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At least 631 records · Page 35Linked to original sources
PubMed2005

Mechanism of actin-based motility: a dynamic state diagram.

Cells move by a dynamical reorganization of their cytoskeleton, orchestrated by a cascade of biochemical reactions directed to the membrane. Designed objects or bacteria can hijack this machinery to undergo actin-based propulsion inside cells or in a cell-like medium. These objects can explore the dynamical regimes of actin-based propulsion, and display different regimes of motion, in a continuous or periodic fashion. We show that bead movement can switch from one regime to the other, by changing the size of the beads or the surface concentration of the protein activating actin polymerization. We experimentally obtain the state diagram of the bead dynamics, in which the transitions between the different regimes can be understood by a theoretical approach based on an elastic force opposing a friction force. Moreover, the experimental characteristics of the movement, such as the velocity and the characteristic times of the periodic movement, are predicted by our theoretical analysis.

Actins↗
PubMed2005

Cortical actomyosin breakage triggers shape oscillations in cells and cell fragments.

Cell shape and movements rely on complex biochemical pathways that regulate actin, microtubules, and substrate adhesions. Some of these pathways act through altering the cortex contractility. Here we examined cellular systems where contractility is enhanced by disassembly of the microtubules. We found that adherent cells, when detached from their substrate, developed a membrane bulge devoid of detectable actin and myosin. A constriction ring at the base of the bulge oscillated from one side of the cell to the other. The movement was accompanied by sequential redistribution of actin and myosin to the membrane. We observed this oscillatory behavior also in cell fragments of various sizes, providing a simplified, nucleus-free system for biophysical studies. Our observations suggest a mechanism based on active gel dynamics and inspired by symmetry breaking of actin gels growing around beads. The proposed mechanism for breakage of the actomyosin cortex may be used for cell polarization.

Actins↗
PubMed1996

Follow-up of bone mineral density in 27 cases of anorexia nervosa.

Cortical and trabecular bone loss can lead to osteoporosis in chronic forms of anorexia nervosa (AN). As there is some debate about the reversibility of this condition, we performed a longitudinal follow-up study of 27 cases in which clinical, biological, X-ray and lumbar and femoral neck dual photon absorptiometry examinations were conducted every 6 months for up to 30 months. Three groups were distinguished: G1, untreated amenorrheic AN (N = 14, total follow-up 126 months); G2, effectively treated AN (N = 11, total follow-up 192 months), with two subgroups: fluoride (N = 5) and estrogen (N = 6); and G3, remitting AN with normalization of the gonadic function (N = 2, total follow-up 36 months). Results were adjusted for each patient to a 6-month variation. Semestrial variations in lumbar bone mineral density (BMD) were -2.1 +/- 1.3%, +2.8 +/- 1.5%, and -0.3 +/- 1.3% (mean +/- SEM), respectively for G1, G2 and G3; those for femoral neck BMD semestrial variations were -5.9 +/- 2.1%, -3.8 +/- 1.2% and -1.0 +/- 0.6%. Femoral neck and lumbar BMD variations for G1 were mainly correlated positively with bone-forming markers (serum osteocalcin, alkaline phosphatase) and negatively with initial lumbar BMD. Estrogen alone increased lumbar BMD by +1.4 +/- 2.3% every 6 months but did not stabilize femoral neck BMD (-3.5 +/- 1.4%). Fluoride increased lumbar BMD by 4.8 +/- 1.8%. Both lumbar and femoral neck BMD were stabilized in the remission group (-0.3 +/- 1.3% and -1.0 +/- 0.6%), despite half of the follow-up time with amenorrhea. In conclusion, untreated AN is associated with a marked trabecular and cortical bone loss (4-10% per year), which can lead to osteoporotic fractures. In prevention of bone loss, the efficacy of estrogen is difficult to investigate in AN, even with a well-controlled trial. Our study could provide argument that, when the observance of this preventive treatment is assessed, lumbar BMD can be stabilized in chronic forms of AN.

Absorptiometry, Photon↗
PubMed1986

Culture of epithelial and stromal cells of guinea-pig endometrium and the effect of oestradiol-17 beta on the epithelial cells.

Epithelial and stromal cells of guinea-pig endometrium were separated by enzymic digestion, isolated by successive centrifugation, and maintained in culture as pure cell types for 5 days on growth medium. On Day 5, ultrastructural studies were performed on the two cell types, demonstrating that epithelial cells can grow as a monolayer composed of cohesive groups of polygonal cells (1.3 X 10(5) cells/cm2), while stromal cells were mostly fibroblastic. The effect of hormones was studied on the epithelial cells in culture. The monolayer was cultured into harvest medium for 3 days to ensure the complete removal of endogenous steroids, then these cells were incubated with 2 X 10(-9) M-oestradiol-17 beta for 3 days. There was a rise in the progesterone receptor level, varying from 1.3 to 10.8 times. The three enzymes known to interfere with oestradiol-17 beta metabolism were present in the epithelial cells grown in our culture conditions. By incubation with oestrone sulphate for 3 days it was demonstrated that, in cultured epithelial cells, oestrone sulphate is converted into oestradiol-17 beta sulphate, and oestrogen sulphates are hydrolysed to active oestrogens.

Animals↗
PubMed1999

Hair and skin disorders as signs of mitochondrial disease.

OBJECTIVE: To compare and explore the skin manifestations of mitochondrial disorders in 14 children with puzzling and unexpected cutaneous presentations. STUDY DESIGN: One hundred forty children with mitochondrial disorders who had been under observation in our hospital for the last 10 years, were carefully examined by the same physicians. Skin and hair characteristics were investigated by the same dermatologist. All the children developed an early unexplained association of symptoms. Metabolic screening for abnormal oxidative-reduction in plasma and mitochondrial enzyme investigations confirmed the diagnosis of oxidative phosphorylation disorders. RESULTS: Fourteen children with mitochondrial disorders (10% of the original cohort) developed specific hair and skin abnormalities. Their cutaneous manifestations were similar, and could be classified into four categories: hair abnormalities, rashes and pigmentation disorders, hypertrichosis, and acrocyanosis. In 3 cases, skin disorders constituted the puzzling and unexpected manifestations of mitochondrial disease. Respiratory chain deficiencies in the cultured skin fibroblasts of 3 patients and heteroplasmic mitochondrial DNA rearrangement in the skin fibroblasts of 1 patient indicated that mitochondrial disorders may be expressed in the skin. CONCLUSION: Hair abnormalities and pigmented skin eruptions might belong to the broad spectrum of presenting symptoms of mitochondrial disease. The association of these dermatologic lesions with unrelated disorders should lead physicians to consider a diagnosis of mitochondriopathy as early as possible.

Age of Onset↗
PubMed2002

Efficacy and safety of pimecrolimus cream in the long-term management of atopic dermatitis in children.

OBJECTIVE: Pimecrolimus cream (SDZ ASM 981), a nonsteroid inhibitor of inflammatory cytokines, is effective in atopic dermatitis (AD). We assessed whether early treatment of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares. METHODS: Early intervention with pimecrolimus was compared with a conventional AD treatment strategy (ie, emollients and topical corticosteroids). In this 1-year, controlled, double-blind study, 713 AD patients (2-17 years) were randomized 2:1 to a pimecrolimus-based or conventional regimen. Both groups used emollients for dry skin. Early AD signs/symptoms were treated with pimecrolimus cream or, in the conventional treatment group, vehicle to prevent progression to flares. If flares occurred, moderately potent topical corticosteroids were mandated. The primary efficacy endpoint was ranked flares at 6 months. Safety was monitored clinically, and a skin recall-antigen test was performed at study completion. RESULTS: BASELINE CHARACTERISTICS OF THE PATIENTS: The mean age for both groups was approximately 8 years, and the majority of patients had moderate disease at baseline. PATIENT FOLLOW-UP AND EXPOSURE TO STUDY MEDICATION: The mean duration of follow-up (+/-standard error) was 303.7 (+/-5.30) days in the pimecrolimus group and 235.2 (+/-9.40) days in the control group. The discontinuation rate was significantly higher in the control group than in the pimecrolimus group (51.5% vs 31.6% at 12 months), and proportionately more patients with severe or very severe disease discontinued in the control group. The main reason for the higher discontinuation rate in the control group was unsatisfactory therapeutic effect (30.4% vs 12.4%). This resulted in a substantially higher mean number of study medication treatment days in the pimecrolimus group compared with the control group: 211.9 (69.8% of study days) versus 156.0 (66.3% of study days). Of those patients who completed 12 months on study, 14.2% and 7.0% of patients in the pimecrolimus and vehicle groups, respectively, used study medication continuously. EFFICACY: Patients in the pimecrolimus group experienced significantly fewer AD flares than those in the control group, according to the primary efficacy analysis on ranked flares of AD (Van Elteren test). The proportion of patients who completed 6 or 12 months with no flares was approximately twice as high in the pimecrolimus group compared with control (61.0% vs 34.2% at 6 months; 50.8% vs 28.3% at 12 months). Fewer flares were observed in the pimecrolimus group regardless of baseline disease severity, so even severe patients derived benefit from the treatment. The analysis of time to first flare showed that treatment with pimecrolimus was associated with a significantly longer flare-free period (log- rank test). Covariate analysis indicated a statistically significant effect on time to first flare of baseline Eczema Area and Severity Index score, and whether patients had "severe" or "very severe" disease at baseline according to the Investigators' Global Assessment, although patients in all baseline disease severity subgroups benefited from treatment. Age had no significant effect. Fewer patients in the pimecrolimus group required topical corticosteroid therapy compared with control (35.0% vs 62.9% at 6 months; 42.6% vs 68.4% at 12 months), and patients in the pimecrolimus group spent fewer days on topical corticosteroid therapy (57.4% vs 31.6% [pimecrolimus vs control, respectively] spent 0 days on topical corticosteroid therapy, 17.1% vs 27.5% 1-14 days, and 25.5% vs 41.0% >14 days over the 12 months of the study). This steroid-sparing effect of pimecrolimus was evident despite pimecrolimus-treated patients being on study longer than patients in the control group. The average proportion of study days spent on second-line corticosteroids was 4.08% in the pimecrolimus group and 9.10% in the control group. Analysis of Eczema Area and Severity Index over time showed significantly lower median scores, thus indicating better disease control in the pimecrolimus group compared with the control group. Similar results were obtained from analysis of the Investigators' Global Assessment (not shown). The treatment groups were well balanced with respect to the number of patients using antihistamines during the study (57.2% vs 62.9%, pimecrolimus vs control, respectively). SAFETY: There were no appreciable differences between treatment groups in the overall incidence of adverse events. The most frequent adverse events were common childhood infections and ailments, including nasopharyngitis, headache, and cough. The incidence of suspected drug-related adverse events was not significantly different in the pimecrolimus group (24.7% vs 18.7%--pimecrolimus vs control), and the incidence of serious adverse events was low (8.3% vs 5.2%--pimecrolimus vs control). Life-table analysis of incidence of adverse events revealed no significant differences between the treatment groups, except for cough. Local tolerability was good in both treatment groups. The most common application site reaction reported was sensation of burning (10.5% vs 9.3%--pimecrolimus vs control). There were no major differences between treatment groups in the duration or severity of application site reactions, most of which were mild-to-moderate and transient, occurring within the first week of treatment. Skin infections were reported in both groups. There were no between-group differences in the life-table analysis of time to first occurrence of bacterial skin infections nor in the adjusted incidence of bacterial skin infections. Although there were no significant differences between treatment groups in the incidence of individual viral skin infections, the incidence of grouped viral skin infections (12.4% vs 6.3%--pimecrolimus vs control) showed a slightly higher incidence in the pimecrolimus group. Laboratory values and vital signs showed no significant between-group differences. There were no significant differences between treatment groups in response to recall antigens in those patients who remained on study for 12 months. CONCLUSIONS: Treatment of early AD signs/symptoms with pimecrolimus was effective in preventing progression to flares in more than half the patients, reducing or eliminating the need for topical corticosteroids. The benefits were consistently seen at 6 months across important disease severity subgroups and with respect to the various predefined efficacy endpoints. Furthermore, these benefits were sustained for 12 months, providing evidence that long-term treatment with pimecrolimus leads to better control of AD. Treatment with pimecrolimus was well tolerated and was not associated with clinically relevant adverse events compared with the conventional treatment group. The results reported here offer the prospect of effective long-term management of AD with reduced need for topical corticosteroids.

Adolescent↗
PubMed2005

Safety and tolerability of 1% pimecrolimus cream among infants: experience with 1133 patients treated for up to 2 years.

Pimecrolimus is a calcineurin inhibitor developed for the topical treatment of atopic dermatitis. During the clinical development of 1% pimecrolimus cream, 1133 patients 3 to 23 months of age with mild to severe atopic dermatitis were treated for up to 2 years. The objective of this review is to discuss the safety and tolerability of 1% pimecrolimus cream among infants, on the basis of the combined results from all studies (4 pharmacokinetic studies and 6 clinical trials) conducted among these patients. Pimecrolimus blood concentrations measured for 35 patients were consistently low (< or =1 ng/mL in >80% of samples), irrespective of the disease severity and extent, and remained low during intermittent treatment for up to 1 year. The level of systemic exposure to pimecrolimus among infants was comparable to that observed for older pediatric patients enrolled in the same studies and treated in the same way with 1% pimecrolimus cream, which indicated that young pediatric patients are not at higher risk of significant percutaneous absorption of topically applied pimecrolimus, despite their large skin surface area/body mass ratio. The 6 clinical trials included a total of 1098 infants, who were treated for periods ranging from 4 weeks to 2 years. Most of these patients (60%) had moderate to severe disease at baseline. The most frequently reported adverse events were common childhood disorders such as nasopharyngitis, pyrexia, upper respiratory tract infections, ear infections, and bronchitis. During the double-blind (DB) studies or DB phases of studies, the incidence rates for the most frequently reported adverse events were similar for patients who received 1% pimecrolimus cream and patients who received the vehicle, except for the incidence of teething, which was higher among the pimecrolimus-treated infants (relative risk: 2.02; 95% confidence interval: 1.32-3.27). Treatment with 1% pimecrolimus cream was not associated with an increase in the overall incidence of nonskin infections, compared with the vehicle (relative risk: 1.015; 95% confidence interval: 0.88-1.18). The incidence density (ID) rates for total bacterial, fungal, parasitic, and viral skin infections during the DB studies or DB phases of studies were comparable for patients treated with 1% pimecrolimus cream and patients who received the vehicle. The ID rate of herpes simplex virus infections was 0.8 cases per 1000 patient-months of follow-up monitoring among patients treated with 1% pimecrolimus cream and 1.7 cases per 1000 patient-months of follow-up monitoring among patients who received the vehicle. Considering all 1098 infants treated with 1% pimecrolimus cream in DB trials and open-label studies, the ID rate of clinically diagnosed eczema herpeticum was 1.3 cases per 1000 patient-months of follow-up monitoring. Burning and erythema were the most frequently reported application site reactions, with ID rates of 2.0 and 1.2 cases per 1000 patient-months of follow-up monitoring, respectively. No sign of immunosuppression was found among infants treated intermittently with 1% pimecrolimus cream for up to 2 years; they demonstrated normal immune responses to vaccinations and did not show increases in the incidence of systemic infections or skin infections over time.

Calcineurin Inhibitors↗
PubMed2000

[Evidence of cerebral involvement in the chronic stage of Chagas disease obtained using the P300 potential and quantified electroencephalography].

It is already known the involvement of the peripheral nervous system in chronic stages of Chagas disease. Tomographic and neuropsychological evidence of brain compromise has been included recently. In order to evaluate the neurophysiological counterpart of cerebral involvement, we studied P300 evoked potential and quantified EEG (qEEG) of 35 patients (26-55 years), and compared to an equal number of control subjects (29-55 years). We have found increased P300 latency compared to the control group (331.24 +/- 24. 02 vs 318.86 +/- 23.18) (p=0.01716). qEEG showed lower relative Beta 1 power in the patients group (p=1.6E5), and the principal frequency 1 Hz slower in the same group (p=0.01077). Multivariate analysis showed three subpopulations: a normal one, pathological one with higher Alpha power and pathological with Alpha decrement and DeltaTheta increment. Pathological findings represented 20% for the qEEG and 11.43% for cognitive potentials. Cardiac and neurologic involvement were not correlated. We conclude that there is clear electrophysiological evidence of cerebral involvement in chronic Chagas disease, thus reinforcing findings obtained by other methods.

Adult↗
PubMed2006

Opacification of the genitourinary collecting system during MDCT urography with enhanced CT digital radiography: nonsaline versus saline bolus.

OBJECTIVE: The purpose of this study was to determine whether a saline bolus during CT urography improves urinary collecting system opacification and whether the addition of enhanced CT digital radiography (CTDR) improves urinary collecting system visualization with or without a saline bolus. MATERIALS AND METHODS: One hundred eight CT urography and enhanced CTDR examinations were reviewed. Fifty-four patients were given a saline bolus during CT urography, and 54 patients underwent CT urography without a saline bolus. Urinary collecting system opacification was evaluated by group (saline vs nonsaline), imaging technique (CT urography alone vs CT urography plus enhanced CTDR), number of enhanced CTDR images, and site of nonopacified urinary segments. Using a multivariate logistic regression model, we determined significance of variables and odds of complete opacification. RESULTS: In the saline group, 248 nonopacified sites were identified on CT urography alone and 95 sites with CT urography plus enhanced CTDR. In the nonsaline group, 185 nonopacified sites were identified on CT urography alone and 59 sites with CT urography plus enhanced CTDR. Combining both groups, 433 nonopacified sites were identified with CT urography alone and 154 sites with CT urography plus enhanced CTDR. Multivariate logistic regression showed significance for group (p = 0.010), imaging method (p < 0.0001), number of enhanced CTDR images (p = 0.048), and site of segment opacification (p < 0.0001). The renal pelvis shows the greatest odds and the distal ureter the lowest odds for complete opacification by group or imaging method. CONCLUSION: The addition of a saline bolus offers no improvement, whereas the addition of enhanced CTDR offers significant improvement in collecting system opacification during CT urography.

Adult↗
PubMed1989

Randomised double-blind placebo-controlled trial of local cyclosporin in atopic dermatitis.

The efficacy of local applications of 10% cyclosporin gel was studied in a randomised double-blind placebo-controlled trial in atopic dermatitis. Twenty atopic patients, presenting with stable symmetrical lesions, participated in the study. They applied cyclosporin gel to one side and placebo gel to the other side twice a day. The lesions were assessed on day 0 and day 14 according to lesional criteria scored from 0 to 3. The mean score for each criterion on day 14 was significantly lower on the sides treated with cyclosporin than on the sides treated with placebo. The total mean score on day 14 was 6.1 +/- 3.9 on the sides treated with CSA and 9.6 +/- 3.9 for placebo (p less than 0.005). These findings suggest the efficacy of local CSA applications on lesions of atopic dermatitis.

Administration, Cutaneous↗
PubMed1977

Verbal productivity and expression of primary process.

The effects of verbal fluency upon the production of primary-process thinking on the Holtzman Inkblot Test as scored by the Holt system were investigated for a group of 49 male university students. Increasing verbal productivity resulted in a significant increase in primary-process scores in both high and low primary-process groups, selected on the basis of a trial of unlimited verbal productivity. In addition there were consistent significant differences in primary-process scores comparing the high and low primary-process groups at different levels of fluency. The importance of considering the level of verbal fluency when using scores from inkblot records in discussed.

Cognition↗
PubMed1995

In vitro rat pancreatic digestive enzyme activities and raw and heated glandless cottonseed and soybean flours.

Higher nitrogen and lipid digestibilities have been obtained with diets containing cottonseed flour rather than soybean flour. To explain these results, in vitro studies were carried out to compare the effects of raw and heated glandless (without gossypol) cottonseed flours versus soybean flours on pancreatic digestive enzyme activities. These effects were compared with those obtained without addition of flour in standard assays. Apparent lipase (lipase colipase dependent) and potential lipase (lipase with saturating amounts of colipase), colipase, phospholipase A2, amylase, trypsin and chymotrypsin activities were measured on specific substrates. Phospholipase A2 and amylase activities were enhanced, while chymotrypsin activity was diminished with both raw and heated flours. Compared with raw and heated soybean flours, raw and heated cottonseed flours promoted higher potential lipase, chymotrypsin, trypsin and lipase activities. Heat treatment of cottonseed flour enhanced apparent lipase, colipase, chymotrypsin, trypsin activities and diminished potential lipase, phospholipase A2 and amylase activities. When soybean flour was heated, apparent lipase, phospholipase A2, chymotrypsin, trypsin and amylase activities were raised while those of potential lipase were decreased. Our findings show that in vitro raw or heated cottonseed flours affect less digestive enzymes than raw or heated soybean flours, apparent lipase activity excepted. Moreover, only chymotrypsin activities were seriously lowered with both flours, especially with raw soybean flour. Hypotheses are suggested to account for the differences in alterations.

Amylases↗
PubMed1978

[Effects of diets rich in triglycerides and phospholipids on lipase and phospholipase A activities in rat pancreatic juice and pancreas].

Lipase and phospholipase A activities were increased in the pancreas and pancreatic juice of rats ingesting during two months 20% phospholipids- or triglycerides-rich diets. The activity of lipase is higher with the triglycerides-rich diet and the phospholipase A activity is higher with the phospholipids-rich diet. After seven days of the experiment, these two enzymes activities were less increased with diet containing 40% lipids.

Animals↗
PubMed2002

Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma.

OBJECT: Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study is to evaluate the efficacy and role of gamma knife radiosurgery (GKS) in the management of residual or recurrent nonfunctioning pituitary adenomas. METHODS: A review was conducted of the data obtained in 42 patients who underwent adjuvant GKS at the University of Pittsburgh between 1987 and 2001. Prior treatments included transsphenoidal resection, craniotomy and resection, or conventional radiotherapy. Endocrinological, ophthalmological, and radiological responses were evaluated. The duration of follow-up review varied from 6 to 102 months (mean 31.2 months). Fifteen patients were observed for more than 40 months. The mean radiation dose to the tumor margin was 16 Gy. Conformal radiosurgery planning was used to restrict the dose to the optic nerve and chiasm. Tumor control after GKS was achieved in 100% of patients with microadenomas and 97% of patients with macroadenomas. Gamma knife radiosurgery was equally effective in controlling adenomas with cavernous sinus invasion and suprasellar extension. No patient developed a new endocrinological deficiency following GKS. One patient's tumor enlarged with an associated decline in visual function. Another patient experienced a deterioration of visual fields despite a decrease in tumor size. CONCLUSIONS: Gamma knife radiosurgery can achieve tumor control in virtually all residual or recurrent nonfunctioning pituitary adenomas. Dose sparing facilitates tumor management even when the adenoma is close to the optic apparatus or invades the cavernous sinus.

Adenoma↗
PubMed1998

Differential transferrin receptor density in human colorectal cancer: A potential probe for diagnosis and therapy.

Transferrin receptor density was investigated in human colorectal surgical specimens. Crude membranes were prepared from 23 cancer tumors (adenocarcinoma or malignant villous tumor) and 3 non-cancer tumors (polyadenoma or villous tumor) and 26 adjacent control mucosa. Contrary to non-cancer tumors, Scatchard analysis of 125I-transferrin binding data evidenced higher maximal transferrin binding capacity and lower dissociation constant in cancer tissues (Bmax cancer 1.828+/-0.320 nmol/g, Kd 24.1+/-4.7 nM), as compared to paired control colonic mucosa (Bmax contol 0.851+/-0.182 nmol/g, Kd 30.7+/-7.3 nM), paired t-tests: Bmax p<0.001, Kd p<0.05). As the cancer/control Bmax ratio was 2.6+/-0.4,transferrin carrier constructs should be proposed for cancer imaging or therapy.

Adult↗
PubMed1981

Associations in filarial infections in man in the savanna zones of Mali and Upper Volta.

In 14 villages located in the West African savanna belt, 1,305 people were examined for microfilariae in blood and skin. The results indicate that the associations between filariae in infected patients are not the result of chance alone. The frequency of associations between Wuchereria bancrofti and Tetrapetalonema perstans was highly significant, whereas Onchocerca volvulus appeared to be associated with W. bancrofti only in the absence of T. perstans.

Burkina Faso↗