bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel evidence of a role for chromosome 1 pericentric heterochromatin in the pathogenesis of B‐cell lymphoma and multiple myeloma
Authors: Le Baccon Patricia , Leroux Dominique , Dascalescu Christina , Duley Samuel , Marais Danielle , Esmenjaud Eliane , Sotto Jean Jacques , Callanan Mary
Published: August 2002

1q rearrangement is a remarkably frequent secondary chromosomal change in both non‐Hodgkin's lymphoma (NHL) and multiple myeloma (MM), where it is associated with tumor progression. To gain insight into 1q rearrangement‐associated disease mechanisms, we used fluorescence in situ hybridization (FISH) to search for recurring 1q breaks in 35 lymphoma samples (31 NHL patients and 4 lymphoma‐derived cell lines) as well as 22 MM patients with cytogenetically determined 1q abnormalities. Strikingly, dual‐color FISH analysis with chromosome 1 centromere and 1q12‐specific probes identified constitutive heterochromatin band 1q12 as the single most frequent breakpoint site in both NHL and MM (39% and 89% of 1q breaks, respectively). These rearrangements consistently generated aberrant heterochromatin/euchromatin junctions and gain of 1q12 material. A further 30% of NHL 1q breaks specifically involved two other novel, closely spaced sites (clusters I and II) within a 2.5 Mb region of proximal 1q21 (D1S3620 to D1S3623). A possible association between these sites and NHL subtype was evident; the cluster I rearrangement was frequent in follicular and diffuse large cell lymphoma, whereas the cluster II rearrangement was more frequently observed in diffuse small‐cell lymphoma (2/2 marginal zone lymphomas, 1/2 atypical chronic lymphocytic leukemias, and 1 lymphoplasmacytic lymphoma in this series). Candidate oncogenes bordering this interval (BCL9 and AF1Q) were not rearranged in any patient except one (AF1Q). This study provides the first evidence of involvement of 1q12 constitutive heterochromatin in the pathogenesis of NHL and MM and indicates proximal 1q21 to be of specific pathological significance in NHL. © 2001 Wiley‐Liss, Inc.
The Ohalo II prehistoric camp (19.5 Ky): New evidence for environmental and tectonic changes at the Sea of Galilee
Authors: Belitzky Shmuel , Nadel Dani
Published: August 2002

Combined archaeological data, shore surveys, and aerial photos of submerged sediments in the Sea of Galilee provide new insights into environmental and tectonic events, their dating, and their impact on the Ohalo II prehistoric camp (ca. 19,500 yr B.P.) and its surroundings. The Ohalo II waterlogged campsite contains excellently preserved brush hut remains and other in situ features, all embedded in late Pleistocene lacustrine strata. The findings indicate relatively short occupation of the site, not more than months or several years at a time. The high quality in situ preservation of delicate organic materials, as well as the short occupation period, suggests a quick and gentle burial by fine sediments. The evident fast submergence (water level rise of the Sea of Galilee) could have been the result of climatic fluctuations towards the end of the last glaciation and/or small‐scale tectonic subsidence. The site is located on a tectonic block formed in the western fault belt of the Dead Sea Rift. We present new evidence of post‐occupational folding of the late Pleistocene strata and recent tilting and faulting. A westward tectonic tilt may have caused the blockage of the old Jordan River outlet after A. D. 1106. Excellent preservation of the fault traces to the east of the site is attributed to the young age of the displacement on the fault. The last displacement apparently post‐dates the blockage of the old Jordan River. © 2002 Wiley Periodicals, Inc.
Embryonic expression of an Nkx2‐5/Cre gene using ROSA26 reporter mice
Authors: Moses Kelvin A. , DeMayo Franco , Braun Renee M. , Reecy James L. , Schwartz Robert J.
Published: August 2002

Summary: Nkx2‐5, one of the earliest cardiac‐specific markers in vertebrate embryos, was used as a genetic locus to knock in the Cre recombinase gene by homologous recombination. Offspring resulting from heterozygous Nkx2‐5/Cre mice mated to ROSA26 (R26R) reporter mice provided a model system for following Nkx2‐5 gene activity by β‐galactosidase (β‐gal) activity. β‐gal activity was initially observed in the early cardiac crescent, cardiomyocytes of the looping heart tube, and in the epithelium of the first pharyngeal arch. In later stage embryos (10.5–13.5 days postcoitum, dpc), β‐gal activity was observed in the stomach and spleen, the dorsum of the tongue, and in the condensing primordium of the tooth. The Nkx2‐5/Cre mouse model should provide a useful genetic resource to elucidate the role of loxP manipulated genetic targets in cardiogenesis and other developmental processes. genesis 31:176–180, 2001. © 2001 Wiley‐Liss, Inc.
Mimosine prevents the death of glucose‐deprived immunostimulated astrocytes by scavenging peroxynitrite
Authors: Choi Jung‐Jin , Oh Yu‐Kyoung , Kim Hyun‐Soo , Kim Hyoung‐Chun , Ko Kwang Ho , Kim Won‐Ki
Published: August 2002

Immunostimulated astrocytes become highly vulnerable to glucose deprivation (Choi and Kim: J Neurosci Res 54:870–875, 1998a). The increased vulnerability is caused by the enhanced level of peroxynitrite endogenously produced in glucose‐deprived immunostimulated astrocytes. In the present study, we report that the plant amino acid mimosine can attenuate the increased death by scavenging peroxynitrite. Treatment with mimosine blocked the increase of nitrotyrosine immunoreactivity, a marker of peroxynitrite, in glucose‐deprived immunostimulated astrocytes. Furthermore, mimosine directly inhibited the nitration of tyrosine residues of bovine serum albumin and the oxidation of dihydrorhodamine‐123 to rhodamine‐123 by peroxynitrite. Mimosine has been used experimentally as a cell cycle G1/S phase transition blocker (Lalande: Exp Cell Res 186:332–339, 1990; Hoffman et al.: Cytometry 12:26–32, 1991). Flow cytometry analysis, however, showed that the cytoprotective effect of mimosine was not attributed to its inhibition of cell cycle progression. Furthermore, under our experimental conditions, mimosine did not alter the levels of cell cycle regulatory proteins, including p21WAF1/CIP1, cyclins D1 and E, and proliferating cell nuclear antigen. In addition, cyclin‐dependent kinase inhibitors olomoucine and roscovitine did not block the increased death. These results indicate that mimosine inhibits the augmented death of glucose‐deprived immunostimulated astrocytes by scavenging peroxynitrite rather than suppressing the cell cycle progression. GLIA 39:37–46, 2002. © 2002 Wiley‐Liss, Inc.
Evidence for possible interactions between PLP and DM20 within the myelin sheath
Authors: McLaughlin M. , Hunter D.J.B. , Thomson C.E. , Yool D. , Kirkham D. , Freer A.A. , Griffiths I.R.
Published: August 2002

PLP and its smaller DM20 isoform constitute the major proteins of CNS myelin. Previous studies indicated a role for the proteins in maintaining the intraperiod line of the myelin sheath and the integrity of axons and suggested that both isoforms were necessary to provide these functions. The present study shows that each isoform is capable individually of inserting into compact myelin. Employing chromatographic extraction procedures designed to maintain the natural conformation of the proteins we found that most PLP and DM20 remained associated. Using an antibody specific to the PLP isoform, we were able to co‐immunoprecipitate DM20 from the major fraction of the extracted equine myelin and from mouse native whole myelin. We suggest that PLP and DM20 may form a hetero‐oligomeric complex within the myelin sheath, probably in association with specific lipids and that this arrangement is essential for the normal structure of myelin and axons. GLIA 39:31–36, 2002. © 2002 Wiley‐Liss, Inc.
Depression in Singapore: failure to demonstrate an age effect on clinical features
Authors: Tan L.L. , Ng L.L. , Tan S. , Roy K. , Brodaty H. , Parker G.
Published: August 2002

Objectives

Studies comparing older and younger depressed patients have variably identified differing and similar clinical feature patterns, an inconsistency requiring clarification and explanation. If influential, age may have a true phenotypic effect or be a secondary influence reflecting depressive sub‐type differences. If age is primarily influential, then, after controlling for depressive sub‐type differences its effect should impact on clinical features — even in non‐western regions.

Methods

We therefore undertook a study in Singapore, comparing 42 elderly and 28 younger patients of a Singapore psychiatric hospital, and with the diagnostic sub‐type profile similar across the age‐based groups.

Results

Despite the elderly group being some 35 years older, both at first episode and when surveyed, and having a distinctly higher rate of physical disorders, few clinical differences were identified. While the elderly group reported a less severe depressed mood and more ‘somatic’ symptoms, analyses indicated that such differences were accounted for by education and language factors, and were compatible with the view that Chinese subjects historically report depression more ‘somatically’.

Conclusion

We conclude that, in a non‐western, largely Chinese sample of depressed patients, few differences in the phenotypic expression of depression were identified, perhaps reflecting similar distributions of depressive sub‐types across the groups, an issue which may have muddied interpretation of western studies. Copyright © 2001 John Wiley & Sons, Ltd.
Primary hyperparathyroidism in an elderly woman: surgical reversibility of profound mental state problems due to mild hypercalcaemia
Authors: Ann McDonald C. , Bruce David G. , Smith David J.
Published: August 2002

Background

Clinical case of primary hyperparathyroidism in an 89 year old woman causing profound neuropsychiatric symptoms associated with relatively mild increases in serum calcium levels.

Objectives

To demonstrate that lowering of serum calcium levels by medical treatment (biphosphonate), provided a scientific basis from which to treat a very elderly woman with neuropsychiatric symptoms with definitive surgery.

Method

Case report.

Results

The use of biphosphonate therapy led to marked but temporary improvements in her mental state.

Conclusion

A trial of reducing serum calcium levels with biphosphonate appears to be indicated in elderly patients with mild primary hyperparathyroidism and neuropsychiatric disorders. Copyright © 2002 John Wiley & Sons, Ltd.
Facilitative Strategies in Action
Authors: Fuller Thara M. A. , Haugabrook Adrian K.
Published: August 2002

Thoughtful collaborations between student and academic affairs enhance the student learning environment.
Lessons Learned: Eight Best Practices for New Partnerships
Authors: Martin James , Samels James E.
Published: August 2002

Partnerships must not only be created; they must be nourished, sustained, and allowed to evolve.
Re‐operation for bleeding after thyroidectomy and parathyroidectomy
Authors: Abbas Ghulam , Dubner Sanford , Heller Keith S.
Published: August 2002

Background

This study was undertaken to determine the frequency and timing of re‐operation for bleeding following thyroidectomy (THY) and parathyroidectomy (PARA) as well as the implications of this concerning the safety of ambulatory surgery.

Methods

Patients requiring re‐operation after THY and PARA were identified from a computerized database of patients undergoing surgery between 3/l/95 and 12/31/99. The medical records of these patients were reviewed in detail.

Results

Six of 918 THY (0.7%) and 4 of 350 PARA (1.1%) required re‐operation for bleeding. In two cases the wounds were opened emergently at the bedside due to worsening airway obstruction. One patient required an emergency tracheostomy. There were no deaths. Excluding one patient who bled five days post‐operatively, the time interval from the completion of surgery to the identification of postoperative hematoma ranged from 2 to 48 hours, the median being 16 hours.

Conclusions

Postoperative bleeding is an uncommon but unavoidable complication of THY and PARA. If treated promptly, serious consequences can be avoided. The relatively long interval between the initial operation and the development of the hematoma needs to be considered when recommending the performance of these procedures on an ambulatory basis. © 2001 John Wiley & Sons, Inc. Head Neck 23: 544–546, 2001.
Impact of spatial variations of land surface parameters on regional evaporation: a case study with remote sensing data
Authors: Farah Hussein O. , Bastiaanssen Wim G. M.
Published: August 2002

Most precipitation in watersheds is consumed by evaporation, thus techniques to appraise regional evaporation are important to assess the availability of water resources. Many algorithms to estimate evaporation from remotely sensed spectral data have been developed in the recent past. In addition to differences in the physical parameterization of surface fluxes, these algorithms have different solutions for describing spatial variations of the parameters in the soil–vegetation–atmosphere–transfer (SVAT) continuum. In this study, the necessity to spatially distinguish SVAT parameters for computing surface heat fluxes is analysed for the Naivasha watershed in the Kenyan Rift Valley. Landsat Thematic Mapper (TM) spectral data have been used to first delineate the watershed into 15 hydrological units using surface temperature, normalized difference vegetation index and surface albedo as attributes. Thereafter, semi‐empirical relationships between these TM‐based parameters and other SVAT parameters have been applied to compute the spatial variation of SVAT parameters and the associated evaporation from the different hydrological units. The impact of using watershed‐constant or watershed‐distributed SVAT parameters on the fluxes is analysed. The determination of watershed averaged evaporation with area‐aggregated SVAT parameters is feasible without significant loss of accuracy. Distributed evaporation in heterogeneous watersheds, however, can be investigated only with remote sensing flux algorithms that can account for spatially variable air temperature, surface roughness, surface albedo and the stability correction of the temperature profile due to buoyancy. Erroneous results can be expected if area‐aggregated SVAT parameters are used to calculate local evaporation. As most of the recently developed remote sensing flux algorithms are based on areal constant SVAT parameters, direct applications in watersheds are still limited. Copyright © 2001 John Wiley & Sons, Ltd.
Geophysical surveys for identifying saline groundwater in the semi‐arid region of the central Altiplano, Bolivia
Authors: Guérin Roger , Descloitres Marc , Coudrain Anne , Talbi Amal , Gallaire Robert
Published: August 2002

In the central part of the Bolivian Altiplano, the shallow groundwater presents electrical conductivities ranging from 0·1 to 20 mS/cm. In order to study the origin of this salinity pattern, a good knowledge is required of the geometry of the aquifer at depth. In this study, geophysics has been used to complement the sparse data available from drill holes. One hundred time‐domain electromagnetic (TDEM) soundings were carried out over an area of 1750 km2. About 20 geological logs were available close to some of the TDEM soundings. Three intermediate results were obtained from the combined data: (i) the relationship between the electrical conductivity of the groundwater and the formation resistivity, (ii) geoelectrical cross‐sections and (iii) geoelectrical maps at various depths. The limited data set shows a relationship between resistivity and the nature of the rock. From the cross‐sections, a conductive substratum with a resistivity of less than 1 Ω·m was identified at most of the sites at depths ranging from 50 to 350 m. This substratum could be a clay‐rich formation containing brines. Using derived relationships, maps of the nature of the formation (sandy, intermediate and clayey sediments) were established at depths of 10 and 50 m. Discrimination between sand and clays was impossible where groundwater conductivity is high (>3 mS/cm). In the central part of the area, where the groundwater conductivity is low, sandy sediments are likely to be present from the surface to a depth of more than 200 m. Clayey sediments are more likely to be present in the south‐east and probably constitute a hydraulic barrier to groundwater flow. In conclusion, the study demonstrates the efficiency of the TDEM sounding method to map conductive zones. Copyright © 2001 John Wiley & Sons, Ltd.
Nutrient cycling associated with the seagrass Halophila ovalis in the Swan–Canning Estuary based on seasonal variations in biomass and tissue nutrients
Authors: Connell E. L. , Walker D. I.
Published: August 2002

Halophila ovalis occupies about 20% (461 ha) of the Swan–Canning Estuary. To assess the role of this plant in the biogeochemical cycling of the estuary, its biomass, nutrient dynamics and oxygen release from its roots to the sediment were investigated. This paper describes a conceptual model developed to extrapolate these findings to the whole estuary.

The model follows changes in H. ovalis meadows in the Swan–Canning Estuary on a seasonal basis over an annual cycle. Total maximum seagrass biomass was estimated as 346 t dry weight (DW) in summer, declining in winter. In spring, although H. ovalis biomass did not increase, tissue nutrient concentrations were higher when external nutrient concentrations were high. From spring to summer, when external nutrient concentrations in the water column were severely depleted, shoot to root–rhizome biomass ratios changed from 1 : 1 in winter to 1 : 1·5 in summer. Plant tissue nutrients also decreased in root–rhizomes and increased in shoots, indicating an allocation of internal nutrient resources to the shoots for growth. Despite depletion of nitrogen in the water column, ammonium was still available in the sediment. Ammonium concentrations in the sediment porewater decreased in summer, suggesting H. ovalis meadows were a sink for ammonium. With an increase in biomass in summer, including the density of roots, oxygen release from H. ovalis roots subsequently increased. H. ovalis meadows act as a substantial sink for nutrients in the Swan–Canning Estuary in spring and summer. In winter, when there are large losses of plant biomass, H. ovalis meadows become a source of nutrients to the estuary. Copyright © 2001 John Wiley & Sons, Ltd.
Overexpression of BclXL in a human ovarian carcinoma cell line: Paradoxic effects on chemosensitivity in vitro versus in vivo
Authors: Rogers Paul M. , Beale Philip J. , Al‐Moundhri Mansour , Boxall Frances , Patterson Lisa , Valenti Melanie , Raynaud Florence , Hobbs Steve , Johnston Stephen , Kelland Lloyd R.
Published: August 2002

The effect of overexpressing the antiapoptotic protein BclXL in a human ovarian carcinoma cell line has been investigated in terms of sensitivity to the 2 major drugs used to treat this disease, paclitaxel and cisplatin. Stable transfection of BclXL into CH1 cells, which are relatively sensitive to cisplatin, resulted in around 2.7‐fold higher expression in comparison with empty vector controls. However, this level of overexpression did not result in significant resistance in vitro to paclitaxel or cisplatin at the 50% inhibition level, using either short‐term (4‐day) growth inhibition or longer term colony‐forming assays. By contrast, parallel subcutaneous xenograft models of these isogenic ovarian carcinoma cells in vivo, differing only in BclXL status, showed that this low‐level BclXL overexpression conferred significant resistance to both paclitaxel and cisplatin in comparison with parent, nontransfected tumours. Whereas parent non‐BclXL transfected tumours were highly responsive, with the disappearance of tumours for at least 50 days post treatment, tumours overexpressing BclXL grew back after 30 and 20 days after treatment with paclitaxel and cisplatin, respectively. These differences in responsiveness to paclitaxel in vivo were not attributable to any significant changes in the delivery of drug to the tumour. These data suggest that the responsiveness of ovarian cancer to paclitaxel and cisplatin in vivo, and therefore perhaps clinically, is influenced by levels of the antiapoptotic protein BclXL. Such effects may be missed in vitro when using short‐term growth inhibition or clonogenic assays. © 2001 Wiley‐Liss, Inc.
BRCA1 and BRCA2 mutations among breast cancer patients from the Philippines
Authors: De Leon Matsuda Maria Lourdes , Liede Alexander , Kwan Elaine , Mapua Cynthia A. , Cutiongco Eva Maria C. , Tan Alex , Borg Åke , Narod Steven A.
Published: August 2002

Age‐adjusted incidence rates of breast cancer vary more than 10‐fold worldwide, with the highest rates reported in North America and Europe. The highest breast cancer incidence rates in Southeast Asia have been reported for the Manila Cancer Registry in the Philippines, with an age‐standardized rate of 47.7 per 100,000 per year. The possible contribution of hereditary factors to these elevated rates has not been investigated. We conducted a case‐control study of 294 unselected incident breast cancer cases and 346 female controls from Manila, Philippines. Cases and controls were selected from women below the age of 65 undergoing evaluation at the PGH in Manila because of a suspicious breast mass. Molecular analysis identified 12 BRCA2 mutations and 3 BRCA1 mutations. We estimate the prevalence of BRCA mutations among unselected breast cancer cases in the Philippines to be 5.1% (95% CI: 2.6–7.6%), with a prevalence of 4.1% (95% CI: 1.8–6.4%) for BRCA2 mutations alone. The BRCA2 4265delCT and 4859delA mutations were found in 2 and 4 unrelated cases, respectively; haplotype analysis confirmed that these, and the BRCA1 5454delC mutation, are founder mutations. BRCA2 mutations were also found in 2 of 346 controls (0.6%; 95% CI: 0.2–1.4%). Compared with non‐carrier cases, the cumulative risk of breast cancer for first‐degree relatives of mutation carriers was 24.3% to age 50, compared with <4% for first‐degree relatives of non‐carrier cases (RR = 6.6; 95% CI: 2.6–17.2; p= 7.5 × 10−6). Our data suggest that penetrance of BRCA mutations is not reduced in the Philippines. Germline mutations in the BRCA2 gene contribute more than mutations BRCA1 to breast cancer in the Philippines, due in large part to the presence of 2 common founder mutations. © 2002 Wiley‐Liss, Inc.
Expression and mutation analyses of P53R2, a newly identified p53 target for DNA repair in human gastric carcinoma
Authors: Byun Do‐Sun , Chae Kwon‐Seok , Ryu Byung‐Kyu , Lee Min‐Goo , Chi Sung‐Gil
Published: August 2002

p53R2, a recently identified putative tumor suppressor located at 8q23.1, encodes a protein with striking similarity to a small subunit of ribonucleotide reductase. p53R2 is directly induced by wild‐type p53 and involved in the p53 checkpoint for repair of damaged DNA, raising the possibility that mutational inactivation of p53R2 may contribute to the development and progression of human malignancies. To explore the p53R2's candidacy for a suppressor in gastric tumorigenesis, we examined the expression and mutation status of p53R2 in 166 gastric specimens including 90 primary adenocarcinomas and 15 cell lines. In response to genotoxic damages, p53R2 transcription was clearly activated in wild‐type but not mutant‐type p53‐carrying cells while basal expression of p53R2 in undamaged cells showed no association with the mutational status of p53. Host cell reactivation assay revealed that p53R2 enhances DNA repair efficiency and plays a role in the p53‐mediated repair of damaged DNA, whereas no significant effect of p53R2 on cell growth and apoptosis was detected in flow cytometry and [3H]thymidine incorporation assays. p53R2 transcript was expressed in all normal and tumor tissues and its expression levels were not significantly different between normal and malignant carcinoma tissues. p53R2 expression showed no correlation with stage, grade and histological types of tumors. Moreover, no tumor‐specific reduction of p53R2 was detected in 30 matched sets. Mutational analysis of p53R2 in 105 carcinomas including 15 cell lines also failed to detect any evidences for genomic deletion or somatic mutations leading to amino acid substitutions or frameshift whereas 31% (28 of 90) of the same primary tumors showed p53 alterations. Whereas 82% (23 of 28) of the mutant p53‐carrying primary tumors expressed abnormally low p21Waf1, no association of p53R2 expression with the p53 status was recognized, suggesting that basal transcription of p53R2 is regulated through the p53‐independent mechanism. Collectively, our study indicates that although p53R2 is induced in a p53‐dependent manner and involved the p53‐mediated DNA repair in gastric epithelial cells, it is not a critical target of genetic inactivation in gastric tumorigenesis. © 2002 Wiley‐Liss, Inc.
Blocking a novel 55 kDa melanoma‐associated cell surface antigen inhibits the development of spontaneous metastases and interactions with frozen lung section
Authors: Baril Patrick , Nejjari Mimoun , Scoazek Jean‐Yves , Boukerche Habib
Published: August 2002

We recently identified a novel 55‐kDa cell‐cell adhesion protein (p55) whose expression is upregulated in primary melanomas in the transition from radial growth phase to vertical growth phase. However, the functional role of p55 in various steps of the metastatic process had not been investigated. We provide evidence that subcutaneous injection of metastatic melanoma variant T1P26 in immunosuppressed newborn rats rapidly caused spontaneous metastatic lung lesions that could be readily detected by histochemical analysis with the anti‐p55 monoclonal antibody (MAb) LY1. Subsequently, we were able to demonstrate that multiple subcutaneous injections of the LY1 MAb starting on the same day after tumor cell inoculation of T1P26 cells specifically blocked the formation of spontaneous lung metastases, yet had no effects on primary tumor growth, suggesting a critical role of p55 in the earlier steps of the intravasation process. To study later stages in spontaneous metastasis, we investigated the role of p55 in organ‐specific cell adhesion of tumor cells in vitro. We showed that the T1P26 variant attached preferentially to lung frozen sections compared with other organs, reflecting the pattern of organ involvement of metastasis in vivo and that LY1 significantly blocked this interaction. However, no significant differences in attachment to lung sections were observed between the parental melanoma cell line M4Beu and its derived variant, although cellular topography analysis indicated a preferential attachment of a T1P26 variant on specific compartments of the lungs such as the perialveolar components, the endothelium and the vessel lumen of pulmonary venules. Attachment of the T1P26 variant to lung sections is not due to alterations of tumor cell adherence to basement membrane matrix by the LY1 MAb, suggesting that p55 is involved in cellular adhesion with cellular elements of the lung. p55 could represent a new functional constituent that contributes to the metastatic spread of melanoma cells by promoting the intravasation process and subsequent specific interactions between tumor cells and the target lung organ. © 2002 Wiley‐Liss, Inc.
Grade of malignancy of cervical cancer in regions of Uganda with varying malarial endemicity
Authors: Odida Michael , Schmauz Rolf , Lwanga Stephen K.
Published: August 2002

As in a prior study on malignant lymphomas, 3 and 6 areas of Uganda showing low and high malarial endemicity, respectively, were selected for analysis and the data retrieved from the Kampala Cancer Registry, which in the 1960s and 1970s collected cases of cancer through a widely used free biopsy service from the whole country. Overall incidence rates were derived from 924 cases from the 12‐year period 1964–1975. For reasons of economy, grade of tumour was determined only in cases pertaining to the 6‐year period 1968–1973. Of 457 cases, 304 could be reviewed histologically. Only the group of squamous cell carcinomas (84.9%, 258 cases) was large enough for subsequent geographic analysis. High incidence rates of CC were found in areas with high malarial endemicity, whereas low incidence rates occurred where malaria was either frequent or rare. A correlate to malarial infection was the proportion of high‐grade carcinomas irrespective of the overall incidence of CC. With high prevalence of malaria and high CPRs of 35–74%, the relative share of high‐grade cancer amounted to 50–67%. Where malaria was rare with low CPRs of 8–11%, these values were lower and varied only from 25–39% with a similar range of 14%. Geographic agreement between malarial endemicity and the PI of high‐grade cancer was high in the 9 study areas and only slightly lower than for BL, for which the association with malaria is beyond doubt. Compared to areas with little malaria, the RR for the incidence of high‐grade carcinomas in areas with severe malaria was increased. The value was 2.04 with a 95% confidence interval of 1.37–3.04. Attributable to secondary immunodeficiency, lifelong exposure to malaria may result in excess frequency of high‐grade malignant tumours not only in the group of malignant lymphomas but also in CC. © 2002 Wiley‐Liss, Inc.
Effect of type of screening laboratory on population‐based occurrence of cervical lesions in Finland
Authors: Nieminen Pekka , Hakama Matti , Tarkkanen Jussi , Anttila Ahti
Published: August 2002

The incidence of cervical cancer decreased in Finland over a 30‐year period because of an effective screening program, but in the beginning of the 1990s it began to increase. Reasons for such an increase are variable: changes in sexual habits, shortcomings in attendance for screening and possibly variation in laboratory quality. We evaluated the impact of 3 laboratories in the greater Helsinki area on screening performance and on the incidence of invasive cervical cancer and preinvasive cervical lesions in the target population. We studied time trends, geographic differences in attendance and detection rates from screening and the incidence of invasive cancer in the greater Helsinki area (population about 1 million) during the 1990s, when screening was reorganized from the Cancer Society of Finland laboratory to the municipal one (Helsinki) and to a private laboratory (Espoo), while in Vantaa screening remained with the same Cancer Society laboratory. The attendance rate for screening increased during the study period in all 3 cities. The numbers of cytologically suspected and histologically confirmed precancerous lesions found, including severe lesions, decreased significantly with the change of laboratory in Espoo; but in Helsinki and Vantaa, they increased. The overall incidence of invasive cervical cancer increased in all cities in the age groups screened but mostly in Espoo. The rather rapid changes and variation in trends in the number of screening findings cannot be explained by changes in etiologic factors or attendance. They may be related more to the quality of the laboratory performance and perhaps to the criteria used in cytology and colposcopy. A well‐organized auditing system is proposed to maintain high quality in screening. © 2002 Wiley‐Liss, Inc.
VEGF expression and enhanced production by gonadotropins in ovarian epithelial tumors
Authors: Wang Jun , Luo Feng , Lu Jean J. , Chen Peter K. , Liu Paul , Zheng Wenxin
Published: August 2002

Vascular endothelial growth factor (VEGF) is a heparin‐binding, dimeric polypeptide with potent mitogenic effects on endothelial cells. VEGF expression has also been reported in ovarian epithelial tumors (OETs), which may be associated with gonadotropin stimulatioin. We recently reported that most OETs, including OET cell lines, express gonadotropin receptors. Here we studied VEGF mRNA expression in 141 OET and 35 benign ovarian samples using reverse transcriptase polymerase chain reaction and in situ hybridization (ISH). We also studied VEGF production by OET cell lines under stimulation of gonadotropins. AO (serous carcinoma), low malignant potential (LMP; SV40‐transformed borderline tumor) and ML‐5 (SV40‐transformed cystadenoma) cells were examined for VEGF protein production under the regulation of gonadotropins in vitro. The biologic function of VEGF was confirmed by using bovine endothelial growth assay. Whereas VEGF was not detected in benign ovarian surface epithelium or in ovarian epithelial inclusions, it was detected in both epithelial and stromal compartments of OETs. For VEGF epithelial expression, only 5% of ovarian cystadenomas and 30% of borderline tumors were positive for VEGF detection by ISH, whereas VEGF mRNA signal was detected in 80% of ovarian carcinoma cases. This increment of VEGF expression in ovarian carcinomas was statistically significant compared with benign and borderline tumors. Within ovarian carcinomas, the percentage of VEGF‐positive cells was significantly associated with the grade of cancer but not with cancer cell types or cancer stages. Both follicle‐stimulating hormone (FSH) and luteinizing hormone (LH) stimulated the expression of VEFG165 in AO cells in a dose‐dependent manner. Maximal induction was obtained for FSH at dose of 40 mIU/ml and for LH at 50 mIU/ml after 48 hr of culture. Compared with the nonstimulated cells, VEGF level was significantly elevated in both LMP and AO cells after stimulation of gonadotropins. Furthermore, the induction of VEGF expression was significantly stronger in carcinoma cells than in borderline OET cells. These observations suggest that VEGF may play a role in the development of ovarian cancer and that the elevated gonadotropins, as found in menopause and in most ovarian cancer patients after surgery, could accelerate tumor growth and tumor recurrence by inducing VEGF expression in OETs. © 2002 Wiley‐Liss, Inc.
Involvement of nucleophosmin/B23 in the response of HeLa cells to UV irradiation
Authors: Wu Ming H. , Chang Jei H. , Chou Chih C. , Yung Benjamin Y.M.
Published: August 2002

The steady‐state mRNA level of nucleophosmin/B23 in HeLa cells increased after UV irradiation. Nucleophosmin/B23 antisense transfection potentiated ultraviolet (UV)‐induced cell killing. A block in G2/M phase, larger peak of apoptotic cells and higher caspase‐3 in vitro activity were noted in nucleophosmin/B23 antisense‐transfected cells compared with vector‐transfected cells after UV treatment. Irradiated cells that received vector plasmid exhibited increased levels of [3H]thymidine incorporation due to DNA repair synthesis. In contrast, irradiated cells that received nucleophosmin/B23 antisense plasmid exhibited no such increase of [3H]thymidine incorporation, indicating inhibition of DNA repair. Cotransfection of cells with vector allowed repair of the damaged chloramphenicol acetyl transferase (CAT) reporter and rescue of CAT activity by host repair machinery. CAT activity in cells cotransfected with nucleophosmin/B23 antisense was less (<50%) than that of vector‐transfected cells, indicating reduction of host nucleotide excision repair activity. Lower protein expressions of nucleophosmin/B23 and proliferating cell nuclear antigen (PCNA) were observed in nucleophosmin/B23 antisense‐transfected cells compared with vector‐transfected cells with or without UV treatment. Cotransfection of nucleophosmin/B23 antisense‐transfected HeLa cells with PCNA construct made the cells less susceptible to UV‐induced cell killing. Our results indicate that nucleophosmin/B23 correlates with PCNA and DNA repair capacity in cellular sensitivity to UV. © 2001 Wiley‐Liss, Inc.
Mammographic mass detection by adaptive thresholding and region growing
Authors: Lee Yong Jin , Park Jeong Mi , Park Hyun Wook
Published: August 2002

We present an efficient method to detect mass lesions on digitized mammograms, which consists of breast region extraction, region partitioning, automatic seed selection, segmentation by region growing, feature extraction, and neural network classification. The method partitions the breast region into a fat region, a fatty and glandular region, and a dense region, so that different threshold values can be applied to each partitioned region during processes of the seed selection and segmentation. The mammographic masses are classified by using four features representing shape, density, and margin of the segmented regions. The method detects subtle mass lesions with various contrast ranges and can facilitate a procedure of mass detection in computer‐aided diagnosis systems. © 2001 John Wiley & Sons, Inc. Int J Imaging Syst Technol, 11, 340–346, 2000
Segments
Authors: Zemsky Robert , Shaman Susan , Shapiro Daniel B.
Published: August 2002

This chapter introduces the authors' market taxonomy, which serves as a tool for reflecting the structure of the market for undergraduate education.
Choices
Authors: Zemsky Robert , Shaman Susan , Shapiro Daniel B.
Published: August 2002

This chapter recounts how the Collegiate Results Instrument became a tool for helping high school juniors and seniors make well‐informed college choices.
Dams and development – an insight to the report of the World Commission on Dams1
Authors: Bird Jeremy , Wallace Pamela
Published: August 2002

The World Commission on Dams was initiated as a new form of global policy making to find a way beyond the intensifying conflicts over dam projects. It was established by diverse groups to conduct an independent global review of the performance and impacts of large dams and develop internationally acceptable criteria and guidelines for the future.

The Commission's Report, Dams and Development: a New Framework for Decision Making, presents an integrated assessment of how large dams have performed against their development targets and what the costs and impacts have been. Performance was highly variable, with a considerable portion of those studied falling short of physical targets, while many continue to generate benefits beyond their projected economic life. Many were less profitable in economic terms than expected, indicating that there is considerable scope for improving performance of existing projects. The Commission considered the adverse impacts on ecosystems and people's livelihoods to be unacceptable and unnecessary.

To move forward beyond conflict, the Commission presents a new framework for decision‐making. It rejects the notion of trading one person's gain against another's loss and proposes an approach based on recognising rights and assessing risks for identifying legitimate stakeholders and negotiating development outcomes. Seven strategic priorities and corresponding policy principles for water and energy resources development were derived from this approach and a series of practical criteria and guidelines are presented.

The Commission's recommendations require more attention to be paid to the preliminary stages of planning. This has time and cost implications, but in the long run, the Commission's Report offers the opportunity to reduce conflict, reduce delays and lower overall costs to the operator, the government and to society in general. Copyright © 2001 John Wiley & Sons Ltd.
Linear models for minimizing misclassification costs in bankruptcy prediction
Authors: Nanda Sudhir , Pendharkar Parag
Published: August 2002

This paper illustrates how a misclassification cost matrix can be incorporated into an evolutionary classification system for bankruptcy prediction. Most classification systems for predicting bankruptcy have attempted to minimize misclassifications. The minimizing misclassification approach assumes that Type I and Type II error costs for misclassifications are equal. There is evidence that these costs are not equal and incorporating costs into the classification systems can lead to better and more desirable results. In this paper, we use the principles of evolution to develop and test a genetic algorithm (GA) based approach that incorporates the asymmetric Type I and Type II error costs. Using simulated and real‐life bankruptcy data, we compare the results of our proposed approach with three linear approaches: statistical linear discriminant analysis (LDA), a goal programming approach, and a GA‐based classification approach that does not incorporate the asymmetric misclassification costs. Our results indicate that the proposed approach, incorporating Type I and Type II error costs, results in lower misclassification costs when compared to LDA and GA approaches that do not incorporate misclassification costs. Copyright © 2001 John Wiley & Sons, Ltd.
Immunogenicity of polymeric implants: Long‐term antibody response against polyester (Dacron) following the implantation of vascular prostheses into LEW.1A rats
Authors: Schlosser M. , Wilhelm L. , Urban G. , Ziegler B. , Ziegler M. , Zippel R.
Published: August 2002

Implanted biomaterials trigger acute and chronic inflammatory responses directly correlated to the central role of phagocytic cells at the host–implant interface. This study was designed to evaluate specific humoral immune responses following repeated intraperitoneal implantations of collagen‐impregnated polyester (Dacron) prosthetic segments into LEWIS rats. Serum antibody detection was performed by enzyme immunoassay with the prosthetic segments as a target. Cutoff values for antibody positivity were greater than or equal to the 99th percentile for control rats. Polymer immunoglobiulin G (IgG) antibodies were significantly increased (p < 0.05) by repeated implantation and were subsequently followed until experimental day 293. Antibody formation was significantly enhanced through the application of complete Freund's adjuvant in combination with the first implantation. All rats within this group were antibody‐positive on day 53, but only 6 of 10 animals that received the prosthesis without the adjuvant were. After preincubation of sera with bovine collagen type I (solid phase adsorbed or in solution), polymer antibody binding was discovered not to be diminished, indicating that the IgG antibodies detected were not directed against the prosthesis impregnation. Furthermore, a significant correlation was obtained between polymer antibody binding to collagen‐impregnated and nonimpregnated prostheses (rs = 0.797, p < 0.001). There was no substantiated correlation between antibody binding to polyester and to an irrelevant polymer (Tecoflex EG 80). We conclude that specific polymer antibodies may indeed provide an additional parameter for biocompatibility testing as well as a possible serological marker of an inflammatory response to implants. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 450–457, 2002
Nanoscale modifications of PET polymer surfaces via oxygen‐plasma discharge yield minimal changes in attachment and growth of mammalian epithelial and mesenchymal cells in vitro
Authors: Xie Yubing , Sproule Taryn , Li Yan , Powell Heather , Lannutti John J. , Kniss Douglas A.
Published: August 2002

Surface topography is believed to be a factor affecting cellular morphology, proliferation, and differentiation. The effect of surface roughness in the micron to supramicron range has been investigated previously. In the current study, the influence of nanoscale surface roughness was examined in terms of its effects on morphology, cytoskeleton expression, proliferation, differentiation, and apoptosis of three model cell types. Polyethylene terephthalate (PET) disks were etched using oxygen plasma to produce uniform and decidedly nanoscale levels of surface roughness. Three distinct types of cell lines—mouse 3T3‐L1 preadipocytes, human JEG‐3 choriocarcinoma cells, and human MCF‐7 breast adenocarcinoma cells—were cultured on the plasma‐treated disks. Untreated PET disks were used as a control. Cytoskeletal proteins (F‐actin and cytokeratin) exhibited similar patterns of expression. Cell morphology also was similar on both surfaces. Cell growth kinetics for the three types of cells and hormone secretion from the JEG‐3 cells were not significantly different from that of the controls (p > 0.05). However, the differentiation of preadipocyte 3T3‐L1 cells into lipid‐laden fat cells was modestly affected by nanoscale surface topography. In addition, 15‐deoxy‐Δ12,14‐prostaglandin J2 (15dPGJ2)‐induced apoptosis of the JEG‐3 and MCF‐7 cells revealed differences between the two surfaces. Plasma‐treated surfaces showed more differentiated and apoptotic cells, respectively, compared to the controls. These results indicate that nanoscale roughness contributes in only moderate ways to cellular adhesion, proliferation, and differentiation in the cell lines tested. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 234–245, 2002
Increase in gap‐junctional intercellular communications (GJIC) of normal human dermal fibroblasts (NHDF) on surfaces coated with high‐molecular‐weight hyaluronic acid (HMW HA)
Authors: Park Jeong Ung , Tsuchiya Toshie
Published: August 2002

Normal human dermal fibroblast (NHDF) cells were used to detect differences in gap‐junctional intercellular communication (GJIC) by hyaluronic acid (HA), a linear polymer built from repeating disaccharide units that consist of N‐acetyl‐D‐glucosamine (GlcNa) and D‐glucuronic acid (GlcA) linked by a β1‐4 glycosidic bond. The NHDF cells were cultured with different molecular weights (MW) of HA for 4 days. The rates of cell attachment in dishes coated with high‐molecular‐weight (HMW; 310 kDa or 800 kDa) HA at 2 mg/dish were significantly reduced at an early time point compared with low‐molecular‐weight (LMW; 4.8 kDa or 48 kDa) HA with the same coating amounts. HA‐coated surfaces were observed by atomic force microscopy (AFM) under air and showed that HA molecules ran parallel in the dish coated with LMW HA and had an aggregated island structure in the dish coated with HMW HA surfaces. The cell functions of GJIC were assayed by a scrape‐loading dye transfer (SLDT) method using a dye solution of Lucifer yellow. Promotion of the dye transfer was clearly obtained in the cell monolayer grown on the surface coated with HMW HA. These results suggest that HMW HA promotes the function of GJIC in NHDF cells. In contrast, when HMW HA was added to the monolayer of NHDF cells, the functions of GJIC clearly were lowered in comparison with the cells grown in the control dish or with those grown on the surface of HMW HA. Therefore it is concluded that the MW size of HA and its application method are important factors for generating biocompatible tissue‐engineered products because of the manner in which the GJIC participates in cell differentiation and cell growth rate. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 541–547, 2002