bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstitution of skinned cardiac fibres with human recombinant cardiac troponin‐I mutants and troponin‐C
Authors: Dohet Catherine , Al-Hillawi Eman , Trayer Ian P. , Rüegg J.C.
Published: May 2003

Troponin C (TnC) could be extracted from skinned porcine cardiac muscle fibres and their Ca2+ sensitivity restored by reconstitution with recombinant human cardiac TnC. After extraction of troponin I (TnI) and TnC using the vanadate treatment method of Strauss et al. [Strauss, J. D., Zeugner, C., Van Eyk, J.E., Bletz, C., Troschka, M. and Rüegg, J.C. (1992) FEBS Lett. 310, 229–234], skinned porcine cardiac muscle fibres were reconstituted with wild‐type recombinant human cardiac TnC and either wild‐type cardiac TnI or several mutant isoforms of human TnI. Reconstitution with wild‐type proteins restored the Ca2+ sensitivity of the tissue and phosphorylation of the TnI with the catalytic subunit of protein kinase A reduced the Ca2+ sensitivity (i.e. ‐log[Ca2+] for 50% of maximal force) as has been shown by others. However, reconstitution with the TnI mutant Ser‐23Asp/Ser‐24Asp mimicking the phosphorylated form of cardiac TnI, led to a reduced Ca2+ sensitivity compared with reconstitution with wild‐type TnI, whereas the mutant Ser‐23Ala/Ser‐24Ala behaved as the dephosphorylated form of TnI. These data confirm the importance of negative charge in this region of the TnI molecule in altering the Ca2+ responsiveness in this system.
A study to survey susceptible genetic factors responsible for troglitazone‐associated hepatotoxicity in Japanese patients with type 2 diabetes mellitus
Authors: Watanabe Ichiro , Tomita Aiko , Shimizu Miho , Sugawara Mie , Yasumo Hiroaki , Koishi Ryuta , Takahashi Tohru , Miyoshi Kaoru , Nakamura Kouichi , Izumi Takashi , Matsushita Yasuyuki , Furukawa Hidehiko , Haruyama Hideyuki , Koga Teiichiro
Published: May 2003

Background and objective

Troglitazone is a 2,4‐thiazolidinedione antidiabetic agent with insulin‐sensitizing activities. This agent had been used efficiently in a large number of patients but was withdrawn from the market in March 2000 because of its association with idiosyncratic hepatotoxicity. To address the susceptible genetic factors responsible for the hepatotoxicity associated with this agent, we performed a genetic polymorphic analysis by a target gene approach in troglitazone‐treated Japanese patients with type 2 diabetes mellitus.

Methods

One hundred ten patients treated with troglitazone were recruited into this study. The case patients (n = 25) were recruited through medical professionals who had previously reported abnormal increases in the levels of ALT or AST among their patients. The control patients (n = 85) were recruited through physicians prescribing troglitazone. For statistical accuracy, efforts were made to maximize the size of the case group. Genotype analysis was performed in 68 polymorphic sites of 51 candidate genes related to drug metabolism, apoptosis, roduction and elimination of reactive oxygen species, and signal transduction pathways of peroxisome proliferator–activated receptor gamma 2 and insulin.

Results

The strong correlation with transaminase elevations was observed in the combined glutathione‐S‐transferase GSTT1‐GSTM1 null genotype (odds ratio, 3.692; 95% confidence interval, 1.354‐10.066; P = .008).

Conclusions

The double null mutation of GSTT1 and GSTM1 might influence troglitazone‐associated abnormal increases of liver enzyme levels.

Clinical Pharmacology & Therapeutics (2003) 73, 435–455; doi: 10.1016/S0009‐9236(03)00014‐6
Characterization of hepatic cytochrome P4503A activity in patients with end‐stage renal disease
Authors: Dowling Thomas C. , Briglia Andrew E. , Fink Jeffrey C. , Hanes Donna S. , Light Paul D. , Stackiewicz Lucy , Karyekar Chetan S. , Eddington Natalie D. , Weir Matthew R. , Henrich William L.
Published: May 2003

Background

The cytochrome P450 (CYP) oxidative enzyme system, located primarily in the liver and small intestine, is responsible for metabolism and detoxification of numerous endogenous and exogenous substances. The most abundant CYP enzyme, CYP3A, is known to be involved in the metabolism of more than 200 commonly used medications. In experimental models of renal failure, both hepatic function and CYP enzyme content are reduced; however, direct evidence in humans is lacking. Evaluation of drug metabolism in patients with end‐stage renal disease is important because these patients use a large number of medications and are at risk of adverse reactions and drug‐drug interactions.

Methods

We measured hepatic CYP3A activity at baseline and after rifampin (INN, rifampicin) enzyme induction in 12 patients with end‐stage renal disease and 12 healthy, age‐matched controls. Hepatic CYP3A phenotype was characterized with the erythromycin breath test, and enzyme induction capacity was evaluated with a short course of rifampin (600 mg/d for 6 days).

Results

The end‐stage renal disease group had 28% lower baseline erythromycin breath test values than controls (P < .05); however, enzyme induction capacity after rifampin administration was similar between groups (P = .70).

Conclusion

The findings suggested that one mechanism by which patients with end‐stage renal disease are at increased risk of drug toxicity is reduced activity of the CYP3A enzyme pathway.

Clinical Pharmacology & Therapeutics (2003) 73, 427–434; doi: 10.1016/S0009‐9236(03)00056‐0
The A20‐binding protein ABIN‐2 exerts unexpected function in mediating transcriptional coactivation
Authors: Chien Chia-Yi , Liu Wei-Kuang , Chou Chen-Kung , Su Jin-Yuan
Published: May 2003

The human ABIN‐2 was originally identified as an A20‐associating cytosolic protein to block NF‐κB activation induced by various stimuli. Here we report that ABIN‐2 has the potential to enter the nucleus and plays a role in mediating transcriptional activation in both yeast and mammalian cells. The Gal4BD–ABIN‐2 fusion protein is able to drive the expression of the GAL4‐responsive reporter gene in yeast efficiently without the need of the Gal4p activation domain, suggesting that ABIN‐2 functions as a transcriptional coactivator and facilitates transcription in yeast. In contrast to the activity in yeast, however, only the C‐terminal fragment of ABIN‐2 exerts the transactivating activity in mammalian cells but not the full‐length ABIN‐2 protein. This observation has led to the identification of the N‐terminal 195 amino acids of ABIN‐2 as a regulatory domain, which retains the full‐length ABIN‐2 in the cytoplasm of mammalian cells and thus cannot transactivate. We have also found that BAF60a, a component of chromatin‐remodeling complex, interacts with ABIN‐2 by the yeast two‐hybrid analysis. Together, our results suggest that the nuclear ABIN‐2 defines a novel transcriptional coactivator and acts presumably by recruiting a chromatin‐remodeling complex to the site of the target gene.
Regulatory mechanism of Cordyceps sinensis mycelium on mouse Leydig cell steroidogenesis
Authors: Hsu Chih-Chao , Tsai Shaw-Jeng , Huang Yuan-Li , Huang Bu-Miin
Published: May 2003

We demonstrate the mechanism by which Cordyceps sinensis (CS) mycelium regulates Leydig cell steroidogenesis. Mouse Leydig cells were treated with forskolin, H89, phorbol 12‐myristate 13‐acetate, staurosporine, or steroidogenic enzyme precursors with or without 3 mg/ml CS; then testosterone production was determined. H89, but not phorbol 12‐myristate 13‐acetate or staurosporine, decreased CS‐treated Leydig cell steroidogenesis. CS inhibited Leydig cell steroidogenesis by suppressing the activity of P450scc enzyme, but not 3β‐hydroxysteroid dehydrogenase, 17α‐hydroxylase, 20α‐hydroxylase, or 17β‐hydroxysteroid dehydrogenase enzymes. Thus, CS activated the cAMP–protein kinase A signal pathway, but not protein kinase C, and attenuated P45scc enzyme activity to reduce human chorionic gonadotropin‐stimulated steroidogenesis in purified mouse Leydig cells.
Down‐regulation of ARC contributes to vulnerability of hippocampal neurons to ischemia/hypoxia
Authors: Hong Yeon-Mi , Jo Dong-Gyu , Lee Joo-Yong , Chang Jae-Woong , Nam Jung-Hyun , Noh Jee Yeon , Koh Jae-Young , Jung Yong-Keun
Published: May 2003

ARC is a caspase recruitment domain‐containing molecule that plays an important role in the regulation of apoptosis. We examined ARC expression during neuronal cell death following ischemic injury in vivo and in vitro. After exposure to transient global ischemic conditions, the expression of ARC was substantially reduced in the CA1 region of hippocampus in a time‐dependent manner with concomitant increase of TUNEL‐positive cells. Quantitative analysis using Western blotting exhibited that most of ARC protein disappeared in the cultured hippocampal neurons exposed to hypoxia for 12 h and showing 60% cell viability. Forced expression of ARC in the primary cultures of hippocampal neurons or B103 neuronal cells significantly reduced hypoxia‐induced cell death. Further, the C‐terminal P/E rich region of ARC was effective to attenuate hypoxic insults. These results suggest that down‐regulation of ARC expression in hippocampal neurons may contribute to neuronal death induced by ischemia/hypoxia.
Aggregates from mutant and wild‐type α‐synuclein proteins and NAC peptide induce apoptotic cell death in human neuroblastoma cells by formation of β‐sheet and amyloid‐like filaments
Authors: El-Agnaf Omar M.A , Jakes Ross , Curran Martin D , Middleton Derek , Ingenito Raffaele , Bianchi Elisabetta , Pessi Antonello , Neill David , Wallace Andrew
Published: May 2003

α‐Synuclein (α‐syn) protein and a fragment of it, called NAC, have been found in association with the pathological lesions of a number of neurodegenerative diseases. Recently, mutations in the α‐syn gene have been reported in families susceptible to an inherited form of Parkinson's disease. We have shown that human wild‐type α‐syn, mutant α‐syn(Ala30Pro) and mutant α‐syn(Ala53Thr) proteins can self‐aggregate and form amyloid‐like filaments. Here we report that aggregates of NAC and α‐syn proteins induced apoptotic cell death in human neuroblastoma SH‐SY5Y cells. These findings indicate that accumulation of α‐syn and its degradation products may play a major role in the development of the pathogenesis of these neurodegenerative diseases.
Oral misoprostol vs. placebo in the management of prelabor rupture of membranes at term
Authors: Hoffmann R.A.M , Anthony J , Fawcus S
Published: May 2003

Objective: To evaluate the efficacy of oral misoprostol for the induction of labor (IOL) in women with prelabor rupture of membranes at term (PROM) and to monitor maternal or fetal complications. Method: This randomized, placebo controlled trial was performed in a secondary referral hospital. The data of 47 patients in the misoprostol — and 49 patients in the placebo group was available for analysis. The former received 100 μg misoprostol orally, repeated once after 6 h if not in active labor, the latter received two doses of vitamin C also after a 6‐h interval. The Mann‐Whitney U‐test was used for analysis. Results: The median treatment to delivery interval in the misoprostol group was 7.5 h and 25 h in the placebo group (P<0.001). No significant differences were found in the incidence of abnormalities on the cardiotocograph, mode of delivery, neonatal outcome, use of antibiotics for the mothers and patient acceptability. Conclusion: Oral misoprostol in the suggested dose is an effective and cheap alternative for IOL in patients with PROM. No adverse effects could be demonstrated.
Whatever happened to the ‘microtrabecular concept’?
Authors: Heuser John
Published: May 2003

Summry— Keith Porter culminated his stellar career as the founding father of biological electron microscopy by acquiring, in the late 1970s, a high‐voltage electron microscope (HVEM). With this magnificent instrument he examined whole‐mounts of cultured cells, and perceived within them a structured cytoplasmic matrix he named the “microtrabecular lattice”. Over the next decade Porter published a series of studies, together with a team of outstanding young colleagues, which elaborated his broader “microtrabecular concept.” This concept posited that microtrabeculae were real physical entities that represented the fundamental organization the cytoplasm, and that they were the physical basis of cytoplasmic motility and of cell‐shape determination. The present review presents Porter's original images of microtrabeculae, after conversion to a more interpretable “digital‐anaglyph” form, and discusses the rise and fall of the microtrabecular concept. Further, it explains how the HVEM images of microtrabeculae finally came to be considered as an artifact of the preparative methods Porter used to prepare whole cells for HVEM. Still, Keith's “microtrabecular concept” foretold of our current appreciation of the complexity and pervasiveness of the cytoskeleton, which has now been found by more modern methods of EM to actually be the fundamental organizing principle of the cytoplasmic matrix. During the impending eclipse of Porter's microtrabecular concept in the late 1980s, many of Keith's colleagues fondly described the cell as being filled, not with protoplasm, but with “Porterplasm.” Despite the fact that Keith's view was clouded by the methods of his time, it would be fitting and apt to retain this name, still today, for the ordered matrix of cytoskeletal macromolecules that exists in the living cell. In the end, the story of what happened to Porter's microtrabecular concept should be an object lesson in scientific hubris that should humble and inform all of us in cell biology, even today — particularly when we begin to think that our most recent methods and observations are achieving “the last word”.
Nitric oxide and S‐nitrosylation: excitotoxic and cell signaling mechanism
Authors: Nelson Eric J , Connolly Jon , McArthur Patrick
Published: May 2003

Abstract This review focuses on the important physiological messenger, nitric oxide (NO), and its role in N‐methyl‐D‐aspartate (NMDA) excitotoxicity. NO has been shown to be a key mediator of voltage‐gated Ca+2 transmembrane proteins. It remains unclear whether NO is implicated during hypoxia, or ischemic/reperfusion injuries as a neuroprotective or neurodegenerative factor. Excitotoxicity results from the excessive stimulation of excitatory glutamate receptors within the CNS. This review maintains that the feed‐forward pathway precipitated by oxidative stress is the discriminating factor in the neuroprotective or neurodegenerative actions of NO.
Structural inheritance in Paramecium: ultrastructural evidence for basal body and associated rootlets polarity transmission through binary fission⋆
Authors: Iftode Francine , Fleury‐Aubusson Anne
Published: May 2003

Abstract One main difference between basal bodies and centrioles resides in the expression of their polarity: centrioles display a structural nine‐fold radial symmetry, whereas basal bodies express a circumferential polarity, thanks to their asymmetric set of rootlets. The origin of this polarity during organelle duplication still remains under debate: is it intrinsic to the nine‐fold structure itself (i.e. the nine microtubular triplets are not equivalent) or imposed by its immediate environment at time of assembly? We have reinvestigated this problem using the Ciliate Paramecium, in which the pattern of basal body duplication is well known. In this cell, all basal bodies produced within ciliary rows appear immediately anterior to parental ones. Observations on cells fixed with the tannic acid protocol suggest that, to be competent for basal body assembly, parental basal bodies have to be individually associated with a complete set of rootlets (monokinetid structure). During pro‐basal body assembly, full microtubular triplets were detected according to a random circumferential sequence; during the whole process, the new basal body and its associated rootlets maintained structural relations with the parental monokinetid structure by way of specific links. These results strongly suggest that basal body and associated rootlets (kinetid) polarity is driven by its immediate environment and provide a basis for the structural heredity property observed by Sonneborn some decades ago.
Heuristic, optimal, static, and dynamic schedules when processing times are uncertain
Authors: Lawrence Stephen R. , Sewell Edward C.
Published: May 2003

In this paper we compare the static and dynamic application of heuristic and optimal solution methods to job‐shop scheduling problems when processing times are uncertain. Recently developed optimizing algorithms and several heuristics are used to evaluate 53 standard job‐shop scheduling problems with a makespan objective when job processing times are known with varying degrees of uncertainty. Results indicate that fixed optimal sequences derived from deterministic assumptions quickly deteriorate with the introduction of processing time uncertainty when compared with dynamically updated heuristic schedules. As processing time uncertainty grows, we demonstrate that simple dispatch heuristics provide performance comparable or superior to that of algorithmically more sophisticated scheduling policies.
Early reattachment does not reverse atrophy and fat accumulation of the supraspinatus—an experimental study in rabbits
Authors: Uhthoff Hans K. , Matsumoto Fujio , Trudel Guy , Himori Ko
Published: May 2003

Introduction: Reattachment of the supraspinatus (SSP) tendon after spontaneous rupture leads to improved shoulder function. Whether this improvement of function is due to a reversal of muscle atrophy and fat accumulation known to occur after SSP rupture is still debated. Our previous study of late reattachment of SSP (12 weeks) failed to confirm a reversal of muscle atrophy and of fat accumulation.

Purpose: To find out whether earlier reattachment (6 weeks) reverses atrophy and fat accumulation of the SSP.

Material and methods: Reattachment group: in seven rabbits unilateral supraspinatus detachment, reattachment after 6 weeks and killing 6 weeks later. Detachment group: in seven rabbits unilateral supraspinatus detachment and killing 12 weeks later. The contralateral shoulders served as controls (n = 14). Determination of the supraspinatus constituents: muscle, extra‐ and intramuscular fat in volume and cross‐sectional area.

Results: Muscle tissue in the reattachment group (8.6 ml ± 1 s.d. = 0.6) and in the detachment group (8.9 ml ± 0.9) were less than in control supraspinati (10.2 ml ± 0.9, both p < 0.05). Extra‐ and intramuscular fat in the reattachment group (8.7% ± 3.2) was greater than in both, the detachment group (4.6% ± 3.5), and control supraspinati (2.8% ± 1.7, both p < 0.05).

Conclusion: In the rabbit, reattachment of the SSP at 6 weeks did neither reverse muscle atrophy nor fat accumulation during the ensuing 6 weeks. However, earlier reattachment (6 weeks) when compared with later reattachment (12 weeks) prevented an increase in fat accumulation. On the other hand, the delay before reattaching the tendon did not lead to an increase in muscle atrophy.

© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Exercise and muscle strength training and their effect on quality of life in patients with chronic heart failure
Authors: Radzewitz Andrea , Miche Eckart , Herrmann Gert , Nowak Mirella , Montanus Uta , Adam Ulrike , Stockmann Ylva , Barth Maria
Published: May 2003

Background:

There is now evidence that moderate training plays an important role in the treatment of chronic heart failure. No clear instructions exist to date as to how such training programs should be carried out.

Aim:

to assess the efficiency of a training program including bicycle ergometer training, moderate muscle strength training and the 6‐min walk test and their influence on quality of life, anxiety and depression.

Methods and results:

Patients (67 male, 21 female) underwent a standardized 4‐week training program. Baseline data: LVEF=31±8%; LVEDD=143±59 ml; peak VO2=13.9±4.6 kg/ml. No adverse side effects could be observed. At discharge LVEF was 37±9%, (P=0.001); LVEDD=131±44ml (P=0.01); and peak VO2=15.4±5.0 kg/ml. Quality of life improved significantly in nearly all domains and in summary score. There were no significant changes in anxiety and depression. There is a negative correlation between the initial workload and changes in physical health (r=−0.42, P=0.001) and only a weak correlation between age and positive changes in physical health (r=0.26, P=0.05).

Conclusions:

A standardized training program including moderate muscle strength training could be performed safely and demonstrated improvement in clinical parameters and quality of life.
Simultaneous angiotensin converting enzyme inhibition moderates ventricular dysfunction caused by doxorubicin
Authors: Vaynblat Mikhail , Shah Himansu R. , Bhaskaran Dinesh , Ramdev Geeta , Davis Wellington J. , Cunningham Joseph N. , Chiavarelli Mario
Published: May 2003

Aims:

The purpose of this study was to determine that the administration of an angiotensin converting enzyme (ACE) inhibitor enalapril would confer protection against doxorubicin‐induced experimental heart failure, and attenuate the development of left ventricular dysfunction.

Methods:

Seventeen dogs were chronically instrumented with an intracoronary catheter and received doxorubicin weekly for 4 weeks. Animals were assigned to two groups: group 1: untreated heart failure; and group 2: simultaneous enalapril administration (5 mg twice a week). Hemodynamic data were obtained at week 0 and 12. Echocardiography was performed weekly.

Results

Survival improved with simultaneous enalapril administration (36% in group 1 vs. 100% in group 2, P=0.04). The increase in the left ventricular end‐diastolic pressure was significantly reduced at week 12 (17±1 mmHg in group 1 vs. 9±1 mmHg in group 2, P=0.0042). The fall in left ventricular stroke work index was significantly prevented (52% in group 1 vs. 21% in group 2, P=0.006). The increase in right ventricular end‐diastolic diameter was significantly reduced by enalapril prophylaxis.

Conclusion:

Simultaneous treatment with enalapril was beneficial in the prevention of doxorubicin‐induced cardiomyopathy.
Increased levels of high sensitive C‐reactive protein in patients with chronic rheumatic valve disease: evidence of ongoing inflammation
Authors: Gölbasi Zehra , Uçar Özgül , Keles Telat , Sahin Ahmet , Çagli Kerim , Çamsari Ahmet , Diker Erdem , Aydogdu Sinan
Published: May 2003

The precise pathogenetic mechanism(s) of rheumatic fever and rheumatic heart disease have never been defined. C‐reactive protein (CRP) is increased in patients with acute rheumatic fever, but it is not known whether plasma levels increase in patients with chronic rheumatic valve disease. The aim of this study was to determine the role of inflammation detected by high sensitivity CRP (hs‐CRP) levels in the progression of chronic rheumatic valve disease. A total of 113 patients with chronic rheumatic valve disease (81 women, 32 men; mean age 40±14 years, range 13–70), 51 patients with prosthetic valve(s) (31 women, 20 men; mean age 48±13 years, range 21–71) and 102 healthy subjects (68 women, 34 men, mean age 41±12 years, range 25–73), as a control group, were assessed. Patients with acute rheumatic fever, acute infection, inflammatory disease, malignancy, acute myocardial infarction and trauma were excluded. hs‐CRP was determined using latex‐enhanced immunonephelometric assays on a BN II analyzer (Behring). Transthoracic echocardiography was performed in all patients in order to evaluate valvular disease. Levels of hs‐CRP were significantly higher in patients with chronic rheumatic heart disease than in patients with prosthetic valve(s) and healthy subjects (0.62±0.64 vs. 0.35±0.41 vs. 0.24±0.18 mg/l, P<0.01 and P<0.001 respectively). No correlation was observed between CRP and age, sex or functional capacity. We found that hs‐CRP is increased in chronic rheumatic heart disease; this may indicate that inflammatory response still persists in the chronic phase.
On solitary wave mediated heat exchange in the Antarctic boundary layer
Authors: Rees J.M. , Koprov B. , Koprov V. , Zimmerman W.B.
Published: May 2003

The adiabatic assumption that the vertical velocity can be estimated from the displacement of isotherms is examined for solitary wave events propagating in the stable boundary layer overlying an Antarctic ice shelf. Implications for the mathematical modelling of such waves when this assumption is invalid are discussed. Copyright © 2003 Royal Meteorological Society. Published by Elsevier Ltd. All rights reserved.
HLA associations in type 1 diabetes: DPB1 alleles may act as markers of other HLA‐complex susceptibility genes
Authors: Johansson S. , Lie B.A. , Pociot F. , Nerup J. , Cambon‐Thomsen A. , Kockum I. , Thorsby E. , Undlien D.E.
Published: May 2003

Abstract:  Alleles at the HLA‐DQB1, ‐DQA1 and ‐DRB1 loci are major determinants for susceptibility to develop type 1 diabetes (T1D). Increasing evidence supports that also other genes in, or near, the HLA complex contribute to the HLA‐encoded risk. Alleles at the DPB1 locus have been suggested to directly influence the risk conferred by DQB1, DQA1 and DRB1 alleles, but the results are conflicting. We therefore genotyped 217 families from Norway, Denmark, Sweden and southern France to address the role of DPB1 alleles in T1D. After taking into account linkage disequilibrium (LD) with DQB1, DQA1 and DRB1 alleles, we found evidence that some DPB1 alleles are associated with modulating the risk of developing T1D. However, we show that the strong LD in the HLA complex, and the presence of extended haplotypes complicate the interpretation of the results. On DQ2‐DR3 haplotypes, both allele 3 at microsatellite D6S2223 located 5.3‐Mb telomeric of DPB1 and the extended DQ2‐DR3‐B18 haplotype display much stronger association than DPB1 alleles. When we exclude these effects, most of the apparent association of DPB1 alleles on DQ2‐DR3 haplotypes disappear. Taken together, although we cannot completely rule out an effect of some DPB1 alleles, we propose that the statistically significant, albeit weak, DPB1 associations found are most likely the result of LD with another unidentified disease‐susceptibility gene(s) in this region.
TNF‐α polymorphisms and type 2 diabetes mellitus in Taiwanese patients
Authors: Shiau M‐Y. , Wu C‐Y. , Huang C‐N. , Hu S‐W. , Lin S‐J. , Chang Y‐H.
Published: May 2003

Abstract:  Type 2 diabetic mellitus (type 2 DM) comprises more than 95% of all Taiwanese patients with DM. Tumor necrosis factor‐alpha (TNF‐α) expression is linked with insulin resistance, and is under strong genetic control. The correlation between TNF promoter genotypes and type 2 DM is still controversial, because discrepancies among different studies exist. Ethnic differences play certain roles in these conflicting results, because the distribution of TNF promoter polymorphisms is different among study subjects with different racial origins. Therefore, we examined the relationship between the incidence of type 2 diabetes in Taiwanese and two polymorphisms of the TNF‐α promoter region (positions ‐238 and ‐308) as well as the correlation between these polymorphisms and the patients' biochemical manifestations. Genomic DNA was extracted from peripheral blood cells of 261 Taiwanese patients with type 2 DM and 189 non‐diabetic control study subjects, and their TNF promoter G‐238A and G‐308A polymorphisms were analyzed by PCR‐RFLP analysis. No significant association between TNF‐α G‐238A and G‐308A polymorphisms with type 2 diabetic incidence was observed. However, associations between TNF‐α G‐238A and low‐density lipoprotein‐cholesterol and between G‐308A promoter polymorphism and high‐fasting plasma glucose levels, using multiple linear regression analysis with adjustment for the subjects' age, sex, body mass index and diabetic status, were found. Our results suggested that though TNF‐α G‐238A and G‐308A polymorphisms were not involved in the pathogenesis of type 2 DM, type 2 diabetic patients carrying TNFA‐A or TNF‐308*2 genotype might be more susceptible to diabetic complications such as atherosclerosis.
New allele frequency database: http://www.allelefrequencies.net
Authors: Middleton D. , Menchaca L. , Rood H. , Komerofsky R.
Published: May 2003

Abstract:  A new website (http://www.allelefrequencies.net) has been compiled to execute the frequency of alleles at various polymorphic regions of different populations in the field of histocompatibility and immunogenetics. Data for HLA alleles has been added but this will be extended to include frequency data of polymorphisms in other immunogenetic regions, e.g. cytokines, KIR receptors, MIC.
Inhibitory effects of green tea catechins on protein tyrosine phosphatase in Prevotella intermedia
Authors: Okamoto M. , Leung K.‐P. , Ansai T. , Sugimoto A. , Maeda N.
Published: May 2003

Members of the Prevotella intermedia group possess protein tyrosine phosphatase (PTPase). The purpose of this study was to investigate the effects of catechin derivatives from Japanese green tea on the activity of PTPase in P. intermedia and related organisms. Multilocus enzyme electrophoresis of alkaline phosphatase derived from P. intermedia, Prevotella nigrescens, Prevotella pallens and Porphyromonas gingivalis revealed a species‐specific migration pattern. Among the tea catechin derivatives tested, (–)‐epigallocatechin gallate (EGCg), similar to orthovanadate, a specific inhibitor for PTPase, was effective in inhibiting the PTPase activity in P. intermedia at 0.5 μm, and related species at 5 μm. The results suggested that the inhibitory effect observed is due to the presence of galloyl moiety in the structure. In contrast, neither the green tea catechins nor orthovanadate inhibited the phosphatase activity in P. gingivalis, suggesting that this organism possessed a different family of alkaline phosphatase.
Granulocyte‐macrophage colony‐stimulating factor responses of oral epithelial cells to Candida albicans
Authors: Dongari‐Bagtzoglou A. , Kashleva H.
Published: May 2003

Candida albicans is the principal fungal species responsible for oropharyngeal candidiasis, the most frequent opportunistic infection associated with immune deficiencies. Cytokines, such as granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), are important in the generation of effective immunity to C. albicans. The purposes of this investigation were to determine whether C. albicans triggers secretion of GM‐CSF by oral epithelial cells in vitro and to investigate mechanisms of host cell–fungal interactions that trigger such responses. Oral epithelial cell lines as well as primary oral mucosal epithelial cells were challenged with stationary phase viable C. albicans, added to human cell cultures at varying yeast:oral cell ratios. Yeast were allowed to germinate for up to 48 h and supernatants were analyzed for GM‐CSF by ELISA. Fixed organisms, germination‐deficient mutants and separation of yeast from epithelial cells using cell culture inserts were used to assess the effects of viability, germination and physical contact, respectively, on the GM‐CSF responses of these cells. Two out of three cell lines and three out of six primary cultures responded to C. albicans with an increase in GM‐CSF secretion. GM‐CSF responses were contact‐dependent, strain‐dependent, required yeast viability and were optimal when the yeast germinated into hyphae.
Adventitious shoot regeneration from Begonia × erythrophylla petiole sections is developmentally sensitive to light quality
Authors: Burritt David J. , Leung David W. M.
Published: May 2003

The influence of light quality on organogenesis in vitro was investigated using Begonia × erythrophylla petiole explants. Pre‐treatment of in vitro donor plants by growth in the dark or under far‐red or blue light reduced their competence for shoot formation when compared with those grown under red or white light. Culture of competent petiole explants under far‐red, blue light or in the dark reduced the number of shoots produced per explant compared to those cultured under red or white light. Explants were found to be developmentally sensitive to both far‐red and blue light, because meristem, but not primordia development was inhibited. In addition, blue light inhibition of shoot formation is not mediated directly through phytochrome, as few shoots formed on explants cultured under a mixture of red and blue light which resulted in a high Pfr/Ptot (0.82) and would allow shoot formation in the absence of blue light. Unlike the inhibitory influence of far‐red light, which is reversible, exposure to blue light permanently reduces an explant's competence for shoot formation. Our results suggest that phytochrome and an independent blue light photoreceptor, possibly a cryptochrome, can regulate shoot production from B. erythrophylla petiole explants.
Refractive errors and visual impairment in 900 adults with intellectual disabilities in the Netherlands
Authors: Van Splunder Jacques , Stilma Jan S. , Bernsen Roos M. D. , Arentz Trudy G. M. H. J. , Evenhuis Heleen M.
Published: May 2003

Purpose:  To collect data on refractive errors and visual impairment in adults with an intellectual disability (ID) in the Netherlands.

Patients:  A randomized sample of 2100 participants was drawn from a base population of 9000 adults with intellectual disabilities in the Netherlands. This article reports on the first 900 participants.

Methods:  All participants underwent a protocol‐based on‐site ophthalmological assessment carried out by skilled investigators.

Results:  Co‐operation was classified according to the number of tests that could be carried out reliably and was good or excellent in 80% of subjects, average in 13% and poor in 7%. Refraction could be reliably assessed in 505/900 (56%) subjects. There was an increased risk of visual impairment in all subgroups compared to the general Dutch population. Visual acuity (VA) was related to the level of ID, but refractive errors were not. New spectacles were prescribed in 106 cases (12%). Of 374 people in whom both monocular VA and the refractive error of the right eye could be reliably assessed, 153 (41%) had a pretest prescription, 16 (10%) of which we found to be inadequate. Of the 221 participants without a pretest prescription, 41 (19%) benefited from correction. Only 38/84 (45%) subjects aged 50 years or older, who could benefit from correction for near vision, had near spectacles. New correction increased the mean distant VA significantly from 0.44 to 0.65 (p < 0.0005).

Conclusions:  With some adaptations, visual screening is feasible in a majority of adults with ID. Visual impairment and refractive errors are much more prevalent in adults with ID than in the normal population. Accurate spectacle correction resulted in significant improvement in distant VA.
The effect of vitamin E on stress‐induced changes in visual evoked potentials (VEPs) in rats exposed to different experimental stress models
Authors: Yargiçoğlu Piraye , Yaraş Nazmi , Ağar Aysel , Gümüşlü Saadet , Bilmen Süreyya , Özkaya Gül
Published: May 2003

Purpose:  The aim of the study was to investigate the effects of vitamin E on stress‐induced changes in visual evoked potentials (VEPs) and lipid peroxidation.

Methods:  Eight experimental groups of 10 rats per group were formed. These consisted of the control group (C); the group treated with vitamin E (E); groups exposed to cold stress (CS), immobilization stress (IS) and both cold and immobilization stress (CIS), and groups exposed to equivalent stresses and treated with vitamin E (CSE, ISE, CISE). Vitamin E was injected intramuscularly in a dose of 30 mg/kg/day.

Results:  Following chronic stress (15 days), plasma corticosterone concentrations in all experimental groups were significantly increased over those in C group. Vitamin E significantly decreased corticosterone levels in all stress groups compared with their respective control groups. Brain nitrite levels were significantly more elevated in all stress groups than in the C group. Vitamin E reduced retina and brain nitrite levels in all stress and E groups compared with their respective control groups. Vitamin E decreased glutathione peroxidase (GSH‐Px) activity in retina and brain tissues in the CSE group, but increased it in the ISE group compared with their respective control groups. Lipid peroxidation was increased in brain and retina tissues in all stress groups as indicated by the significant increase in thiobarbituric acid‐reactive substance (TBARS) levels with respect to the C group. Vitamin E produced a significant decrease in brain and retina TBARS levels in all stress groups with respect to their corresponding control groups. The mean latencies of P1, N1, P2, N2 and P3 components were significantly prolonged in all stress groups compared with the C group.

Conclusion:  Vitamin E returned the VEP latencies in the stress groups to control values. Our findings clearly indicated that vitamin E has the potential to prevent VEP changes caused by stress.
Topical α‐interferon in recurrent conjunctival papilloma
Authors: De Keizer R. J. W. , De Wolff‐Rouendaal D.
Published: May 2003

Purpose:  To report the effect of topical α‐interferon (α‐IF) in two cases of recurrent conjunctival papillomas.

Methods:  One patient with a conjunctival papilloma and one patient with a limbus‐based papilloma were treated with excision and cryotherapy. Recurrences included one in situ carcinoma. Retreatment included systemic and topical α‐IF.

Results:  In Case 1, the papillomas regressed with systemic α‐IF followed by topical application of α‐IF (2.8 × 106 U) for 1 year against recurrence. In Case 2, the papillomas disappeared with topical α‐IF over 1 year. No recurrences were seen during follow‐up (84 and 91 months, respectively). The possible side effect of topical α‐IF was superficial keratitis. Retrospective polymerase chain reaction tests for HPV were positive and showed type 6 in Case 1 and type 33 in Case 2.

Conclusion:  Topical α‐IF can be used as adjuvant therapy in recurrent conjunctival papillomas.
A psychopathological study into the relationship between attention deficit hyperactivity disorder in adult patients and recurrent brief depression
Authors: Hesslinger B. , Tebartz van Elst L. , Mochan F. , Ebert D.
Published: May 2003

Objective: Clinical and epidemiological observations and neurobiological data suggest that there might be an inherent link between attention deficit hyperactivity disorder (ADHD) and recurrent brief depression (RBD). In this psychopathological study, we investigated the comorbidity between these two conditions.

Method: Using an index patient approach 40 adult out‐patients fulfilling the criteria for ADHD were investigated for lifetime history of RBD and another 40 out‐patients with the primary diagnosis of RBD were investigated for a lifetime history of ADHD.

Results: We found a high prevalence of RBD in patients with ADHD (70%) while the prevalence of ADHD in the index sample with RBD was smaller (about 40%).

Conclusion: In terms of comorbidity ADHD was the second commonest psychiatric disorder in patients with RBD next to other affective disorders. The psychopathological pattern of lifetime comorbidity might be of clinical relevance in terms of medical treatment.
Aging and outcome in schizophrenia
Authors: Jeste D. V. , Twamley E. W. , Eyler Zorrilla L. T. , Golshan S. , Patterson T. L. , Palmer B. W.
Published: May 2003

Objective:  Controversy exists about long‐term outcome of schizophrenia, but few studies have compared older out‐patients to normal subjects. We sought to examine the relationship of age to clinical features, psychopathology, movement abnormalities, quality of well‐being, and everyday functioning in schizophrenia out‐patients and normal comparison subjects, and to further characterize these outcomes in elderly schizophrenia out‐patients.

Method:  A total of 290 out‐patients and 144 comparison subjects, aged 40–85 years, underwent comprehensive assessments.

Results:  Among patients, aging was associated with decreased psychopathology, even after controlling for duration of illness. There was no accelerated aging‐related decline on any measure in the patients. Yet, elderly patients were more impaired than comparison subjects on various measures.

Conclusion:  The course of schizophrenia in late life appears stable, but most elderly patients remain symptomatic and impaired. Our findings dispute notions of either progressive deterioration or marked improvement in aging schizophrenia out‐patients.
Neutrophil apoptosis pathways and their modifications in inflammation
Authors: Simon Hans‐Uwe
Published: May 2003

Summary:  Neutrophils are constantly produced in large numbers in the bone marrow, and the same numbers of cells need to die within a defined time period in order to keep cellular homeostasis under physiologic conditions. Changing the rate of apoptosis rapidly changes cell numbers in such systems. For instance, in many bacterial and autoimmune inflammatory diseases, delayed apoptosis is one important mechanism for neutrophil accumulation. Excessive production of granulocyte/macrophage colony‐stimulating factor (GM‐CSF) and granulocyte colony‐stimulating factor (G‐CSF), two important neutrophil survival factors, is often observed in such inflammatory responses. Cytokine withdrawal, as it occurs in the resolution phase of inflammation, leads to the induction of apoptosis. Moreover, neutrophil apoptosis can be accelerated both in the presence and in the absence of survival factors by activation of distinct members of the tumor necrosis factor/nerve growth factor receptor family. This review focuses on recently published work regarding signaling pathways that regulate neutrophil apoptosis.
Activation‐induced cell death in T cells
Authors: Green Douglas R. , Droin Nathalie , Pinkoski Michael
Published: May 2003

Summary:  A properly functioning immune system is dependent on programmed cell death at virtually every stage of lymphocyte development and activity. This review addresses the phenomenon of activation‐induced cell death (AICD) in T lymphocytes, in which activation through the T‐cell receptor results in apoptosis. AICD can occur in a cell‐autonomous manner and is influenced by the nature of the initial T‐cell activation events. It plays essential roles in both central and peripheral deletion events involved in tolerance and homeostasis, although it is likely that different forms of AICD proceed via different mechanisms. For example, while AICD in peripheral T cells is often caused by the induction of expression of the death ligand, Fas ligand (CD95 ligand, FasL), it does not appear to be involved in AICD in thymocytes. This and other mechanisms of AICD are discussed. One emerging model that may complement other forms of AICD involves the inducible expression of FasL by nonlymphoid tissues in response to activated T lymphocytes. Induction of nonlymphoid FasL in this manner may serve as a sensing mechanism for immune cell infiltration, which contributes to peripheral deletion.
Sites of recurrence in oral and oropharyngeal cancers according to the treatment approach
Authors: Carvalho AL , Magrin J , Kowalski LP
Published: May 2003

OBJECTIVE: The purpose of this study is to evaluate the rates and the sites of tumour recurrence in patients with oral and oropharyngeal carcinomas.

DESIGN: This is a retrospective study of a series of cases treated in a single institution.

PATIENTS AND METHODS: A series of 2067 patients with oral and oropharyngeal squamous carcinoma, treated from 1954 to 1998 were analysed. The treatment approach was: surgery, 624 cases (30.2%); radiotherapy alone, 729 cases (35.3%); radiotherapy and surgery, 552 cases (26.7%) and radiotherapy and chemotherapy, 162 cases (7.8%).

MAIN OUTCOME MEASURES: Tumour recurrence was observed in 1079 patients (52.2%): 561 cases of local recurrences (27.1%); 168 neck recurrences (8.1%); 252 locoregional recurrences (12.2%); 59, distant metastasis (2.9%) and 39 (1.9%), combination of distant metastasis with local, neck or locoregional recurrence.

RESULTS: The rates of recurrence varied significantly according to the treatment performed. Oral cavity cancer patients undergoing radiotherapy alone or in combination with chemotherapy presented the highest rates of neck recurrences (22.5 and 40.0%, respectively) for clinical stage (CS) I/II and of local (41.2 and 30.1%) and locoregional (21.7 and 31.1%) recurrences for CS III/IV; yet, for CS III/IV, surgery without neck dissection was associated with the highest rates of neck recurrences (20.7%), but no differences were observed in the rates of local or locoregional recurrences for CS I/II patients. For oropharynx cancer patients with CS I/II there was no difference in the rate of locoregional failures according to the treatment. However, patients with CS III/IV undergoing radiotherapy present a highest rate of local (42.3%) and locoregional (28.8%) failures.

CONCLUSION:

The results suggest that surgery should be the first option for initial clinical stage oral and oropharyngeal cancers. For advanced cases independently of the site of the tumour, surgery and postoperative radiotherapy should be the standard of care because it is associated with the lowest rates of locoregional recurrence.
Evaluation of serum sialic acid, sialyltransferase and sialoproteins in oral cavity cancer
Authors: Raval GN , Patel DD , Parekh LJ , Patel JB , Shah MH , Patel PS
Published: May 2003

OBJECTIVE:Altered glycosylation of glycoconjugates is among the important molecular changes that accompany malignant transformation. The aim of our study was to investigate clinical usefulness of circulatory levels of sialic acid, sialoproteins and sialyltransferase for early diagnosis and management of oral cavity cancer (OC) patients.

MATERIALS AND METHODS:Blood samples collected from 210 untreated OC patients, 100 patients with oral precancerous conditions (OPC) and 100 healthy males. OC patients were followed after initiation of anticancer treatment and 394 follow‐up samples were also collected. Serum sialic acid levels were measured spectrophotometrically. Sialyltransferase activity was analysed using radioassay.α2‐6 sialoproteins were isolated using lectin affinity chromatography.

RESULTS:Serum levels of free, protein bound and total sialic acid as well as their ratio with total proteins were significantly elevated in untreated OC patients compared with healthy individuals, patients with OPC as well as complete responders (CR). Levels of the markers were comparable between untreated OC patients and non‐responders. We observed positive correlation between serum levels of the markers and extent of malignant disease. Serum sialyltransferase activity showed significant elevations in OC patients compared with the controls (P<0.001), patients with OPC (P<0.05) and CR (P<0.05). Higher sialic acid levels in OC patients at the time of diagnosis showed poor survival. The changes in serum proteins with terminalα2‐6 sialic acid correlated well with the alterations in the levels of sialic acid forms and sialyltransferase activity.

CONCLUSION:Our results confirmed the elevations in sialic acid and sialyltransferase levels in OC patients and suggested potential utility of these parameters in prognostication and treatment monitoring of this neoplasm. The alterations in these parameters in circulation were in accordance with the changes inα2‐6 sialylated proteins.
Traumatic neuroma in the lower lip arising following laser/cryosurgery to treat a mucocele
Authors: Zhang M , Hayashi H , Fukuyama H , Nakamura T , Kurokawa H , Takahashi T
Published: May 2003

A 15‐year‐old girl presented with a painless recurrent swelling on her right lower lip mucosa for about 10 months. She had a past history of treatment with laser surgery and cryosurgery. The clinical diagnosis was a ‘recurrent mucocele’. Histopathological examination of the surgical specimen revealed a mucocele close to a neuroma with irregular nerve fascicles, leading to a diagnosis ‘mucocele accompanied with a traumatic neuroma’. In the present report, the traumatic neuroma appears to have arisen following laser or cryosurgery.