bluuebunny/crossref_metadata_2025 huggingface dataset:
Fossilized embryos are widespread but the record is temporally and taxonomically biased
Authors: Donoghue Philip C. J. , Kouchinsky Artem , Waloszek Dieter , Bengtson Stefan , Dong Xi‐ping , Val'kov Anatoly K. , Cunningham John A. , Repetski John E.
Published: February 2006

SUMMARY
We report new discoveries of embryos and egg capsules from the Lower Cambrian of Siberia, Middle Cambrian of Australia and Lower Ordovician of North America. Together with existing records, embryos have now been recorded from four of the seven continents. However, the new discoveries highlight secular and systematic biases in the fossil record of embryonic stages. The temporal window within which the embryos and egg capsules are found is of relatively short duration; it ends in the Early Ordovician and is roughly coincident with that of typical “Orsten”‐type faunas. The reduced occurrence of such fossils has been attributed to reducing levels of phosphate in marine waters during the early Paleozoic, but may also be owing to the increasing depth of sediment mixing by infaunal metazoans. Furthermore, most records younger than the earliest Cambrian are of a single kind—large eggs and embryos of the priapulid‐like scalidophoran Markuelia. We explore alternative explanations for the low taxonomic diversity of embryos recovered thus far, including sampling, size, anatomy, ecology, and environment, concluding that the preponderance of Markuelia embryos is due to its precocious development of cuticle at an embryonic stage, predisposing it to preservation through action as a substrate on which microbially mediated precipitation of authigenic calcium phosphate may occur. The fossil record of embryos may be limited to a late Neoproterozoic to early Ordovician snapshot that is subject to dramatic systematic bias. Together, these biases must be considered seriously in attempts to use the fossil record to arbitrate between hypotheses of developmental and life history evolution implicated in the origin of metazoan clades.
Predictors of Lamotrigine‐associated Rash
Authors: Hirsch Lawrence J. , Weintraub David B. , Buchsbaum Richard , Spencer Hilary T. , Straka Tara , Hager Melissa , Resor Stanley R.
Published: February 2006

Summary:  Purpose: To determine the predictors of lamotrigine‐associated rash (LTG‐rash) and the incidence of serious and benign LTG‐rash to individualize risk assessment in a given patient.

Methods: We reviewed the charts of all 988 outpatients seen at the Columbia Comprehensive Epilepsy Center between January 1, 2000, and December 31, 2003, who received LTG. Charts were reviewed for documentation of rash developing from any medication, including antiepileptic drugs (AEDs) and non‐AEDs, and including remote histories of drug‐related rashes. Demographics, medical history, and medication variables were tested as potential predictors of LTG‐rash.

Results: Fifty‐six (5.7%) of 988 patients experienced rash attributed to LTG, and 39 (3.9%) discontinued LTG because of rash. No patients experienced toxic epidermal necrolysis or required hospitalization because of LTG‐rash. One case of mild probable Stevens–Johnson syndrome occurred. In multivariate analysis, a history of rash after another AED was the strongest predictor of LTG‐rash (13.9% vs. 4.6%; OR = 3.62; p < 0.001), with children younger than 13 years also experiencing significantly more LTG‐rash (10.7% vs. 4.3%; OR = 2.77; p < 0.001). In children with a rash attributed to another AED, 18.2% experienced LTG‐rash, whereas in adults without a rash from another AED, 3% experienced LTG‐rash.

Conclusions: Based on this retrospective analysis, a history of another AED‐related rash is the greatest risk factor for developing rash to LTG; age younger than 13 years is also a risk factor. Severe rash is rare when using the currently recommended titration rate.
AEDs Availability and Professional Practices in Delivery Outlets in a City Center in Southern Vietnam
Authors: Mac Tu Luong , Le Van Tuan , Vu Anh Nhi , Preux Pierre‐Marie , Ratsimbazafy Voa
Published: February 2006

Summary:  In developing countries, from 80 to 90% of the people with active epilepsy do not have access to treatment. A multitude of factors such as nonavailability of antiepileptic drugs (AEDs) contributes to the treatment gap in epilepsy. Our study carried out in 2003 in southern Vietnam showed that 57% of pharmacies had AEDs. A majority of these pharmacies were located in specific areas like market area or hospital area. The pharmacist in charge was present in only 24% of the pharmacies. The different kinds of AEDs available were carbamazepine (94%), phenytoin (61%), valproate (56%) and diazepam (16%). The maximum stock of a drug was two box. The availability of AEDs in southern Vietnam can be regarded as sufficient but does not allow an adequate treatment for a long time. An effort must be made to sensitize professional health workers to decrease the treatment gap in epilepsy.
Absence of Seizures Despite High Prevalence of Epileptiform EEG Abnormalities in Children with Autism Monitored in a Tertiary Care Center
Authors: Kim Howard L. , Donnelly Joseph H. , Tournay Anne E. , Book Teri M. , Filipek Pauline
Published: February 2006

Summary:  Purpose: Children with autism are commonly referred for video‐EEG monitoring to determine the precise nature of their seizure‐like events.

Methods: We studied 32 children with autism by using continuous video‐EEG telemetry (VEEG) monitoring at a tertiary care referral center.

Results: Of the 32 total patients, 22 were primarily referred for seizure evaluation and 10 for 24‐h interictal EEG recording. Studies in two additional patients were prematurely terminated because of intolerance (they are not included in the analyses). The median monitoring duration was 1 day (range, 1–7 days). Of 22 patients referred for seizure evaluation, 15 had recorded events, but none was an epileptic seizure; the other seven patients had no recorded events. Interictal epileptiform EEG abnormalities were detected in 19 (59%) of 32 patients. These abnormalities included focal sharp waves (in eight patients), multifocal sharp waves (in six patients), generalized spike–wave complexes (in 11 patients), and generalized paroxysmal fast activity/polyspikes (in two patients). Focal/multifocal and generalized epileptiform abnormalities coexisted in six patients. Notably, 11 (73%) of the 15 patients with nonepileptic events had interictal epileptiform EEG abnormalities.

Conclusions
: Video‐EEG evaluation of children with autism reveals epileptiform EEG abnormalities in the majority. However, many recorded seizure‐like events are not epileptic, even in children with epileptiform EEG abnormalities.
School Performance of Nigerian Adolescents with Epilepsy
Authors: Adewuya Abiodun O. , Oseni Saheed B. A. , Okeniyi John A. O.
Published: February 2006

Summary:  Purpose: The study assessed the school performance of Nigerian adolescents with epilepsy compared with healthy controls and examined the variables correlating with their academic difficulties.

Methods: The school grades of adolescents with epilepsy aged 12 to 18 years (n = 73) over the past academic year were compared with the grades of their classmates of the same age and gender. Risk factors possibly associated with school performance, such as adolescent variables (age, gender, perceived stigma, attitude toward epilepsy, and psychopathology), seizure variables (age at onset of illness, years of illness, types of seizures, and frequency of seizures per month), drug variables [types of antiepileptic drugs (AEDs), number of AEDs and side effects of AEDs], and family variables (family's socioeconomic status, family functioning, caretakers' psychopathology, and caretakers' perceived stigma) were assessed.

Results: The mean school grades of adolescents with epilepsy are significantly lower than are those of their healthy controls (p < 0.001) in all the subjects. The variables that significantly predict poor school performance in adolescents with epilepsy include psychopathology in the caretaker (p < 0.001), adolescents' perceived poor family functioning (p = 0.002), adolescents' attitude toward the illness (p = 0.001), adolescents' felt stigma (p = 0.002), externalizing symptoms in the adolescents (p = 0.004), and duration of illness (p = 0.024).

Conclusions: The determinants of poor school performance in adolescents with epilepsy in Nigeria are multivariate, with psychosocial factors most important. These should be noted for early identification and screening of those children at greatest risk for academic failure and the greatest need for appropriate educational remediation services.
Silymarin Protects Against Acute Ethanol‐Induced Hepatotoxicity in Mice
Authors: Song Zhenyuan , Deaciuc Ion , Song Ming , Lee David Y.‐W. , Liu Yanze , Ji Xiaosheng , McClain Craig
Published: February 2006

Background: Accumulated evidence has demonstrated that both oxidative stress and abnormal cytokine production, especially tumor necrosis factor‐α (TNF), play important etiological roles in the pathogenesis of alcoholic liver disease (ALD). Agents that have both antioxidant and anti‐inflammation properties, particularly anti‐TNF production, represent promising therapeutic interventions for ALD. We investigated the effects and the possible mechanism(s) of silymarin on liver injury induced by acute ethanol (EtOH) administration.

Methods: Nine‐week‐old mice were divided into 4 groups, control, silymarin treatment, EtOH treatment, and silymarin/EtOH treatment, with 6 mice in each group. Because control and silymarin values were virtually identical, only control treatment is shown for ease of viewing. Ethanol‐treated mice received EtOH [5 g/kg body weight (BW)] by gavage every 12 hours for a total of 3 doses. Control mice received an isocalorical maltose solution. In the silymarin/EtOH group, silymarin was dissolved in the EtOH and gavaged simultaneously with EtOH at a dose of 200 mg/kg BW. At 4 hours after the last dosing, the mice were anesthetized and subsequent serum alanine aminotransferase (ALT) level, hepatic lipid peroxidation, enzymatic activity of hepatic cytochrome P450 2E1, hepatic TNF‐α, and glutathione (GSH) levels were measured. Histopathological change was assessed by hematoxylin and eosin staining.

Results: Acute EtOH administration caused prominent hepatic microvesicular steatosis with mild necrosis and an elevation of serum ALT activity, induced a significant decrease in hepatic GSH in conjunction with enhanced lipid peroxidation, and increased hepatic TNF production. Supplementation with a standardized silymarin attenuated these adverse changes induced by acute EtOH administration.

Conclusions: Silymarin protects against the liver injury caused by acute EtOH administration. In view of its nontoxic nature, it may be developed as an effective therapeutic agent for alcohol‐induced liver disease by its antioxidative stress and anti‐inflammatory features.
Gelatin “Shots” as a New Method for Alcohol Administration in a Laboratory Setting
Authors: Ralevski Elizabeth , Gueorguieva Ralitza , Limoncelli Diana D. , Husain Reema , Serrita Jane J. , Petrakis Ismene
Published: February 2006

Background: This experiment was designed to compare gelatin “shots”—a new procedure for administering alcohol in a laboratory setting—to the alcohol beverage method. We proceeded to test whether the two methods were comparable in terms of alcohol absorption, metabolism, and effects on mood and whether gelatin “shots” were better than the beverage in disguising alcohol in a blind, placebo comparison.

Methods: Healthy volunteers participated in a two‐phase trial. In the first phase they completed 2 days of testing during which the effects of alcohol—delivered in beverage (1 day) or gelatin “shots” (alternative day)—on blood and breathalyzer concentrations and mood were assessed. In the second phase participants completed 2 days of testing and were asked to identify if samples contained alcohol or placebo. The presentation of alcohol and placebo and the presentation of beverage or gelatin “shots” were random.

Results: In the first phase there was a significant time‐by‐condition interaction in the blood alcohol concentration. Two‐and‐a‐half hours after the alcohol was administered, those given gelatin “shots” had slightly lower but statistically significant blood alcohol concentrations. There was a significant time effect for breathalyzer alcohol levels but no condition or condition‐by‐time interaction. There were no differences between the two methods on any of the subjective mood measures. In the second phase of the study there were differences in the ability to differentiate alcohol from placebo between the two conditions with significantly more participants making errors in the gelatin “shots” than in the beverage condition.

Conclusions: Our findings indicate that gelatin “shots” are an effective method for delivering alcohol to humans in a laboratory setting. This method may be superior to the alcohol beverage mixture in a placebo‐controlled design because gelatin “shots” mask the alcohol much better than a beverage and are easier to administer.
Survivor Swaps
Authors: Dowd Kevin , Blake David , Cairns Andrew J. G. , Dawson Paul
Published: February 2006

Abstract

A survivor swap (SS) is an agreement to exchange cash flows in the future based on the outcome of at least one survivor index. This article discusses the possible uses of SSs as instruments for managing, hedging, and trading mortality‐dependent risks. SSs are especially useful for insurance companies, but also offer other interested parties low beta avenues into the acquisition of mortality risk exposure. The article also investigates vanilla SSs in some detail, and suggests how their premiums and values might be determined in an incomplete market setting.
To Hedge or Not to Hedge: Managing Demographic Risk in Life Insurance Companies
Authors: Gründl Helmut , Post Thomas , Schulze Roman N.
Published: February 2006

Abstract

Demographic risk, i.e., the risk that life tables change in a nondeterministic way, is a serious threat to the financial stability of an insurance company having underwritten life insurance and annuity business. The inverse influence of changes in mortality laws on the market value of life insurance and annuity liabilities creates natural hedging opportunities. Within a realistically calibrated shareholder value (SHV) maximization framework, we analyze the implications of demographic risk on the optimal risk management mix (equity capital, asset allocation, and product policy) for a limited liability insurance company operating in a market with insolvency‐averse insurance buyers. Our results show that the utilization of natural hedging is optimal only if equity is scarce. Otherwise, hedging can even destroy SHV. A sensitivity analysis shows that a misspecification of demographic risk has severe consequences for both the insurer and the insured. This result highlights the importance of further research in the field of demographic risk.
Food sources for adult Diachasmimorpha longicaudata, a parasitoid of tephritid fruit flies: effects on longevity and fecundity
Authors: Sivinski John , Aluja Martin , Holler Tim
Published: February 2006

We report the results of a study on potential food sources of the widely distributed Indo‐Australian braconid fruit fly parasitoid Diachasmimorpha longicaudata (Ashmead) (Hymenoptera: Braconidae). Adults sustained life on diets of fruit juice or fruit pulp, a homopteran and its associated honeydew, or extrafloral nectary secretions. Longevities on all these foods and fecundity on fruit juice were comparable to those achieved on the honey that is typically provided in mass‐rearing programs. Certain of the flower species Bidens alba (L.), Spermacoce verticillata L., Lobularia maritima (L.) Desv., Brassica nigra (L.), Lantana camara L., their nectar or pollen, provided a diet that resulted in longer maximum life spans than water alone. Unlike some tephritid flies, the braconid did not feed on fresh bird feces or leaf‐surface exudates. Feeding by D. longicaudata on wounded host fruits of tephritid flies suggests that adult parasitoids would not need separate forays for adult food and oviposition sites, as these occur in the same locations. We conclude that an inventory of adult foods may help target inundative releases of D. longicaudata and lead to improvements in diets used for mass rearing.
Functional response ofTrichogramma chilonistoGalleria mellonellaandChilo sacchariphaguseggs
Authors: Reay‐Jones F.P.F. , Rochat J. , Goebel R. , Tabone E.
Published: February 2006

A biological control programme using inundative releases ofTrichogramma chilonisIschii (Hymenoptera: Trichogrammatidae) reared onGalleria mellonellaL. (Lepidoptera: Pyralidae) is currently underway to reduce infestations ofChilo sacchariphagusBojer (Lepidoptera: Crambidae) in sugarcane,Saccharumspp., on Réunion Island. To assess the potential of the parasitoid as an inundative biocontrol agent, the functional response of threeT. chilonisstrains was tested withG. mellonellaand one strain withC. sacchariphagushost eggs in glass tubes in the laboratory. The shape of the functional response (type II or III) was determined using logistic regression, and attack coefficients and handling times (Th) were determined using non‐linear least‐square regression. The behaviour of all three strains withG. mellonellahost eggs corresponded to a type III response. The St BenoîtT. chilonisstrain had a significantly shorter estimate of Ththan the St Pierre strain (P<0.05) and may, therefore, be more appropriate as a biocontrol agent. The functional response withC. sacchariphagushost eggs was a type II with the St BenoîtT. chilonisstrain. MoreT. chiloniswasps developed per host egg from the largerC. sacchariphagushost eggs (2.9) relative toG. mellonella(1.1). Superparasitism at low host egg densities was, therefore, likely to have been less frequent withC. sacchariphagus. Black eggs were chosen as an estimate of number of eggs parasitized, although they represent the number of eggs where parasitism led to complete pupal development. The low rate of detected parasitism at low host densities withG. mellonellaeggs may be due to incomplete pupal development due to superparasitism rather than lack of parasitism, thus explaining the type III functional response.
Genetic differentiation between eastern populations and recent introductions of potato psyllid (Bactericera cockerelli) into western North America
Authors: Liu Deguang , Trumble John T. , Stouthamer Richard
Published: February 2006

Although tomato psyllid, Bactericera cockerelli (Sulc) (Homoptera, Psyllidae), annually causes significant losses in potato and tomato crops in eastern Mexico and the central United States, infestations in western North America have been historically rare. However, substantial populations appeared in 2001 in western North America and caused losses in tomato production exceeding 80%; losses in 2004 reached 50%. To determine if these new outbreaks were the result of a simple range expansion or the evolution of a new B. cockerelli biotype, inter simple sequence repeat (ISSR) markers, as well as mitochondrial gene cytochrome oxidase I (COI), internal transcribed spacer 2 (ITS2), and wsp sequence data were used to characterize populations of the psyllid. Western populations from Baja, Mexico, Orange County, and Ventura County were compared with populations from central USA (Colorado and Nebraska) and eastern Mexico (Coahuila). Based on ISSR markers, the psyllid populations clustered into two groups, with one group including populations from western North America and the other group including populations from central USA and eastern Mexico. For COI comparisons, there was one base‐pair difference found in the 544 bp‐long COI fragments, but the populations again segregated along the same geographic lines. Two strains of Wolbachia were identified, the maximal differences between wsp clones from all populations was 5 bp for strain Bac1 and 23 bp for strain Bac2 out of a 555‐bp fragment. The ISSR data, therefore, were consistent in indicating the development of a new psyllid biotype that has adapted to western North America rather than a simple range expansion, but the other genetic data sets were less conclusive.
Genetic analysis of larval host‐plant preference in two sibling species of Helicoverpa
Authors: Tang Qing‐Bo , Jiang Jin‐Wei , Yan Yun‐Hua , van Loon Joop J.A. , Wang Chen‐Zhu
Published: February 2006

The genetic basis of larval host‐plant preference was investigated in reciprocal F1, F2, and backcrossed generations derived from hybrid crosses between the generalist species Helicoverpa armigera (Hübner) and the closely related specialist species Helicoverpa assulta (Guenée) (Lepidoptera: Noctuidae). Host‐plant preference for cotton [Gossypium arboreum L. (Malvaceae)] and pepper [Capsicum frutescens L. (Solanaceae)] of fifth‐instar caterpillars was tested by using a two‐choice leaf‐disk assay. Helicoverpa armigera and H. assulta were significantly different in their feeding preferences, but the difference was not significant in the reciprocal hybrids, which showed there were no maternal/cytoplasmic effects. Comparisons of feeding preference between different groups of females or males demonstrated that the trait was not controlled by sex‐linked loci. The distributions of feeding preference index values for crosses that carried similar complements of autosomal genes were not significantly different, whereas crosses with different complements of autosomal genes were associated with significantly different feeding preferences, indicating that feeding preference of the two species for cotton and pepper, respectively, is controlled by autosomal genes. It was found that one major autosomal locus affected this feeding preference, with the H. armigera‐derived alleles being partially dominant to those carried by H. assulta. The genetic analysis of hybrids contributes to understand the evolution of feeding preference in these closely related species.
Perinatal expression of HSP70 and VEGF in neonatal rat lung vessels exposed to nicotine during gestation
Authors: CANOZ OZLEM , GUNES TAMER , DENIZ KEMAL , AKGUN HULYA , BALKANLI SULEYMAN
Published: February 2006

We assessed the influence of maternal nicotine exposure during gestation on perinatal expression of HSP70 and VEGF in rat lung parenchyma and lung vessels. Adult white Sprague‐Dawley virgin rats were mated with adult male rats over 2 days, with two females for every male. After confirming pregnancy, 30 gravid rats (dams) were then randomly assigned to two equal groups (one experimental and one control; n=15 in each). Experimental dams were treated with subcutaneus (s.c.) (‐)‐nicotine tartrate, 3 mg/kg body weight/day, during pregnancy from gestational days 9 through 21. After sacrifice, lungs were removed en bloc and formalin‐fixed, and paraffinembedded tissue sections were evaluated by immunohistochemistry using a three‐step streptavidin‐biotin‐peroxidase method with monoclonal antibodies directed against HSP70 or VEGF. HSP70 and VEGF expression was increased in the vascular smooth muscle cells of the experimental group (t1) compared to the control group (t2)t1=7.593, t2=4.666, p<0.05). The number of bronchioles that stained positively with HSP70 was higher in the nicotineexposed group than in the control group (t1=9.274, t2=6.956, p<0.05). In conclusion, gestational nicotine exposure increased the expression of VEGF and HSP70 in rat lung parenchyma, especially in the airway epithelium and vascular smooth muscle cells. In vascular smooth muscle cells, these molecules may contribute to nicotine‐related hypoxic pulmonary hypertension.
Detection of bacterial strains producing sulbactam‐ or tazobactam‐sensitive β‐lactamases by the use of disks containing the inhibitors alone instead of combining them with antibiotics
Authors: BANIC S.
Published: February 2006

The author demonstrated that disks containing β‐lactamase inhibitors sulbactam or tazobactam combined with ampicillin (SAM) and piperacillin (TZP) are not suitable for performing the double‐disk synergy test (DDST) with the aim of determining the sensitivity of β‐lactamases to these inhibitors. The presence of antibiotics (especially of piperacillin) is so disturbing that the results of testing are not specific. In contrast, the use of disks containing sulbactam or tazobactam alone yields very specific results. The author suggested to the firms producing sensi‐disks that they make these commercially available to laboratory workers.
Altered expression of CDX2 in colorectal cancers
Authors: CHOI BYUNG JUN , KIM CHANG JAE , CHO YONG GU , SONG JAE HWI , KIM SU YOUNG , NAM SUK WOO , LEE SUG HYUNG , YOO NAM JIN , LEE JUNG YOUNG , PARK WON SANG
Published: February 2006

CDX2 is a caudal‐related homeobox transcription factor whose expression in the adult is normally restricted to the intestinal epithelium; it is implicated in the development and maintenance of the intestinal mucosa. The specific aim of this study was to elucidate the potential etiological role of CDX2 protein in colorectal carcinogenesis. We have analyzed the expression pattern of CDX2 protein in relation to the phenotype of 123 sporadic colorectal cancers by immunohistochemistry using tissue microarray. Strong CDX2 immunostaining was seen in the nuclei of corresponding normal intestinal epithelium. Interestingly, loss of CDX2 immunostaining was observed in 29 (23.6%) of 123 colorectal adenocarcinomas and its expression was correlated with the differentiation grade of the carcinoma (Chi‐Square test, p<0.01). Clinically, CDX2 protein was immunopositive in 11 (91.7%) of 12 cases corresponding to stage A, 40 (85.1%) of 47 corresponding to stage B, 39 (69.6%) of 56 corresponding to stage C, and 4 (50.0%) of 8 corresponding to stage D. Statistically, CDX2 protein expression was related to tumor stage (Bartholomew test, p<0.05) and lymph node metastasis (Chi‐Square test, p<0.05). These results indicate that loss of expression of CDX2 protein may play an important role in the tumorigenesis of colorectal cancers and that CDX2 expression represents a highly significant marker, which is able to identify a subset of patients at high risk.
Appendicitis associated with presence of Schistosoma haematobium eggs: an unusual pathology for Europe
Authors: RIVASI FRANCESCO , PAMPIGLIONE SILVIO
Published: February 2006

Three cases of appendicitis associated with presence of Schistosoma haematobium eggs in the appendix tissue are reported. The patients (two males and one female) were all from Ghana and had immigrated to Italy a few years previously. It is difficult to attribute the cause of the appendicitis to the parasite; it is more probable that the appendicular location of the eggs occurred accidentally many years earlier in an endemic zone of the country of origin, and that recently bacterial agents were able to provoke the present appendicitis. Since it is probable that with the increase in the number of immigrants to Europe from endemic countries (sub‐Saharan Africa in particular) other similar cases may occur, it is important that the surgeon and the pathologist be aware of this pathology, which has so far been considered unusual.
Inhibition of T‐cell responses by CD4 on an antigen‐presenting cell
Authors: HANSEN TORBJØRN
Published: February 2006

In addition to T‐helper cells, CD4 is expressed on monocytes, macrophages and dendritic cells. To see whether CD4 molecules on antigen‐presenting cells affect T‐cell responses, we expressed CD4 on Raji cells, and compared positive and negative cells as stimulator cells for peripheral blood mononuclear cells in mixed lymphocyte reactions. We found that expression of CD4 on Raji had an inhibitory effect on production of IFN‐γ and other cytokines.
Fas and Fas ligand expression on germinal center type‐diffuse large B‐cell lymphoma is associated with the clinical outcome
Authors: Kojima Yasushi , Tsurumi Hisashi , Goto Naoe , Shimizu Masahito , Kasahara Senji , Yamada Toshiki , Kanemura Nobuhiro , Hara Takeshi , Sawada Michio , Saio Masanao , Yamada Tetsuya , Takahashi Takeshi , Tomita Eiichi , Takami Tsuyoshi , Moriwaki Hisataka
Published: February 2006

Abstract:  In recent years, diffuse large B‐cell lymphoma (DLBCL) has been classified by DNA microarray analysis into the germinal center B‐cell‐like (GC) type, the activated B‐cell‐like (ABC) type and type 3. The latter two types can be collectively categorized as the non‐GC (NGC) type. From the prognostic perspective, the GC type has a favorable clinical outcome when compared with the NGC type. The protein Fas induces apoptosis of lymphocytes by binding with the Fas ligand (FasL), and escape from such apoptosis is considered to lead to malignant transformation of the cells and unrestricted growth of lymphoma. We proposed a hypothesis that Fas/FasL expression could be possibly related with a better survival of GC type DLBCL and evaluated 69 DLBCL cases immunohistochemically with CD10, Bcl‐6, MUM1, Fas and FasL. These lymphomas were classified as GC type (positive for CD10 or Bcl‐6 and negative for MUM1) or NGC type. The GC type had a better overall survival rate than the NGC type (P = 0.0723). Among markers as given above, positive CD10 was the most significant prognostic factor for overall survival in total DLBCL (P < 0.05). In the GC type, Fas and FasL expressions were significantly associated with a favorable overall survival (Fas: P < 0.005; FasL: P < 0.05). Hence, Fas or FasL expression might contribute to a better prognosis of this type of DLBCL.
Mechanistic studies of melanogenesis: the influence of N‐substitution on dopamine quinone cyclization
Authors: Borovansky Jan , Edge Ruth , Land Edward J. , Navaratnam Suppiah , Pavel Stan , Ramsden Christopher A. , Riley Patrick A. , Smit Nico P. M.
Published: February 2006

The influence of side‐chain structure on the mode of reaction of ortho‐quinone amines has been investigated with a view, ultimately, to developing potential methods of therapeutic intervention by manipulating the early stages of melanogenesis. Four N‐substituted dopamine derivatives have been prepared and quinone formation studied using pulse radiolysis and tyrosinase‐oximetry. Ortho‐quinones with an amide or urea side chain were relatively stable, although evidence for slow formation of isomeric para‐quinomethanes was observed. A thiourea derivative cyclized fairly rapidly (k = 1.7/s) to a product containing a seven‐membered ring, whereas a related amidine gave more rapidly (k ∼ 2.5 × 102/s) a stable spirocyclic product. The results suggest that cyclization of amides, ureas and carbamates (NHCO‐X; X = R, NHR or OR) does not occur and is not, therefore, a viable approach to the formation of tyrosinase‐activated antimelanoma prodrugs. It is also concluded that for N‐acetyldopamine spontaneous ortho‐quinone to para‐quinomethane isomerization is slow.
Determination of eumelanin in human urine
Authors: Wakamatsu Kazumasa , Takasaki Akihiko , Kågedal Bertil , Kageshita Toshiro , Ito Shosuke
Published: February 2006

Normal and malignant melanocytes produce melanins and melanin‐related metabolites, most of which are retained in the cells but some are secreted into the blood and then excreted in the urine. In this study, we developed a method to measure levels of eumelanin in urine samples and evaluated its clinical significance in comparison with the melanin‐related metabolites 6‐hydroxy‐5‐methoxyindole‐2‐carboxylic acid (6H5MI2C) and 5‐S‐cysteinyldopa (5‐S‐CD), and with pheomelanin, measured after degradation as 4‐amino‐3‐hydroxyphenylalanine (4‐AHP). The method is based on the production of pyrrole‐2,3,5‐tricarboxylic acid (PTCA) on permanganate oxidation of eumelanin, followed by quantification by liquid chromatography. For 118 urine samples from 10 control subjects, mean urinary excretions of PTCA, 6H5MI2C, 5‐S‐CD and 4‐AHP were 19, 67, 37 and 59 μmol/mol creatinine respectively. In melanoma patients (n = 45), the mean urinary excretions of PTCA, 6H5MI2C, 5‐S‐CD, and 4‐AHP were 91, 926, 4070 and 3530 μmol/mol creatinine respectively. Median level of PTCA in melanoma patients was elevated 2.1‐fold compared with control subjects. The degrees of elevation for 6H5MI2C, 5‐S‐CD, and 4‐AHP were 1.8‐, 22‐ and 6.2‐fold respectively. Thus, although urinary PTCA is of little clinical value in following the progression of melanoma, urinary 4‐AHP appears to be of considerable value in this respect.
A tumor necrosis factor‐α antagonist inhibits inflammatory bone resorption induced by Porphyromonas gingivalis infection in mice
Authors: Suzuki Yoshifumi , Aoki Kazuhiro , Saito Hiroaki , Umeda Makoto , Nitta Hiroshi , Baron Roland , Ohya Keiichi
Published: February 2006

Background:  A tumor‐necrosis factor‐α (TNF‐α) antagonist, the WP9QY peptide, was designed based on the crystal structure of the TNF‐β/TNF‐receptor complex in order to overcome the disadvantages of macromolecules such as antibodies or soluble receptors by reducing the molecular size of TNF‐α antagonists. It efficiently antagonizes the effect of TNF‐α binding to the TNF receptor (I).

Objectives:  The aim of the present study was to assess the effects of the WP9QY peptide on inflammatory bone resorption and osteoclast formation in the periodontal pathogen‐infection model.

Material and methods:  Live Porphyromonas gingivalis ATCC 33277 was injected once daily for 6 days into the subcutaneous tissue overlying the calvariae in mice. At the same time, the WP9QY peptide (1 mg/kg, 2 mg/kg or 4 mg/kg per day) was administrated via osmotic minipumps for 7 days. Histological observations and the radiological assessments of the calvariae as well as bone mineral density measurements were performed.

Results:  The WP9QY peptide significantly prevented the P. gingivalis‐induced reduction in the bone mineral density at the calvariae. The histomorphometric assessments revealed the inhibitiory effects of the WP9QY peptide on the P. gingivalis‐induced increase in the number of the inflammatory cells and in the area of sagittal suture at the calvariae. Furthermore, there was also an inhibitory effect on the P. gingivalis‐induced increase in the number of osteoclasts per unit bone surface at the calvariae.

Conclusion:  These results suggest that the strategy for the design to reduce the molecular size of the TNF‐α antagonists would be beneficial for the treatment of local inflammatory bone loss induced by periodontal‐pathogen infection.
Gingival crevicular fluid levels of calprotectin and myeloperoxidase during therapy for generalized aggressive periodontitis
Authors: Kaner Doğan , Bernimoulin Jean‐Pierre , Kleber Bernd‐Michael , Heizmann Wolfgang R. , Friedmann Anton
Published: February 2006

Background:  Levels of the inflammation marker calprotectin in gingival crevicular fluid correspond to clinical and biochemical parameters of periodontal inflammation. Neutrophil granulocytes (polymorphonuclear neutrophils: PMNs) are supposed to be the main source of calprotectin in gingival crevicular fluid, but evidence is still lacking. The influence of periodontal therapy on gingival crevicular fluid levels of calprotectin has not yet been determined.

Objectives:  Gingival crevicular fluid levels of calprotectin were monitored during therapy for generalized aggressive periodontitis. Interrelations between calprotectin and the PMN marker myeloperoxidase (MPO) were evaluated.

Material and methods:  Gingival crevicular fluid samples were collected from 23 patients with generalized aggressive periodontitis before and 3 months after non‐surgical therapy with an adjunctive antimicrobial medication. Clinical parameters were recorded with a pressure‐calibrated electronic probe. Levels of calprotectin and MPO in gingival crevicular fluid were analysed by enzyme‐linked immunosorbent assay (ELISA) procedures.

Results:  At baseline, levels of calprotectin and MPO were highly correlated. Bleeding and suppurating sites showed significantly higher levels of calprotectin and MPO than non‐bleeding, non‐suppurating sites. Therapy significantly decreased levels of both biomarkers. These changes of calprotectin and MPO were highly correlated and also related to probing‐depth reduction. Three months after therapy, the levels of both markers still showed significant correlations in initially deep sites, whereas in initially shallow sites no significant correlation was found. After therapy, levels of markers in bleeding and non‐bleeding sites were comparable.

Conclusion:  The correlations between calprotectin and MPO indicate that PMNs are a major contributor to the calprotectin content in gingival crevicular fluid of severely affected sites. Calprotectin levels in gingival crevicular fluid and their changes reflect periodontal inflammation as well as the clinical treatment outcome. A prognostic potential of this marker substance remains to be determined.
Can We Really Trust MRI in Diagnosing Knee Injuries in Athletes?
Authors: Rolf Christer G. , Riyami Masoud
Published: February 2006

This review discusses the so frequent dilemma for a sports physician or orthopaedic surgeon to stand in front of a professional soccer or rugby player with a knee injury, showing clear clinical signs of a meniscus tear or possibly chondral injury, but with an magnetic resonance imaging (MRI) which has been reported as normal. When arthroscopy finally is undertaken after a lot of discussion and delay caused by the reportedly normal MRI, the clinical suspicion is verified. The opposite situation may of course also occur. A clinician usually refers to MRI when the clinical diagnosis is unclear. However, among professional clubs in the UK the referral to a tertiary specialist is in many cases accompanied with an already undertaken MRI. In this review, we demonstrate several illustrative cases, where MRI has led to unnecessary management delays. The review focuses on meniscus and focal cartilage injuries. We suggest a range of possible solutions, which may improve the situation. There are several controversies to be addressed. First, detailed communication between the clinician and radiologist are often hampered by formal procedures. A referral is sent to the Radiology Department and a radiographer will perform a routine MRI protocol. The referral question may not always point to the correct injury, and is depending on the experience of the clinician. Usually, the radiologist is not present during scanning and instead puts together a protocol and subsequently reports on the images without having seen the injured player. Secondly, the use of different routine protocols for investigation of different structures is often not known in detail by the clinician. Thirdly, there is often a lack of standardized reporting of exact location, size and severity of focal cartilage injury in relation to the patients sporting demands. Furthermore, the quality of healed cartilage in a treated focal defect is of course of vital interest for allowing return to sport. Last but not least, inability to verify dynamic instabilities and structural behaviour during movement of the injured knee decreases the clinical value of MRI when compared with arthroscopy for a number of common sport injuries of the knee.
Computed Tomography of Knee Injuries
Authors: Ahn J. M. , El‐Khoury G. Y.
Published: February 2006

The knee is the largest and most complex joint in the body and a wide variety of bone and soft tissue injuries are seen in the knee. Trauma to the knee can result in injury to the bone, articular cartilage, meniscus and ligaments. Fractures of the proximal tibia, particularly those that extend into the knee joint, are serious injuries that frequently result in functional impairment. Recent advances in cross‐sectional imaging, particularly in computed tomography (CT), have given this modality a prominent role in the detection and classification of fractures in and around the knee. With the advent of high‐performance multi‐detector CT, isotropic data sets can be generated with subsecond gantry rotation times and submillimetre slice thickness. CT arthrography can clearly demonstrate many lesions in the plethora of internal derangement of the knee. CT arthrography also deserves its advantage as it may be used to evaluate knee injuries in patients where magnetic resonance imaging is contraindicated. In this article we discuss the indications for imaging of knee injuries by CT, present the advantages of multi‐detector CT and CT arthrography, and provide examples that highlight the utility of CT in the evaluation of the knee injuries.
Imaging of the Postoperative Knee
Authors: Galla M. , Agneskirchner J. D. , Lobenhoffer P.
Published: February 2006

As imaging techniques develop rapidly, it has become essential to differentiate which techniques are suitable for evaluation of postoperative results. Depending on the surgical procedure, standard radiography, magnetic resonance imaging and computed tomography can be employed for imaging of the postoperative knee. For accurate assessment of the postoperative status knowledge of the utilized surgical methods and the expected imaging appearances of the structures that have been reconstructed, resected or replaced is necessary. Both radiologists and orthopaedic surgeons must be familiar with the possibilities of each imaging method and its indications resp. contraindications. As a single technique is not always sufficient to provide all the information, all imaging methods should be considered complementary. This article will give an overview on different imaging techniques, their indications and their problems in postoperative assessment of surgical results around the knee joint.
MPP3 is recruited to the MPP5 protein scaffold at the retinal outer limiting membrane
Authors: Kantardzhieva Albena , Alexeeva Svetlana , Versteeg Inge , Wijnholds Jan
Published: February 2006

Mutations in the human Crumbs homologue 1 (CRB1) gene are a frequent cause of various forms of retinitis pigmentosa. The CRB1–membrane‐associated palmitoylated protein (MPP)5 protein complex is thought to organize an intracellular protein scaffold in the retina that is involved in maintenance of photoreceptor–Müller glia cell adhesion. This study focused on the binding characteristics and subcellular localization of MPP3, a novel member of the MPP5 protein scaffold at the outer limiting membrane (OLM), and of the DLG1 protein scaffold at the outer plexiform layer of the retina. MPP3 localized at the photoreceptor synapse and at the subapical region adjacent to adherens junctions at the OLM. Localization studies in human retinae revealed that MPP3 colocalized with MPP5 and CRB1 at the subapical region. MPP3 and MPP4 colocalized with DLG1 at the outer plexiform layer. Mouse Dlg1 formed separate complexes with Mpp3 and Mpp4 in vivo. These data implicate a role for MPP3 in photoreceptor polarity and, by association with MPP5, pinpoint MPP3 as a functional candidate gene for inherited retinopathies. The separate Mpp3/Dlg1 and Mpp4/Dlg1 complexes at the outer plexiform layer point towards additional yet unrecognized functions of these membrane associated guanylate kinase proteins.
Sequence variants of chicken linker histone H1.a
Authors: Górnicka‐Michalska Ewa , Pałyga Jan , Kowalski Andrzej , Cywa‐Benko Katarzyna
Published: February 2006

Two allelic isoforms (H1.a1 and H1.a2) of histone H1.a were identified within two conservative flocks (R11 and R55) of Rhode Island Red chickens. These proteins form three phenotypes: a1, a2 and a1a2. Birds with phenotype a1 were most common (frequency 0.825–0.980) while the a1a2 chickens appeared relatively rarely (0.017–0.175). The third phenotype a2, not detected in the tested populations, has only been revealed in progeny of the purpose‐mated a1a2 birds. The polymorphism of histone H1.a was observed in all examined chicken tissues, so that the H1 preparations isolated from the lung, spleen, kidney and testis from the same individual exhibited identical phenotypes (a1, a2, or a1a2). This finding, together with inheritance data, supports the genetic nature of the H1.a polymorphism. As indicated by cleavages with α‐chymotrypsin and protease V8, the H1.a1 and H1.a2 are two highly related proteins which differ within N‐terminal part of their C‐terminal tails. Only a single nonconservative amino acid substitution between both H1.a allelic isoforms was detected by Edman degradation: glutamic acid present at position 117 in histone H1.a1 was replaced by lysine in histone H1.a2. Furthermore, using microsequencing techniques we have found a sequence homology between the N‐ and C‐terminal parts of an unknown minor protein H1.y, present in the phenotype a2, and similar regions of histone H1.b.
The transcription regulator RbsR represents a novel interaction partner of the phosphoprotein HPr‐Ser46‐P in Bacillus subtilis
Authors: Müller Wolfgang , Horstmann Nicola , Hillen Wolfgang , Sticht Heinrich
Published: February 2006

Histidine‐containing protein (HPr) is a central metabolic sensor in low‐GC Gram‐positive bacteria and plays a dual role in sugar uptake by the phosphoenolpyruvate–sugar phosphotransferase system and in transcriptional control during carbon catabolite repression. The latter process is mediated by interaction between HPr and the carbon catabolite repression master transcription regulator, carbon catabolite protein A (CcpA), a member of the LacI‐GalR family of DNA‐binding proteins. We investigated, with a combination of computational and experimental tools, whether HPr can also interact with other transcriptional regulators. To allow rapid identification of paralogous LacI‐GalR family members that might interact with HPr in a similar fashion to CcpA, a structure‐based computational approach was developed which relies on the analysis of the similarity of protein–protein interfaces between different complexes. A key element of this method is an empirical pair potential derived from a group of orthologous complexes and subsequently used to identify paralogs that exhibit similar properties of their protein interfaces. Application of this method to the family of LacI‐GalR repressors in Bacillus subtilis predicted the ribose operon repressor (RbsR) as a novel interaction partner of HPr. This interaction was subsequently confirmed experimentally and suggests that HPr plays an even larger role in transcriptional control than previously expected.
Protective effects of endomorphins, endogenous opioid peptides in the brain, on human low density lipoprotein oxidation
Authors: Lin Xin , Xue Li‐Ying , Wang Rui , Zhao Qian‐Yu , Chen Qiang
Published: February 2006

Neurodegenerative disorders are associated with oxidative stress. Low density lipoprotein (LDL) exists in the brain and is especially sensitive to oxidative damage. Oxidative modification of LDL has been implicated in the pathogenesis of neurodegenerative diseases. Therefore, protecting LDL from oxidation may be essential in the brain. The antioxidative effects of endomorphin 1 (EM1) and endomorphin 2 (EM2), endogenous opioid peptides in the brain, on LDL oxidation has been investigatedin vitro. The peroxidation was initiated by either copper ions or a water‐soluble initiator 2,2′‐azobis(2‐amidinopropane hydrochloride) (AAPH). Oxidation of the LDL lipid moiety was monitored by measuring conjugated dienes, thiobarbituric acid reactive substances, and the relative electrophoretic mobility. Low density lipoprotein oxidative modifications were assessed by evaluating apoB carbonylation and fragmentation. Endomorphins markedly and in a concentration‐dependent manner inhibited Cu2+and AAPH induced the oxidation of LDL, due to the free radical scavenging effects of endomorphins. In all assay systems, EM1 was more potent than EM2 andl‐glutathione, a major intracellular water‐soluble antioxidant. We propose that endomorphins provide protection against free radical‐induced neurodegenerative disorders.