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Biomedical subjects

M Lucas

Publications and source records attributed to M Lucas.

At least 37 records · Page 2Linked to original sources

Photoproduction of the rho(0) meson on the proton at large momentum transfer.

The differential cross section, d sigma/dt, for rho(0) meson photoproduction on the proton above the resonance region was measured up to a momentum transfer -t = 5 GeV2 using the CLAS detector at the Thomas Jefferson National Accelerator Facility. The rho(0) channel was extracted from the measured two charged-pion cross sections by fitting the pi(+)pi(-) and p pi(+) invariant masses. The low momentum transfer region shows the typical diffractive pattern expected from Reggeon exchange. The flatter behavior at large -t cannot be explained solely in terms of QCD-inspired two-gluon exchange models. The data indicate that other processes, like quark interchange, are important to fully describe rho photoproduction.

Journal Article↗

Adiponutrin, a transmembrane protein corresponding to a novel dietary- and obesity-linked mRNA specifically expressed in the adipose lineage.

We have used a mRNA differential display technique to identify new genes involved in the reprogramming of gene expression during the adipose conversion of mouse 3T3 preadipocyte cell lines. We report here on the identification and cloning of a novel adipose-specific cDNA encoding a predicted membrane protein of 413 amino acids. The level of the corresponding 3.2-kilobase mRNA is tremendously increased during 3T3-L1 and 3T3-F442A differentiation into adipocytes. A single, very abundant 3.2-kilobase transcript is also found in inguinal and epididymal white adipose tissues and in interscapular brown adipose tissue but not in any other tissues examined. Its expression in adipose tissue is under tight nutritional regulation. The level of this novel 3.2-kilobase transcript becomes virtually nondetectable during fasting but is dramatically increased when fasted mice are refed a high carbohydrate diet. Based on its adipose specificity and dietary regulation, the novel gene product has been designated adiponutrin. The expression of adiponutrin mRNA is also 50-fold elevated in genetically obese fa/fa rats, indicating a link between adiponutrin and obesity. Western blot and confocal imagery analyses with epitope-tagged protein transiently expressed in 3T3-L1 adipocytes, and COS cells show that adiponutrin strictly localizes to membranes and is absent from the cytosol. Sequence analysis reveals homologies with several other members of related eukaryotic proteins, including a human paralog, which has been recently described in vesicular transport mechanisms. This leads us to suggest that adiponutrin could be involved in vesicular targeting and protein transport restricted to the adipocyte function.

3T3 Cells↗

Association of a CA repeat polymorphism upstream of the Fas ligand gene with multiple sclerosis.

We have analyzed a CA repeat polymorphism localized 46-kb upstream of the Fas ligand gene in Spanish and American populations that include 139 healthy controls and a cohort of 177 unrelated relapsing and remitting multiple sclerosis (MS) patients. The MS patients consisted of two groups, one with a family history of MS and one without. The frequency of the 13 CA repeats (allele B) was lower (p=0.01) in MS patients than in controls, 0.45 and 0.55 respectively. The odds ratio (BB vs. AB/AA) for MS patients vs. healthy controls was 0.51 (95% CI 0.3-0.9; p=0.01). The odds ratio (BB vs. AB/AA) for MS patients extracted from multiply affected families vs. healthy controls was 0.22 (95% CI 0.07-0.62; p=0.002). The HLA DRB1*1501-DQB1*0602 haplotype is associated with B allele with a relative frequency higher than A allele (0.52 and 0.48 in patients vs. 0.68 and 0.32 in controls). The results suggest that chromosomes with B allele have a genetic background that reduces susceptibility to MS, particularly in the familial forms.

Alleles↗

The ep -->e'p eta reaction at and above the S11(1535) baryon resonance.

New cross sections for the reaction e p-->e p eta are reported for total center of mass energy W = 1.5--1.86 GeV and invariant momentum transfer Q2 = 0.25--1.5 (GeV/c)(2). This large kinematic range allows extraction of important new information about response functions, photocouplings, and eta N coupling strengths of baryon resonances. Newly observed structure at W approximately 1.65 GeV is shown to come from interference between S and P waves and can be interpreted with known resonances. Improved values are derived for the photon coupling amplitude for the S11(1535) resonance.

Journal Article↗

Effectiveness of a nonselective ET(A/B) and a selective ET(A) antagonist in rats with monocrotaline-induced pulmonary hypertension.

BACKGROUND: Both nonselective ET(A/B) receptor and selective ET(A) receptor antagonists can reduce pulmonary hypertension (PH) and right ventricular hypertrophy (RVH) in various animal models. Depending on their net effects after blockade of endothelial and smooth muscle ET(B) receptors, nonselective ET(A/B) antagonists could be more or less effective than selective ET(A) antagonists. METHODS AND RESULTS: Two weeks after injection of saline or 60 mg/kg monocrotaline (MCT), rats received 50 mg x kg(-1) x d(-1) of a selective (LU135252) or nonselective (BSF420627) antagonist for 3 weeks. This resulted in 4 groups: control (n=15), MCT (n=60), MCT+ET(A) (n=39), and MCT+ET(A/B) (n=40). Five-week survival was 35% in the MCT group; this was increased to 56% in the MCT+ET(A) group (P:=0.10) and to 67% in the MCT+ET(A/B) group (P:=0.0015). Drug administration was stopped 48 hours before hemodynamic measurements to evaluate the chronic effects of therapy: PH in the MCT group (RV systolic pressure 87+/-1 mm Hg) was improved similarly in both MCT+ET(A) and MCT+ET(A/B) groups (72+/-3 and 70+/-3 mm Hg, respectively, P:<0.05). Severe RVH in the MCT group (RV/left ventricle+septum weight ratio 73+/-1%) was not affected by the selective antagonist (70+/-2%) but was reduced to 54+/-2% in the MCT+ET(A/B) group (P:<0.01). Pulmonary resistive properties, assessed from isolated lung pressure-flow relationships, were improved similarly in survivors from both treated groups. CONCLUSIONS: Both the nonselective ET(A/B) antagonist BSF420627 and the selective ET(A) antagonist LU135252 are effective in this model of PH. Similar direct comparative studies in other models of PH and with various dosage regimens are warranted to define the optimal pharmacological approach of PH when ET receptor antagonists are used.

Animals↗

Systemic sclerosis with renal crisis and pulmonary hypertension: a report of eleven cases.

OBJECTIVE: To describe a series of systemic sclerosis (SSc) patients with the unusual combination of scleroderma renal crisis (SRC) and pulmonary hypertension (PHT) without interstitial lung disease. METHODS: The medical records of 2,459 SSc patients in the University of Pittsburgh Scleroderma Databank first evaluated between 1972 and 1999 were reviewed. RESULTS: Eleven patients (0.45%) had both SRC and PHT. All had been evaluated since 1979, when angiotensin-converting enzyme (ACE) inhibitor therapy for SRC became available. Seven had SSc with limited cutaneous involvement, and 4 had SSc with diffuse cutaneous involvement. SRC occurred first in all patients except 1, in whom the onsets of SRC and PHT were simultaneous. SRC preceded PHT by a mean of 4.3 years. Four patients had anti-Th/To antibody, 5 had anti-RNA polymerase III antibody, 2 had anti-U3 RNP antibody, and none had anticentromere or antitopoisomerase I antibody. Ten of the 11 patients died, 8 from PHT. Ten patients were being treated with ACE inhibitor drugs when PHT developed. CONCLUSION: In SSc, SRC and PHT are not mutually exclusive complications. SSc patients surviving SRC who have serum antibodies to Th/To, RNA polymerase III, or U3 RNP are at increased risk to develop PHT. ACE inhibitor therapy did not prevent the development of PHT.

Acute Kidney Injury↗

Effect of ET(A) receptor antagonist on pulmonary hypertension and vascular reactivity in rats with congestive heart failure.

BACKGROUND: We evaluated the effects of chronic therapy with the selective ET(A)receptor antagonist LU 135252 (LU) on pulmonary vascular reactivity in congestive heart failure. METHODS AND RESULTS: After myocardial infarction (MI) or sham operation, rats were gavaged with LU or saline for 4 weeks. Studies were performed in isolated lungs and to differentiate acute from chronic effects, some experiments were performed with LU in the perfusate. The MI+saline group developed moderate pulmonary hypertension (PH) and right ventricular hypertrophy (RVH). This was improved by LU therapy despite no change in left ventricular function and a larger scar area. Vasodilation to sodium nitroprusside (SNP) was reduced after MI and modestly improved by LU therapy. Vasodilation to acetylcholine (Ach) was similar among the four groups, but accentuated after acute LU administration in the sham+saline and MI+saline groups. A23187 produced higher vasoconstriction (18+/-4%) in the MI+LU compared to the MI+saline (10+/-3%, P<0.05) and the two control groups (3+/-1% and 4+/-3%, with and without LU, P<0.01): this was reversed to vasodilation following the acute addition of LU. CONCLUSION: ET(A)receptor blockade after MI reduces PH and RVH. LU therapy mildly improves dilation to SNP and favorably modulates pulmonary endothelium-dependent responses. These results support future studies to better define the mechanisms of improvement in pulmonary vascular reactivity after ET receptor antagonist therapy.

Animals↗

["High pouch output" syndrome. Role of mineralocorticoid diagnosis after restorative proctocolectomy].

UNLABELLED: The two-phase restorative proctocolectomy is the treatment of choice for surgical therapy of the familial adenomatous polyposis (FAP) and also for the ulcerative colitis (UC). Besides the well-known complications the entire removal of the colorectum leads to an impairment of fluid and electrolyte resorption. PATIENTS AND METHODS: Over a time period of two years we observed 320 proctocolectomized patients with ileal pouch-anal anastomosis (IPAA). All patients with high pouch output but without organic malfunction were identified. The organic reasons were excluded with the help of pouchoscopy, radiography or MR imaging. We evaluated routine parameters, the kidney function, the electrolyte changes, the acid-base balance and the urine pH, as well as the hormonal changes of the suprarenal glands. We identified seven patients with 'high pouch output' out of 320 patients observed. The control group consisted of 14 proctocolectomized patients without hints of complications in the endoscopic, radiographic and routine laboratory diagnostics. RESULTS: Neither group showed any significant differences in the analysis of the routine parameters. A significant drop of the urine sodium concentration of 40.5 +/- 18.7 mmol/l (control group 98 +/- 43.4 mmol/l) was observed in the group with 'high pouch output'. In this group the plasma aldosterone values were strongly increased with an average of 42.6 +/- 28.9 ng/dl (control group 13.2 +/- 6.8 ng/dl) as well as the plasma 18-hydroxycorticosterone with an average of 153.7 +/- 121.1 ng/dl (control group 153.7 +/- 121.1 ng/dl). Neither group of patients showed increased activity of free corticosterone and free cortisol. Only free 11-desoxycorticosterone was elevated in the group with 'high pouch output'. CONCLUSION: Our results prove that the mineralocorticoid adrenal activity plays a central role in order to preserve the volume and electrolyte homeostasis. The low frequency of 'high-pouch-output'-complications in realms of the restorative proctocolectomy proves the excellent compensation of the removal of the colon mucosa. Plasma aldosterone seems to be a diagnostic marker encapsulating the reabsorption problems of intestinal salt and volume losses after proctocolectomy.

18-Hydroxycorticosterone↗

Essential and perceptual attributes of words in reflective and on-line processing.

Access to essential and perceptual attributes of word meanings was investigated in a series of tasks. First, perceptual attributes of a number of natural kind concepts were determined by asking participants to generate the most salient features of those concepts; they were asked to assess the importance of both thosefeatures and features that fit criteria for essential attributes. Attributes fitting the criteria for essential attributes were found to be judged more important than perceptual attributes in identifying an object and to have more connections to other attributes of the concept. Semantic priming for both types offeatures was then investigated. Prime-target pairs consisting of the natural kind concept term and the perceptual or essential attribute were presented for lexical decision (Experiments 1a and 1b) or naming (Experiments 2a and 2b). Interstimulus intervals were either 0 or 200 ms. Both types of features were primed at a 200 ms interstimulus interval but only in the lexical decision task.

Humans↗

Viral escape mechanisms--escapology taught by viruses.

Viruses have 'studied' immunology over millions of years of coevolution with their hosts. During this ongoing education they have developed countless mechanisms to escape from the host's immune system. To illustrate the most common strategies of viral immune escape we have focused on two murine models of persistent infection, lymphocytic choriomeningitis virus (LCMV) and murine cytomegalovirus (MCMV). LCMV is a fast replicating small RNA virus with a genome prone to mutations. Therefore, LCMV escapes from the immune system mainly by two strategies: 'speed' and 'shape change'. At the opposite extreme, MCMV is a large, complex DNA virus with a more rigid genome and thus the strategies used by LCMV are no option. However, MCMV has the coding capacity for additional genes which interfere specifically with the immune response of the host. These escape strategies have been described as 'camouflage' and 'sabotage'. Using these simple concepts we describe the spectrum of viral escapology, giving credit not only to the researchers who uncovered this fascinating area of immunology but also to the viruses themselves, who still have a few lessons to teach.

Animals↗

Backwash ileitis is strongly associated with colorectal carcinoma in ulcerative colitis.

BACKGROUND & AIMS: Commonly accepted risk factors for colorectal carcinoma (CRC) in ulcerative colitis are duration and extent of disease. By identifying still unknown risk factors, surveillance strategies may be improved further. We investigated whether backwash ileitis is also a factor associated with CRC in ulcerative colitis. METHODS: Five hundred ninety consecutive patients with ulcerative colitis who received restorative proctocolectomy were classified into 3 groups: (1) pancolitis with backwash ileitis, (2) pancolitis without backwash ileitis, and (3) left-sided colitis. The association with CRC was analyzed in these 3 groups of patients. As further risk factors, we investigated disease duration, dysplasia, primary sclerosing cholangitis, age at diagnosis of disease, disease activity, and gender. Univariate and multivariate logistic regression were used for analysis. RESULTS: CRC was diagnosed in 11.2% of all patients. CRC was found in 29.0% of 107 patients in group 1, compared with 9.0% of 369 patients in group 2, and in 1.8% of 114 patients in group 3 (P < 0.001). Cancer patients in group 1 showed significantly more multiple tumor growth (45.2%) than patients in group 2 (24.2%) and group 3 (0%) (P = 0.041). Estimating the relative risk for CRC in the multivariate analysis, patients in group 1 showed a significantly higher odds ratio than patients in groups 2 and 3 (odds ratio: 19.36 vs. 9.58 vs. 1; P < 0.001). High-grade dysplasia, low-grade dysplasia, disease duration of more than 10 years, and disease duration of less than 10 years in patients older than 45 years were further factors with significantly increased risk (odds ratios: 21.69, 6.36, 3.63, 4.37), but primary sclerosing cholangitis was not (P = 0.080). However, primary sclerosing cholangitis was strongly associated with backwash ileitis. CONCLUSIONS: There is a strong association of backwash ileitis with CRC in patients with ulcerative colitis who undergo proctocolectomy. The predictive value of backwash ileitis for CRC and premalignant dysplasia in patients with ulcerative colitis should be investigated in future studies based on colonoscopic surveillance.

Adolescent↗

Segmental mandibular reconstruction by microincremental automatic distraction osteogenesis: an animal study.

We investigated the reconstruction of a surgically created critical size mandibular defect in sheep using a newly developed automatic distraction device. The device has an implantable component, which is fixed to the mandible to allow the transfer of the transport disc across the created defect, and an external component which is mounted on the activation pump and secured away from the site of bone distraction. Compression of the bellows in the external component causes fluid to be forced through the connecting tube into the distraction component. Distraction at a rate of 1 mm over 24 h was achieved in six sheep. New bone generated at the site of the created defects both anterior (compression side) and posterior (tension side) to the transport disc and had similar radiodensity to the adjacent mandibular bone eight weeks after the completion of distraction.

Angiography↗

Resolution of oral ulcerations after decreasing the dosage of tacrolimus in a liver transplantation recipient.

Oral ulcers have may possible causes, including immunosuppression and drug therapy. Severe cases of oral ulceration merit special consideration because the ulcers may become large enough to alter the quality of life of the patient. The present case involves a male patient who in 1994 received an orthotopic liver transplantation because of alcoholic cirrhosis. The initial immunosuppressive regimen was induced with tacrolimus (4 mg/d) and prednisone (20 mg/d). Ten months after orthotopic liver transplantation, the patient complained of multiple recurrent oral ulcers, dysphagia, and severe oral pain, which did not respond to any of the treatments over a 3-year period. Approximately 3(1/4) years after these unresponsive ulcers appeared, the reduction of the oral dosage of tacrolimus resulted in the total remission of the ulcers. A retrospective analysis demonstrated that appearance of the ulcers coincided with a dose of 9 mg/d of tacrolimus (whole blood levels of 12 ng/mL); the ulcers did not disappear until the dose was reduced to 4 mg/d (whole blood level of 6.6 ng/mL).

Administration, Oral↗

D-penicillamine in systemic sclerosis? Yes!

The use of D-penicillamine in systemic sclerosis (SSc) has been controversial. We have reviewed the major published studies on this drug in SSc with diffuse cutaneous (dc) involvement and summarized our own recent experience in dcSSc patients treated with and without D-penicillamine. We conclude that D-penicillamine favourably alters the natural history of skin involvement in dcSSc, even when used in low dose. Furthermore, recurrence of diffuse skin change after discontinuation of D-penicillamine and improvement in skin thickening after reinitiation of the drug support its effectiveness. We believe that the rheumatologic community should use D-penicillamine in patients with early dcSSc.

Antirheumatic Agents↗

One- or two-stage procedure for restorative proctocolectomy: rationale for a surgical strategy in ulcerative colitis.

OBJECTIVE: To analyze the results of different strategies for restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) in ulcerative colitis. SUMMARY BACKGROUND DATA: No commonly accepted criteria exist for choosing between the one-stage or the two-stage procedure (with or without temporary diverting ileostomy) for IPAA. The authors analyzed the outcome of patients principally suitable for either of the two alternative surgical strategies. METHODS: A matched-pair control study was performed, comparing surgical details and the early and late outcome of the one-stage (study group, n = 57) versus the two-stage procedure (control group, n = 114), for IPAA. RESULTS: No differences were found between the study group and the control group regarding the matching criteria gender, median age at IPAA, systemic corticoid medication, or activity of colitis. Comparing the patients who underwent a one-stage procedure with those who underwent a two-stage procedure, the proportion of patients without complications was significantly higher (P =.0042) and the frequency of late complications was significantly lower (P =.0022) in patients who underwent the one-stage procedure. The percentage of patients with anastomotic strictures was significantly higher in the control group than in the study group (P =.0022). No significant difference was found between the two groups regarding early complications, pouch-related septic complications, pouchitis, median duration of surgery for IPAA, median blood loss, need for transfusion, or median hospital stay. CONCLUSIONS: In patients with ulcerative colitis in whom there is a choice between a one-stage procedure or a two-stage procedure with a defunctioning ileostomy, the one-stage procedure is clearly superior. This finding is of great clinical relevance both for the subjective interests of the patient and from an economic point of view.

Adult↗

Thapsigargin-induced calcium entry and apoptotic death of neutrophils are blocked by activation of protein kinase C.

Intracellular free calcium ([Ca(2+)](i)) concentration, free oxygen radical (FOR) production, DNA breakdown, and plasma membrane phosphorylation were studied in human neutrophils activated with thapsigargin and phorbol myrisate acetate (PMA). Thapsigargin produced a rapid and sustained rise of [Ca(2+)](i), activated the endonuclease, and caused the breakdown of the neutrophil's DNA with a half-time close to 6 h. The protein kinase C activator PMA failed to inhibit the initial rise of [Ca(2+)](i), but inhibited the second phase of thapsigargin-induced calcium transient and completely blocked the activation of the endonuclease induced by thapsigargin. Thapsigargin induced a minor and delayed production of FOR, whereas PMA caused an abrupt and sustained FOR production that was enhanced by thapsigargin. Two plasma membrane proteins close to 50 and 64 kD were phosphorylated in PMA-activated neutrophils. These results suggest that the nonphosphorylated form of the membrane protein permits basal and thapsigargin-induced calcium entry. Phosphorylation by PMA of plasma membrane protein inhibits calcium uptake in both resting and thapsigargin-activated neutrophils and contributes to the block of the activation of the apoptotic endonuclease.

Adenosine Triphosphatases↗