Premature termination of hair follicle morphogenesis and accelerated hair follicle cycling in Iasi congenital atrichia (fzica) mice points to fuzzy as a key element of hair cycle control

Inbred laboratory mice have proven to be useful model systems for studying hair biology and pathomechanisms of hair loss. Fuzzy (fz) is an autosomal recessive mutation that results in hair coat abnormalities. Though this mutant has long been known, its cutaneous abnormalities still await systematic analysis. Here, we provide a systematic skin phenotype analysis of mice that are homozygous for Iasi congenital atrichia (fzica/fzica), which is allelic to fz. Homozygous mice exhibit a sparse hair coat after birth and completely loose their hair at around postnatal day 120. Although early and mid stages of hair follicle morphogenesis are normal, late hair follicle morphogenesis reveals multifocal cell degeneration within the Huxley layer of the inner root sheath (IRS) and a complete lack of the hair shaft medulla. In addition, hair follicle development is prematurely terminated by induction of the first postnatal hair cycle with premature entry into catagen. Subsequently, a dramatically shortened telogen is immediately followed by premature anagen development, resulting in a marked, generalized acceleration of hair follicle cycling. This suggests that fuzzy is not only involved in structural hair shaft integrity and differentiation of the IRS and medulla, but also plays an important role in the control of hair follicle cycling. Our data show that fuzzy is involved in controlling both catagen and anagen initiation, designating fuzzy an exciting target for characterizing the intracutaneous oscillator system that drives hair follicle cycling.     

Progressive differentiation of human sebocytes in vitro is characterized by increasing cell size and altering antigen expression and is regulated by culture duration and retinoids

Abstract Increasing cell size, lipid accumulation, and altered antigen expression are features of sebaceous differentiation in vivo. Enhanced lipid synthesis with progressive differentiation is also present in cultured human sebocytes. This study was conducted to investigate the evolution of cell size and antigen expression of human sebocyles with progressive differentiation in vitro. Subconlluent human sebocyte cultures were examined for sebocyte differentiation evaluated on cytocentrifuge preparations by light microscopy and classified in stages according to morphological criteria described for sebocytes in vivo. Rates of 5.1 ±2. 2% undifferentiated sebocytes. 29.2 ±4.9% early differentiated, 20.7 ±4.1% advanced differentiated, 37.6±6.4% fully differentiated, and 5.9± 1.9% mature sebocytes were calculated in secondary cultures. The size of cultured sebocytes measured by computer-assisted planimetry significantly increased with progressive differentiation up to 4-5.5 times. The low rates of mature sebocytes and the only moderate increase of their size with progressive differentiation indicate an incomplete terminal differentiation in vitro. Sebocytes were subsequently stained with a series of monoclonal antibodies (mAb) to determine antigen expression using the alkaline phosphatase anti-alkaline phosphatase technique. The number of sebocytes labeled with the anti-keratin mAb CK8.12 and KLI, and the mAb 34DII (82 kD protein) increased with progressive differentiation; significant differences were found after comparing early and advanced differentiated sebocytes. Sebocytes were positively stained with the anti-keratin mAb 6BIO (K 4). RPNI162 (K 7), CK.I3 (K 13), RPNI165 (K 19). CK.8.60, and the mAb 115F5 (MAM-6c). OM-I (sebaceous gland antigen), and 24F10 (basic polypeptides) only at late-stage differentiation. The expression of keratins 4, 7, 13, and 19 was confirmed by gel electrophoresis and immunoblotting. The data obtained were used to study the effects of the duration of cultivation and of the retinoids isotretinoin and tretinoin on sebocyte differentiation in vitro. Subcultivalion of sebocytes upregulaled, and treatment with isotretinoin but not with tretinoin downregulated labeling with mAb which recognize indicating progressive and late-stage differentiation.     

Are anti-Chlamydia pneumoniae antibodies prognosis indicators for peripartum cardiomyopathy?

BACKGROUND: The authors recently pointed out an epidemiological relation between specific anti-Chlamydia pneumoniae antibodies and peripartum cardiomyopathy in Niamey (Republic of Niger). DESIGN: In this work, they studied the prognosis value of such specific antibodies. METHODS: The serological status for specific IgG, IgA and IgM anti-C. pneumoniae antibodies of 50 African women (age, mean+/-SD = 30.2 +/- 7 years) hospitalized in Niamey, with peripartum cardiomyopathy, was determined at the time of diagnosis. The diagnosis was categorized as 'complete remission' (13 patients, age = 29.3 +/- 6.5 years, observation delay = 27 months), 'incomplete remission' (27 patients, age = 30.7 +/- 7.6 years, observation delay = 14 months) and 'deceased' (10 patients, age = 30.3 +/- 6.2 years, observation delay = 13 months). The control group comprised 27 African women (age = 25.2 +/- 4.6 years), living in the same area. The Mann-Whitney and Fisher's exact tests were used for the statistical comparison. RESULTS: The dilution of IgG specific anti-C. pneumoniae antibodies was higher (P = 0.047) in the 'incomplete remission' compared with 'complete remission'. The dilution of IgA specific anti-C. pneumoniae antibodies was higher (P = 0.033) in the patients with a severe evolution ('deceased' + 'incomplete remission') compared with 'complete remission'. There was no significant difference between patients in 'complete remission' compared with 'controls'. CONCLUSIONS: At the time of peripartum cardiomyopathy diagnosis the specific IgG and IgA anti-C. pneumoniae antibodies are of prognosis value: a high dilution is more often associated with a poor prognosis. This is the first identified prognosis factor during the precocious evolution of peripartum cardiomyopathy.     

Diagnostic criteria in predicting a biliary origin of acute pancreatitis in the era of endoscopic ultrasound: multicentre prospective evaluation of 213 patients.

BACKGROUND: No study on bioclinical criteria predicting a biliary origin for acute pancreatitis has included endosonography as a reference examination. Re-examination of bioclinical parameters deserves consideration in the era where other causes are known (e.g. hereditary, autoimmune). AIM AND METHODS: To determine the performance of bioclinical markers in predicting a biliary origin of acute pancreatitis where the diagnosis of biliary lithiasis was established or ruled out using endosonography. Only patients with a first acute episode of pancreatitis were included. RESULTS: 213 patients (male: 55%; median age: 56 years) were prospectively included in 14 centres. Causes of acute pancreatitis were: biliary (62%), alcoholic (25%), other (13%). Delay between symptom-onset and admission was <48 h in 80%. Endosonography was the sole method establishing the diagnosis of biliary pancreatitis in 15% of patients. At univariate analysis, age, female sex, declared alcohol consumption, elevated aspartate and alanine transaminases on admission, gammaglutamyl transferase, alkaline phosphatase, total bilirubin, lipase, mean corpuscular volume were predictive of a biliary origin. Only age (p < 0.0001), sex (p < 0.0008) and alanine transaminase (p < 0.0004) remained significant at multivariate analysis. At age 50, the respective sensitivity and specificity were 73 and 65%. With an elevated alanine transaminase at 2 times the upper limit of normal range, the respective sensitivity and specificity were 74 and 84%. The probability of a biliary origin of acute pancreatitis could be estimated by the following formula: = 1/1 + exp(4.6967 - 0.0656 x age + 1.1208 x sex - 0.6909 x alanine transaminase). CONCLUSION: When endosonography is performed to confirm or exclude a biliary origin of acute pancreatitis, age, sex and alanine transaminase at admission are the only factors predictive of a biliary cause.     

L-carnitine supplementation and physical exercise restore age-associated decline in some mitochondrial functions in the rat

In mammals, during the aging process, an atrophy of the muscle fibers, an increase in body fat mass, and a decrease in skeletal muscle oxidative capacities occur. Compounds and activities that interact with lipid oxidative metabolism may be useful in limiting damages that occur in aging muscle. In this study, we evaluated the effect of L-carnitine and physical exercise on several parameters related to muscle physiology. We described that supplementing old rats with L-carnitine at 30 mg/kg body weight for 12 weeks (a) allowed the restoration of L-carnitine level in muscle cells, (b) restored muscle oxidative activity in the soleus, and (c) induced positive changes in body composition: a decrease in abdominal fat mass and an increase in muscle capabilities without any change in food intake. Moderate physical exercise was also effective in (a) limiting fat mass gain and (b) inducing an increase in the capacities of the soleus to oxidize fatty acids.     

Effect of bipolar electrode orientation on local electrogram properties

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Diagnostic approaches to suspected deep vein thrombosis and pulmonary embolism

The present paper aims at reviewing our present knowledge on the diagnosis of deep vein thrombosis and pulmonary embolism with a particular emphasis on clinically suspected outpatients. The various contemporary diagnostic tools (including clinical probability assessment, fibrin D-Dimer measurement, venous compression ultrasonography, ventilation/perfusion lung scintigraphy, helical CT scan, and echocardiography) are presented and rational sequential strategies are discussed in their various aspects, including validation in outcome studies, and cost-effectiveness analyses.     

Successful heart transplantation following melphalan plus dexamethasone therapy in systemic AL amyloidosis

Recurrence in the allograft and progression in other organs increase mortality after cardiac transplantation in AL amyloidosis. Survival may be improved after suppression of monoclonal light chain (LC) production following high dose melphalan and autologous stem cell transplantation (HDM/ASCT). However, because of high treatment related mortality, this tandem approach is restricted to few patients without significant extra-cardiac involvement. A diagnosis of systemic AL amyloidosis was established in a 45-year old patient with congestive heart failure related to restrictive cardiomyopathy, nephrotic syndrome, peripheral neuropathy, postural hypotension, macroglossia, and lambda LC monoclonal gammopathy. After melphalan and dexamethasone (M-Dex) therapy, which resulted in 80% reduction of serum free lambda LC, he underwent orthotopic cardiac transplantation. Two years later, he remains in a sustained hematologic remission, with no evidence of allograft or extra-cardiac amyloid accumulation. M-Dex should be considered as an alternative therapy in AL amyloid heart transplant recipients ineligible for HDM/ASCT.     

Inflammation,a link between obesity and atrial fibrillation

Inflammation Research - Despite the long belief that the role of the adipose tissue was restricted to that of a passive store of triglycerides and a rich source of fatty acids, accumulating data...