Mirrors used in the LIGO interferometers for first detection of gravitational waves.

For the first time, direct detection of gravitational waves occurred in the Laser Interferometer Gravitational-wave Observatory (LIGO) interferometers. These advanced detectors require large fused silica mirrors with optical and mechanical properties and have never been reached until now. This paper details the main achievements of these ion beam sputtering coatings.

Crosstalk between leukemia-associated proteins MOZ and MLL regulates HOX gene expression in human cord blood CD34+ cells.

MOZ and MLL, encoding a histone acetyltransferase (HAT) and a histone methyltransferase, respectively, are targets for recurrent chromosomal translocations found in acute myeloblastic or lymphoblastic leukemia. In MOZ (MOnocytic leukemia Zinc-finger protein)/CBP- or mixed lineage leukemia (MLL)-rearranged leukemias, abnormal levels of HOX transcription factors have been found to be critical for leukemogenesis. We show that MOZ and MLL cooperate to regulate these key genes in human cord blood CD34+ cells. These chromatin-modifying enzymes interact, colocalize and functionally cooperate, and both are recruited to multiple HOX promoters. We also found that WDR5, an adaptor protein essential for lysine 4 trimethylation of histone H3 (H3K4me3) by MLL, colocalizes and interacts with MOZ. We detected the binding of the HAT MOZ to H3K4me3, thus linking histone methylation to acetylation. In CD34+ cells, depletion of MLL causes release of MOZ from HOX promoters, which is correlated to defective histone activation marks, leading to repression of HOX gene expression and alteration of commitment of CD34+ cells into myeloid progenitors. Thus, our results unveil the role of the interaction between MOZ and MLL in CD34+ cells in which both proteins have a critical role in hematopoietic cell-fate decision, suggesting a new molecular mechanism by which MOZ or MLL deregulation leads to leukemogenesis.

Association of Sweet's syndrome and acute sarcoidosis: report of a case and review of the literature.

Sweet's syndrome (acute febrile neutrophilic dermatosis, SS) may be considered a reactional dermatosis with numerous associated diseases. We describe a rare association between SS and acute sarcoidosis in a 55-year-old woman. The atypical feature of positive tuberculin reaction is discussed. In this association, diagnosis may be challenging with coexistent skin lesions of both diseases. Acute sarcoidosis should be considered when SS is accompanied with mediastinal lymphadenopathy, uveitis or erythema nodosum. Deep-seated nodular lesions in the context of SS are not always 'deep' SS lesions.

Generation of a flat-top laser beam for gravitational wave detectors by means of a nonspherical Fabry-Perot resonator.

We have tested a new kind of Fabry-Perot long-baseline optical resonator proposed to reduce the thermal noise sensitivity of gravitational wave interferometric detectors--the "mesa beam" cavity--whose flat top beam shape is achieved by means of an aspherical end mirror. We present the fundamental mode intensity pattern for this cavity and its distortion due to surface imperfections and tilt misalignments, and contrast the higher order mode patterns to the Gauss-Laguerre modes of a spherical mirror cavity. We discuss the effects of mirror tilts on cavity alignment and locking and present measurements of the mesa beam tilt sensitivity.

[Pustular vasculitis disclosing Behçet disease]. / Vasculite pustuleuse révélatrice d'une maladie de Behçet.

INTRODUCTION: Pustular vasculitis is a classical manifestation of Behçet's disease. We report a case where the papulopustular eruption formed an arch on the skin and the histology examination showed predominant lymphocytic infiltration. CASE REPORT: A 29 year-old with a past history of recurrent buccal aphthosis had developed episodic papulopustular eruptions over the past 3 years. The diagnostic of Behçet's disease was made on the basis of an association with lymphocytic meningis, uveitis and erythema nodosum. General corticosteroid therapy was effective, but did not prevent skin relapse, controlled with colchicine. DISCUSSION: Pustular vasculitis usually presents with pustular eruptions on purpuric lesions and polynuclear infiltration of the dermis. Predominant lymphocytic infiltration is usually due to a pathergy phenomenon and would be specific for Behçet's disease. In our patient, colchicine was effective, although the mechanism remains to be explained.

Ketoacid production in acute respiratory and metabolic acidosis and alkalosis in rats.

Metabolic acidosis inhibits and alkalosis enhances ketoacid production in ketotic humans and animals. To compare these effects with those of superimposed respiratory acid-base disturbances, ketone output was evaluated in awake ketotic rats during metabolic (intravenous infusions of HCl or NaHCO3) or respiratory (hyper or hypocapnia) disorders. With decreases in blood pH of 0.1-0.2 units over 3 h, blood ketone concentrations significantly decreased an average of 1.9 mM (metabolic) and 1.1 mM (respiratory) and urinary ketone excretion rates significantly decreased by 1.3 mumol/min (metabolic). With increases in systemic pH, blood ketone concentrations and urinary ketone excretion rates were significantly increased. Changes in blood pH correlated with changes in urinary ketone excretion rates in both metabolic (r = 0.87) and respiratory (r = 0.67) acid-base disturbances. The alterations occurred promptly and were rapidly reversible. These findings indicate that modest changes in systemic pH from metabolic or respiratory acid-base disturbances modify net ketoacid production in ketotic rats, confirm pH control of endogenous acid output as an acid-base regulator, and show that systemic pH, not bicarbonate concentration, mediates the process.

Effects of aerobic exercise on energy expenditure and nitrogen balance during very low calorie dieting.

Aerobic exercise in addition to severe caloric restriction was studied for its effects on resting energy expenditure (REE), weight loss, and lean tissue preservation in adult women. A formula diet providing 1.5 g protein and 0.5 g carbohydrate (CHO) per kilogram of ideal body weight daily (mean intake 720 kcal/d) was given to 12 overweight inpatients for 4 to 5 weeks. Six subjects remained sedentary (group 1), while the other six subjects (group 2) performed supervised endurance exercise (a total of 27 hours at 50% of maximal oxygen uptake (VO2max) over 4 weeks). Lean tissue preservation was excellent in both groups and was unaffected by the group 2 exercise regimen. Weight loss over 4 weeks in the two groups did not differ (group 1, 6.9 +/- 0.7 kg; group 2, 6.5 +/- 0.7 kg). The VO2max was not increased after 4 weeks of exercise compared with controls. The resting oxygen consumption (rVO2) of both groups declined 10% (P less than .001) in the first seven days of dieting. Thereafter the rVO2 in group 1 remained stable, but a further 17% reduction occurred in group 2 (P less than .03) by the third week of exercise. The free triiodothyronine (fT3) concentration also fell more in group 2 (P less than .05), suggesting a relationship between fT3 and energy expenditure during severe caloric restriction. The ergometer exercise for up to two hours daily was well tolerated. The absence of either a training effect or accelerated weight loss in group 2 may be due to the limited duration (4 weeks) or intensity of the exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of methionine on net ketoacid production in humans.

An exogenous acid load (NH4Cl) inhibits net ketoacid production in the first week of starvation and the fourth to eighth weeks of ketogenic dieting. To determine whether an acid load produced by amino acid metabolism can similarly modify ketosis, five overweight volunteers ingested methionine (H2SO4), NH4Cl, and NaCl (control), in varying order, each day for seven days during weeks 5 to 8 of hypocaloric ketogenic dieting. During days 5 to 7 of each phase, blood pH, bicarbonate, and pCO2 were stable but lower in the NH4Cl phase (7.32 +/- 0.02, 18.1 +/- 1.2 mmol/L, 35.8 +/- 1.4 mmHg) and the methionine phase (7.33 +/- 0.01, 17.1 +/- 0.9 mmol/L, 34.0 +/- 2.0 mmHg) than in the NaCl phase (7.38 +/- 0.01, 22.3 +/- 0.2 mmol/L, 37.6 +/- 1.6 mmHg), P less than .05. Over this period, blood acetoacetate concentration was lower during the methionine and NH4Cl phases than during NaCl, P less than .05. In addition blood beta-hydroxybutyrate and total ketone-body concentrations were lower in the methionine than NaCl phases, P less than .05. Urinary acetoacetate and beta-hydroxybutyrate excretion fell with both acid loads, P less than .05. Compared with control values, urinary total ketone excretion was suppressed by 67 +/- 10% in the NH4Cl and 89 +/- 3% in the methionine periods. When NaCl was ingested after either of the acid loads, urinary ketone excretion increased by 300% to 700%. Thus, methionine ingestion, which results in an acid challenge equivalent to that of a large protein load, has an impact on net ketoacid production similar to that of NH4Cl.(ABSTRACT TRUNCATED AT 250 WORDS)

[The association of dermatomyositis and toxoplasmosis]. / Association dermatomyosite-toxoplasmose.

IF: negative test: less than 10 UI/ml; doubtful test 10-100 UI/ml; positive test greater than 100 UI/ml. HA: negative test: less than 8 dilutions; doubtful test 16-24; positive test greater than 128. The antibodies kinetics vary with the pattern of the infection (primary infection or reinfection), with the method of identification, and with the subjects. In the case of primary infection, the IgM appear since the first week following the acquisition of the infection; they reach their highest titre at the first month (variability: 15th day-3rd month); they disappear during the fourth month (variability: 2-9 months). The antibodies detected by HA after 2 ME must be reduced by at least 3 dilutions to be significant. The IgG appear later. They are detected at the beginning of the second week by IF or of the 4th month by HA, reach their highest titre at the 4th month by IF (variability: 2-9 months) or at the 9th month by HA (variability: 4th month-2nd year); they then decrease to reach lower titres within the space of 1 or 5 years. The antibodies detected in the case of reinfection are usually of higher titre with a steeper rate of increase, and are more persistent than following a primary infection.

[Oral provocation tests (OPT) in the skin pathology of children]. / Les tests de provocation orale (TPO) dans la pathologie cutanée de l'enfant.

The purpose of oral food challenges is to detect food intolerance. Challenges of food additives and drugs are not often used in children. The authors report methods and protocols that they used for food, food additives and contaminants and emphasize the potential dangers of these tests. Atopic diseases and chronic urticaria are the principal indications. Cow's milk, eggs and fish are the allergens that are most often incriminated. Oral challenges are only to be done as part of an integrated investigation together with skin tests, in vitro tests and a study of intestinal permeability. Food avoidance and therapy should be decided after the challenge data are available.

Effect of elevated FFA on carbohydrate and lipid oxidation during prolonged exercise in humans.

Increased availability of circulating free fatty acids (FFA) inhibits the rate of glycolysis in heart and resting skeletal muscle (Randle effect). Whether elevated FFA may play a role in decreasing carbohydrate oxidation during prolonged exercise in humans is more controversial. Using respiratory exchange measurements, we measured substrate utilization during 2.5 h of exercise at approximately 44 +/- 1% maximal O2 uptake (VO2 max) in the presence or absence of elevated FFA levels. After 30 min of base-line determinations, 1,000 U heparin was given intravenously and a 3-h constant infusion of Intralipid 10% (150 g/h) and heparin (500 U/h) was started. After an additional 30 min of rest, subjects exercised for 2.5 h (study 1, n = 6). In another five subjects (study 2) 100 g glucose was ingested after 30 min of exercise. The same protocols (studies 1 and 2) were also performed during a 0.9%-saline infusion. During exercise, without glucose ingestion, higher FFA concentrations prevailed during the Intralipid infusion (1,122 +/- 40 vs. 782 +/- 65 mumol/l), but the relative contributions of carbohydrate (49 +/- 4 vs. 50 +/- 4%) or lipid (49 +/- 4 vs. 47 +/- 6%) oxidation to the total energy expenditure were different only during the first 30 min of exercise. Similarly, higher FFA levels (1,032 +/- 62 vs. 568 +/- 46 mumol/l) did not alter the relative contributions of carbohydrate (62 +/- 4 vs. 69 +/- 2%) or lipid (36 +/- 4 vs. 29 +/- 2%) oxidation to the total energy expenditure after glucose feeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Absence of exercise-induced hypoglycaemia in type i (insulin-dependent) diabetic patients during maintenance of normoglycaemia by short-term, open-loop insulin infusion.

To assess the risk and possible mechanisms of hypoglycaemia during moderate exercise in Type I (insulin-dependent) diabetic patients receiving constant insulin infusion, five insulin-dependent male diabetic patients were exercised 18 h after their last meal and 30 h after their last injection of intermediate acting insulin. Intravenous insulin was initially delivered via a closed-loop infusion system programmed to lower mean blood glucose from 11.3 +/- 1.8 to 4.8 +/- 0.4 mmol/l over approximately 3.5 h. Blood glucose was then maintained at this level for 4 h. At this time, the closed-loop infusion was discontinued and replaced by an open-loop system. The average amount of insulin infused per min during the 4 h normoglycaemic closed-loop period was calculated and this amount was infused at a constant rate during both a 30 min period of exercise on a bicycle ergometer (approximately 65% maximum oxygen uptake) and a 30 min rest period which followed. Five nondiabetic males served as control subjects. Despite significantly higher free insulin concentrations (p less than 0.05) and identical pre-exercise blood glucose concentrations, blood glucose rose during exercise only in the diabetic group (0.5 +/- 0.2 mmol/l; p less than 0.01). Changes in the serum concentrations of lactate, glycerol, glucagon, cortisol, non-esterified fatty acids and growth hormone were similar in the two groups and did not account for the increment of blood glucose in the diabetic patients. Beta-hydroxybutyrate concentrations were, however, higher in the diabetic patients at the onset of exercise (p less than 0.01) and decreased significantly more than the control subjects during exercise. We conclude that exercise under these conditions in diabetic patients is not attended by hypoglycaemia.

Comparison of carbohydrate-containing and carbohydrate-restricted hypocaloric diets in the treatment of obesity. Endurance and metabolic fuel homeostasis during strenuous exercise.

UNLABELLED: Eight untrained, obese females (greater than 30% body fat), ages 25-33 yr, were studied before, at 1 wk, and after 6 wk while taking either of two 830-kcal/d diets: carbohydrate-containing (CC) group (n = 4): 35% protein, 29% fat, 36% carbohydrate-restricted (CR) group (n = 4): 35% protein, 64% fat, 1% carbohydrate. Endurance, at approximately 75% of VO2max (maximum oxygen uptake) on a cycle decreased from base line by 50% at 1 and 6 wk in the CR group, but there was no change in the CC group. Preexercise muscle glycogen (vastus lateralis) did not change significantly in the CC group, but was decreased by 49% in the CR group after 1 wk, and by 51% after 6 wk. There was a close correlation between percent decrease in resting muscle glycogen and percent decrease in endurance (r = 0.79, P less than 0.01). The mean fasting and exercise plasma glucose concentration was lower in the CR group than in the CC group after 6 wk, but no subject became hypoglycemic during exercise. Serum FFA, lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, insulin, and glucagon changed similarly in the two groups during exercise at base line, 1 and 6 wk. Glycerol concentration was higher in the CR group during exercise only after 6 wk. Increases in serum lactate concentrations, and a mean exercise respiratory quotient of 0.93 suggested that cycle exercise at approximately 75% VO2max used predominantly glucose as a fuel. CONCLUSIONS: Resting muscle glycogen and endurance, during cycle exercise at approximately 75% VO2max, were maintained during a 36% carbohydrate, 830-kcal/d diet. In contrast, significant decreases, occurred in resting muscle glycogen and endurance, during similar exercise, after 6 wk of a 1% carbohydrate, 830-kcal/d diet.

Capacity for moderate exercise in obese subjects after adaptation to a hypocaloric, ketogenic diet.

To study the capacity for moderate endurance exercise and change in metabolic fuel utilization during adaptation to a ketogenic diet, six moderately obese, untrained subjects were fed a eucaloric, balanced diet (base line) for 2 wk, followed by 6 wk of a protein-supplemented fast (PSF), which provided 1.2 g of protein/kg ideal body wt, supplemented with minerals and vitamins. The mean weight loss was 10.6 kg. The duration of treadmill exercise to subjective exhaustion was 80% of base line after 1 wk of the PSF, but increased to 155% after 6 wk. Despite adjusting up to base line, with a backpack, the subjects' exercise weight after 6 wk of dieting, the final exercise test was performed at a mean of 60% of maximum aerobic capacity, whereas the base-line level was 76%. Resting vastus lateralis glycogen content fell to 57% of base line after 1 wk of the PSF, but rose to 69% after 6 wk, at which time no decrement in muscle glycogen was measured after >4 h of uphill walking. The respiratory quotient (RQ) during steady-state exercise was 0.76 during base line, and fell progressively to 0.66 after 6 wk of the PSF. Blood glucose was well maintained during exercise in ketosis. The sum of acetoacetate and beta hydroxybutyrate rose from 3.28 to 5.03 mM during exercise after 6 wk of the PSF, explaining in part the low exercise RQ. The low RQ and the fact that blood glucose and muscle glycogen were maintained during exhausting exercise after 6 wk of a PSF suggest that prolonged ketosis results in an adaptation, after which lipid becomes the major metabolic fuel, and net carbohydrate utilization is markedly reduced during moderate but ultimately exhausting exercise.