bluuebunny/crossref_metadata_2025 huggingface dataset:
Three‐dimensional lithospheric structure below the New Zealand Southern Alps
Authors: Kohler Monica D. , Eberhart‐Phillips Donna
Published: October 2003

Uppermost mantle seismic structure below the Southern Alps in South Island, New Zealand, is investigated by teleseismic P wave travel time residual inversion. The three‐dimensional tomographic images show a near‐vertical, high‐velocity (2–4%) structure in the uppermost mantle that directly underlies thickened crust along the NNE‐SSW axis of the Southern Alps. The center of the high‐velocity anomaly lies to the east of the Alpine fault which bounds Pacific and Australian plate rocks. The oblique collision of these plates resulted in the uplift of the Southern Alps during the past 5–7 m.y. Also, a high‐velocity anomaly (3–5%) corresponding to the Hikurangi subduction zone lies to the northeast of the Southern Alps anomaly, and low‐velocity anomalies (−3%) underlying parts of northwestern and southern South Island may be signatures of late Tertiary extension and volcanism. The data consist of teleseismic arrival times from the New Zealand National Seismograph Network and arrival times recorded during the 1995–1996 Southern Alps Passive Seismic Experiment. Crustal heterogeneity was accounted for by back projecting the rays through an independently obtained three‐dimensional crustal velocity and Moho depth model. The Southern Alps uppermost mantle velocity anomalies are most simply explained by lithospheric thickening below the center of convergence accompanied by thinning and asthenospheric upwelling adjacent to the region of convergence.
Sudden solar wind dynamic pressure enhancements and dayside detached auroras: IMAGE and DMSP observations
Authors: Zhang Y. , Paxton L. J. , Immel T. J. , Frey H. U. , Mende S. B.
Published: October 2003

Dayside detached auroras (DDA) refer to auroras observed separate from the equatorward edge of the main oval on the dayside. They are studied here using IMAGE FUV and DMSP particle data. Occurrence of these DDA appears to be correlated with sudden solar wind dynamic pressure enhancements and northward interplanetary magnetic field, as monitored by the Wind satellite. They are usually very dynamic and short‐lived with a lifetime of the order of 10 minutes. Out of the three FUV instrument channels on IMAGE, DDA are best detected by the IMAGE FUV SI‐12 instrument, which measures intensities of the Doppler red‐shifted Hydrogen Lyman Alpha line. This indicates that energetic proton precipitation is the major component. Simultaneous DMSP particle observations confirm that energetic protons (>10 keV) in the dayside inner magnetosphere are the primary source of those DDA detected by the SI‐12 instrument. DMSP also detected significant electron fluxes associated with the DDA, but the electron precipitations have little or no contribution to the DDA intensities detected by the SI‐12 instrument. Precipitations of energetic protons (electrons) which caused DDA could be explained by enhanced cyclotron instability which arose from adiabatic compression following sudden solar wind dynamic pressure enhancements.
Wild 2 and interstellar sample collection and Earth return
Authors: Tsou P. , Brownlee D. E. , Sandford S. A. , Hörz F. , Zolensky M. E.
Published: October 2003

Stardust, launched in 1999, is the first mission designed to bring samples from a known, recently deflected comet, 81P/Wild 2, on 2 January 2004 and is also the first to capture newly discovered contemporary interstellar dust streaming through our solar system. The Stardust aerogel collector accomplishes Stardust's primary science and will be returned to Earth with its captured samples on 15 January 2006 in a reentry capsule. Wild 2 samples will be captured at 6.12 km/s and represent well‐preserved relics of the outer regions of our solar nebula and fundamental building blocks of our planetary system. Interstellar grains captured at velocities of less than 10 km/s are expected to survive intact and represent the main repositories of condensable elements that permeate the galaxy. These solid cometary and interstellar samples will be captured in two back‐to‐back sample collection trays filled with variable‐density aerogel. There are 132 silica aerogel capture cells of 3 cm and 1 cm thickness for the cometary and the interstellar sides, respectively. The aerogel capture cells were wedged into the sample collection trays and wrapped on all four sides with 100‐μm‐thick pure aluminum foil to facilitate aerogel cell removal. The total exposed Wild 2 surface area is 1039 cm2 of aerogel and 153 cm2 of aluminum foil. Results from a preliminary examination for the Wild 2 samples will be reported within 9 months of sample return and for the interstellar samples a year later. After preliminary examination the samples will be transferred to the NASA Office of the Curator and made available to the general science community.
No evidence of attentional deficits in stabilized bipolar youth relative to unipolar and control comparators
Authors: Robertson Heather A , Kutcher Stanley P , Lagace Diane C
Published: October 2003

Objective: The purpose of this study was to determine the presence or absence of attentional problems and prior diagnosis of ADHD in a cohort of stabilized bipolar I relative to unipolar and normal control.

Method: Indices of attention were obtained from bipolar (n = 44), unipolar (n = 30), and normal controls (n = 45). Measures included: Freedom from Distractibility (FD) Composite Index of the WISC III, Conners’ Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), and a checklist measure of subjective cognitive/attentional problems (SIP‐AV).

Results: Bipolar (6.8%), unipolar (10%), and no control youth report a prior diagnosis of ADHD. No significant group or sex differences were observed on FD Composite Index, various CPT indices, or the WCST. Despite normative attentional function by objective testing, subjectively experienced cognitive problems in the clinical probands were reported.

Conclusions: This cohort of well‐functioning bipolar youth diagnosed on average 3–4 years prior to assessment do not possess attentional deficits based on a variety of objective tests compared to unipolar or control youth, but self report subjective difficulties in attentional/problem solving ability. In contrast to other authors, we do not find that bipolar youth have high rates of comorbid ADHD.
An overview of recent findings of the Stanley Foundation Bipolar Network (Part I)
Authors: Post Robert M , Leverich Gabriele S , Altshuler Lori L , Frye Mark A , Suppes Trisha M , Keck Paul E , McElroy Susan L , Kupka Ralph , Nolen Willem A , Grunze Heinz , Walden Jorg
Published: October 2003

Aim and Methods: Selected recent findings of the Stanley Foundation Bipolar Network are briefly reviewed and their clinical implications discussed.

Results: Daily prospective ratings on the NIMH‐LCM indicate a high degree of residual depressive morbidity (three times that of hypomania or mania) despite active psychopharmacological treatment with a variety of modalities including mood stabilizers, antidepressants, and benzodiazepines, as well as antipsychotics as necessary. The rates of switching into brief to full hypomania or mania during the use of antidepressants is described, and new data suggesting the potential utility of continuing antidepressants in the small group of patients showing an initial acute and persistent response is noted. Bipolar patients with a history of major environmental adversities in childhood have a more severe course of illness and an increased incidence of suicide attempts compared with those without. Preliminary open data suggest useful antidepressant effects of the atypical antipsychotic quetiapine, while a double‐blind randomized controlled study failed to show efficacy of omega‐3 fatty acids (6 g of eicosapentaenoic acid compared with placebo for 4 months) in the treatment of either acute depression or rapid cycling. The high prevalence of overweight and increased incidence of antithyroid antibodies in patients with bipolar illness is highlighted.

Conclusions: Together, these findings suggest a very high degree of comorbidity and treatment resistance in outpatients with bipolar illness treated in academic settings and the need to develop not only new treatment approaches, but also much earlier illness recognition, diagnosis, and intervention in an attempt to reverse or prevent this illness burden.
Tissue distribution of histo‐blood group antigens.
Authors: Ravn Vibeke , Dabelsteen Erik
Published: October 2003

The introduction of immunohistochemical techniques and monoclonal antibodies to specific carbohydrate epitopes has made it possible to study in detail the tissue distribution of histo‐blood group antigens and related carbohydrate structures. The present paper summarizes the available data concerning the histological distribution of histo‐blood group antigens and their precursor structures in normal human tissues. Studies performed have concentrated on carbohydrate antigens related to the ABO, Lewis, and TTn blood group systems, i.e. histo‐blood group antigens carried by type 1, 2, and 3 chain carrier carbohydrate chains. Histo‐blood group antigens are found in most epithelial tissues. Meanwhile, several factors influence the type, the amount, and the histological distribution of histo‐blood group antigens, i.e. the ABO, Lewis, and saliva‐secretor type of the individual, and the cell‐and tissue type. Oligosaccharides with blood‐group specificity are synthesized by the stepwise action of specific gene‐encoded glycosyltransferases. In general, this stepwise synthesis of histo‐blood group antigens correlates with cellular differentiation. The H and the Se genes both encode an α1–2fucosyltransferase, which is responsible for the synthesis of blood group antigen H from precursor disaccharides. A new model for the participation of the Se/H‐gene‐encoded glycosyl transferases in synthesis of terminal histo‐blood group antigens in human tissues is proposed; the type and degree of differentiation rather than the embryologic origin determines whether it is the H or the Se gene‐encoded transferases that influence expression of terminal histo‐blood group antigens in tissues.
Expression of topoisomerase II alpha, Ki‐67 and p53 in early stage laryngeal carcinomas not featuring vocal cord fixation
Authors: Horibe YOSHIMUNE , Murakami MASAMOTO , Komori KATSUHIKO , Imaeda YOSHIHIRO , Kasahara MASAO
Published: October 2003

Aim. To determine whether topoisomerase II alpha (topolla) expression is an additional prognostic marker for less advanced stage laryngeal cancers first treated without surgery. Ki‐67 and p53 protein levels were also assessed for comparison. Experimental design. Formalin‐fixed, paraffin‐embedded tumor material from 63 cases of squamous cell carcinoma (SCC) of the larynx (glottis, stages 0,1,2) was immunohistochemically stained for topolla, Ki‐67 (MIB‐1) and p53 (DO‐7) and the results were compared with clinicopathologic findings. Results. There were 7 stage 0 (TisNOMO), 33 stage I (T1N0M0), and 23 stage II (T2N0M0) SCCs with the TNM classification. Significant differences between carcinomas and normal mucosa were found for the topoIIa‐LI, Ki‐67‐LI, and topolla‐to‐Ki‐67 ratio. Regarding histologic grade, a significant difference in topoIIa‐to‐Ki‐67 ratio was evident between well or moderately and poorly differentiated lesions. There were 19 cases of recurrence and 44 cases of nonrecurrence, but no significant differences were found for either of the indices or their ratio. No significant variation with p53 positivity was evident with reference to histologic differentiation, T‐factor, clinical course, or proliferation. Conclusions. The results demonstrate that the topoIIa‐to‐Ki‐67 ratio is a more sensitive parameter reflecting proliferation, for histologic grading of less advanced laryngeal SCCs, than topolla‐ or Ki‐67‐LIs.
Prevalence of EHEC O157:H7 in patients with diarrhoea in Lagos, Nigeria
Authors: Olorunshola ISAAC D. , Smith STELLA I. , Coker AKITOYE O.
Published: October 2003

The prevalence of sorbitol‐nonfermenting Escherichia coli O157:H7 (EHEC) was assessed in 100 patients with diarrhoea by stool culture on sorbitol MacConkey agar. The cytotoxicity of the EHEC strains was analysed by Vero cell assay and the antimicrobial susceptibility pattern of the isolates was determined. Detection rate of EHEC O157:H7 was 6%. Five of the six patients were males. Three of the isolates were from children and one was from a teenager. All strains induced cytotoxic effects in the Vero cell assay. All isolates were susceptible to most of the antimicrobials tested. The results showed that diarrhoea caused by EHEC O157:H7, a potentially life‐threatening pathogen, has remained common particularly among the child population of Lagos during the past 10 years (5). There must therefore be adequate meat and food inspection to improve the general hygiene of local fast food restaurants, so‐called ‘bukkas’, which are regarded as likely sources of infection.
Vasitis nodosa: Immunohistochemical findings – Case report
Authors: Sakaki Mika , Hirokawa Mitsuyoshi , Horiguchi Hidehisa , Wakatsuki Shingo , Sano Toshiaki
Published: October 2003

We report the immunohistochemical features of vasitis nodosa and discuss the differential diagnosis. The patient was a 42‐year‐old Japanese man with bilateral small indurations of the vas deferens at the site of a previous vasectomy. Microscopically, small‐sized ducts proliferated within the muscular wall of the vas deferens, and focally in the surrounding connective tissue. Immunohistochemically, most proliferating glandular cells were strongly positive for cytokeratins 7, 19, and 34βE12, and vimentin. Epithelial membrane antigen and Leu‐M1 reacted against the luminal surface of the cells. Focally, glandular cells were also positive for CA125. Cytokeratin 20, carcinoembryonic antigen, and prostate‐specific antigen were negative. We discuss the immunohistochemical differentiation of vasitis nodosa from prostatic adenocarcinoma, adenocarcinoma of the rete testis, and adenomatoid tumor.
Congenital laryngeal atresia: two autopsy cases, one describing the use of computed tomography
Authors: Asano Shigeyuki , Yamagiwa Kazuhiro , Konnai Ikuo
Published: October 2003

Two autopsy cases of congenital laryngeal atresia (CLA) were studied. In the first case (a boy delivered at 37 weeks of gestation) the subglottic lumen was almost totally occupied by a dome shaped cricoid cartilage with a pharyngotracheal duct (PTD). No tracheoesophageal fistula (TEF) was found. In the second case (a girl born at 41 weeks of gestation) histology showed that the subglottic lumen was almost occluded by an epithelial lamina and a dome‐shaped cricoid cartilage. Again no TEF was found. Both cases had PTD and showed normal development of the lungs. These deformities coincided with Smith & Bain's type II subglottic atresia. The anatomy of the lesion was confirmed by postmortem three‐dimensional reconstruction CT, the use of which has not previously been reported.
Nodular granulomatous Pneumocystis carinii pneumonia in a bone marrow transplant recipient
Authors: Leroy Xavier , Copin Marie‐Christine , RAMON PHILIPPE , Jouet Jean‐Pierre , Gosselin Bernard
Published: October 2003

We report a case of nodular granulomatous Pneumocystis carinii pneumonia following bone marrow transplantation.

The patient was a 40‐year‐old man who had undergone bone marrow transplantation for myeloblastic acute leukemia. He presented with fever, dyspnea and bilateral diffuse nodular infiltration of the lungs. Bronchoalveolar lavage was negative. Open lung biopsy was performed. Histological examination revealed a granulomatous reaction with central necrosis surrounded by epithelioid and giant cells. Toluidine blue and Gomori‐Grocott stains identified a few P. carinii. Mycobacterial and fungal cultures were negative. A granulomatous reaction is rarely observed and almost only in HIV‐infected patients. To our knowledge this is the first description in a bone marrow transplant recipient.
Aerogenous infection of microbiologically defined minipigs with Streptococcus suis serotype 2
Authors: Madsen Lars W. , Aalbæk Bent , Nielsen Ole L. , Jensen Henrik E.
Published: October 2003

Streptococcus suis serotype 2 is the cause of serious infections in animals and humans, but certain aspects of the infection pathogenesis still remain unclear. In this study an experimental model of aerogenous infection and induction of septicemia with S. suis serotype 2 was established in microbiologically defined Göttingen minipigs. Ten animals were exposed to aerosolized S. suis after previous exposure to mild acetic acid in aerosol. Six of the animals were immunosuppressed with prednisolone acetate on different days. All the animals were monitored clinically until euthanasia on days 6 to 13 after exposure. Necropsy was performed and samples were taken for microbiology, histopathology, and immunohistochemistry. Three out of four animals immunosuppressed on days 5 to 7 after exposure developed S. suis septicemia, and S. suis could be detected in the tonsil of the soft palate and/or the nasal cavity of all exposed animals. Thus, using the presented model, local as well as systemic infection with S. suis serotype 2 was established in the Göttingen minipig. Since this breed is defined as free of S. suis and a range of other endemic porcine pathogens, the experimental model could prove useful in the study of this infection.
The prognostic importance of the nucleolar organizer region (AgNOR), Ki‐67 and proliferating cell nuclear antigen (PCNA) in primary nonurachal bladder adenocarcinoma
Authors: ÖZDEMIR B. HANDAN , ÖZDEMIR O. GÜRHAN , SERTÇELIK AYSE
Published: October 2003

The aim of this study was to investigate the role of tumor proliferation in patients with nonurachal bladder adenocarcinoma. Samples were obtained from 16 patients (12 men and 4 women, mean age 62 years) with primary nonrurachal bladder adenocarcinoma. The 16 formalin‐fixed specimens were stained immunohistochemically for Ki‐67 antigen and PCNA using MIB‐1 and PC‐10 antibodies. In addition, the AgNOR quantity was assessed using the colloid silver nitrate staining technique in all cases. The Ki‐67, PCNA and AgNOR proliferation indices were found to be significantly higher in high‐grade and invasive tumors. The higher the grade (p<0.01) and stage (p<0.01), the higher were the proliferation indices. Patients whose tumor samples had a high Ki‐67, PCNA and AgNOR proliferation index showed a higher incidence of local recurrence (p<0.01) and distant metastasis (p<0.01). In conclusion, our results suggest that Ki‐67, PCNA and AgNOR proliferation scores may be important prognostic indices in nonurachal bladder adenocarcinomas.
Rapid immunodiagnosis of streptococci and enterococci in blood culturesNote
Authors: Kristensen Brian , Højbjerg Tove , Schønheyder Henrik Carl
Published: October 2003

We evaluated a procedure for rapid identification of blood culture isolates of pneumococci, enterococci and beta‐haemolytic streptococci groups A, B, C, and G. Immunological tests were applied directly to blood culture medium and included a quellung reaction for pneumococci, and latex agglutination tests (LAT) for pneumococcal antigen and Lancefield antigens A, B, C, D and G. During a one‐year trial period with approximately 12,000 blood culture sets (BacT/Alert®, Organon‐Teknika), 208 sets showed pure growth of Gram‐positive cocci in pairs or chains by direct microscopy. Overall, a correct diagnosis was noted for 103 (63.2%, 95% CI: 55.3–70.6%) of 163 sets yielding pneumococci, beta‐haemolytic streptococci, or enterococci. A procedure excluding Lancefield antigens only A, B, and D was implemented during a one‐year follow‐up period. With this simplified procedure positive and negative predictive values, respectively, were 1.00 and 0.87 for pneumococci, 1.00 and 0.94 for beta‐haemolytic streptococci group A, 0.60 and 1.00 for beta‐haemolytic streptococci group B, and 0.91 and 0.88 for enterococci. We conclude that rapid identification of Gram‐positive cocci is feasible and may improve the information given to clinicians at the first notification of positive blood cultures.
A cellular model system of differentiated human myotubes
Authors: GASTER M. , KRISTENSEN S. R. , BECK‐NIELSEN H. , SCHRØDER H. D.
Published: October 2003

The aim of this study was to select an effective and stable protocol for the differentiation of human satellite cells (Sc) and to identify the optimal time period for the experimental use of differentiated human Sc‐cultures. In order to identify the differentiation conditions which give a good survival of myotubes and a high grade of differentiation, Sc‐cultures were induced to differentiate in media supplemented with either 2% fetal calf serum (FCS) 2% horse serum (HS) or 10% HS. Based on higher CK‐activities in cultures differentiating in FCS‐supplemented media compared to horse sera, fetal calf serum was chosen to induce differentiation. The ATP, DNA and protein content increased during the first 4 days after induction of differentiation and was followed by a period with minor changes. The maximal differences of ATP, DNA and protein between days 4–10 were evaluated and the differences in the three components were found to be less than 20% of the average value with a certainity of more than 0.9. Day 8‐myotubes were investigated morphologically and were found immunoreactive for fast myosin, and expressed areas with clear cross striation. We recommend the use of differentiated Sc‐cultures in the period from day 4 to 8 after induction of differentiation as only minor differentation‐related changes will take place in the cells during this period of time.
Expression of RNAs encoding for α and β integrin subunits in periodontitis and in cyclosporin A gingival overgrowth
Authors: Bolcato‐Bellemin A.‐L. , Elkaim R. , Tenenbaum H.
Published: October 2003

Background: Variation of integrin expression in healthy and diseased gingiva revealed a potential biological role for these cell matrix receptors during gingival remodeling.

Aim: Here we determined the level of RNA and tissue localization of different integrin subunits in periodontitis and cyclosporin A‐induced gingival overgrowth.

Methods: The level of expression was determined by Reverse Transcriptase Polymerase Chain Reaction in 12 periodontitis‐affected patients, four patients exhibiting severe cyclosporin A‐induced gingival overgrowth and seven healthy patients as controls.

Results: The RNA encoding for β1, α2 and α5 integrin subunits were reduced in periodontitis gingiva. The reduction observed was stronger in cyclosporin A‐treated patients as compared to the healthy controls, while RNA encoding for α1 subunit was increased. The RNA encoding for α6 integrin was only reduced in cyclosporin A‐treated gingiva. Immunohistochemistry showed that i) integrin α2 expression is restricted to the gingival epithelium of cyclosporin A‐treated patients, ii) the reduction of α6 integrin expression in cyclosporin A‐treated gingiva is due to loss of expression at focal contacts and iii) β1 integrin is evenly distributed in the three populations with an intensity decrease in periodontitis and cyclosporin A‐treated gingiva.

Conclusion: Taken together these results showed a role for the integrin receptors in periodontal diseases and cyclosporin A‐induced gingival overgrowth.
Gm (23) allotypes and Fcγ receptor genotypes as risk factors for various forms of periodontitis
Authors: Chung Hsien‐Yang , Lu Hsi‐Chi , Chen Woan‐Ling , Lu Chun‐Tai , Yang Yi‐Hsin , Tsai Chi‐Cheng
Published: October 2003

Objectives: Given the diversity of the distribution of the Gm (23) allotypes and FcγR genotypes in different ethnic groups, it was our purpose to examine their clinical significance in periodontitis in Taiwan.

Material & Methods: Genomic DNA of 50 patients with chronic periodontitis (CP), 30 patients with generalized aggressive periodontitis (G‐AP) and 74 healthy controls were harvested. The Gm (23) allotypes were determined by radial immunodiffusion test, and the FcγR IIa (CD32) and IIIb (CD16) genotypes were determined by polymerase chain reaction‐based allele‐specific oligonucleotide hybridization.

Results: The overall carrier rate of the Gm (23+) allotype was higher than 85%, and the Gm (23−) allotype was statistically over‐represented in patients with CP compared to the controls. There were no differences in the distributions of the three genotypes of FcγR IIa and IIIb among the three tested groups. The frequency of the R131 allele of the FcγR IIa polymorphisms was higher in G‐AP than in CP when R/H allelic frequencies (p=0.01) were examined by the χ2 test.

Conclusion: The Gm (23−) allotype might be a potential risk factor for CP. Although the R131 allele of FcγR IIa occurred more frequently in G‐AP than in CP, its clinical significance could not be justified in this study.
Perceived risk of deteriorating periodontal conditions
Authors: Rutger Persson G. , Attström Rolf , Lang Niklaus P. , Page Roy C.
Published: October 2003

Background: Interpretation of risk for periodontitis is critical for treatment planning. How periodontists assess risk for periodontitis is unclear.

Purpose: To study (1) what factors periodontists use when assessing the risks for worsening periodontal conditions anticipating that no treatment would be provided, and (2) if risk assessment is consistent and independent of specialty background training.

Material and Methods: Medical history, clinical dental data, full‐mouth intra‐oral radiographs, and slide pictures were obtained from each of 51 subjects, and the information was provided to 23 examiners.

Results: The mean age of the study subjects was 51.5 years (SD±17.7, range 23–81), with 28 women included. In 10 of the subjects, only gingivitis was identified, while 22 subjects had advanced chronic periodontitis. Risk scores assigned for 2 and 4 years differed significantly between European‐ and US‐trained periodontists (p<0.001) and between graduate students in training and periodontists from either the US or Europe (p<0.01) (Wilcoxon n‐pair test), with European periodontists scoring the lowest risks. Risk scores were correlated between groups (p<0.01 with ρ range 0.82–0.89) (Spearman's rank correlation). The best‐fit model (r2=0.86) to assess perceived risk for worsening periodontal conditions based on data from all examiners combined included the following variables: (1) overall horizontal alveolar bone loss (p<0.000), (2) age‐adjusted proportional radiographic bone height score for the worst site (p<0.000), and (3) proportion of pocket probing depths 6.0 mm.

Conclusions: Differences exist on the scale of risk values based on specialty training. Consistency in scoring patterns exists. The examiners based their assigned risk scores almost exclusively on measures of existing disease severity, including radiographic bone loss and numbers of periodontal pockets 6.0 mm, and excluding most known risk factors such as smoking, diabetes, and poor oral hygiene.
Geometrical capillary network analysis
Authors: Sainthillier Jean‐Marie , Degouy Arnaud , Gharbi Tijani , Pieralli Christian , Humbert Philippe
Published: October 2003

Background: Skin microcirculation, especially the superficial network, can be assessed by a computer capillary video microscope system. The study of morphology and dynamics of microcirculation must include all dynamic and cooperative processes between the capillaries. For characterizing capillary ensembles, the statistical and geometrical properties of the network need to be explored.

Methods: The microvaculature of the skin and the microcirculation were investigated by combining videocapillaroscopy (VCP) and image processing techniques based on computational geometry and graph theory. Our goal was to characterize the capillary network in noisy pictures of the scalp. Different geometric methods were developed, based on proximity parameters (distance and surface) in order to circumscribe and construct this network.

Results: By studying the distribution of these parameters, extreme values or outliers, which usually correspond to artifact subregions in the pictures could be eliminated. Different algorithms were developed and has been implemented in an image processing software (Capilab Toolbox).

Conclusion: This computerized system is capable of real‐time processings, increasing the quality of videocapillaroscope images and minimizing the disturbance of artifacts. The algorithms presented here are easy to implement and can process any kind of images of the skin, even in the scalp. In association with an example‐based detection system, this method can be generalized to other stimuli in the same conditions.
Assessment of skin viability: is it necessary to use different methodologies?
Authors: Messager Syndie , Hann A.C. , Goddard P.A. , Dettmar P.W. , Maillard J.‐Y.
Published: October 2003

Background/aim: Skin is complex and may display variable structural and metabolic change ‘ex vivo’. The present study aimed to follow measures of skin viability and evaluate their usefulness as markers of viability.

Materials and methods: We evaluated the viability of skin samples fresh or after being frozen and subsequently thawed. Assessments included histopathological appearance, lactate dehydrogenase (LDH) activity, oxygen consumption and skin pH.

Results: Morphological investigations of fresh and frozen skin samples using light and electron microscopy showed samples with relatively well‐defined epidermis and dermis. Frozen samples showed some sign of stratum corneum fragmentation, although this was not obvious. LDH activity measured in fresh samples kept at 4°C was low, but it was stable up to 7 days. Fresh samples kept at 32°C had a comparable LDH activity to the ones kept in the fridge up to 4 days. Frozen samples, thawed and then kept at 4°C showed a stable LDH activity after 24 h of incubation. However, frozen samples incubated at 32°C demonstrated a high variability in results, with up to 800 U/L of LDH activity after 5 days of incubation. Freshly excised as well as freshly thawed samples showed the highest respiration rates. Fresh and thawed samples stored for a long period of time had a significantly lower (sometimes non‐existent) oxygen consumption rate. Our results also showed an increase in the oxygen consumption rate of fresh samples being incubated at 32°C for 24 h. The oxygen consumption rate for all samples reached a plateau within the 15‐min measurement period and even the fresh samples did not deplete all the oxygen from the medium. Skin samples ex vivo showed a significantly higher pH than human skin in vivo, and when incubated for 46 h at 32°C, fresh samples had a significantly lower pH than frozen samples. All protocols were reproducible and freshly excised and freshly thawed skin samples showed the highest rates of viability.

Conclusion: ex vivo skin shows variation of several parameters over time. It is recommended to use two or three techniques for evaluation of skin viability including at least oxygen measurement and an enzyme assay.
Further Experience with Intravenous Immunoglobulin in Women with Recurrent Miscarriage and a Poor Prognosis
Authors: CARP H.J.A. , AHIRON R. , MASHIACH S. , CARP H.J.A. , TODER V. , TORCHINSKI A. , SHOENFELD Y. , GAZIT E.
Published: October 2003

PROBLEM: Women with three or more unexplained miscarriages have a 60% chance of a subsequent live birth. Intravenous immunoglobulin (IVIG) has not been conclusively shown to improve this prognosis. This study assessed the effect of IVIG in patients expected to have a poor outcome if untreated, i.e. women with five or more abortions, who have aborted after paternal leukocyte immunization or who continue to abort despite expressing anti‐paternal complement dependent antibody.  METHODS: Seventy‐six women received IVIG in a dose of 400 mg/kg body weight, in one day (total 30–45 g) in the follicular phase of a cycle in which pregnancy was planned. A booster dose was administered when pregnancy was diagnosed. Their results were compared to an untreated control group of 74 women.  RESULTS: Thirty‐five (49%) pregnancies in treated women have resulted in live births or passed their previous stages of abortion compared to 23 (31%) in control patients (P=0.04).  CONCLUSIONS: These figures indicate that IVIG may prevent further miscarriages in this poor prognosis population. These figures are especially significant considering the doubt concerning the efficacy of IVIG in patients with three miscarriages and therefore a relatively good prognosis.
Human Papilloma Virus (HPV)‐E6/E7 and Epidermal Growth Factor Receptor (EGF‐R) Protein Levels in Cervical Cancer and Cervical Intraepithelial Neoplasia (CIN)
Authors: MATHUR SUBBI P. , MATHUR RAJESH S. , YOUNG ROGER C. , RUST PHILIP F.
Published: October 2003

BACKGROUND: About 90% of cervical cancers and advanced cervical intraepithelial neoplasia (CIN II/III) are squamous epithelial cells with mRNA for human papillomavirus (HPV)16 and 18 and up‐regulated epidermal growth factor receptor (EGF‐R). Since presence of proteins rather than mRNA may be truly indicative of active infection or disease progression, establishing reliable methods for quantifying these proteins in cervical biopsies is important.  METHOD: We have established an objective semi‐quantitative immunofluorescent antibody assay to reliably assess the levels of HPV‐E6/E7 and EGF‐R proteins in the cervical biopsies from 12 normal women, five women with CIN I, 15 with CIN II/III and ten with cervical cancer.  RESULTS: HPV‐E6/E7 and EGF‐R, when present, were specific to para‐basal, basal and squamous epithelial cells (negative in stromal cells). Nine of ten women with cervical cancer and 15 (14 CIN II/III; 1 CIN I) of 20 women with CIN were positive for HPV‐E6/E7. All 12 controls were HPV‐negative. The controls and six women with CIN (four with CIN I) negative for HPV had low levels of EGF‐R. The only exception was one woman with cervical cancer negative for HPV, with high levels of EGF‐R. Levels of HPV‐E6/E7 and EGF‐R were significantly higher (P<0.001 vs. controls) in women with advanced CIN II and III (P<0.05 vs. controls in CIN I) and cervical cancer. The HPV‐E6/E7 and EGF‐R levels correlated significantly (r=18.98; P<0.001, by linear regression analysis).  CONCLUSION: We have established a highly specific and sensitive semi‐quantitative immunofluorescent antibody assay for measuring levels of HPV‐E6/E7 proteins and EGF‐R in archival cervical biopsies. Our data suggest an association between HPV‐E6/E7 and EGF‐R.
Immune Disorders in Women with Premature Ovarian Failure in Initial Period
Authors: CHERNYSHOV VICTOR P. , RADYSH TATYANA V. , GURA IRENE V. , TATARCHUK TATYANA P. , KHOMINSKAYA ZINAIDE B.
Published: October 2003

PROBLEM: Premature ovarian failure (POF) may be considered as an autoimmune endocrine disease. Autoantibodies and lymphocyte subset changes are associated with premature ovarian failure. Immune cell parameters were studied in relation with anticardiolipin antibodies (ACAB) classes M and G in the initial period of POF.  METHODS: Two‐color flow cytometry was used to determine lymphocyte subsets and enzyme‐linked immunosorbent assay (ELISA) was used to detect ACAB and hormones in the peripheral blood of 68 POF patients, 32 women with normal menopause (NM) and 13 healthy women as a normal control (NC).  RESULTS: Patients in the initial period of POF had decreased levels of CD3+, CD19+, CD3+8+, and CD8+57+ lymphocytes and a high percentage of CD5 positive in CD19+ cell population compared to the control; frequencies of IgM ACAB in POF patients were significantly higher than both IgG ACAB and IgM ACAB in NC; correlation between lymphocyte subsets and hormone levels was absent. Women with early NM showed a low number of CD3+, CD3+4+, and CD3+8+ lymphocytes, a high number of CD3+DR, and elevation of the percentage of CD5 positive in CD19+ lymphocytes compared with the control. The frequencies of both IgM and IgG ACAB were high; the levels of lymphocyte subsets had correlations with progesterone and estradiol concentrations.  CONCLUSIONS: An increase of autoantibody producing B cells (CD5+19+) and a low number of effector suppressor/cytotoxic lymphocytes (CD8+57+) with active production of anticardiolipin autoantibodies class M were found. This suggested a primary autoimmune process in the initial period of POF. Autoimmune defeat of the ovary could be the primary cause of POF, whereas in NM autoimmunity is a result of hormone dysfunction.
Functional studies of hephaestin in yeast: evidence for multicopper oxidase activity in the endocytic pathway
Authors: LI Liangtao , VULPE Chris D. , KAPLAN Jerry
Published: October 2003

Hephaestin is a mammalian gene that encodes a predicted multicopper oxidase required for intestinal iron export. To examine if hephaestin can act as a ferroxidase, we studied yeast strains transformed with plasmids containing both a full-length hephaestin and a hephaestin lacking a transmembrane domain. Yeast with a deletion in FET3, which encodes a cell-surface multicopper oxidase, cannot grow on low-iron media. Expression of full-length hephaestin could complement the low-iron growth phenotype of a Δfet3 strain. Complementation of Δfet3 cells by hephaestin required genes that encode proteins necessary for the copper loading of Fet3p, including CCC2 and GEF1. Expression of hephaestin in Δfet3 cells led to an increase in both iron transport and oxidase activity. These results demonstrate that hephaestin is a copper-dependent protein. In contrast with Fet3p, which is found on the cell surface, hephaestin was co-localized with Pep12p-containing vesicles. Inhibition of endocytosis or deletion of both the vacuolar iron transporters (SMF3 and FET5/FTH1) prevented hephaestin from complementing the low-iron growth phenotype of Δfet3 cells, suggesting that hephaestin is functioning within the endocytic apparatus.
Chemical synthesis and microvascular effects of new nitric oxide donors in humans
Authors: KHAN Faisel , PEARSON Russell J. , NEWTON David J. , BELCH Jill J. F. , BUTLER Anthony R.
Published: October 2003

Nitric oxide (NO) is produced continuously from the endothelium and plays a pivotal role in the control of vascular tone. Many of the current therapeutic agents that increase blood flow through production of NO have to be taken orally and can produce significant adverse side effects. We now report on some novel NO-donor drugs, based on thiosugars that generate NO spontaneously. From the range of compounds synthesized, D-SNAG (S-nitroso-1-thio-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose) was as effective a vasodilator as any other and, as it was the easiest to synthesize, we undertook a more detailed evaluation to understand the chemistry and mode of action of its vasodilator effect. From the chemical kinetic data, we found that NO release occurred predominantly by thermal decomposition, with a 20-fold increase in decomposition rate between 19 and 37 °C. In the forearm of eight normal male subjects, we found that D-SNAG produced a significant dose-dependent vasodilator effect (P=0.001) with good reproducibility (19%) on repeated testing. We propose that delivery of NO from D-SNAG to the forearm skin microvessels most probably occurs by diffusion across the epidermis. Since such compounds release NO in a non-enzymic manner following topical application, they might produce an attractive therapeutic source of localized NO delivery without inducing systemic side effects.
The minimal model: an evolving methodology
Authors: GODSLAND Ian F.
Published: October 2003

After more than 20 years, minimal model analysis of intravenous glucose tolerance test glucose and insulin concentrations continues to be widely employed in studies of insulin sensitivity and insulin resistance. Moreover, problems encountered in solving the minimal model equations continue to find new solutions. Bayesian techniques enable prior knowledge to be incorporated into parameter estimation routines. They offer particular advantages in the measurement of insulin sensitivity with the minimal model, and provide an elegant means of improving model identification success rates and parameter precision. This comment describes the study by Agbaje and colleagues in this issue of Clinical Science that exemplifies a new phase in the evolution of minimal model practice.
Ventricular dysfunction in early diabetic heart disease: detection, mechanisms and significance
Authors: WATTS Gerald F. , MARWICK Thomas H.
Published: October 2003

The detection of preclinical heart disease is a new direction in diabetes care. This comment describes the study by Vinereanu and co-workers in this issue of Clinical Science in which tissue Doppler echocardiography has been employed to demonstrate subtle systolic and diastolic dysfunction in Type II diabetic patients who had normal global systolic function and were free of coronary artery disease. The aetiology of early ventricular dysfunction in diabetes relates to complex intramyocardial and extramyocardial mechanisms. The initiating event may be due to insulin resistance, and involves abnormal myocardial substrate utilization and uncoupling of mitochondrial oxidative phosphorylation. Dysglycaemia plays an important role via the effects of oxidative stress, protein kinase C activation and advanced glycosylation end-products on inflammatory signalling, collagen metabolism and fibrosis. Extramyocardial mechanisms involve peripheral endothelial dysfunction, arterial stiffening and autonomic neuropathy. The clinical significance of the ventricular abnormalities described is unknown. Confirmation of their prognostic importance for cardiac disease in diabetes would justify routine screening for presymptomatic ventricular dysfunction, as well as clinical trials of novel agents for correcting causal mechanisms. These considerations could also have implications for patients with obesity and the metabolic syndrome.
The Arabidopsis mutant iop1 exhibits induced over‐expression of the plant defensin gene PDF1.2 and enhanced pathogen resistance
Authors: Penninckx Iris A. M. A. , Eggermont Kristel , Schenk Peer M. , Van den Ackerveken Guido , Cammue Bruno P. A. , Thomma Bart P. H. J.
Published: October 2003

Jasmonate and ethylene are concomitantly involved in the induction of the Arabidopsis plant defensin gene PDF1.2. To define genes in the signal transduction pathway leading to the induction of PDF1.2, we screened for mutants with induced over‐expression of a β‐glucuronidase reporter, under the control of the PDF1.2 promoter. One mutant, iop1 (induced over‐expressor of PDF1.2) produced small plants that showed induced over‐expression of the pathogenesis‐related genes PR‐3, PR‐4 and PR‐1,2 (PDF1.2), combined with a down‐regulated induction of PR‐1 upon pathogen inoculation. The iop1 mutant showed enhanced resistance to a number of necrotrophic pathogens.
Olfaction in bird dogs during hunting
Authors: STEEN J. B. , MOHUS I. , KVESETBERG T. , WALLØE L.
Published: October 2003

The ability to catch scent continuously while running, which may be an essential skill for many animals of prey, requires that ambient air flows inward through the nose also during expiration. In this study on bird dogs, the direction of air flow was detected by measuring the temperature in the air inside the nostril. While resting, nose ventilation was synchronous with lung ventilation. While searching for ground scent, the dog was sniffing at a frequency of up to 200 s‐1, a strategy which may create turbulence in the nasal passages and thereby enhance transport of scent molecules to the receptors in the ethmoidal cavity. When the bird dog was searching for game while running with its head high against the wind, it maintained a continuous inward air stream through the nose for up to 40 s spanning at least 30 respiratory cycles. We suggest that expiratory gas flowing at high velocity from the trachea to the mouth cavity creates a lower pressure than in the nose thus causing an inward air stream through the nose during expiration by a Bernoulli effect.
Anaerobic capacity and maximal oxygen uptake during arm stroke, leg kicking and whole body swimming
Authors: OGITA F. , HARA M. , TABATA I.
Published: October 2003

In the present study, we determined both anaerobic capacity (the maximal accumulated oxygen deficit) and maximal oxygen uptake (VPo2max) during arm stroke (A), leg kicking (K), and whole body swimming (S), and compared them. The subjects were six trained college swimmers (two male and four female), aged 20±1 years. To determine VPo2max for A, K and S, VPo2max was measured during a 6‐min swim at constant water flow rates. VPo2 was measured by the Douglas bag method. Anaerobic capacity was determined by accumulated oxygen deficit during exercise lasting 2–3 min according to the methods of Medbøet al. Mean values of VPo2max during A, K and S were 2.53±0.37 L min‐1, 2.93±0.37 L min‐1, and 3.23±0.43 L min‐1, respectively. Those in A and K corresponded to 78.2% and 91.0% of that in S. Mean values of anaerobic capacity during A, K and S were 2.15±0.31 L, 2.52±1.08 L and 2.99±0.52 L, respectively. Those in A and K corresponded to 73.3% and 81.7% of that in S. Both VPo2max and anaerobic capacity in S were much lower than the sum of A and K, corresponding to only 59.3% and 65.9%, respectively. These results suggest that the total energy production during S is lower than simply the sum of A and K because the potentials of both the anaerobic and aerobic energy releasing processes in the muscle groups involved in A and K cannot be fully reached during S.
Increased expression of xanthine oxidase and insulin‐like growth factor I (IGF‐I) immunoreactivity in skeletal muscle after strenuous exercise in humans
Authors: HELLSTEN Y. , HANSSON H.‐A. , JOHNSON L. , FRANDSEN U. , SJÖDIN B.
Published: October 2003

The present study investigated the effect of 7 days of strenuous exercise on the quantity of xanthine oxidase and IGF‐I in muscle. Fifteen male military trainees performed 1 week of terrain marching and warfare exercises. Muscle biopsies and blood samples were obtained prior to and after the week. After the week, the number of xanthine oxidase immunoreactive cells, identified as capillary endothelial cells and leucocytes, and the number of IGF‐I immunoreactive cells, mainly vascular cells but also cells tentatively identified as satellite cells, were higher in the muscle (P<0.05). Plasma creatine kinase activity was 650% higher after the week (P<0.001) and the muscle content of hydroxyproline was elevated by 160% 2 months post‐exercise (P< 0.05), both findings implying injury to the muscle. The present data provide a first observation of an elevated level of xanthine oxidase and IGF‐I in human skeletal muscle after exercise. It is proposed that both substances increased as a result of cellular damage: xanthine oxidase because of the influence of immunomodulators, and IGF‐I in association with regenerative processes. The increased expression of IGF‐I in the muscle could, however, also reflect cellular growth in response to an elevated load on the muscle and the vascular bed.