The Footprint method to assess transmalleolar axis.

Torsional deformities of the lower extremities are a common reason for an orthopaedic consultation and are also part of the evaluation of a patient in gait analysis. This study assessed the level of agreement between, and the repeatability of, the Footprint method and two other methods (Prone and Jig) of measuring the transmalleolar axis (TMA) clinically. The Footprint method measures the TMA as the patient sits by projecting the position of the malleoli downwards onto lined paper while the lines of the paper are aligned with the knee axis. The Prone method projects the position of the malleoli upwards onto the sole of the foot and this is related to the visually estimated knee axis. The Jig method uses a tropometer to relate the angle between the tibial tubercle and the two malleoli. Two assessors measured twelve subjects using the three methods and six subjects were re-measured approximately 1 week later for repeatability. There was poor agreement between the three methods but the Footprint method was the most repeatable (coefficient of repeatability: 5.4). One observer then assessed the repeatability of the effect of simulated equinus on the Footprint method in 10 normal subjects on 2 separate occasions 1 week apart. Equinus was obtained by having the subjects sit and firstly extend their knee and place the foot on the floor and secondly by placing the foot under consideration on a wedge. Both conditions introduced an offset into the measurement of the TMA when compared to the measurements with the ankle at neutral in the same subjects. The reliability of the Footprint method was then assessed using 10 inexperienced observers who measured nine normal subjects each on 2 separate occasions and their results compared with those from an experienced observer. The inexperienced observers were less repeatable than an experienced observer (coefficients of repeatability 9.2 and 6.9, respectively). We recommend that different methods of measuring TMA should not be used interchangeably in clinical practice. The Footprint method was the most repeatable of the three methods tested and can be used for patients who have fixed equinus but the measurement was less repeatable when used by inexperienced observers.

Intracellular calcium mobilization in rat platelets is adversely affected by copper deficiency.

The influence of copper deficiency on the mobilization of Ca2+ from intracellular stores following ionomycin treatment or thrombin activation of rat platelets was examined using the fluorescent indicator, fura-2, to measure changes in cytosolic Ca2+ concentration ([Ca2+]i). Platelets, obtained from copper-deficient and control rats and loaded with fura-2, were suspended in medium containing 1 mM EGTA and no added Ca2+. The size of the internal Ca2+ pools in the suspended platelets was estimated from the rise in [Ca2+]i following maximal discharge of stored Ca2+ by treatment with 1 microM ionomycin. Peak [Ca2+]i following ionomycin treatment was lower in platelets from copper-deficient rats compared to control rats (148 +/- 27 nM vs. 188 +/- 17 nM), suggesting that the size of the Ca2+ storage pools was decreased by copper deficiency. Furthermore, once internal Ca2+ stores were discharged by ionomycin, [Ca2+]i remained elevated in platelets from copper-deficient rats, but decreased in control rats. These data indicate that copper deficiency may inhibit the efflux of Ca2+ from platelets after its release from internal stores by ionomycin treatment. In platelets from copper-deficient and control rats, stimulation with 0.1 U/ml thrombin led to rapid rise followed by a slow decay in [Ca2+]i. However, peak [Ca2+]i was lower in platelets from copper-deficient rats than in control rats (94 +/- 19 nM vs. 131 +/- 16 nM). These findings imply that by reducing the amount of Ca2+ available for release from intracellular stores, copper deficiency also reduces [Ca2+]i following thrombin activation in the absence of external Ca2+.

Stimulation by polyamines of carbamylphosphate:glucose phosphotransferase and glucose-6-phosphate phosphohydrolase activities of multifunctional glucose-6-phosphatase.

The effects of added polyamines on carbamylphosphate (carbamyl-P):glucose phosphotransferase and glucose-6-phosphate (Glc-6-P) phosphohydrolase activities of rat hepatic D-Glc-6-P phosphohydrolase (EC 3.1.3.9) of intact and detergent-treated microsomes have been investigated. With the former preparation, in the presence of 1.4 mM phosphate substrate and 90 mM D-glucose (phosphotransferase), 1 mM spermine, spermidine, and putrescine activated Glc-6-P phosphohydrolase 67%, 57%, and 35%, respectively. Carbamyl-P:glucose phosphotransferase, under comparable conditions, was activated 57%, 34%, and 18%. NH+4 (0.25--5.0 mM) produced at best but a minor activation (0--14%), while poly(L-lysine) (Mr = 3400; degree of polymerization 16) equimolar relative to other polyamines with respect to ionized free amino groups activated the hydrolase 358% and the transferase 222%. Treatment of microsomes with the detergent deoxycholate reduced, but did not abolish, polyamine-induced activation. The stimulatory effects of polyamines persisted in the presence of excess catalase, indicating their independence from H2O2 formation; and were eliminated in the presence of Ca2+. Kinetic analysis revealed that all tested polyamines decreased the apparent Michaelis constant values for carbamyl-P and Glc-6-P, but had no effect on the Km for glucose. Poly(L-lysine) increased the V value for both Glc-6-P phosphohydrolase and apparent V values for phosphotransferase extrapolated to infinite concentrations of either carbamyl-P or glucose. The other tested polyamines elevated only this last velocity parameter. It is proposed that a major mechanism by which polyamines activate glucose-6-phosphatase-phosphotransferase is through their electrostatic interactions with phospholipids of the membrane of the endoplasmic reticulum of which this enzyme is a part. Conformational alterations thus induced may in turn affect catalytic behavior. It is suggested that polyamines, or similar positively charged peptides, might participate in the cellular regulation of synthetic and hydrolytic activities of glucose-6-phosphatase.

Effect of streptozocin-induced diabetes on insulin-receptor tyrosine kinase activity in obese Zucker rats.

We examined insulin binding, insulin-stimulated autophosphorylation, and phosphorylation of poly(Glu.Na,Tyr)4:1 by liver and skeletal muscle insulin receptor from lean, obese, and obese streptozocin-induced diabetic Zucker rats. Induction of diabetes with streptozocin (30 mg/kg) lowered the lasting insulin level from 11.4 to 3.8 ng/ml, which was not significantly greater than the lean control level. Autophosphorylation and tyrosine kinase activity of liver insulin receptors were increased 70-100% in the obese control group (relative to lean rats), but diabetes reversed this hyperresponsiveness to insulin. In muscle, obesity was associated with a 40-50% decrease in autophosphorylation and tyrosine kinase activity, which was also reversed in the diabetic state. Autophosphorylation and tyrosine kinase activity were significantly correlated in liver and muscle and were also correlated with fasting insulin levels. These data suggest that insulin-receptor tyrosine kinase activity is regulated differently in liver and muscle and that the abnormalities in kinase activity associated with the obese Zucker rat are at least partly secondary to hyperinsulinemia.

Metabolic and hemodynamic effects of moxonidine in the Zucker diabetic fatty rat model of type 2 diabetes.

We studied the effect of moxonidine, an imidazoline ligand, on metabolic and hemodynamic parameters in Zucker diabetic fatty rats, a model of type 2 diabetes. In one group (metabolic group), 8-week-old rats were started on a diet containing either moxonidine (3 or 10 mg x kg(-1) x day(-1)) or vehicle for 4 weeks. Body weight and food intake were monitored daily, plasma insulin and glucose were monitored weekly, and an oral glucose tolerance test (OGTT) was performed at study's end. In another group of rats (hemodynamic group), radio frequency transmitters were implanted 1 week before starting the diet, and mean blood pressure, heart rate, and motor activity were continuously monitored at baseline and for 4 weeks after beginning drug exposure. Moxonidine (10 mg x kg(-1) x day(-1)) significantly decreased elevated glucose levels and prevented the decrease in plasma insulin noted in vehicle-treated or pair-fed groups. Moxonidine also decreased fasting glucose (3 and 10 mg x kg(-1) x day(-1)) and prevented the decrease in fasting insulin (10 mg x kg(-1) x day(-1)) compared with vehicle. Fasting glucose at 10 mg x kg(-1) x day(-1) was equivalent to lean littermates. Both doses significantly increased glucose disposal and the insulin secretory response during the OGTT. Moxonidine lowered daily mean arterial pressure compared with both baseline values and vehicle and decreased daily heart rates. Motor activity was unaffected, except for an increase in the 10 mg x kg(-1) x day(-1) group during low activity periods. Moxonidine did not significantly affect body weight, fluid intake, or urine volume, but the 10 mg x kg(-1) x day(-1) dose reduced urinary protein excretion compared with vehicle-treated animals. These results demonstrate that, in an animal model of type 2 diabetes, the antihypertensive agent moxonidine induces a beneficial effect on abnormal glucose metabolism and renal protein excretion at doses that are effective in lowering arterial blood pressures and heart rate.

Acylation of human insulin with palmitic acid extends the time action of human insulin in diabetic dogs.

To test whether the binding of insulin to an endogenous serum protein can be used to extend the time action of insulin, human insulin was acylated at the epsilon-amino group of Lys(B29) with palmitic acid to promote binding to serum albumin. Size-exclusion chromatography was used to demonstrate specific binding of the resulting analog, [N(epsilon)-palmitoyl Lys(B29)] human insulin, to serum albumin in vitro, and the time action and activity of the analog were determined in vivo using overnight-fasted, insulin-withdrawn diabetic dogs. In the diabetic animal model, the duration of action of [N(epsilon)-palmitoyl Lys(B29)] human insulin administered intravenously was nearly twice that of unmodified human insulin, and the plasma half-life was nearly sevenfold that of the unmodified protein. Administered subcutaneously, [N(epsilon)-palmitoyl Lys(B29)] human insulin had a longer duration of action; a flatter more basal plasma insulin profile; and a lower intersubject variability of response than the intermediate-acting insulin suspension Humulin L (Lilly, Indianapolis, IN). These studies support the concept that modification of insulin to promote binding to an existing serum protein can be used to extend the time action of human insulin. In addition, the time action, pattern, and decreased variability of response to [N(epsilon)-palmitoyl Lys(B29)] human insulin support the development and further testing of this soluble insulin analog as a basal insulin to increase the safety of intensive insulin therapy.

Cardiovascular correlates of attention in normal and psychiatrically disturbed children. Blood pressure, peripheral blood flow, and peripheral vascular resistance.

Blood pressure, peripheral blood flow, and peripheral vascular resistance were measured in normal adults and children and in children with autism and severe disturbances in personality development while the individuals were engaged in a variety of attentional tasks. The tasks were designed to elicit outward direction of attention (and intake of sensory input) or inward direction of attention (and relative rejection of external sensory input). During tasks involving sensory rejection, normal adults and normal children showed increased blood flow and decreased peripheral vascular resistance; with sensory intake, blood flow was decreased and resistance was increased. The most severely impaired children showed little alteration in their physiological response to task requirements. Autistic children had higher mean blood flow and lower peripheral vascular resistance than normal children and adults. Some autistic children characteristically may be in a state of sensory rejection associated with generally higher levels of arousal or defense against environmental bombardment.

In vivo oxidative modification of erythrocyte membrane proteins in copper deficiency.

Oxidative stress has been postulated to contribute to the pathology associated with dietary copper deficiency. In vivo, erythrocytes are probable targets of oxidative damage because they are exposed to high concentrations of oxygen and contain heme iron that can autoxidize, which results in the formation of superoxide anions. Activity of the important antioxidant enzyme, copper, zinc superoxide dismutase, decreases markedly in erythrocytes during copper deficiency. The effect of dietary copper deficiency on indicators of oxidative stress was examined in erythrocyte membranes of rats maintained on a purified copper-deficient diet for 35 days after weaning. Erythrocytes were separated into young and old populations on a Percoll gradient prior to membrane isolation and quantification of lipid peroxides and protein carbonyls. Protein carbonyls, determined by Western blot immunoassay, were detected predominantly in both the alpha and beta chains of spectrin. Alpha and beta subunits of spectrin in erythrocyte membranes from copper-deficient rats contained higher amounts of carbonyls than controls, regardless of the population of erythrocytes studied. This study suggests that spectrin may be a specific target for oxidative damage when erythrocyte copper, zinc superoxide dismutase activity is reduced by copper deficiency.

Amelioration of effects of severe dietary copper deficiency by food restriction in rats.

To test the effect of food restriction on responses to dietary copper deficiency, male weanling rats were fed two amounts of dietary copper via five dietary-intake regimens ranging from ad libitum to 70% of ad libitum intake. Copper-deficient rats exhibited characteristic signs, including depressed organ copper content, reduced activity of copper-dependent enzymes, enlarged hearts, and anemia. Food restriction attenuated the cardiac enlargement, red blood cell defects, and reduction of superoxide dismutase activity in copper-deficient rats. Mineral and enzyme assays suggested that possible mechanisms for this amelioration are the correction of copper status and/or the improvement of antioxidant status. Also, food restriction depressed serum cholesterol and enhanced cytochrome c oxidase activity in both copper-adequate and copper-deficient rats, which compensated for effects of copper deficiency. A second experiment illustrated that the mortality associated with severe copper deficiency was also inhibited by food restriction.

Arterial intimal embrittlement. A possible factor in atherogenesis.

Sections of aorta, coronary artery, basilar artery and vena cava were collected at autopsy. Macroscopically normal intimal specimens were removed by stripping. Intimal collagen was measured as hydroxyproline. Intimal film embrittlement was measured in vitro by a bursting volume distensibility test developed in our laboratory. There was an average increase of over 100% in the collagen content of apparently lesion-free human arterial intima on aging over a fifty-year period. This includes an increase of 113% for aortic intima, 49% increase for coronary artery intima, and an increase of 158% in collagen in basilar artery intima. In contrast the collagen level in the vena caval intima decreases on aging, by 42% in fifty years. The large increase in collagen in arterial intima is accompanied by a large increase in intimal embrittlement. The decreasing collagen content of the venous intima on aging results in increased distensibility. Increased aortic intimal film embrittlement (lower distensibility) correlates with age (R = 0.699), but even better with intimal collagen (R = 0.911), suggesting that aortic intimal collagen level is a more important determinant of intimal embrittlement than age. Men, older than 55, have significantly higher aortic intimal collagen levels than women. Embrittlement of arterial intima should make it more susceptible to injury under the pulsatile pressure of the blood. Decreased venous intimal collagen and greater distensibility on aging could be factors in the development of venous valvular insufficiency and varicose veins. However, our study of veins was performed primarily as a control in this instance. Fundamental elements in the atherogenic process are increased intimal collagen, increased intimal brittleness, endothelial injury, followed by intimal cell proliferation. In the vena caval intima on aging there is decreased collagen, increased intimal distensibility, no injury due to increased pulse or blood pressure, and, therefore, no cell proliferation and no intimal lesion.

Herpes zoster during pregnancy.

Herpes zoster has rarely been noted to occur during pregnancy. We report the case of a woman at 37 weeks' gestation who developed herpes zoster and 3 weeks later delivered a normal infant. A 6-month follow-up has revealed no sequelae in the child. Pertinent clinical aspects of herpes zoster and a review of the literature indicating a favorable prognosis for infants exposed in utero are presented.

Cutaneous chylous reflux. The weeping scrotum.

The cutaneous lesions associated with reflux of lymphatic fluid and chyle from the skin have received little attention in the dermatologic literature. We describe a patient with such lesions, and discuss the clinical, histopathologic, and lymphangiographic manifestations. We review the classification of lymphedema and the commonly seen cutaneous lesions.

Clinical syndrome of chemotaxis defect, infections, and hyperimmunoglobulinemia E. A case report.

A 17-year-old girl had a clinical syndrome that consisted of neutrophil chemotaxis defect, recurrent bacterial infections, and hyperimmunoglobulinemia E. Neutrophil chemotaxis was quantitated by a radioassay technique that used 51Cr-labeled neutrophils and a double micropore filter chemotaxis chamber. A table of the features of other cases of this syndrome is presented. Since ten of the 13 patients who are described had a chronic eczematoid dermatitis, we suggest that this may be a fourth feature of this syndrome. Red hair and fair skin were not consistent findings in these patients. In the evaluation of patients with chronic, recurrent bacterial infections of the skin of undetermined origin, we recommend determination of serum IgE levels. If IgE is found to be elevated, one should consider the presence of this syndrome, and neutrophil chemotaxis should then be examined.

The acrodermatitis enteropathica-like syndrome.

An acrodermatitis enteropathica-like syndrome occurred as a result of severe bowel disease and the use of zinc-deficient hyperalimentation regimens. Emphasis is placed on early and adequate zinc replacement to effectively prevent or reverse this entity.

Unilateral blepharochalasis.

True blepharochalasis occurring in young adults and associated with recurrent bouts of eyelid swelling and eventual lid laxity is an uncommon entity. We report the case of an 18-year-old woman who had a nine-year history of unilateral blepharochalasis. A skin biopsy specimen that showed the absence of stainable elastic tissue confirmed the clinical impression, and appropriate surgical correction was carried out.

Effects of topical and systemic nicotine on gingival blood flow in dogs.

It has been suggested that due to its vasoconstrictive action, nicotine may have a deleterious effect on the periodontium. This study examined the effects of topical and systemic nicotine administration on gingival blood flow. Eighteen young adult dogs were divided into three groups receiving the following treatments for 28 days; topical nicotine in orabase, systemic nicotine via osmotic mini-pumps, and topical orabase or systemic saline via osmotic mini-pumps. Blood flow to the gingiva was measured (at days 0 and 28) by the radiolabeled microsphere method. Blood flow was consistently increased from day 0 to day 28 in the nicotine-treated animals. Comparison of days 0 and 28 blood-flow values demonstrated a statistically significant change (p less than 0.05) in the anterior regions of the topical-nicotine group as compared with the control group. The increased flow may be a reflection of the mode of nicotine delivery and timing of the blood-flow determination procedures.

Effect of ultrasonic vibration on post removal in extracted human premolar teeth.

The purpose of this study was to determine the effectiveness of ultrasonic vibration in removing Paraposts from extracted teeth. Paraposts were cemented in mandibular premolars to a depth of 9 mm with zinc phosphate cement and the teeth placed in four groups. Group 1 received no vibration. Group 2 received vibration for 4 min, group 3 received vibration for 12 min, and group 4 received vibration for 16 min. Tensile forces were applied to the posts and mean dislodgment forces compared. The mean force (kg) required to dislodge the Parapost in group 1 was 24.92 +/- 1.64 SEM; in group 2, 25.01 +/- 1.80; in group 3, 24.08 +/- 2.29; and in group 4, 12.41 +/- 2.60. There was a significant difference between group 4 and groups 1 to 3 (p = 0.0003). Results of this study indicate that 16 min ultrasonic vibration is an effective method for removing Paraposts from human premolar teeth.

Breakage of ultrasonic root-end preparation tips.

Modified ultrasonic tips are used to prepare rootend cavities during endodontic surgery. The purpose of this study was to determine whether such tips are prone to breakage during use. Ten different tip designs were driven by an ultrasonic unit at maximum power. Multirooted teeth were instrumented, the apex removed, and the tooth was placed horizontally on a pan balance. The apex was instrumented by each ultrasonic tip in turn for 15 min, with the load being increased by 100 g every 5 min. Those tips with curvatures of 70 degrees or greater fractured within the first 5-min loading period. Breakage occurred approximately 2 to 3 mm from the end and always at a bend. Scanning electron microscopy revealed that the fractures were brittle in nature, with little change in the remaining section. Two tips bent: one isthmus preparation tip and one silver point removal tip. All the other designs were deemed satisfactory after experimentation. This study shows that fracture of ultrasonic tips can occur and is related to the degree of bending.