bluuebunny/crossref_metadata_2025 huggingface dataset:
Mini extracorporeal circuit for coronary artery bypass grafting: initial clinical and biochemical results
Authors: van Boven W J , Gerritsen W B , Waanders F G , Haas F J , Aarts L P
Published: July 2004

Background: The new concept of mini-extracorporeal circulation (MECC) for coronary artery bypass grafts (MCABG) consists of minimal priming volume, a heparin-coated closed circuit, a centrifugal pump, active drainage, blood cardioplegia and a cell-saving device. The potential organ protective effect of this technique during CABG is unknown. Initial clinical outcomes, oxidative stress, alveolar shunting and need for blood transfusion were investigated for MCABG patients. Subsets of these data were compared to outcomes of matched groups of patients operated conventionally (CCABG) and off-pump (OPCAB).

Methods: Data of 184 patients were gathered and analysed from a prospective observational database system. This database consists of the initial experience with the first 114 MCABG operations. Of these, the clinical outcome was investigated. In a subset of 60 MCABGs, need for transfusion was monitored and compared to 60 CCABGs. Serum concentrations of malondialdehyde (MDA), allantoin/urate ratios, shunt fractions and lung epithelium-specific proteins (CC16) were measured as biomarkers of damage during MCABG, CCABG and OPCAB (n-30).

Results: Patient groups were similar concerning age, risk and number of distal anastomoses. Clinical outcomes are shown for MCABGs only. During MCABG, need for trans-fusion was significantly reduced compared to CCABG (pB/0.001). Serum concentrations of MDA and allantoin/urate ratios showed significantly reduced oxidative stress during MCABG compared to CCABG. During MCABG, F-shunts were reduced shortly after surgery. Increased concentrations of pneumoprotein CC16 were measured during CCABG compared to MCABG (data submitted).

Conclusion: Short-term clinical outcomes of MCABG patients are satisfactory. Compared to CCABG the need for transfusion is significantly reduced when a MECC is used. Oxidative stress parameters show a tendency towards improved global organ protection compared to CCABG. F-shunt fractions and CC16 concentrations suggest reduced alveolar damage during MCABG. In a prospective study, the protective effect of mini-CABG has to be confirmed.
Compact intra-and extracorporeal oxygenator developments
Authors: Cattaneo Giorgio , Strauß Andreas , Reul Helmut
Published: July 2004

For patients with acute lung failure, mechanical ventilation entails the risk of lung tissue damage due to high oxygen pressure and concentration. Membrane oxygenation for one to two weeks can rest the lungs due to decreased ventilation parameters, representing a potential bridge to recovery, but implies the substantial risks of blood damage, plasma leakage and infection, which often have fatal results for patients.

At the Helmholtz Institute in Aachen, two types of membrane oxygenators, which aim to overcome previous limits, are under development. Both present compact designs, reduced surface and priming volumes and easier handling.

HEXMO is a miniaturized extracorporeal membrane oxygenator. The integration of a small rotary blood pump into the centre of the oxygenator reduces the amount of tubing and connectors in the system. Blood is convectively warmed by the pump motor housing, thus, the use of a heat-exchanger can be avoided. This compact design reduces surface and priming volume and allows better handling, especially in critical situations.

A second development is the intravascular oxygenator HIMOX, which is inserted directly into the vena cava. Priming volume and blood contact surface are reduced, as well as infection risk and control needs for the patient. A new cross-flow fibre configuration is used for improving gas transfer within the limited space inside the vena cava. A microaxial blood pump is integrated into the device for compensating the pressure drop across the fibres and allowing venous return and physiological pressure in the organs proximal to the oxygenator.
Vascular disease/risk and late-life depression in a Korean community population
Authors: Kim Jae-Min , Stewart Robert , Shin Il-Seon , Yoon Jin-Sang
Published: July 2004

Background

Associations between vascular risk factors and late-life depression are controversial.

Aims

To investigate the association between measures of vascular disease/ risk and depression and confounding and effect modification by APOE genotype and cognitive function.

Method

In a Korean community population aged 65+ (n=732), diagnosis of depression (Geriatric Mental State Schedule) and information on vascular status, disability, APOE genotype and cognitive function were obtained.

Results

Previous stroke and lower high-density lipoprotein cholesterol level (but neither hypertension nor diabetes) were significantly associated with depression (independently of disability and cognitive function). These associations were stronger in participants with borderline cognitive impairment, although not to a significant extent.

Conclusions

Except for previous stroke and an atherogenic lipid profile, associations between depression and other common risk factors for cerebrovascular disease were not evident.
Psychological impact of severe acute respiratory syndrome on health workers in a tertiary hospital
Authors: Chong Mian-Yoon , Wang Wen-Chih , Hsieh Wen-Chien , Lee Chun-Yi , Chiu Nien-Mu , Yeh Wei-Chiang , Huang Tiao-Lai , Wen Jung-Kwang , Chen Chao-Long
Published: July 2004

Background

The sudden emergence of severe acute respiratory syndrome (SARS) caused international anxiety owing to its highly contagious and pandemic transmission. Health workers are vulnerable and are at high risk of infection.

Aims

To assess SARS-related stress and its immediate psychological impact and responses among health workers.

Method

Health workers in a tertiary hospital affected by SARS were invited to complete a questionnaire designed to evaluate exposure experience, psychological impact and psychiatric morbidity. The risk and rates of psychiatric morbidity were estimated for exposure experience.

Results

Altogether, 1257 health workers successfully completed the survey. In the initial phase of the outbreak, when the infection was spreading rapidly, feelings of extreme vulnerability, uncertainty and threat to life were perceived, dominated by somatic and cognitive symptoms of anxiety. During the ‘repair’ phase, when the infection was being brought under control, depression and avoidance were evident. The estimated prevalence of psychiatric morbidity measured by the Chinese Health Questionnaire was about 75%.

Conclusions

The outbreak of SARS could be regarded as an acute episode of a bio-disaster, leading to a significantly high rate of psychiatric morbidity.
Childhood experience and health care use in adulthood
Authors: Kapur Navneet , Hunt Isabelle , Macfarlane Gary , McBeth John , Creed Francis
Published: July 2004

Background

Few studies have considered the role of childhood experiences in adult health care use.

Aims

To examine the hypotheses that individuals frequently attending primary care report childhood adversities and illness exposures more commonly than the remainder of patients and that any association is independent of adult psychiatric disorder.

Method

A nested case–control study was carried out in a single general practice in Manchester, UK. Fifty frequent attenders (randomly selected from adult patients in the top decile of consultation frequency) and fifty normal attenders (randomly selected from the remainder of adult patients) underwent a structured psychiatric interview and a detailed, semi-structured interview of childhood experience.

Results

There was a strong association between frequent attendance and childhood experiences. Multivariate analysis suggested that reported childhood illness exposures and reports of childhood adversity were each associated independently with adult consultation behaviour, even after adjustment for adult psychiatric disorder.

Conclusions

Interventions for high users of health care may need to address childhood experiences of illness and childhood adversities, as well as adult psychiatric disorder.
Prolactin levels in antipsychotic treatment of patients with schizophrenia carrying the DRD2*A1 allele
Authors: Young Ross Mcd. , Lawford Bruce R. , Barnes Mark , Burton Simon C. , Ritchie Terry , Ward Warren K. , Noble Ernest P.
Published: July 2004

Background

Hyperprolactinaemia induced by D2 dopamine receptor antagonist antipsychotic medication can result in significant health problems.

Aims

To examine the role of DRD2 polymorphism on prolactin levels in patients treated with antipsychotic medication.

Method

Antipsychotic drugs with different degrees of D2 receptor binding were given to 144 patients with schizophrenia. Serum prolactin levels were obtained and Taq1A DRD2 alleles were determined.

Results

Prolactin levels increased across medication groups reflecting increasingly tight D2 receptor binding (clozapine, olanzapine, typical antipsychotics and risperidone). In the combined medication group, patients with the DRD2∗A1 allele had 40% higher prolactin levels than patients without this allele. In patients treated with clozapine (the loosest D2 receptor binding agent), patients with the DRD2∗A1 allele had prolactin levels twice those of patients without this allele.

Conclusions

Patients with the DRD2A1 allele receiving antipsychotic medications had higher prolactin levels and were overrepresented among those with hyperprolactinaemia, suggesting greater functional D2 receptor binding in this group.
Testing for diabetes in hospitalised patients prescribed antipsychotic drugs
Authors: Taylor David , Young Corina , Esop Raadiyya , Paton Carol , Walwyn Rebecca
Published: July 2004

Background

Studies using computer databases suggest that atypical antipsychotic agents are more likely to be associated with diabetes than are conventional drugs.

Aims

To discover the extent of testing for diabetes mellitus in hospital in-patients prescribed antipsychotics.

Method

Prescription charts were screened to identify patients prescribed antipsychotics. Case notes were then searched for evidence of testing for diabetes.

Results

In all, 606 patients were prescribed antipsychotics, of whom 250 (41.3%) had evidence of prior testing for diabetes. Patients prescribed atypicals were 40% more likely to have been tested than those prescribed conventional drugs (RR = 1.4, 95% C11.1–1.9). Adjusted odds ratiosv.conventional antipsychotics for testing were significantly higher for clozapine (OR = 4.64, 95% C12.42–8.90), olanzapine (OR= 1.85, 95% C11.04–3.30) and antipsychotic polypharmacy (OR= 2.96, 95% C11.59–5.52).

Conclusions

Testing for diabetes was undertaken in less than half of the patients studied. Testing was more common in those receiving atypical antipsychotics. Apparent differences in claimed causal association of the use of some antipsychotics with diabetes may in part reflect different rates of testing.
Psychiatry in the future
Authors: Burns Tom
Published: July 2004

The 1990s witnessed a strikingly accelerated rate of change in the structure and delivery of mental health care in the UK. The preceding 15 years had been marked, in my practice, by two inexorable processes which transformed the face of clinical psychiatry, but without the convulsive upheavals and discontinuities that we have come to live with since. The first was the running down and eventual closure of the large mental hospitals – a change so fundamental that it may be difficult for those trained recently to grasp just how different mental health care was then. The second was the internationalisation of research, and the growing influence of evidence and formal instruction as a determinant of practice, rather than simply relying on the consultants to whom one was apprenticed. For all the occasional criticisms of it, evidence-based medicine dominates modern psychiatry, and this is evident in the much greater consistency of practice than 30 years ago. The changes in the 1970s and early 1980s were essentially egosyntonic within the profession; the past 15 years have been more dramatic and less comfortable.
Subjective experience of electroconvulsive therapy
Authors: Benbow Susan M. , Crentsil Joe
Published: July 2004

Aims and Method

People receiving electroconvulsive therapy (ECT) in one clinic completed side-effect rating questionnaires during treatment, and a questionnaire rating their experience of different aspects of treatment on completion of the treatment course.

Results

Side-effects were commonly reported, but predominantly rated as mild or moderate. Most people reported that ECT had made them a little or a lot better, and that the treatment had been fairly or very well explained. Fewer than a fifth of respondents rated ECT as slightly or much worse than going to the dentist.

Clinical Implications

We recommend routine monitoring of the subjective experience of ECT, during treatment and on completion of the course. Ratings should inform the treatment plan, the policies and procedures of the ECT clinic.
A Randomized Trial Comparing Defined-Duration With Continuous Irinotecan Until Disease Progression in Fluoropyrimidine and Thymidylate Synthase Inhibitor—Resistant Advanced Colorectal Cancer
Authors: Lal Rohit , Dickson James , Cunningham David , Chau Ian , Norman Andrew R. , Ross Paul J. , Topham Clare , Middleton Gary , Hill Mark , Oates Jacqui
Published: July 2004

Purpose

Irinotecan given until disease progression is an accepted standard treatment for advanced colorectal cancer (CRC) resistant to fluoropyrimidines. It is not known whether a predefined period of irinotecan treatment would result in similar duration of disease control. We performed a multicenter phase III trial to compare the two policies of defined-duration versus continuous irinotecan treatment.

Patients and Methods

Three hundred thirty-three eligible patients with advanced CRC progressing on or within 24 weeks of completing fluoropyrimidine-based chemotherapy were prospectively registered. After receiving eight cycles of irinotecan given at 350 mg/m2 once every 3 weeks, 55 patients with responding or stable disease were randomly assigned to stop irinotecan (n = 30) or continue until disease progression (n = 25). Registered patients were not randomly assigned predominantly due to disease progression (n = 236) and intolerable toxicity (n = 38).

Results

From the time of random assignment, there were no differences in failure-free survival (P = .999) or overall survival (P = .11) between the two arms. No difference was seen in mean global health status quality-of-life score between the two arms at 12 weeks after random assignment. No grade 3 diarrhea and febrile neutropenia was seen in the continue-irinotecan arm after random assignment.

Conclusion

For most patients, the decision to continue on irinotecan beyond 24 weeks is influenced by disease progression or treatment-related toxicity. However, for 17% of patients in whom this decision is clinically relevant, there seems to be little benefit from continuing irinotecan, though the drug was well tolerated without any deterioration in quality of life.
Long-Term Silicone Central Venous Catheters Impregnated With Minocycline and Rifampin Decrease Rates of Catheter-Related Bloodstream Infection in Cancer Patients: A Prospective Randomized Clinical Trial
Authors: Hanna Hend , Benjamin Robert , Chatzinikolaou Ioannis , Alakech Badie , Richardson Deborah , Mansfield Paul , Dvorak Tanya , Munsell Mark F. , Darouiche Rabih , Kantarjian Hagop , Raad Issam
Published: July 2004

Purpose

To evaluate the efficacy of long-term nontunneled silicone catheters impregnated with minocycline and rifampin (M-R) in reducing catheter-related bloodstream infections.

Patients and Methods

This prospective, randomized, double-blind clinical trial was conducted at M.D. Anderson Cancer Center, a tertiary care hospital in Houston, TX. All patients in the trial had a malignancy.

Results

Between September 1999 and May 2002, 356 assessable catheters were used: 182 M-R and 174 nonimpregnated. The patients' characteristics were comparable between the two study groups. The mean (± standard deviation) duration of catheterization with M-R catheters was comparable to that of nonimpregnated catheters (66.21 ± 30.88 v 63.01 ± 30.80 days). A total of 17 catheter-related bloodstream infections occurred during the course of the study. Three were associated with the use of M-R catheters and 14 were associated with the nonimpregnated catheters, with a rate of catheter-related bloodstream infection of 0.25 and 1.28/1,000 catheter-days, respectively (P = .003). Gram-positive cocci accounted for the majority of the organisms causing the infections. There were no allergic reactions associated with M-R catheters.

Conclusion

Long-term nontunneled central venous catheters impregnated with minocycline and rifampin are efficacious and safe in reducing catheter-related bloodstream infections in cancer patients.
Phase III Study of Cisplatin With or Without Paclitaxel in Stage IVB, Recurrent, or Persistent Squamous Cell Carcinoma of the Cervix: A Gynecologic Oncology Group Study
Authors: Moore David H. , Blessing John A. , McQuellon Richard P. , Thaler Howard T. , Cella David , Benda Jo , Miller David S. , Olt George , King Stephanie , Boggess John F. , Rocereto Thomas F.
Published: July 2004

Purpose

To determine whether cisplatin plus paclitaxel (C+P) improved response rate, progression-free survival (PFS), or survival compared with cisplatin alone in patients with stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix.

Patients and Methods

Eligible patients with measurable disease, performance status (PS) 0 to 2, and adequate hematologic, hepatic, and renal function received either cisplatin 50 mg/m2 or C+P (cisplatin 50 mg/m2 plus paclitaxel 135 mg/m2) every 3 weeks for six cycles. Tumor measurements and quality-of-life (QOL) assessments were obtained before each treatment cycle.

Results

Of 280 patients entered, 6% were ineligible. Among 264 eligible patients, 134 received cisplatin and 130 received C+P. Groups were well matched with respect to age, ethnicity, PS, tumor grade, disease site, and number of cycles received. The majority of all patients had prior radiation therapy (cisplatin, 92%; C+P, 91%). Objective responses occurred in 19% (6% complete plus 13% partial) of patients receiving cisplatin versus 36% (15% complete plus 21% partial) receiving C+P (P = .002). The median PFS was 2.8 and 4.8 months, respectively, for cisplatin versus C+P (P < .001). There was no difference in median survival (8.8 months v 9.7 months). Grade 3 to 4 anemia and neutropenia were more common in the combination arm. There was no significant difference in QOL scores, although a disproportionate number of patients (cisplatin, n= 50; C+P, n = 33) dropped out of the QOL component, presumably because of increasing disease, deteriorating health status, or early death.

Conclusion

C+P is superior to cisplatin alone with respect to response rate and PFS with sustained QOL.
Evaluation of Biologic End Points and Pharmacokinetics in Patients With Metastatic Breast Cancer After Treatment With Erlotinib, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor
Authors: Tan Antoinette R. , Yang Xiaowei , Hewitt Stephen M. , Berman Arlene , Lepper Erin R. , Sparreboom Alex , Parr Allyson L. , Figg William D. , Chow Catherine , Steinberg Seth M. , Bacharach Stephen L. , Whatley Millie , Carrasquillo Jorge A. , Brahim Jaime S. , Ettenberg Seth A. , Lipkowitz Stan , Swain Sandra M.
Published: July 2004

Purpose

To evaluate changes in epidermal growth factor receptor (EGFR) phosphorylation and its downstream signaling in tumor and surrogate tissue biopsies in patients with metastatic breast cancer treated with erlotinib, an EGFR tyrosine kinase inhibitor, and to assess relationships between biomarkers in tumor and normal tissues and between biomarkers and pharmacokinetics.

Patients and Methods

Eighteen patients were treated orally with 150 mg/d of erlotinib. Ki67, EGFR, phosphorylated EGFR (pEGFR), phosphorylated mitogen-activated protein kinase (pMAPK), and phosphorylated AKT (pAKT) in 15 paired tumor, skin, and buccal mucosa biopsies (at baseline and after 1 month of therapy) were examined by immunohistochemistry and analyzed quantitatively. Pharmacokinetic sampling was also obtained.

Results

The stratum corneum layer and Ki67 in keratinocytes of the epidermis in 15 paired skin biopsies significantly decreased after treatment (P = .0005 and P = .0003, respectively). No significant change in Ki67 was detected in 15 tumors, and no responses were observed. One was EGFR-positive and displayed heterogeneous expression of the receptor, and 14 were EGFR-negative. In the EGFR-positive tumor, pEGFR, pMAPK, and pAKT were reduced after treatment. Paradoxically, pEGFR was increased in EGFR-negative tumors post-treatment (P = .001). Although markers were reduced in surrogate and tumor tissues in the patient with EGFR-positive tumor, no apparent associations were observed in patients with EGFR-negative tumor.

Conclusion

Erlotinib has inhibitory biologic effects on normal surrogate tissues and on an EGFR-positive tumor. The lack of reduced tumor proliferation may be attributed to the heterogeneous expression of receptor in the EGFR-positive patient and absence of target in this cohort of heavily pretreated patients.
Cardiovascular Status in Long-Term Survivors of Hodgkin's Disease Treated With Chest Radiotherapy
Authors: Adams M. Jacob , Lipsitz Stuart R. , Colan Steven D. , Tarbell Nancy J. , Treves S. Ted , Diller Lisa , Greenbaum Nina , Mauch Peter , Lipshultz Steven E.
Published: July 2004

Purpose

Cardiovascular status was assessed in 48 Hodgkin's disease (HD) survivors at a median of 14.3 years (range, 5.9 to 27.5 years) after diagnosis because they may be at increased risk for cardiovascular abnormalities.

Patients and Methods

Patients completed the Short-Form 36 quality-of-life instrument and were screened by echocardiography, exercise stress testing, and resting and 24-hour ECG.

Results

All patients received mediastinal irradiation (median, 40.0 Gy; range, 27.0 to 51.7 Gy) at a median age of 16.5 years (range, 6.4 to 25.0 years). Four patients received an anthracycline. Although every patient described their health as good or better, and none had symptomatic heart disease at screening, all but one had cardiac abnormalities on screening. Restrictive cardiomyopathy was suggested by reduced average left ventricular (LV) dimension (P < .001) and mass (P < .001), without increased LV wall thickness. Significant valvular defects were present in 42%; 75% had conduction defects. One survivor developed complete heart block shortly after the study visit. Autonomic dysfunction was suggested by a monotonous heart rate in 57%, persistent tachycardia in 31%, and blunted hemodynamic responses to exercise in 27%. Peak oxygen uptake (VO2max) during exercise, a predictor of mortality in heart failure, was significantly reduced (< 20 mL/kg/m2) in 30% of survivors. VO2max was correlated with increasing fatigue, increasing shortness of breath (both, r = −0.35; P = .02), and decreasing physical component score on the SF-36 (r = 0.554; P = .00017).

Conclusion

A variety of unsuspected, clinically significant cardiovascular abnormalities are common in long-term survivors of HD who are treated at a young age with mediastinal irradiation. We recommend serial, comprehensive cardiac screening of HD survivors who fit this profile.
Temozolomide As Initial Treatment for Adults With Low-Grade Oligodendrogliomas or Oligoastrocytomas and Correlation With Chromosome 1p Deletions
Authors: Hoang-Xuan K. , Capelle L. , Kujas M. , Taillibert S. , Duffau H. , Lejeune J. , Polivka M. , Crinière E. , Marie Y. , Mokhtari K. , Carpentier A.F. , Laigle F. , Simon J.M. , Cornu P. , Broët P. , Sanson M. , Delattre J.Y.
Published: July 2004

Purpose

To determine the response rate of low-grade oligodendroglial tumors (LGOT) to temozolomide (TMZ) as initial treatment and to evaluate the predictive value of chromosome 1p deletion on the radiologic response.

Patients and Methods

Adult patients with pathologically proven LGOT with progressive disease on magnetic resonance imaging (MRI) were eligible for the study. TMZ was administered at the starting dose of 200 mg/m2/d for 5 days, repeated every 28 days. Response was evaluated clinically and by central review of MRIs. Chromosome 1p and 19q deletions were detected by the loss of heterozygosity technique.

Results

Sixty consecutive patients were included in the study. At the time of analysis, the median number of TMZ cycles delivered was 11. Clinically, 51% of patients improved, particularly those with uncontrolled epilepsy. The objective radiologic response rate was 31% (17% partial response and 14% minor response), whereas 61% of patients had stable disease and 8% experienced disease progression. The median time to maximum tumor response was 12 months (range, 5 to 20 months). Myelosuppression was the most frequent side effect, with grade 3 to 4 toxicity in 8% of patients. Loss of chromosome 1p was associated with objective tumor response (P < .004).

Conclusion

TMZ is well tolerated and provides a substantial rate of response in LGOT. Chromosome 1p loss is correlated with radiographic response and could be a helpful marker for guiding therapeutic decision making in LGOT.
Transcription Suppression of Peroxisome Proliferator-Activated Receptor γ2 Gene Expression by Tumor Necrosis Factor α via an Inhibition of CCAAT/ Enhancer-binding Protein δ during the Early Stage of Adipocyte Differentiation
Authors: Kudo Masataka , Sugawara Akira , Uruno Akira , Takeuchi Kazuhisa , Ito Sadayoshi
Published: July 2004

TNFα is known to inhibit adipocyte differentiation and induce insulin resistance. Moreover, TNFα is known to down-regulate peroxisome proliferator-activated receptor (PPAR)γ2, an adipocyte-specific nuclear receptor of insulin-sensitizer thiazolidinediones. To clarify molecular mechanisms of TNFα- mediated PPARγ2 down-regulation, we here examined the effect of TNFα on transcription regulation of PPARγ2 gene expression during the early stage of adipocyte differentiation. 3T3-L1 preadipocytes (2 d after 100% confluent) were incubated in a differentiation mixture (dexamethasone, insulin, 3-isobutyl-1-methlxanthine), with or without 50 ng/ml TNFα, for 24 h. TNFα significantly decreased PPARγ2 expression both at mRNA and protein levels (to ∼40%), as well as aP2 mRNA expression. The mouse PPARγ2 gene promoter region (2.2-kb) was isolated and was used for luciferase reporter assays by transient transfection. TNFα significantly suppressed PPARγ2 gene transcription (to ∼50%), and deletion analyses demonstrated that the suppression was mediated via CCAAT/enhancer-binding protein (C/EBP) binding elements at the −320/−340 region of the promoter. Moreover, TNFα significantly decreased expression of C/EBPδ mRNA and protein levels (to ∼40%). EMSA, using 3T3-L1 cells nuclear extracts with the −320/−340 region as a probe, demonstrated the binding of C/EBPδ to the element, which was significantly decreased by TNFα treatment. Overexpression of CEBP/δ prevented the TNFα-mediated suppression of PPARγ2 transactivation. Taken together, TNFα suppresses PPARγ2 gene transcription by the inhibition of C/EBPδ expression and its DNA binding during the early stage of adipocyte differentiation, which may contribute to the inhibition of adipocyte differentiation, as well as the induction of insulin resistance.
Transgenic Mice Overexpressing Human Fibroblast Growth Factor 23 (R176Q) Delineate a Putative Role for Parathyroid Hormone in Renal Phosphate Wasting Disorders
Authors: Bai Xiuying , Miao Dengshun , Li Jiarong , Goltzman David , Karaplis Andrew C.
Published: July 2004

Fibroblast growth factor 23 (FGF23) is a recently characterized protein likely involved in the regulation of serum phosphate homeostasis. Increased circulating levels of FGF23 have been reported in patients with renal phosphate-wasting disorders, but it is unclear whether FGF23 is the direct mediator responsible for the decreased phosphate transport at the proximal renal tubules and the altered vitamin D metabolism associated with these states. To examine this question, we generated transgenic mice expressing and secreting from the liver human FGF23 (R176Q), a mutant form that fails to be degraded by furin proteases. At 1 and 2 months of age, mice carrying the transgene recapitulated the biochemical (decreased urinary phosphate reabsorption, hypophosphatemia, low serum 1,25-dihydroxyvitamin D3) and skeletal (rickets and osteomalacia) alterations associated with these disorders. Unexpectantly, marked changes in parameters of calcium homeostasis were also observed, consistent with secondary hyperparathyroidism. Moreover, in the kidney the anticipated alterations in the expression of hydroxylases associated with vitamin D metabolism were not observed despite the profound hypophosphatemia and increased circulating levels of PTH, both major physiological stimuli for 1,25-dihydroxyvitamin D3 production. Our findings strongly support the novel concept that high circulating levels of FGF23 are associated with profound disturbances in the regulation of phosphate and vitamin D metabolism as well as calcium homeostasis and that elevated PTH levels likely also contribute to the renal phosphate wasting associated with these disorders.
Molecular and Functional Characterization of Sex Hormone Binding Globulin in Zebrafish
Authors: Miguel-Queralt Solange , Knowlton Michelle , Avvakumov George V. , Al-Nouno Rana , Kelly Greg M. , Hammond Geoffrey L.
Published: July 2004

SHBG (sex hormone binding globulin) transports androgens and estrogens in the blood of vertebrates including fish. Orthologs of SHBG in fish are poorly defined, and we have now obtained a zebrafish SHBG cDNA and characterized the zebrafish SHBG gene and protein through molecular biological, biochemical, and informatics approaches. Amino-terminal analysis of zebrafish SHBG indicated that its deduced precursor sequence includes a 25-residue secretion polypeptide and exhibits 22–27% homology with mammalian SHBG sequences and 41% with a deduced fugufish SHBG sequence. The 356-residue mature zebrafish SHBG (39,243 Da) sequence comprises a tandem repeat of laminin G-like domains typical of SHBG sequences; contains three N-glycosylation sites; and exists as a 105,000 ± 8700 Da homodimer. Zebrafish SHBG exhibits a high affinity and specificity for sex steroids. An RT-PCR indicated that SHBG mRNA first appears in zebrafish larva, and SHBG mRNA was localized within the liver and gut at this stage of development by whole-mount in situ hybridization. In adult fish, SHBG mRNA was found in liver, testis, and gut. In the liver, immunoreactive SHBG was present in hepatocytes and concentrated in intrahepatic bile duct cells, whereas in the testis it was confined to cells surrounding the seminiferous tubule cysts. In the intestine, immunoreactive SHBG was present in the stroma and epithelial cells of the villous projections and the surrounding muscle. The production and presence of SHBG in the gut of developing and adult zebrafish suggests a novel role for this protein in regulating sex steroid action at this site.
Inner envelope protein 32 is imported into chloroplasts by a novel pathway
Authors: Nada Ahmed , Soll Jürgen
Published: July 2004

The 32 kDa chloroplast inner envelope protein (IEP32) is imported into the organelle in the absence of a cleavable N-terminal pre-sequence. The ten N-terminal amino acids form an essential portion of this targeting information as deduced from deletion mutants. Recognition and translocation of IEP32 is not catalysed by the general chloroplast outer envelope translocon subunits Toc159, Toc75III and Toc34, because IEP32 import is neither inhibited by proteolytic removal of Toc34 and Toc159 nor by inhibition of the Toc75 import channel by CuCl2 or spermine. Import of IEP32 only requires ATP concentrations of below 20 μM indicating that stromal chaperones are not involved in the process, but that IEP32 might be directly inserted from the intermembrane space into the inner envelope by a so far unidentified pathway. IEP32 may require the assistance of Tic22, an intermembrane space translocon subunit for import as indicated by the presence of a chemical crosslinked product between both polypeptides.
Human Dlg protein binds to the envelope glycoproteins of human T-cell leukemia virus type 1 and regulates envelope mediated cell-cell fusion in T lymphocytes
Authors: Blot Vincent , Delamarre Lélia , Perugi Fabien , Pham Danielle , Bénichou Serge , Benarous Richard , Hanada Toshihiko , Chishti Athar H. , Dokhélar Marie-Christine , Pique Claudine
Published: July 2004

Human homologue of the Drosophila Dlg tumor suppressor (hDlg) is a widely expressed scaffold protein implicated in the organization of multi-protein complexes at cell adhesion sites such as the neuronal synapse. hDlg contains three PDZ domains that mediate its binding to the consensus motifs present at the C-termini of various cell surface proteins, thus inducing their clustering and/or stabilization at the plasma membrane. Using a yeast two-hybrid screen, we identified hDlg as a cellular binding partner of a viral membrane integral protein, the envelope glycoprotein (Env) of human T-cell leukemia virus type 1 (HTLV-1). HTLV-1 is a human retrovirus that infects CD4+ T lymphocytes and is preferentially transmitted via direct contacts between infected and target cells, through a structure referred to as the virological synapse. Here, we demonstrate that hDlg interacts with a classical PDZ domain-binding motif present at the C-terminus of the cytoplasmic domain of HTLV-1 Env and conserved in the related HTLV-2 virus. We further document that, in HTLV-1 infected primary T cells, hDlg and Env are concentrated in restricted areas of the plasma membrane, enriched in molecules involved in T-cell contacts. The presence of Gag proteins responsible for viral assembly and budding in these areas indicated that they constitute platforms for viral assembly and transmission. Finally, a mutant virus unable to bind hDlg exhibited a decreased ability to trigger Env mediated cell fusion between T lymphocytes. We thus propose that hDlg stabilizes HTLV-1 envelope glycoproteins at the virological synapse formed between infected and target cells, hence assisting the cell-to-cell transmission of the virus.
Peroxisome elongation and constriction but not fission can occur independently of dynamin-like protein 1
Authors: Koch Annett , Schneider Gabriele , Lüers Georg H. , Schrader Michael
Published: July 2004

The mammalian dynamin-like protein DLP1 belongs to the dynamin family of large GTPases, which have been implicated in tubulation and fission events of cellular membranes. We have previously shown that the expression of a dominant-negative DLP1 mutant deficient in GTP hydrolysis (K38A) inhibited peroxisomal division in mammalian cells. In this study, we conducted RNA interference experiments to `knock down' the expression of DLP1 in COS-7 cells stably expressing a GFP construct bearing the C-terminal peroxisomal targeting signal 1. The peroxisomes in DLP1-silenced cells were highly elongated with a segmented morphology. Ultrastructural and quantitative studies confirmed that the tubular peroxisomes induced by DLP1-silencing retained the ability to constrict their membranes but were not able to divide into spherical organelles. Co-transfection of DLP1 siRNA with Pex11pβ, a peroxisomal membrane protein involved in peroxisome proliferation, induced further elongation and network formation of the peroxisomal compartment. Time-lapse microscopy of living cells silenced for DLP1 revealed that the elongated peroxisomes moved in a microtubule-dependent manner and emanated tubular projections. DLP1-silencing in COS-7 cells also resulted in a pronounced elongation of mitochondria, and in more dispersed, elongated Golgi structures, whereas morphological changes of the rER, lysosomes and the cytoskeleton were not detected. These observations clearly demonstrate that DLP1 acts on multiple membranous organelles. They further indicate that peroxisomal elongation, constriction and fission require distinct sets of proteins, and that the dynamin-like protein DLP1 functions primarily in the latter process.
MAP kinases as structural adaptors and enzymatic activators in transcription complexes
Authors: Edmunds John W. , Mahadevan Louis C.
Published: July 2004

Mitogen-activated protein kinase (MAPK) pathways regulate eukaryotic gene expression in response to extracellular stimuli. MAPKs and their downstream kinases phosphorylate transcription factors, co-regulators and chromatin proteins to initiate transcriptional changes. However, the spatial context in which the MAPKs operate in transcription complexes is poorly understood. Recent findings in budding yeast show that MAPKs can form integral components of transcription complexes and have novel structural functions in addition to phosphorylating local substrates. Hog1p MAPK is stably recruited to target promoters by specific transcription factors in response to osmotic stress, and acts as both a structural adaptor and enzymatic activator driving the assembly and activation of the transcription complex. We review the evidence that suggests a similar bifunctional role for MAPKs in mammalian transcription complexes.
Optimizing the assessment of quality of life after laryngeal cancer treatment
Authors: Lee-Preston V. , Steen I. N. , Dear A. , Kelly C. G. , Welch A. R. , Meikle D. , Stafford F. W. , Wilson J. A.
Published: July 2004

Reports of the impact of larynx cancer treatment modality on quality of life are conflicting, in part due to varying study methodology. The aims of this study were to (1) provide preliminary comparisons of quality of life following radiotherapy or combination therapy; (2) evaluate a number of measures of quality of life and thereby (3) inform future prospective studies. Thirty-six laryngeal cancer patients, 24 following radiotherapy, 12 following radiotherapy and laryngectomy completed the Functional Assessment of Cancer Therapy (FACT) - General/Head and Neck subscale; Nottingham Health Profile (NHP); and the Hospital Anxiety and Depression scale (HAD), three to 12 months post-treatment. Results showed trends towards a less good quality of life in the combined therapy group over a wide range of outcomes, significant for the disease specific FACT head and neck subscale, NHP emotion (p = 0.04) and isolation (p = 0.027). To the authors' knowledge, however, this is the first demonstration of greater impact of laryngeal cancer on quality of life in younger subjects, who had lower scores among others on emotional wellbeing (p = 0.015) and anxiety (p = 0.035). Younger patients thus appear more likely to need more intensive support through treatment. Many of the physical and psychosocial domains derived from the three tools used were highly correlated. In other words, given the known high morbidity of the disease and its treatment, the selection of tools for head and neck quality of life assessment may be much less important than their universal application.
Subcutaneous emphysema of the neck in infancy: under-recognized presentation of child abuse
Authors: Ramnarayan Padmanabhan , Qayyum Asad , Tolley Neil , Nadel Simon
Published: July 2004

Two cases of subcutaneous emphysema of the neck as a result of abuse in infancy are presented to add to the variety of findings associated with the maltreatment of infants. Pharyngeal perforations as a result of abuse are rare. These cases are presented as a reminder to the attending clinician that although most cases of subcutaneous emphysema may resolve without any complications a detailed examination for the cause should be performed and the history carefully verified.
Post‐traumatic stress disorder and anxiety symptoms in children exposed to the 1999 Greek earthquake
Authors: Groome David , Soureti Anastasia
Published: July 2004

Five months after the Athens earthquake of September 1999, 178 children from three districts of Athens at increasing distances from the epicenter were administered questionnaires to identify symptoms of post‐traumatic stress disorder (PTSD), anxiety and the extent of personal threat experienced. It was found that PTSD and anxiety symptoms were significantly related to proximity to the epicenter, exposure to threat and female gender. Age did not have a significant main effect on either anxiety or PTSD symptoms, but there were significant interactions between age and the other main variables. In the region closest to the epicenter, the youngest children reported the highest PTSD and anxiety symptom scores, but in the group furthest from the epicenter the older children reported the highest PTSD and anxiety symptom scores. These findings were discussed in relation to direct and media‐imparted exposure to the earthquake.
Temporal processing deficits in high‐functioning children with autism
Authors: Szelag Elzbieta , Kowalska Joanna , Galkowski Tadeusz , Pöppel Ernst
Published: July 2004

It is well known that complex functions (e.g. perception, attention, memory, emotions, social interactions and language) are usually disturbed in autism. As these functions are characterized by specific temporal patterns, the present study examined whether children with autism show typical temporal processing in the time domain of a few seconds. Using a temporal‐reproduction paradigm, we found that they were unable to link their responses to stimulus duration. Independently of stimulus duration, they reproduced auditory or visual stimuli with the same response duration of, on average, 3 s. These results demonstrate important deficits in duration judgment in individuals with autism. As other experiments provide evidence for a temporal processing platform of ≅ 2 — 3 s in normal individuals, this platform may be preserved in a residual form in autism.
Beobachtergestützte Überwachung vernetzter regelungstechnischer Systeme (Observer Schemes for Networked Control Systems)
Authors: Ding Steven X. , Zhang Ping , Weinhold Nick
Published: July 2004

Die Überwachung vernetzter regelungstechnischer Systeme gewinnt in der Prozessautomatisierung zunehmend an Bedeutung. Da das Gesamtsystemverhalten verstärkt von technischen Gegebenheiten des eingesetzten Bussystems beeinflusst wird, werden im vorliegenden Beitrag vernetzte Systeme zunächst modelliert, indem die unbekannten und statistisch schwankenden Datenübertragungszeiten als Modellunsicherheit erfasst werden. Basierend darauf werden zwei beobachtergestützte Ansätze erarbeitet, welche die Schätzung der Prozesszustandsgrößen bzw. der Störgrößen ermöglichen. Anhand eines Beispiels wird schließlich die Anwendbarkeit dieser Ansätze demonstriert.
Effect of constricted polymerization time on nanofiltration membrane characteristic and performance: A study using the Donnan Steric Pore Flow Model
Authors: Ahmad A. L. , Ooi B. S. , Wahab Mohammad A. , Choudhury J. P.
Published: July 2004

Polyamide composite nanofiltration membranes are fabricated under constricted polymerization time. The membranes were characterized for pore size, effective thickness/porosity as well as effective membrane charge density using the Donnan Steric Pore Flow Model. The effect of polymerization (reaction) time on the membrane characteristics and membrane performance (flux and rejection) was studied. The effect of polymerization time on pore size is not significant for reaction times less than 120 s but the effective thickness/porosity seems to be increasing proportionally with polymerization time. Effective membrane charge density for all the membranes depended on the degree of condensation and hydrolysis process. Polymerization time is an important process condition that could change the effective thickness/porosity, pore size, and effective volume charge density and subsequently affect the membrane performance in terms of flux and rejection. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 394–399, 2004
Influence of some additives on rheological properties, viscosity, and dynamic mechanical properties in NR compounds
Authors: Ibarra L. , Posadas P. , Esteban‐Martinez M.
Published: July 2004

The effect of some processing aids, Redex‐2, Redex‐SP‐2, and Redex‐A, on rheological properties, tensile properties, and dynamic mechanical properties of natural rubber compounds has been studied. The optimum level of these additives was determined and the changes caused by the use of these additives were evaluated by comparison with an additive‐free control compound mixed under similar conditions. Redex‐2 and Redex‐SP‐2 improve the processability of the natural rubber compounds, giving a reduction of both Mooney viscosity and shear viscosity, but the concentration of the processing aid necessary to this improvement is different; the optimum concentration is 1.75 phr on Redex‐2 compounds, and the optimum concentration is 3 phr on Redex‐SP‐2 compounds. However, Redex‐A behaves as a plasticizer, reducing the Mooney viscosity, the shear viscosity, and the Tg, improving behavior at low temperatures. The optimum proportion is 3 phr. The behavior of these processing aids is related to the temperature, too. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 332–344, 2004
Catalyst effect on cure reactions in the blend of aromatic dicyanate ester and bismaleimide
Authors: Lin Rong‐Hsien , Lee An‐Cheng , Lu Wei‐Hua , Lin Chih‐Wei
Published: July 2004

Catalyst effects on cure reactions of a bismaleimide [4,4′‐bismaleimidodiphenylmethane (BMI)] associated with a liquid aromatic dicyanate ester [1,1′‐bis(4‐cyanatophenyl)ethane (BEDCy)] and with a powder type of aromatic dicyanate ester [bisphenol A dicyanate (BADCy)] were thoroughly investigated by in situ FTIR and DSC dynamic scanning. In noncatalyzed blend systems, coreactions between the dicyanate ester and bismaleimide always occur, and thus the formation of the pyrimidine and/or pyridine structures occurs. The pyrimidine structure always predominates. The use of a dicyanate‐sensitive catalyst facilitates the formation of a sequential interpenetrating network (IPN). The extent of the sequential IPN depends on the level of catalyst and the type of matrix materials, and thus the extent of coreactions. Probable reaction paths were also proposed for various formulations of hybrid blends. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 345–354, 2004
Synthesis and characterization of polyimide/silica hybrid nanocomposites
Authors: Chen Bor‐Kuan , Chiu T.‐M. , Tsay Sun‐Yuan
Published: July 2004

Polyimide/silica (PI/SiO2) hybrid nanocomposites were prepared by the sol‐gel process directly from a soluble polyimide. This soluble PI was synthesized from a diamine with a pendant phenyl hydroxyl group, 4,4′‐diamino‐4″‐hydroxy triphenyl methane (DHTM) and a dianhydride, pyromellitic dianhydride (PMDA), followed by cyclodehydration. Three ways of preparing PI/SiO2 hybrid nanocomposites were investigated in this study. Two of them used the coupling agent 3‐glycidyloxy propyl trimethoxysilane (GPTMOS) to enhance the compatibility between PI and silica. The coupling agent can react with the PI to form covalent bonds. The structures of the modified hybrid nanocomposites were identified with a FTIR, whereas the size of the silica in polyimides was characterized with a scanning electron microscope. The size of silica particles in the modified system was <100 nm. The covalently bonded PI/SiO2 hybrid nanocomposites prepared by the novel third approach exhibited good transparency when the silica content was <15%. Moreover, their thermal and mechanical properties exhibited a significant improvement. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 382–393, 2004