Quantum Critical Point in the Itinerant Ferromagnet Ni_{1-x}Rh_{x}.

We report a chemical substitution-induced ferromagnetic quantum critical point in polycrystalline Ni_{1-x}Rh_{x} alloys. Through magnetization and muon spin relaxation measurements, we show that the ferromagnetic ordering temperature is suppressed continuously to zero at x_{crit}=0.375 while the magnetic volume fraction remains 100% up to x_{crit}, pointing to a second order transition. Non-Fermi liquid behavior is observed close to x_{crit}, where the electronic specific heat C_{el}/T diverges logarithmically, while immediately above x_{crit} the volume thermal expansion coefficient α_{V}/T and the Grüneisen ratio Γ=α_{V}/C_{el} both diverge logarithmically in the low temperature limit, further indication of a ferromagnetic quantum critical point in Ni_{1-x}Rh_{x}.

Magnetic and Structural Quantum Phase Transitions in CeCu_{6-x}Au_{x} are Independent.

The heavy-fermion compound CeCu_{6-x}Au_{x} has become a model system for unconventional magnetic quantum criticality. For small Au concentrations 0≤x<0.16, the compound undergoes a structural transition from orthorhombic to monoclinic crystal symmetry at a temperature T_{s} with T_{s}→0 for x≈0.15. Antiferromagnetic order sets in close to x≈0.1. To shed light on the interplay between quantum-critical magnetic and structural fluctuations we performed neutron-scattering and thermodynamic measurements on samples with 0≤x≤0.3. The resulting phase diagram shows that the antiferromagnetic and monoclinic phase coexist in a tiny Au concentration range between x≈0.1 and 0.15. The application of hydrostatic and chemical pressure allows us to clearly separate the transitions from each other and to explore a possible effect of the structural transition on the magnetic quantum-critical behavior. Our measurements demonstrate that at low temperatures the unconventional quantum criticality exclusively arises from magnetic fluctuations and is not affected by the monoclinic distortion.

Vascular complication after percutaneous femoral cerclage wire.

Cerclage wire is an effective fracture fixation method. However, its mechanical benefits are countered by local ischemia. Its efficacy for treating femoral periprosthetic fractures has been demonstrated since femoral fixation is possible even there is a stem in the diaphysis. It securely holds the proximal femur typically with an additional plate. The development of minimally-invasive surgery with plate fixation has led to the cerclage wire being inserted percutaneously. Here, we report on a case of secondary femoral ischemia following percutaneous cerclage wire of a periprosthetic femoral fracture. This was a Vancouver type B1 fracture. On the 3rd day after admission, minimally-invasive fixation with a femoral locking plate was performed with five cerclage wires added percutaneously. During the immediate postoperative course, the patient developed ischemia of the operated leg that required vascular surgery after confirmation by CT angiography. An arterial stop was visible with deviation of the superior femoral artery, which was not properly surrounded by the cerclage wire. The latter pulled perivascular tissues towards the femur. When combined with reduced arterial elasticity due to severe atherosclerosis, it resulted in arterial plication. The postoperative course was marked by multiple organ failure and death of the patient. Percutaneous surgery is an attractive option but has risks. The presence of severe atherosclerosis is a warning sign for loss of tissue elasticity. This complication can be prevented by preparing the bone surfaces and carefully positioning the patient on the traction table to avoid forced adduction. The surgeon must also be familiar with alternative techniques to cerclage wire such as polyaxial screws and additional plates.

Biliary copper excretion by hepatocyte lysosomes in the rat. Major excretory pathway in experimental copper overload.

We investigated the hypothesis that lysosomes are the main source of biliary copper in conditions of hepatic copper overload. We used a rat model of oral copper loading and studied the relationship between the biliary output of copper and lysosomal hydrolases. Male Sprague-Dawley rats were given tap water with or without 0.125% copper acetate for up to 36 wk. Copper loading produced a 23-fold increase in the hepatic copper concentration and a 30-65% increase in hepatic lysosomal enzyme activity. Acid phosphatase histochemistry showed that copper-loaded livers contained an increased number of hepatocyte lysosomes; increased copper concentration of these organelles was confirmed directly by both x ray microanalysis and tissue fractionation. The copper-loaded rats showed a 16-fold increase in biliary copper output and a 50-300% increase in biliary lysosomal enzyme output. In the basal state, excretory profiles over time were similar for biliary outputs of lysosomal enzymes and copper in the copper-loaded animals but not in controls. After pharmacologic stimulation of lysosomal exocytosis, biliary outputs of copper and lysosomal hydrolases in the copper-loaded animals remained coupled: injection of colchicine or vinblastine produced an acute rise in the biliary output of both lysosomal enzymes and copper to 150-250% of baseline rates. After these same drugs, control animals showed only the expected increase in lysosomal enzyme output without a corresponding increase in copper output. We conclude that the hepatocyte responds to an increased copper load by sequestering excess copper in an increased number of lysosomes that then empty their contents directly into bile. The results provide direct evidence that exocytosis of lysosomal contents into biliary canaliculi is the major mechanism for biliary copper excretion in hepatic copper overload.

Alterations in the structure, physicochemical properties, and pH of hepatocyte lysosomes in experimental iron overload.

While hemochromatosis is characterized by sequestration of iron-protein complexes in hepatocyte lysosomes, little is known about the effects of excess iron on these organelles. Therefore, we studied the effects of experimental iron overload on hepatocyte lysosomal structure, physicochemical properties, and function in rats fed carbonyl iron. A sixfold increase (P less than 0.0001) in hepatic iron and a fivefold increase in lysosomal iron (P less than 0.01) was observed after iron loading; as a result, hepatocyte lysosomes became enlarged and misshapen. These lysosomes displayed increased (P less than 0.0001) fragility; moreover, the fluidity of lysosomal membranes isolated from livers of iron-loaded rats was decreased (P less than 0.0003) as measured by fluorescence polarization. Malondialdehyde, an end product of lipid peroxidation, was increased by 73% (P less than 0.008) in lysosomal membranes isolated from livers of iron-overloaded rats. While amounts of several individual fatty acids in isolated lysosomal membranes were altered after iron overload, cholesterol/phospholipid ratios, lipid/protein ratios, double-bond index, and total saturated and unsaturated fatty acids remained unchanged. The pH of lysosomes in hepatocytes isolated from livers of iron-loaded rats and measured by digitized video microscopy was increased (control, 4.70 +/- 0.05; iron overload, 5.21 +/- 0.10; P less than 0.01). Our results demonstrate that experimental iron overload causes marked alterations in hepatocyte lysosomal morphology, an increase in lysosomal membrane fragility, a decrease in lysosomal membrane fluidity, and an increase in intralysosomal pH. Iron-catalyzed lipid peroxidation is likely the mechanism of these structural, physicochemical, and functional disturbances.

Female-enriched and thermosensitive expression of steroidogenic factor-1 during gonadal differentiation in Pleurodeles waltl.

In the urodele amphibian Pleurodeles waltl, sex differentiation is genetically controlled, that is, ZZ male vs ZW female, but may be influenced by temperature, which induces a female-to-male sex reversal. We investigated whether steroidogenic factor 1 (SF-1) could be involved in Pleurodeles sex differentiation or in temperature-dependent sex reversal by cloning a Pleurodeles SF-1 cDNA and examining its developmental expression. The 468-amino-acid deduced protein is highly conserved in comparison with other species. In ZZ and ZW control larvae, SF-1 mRNA is detected at the first stage of the thermosensitive period (TSP) in the gonad-mesonephros-interrenal complex (GMI). By the end of TSP at stage 55, SF-1 is expressed in the gonad (Gd) and in the mesonephros-interrenal (MI) both in ZZ and ZW larvae. During this stage, a transient, ZW-specific increase of SF-1 transcription occurs not only in Gd but also in MI, this increase starting earlier in Gd than in MI. Therefore, in P. waltl, an SF-1 upregulation occurs after the onset of the ovarian-specific increase of aromatase mRNA expression. At the end of metamorphosis, the SF-1 transcription level in Gd and MI is nearly the same in both ZZ and ZW larvae. Besides, after long-term heat treatment leading to sex reversal, SF-1 mRNA upregulation is not observed in ZW larvae, in either Gd or MI. However, SF-1 expression is not decreased after a 48-h heat shock applied at the end of the TSP, suggesting that temperature has no inhibitory effect by itself in long-term heat treatment. Estradiol benzoate treatments show that, at the end of the TSP, SF-1 gene transcription could be controlled by the estrogen level. This is in accordance with the female-enriched SF-1 expression and the decreased SF-1 expression following long-term, sex-reversing heat treatment, which is known to decrease aromatase expression and activity. Thus, it is unlikely that SF-1 is directly involved in Pleurodeles temperature-dependent sex reversal.

Dietary flavone is a potent apoptosis inducer in human colon carcinoma cells.

Flavonoids are polyphenolic compounds that occur ubiquitously in plants. They are discussed to represent cancer preventive food components in a human diet that is rich in fruits and vegetables. To understand the molecular basis of the putative anticancer activity of flavonoids, we investigated whether and how the core structure of the flavones, 2-phenyl-4H-1-benzopyran-4-one (flavone) affects proliferation, differentiation, and apoptosis in HT-29 human colon cancer cells. Moreover, the effects of flavone in transformed epithelial cells were compared with those obtained in nontransformed primary mouse colonocytes. Proliferation, differentiation, and apoptosis in transformed as well as nontransformed colon cells were measured by fluorescence-based techniques. Apoptosis was also determined by changes in membrane permeability, FACScan analysis, and detection of DNA fragmentation. Semiquantitative reverse transcription PCR was performed to assess the effects of flavone on transcript levels. Flavone was found to reduce cell proliferation in HT-29 cells with an EC(50) value of 54.8 +/- 1.3 microM and to potently induce differentiation as well as apoptosis. The flavonoid proved to be a stronger apoptosis inducer than the clinically established antitumor agent camptothecin. The effects of flavone in HT-29 cells were associated with changed mRNA levels of cell-cycle- and apoptosis-related genes including cyclooxygenase-2 (COX-2), nuclear transcription factor kappaB (NF-kappaB), and bcl-X(L). Moreover, flavone, but not camptothecin, displayed a high selectivity for the induction of apoptosis and of growth inhibition only in the transformed colonocytes. In conclusion, the plant polyphenol flavone induces effectively programmed cell death, differentiation, and growth inhibition in transformed colonocytes by acting at the mRNA levels of genes involved in these processes. Because these genes play a crucial role in colon carcinogenesis, flavone may prove to be a potent new cytostatic compound with improved selectivity toward transformed cells.

Light, electron, and confocal microscopic study of the mouse superior mesenteric ganglion.

The superior mesenteric ganglion (S.m.g.), a sympathetic prevertebral ganglion, is an integrating center for gastrointestinal reflexes. Many details of its structure are still lacking. In the present study, mouse S.m.g. neurons were studied by light, electron, and confocal microscopy. Neurons had an average of 5-6 primary dendrites. Total dendritic length averaged 963 microns. Confocal microscopy and three-dimensional reconstructed images revealed cell body surface features, precise location where axons and dendrites emerged from it, cell body size, and extent of dendritic projection in three axes. Cell body diameter and dendritic projections were less in the dorsoventral than in the rostrocaudal or mediolateral axes. Cell body surface area and volume averaged 4,271 microns 2 and 4,908 microns 3, respectively. Dendritic surface areas and volumes were 5-6 times larger. Two main neuron types (projecting caudally or rostrally) were distinguished. The former were found throughout the S.m.g., whereas the latter were found only in the cephalad region, comprising about 40% of neurons found there. Rostrally projecting neurons had fewer primary dendrites, fewer total dendritic branches, and shorter total dendritic length than caudally projecting neurons. There were regional differences in percentage of neurons responding to electrical stimulation of left or right hypogastric, lumbar colonic, or left splanchnic nerves but not in nerve fibers connecting the S.m.g. and celiac ganglion. A greater percentage of caudally than rostrally projecting cephalad neurons responded to stimulation of any nerve trunk. These results indicate that the mouse S.m.g. contains at least two distinct types of neurons that differ in their morphology and their source of preganglionic synaptic input.

Steroids, aromatase and sex differentiation of the newt Pleurodeles waltl.

In the newt Pleurodeles waltl, genetic sex determination obeys female heterogamety (female ZW, male ZZ). In this species as in most of non-mammalian vertebrates, steroid hormones play a key role in sexual differentiation of gonads. In that context, male to female sex reversal can be obtained by treatment of ZZ larvae with estradiol. Male to female sex reversal has also been observed following treatment of ZZ larvae with testosterone, a phenomenon that was called the "paradoxical effect". Female to male sex reversal occurs when ZW larvae are reared at 32 degrees C during a thermosensitive period (TSP) that takes place from stage 42 to stage 54 of development. Since steroids play an important part in sex differentiation, we focussed our studies on the estrogen-producing enzyme aromatase during normal sex differentiation as well as in experimentally induced sex reversal situations. Our results based on treatment with non-aromatizable androgens, aromatase activity measurements and aromatase expression studies demonstrate that aromatase (i) is differentially active in ZZ and ZW larvae, (ii) is involved in the paradoxical effect and (iii) might be a target of temperature. Thus, the gene encoding aromatase might be one of the master genes in the process leading to the differentiation of the gonad in Pleurodeles waltl.

Increased expression of the lymphocyte early activation marker CD69 in peripheral blood correlates with histologic evidence of cardiac allograft rejection.

BACKGROUND: The human leukocyte membrane protein CD69 is an early activation marker induced in T lymphocytes, B cells, and natural killer cells in response to inflammatory stimuli. Cardiac catheterization and endomyocardial biopsy remain the "gold standard" for diagnosis of rejection after transplantation, and noninvasive methods of rejection surveillance have long been sought. We studied CD69 membrane protein expression in peripheral blood T lymphocytes obtained from pediatric cardiac transplant recipients at the time of biopsy and correlated the results with histologic rejection scores. METHODS: Heparinized whole blood samples were obtained from pediatric cardiac transplant recipients at the time of cardiac biopsy, as well as from control subjects. Lymphocytes were labeled with antibodies for CD3, CD4, CD8, and CD69 and analysis performed using flow cytometric methods. RESULTS: Resting CD69 expression (measured as a percentage of gated events) was significantly increased in patients with concurrent histologic evidence of rejection (International Society for Heart and Lung Transplantation grade > or =3A) when compared to those with minimal or no rejection and controls. Although statistically significant for both lymphocyte subsets, this relationship was more pronounced for CD8+ T cells (P<0.001) than for CD4+ T cells (P=0.001). When data were analyzed by rejection score, a percentage activation of the CD8+ subset (CD69+/CD8+ cells as a percentage of total gated events) exceeding 15% correlated with significant rejection. CONCLUSIONS: Measurement of the expression of the early activation marker CD69 in peripheral blood lymphocytes by flow cytometry may provide a noninvasive means of assessing immune activation and possible rejection in cardiac transplant recipients.

M-mode analysis of mitral annulus motion for detection of pseudonormalization of the mitral inflow pattern.

Left ventricular (LV) diastolic dysfunction is a frequent cause of heart failure. Doppler echocardiography has become the method of choice for the noninvasive evaluation of LV diastolic dysfunction. However, pseudonormalization of mitral inflow often presents a diagnostic problem in clinical practice. We sought to define the role of mitral annulus motion in this setting. We performed echocardiography in 36 consecutive subjects (age 59 +/- 10 years). Eighteen had recently (within 3 months) been diagnosed with coronary artery disease, 18 had clinical suspicion of coronary artery disease, and 15 had symptoms of heart failure (New York Heart Association class 2.4 +/- 0.5). The amplitude (E(M)) and the slope (slope E) of early diastolic motion of the septal mitral annulus were derived from M-mode analysis. Left heart catheterization was performed for direct measurement of LV end-diastolic pressure. Pseudonormalization defined by an E/A ratio > 1 and a LV end-diastolic pressure > or = 16 mm Hg was found in 9 patients. All patients with pseudonormalization were symptomatic (New York Heart Association class 2.8 +/- 0.5). Patients with and without pseudonormalization did not differ with respect to the E/A ratio (1.29 +/- 0.44 vs 1.16 +/- 0.23, p = NS), deceleration time (182 +/- 38 vs 205 +/- 42 ms, p = NS), and isovolumic relaxation time (88 +/- 24 vs 92 +/- 18 ms, p = NS). In the group with pseudonormalization, a significant reduction of E(M) (3.9 +/- 1.6 vs 5.7 +/- 1.5 mm, p = 0.008) and slope E (24.5 +/- 11.8 vs 43.9 +/- 7.7 mm/s, p <0.001) was detected. Using E(M) <4.3 mm and slope E <35 mm/s as cut points, sensitivity and specificity for the detection of pseudonormalization were 66% and 82% for E(M) and 77% and 87% for slope E, respectively. There was no significant relation between LV end-diastolic pressure as a measure of preload and either E(M) (r = 0.44, p >0.5) or slope E (r = 0.30, p >0.2). Thus, E(M) and slope E may be preload-independent tools for assessing LV diastolic dysfunction in symptomatic patients with a pseudonormal mitral inflow pattern and elevated filling pressures.

Differential expression of P450 aromatase during gonadal sex differentiation and sex reversal of the newt Pleurodeles waltl.

A better understanding of vertebrate sexual differentiation could be provided by a study of models in which genetic sex determination (GSD) of gonads can be reversed by temperature. In the newt Pleurodeles waltl, a P450 aromatase cDNA was isolated from adult gonads, and the nucleotide or deduced amino acid sequences showed a high level of identity with various vertebrate species. In adults, aromatase expression was found in gonads and brain. In developing gonads, the expression was found to fit with the thermo-sensitive period (TSP) and was detected in both ZZ and ZW larvae, as well as in ZW submitted during the whole TSP to a masculinizing temperature. In the latter individuals, in situ hybridization and semi quantitative RT-PCR showed that, at the end of TSP, aromatase expression was at the same level than in normal ZZ larvae and was significantly lower than in normal ZW ones. Furthermore, temperature-induced down regulation did not occur when heating was performed at the end of TSP. Our results confirm the importance of aromatase regulation in female versus male differentiation and demonstrate that a down regulation of aromatase expression is involved in the process of sex reversal.

Challenges in research with incarcerated parents and importance in violence prevention.

Incarcerated parents present several risk factors for later violence by their children. This study uses comparison groups and repeated measures to evaluate an inmate parenting program. Subjects are inmates at a county detention center, their children, and primary caregivers. Challenges to program implementation and longitudinal research with inmates were identified, along with recommendations to assist future research and programming. Training material should use illustrated, basic language format. Acceptance and participation by inmates and staff require ongoing outreach and communication. Severed relationships are common and future research on inmates with stable family relationships is recommended. Because of inmate transience, integrating parent training into post-release programming is suggested.

Stimulated acoustic emission: pseudo-Doppler shifts seen during the destruction of nonmoving microbubbles.

The purpose of this study was to evaluate the appearance and the characteristics of stimulated acoustic emission (SAE) as an echo contrast-specific color Doppler phenomenon with impact on myocardial contrast echocardiography (MCE). Stationary microbubbles of the new contrast agent SH-U 563A (Schering AG) were embedded within a tissue-mimicking gel material. Harmonic power Doppler imaging (H-PDI), color Doppler and pulse-wave Doppler data were acquired using an HDI-5000 equipped with a phased-array transducer (1.67/3.3 MHz). In color Doppler mode, bubble destruction resulted in random noise like Doppler signals. PW-Doppler revealed short "pseudo-Doppler" shifts with a broadband frequency spectrum. Quantification of SAE events by H-PDI demonstrated an exponential decay of signal intensities over successive frames. A strong linear relationship was found between bubble concentration and the square root of the linearized H-PDI signal for a range of concentrations of more than two orders of magnitude (R = 0.993, p < 0.0001). Intensity of the H-PDI signals correlated well with emission power (R = 0.96, p = 0.0014). SAE results from disintegration of microbubbles and can be demonstrated by all Doppler imaging modalities, including H-PDI. Intensity of SAE signals is influenced by the applied acoustic power and correlates highly with the concentration of microbubbles. Because intensity of SAE signals correlates highly with echo contrast concentrations, analysis of SAE signals might be used for quantitative MCE.

Effect of cadmium on gonadogenesis and metamorphosis in Pleurodeles waltl (urodele amphibian).

In the amphibian Pleurodeles waltl, steroid hormones play a key role in sex differentiation. Since cadmium has been reported to block receptors of sex steroid hormones, we analyzed the effects of this heavy metal on Pleurodeles larvae gonadogenesis. At stage 42, larvae die in the presence of 10.9 microM Cd in the rearing tap water, with TL(50) of 46.3 h, but the concentration of 5.5 microM is tolerated for more than 60 days. When used at 5.5 microM cadmium accumulation measured by atomic absorption spectrophotometry (AAS) in total homogenates of larvae at stage 54 (after 77 days of exposure to the heavy metal) reached 58.1 microg/g of dry weight. At stage 54, we did not detect inhibitory effects on gonadogenesis in larvae reared in the presence of 5.5 microM Cd since stage 42. When the exposure to 5.5 microM Cd was lengthened after stage 54, metamorphosis was delayed and could not be completed. When larvae were exposed to 10.9 microM Cd from stage 54, metamorphosis did not occur and gonad development was stopped. Our study demonstrates a lack of a direct effect of cadmium on sex determination-differentiation but a strong inhibitory effect on metamorphosis, which impairs further gonadal development.

[Heart failure as a cardiac symptom of sarcoidosis. Successful treatment of heart failure with steroids, digitalis and an angiotensin-1-receptor antagonist in sarcoidosis]. / Herzinsuffizienz als kardiale Manifestation einer Sarkoidose. Erfolgreiche Therapie der Herzinsuffizienz mit Steroiden, Digitalis und einem Angiotensin-1-Rezeptor-Antagonisten bei Sarkoidose.

BACKGROUND: Sarcoidosis is a multisystemic disorder that may involve every organ. A symptomatic manifestation of the myocardium is possible, in these cases arrhythmias are the most common symptoms. CASE REPORT: This case report presents a 26-year-old female with the recurrence of Boeck's sarcoid. Fever, chill and a severe reduction in stress tolerance were the first symptoms. At the time of admission she complained of Grade III dyspnea according to the NYHA classification. The echocardiogram showed a severe impairment of the global and left ventricular function. The left ventricular ejection fraction was reduced to 30% and the Tei index was elevated to 1.0. A specimen taken from a mediastinal tumor confirmed the hypothesis of the recurrence of the sarcoidosis. Myocardial perfusion scintigraphy showed typical lesions for myocardial sarcoidosis. There were signs of an old anteroseptal infarction in the resting ECG without evidence of myocardial ischemia during a stress test. Repeated Holter-ECGs were without signs of severe arrhythmias whereas ventricular late potentials were positive. After the combined therapy with steroids, digitalis and an angiotensin-1 receptor antagonist, mediastinal mass and Tei index were reduced and the ejection fraction moved to 56%. Dyspnoea was classified with Grade II according to the NYHA classification. CONCLUSION: Treatment of asymptomatic sarcoidosis is still controversial, whereas the treatment of life-threatening sarcoidosis, eye involvement or severe hypercalcemia is accepted. This case report presents the successful treatment of severe heart failure with prednisone, glycosides and an angiotensin-1 receptor antagonist. With this combined therapy an improvement of subjective and objective parameters was possible.