bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationships between ocular dimensions and adult stature among participants in the Reykjavik Eye Study
Authors: Eysteinsson Thor , Jonasson Fridbert , Arnarsson Ársæll , Sasaki Hiroshi , Sasaki Kazuyuki
Published: September 2005

Purpose:  To examine the relationships between adult stature, age and ocular dimensions in a large homogenous, white population.

Methods:  We used the national population census for Reykjavik to select a random sample of adults aged 50 years or older. A total of 846 persons were examined. Scheimpflug images were used to measure anterior chamber depth. Ultrasound was used to measure axial length, lens thickness and vitreous chamber depth. An autorefracto‐keratometer was used to measure autorefractive and keratometric values, including the radius of the corneal curvature. Stereo fundus photographs were taken of the optic disc and measurements of the disc diameters were made using computer software.

Results:  Height correlated positively with axial length in the multivariate model (B = 0.020, 95% CI 0.006–0.034, p < 0.01). Both age and height showed significant correlations with vitreous chamber depth, where the correlation with age was negative (B = − 0.016, 95% CI − 0.006 to − 0.025, p < 0.005) and the correlation with height was positive (B = 0.019, 95% CI 0.005–0.034, p < 0.01). Height also showed a positive correlation with the radius of the corneal curvature (B = 0.008, 95% CI 0.004–0.011, p < 0.001). Anterior chamber depth had a negative correlation with age (B = − 0.013, 95% CI − 0.010 to − 0.016, p < 0.001), whereas lens thickness had a significant positive correlation with age (B = 0.019, 95% CI 0.016–0.023, p < 0.001). We found a significant negative correlation between axial length and refraction/spherical equivalent (r = – 0.595, p < 0.0001).

Discussion:  Our results indicate that there is a significant relationship between height and several ocular dimensions in this adult population and confirms a negative correlation between axial length and refraction.
Screening compliance and visual outcome in diabetes
Authors: Zoega Gunnar Már , Gunnarsdóttir Þóra , Björnsdóttir Sigríður , Hreiðarsson Ástradur B. , Viggósson Guðmundur , Stefánsson Einar
Published: September 2005

Purpose:  To study the relationship between screening compliance and visual outcome in a screening programme for diabetic eye disease.

Methods:  A retrospective case control study. The screening compliance of all the diabetes patients (n = 22) listed at the Icelandic National Registry for the Blind (visual acuity <0.3) was compared to a matched group of 44 non‐blind diabetes patients (visual acuity ≥0.3) who participated in the same screening programme for diabetic retinopathy. Glycaemic control (HbA1c), office blood pressure and cholesterol levels were assessed.

Results:  The study group had a significantly lower level of compliance with the screening programme (27% ± 38% [mean ± SD] versus 77% ± 26% [mean ± SD]; p < 0.0001). Macular oedema or proliferative diabetic retinopathy was found in 60% (13/22) of the study group when entering the screening programme, compared to 7% (3/44) in the control group. Blood pressure (except diastolic BP among type 1 diabetes mellitus), blood glucose and cholesterol levels were identical. The prevalence of blindness and low vision amongst diabetes patients in Iceland is about 0.5%.

Conclusions:  There was a significant relationship between screening compliance and visual outcome in diabetes patients in our screening programme.
Differential diagnosis of anterior chamber cysts with ultrasound biomicroscopy: ciliary body medulloepithelioma
Authors: Zhou Min , Xu Gezhi , Bojanowski Christine M. , Song Yuelian , Chen Rongjia , Sun Xinhuai , Wang Weiji , Chan Chi‐Chao
Published: September 2005

Purpose:  To describe a case with motile cyst in the anterior chamber in the right eye of a 7‐year‐old boy.

Methods:  The right eye's visual acuity was 20/50. Intraocular pressure was 59 mmHg. Slit‐lamp examination showed prominent rubeosis iridis and a grey‐white mass floating freely in the anterior chamber. Ultrasound biomicroscopy revealed a cystic mass in the anterior chamber. A diagnostic cyclectomy with removal of the anterior chamber cyst was performed. Histopathology of the anterior chamber lesion showed an intact cyst composed of medullary epithelial cells. Medulloepithelioma with malignant criteria was diagnosed and the eye was enucleated.

Results:  Pathology demonstrated an medulloepithelioma with a few mitotic figures and nuclear pleomorphisms within the ciliary body. The patient was followed for 8 months without any metastasis in the orbit or elsewhere.

Conclusion:  Intraocular medulloepithelioma is a rare embryonic benign or malignant neoplasm typically diagnosed in the first decade of life as a ciliary body mass. A dislodged, free‐floating anterior chamber cyst associated with neovascular glaucoma is typical of medulloepithelioma in children. This unique presentation should be differentiated from congenital iris epithelial, post‐traumatic, epithelial, parasitic and neoplastic cysts. Ultrasound biomicroscopy is useful for analysing the structure of the anterior segment mass. Ciliary body medulloepithelioma is characterized by echogenic mass heterogeneity and an irregular surface containing multiple cystic cavities. Lack of glial differentiation may predict a better clinical outcome in primary neuroectodermal brain tumours.
Caruncular lesions in Denmark 1978–2002: a histopathological study with correlation to clinical referral diagnosis
Authors: Østergaard Jens , Prause Jan Ulrik , Heegaard Steffen
Published: September 2005

Purpose:  To carry out a retrospective clinicopathological evaluation of caruncular lesions.

Methods:  Data were collected from all surgically removed and histopathologically evaluated caruncular lesions registered by Danish pathology departments during the 25‐year period 1978–2002.

Results:  A total of 574 caruncular lesions were identified. The number of caruncular lesions increased significantly during the 25‐year period. This was due to an increase in the number of benign lesions, whereas the number of premalignant and malignant lesions remained constant. A total of 550 (96%) of the lesions were benign. Naevus (n = 248, 43%) and papilloma (n = 131, 23%) were the most common neoplasms. Premalignant lesions (n = 10, 1.7%) were dominated by primary acquired melanosis (PAM) with atypia and epithelial dysplasia. Malignant lesions constituted a total of 14 neoplasms (2.4%), with basal cell carcinoma (n = 4, 0.7%) and lymphoma (n = 4, 0.7%) being the most frequent. The preoperative clinical diagnosis was correct in 286 (50%) of cases.

Conclusion:  Caruncular lesions are predominately benign but the lesions are rare and diverse, making clinical diagnosis difficult. Referral of excised lesions for pathological examination is recommended.
Vascular endothelial growth factor 121 is the predominant isoform in psoriatic scales
Authors: Zhang Yan , Matsuo Hiroaki , Morita Eishin
Published: September 2005

Abstract:  Vascular endothelial growth factor (VEGF) is a powerful agent that causes hyperpermeability of blood vessels as well as endothelial cell proliferation. Recent investigations have revealed that production of VEGF increases in epidermis of psoriatic lesions, and the overproduced VEGF plays an important role in the pathogenesis of psoriasis. In this study, we used immunohistochemical staining as well as extraction of stratum corneum with physiological saline to further analyse VEGF produced in psoriatic lesions. Biological activity of VEGF in the psoriatic scales was assayed by cultured human umbilical vein endothelial cells in vitro. The immunohistochemical examination confirmed an increased production of VEGF in the keratinocytes of psoriatic lesions. In addition, we found that the content of VEGF contained in the psoriatic scales was approximately 50 times greater than that in normal stratum corneum. We also found that VEGF 121 isoform, which has an exclusive ability to cause hyperpermeability of blood vessels, was predominantly detected in psoriatic scales, suggesting a major role of VEGF 121 isoform on the altered structure of microvessels in psoriatic lesions.
Role of Apaf‐1, a key regulator of apoptosis, in melanoma progression and chemoresistance
Authors: Campioni Mara , Santini Daniele , Tonini Giuseppe , Murace Raffaele , Dragonetti Emanuele , Spugnini Enrico P. , Baldi Alfonso
Published: September 2005

Abstract:  Apoptosis protease‐activating factor‐1 (Apaf‐1) is a key regulator of the mitochondrial apoptotic pathway, being the central element of the multimeric apoptosome formed by procaspase 9, cytochrome c, and Apaf‐1 itself. In this review, the principal aspects about Apaf‐1 gene structure and function, and its role in the apoptotic machinery, are described. Moreover, the most recent findings about the involvement of this molecule in melanoma progression and chemoresistance, as well as the clinico‐pathological relevance of these findings in the treatment of this deadly disease, are reported.
Current trends of HIV disease of the mouth
Authors: Frezzini Cristina , Leao Jair C , Porter Stephen
Published: September 2005

HIV infection affects residents of all countries of the world, but the greater majority of affected individuals reside in the developing world. In the past decade there have been substantial changes in the management of HIV disease, particularly the introduction of highly active antiretroviral therapy (HAART). Such agents have reduced significantly the morbidity and mortality associated with HIV disease, however, they are not available for most HIV‐infected individuals in the developing world. There is now considerable understanding of the molecular epidemiology, transmission and therapy of the common opportunistic oral infections of HIV disease, and as a consequence of improved anti‐HIV strategies, the frequency and severity of oral disease associated with HIV infection have reduced considerably, although HAART may predispose to human papilloma virus infection of the mouth and potentially increase the risk of later oral squamous cell carcinoma. Despite advances in clinical care the majority of individuals with HIV disease worldwide will continue to develop oral disease, as they are resident in the developing world and do not have ready access to even simple therapies.
HMB‐45 may be a more sensitive maker than S‐100 or Melan‐A for immunohistochemical diagnosis of primary oral and nasal mucosal melanomas
Authors: Yu Chuan‐Hang , Chen Huang‐Hsu , Liu Chia‐Ming , Jeng Yung‐Ming , Wang Jeng‐Tzung , Wang Yi‐Ping , Liu Bu‐Yuan , Sun Andy , Chiang Chun‐Pin
Published: September 2005

Background:  Primary mucosal melanomas (MMs) of the head and neck are a rare entity. Melanomas with characteristic melanin‐pigmented tumor cells are easy to diagnose, but those without melanin‐pigmented tumor cells, amelanotic melanomas, are difficult to identify and need immunohistochemistry (IHC) to confirm the final diagnosis. In this study, we examined the expression of three melanocytic differentiation markers, HMB‐45, S‐100, and Melan‐A in primary oral and nasal MMs. We tried to evaluate whether HMB‐45, S‐100, and Melan‐A were useful for diagnosis of primary oral and nasal MMs and to find out which marker was the best of the three.

Methods:  This study used IHC to examine the expression of HMB‐45, S‐100, and Melan‐A in 17 formalin‐fixed paraffin‐embedded specimens of primary oral and nasal MMs. The staining intensities (SIs) and labeling indices (LIs) of HMB‐45, S‐100, and Melan‐A in 17 MMs were calculated and compared between any two markers.

Results:  Immunostaining results showed that the positive rate was 94% (16 of 17) for HMB‐45, 88% (15 of 17) for S‐100, and 71% (12 of 17) for Melan‐A in 17 MMs. The SI of HMB‐45 was significantly higher than that of S‐100 (P = 0.0011) or of Melan‐A (P = 0.0034). In addition, the mean LI of Melan‐A (59 ± 43%) was significantly lower than that of HMB‐45 (83 ± 28%, P = 0.0065) or of S‐100 (79 ± 33%, P = 0.0237).

Conclusions:  Our results indicate that both HMB‐45 and S‐100 show a high positive rate and LI in MMs and therefore may be good markers for immunohistochemical diagnosis of primary oral and nasal MMs. In addition, HMB‐45 may be a more sensitive marker than S‐100 because HMB‐45 shows a significantly higher SI than S‐100 in this study.
Electrophoretically separation of the synovial fluid proteins in rabbit temporomandibular arthritis induced by mechanical loading
Authors: Fujimura K. , Kobayashi S. , Yoshitake Y. , Tsuruoka N. , Kaneyama K. , Segami N.
Published: September 2005

Background:  The concentration of protein in synovial fluid (SF) of temporomandibular joints (TMJs) with disorders tends to be increased. We investigated the protein composition of SF of rabbits in which arthritis of the TMJ was induced.

Method:  Arthritis was induced in six TMJs in six rabbits by exertion of a load for 4 weeks. Six non‐loaded TMJs in six rabbits served as controls. The protein concentration and content in TMJ SF of the two groups were compared.

Results:  The mean protein concentration was higher in the SF of the loaded group than in that of the non‐loaded group (1824 μg/ml vs. 398 μg/ml, P = 0.002). Proteins with molecular weights of more than 95 kDa were abundant in the loaded group (P < 0.05).

Conclusion:  Temporomandibular arthritis induced by mechanical loading in rabbit is accompanied by an increase in the abundance of relatively high molecular weight proteins in SF.
Cytokeratin expression patterns for distinction of odontogenic keratocysts from dentigerous and radicular cysts
Authors: Stoll Christian , Stollenwerk Carolin , Riediger Dieter , Mittermayer Christian , Alfer Joachim
Published: September 2005

Background: The clinical outcome of treatment of odontogenic cysts differs depending on separate entities. Particular clinical relevance must be attached to the distinction between odontogenic keratocysts, which have an evident tendency to recur, and other odontogenic cysts. The aim of this study was to evaluate cytokeratin (CK) expression patterns as an additional tool for characterization of different cysts as the histomorphologic appearance often is not decisive.

Methods: Thirty cases of dentigerous and radicular cysts respectively as well as 15 cases of odontogenic keratocysts were considered. Expression of CK 5/6, 7, 10, 13, 17, 19 and 20 was determined in addition to Ki‐67 immunohistochemically.

Results: Expression of CK 17 was discernible in 93.3% of the odontogenic keratocysts, but only in 35.0% of dentigerous and radicular cysts under study (P < 0.001). CK 19 could be detected in 48.3% of dentigerous and radicular cysts, whereas odontogenic keratocysts were completely negative (P < 0.002).

Conclusion: Immunohistochemical detection of CK 17 and 19 seems to be a valuable additional parameter distinguishing between odontogenic keratocysts and other odontogenic – especially dentigerous – cysts which clinically are likely the most significant differential diagnoses in this context.
Diacylglycerol‐Activated Hmunc13 Serves as an Effector of the GTPase Rab34
Authors: Speight Pam , Silverman Mel
Published: September 2005

Hmunc13 is a cytosolic diacylglycerol (DAG)‐binding protein, which is upregulated in renal cortical tubule and mesangial cells by hyperglycemia. In response to DAG activation, hmunc13 translocates to the Golgi. To investigate how this may relate to its function, we used a bacterial two‐hybrid screen to look for hmunc13‐interacting proteins. Full‐length Rab34 was specifically isolated from a human kidney cDNA library. Co‐expression of the two proteins confirmed Rab34 as a Golgi‐associated protein, which was immunoprecipitated from cell lysates by hmunc13. Glutathione S‐transferase fusion proteins of WT, Q111L (GTP bound), and T66N (GDP bound) mutants were created, and their GTP‐binding activity verified by radioactive overlay assay. Binding of hmunc13 was observed with Q111L, barely detectable with T66N and enhanced with Rab34WT loaded with GTPγS compared with GDP loaded. Deletion of munc homolgy domain (MHD)‐2, eliminated the hmunc13/Rab34 interaction. The Q111L mutant localized to the Golgi apparatus, but T66N was cytosolic. Localization of both mutants and Rab34WT was unchanged by DAG activation. The data suggest that DAG activation of hmunc13 causes it to be translocated to the Golgi, where it binds to GTP‐bound Rab34 via MHD‐2. Because Rab34 is known to regulate intracellular lysosome positioning, we propose that hmunc13 serves as an effector of Rab34, mediating lysosome–Golgi trafficking.
Intragranular Vesiculotubular Compartments are Involved in Piecemeal Degranulation by Activated Human Eosinophils
Authors: Melo Rossana C.N. , Perez Sandra A.C. , Spencer Lisa A. , Dvorak Ann M. , Weller Peter F.
Published: September 2005

Eosinophils, leukocytes involved in allergic, inflammatory and immunoregulatory responses, have a distinct capacity to rapidly secrete preformed granule‐stored proteins through piecemeal degranulation (PMD), a secretion process based on vesicular transport of proteins from within granules for extracellular release. Eosinophil‐specific granules contain cytokines and cationic proteins, such as major basic protein (MBP). We evaluated structural mechanisms responsible for mobilizing proteins from within eosinophil granules. Human eosinophils stimulated for 30–60 min with eotaxin, regulated on activation, normal, T‐cell expressed and secreted (RANTES) or platelet activating factor exhibited ultrastructural features of PMD (e.g. losses of granule contents) and extensive vesiculotubular networks within emptying granules. Brefeldin A inhibited granule emptying and collapsed intragranular vesiculotubular networks. By immunonanogold ultrastructural labelings, CD63, a tetraspanin membrane protein, was localized within granules and on vesicles outside of granules, and mobilization of MBP into vesicles within and extending from granules was demonstrated. Electron tomography with three dimension reconstructions revealed granule internal membranes to constitute an elaborate tubular network able to sequester and relocate granule products upon stimulation. We provide new insights into PMD and identify eosinophil specific granules as organelles whose internal tubulovesicular networks are important for the capacity of eosinophils to secrete, by vesicular transport, their content of preformed and granule‐stored cytokines and cationic proteins.
The Functionally Exchangeable L Domains in RSV and HIV‐1 Gag Direct Particle Release Through Pathways Linked by Tsg101
Authors: Medina Gisselle , Zhang Yongjun , Tang Yi , Gottwein Eva , Vana Marcy L. , Bouamr Fadila , Leis Jonathan , Carter Carol A.
Published: September 2005

The functionally exchangeable L domains of HIV‐1 and Rous sarcoma virus (RSV) Gag bind Tsg101 and Nedd4, respectively. Tsg101 and Nedd4 function in endocytic trafficking, and studies show that expression of Tsg101 or Nedd4 fragments interfere with release of HIV‐1 or RSV Gag, respectively, as virus‐like particles (VLPs). To determine whether functional exchangeability reflects use of the same trafficking pathway, we tested the effect on RSV Gag release of co‐expression with mutated forms of Vps4, Nedd4 and Tsg101. A dominant‐negative mutant of Vps4A, an AAA ATPase required for utilization of endosomal sorting proteins that was shown previously to interfere with HIV‐1 budding, also inhibited RSV Gag release, indicating that RSV uses the endocytic trafficking machinery, as does HIV. Nedd4 and Tsg101 interacted in the presence or absence of Gag and, through its binding of Nedd4, RSV Gag interacted with Tsg101. Deletion of the N‐terminal region of Tsg101 or the HECT domain of Nedd4 did not prevent interaction; however, three‐dimensional spatial imaging suggested that the interaction of RSV Gag with full‐length Tsg101 and N‐terminally truncated Tsg101 was not the same. Co‐expression of RSV Gag with the Tsg101 C‐terminal fragment interfered with VLP release minimally; however, a significant fraction of the released VLPs was tethered to each other. The results suggest that, while Tsg101 is not required for RSV VLP release, alterations in the protein interfere with VLP budding/fission events. We conclude that RSV and HIV‐1 Gag direct particle release through independent ESCRT‐mediated pathways that are linked through Tsg101–Nedd4 interaction.
Cytoplasmic Organization of POXvirus DNA Replication
Authors: Schramm Birgit , Locker Jacomine Krijnse
Published: September 2005

Poxviruses, a family of large DNA viruses, are unique among DNA viruses, because they carry out DNA replication in the cytoplasm rather than the nucleus. This process does not occur randomly, but instead, these viruses create cytoplasmic ‘mini‐nuclei’, distinct sites that are surrounded by membranes derived from the rough endoplasmic reticulum (ER) that support viral replication. This review summarizes how distinct steps preceding cytoplasmic DNA replication, as well as replication itself, operate in the host cell. The collective data point to an important role for both the rough ER and the microtubules and indicate that these cellular structures help to co‐ordinate the virus life cycle to ensure that individual steps occur at the right time and place. In a broader sense, they emphasize how viruses have evolved sophisticated ways to use host cells to optimize their life cycles to ensure efficient production of infectious progeny.
A Yeast Model System for Functional Analysis of the Niemann–Pick Type C Protein 1 Homolog, Ncr1p
Authors: Berger Adam C. , Hanson Pamela K. , Wylie Nichols J. , Corbett Anita H.
Published: September 2005

Niemann–Pick disease type C (NP‐C) is a progressive, ultimately fatal, autosomal recessive neurodegenerative disorder. The major biochemical hallmark of the disease is the endocytic accumulation of low‐density lipoprotein‐derived cholesterol. The majority of NP‐C patients have mutations in the Niemann‐Pick type C1 gene, NPC1. This study focuses on the Saccharomyces cerevisiae homolog of the human NPC1 protein encoded by the NCR1 gene. Ncr1p localizes to the vacuole, the yeast equivalent to the mammalian endosome‐lysosome system. Here, we identify the first phenotype caused by deletion of NCR1 from the yeast genome, resistance to the ether lipid drug, edelfosine. Our results indicate that edelfosine has a cytotoxic, rather than cytostatic, effect on wildtype yeast cells. We exploit the edelfosine resistance phenotype to assess the function of yeast Ncr1 proteins carrying amino acid changes corresponding to human NPC1 patient mutations. We find that one of these amino acid changes severely compromises Ncr1p function as assessed using the edelfosine resistance assay. These findings establish S. cerevisiae as a model system that can be exploited to analyze the molecular consequences of patient mutations in NPC1 and provide the basis for future genetic studies using yeast.
Differential Control of Clathrin Subunit Dynamics Measured with EW‐FRAP Microscopy
Authors: Loerke Dinah , Wienisch Martin , Kochubey Olexiy , Klingauf Jurgen
Published: September 2005

The clathrin triskelion is composed of three light chain (LC) and three heavy chain (HC) subunits. Cellular control of clathrin function is thought to be aimed at the LC subunit, mainly on the basis of structural information. To test this hypothesis in vivo, we used evanescent‐wave photobleaching recovery to study clathrin exchange from single pits using LC (LCa and LCb) and HC enhanced green fluorescent protein fusion constructs. The recovery signal was corrected for cytosolic diffusional background, yielding the pure exchange reaction times. For LCa, we measured an unbinding time constant τLEa = 18.9 ± 1.0 seconds at room temperature, faster than previously published; for LCb, we found τLCb = 10.6 ± 1.9 seconds and for HC τHC = 15.9 ± 1.0 seconds. Sucrose treatment, ATP or Ca2+ depletion blocked exchange of LCa completely, but only partially of HC, lowering its time constant to τ = 10.0 ± 0.9 seconds, identical to the one for LCb exchange. The latter was also not blocked by Ca2+ depletion or sucrose. We conclude that HCs bound both to LCa and to LCb contribute side by side to pit formation in vivo, but the affinity of LCa‐free HC in pits is reduced, and the Ca2+‐ and ATP‐mediated control of clathrin function is lost.
Cyclase‐Associated Protein is Essential for the Functioning of the Endo‐Lysosomal System and Provides a Link to the Actin Cytoskeleton
Authors: Sultana Hameeda , Rivero Francisco , Blau‐Wasser Rosemarie , Schwager Stephan , Balbo Alessandra , Bozzaro Salvatore , Schleicher Michael , Noegel Angelika A.
Published: September 2005

Data from mutant analysis in yeast and Dictyostelium indicate a role for the cyclase‐associated protein (CAP) in endocytosis and vesicle transport. We have used genetic and biochemical approaches to identify novel interacting partners of Dictyostelium CAP to help explain its molecular interactions in these processes. Cyclase‐associated protein associates and interacts with subunits of the highly conserved vacuolar H+‐ATPase (V‐ATPase) and co‐localizes to some extent with the V‐ATPase. Furthermore, CAP is essential for maintaining the structural organization, integrity and functioning of the endo‐lysosomal system, as distribution and morphology of V‐ATPase‐ and Nramp1‐decorated membranes were disturbed in a CAP mutant (CAP bsr) accompanied by an increased endosomal pH. Moreover, concanamycin A (CMA), a specific inhibitor of the V‐ATPase, had a more severe effect on CAP bsr than on wild‐type cells, and the mutant did not show adaptation to the drug. Also, the distribution of green fluorescent protein‐CAP was affected upon CMA treatment in the wildtype and recovered after adaptation. Distribution of the V‐ATPase in CAP bsr was drastically altered upon hypo‐osmotic shock, and growth was slower and reached lower saturation densities in the mutant under hyper‐osmotic conditions. Taken together, our data unravel a link of CAP with the actin cytoskeleton and endocytosis and suggest that CAP is an essential component of the endo‐lysosomal system in Dictyostelium.
Nuclear Translocation of Cell‐Surface Receptors: Lessons from Fibroblast Growth Factor
Authors: Bryant David M. , Stow Jennifer L.
Published: September 2005

The nuclear localization of a number of growth factors, cytokine ligands and their receptors has been reported in various cell lines and tissues. These include members of the fibroblast growth factor (FGF), epidermal growth factor and growth hormone families. Accordingly, a number of nuclear functions have begun to emerge for these protein families. The demonstration of functional interactions of these proteins with the nuclear import machinery has further supported their functions as nuclear signal transducers. Here, we review the membrane‐ trafficking machinery and pathways demonstrated to regulate this cell surface to nucleus‐trafficking event and highlight the many remaining unanswered questions. We focus on the FGF family, which is providing many of the clues as to the process of this unusual phenomenon.
Long-Run IPO Performance Analysis of German and Spanish Family-Owned Businesses
Authors: Jaskiewicz Peter , González Víctor M. , Menéndez Susana , Schiereck Dirk
Published: September 2005

This article examines the long-run stock market performance of German and Spanish initial public offerings (IPOs) between 1990 and 2000. We distinguish between family-and nonfamily-owned business IPOs by using the power subscale of the F-PEC. Buy-and-hold-abnormal returns (BHAR) are calculated in order to determine abnormal returns. Our results show that three years after going public, investors, on average, realized an abnormal return of − 32.8% for German and − 36.7% for Spanish IPOs. In both countries, nonfamily business IPOs perform insignificantly better. Regression analyses show that for the whole sample there is a positive company size effect. In family-owned businesses, strong family involvement has a positive impact on the long-run stock market performance, whereas the age of the firm has a negative influence.
Real Versus Sample-Based Differences in Comparative Family Business Research
Authors: Jorissen Ann , Laveren Eddy , Martens Rudy , Reheul Anne-Mie
Published: September 2005

This article analyzes the impact of not controlling for “demographic sample” differences on research results in the area of comparative family/nonfamily business research. Using different statistical methods with and without control for “demographic sample” differences, the results show that controlling for these firm demographics in a bivariate as well as a multivariate framework is very important to discover “real” differences between family and nonfamily firms. We found “real” differences for export, budgeting, variable reward systems, profitability and gender, educational degree, and tenure of the CEO. Strategy, networking, long-term planning and control systems, perceived environmental uncertainty, growth, and management training, classified by prior empirical research as different between family and nonfamily firms, do not differ.
The undecided serpin
Authors: Medcalf Robert L. , Stasinopoulos Stan J.
Published: September 2005

Plasminogen activator inhibitor type‐2 (PAI‐2) is a nonconventional serine protease inhibitor (serpin) with unique and tantalizing properties that is generally considered to be an authentic and physiological inhibitor of urokinase. However, the fact that only a small percentage of PAI‐2 is secreted has been a long‐standing argument for alternative roles for this serpin. Indeed, PAI‐2 has been shown to have a number of intracellular roles: it can alter gene expression, influence the rate of cell proliferation and differentiation, and inhibit apoptosis in a manner independent of urokinase inhibition. Despite these recent advances in defining the intracellular function of PAI‐2, it still remains one of the most mysterious and enigmatic members of the serpin superfamily.
Antiplasmin
Authors: Coughlin Paul B.
Published: September 2005

Much of the basic biochemistry of antiplasmin was described more than 20 years ago and yet it remains an enigmatic member of the serine protease inhibitor (serpin) family. It possesses all of the characteristics of other inhibitory serpins but in addition it has unique N‐ and C‐terminal extensions which significantly modify its activities. The N‐terminus serves as a substrate for Factor XIIIa leading to crosslinking and incorporation of antiplasmin into a clot as it is formed. Although free antiplasmin is an excellent inhibitor of plasmin, the fibrin bound form of the serpin appears to be the major regulator of clot lysis. The C‐terminal portion of antiplasmin is highly conserved between species and contains several charged amino acids including four lysines with one of these at the C‐terminus. This portion of the molecule mediates the initial interaction with plasmin and is a key component of antiplasmin's rapid and efficient inhibitory mechanism. Studies of mice with targeted deletion of antiplasmin have confirmed its importance as a major regulator of fibrinolysis and re‐emphasized its value as a potential therapeutic target.
A client‐binding site of Cdc37
Authors: Terasawa Kazuya , Minami Yasufumi
Published: September 2005

The molecular chaperone Hsp90 is distinct from Hsp70 and chaperonin in that client proteins are apparently restricted to a subset of proteins categorized as cellular signaling molecules. Among these, many specific protein kinases require the assistance of Hsp90 and its co‐chaperone Cdc37/p50 for their biogenesis. A series of Cdc37 deletion mutants revealed that all mutants capable of binding Raf‐1 possess amino acid residues between 181 and 200. The 20‐residue region is sufficient and, in particular, a five‐residue segment (residue 191–195) is essential for binding to Raf‐1. These five residues are present in one α helix (residues 184–199) in the middle of Cdc37, which is unexpectedly nested within the Hsp90‐interacting domain of Cdc37, which was recently determined by crystallography, but does not seem to contribute to direct contact with Hsp90. Furthermore, an N‐terminally truncated mutant of Cdc37 composed of residues 181–378 was shown to bind the N‐terminal portion of Raf‐1 (subdomains I–IV). This mutant can bind not only other Hsp90 client protein kinases, Akt1, Aurora B and Cdk4, but also Cdc2 and Cdk2, which to date have not been shown to physically interact with Cdc37. These results suggest that a region of Cdc37 other than the client‐binding site may be responsible for discriminating client protein kinases from others.
The signature amidase from Sulfolobus solfataricus belongs to the CX3C subgroup of enzymes cleaving both amides and nitriles
Authors: Cilia Elisa , Fabbri Armando , Uriani Monica , Scialdone Giuseppe G. , Ammendola Sergio
Published: September 2005

The signature amidase from the extremophile archeum Sulfolobus solfataricus is an enantioselective enzyme that cleaves S‐amides. We report here that this enzyme also converts nitriles in the corresponding organic acid, similarly to the well characterized amidase from Rhodococcus rhodochrous J1. The archaeal and rhodococcal enzymes belong to the signature amidases and contain the typical serine‐glycine rich motif. They work at different optimal temperature, share a high sequence similarity and both contain an additional CX3C motif. To explain their dual specificity, we built a 3D model of the structure of the S. solfataricus enzyme, which suggests that, in addition to the classical catalytic Ser‐cisSer‐Lys, a putative additional Cys‐cisSer‐Lys catalytic site, likely to be responsible for nitrile hydrolysis, is present in these proteins. The results of random and site‐directed mutagenesis experiments, as well as inhibition studies support our hypothesis.
Modulatory effects of plant phenols on human multidrug‐resistance proteins 1, 4 and 5 (ABCC1, 4 and 5)
Authors: Wu Chung‐Pu , Calcagno Anna Maria , Hladky Stephen B. , Ambudkar Suresh V. , Barrand Margery A.
Published: September 2005

Plant flavonoids are polyphenolic compounds, commonly found in vegetables, fruits and many food sources that form a significant portion of our diet. These compounds have been shown to interact with several ATP‐binding cassette transporters that are linked with anticancer and antiviral drug resistance and, as such, may be beneficial in modulating drug resistance. This study investigates the interactions of six common polyphenols; quercetin, silymarin, resveratrol, naringenin, daidzein and hesperetin with the multidrug‐resistance‐associated proteins, MRP1, MRP4 and MRP5. At nontoxic concentrations, several of the polyphenols were able to modulate MRP1‐, MRP4‐ and MRP5‐mediated drug resistance, though to varying extents. The polyphenols also reversed resistance to NSC251820, a compound that appears to be a good substrate for MRP4, as predicted by data‐mining studies. Furthermore, most of the polyphenols showed direct inhibition of MRP1‐mediated [3H]dinitrophenyl S‐glutathione and MRP4‐mediated [3H]cGMP transport in inside‐out vesicles prepared from human erythrocytes. Also, both quercetin and silymarin were found to inhibit MRP1‐, MRP4‐ and MRP5‐mediated transport from intact cells with high affinity. They also had significant effects on the ATPase activity of MRP1 and MRP4 without having any effect on [32P]8‐azidoATP[αP] binding to these proteins. This suggests that these flavonoids most likely interact at the transporter's substrate‐binding sites. Collectively, these results suggest that dietary flavonoids such as quercetin and silymarin can modulate transport activities of MRP1, ‐4 and ‐5. Such interactions could influence bioavailability of anticancer and antiviral drugs in vivo and thus, should be considered for increasing efficacy in drug therapies.
15‐Deoxy Δ12,14‐prostaglandin J2 suppresses transcription by promoter 3 of the human thromboxane A2 receptor gene through peroxisome proliferator‐activated receptor γ in human erythroleukemia cells
Authors: Coyle Adrian T. , O'Keeffe Martina B. , Kinsella B. Therese
Published: September 2005

In humans, thromboxane (TX) A2 signals through two receptor isoforms, thromboxane receptor (TP)α and TPβ, which are transcriptionally regulated by distinct promoters, Prm1 and Prm3, respectively, within the single TP gene. The aim of the current study was to investigate the ability of the endogenous peroxisome proliferator‐activated receptor (PPAR)γ ligand 15‐deoxy‐Δ12,14‐prostaglandin J2 (15d‐PGJ2) to regulate expression of the human TP gene and to ascertain its potential effects on the individual TPα and TPβ isoforms. 15d‐PGJ2 suppressed Prm3 transcriptional activity and TPβ mRNA expression in the platelet progenitor megakaryocytic human erythroleukemia (HEL) 92.1.7 cell line but had no effect on Prm1 or Prm2 activity or on TPα mRNA expression. 15d‐PGJ2 also resulted in reductions in the overall level of TP protein expression and TP‐mediated intracellular calcium mobilization in HEL cells. 15d‐PGJ2 suppression of Prm3 transcriptional activity and TPβ mRNA expression was found to occur through a novel mechanism involving direct binding of PPARγ–retinoic acid X receptor (RXR) heterodimers to a PPARγ response element (PPRE) composed of two imperfect hexameric direct repeat (DR) sequences centred at −159 and −148, respectively, spaced by five nucleotides (DR5). These data provide direct evidence for the role of PPARγ in the regulation of human TP gene expression within the vasculature and point to further critical differences in the modes of transcriptional regulation of TPα and TPβ in humans. Moreover, these data highlight a further link between enhanced risk of cardiovascular disease in diabetes mellitus associated with increased synthesis and action of thromboxane A2 (TXA2).
Homoadenosylcobalamins as probes for exploring the active sites of coenzyme B12‐dependent diol dehydratase and ethanolamine ammonia‐lyase
Authors: Fukuoka Masaki , Nakanishi Yuka , Hannak Renate B. , Kräutler Bernhard , Toraya Tetsuo
Published: September 2005

[ω‐(Adenosyl)alkyl]cobalamins (homoadenosylcobalamins) are useful analogues of adenosylcobalamin to get information about the distance between Co and C5′, which is critical for Co‐C bond activation. In order to use them as probes for exploring the active sites of enzymes, the coenzymic properties of homoadenosylcobalamins for diol dehydratase and ethanolamine ammonia‐lyase were investigated. The kcat and kcat/Km values for adenosylmethylcobalamin were about 0.27% and 0.15% that for the regular coenzyme with diol dehydratase, respectively. The kcat/kinact value showed that the holoenzyme with this analogue becomes inactivated on average after about 3000 catalytic turnovers, indicating that the probability of inactivation during catalysis is almost 500 times higher than that for the regular holoenzyme. The kcat value for adenosylmethylcobalamin was about 0.13% that of the regular coenzyme for ethanolamine ammonia‐lyase, as judged from the initial velocity, but the holoenzyme with this analogue underwent inactivation after on average about 50 catalytic turnovers. This probability of inactivation is 3800 times higher than that for the regular holoenzyme. When estimated from the spectra of reacting holoenzymes, the steady state concentration of cob(II)alamin intermediate from adenosylmethylcobalamin was very low with either diol dehydratase or ethanolamine ammonia‐lyase, which is consistent with its extremely low coenzymic activity. In contrast, neither adenosylethylcobalamin nor adeninylpentylcobalamin served as active coenzyme for either enzyme and did not undergo Co‐C bond cleavage upon binding to apoenzymes.
Development of the Nursing Outcome (NOC) Label: Hyperactivity Level
Authors: Caldwell Carol L. , Wasson Dianne , Anderson Mary Ann , Brighton Veronica , Dixon Lois
Published: September 2005

TOPIC: Hyperactivity, a persistent, severe pattern of inattention or impulsivity, places children at risk for impaired functioning in many developmental areas. This behavior is characterized by short attention span, low frustration tolerance, impulsivity, distractibility, and increased physical activity. Responses from multiple sources in the child's environment must be monitored to manage childhood hyperactivity.

PURPOSE: Success at school, in peer relationships, and parent‐child interactions is frequently affected by hyperactivity. Using a focus group approach, a Nursing Outcomes Classification (NOC) label, definition, and indicators were developed for Hyperactivity Level.

SOURCES: Review of the literature allowed for a content analysis approach and conceptualization of hyperactivity at several levels.

CONCLUSION: Twenty three (23) measurable indicators were formulated and refined into conceptually and clinically coherent outcomes. Clinical relevance and utility were presented through a case study approach.
Patterns of Treatment Services and Costs for Young Offenders with Mental Disorders
Authors: Shelton Deborah
Published: September 2005

PROBLEM:  This study describes mental health treatment service delivery patterns and costs for youth in a juvenile justice system.

METHODS:  A secondary data analysis on a random sample of juvenile offenders (N = 312) was completed. Service patterns and costs were described. Selected variables were examined for their ability to predict who received treatment.

FINDINGS:  Only 23% of youth diagnosed with a mental disorder received any treatment. Older youth and African American youth received fewer services, and race was the only significant predictor for receiving treatment (p = .001).

CONCLUSIONS:  Mental health treatment services were scarce, and the data reflects a race bias in the provision of services. Although the law protects the right to treatment for these individuals, provision of services remains a challenge.
Milieu Management of a Child with Bipolar Illness
Authors: Beal Davena , Delaney Kathleen R.
Published: September 2005

ABSTRACT:  During inpatient psychiatric treatment, children with bipolar disorder may present particular management issues. They may experience intense periods of affect regulation that can spiral into frenetic, aggressive behaviors that are difficult to interrupt with de‐escalation techniques. This case study presents such a child and the behavior patterns that resulted in seclusion and PRN medication. Also presented is the plan that staff derived which eventually helped this young boy regulate his behavior.
Disclosing the Details of Child Sexual Abuse: Can Imaginative Literature Help Ease the Suffering?
Authors: Harrison Elizabeth
Published: September 2005

PROBLEM:  Research indicates that full disclosure of the events surrounding child sexual abuse, while therapeutic, is often difficult to achieve.

METHODS:  A nonconventional research approach was employed in order to examine more closely the lived experience of these children. Two novels were analyzed using close reading.

FINDINGS:  Details of the events and resultant dehumanization of the children were uncovered, as well as the rescuing role of the ancestor. Writing emerged also as a therapeutic tool that facilitated disclosure and helped to promote healing.

Conclusions:  The analysis of imaginative literature enables the reader to examine sensitive topics like sexual abuse and contributes to its treatment.
Using Dance/Movement Therapy to Augment the Effectiveness of Therapeutic Holding with Children
Authors: Lundy Heather , McGuffin Patrick
Published: September 2005

PROBLEM:  Therapeutic holding is a commonly used tool for the containment of aggressive behavior in children. Although often effective, the intervention has inherent physical and emotional safety risks. Can a body‐based therapy be used to limit these risks?

METHODS:  Research was conducted incorporating dance/movement therapy techniques (D/MT) before and after therapeutic holding to investigate this question. Volunteer residential treatment center staff participated in a 4‐hour D/MT‐based training workshop integrating the techniques with the intervention. Children participated via self‐report.

FINDINGS:  D/MT training increased adult awareness, sensitivity, perspective shifting ability, and confidence in the intervention while decreasing the necessity for physicality.

CONCLUSION:  Integrating D/MT therapy training with therapeutic holding decreased the threat of trauma to adult participants. Further research into the integration of D/MT techniques with safe holding procedures may prove helpful in the challenge of making restraints safer for both children and adults.
Social Studies Education in the Age of Testing and Accountability
Authors: Burroughs Susie , Groce Eric , Webeck Mary Lee
Published: September 2005

With 3 years and counting since its inception, the scope and impact of No Child Left Behind is now being felt in classrooms across the nation. Although some successes have been identified, concerns about the implementation and expectations of the legislation are emerging. As a result of the legislation's emphasis on the development of standards and assessment systems in reading, mathematics, and science, educators of other core and elective subjects are weighing the impact of being left out of the No Child Left Behind formula of testing and accountability. In an attempt to ascertain the perceptions and sentiments of social studies teachers concerning the impact of No Child Left Behind and the concomitant issue of state‐level testing and accountability policy, a tristate study was conducted. The findings of this research indicate that although elementary, middle, and high school social studies educators recognize the negative consequences of being left out of No Child Left Behind, they are not convinced that being included would be better for them, their students, or social studies education in general.
Measurement 101: Some Fundamentals Revisited
Authors: Frisbie David A.
Published: September 2005

The author takes the position that many of the fundamental measurement concepts and relationships often are used in our written communications in ways that demonstrate misunderstanding and lead to confusion. Illustrations of the misuses are provided, anecdotes and speculation about the implications are offered, and suggestions for addressing the problem are presented.
QUANTIFICATION OF FLUX DECLINE OF DEPECTINIZED MOSAMBI (CITRUS SINENSIS[L.] OSBECK) JUICE USING UNSTIRRED BATCH ULTRAFILTRATION
Authors: RAI P. , MAJUMDAR G.C. , DASGUPTA S. , DE S.
Published: September 2005

Ultrafiltration of enzymatically treated mosambi (Citrus sinensis [L.] Osbeck) juice was performed in a batch, unstirred membrane cell. Thin film composite polyamide membrane of molecular weight cut‐off 50,000 was used. The flux‐decline mechanism was identified by the growth of a gel‐type layer over the membrane surface. The flux decline, the gel resistance, the gel‐layer thickness and various domains of resistances were calculated at a constant pressure difference in the range of 276–552 kPa. The conventional gel‐filtration theory was employed to analyze the flux‐decline behavior. The calculated permeate flux and gel‐layer resistances were consistent with the experimental results. The calculated gel‐layer thickness varied from 4.12 to 74.1 µm for different operating condition (pressure) and time. The time at which the gel resistance becomes equal to the membrane‐hydraulic resistance ranged from 13 to 31 s for the pressure range studied herein. Thus, the deposited layer resistance to permeate flow was substantial, throughout the whole operation, except in the first few seconds.