bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin amyloid fibrillation at above 100°C: New insights into protein folding under extreme temperatures
Authors: Arora Anubhav , Ha Chanki , Park Chan Beum 
Published: August 2004

AbstractTo investigate the folding behavior of amyloidogenic proteins under extreme temperatures, the kinetics of fibrillation and accompanying secondary structure transitions of bovine insulin were studied for temperatures ranging up to 140°C. The presence of extreme heat stress had traditionally been associated with irreversible denaturation of protein while the initial steps of such a denaturation process may be common with a fibril formation pathway of amyloidogenic proteins. The present work demonstrates the ability of insulin to form amyloid fibrils at above 100°C. Amyloid formation was gradually replaced by random coil generation after ∼80°C until no amyloid was detected at 140°C. The morphology of insulin amyloid fibrils underwent sharp changes with increasing the temperature. The dependence of amyloid formation rate on incubation temperature followed non‐Arrhenius kinetics, which is explained by temperature‐dependent enthalpy change for amyloid formation. The intermediate stage of amyloid formation and random coil generation consisted of a partially folded intermediate common to both pathways. The fully unfolded monomers in random coil conformation showed partial reversibility through this intermediate by reverting back to the amyloid pathway when formed at 140°C and incubated at 100°C. This study highlights the non‐Arrhenius kinetics of amyloid fibrillation under extreme temperatures, and elucidates its intermediate stage common with random coil formation.
Changes in wheat root enzymes correlated with resistance to cereal cyst nematodes
Authors: Andres M. F. , Melillo M. T. , Delibes A. , Romero M. D. , Bleve‐Zacheo T. 
Published: July 2004

Summary

The response of the resistant wheat/Aegilops ventricosa introgression line, H‐93‐8, to a Spanish population of the cereal cyst nematode, Heterodera avenae, was studied in order to determine changes in gene expression correlated with resistance.
Roots of susceptible (Triticum aestivum cv. Anza) and resistant wheat seedlings were analysed using histological (electron microscopy), cytochemical (at tissue and cytological level) and biochemical (isoelectrofocusing) techniques.
Infection of resistant wheat lines with H. avenae resulted in a hypersensitive reaction, with syncytial cells deteriorating in a few days. Following nematode infection, peroxidase, esterase and superoxide dismutase activities were increased in H‐93‐8 roots compared with the susceptible wheat. Syncytial cells in roots of resistant lines were highly reactive to diaminobenzidine and homovanillic acid oxidase, the latter associated with plasma and nuclear membranes and vacuoles. The same syncytial cells showed early positive reaction to phloroglucinol, indicating lignification.
The Cre2 resistance gene in H‐93‐8 inhibited reproduction of H. avenae. Peroxidases, esterases and superoxide dismutase might represent products of genes whose expression is correlated with the resistance response to this nematode.
Calcipotriene and Corticosteroid Combination Therapy for Vitiligo
Authors: Travis Lisa B. , Silverberg Nanette B. 
Published: July 2004

Abstract:  Corticosteroids and photochemotherapy, using a combination of psoralen and ultraviolet A (PUVA) exposure, are the most widely prescribed therapies for vitiligo. These treatments are not uniformly effective and many patients have inadequate responses. Calcipotriene has been shown to be effective in adults and children with psoriasis when used as monotherapy and in combination with corticosteroids and phototherapy. We hypothesized that since the mechanisms of action for calcipotriene and corticosteroids are different, patients may develop more repigmentation with a combination of the two agents, while decreasing the side effects from both agents. Twelve patients with vitiligo (average age 13.1 years) were advised to use topical corticosteroids in the morning and topical calcipotriene in the evening. Of the 12 patients, 83% responded to therapy, with an average of 95% repigmentation by body surface area. Four of the patients who responded had previously failed trials of topical corticosteroids alone. All of the patients in this group had repigmentation. Eyelid and facial skin responded best to this therapy. None of the patients had adverse reactions to the treatment. Our results show that topical calcipotriene in combination with corticosteroids can repigment vitiligo, even in those patients who were previous topical corticosteroid failures.
Responsive and Proactive Market Orientation and New‐Product Success*
Authors: Narver John C. , Slater Stanley F. , MacLachlan Douglas L. 
Published: August 2004

What is the relationship between market orientation and new‐product success? This important question has not been examined adequately to date because the concept of market orientation has been measured too narrowly. The concept of market orientation implies both responsive market orientation, which addresses the expressed needs of customers, and proactive market orientation, which addresses the latent needs of customers—that is, opportunities for customer value of which the customer is unaware. In the numerous market orientation–performance studies to date, the measure of market orientation has consisted virtually entirely of behaviors related to satisfying customers' expressed needs rather than satisfying their latent needs as well.The present study extends the measurement of market orientation to match the full scope of the concept—to measure both responsive market orientation and proactive market orientation. Using data from a sample of technologically diverse businesses, the present study develops a measure of proactive market orientation, refines the extant measure of responsive market orientation, and analyzes the relationship of a business's responsive and proactive market orientation to its new‐product success. The study findings imply that for any business to create and to sustain new‐product success, a responsive market orientation is not sufficient and, thus, that a proactive market orientation plays a very important positive role in a business's new‐product success. These findings make intuitive sense. For if in developing its new products a business relies solely on what customers state as their new product needs, the business is very vulnerable economically. Such a business is vulnerable not only for relying on customers' best guesses for new products, many or most of which may have little long‐term economic value for either party, but also to competitors' parallel new product responses and the inevitable resulting price competition. A business that relies solely on customers' expressed needs to develop its new products creates no new insights into value‐adding opportunities for the customer and thereby creates little or no customer dependence and foundation for customer loyalty. The important role for proactive market orientation in new‐product success is intuitively obvious—and is supported empirically in this study.
Cellular mechanism of renin release
Authors: Schweda F. , Kurtz A. 
Published: July 2004

AbstractIn this review we aim to give a comprehensive overview over the current knowledge of the cellular control of renin release. We hereby focus on the inhibitory effects of calcium on the exocytosis of renin. After a short introduction into general aspects of the regulation of renin release, including a brief summary on the role of the second messengers cAMP and cGMP, we will discuss parts of the literature on the effects of calcium on the renin system together with recent studies from our laboratory, investigating putative calcium influx and extrusion pathways of juxtaglomerular cells. Finally, as the precise mechanisms by which calcium inhibits the exocytosis of renin are far from being understood, we will present some hypotheses on the intracellular events being involved in the suppression of renin release by calcium.
Tumour necrosis factor‐α receptor 1 and 2 polymorphisms in inflammatory bowel disease and their association with response to infliximab
Authors: Pierik M. , Vermeire S. , Steen K. V. , Joossens S. , Claessens G. , Vlietinck R. , Rutgeerts P. 
Published: July 2004

SummaryBackground : The role of tumour necrosis factor‐α in the pathogenesis of inflammatory bowel disorders is well‐known and is underscored by the effectiveness of antitumour necrosis factor‐α treatment. Tumour necrosis factor‐α exerts its effect by binding TNFR1 and TNFR2, which genes map to inflammatory bowel disorders susceptibility loci.Aims and methods : Since TNFR1 and TNFR2 are good candidate genes for inflammatory bowel disorders, we studied the functional TNFR2T587G and the TNFR1A36G mutation in 344 Crohn's disease and 152 ulcerative colitis patients and investigated the relation with disease phenotypes. An association with response to infliximab was evaluated in 166 Crohn's disease patients.Results : The TNFR2 587G allele was more frequent in ulcerative colitis compared with controls (P = 0.03). Both single nucleotide polymorphisms were negatively associated with smoking at diagnosis in Crohn's disease (TNFR1A36G odds ratio: 0.614, 95% confidence interval: 0.452, 0.99 and TNFR2T587G odds ratio: 0.572, 95% confidence interval: 0.820, 0.875). There was a positive association between pancolitis and the TNFR1A36G polymorphism in ulcerative colitis (odds ratio: 5.341, 95% confidence interval: 1.484, 19.39). The biological response to infliximab was lower in patients carrying TNFR1 36G (odds ratio: 0.47, 95% confidence interval: 0.234, 0.946).Conclusion : The TNFR2 587G allele was more frequent in ulcerative colitis. Both single nucleotide polymorphisms were negatively associated with smoking in Crohn's disease. A relation between TNFR1A36G and pancolitis was found in ulcerative colitis. There was no clear effect of the polymorphisms on infliximab response although, the TNFR1 minor was associated with a lower response to infliximab.
A new questionnaire for constipation and faecal incontinence
Authors: Bharucha A. E. , Locke G. R. , Seide B. M. , Zinsmeister A. R. 
Published: July 2004

SummaryBackground : The prevalence, severity and risk factors of faecal incontinence in women in the community are incompletely characterized.Aim : To develop and validate a self‐report questionnaire (faecal incontinence and constipation assessment) to address these issues.Method : Eighty‐three women completed the instrument; 20 randomly selected patients answered the faecal incontinence and constipation assessment again 6 weeks later. A gastroenterologist also completed the faecal incontinence and constipation assessment in all 83 subjects after a detailed clinical assessment. Concurrent validity was evaluated by comparing the patient's self‐report to a doctor interview for every question. Reproducibility was evaluated by a test–retest approach for every question. The severity of faecal incontinence was rated by incorporating the frequency and type of faecal incontinence, rectal urgency and use of sanitary devices.Results : The questionnaire was well‐understood. Reproducibility [median κ statistic, 0.80 (interquartile range: 0.66–0.90)]; and concurrent validity [0.59 (0.47–0.67)] were acceptable. For the index question on faecal incontinence, the κ for reproducibility and concurrent validity was 0.90 and 0.95, respectively. The faecal incontinence severity score was also valid (κ = 0.5).Conclusion : The faecal incontinence and constipation assessment has excellent reproducibility and reasonable validity for assessing the presence, risk factors and severity of faecal incontinence and associated bowel disorders in women when compared against clinical assessment.
In vivo evaluation of a novel pH‐ and time‐based multiunit colonic drug delivery system
Authors: Bott C. , Rudolph M. W. , Schneider A. R. J. , Schirrmacher S. , Skalsky B. , Petereit H.‐U. , Langguth P. , Dressman J. B. , Stein J. 
Published: July 2004

SummaryBackground : Targeted drug delivery to the colon is important for topical treatment of inflammatory bowel diseases. Established targeting systems predominantly focus on either pH‐ or time‐dependent release, or bacterial degradation.Aim : To perform a three‐phase, crossover design trial evaluating a novel combined pH‐ and time‐based multiunit delivery system.Methods : Twelve healthy male volunteers each received 200 mg of caffeine as either uncoated immediate release tablets, coated pellets with pH‐dependent rapid release (EUDRAGIT FS 30D), and pellets with pH‐ and time‐based release (inner layer EUDRAGIT RL/RS 30D; outer layer EUDRAGIT FS 30D). Orocecal transit time was measured using lactose‐[13C]ureide. Serum concentrations of caffeine were measured by high‐performance liquid chromatography.Results : In contrast to the uncoated tablet, both coated systems reached the ileocecal region almost at the same time (3.19 ± 0.71 and 3.33 ± 0.81 h). Serum caffeine profiles were significantly prolonged for the pH and time delivery system compared with the pH‐only based system (median tmax 12.0 vs. 5.5 h; P < 0.001). This was further reflected by a lower Cmax value and a lower area under the curve within 24 h after application.Conclusion : Compared with the conventional delivery systems, drug release from the new dosage form may offer a new dimension for the oral treatment of mid to distal ulcerative colitis.
Prevalence of irritable bowel syndrome according to different diagnostic criteria in a non‐selected adult population
Authors: Hillilä M. T. , Färkkilä M. A. 
Published: July 2004

SummaryBackground : Prevalence of irritable bowel syndrome shows great variation among epidemiological studies, which may be due to different diagnostic criteria.Aim : To assess prevalence of irritable bowel syndrome according to various diagnostic criteria and to study differences in symptom severity, psychopathology, and use of health care resources between subjects fulfilling different diagnostic criteria.Methods : A questionnaire was mailed to 5000 randomly selected adults. Presence of irritable bowel syndrome was assessed by four diagnostic criteria: Manning 2 (at least two Manning symptoms), Manning 3 (at least three Manning symptoms), Rome I and Rome II.Results : Response rate was 73%. Prevalence of irritable bowel syndrome by Manning 2, Manning 3, Rome I and Rome II criteria was 16.2%, 9.7%, 5.6%, and 5.1% respectively. Of those fulfilling Rome II criteria, 97% fulfilled Manning 2. Severe or very severe abdominal pain was reported by 27–30% of Manning‐positive subjects, and 44% of Rome‐positives. Prevalence of depression in Manning 2, and Rome II groups was 30.6 and 39.3%.Conclusions : Prevalence of irritable bowel syndrome by Rome II criteria is considerably lower than by Manning criteria. Subjects fulfilling Rome criteria form a subgroup of Manning‐positive subjects with more severe abdominal symptoms, more psychopathology, and more frequent use of the health care system.
Effect of the motilin agonist KC 11458 on gastric emptying in diabetic gastroparesis
Authors: Russo A. , Stevens J. E. , Giles N. , Krause G. , O'Donovan D. G. , Horowitz M. , Jones K. L. 
Published: July 2004

SummaryBackground : KC 11458, a motilin agonist without antibiotic properties, accelerates gastric emptying in animals and healthy humans.Aim : To evaluate the acute effects of KC 11458 on gastric emptying in diabetic gastroparesis.Methods : Twenty‐nine patients (6 type 1 and 23 type 2) with gastroparesis underwent assessments of: (i) gastric emptying of a solid/liquid meal using scintigraphy, (ii) glycaemic control (blood glucose at 0, 30, 60, 90 and 120 min during the gastric emptying measurement) and (iii) upper gastrointestinal and ‘meal‐related’ symptoms (questionnaire), at baseline and after treatment with KC 11458 in a dose of 8 mg t.d.s., or placebo for 8 days.Results : KC 11458 had no statistically significant or clinically relevant effect on gastric emptying of either the solid intragastric retention at 100 min (T100) (P = 0.87) or liquid 50% emptying time (T50) (P = 0.17) components of the meal. KC 11458 slightly worsened (P = 0.04) upper gastrointestinal symptoms when compared with placebo. The magnitude of the change in solid gastric emptying correlated with the change in the blood glucose concentration (r = 0.49; P < 0.05).Conclusions : KC 11458, in a dose of 8 mg t.d.s. for 8 days, does not accelerate gastric emptying in patients with diabetic gastroparesis. The absence of efficacy may relate to an effect of hyperglycaemia.
The evolving role of liver biopsy
Authors: Campbell M. S. , R. Reddy K. 
Published: July 2004

SummaryLiver biopsy is traditionally the ‘gold standard‘ for the evaluation of liver diseases. There are several situations in which its role is being challenged. In hepatitis C, liver biopsy helps assess prognosis and treatment candidacy. An important exception is genotype 2 or 3 because treatment is more likely to succeed and therapy is relatively short in duration. For hepatitis B, liver biopsy gives some prognostic information, but serologic tests and hepatic biochemical tests are the primary determinants of treatment candidacy. Non‐alcoholic fatty liver disease can be accurately diagnosed without a liver biopsy and, furthermore, there are no specific therapies available. The role of liver biopsy to assess methotrexate‐associated hepatotoxicity remains controversial. Finally, patients with focal liver lesions usually do not require biopsy and, in the case of hepatocellular carcinoma, biopsy carries a risk of needle‐track seeding. In short, the need for liver biopsy depends on the specific situation and should be performed when there is sufficient uncertainty about diagnosis, severity of disease, prognosis, and treatment decisions.
Reproducibility of a symptom response to omeprazole therapy in functional dyspepsia evaluated by a random‐starting‐day trial design
Authors: Madsen L. G. , Bytzer P. 
Published: July 2004

SummaryBackground : Satisfactory treatment options for functional dyspepsia are lacking. Single subject trial designs may identify subgroups of patients with a uniform response to therapy.Aim : To test reproducibility of response in a new random‐starting‐day trial design developed to identify acid‐related symptoms in functional dyspepsia.Methods : One hundred and nineteen patients with functional dyspepsia completed a 12‐day, double‐blind random‐starting‐day trial with an initial placebo run‐in followed by switch to omeprazole on a randomized and blinded day (between days 5 and 9) with active treatment continuing for the rest of the trial. Response was defined as a sustained ≥50% reduction of a daily symptom‐score within 3 days of active treatment. Fifty‐nine patients repeated the random‐starting‐day trial at relapse of symptoms.Results : After exclusion of placebo responders, 14% (15 of 106) were classified as responders in the first and 20% (10 of 50) in the subsequent random‐starting‐day trial series. Sixty‐eight per cent (40 of 59) of the patients reproduced their initial response with a chance‐corrected agreement of 0.29. Comparing response patterns using different symptom rating‐scales showed good correlation (kappa 0.60).Conclusion : Reproducibility of response in a random‐starting‐day trial was imperfect, mainly because of the low response rates and strict response criteria. Lack of symptom stability impairs the value of the random‐starting‐day trial and only patients with frequent and stable symptoms should be evaluated in this design.
Four years of treatment with lamivudine: clinical and virological evaluations in HBe antigen‐negative chronic hepatitis B
Authors: Gaia S. , Marzano A. , Smedile A. , Barbon V. , Abate M. L. , Olivero A. , Lagget M. , Paganin S. , Fadda M. , Niro G. , Rizzetto M. 
Published: July 2004

SummaryAim : To evaluate the clinical and virological impact of the prolonged use of lamivudine in 94 patients with HBe antigen‐negative chronic hepatitis B.Methods : Initial virological and biochemical responses were obtained in 84 (89%) and in 83 (88%) patients respectively.Results : The virological response peaked within the first 12 months, but diminished to 39% at 48 months because of drug resistance. Overall a virological breakthrough developed in 44 patients (52.4%). After virological breakthrough, the actuarial probability of maintaining biochemical remission diminished to 15% at 24 months and 0% at 29 months. There was no response in 10.6%. Polymerase gene mutations were observed in 82.5% of virological breakthroughs but also in 75% of the non‐responders. Overall 7.4% of patients developed a hepatocellular carcinoma.Conclusion : Almost 90% of patients responded initially to lamivudine but the emergence of drug resistance progressively reduced the rate of virological remission to 39% at the fourth year of therapy. YMDD mutants explained the 75% of lamivudine resistances and were also selected very early in non‐responders. Although the biochemical response is invariably lost within 29 months of the YMDD mutant's duration, the clinical outcome was benign despite severe postvirological breakthrough hepatitic flares in about 12% of cases.
Increased thrombin generation and circulating levels of tumour necrosis factor‐α in patients with chronic Helicobacter pylori‐positive gastritis
Authors: Consolazio A. , Borgia M. C. , Ferro D. , Iacopini F. , Paoluzi O. A. , Crispino P. , Nardi F. , Rivera M. , Paoluzi P. 
Published: July 2004

SummaryBackground : Conflicting data have been reported concerning the relationship between Helicobacter pylori infection and coronary heart disease.Aim : To evaluate clotting system activation and plasma levels of tumour necrosis factor‐α, a procoagulant cytokine, in patients with H. pylori‐positive and ‐negative gastritis.Methods : Three groups of patients were identified: 38 with H. pylori‐positive gastritis, 18 with H. pylori‐negative gastritis, and 40 H. pylori‐negative controls with normal gastric mucosa. Plasma levels of prothrombin fragment 1 + 2 (F1 + 2) and tumour necrosis factor‐α were assayed. Patients were also controlled after 2 and 6 months following standard H. pylori eradication treatment.Results : At baseline, fragment 1 + 2 and tumour necrosis factor‐α levels in H. pylori‐positive patients were significantly higher than those in H. pylori‐negative patients with gastritis (P < 0.05 and P < 0.01, respectively). After H. pylori eradication, fragment 1 + 2 and tumour necrosis factor‐α levels showed a significant decrease at 2 months (P = 0.03 and P = 0.02, respectively) and a further reduction at 6 months, reaching levels observed in H. pylori‐negative patients and controls.Conclusions : The increase thrombin generation rate and the correlation of plasma fragment 1 + 2 and tumour necrosis factor‐α levels in H. pylori‐positive patients suggest a role for inflammation in mediating the relationship between H. pylori infection and activation of the clotting system.