bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of Bcl-2 and Ki-67 in Endometrial Hyperplasia and Disordered Endometrium: A Cross-sectional Study
Authors: Manimaran Akalya , Dongapure Savita
Published: January 2024

Introduction: Endometrial hyperplasia affects both premenopausal and postmenopausal women and is a pathological condition that ranges from mild, reversible glandular proliferations to direct precursors of cancer. B-cell Lymphoma 2 (Bcl-2), an antiapoptotic gene involved in the regulation of apoptosis, and Ki-67, a proliferation marker, serve as indicators for cell proliferation from endometrial hyperplasia to endometrial carcinoma. Aim: To examine the expression of Bcl-2 and Ki-67 in endometrial hyperplasia and disordered endometrium. Materials and Methods: A cross-sectional study was conducted in the Department of Pathology at MVJ Medical College and Research Hospital, located in Hoskote, Karnataka, India, over a period of two years, from September 2020 to September 2022. All endometrial samples and hysterectomy specimens were included. Immunohistochemical staining was performed using Bcl-2 and Ki-67 in disordered proliferative endometrium and endometrial hyperplasia, and the staining and intensity were graded. Statistical analysis was performed, with qualitative variables presented as percentages and quantitative variables presented as Mean±Standard Deviation (SD). A p-value <0.05 was considered statistically significant. Results: The mean age of the study participants was 49.36 years. A total of 33 cases were included in the study, with 15 cases of disordered proliferative endometrium and 18 cases of endometrial hyperplasia. Bcl-2 expression in the 15 cases of disordered proliferative endometrium showed a score 4 positivity in 2 (13.3%) cases, score 8 positivity in 3 (20%) cases, and score 12 positivity in 10 (66.7%) cases, with a mean score of 10.13. Ki-67 expression in the 15 cases of disordered proliferative endometrium showed a score 4 positivity in 10 cases (66.7%), score 8 positivity in 4 (26.7%), and score 12 positivity in 1 (6.67%) case, with a mean score of 5.6. Conclusion: The overexpression of Bcl-2 in endometrial hyperplasia is considered to be an indicative of progression towards frank malignancy. Ki-67, the proliferation marker, is used to determine the progression of endometrial hyperplasia to carcinoma.
Clinical Utilisation of Cryoprecipitate at a Tertiary Care Centre in Telangana, India: A Quasi-experimental Study
Authors: Vujhini Sudhir Kumar , Kumar Kandukuri Mahesh , Bogi Murali Krishna , Bonagiri Shanthi
Published: January 2024

Introduction: Cryoprecipitate is a slushy product derived from Fresh Frozen Plasma (FFP) through centrifugation at specific temperatures and speeds. It is rich in factor VIII or antihaemorrhagic factor, fibrinogen, and minor amounts of other clotting factors. Cryoprecipitate is primarily used to correct hypofibrinogenaemia or replenish depleted fibrinogen levels. Aim: To examine the appropriate clinical utilisation of cryoprecipitate (cryo) by various departments in the Institute and evaluate the improvement in patients through laboratory tests. Materials and Methods: A single group quasi-experimental study was conducted in the Department of Immunohaematology and Transfusion Medicine (IHBT) at Nizam’s Institute of Medical Sciences (NIMS), Hyderabad, Telangana, India. The duration of the study was over a period of six years, from May 2016 to April 2022.. A total of 486 cases where cryoprecipitate was requested were included in the present study. The results were analysed using Prothrombin Time (PT) and International Normalised Ratio (INR). Percentages and means were used to assess various parameters in this study. All statistical analyses were performed using Statistical Package for Social Sciences (SPSS) version 25.0. Results: The mean age of the study participants was 52.7 years. A total of 486 cases were included over a period of six years, with 3375 cryoprecipitate transfusions performed. The youngest patient was a 9-year-old male, the oldest patient was an 83-year-old male. Most of the cryoprecipitate was appropriately utilised by the Medical Oncology Department (995 cases, 995 units, 20-25 mL per unit-29.48%), while the Cardiology Department had the lowest utilisation (12 cases, 12 units-0.35%). Utilisation by other departments ranged between 45 and 564 cases or units (1.33% to 16.71% per department). The majority of cryoprecipitate units were issued for multiple myeloma and acute leukaemias (new cases and relapse)-28.38% (958 units), while the least were issued for minor surgery and medical cases (29 cases or 29 units- 0.85%). Conclusion: Cryoprecipitate should be used appropriately to achieve desired results and avoid unnecessary transmission. Clinicians, residents, and surgeons should adhere to comprehensive regulatory guidelines for the appropriate usage of cryoprecipitate or any other blood products, as outlined by their hospital transfusion committee.
External Auditory Canal Granulations of Varying Aetiology Other than Cholesteatoma: A Series of Seven Cases
Authors: Satpathy Manas Ranjan , Mahapatra Rashmi Rekha , Hembram Kckdn
Published: January 2024

External Auditory Canal (EAC) granulations can occur due to various causes, each with different presenting features, treatment options, and prognoses. They can arise from trivial situations, such as a neglected Foreign Body (FB), or indicate serious pathology like squamous cell carcinoma. The most common causes of EAC granulations are otitis media, including squamous and mucosal types. However, clinical practice encounters numerous other rare and common causes. The present case series describes seven patients with EAC granulations resulting from different aetiologies apart from Chronic Suppurative Otitis Media (CSOM). The study was conducted over a six-month period at a Government Medical College (GMC) in North Odisha. It aims to assist clinicians in considering these situations when managing patients with EAC granulation. Proper diagnosis and treatment of these patients resulted in successful outcomes. Therefore, the author recommends considering these underlying causes whenever EAC granulations do not respond to appropriate medical treatment with antibiotics. Radiological imaging, fine needle aspiration cytology, and histopathological studies can help exclude many of these causes from the list of differential diagnoses.
Search Query Refinement Using Context, Knowledge and Long-term Memorization
Authors: Gupta Sudhanshu , Tiwari Krishna Kumar
Published: January 2024

In the era of information overload, search tools are crucial, yet users often struggle to articulate their precise dataneeds, resulting in sub-optimal search outcomes. This is often due to users associating products with influencers or celebrities rather than knowing the specific brand or product name. This research aims to enable users to find products based on real-life associ- ations, emphasizing the importance of upgrading search query refinement for accuracy and relevance. A significant challenge faced by existing web tools is refining queries involving unrelated entities. This research addresses this gap by proposing a compre- hensive approach that integrates context, knowledge represen- tation, and long-term memorization. The framework combines contextual information with advanced knowledge representation techniques, enhancing the system’s understanding of user intent and domain-specific concepts. Long-term memorization reduces the time complexity of query refinement by leveraging past search experiences. This study underscores the potential of incorporating context, knowledge representation, and long-term memorization in refining search queries, offering more accurate results. As the digital landscape evolves, our approach has the potential to upgrade the search engine experience, providing personalized and contextually relevant results globally.
Impacts of the Use of Chrysophyllum albidum G. Don on Its Vulnerability and Its Conservation in Benin
Authors: Alowanou-Kélé Blaise , Missihoun Antoine Abel , Agbo Relique Ignace , Ewédjè Eben-Ezer B. K. , Yédomonhan Hounnankpon , Agbangla Clément
Published: January 2024

Aims / Objectives: Chrysophyllum albidum is a fruit tree of great socio-economic importance in West Africa. In several localities in Benin, despite the species over-exploitation of the species, few data relating to its viability and the conservation of its genetic diversity exist. The objective of this study is to determine the values and forms of uses, of various organs of the species by the populations, in order to identify their impacts on the vulnerability of the species and its sustainable use.

Methodology: A semi-structured survey has collected from 877 an (eight hundred and seventy-seven) person’s taken at random, ethnobotanical data on the species. The frequencies of use of the different organs, the index vulnerability of the species, as well as the dendrometric parameters were evaluated. In addition, Cramer's V test was used to analyze the influence of sex and socio-cultural groups on the different uses made of the species.

Results: It appears that the species is more and more essential, because it is better known and has priority used in human and animal food, the cure of certain bodily and spiritual diseases but also serves as energy wood and lumber. The frequency of use organs varies from 2.28% (flower) to 99.54% (fruits), passing through 25.88% (root), 35.23% (bark), 49.82% (leaves) and 82.78% (wood). Furthermore, the high number of categories of use (NCU = 6), the frequency of use (FUO = 49.25%), the method of collection (picking and cutting), the types of organs used (wood, fruits, bark, leaves, flower and root), the presence or density of trees of the species in the study environment (less abundant), and the stage of development (adult), made it possible to have the value 2.5 as a vulnerability index. Thus, the degree of stress on the different organs of C. albidum makes the species very vulnerable (VI = 2.50) in Benin.

Conclusion: These different data reveal the need to design strategies for the sustainable management of the plant genetic resources of this species useful in Benin.
Responses of Phosphorus and Zinc on Growth and Yield in Chickpea (Cicer arietinum L.)
Authors: Singh Krishna Kumar , Singh Devendra , Dheer Vineet , Singh Jaykar , Kumar Anil , Sachan Kushal , Yadav Ankit , Tiwari Tapasya , Kumar Ravindra
Published: January 2024

The investigation was taken up at Student's Instructional Farm, Nawabganj at Chandra Shekhar Azad University of Agriculture and Technology, Kanpur, (U.P.) India, during Rabi 2020-21. The 2 factors in sixteen treatment combinations viz., P0Zn0 (control), P0Zn2.5, P0Zn5, P0Zn10, P30Zn0, P30Zn2.5, P30Zn5, P30Zn10, P60Zn0. P60Zn2.5, P60Zn5, P60Zn10, P90Zn0, P90Zn2.5, P90Zn5 and P90Zn10 were experimented in randomized block design with 3 replications. All the growth and yield parameters increased significantly with increasing levels of phosphorus up to 90 kg ha-1. However, growth and yield parameters of chickpea were increased up to 5 kg Zn ha-1 and further increase in the level of Zn does not show significant influence on growth and yield of chickpea. Interaction effect of P and Zn levels on the grain and straw yield of chickpea was significant during study. Thus, it may be concluded that application of phosphorus and zinc proved more beneficial in improving the productivity of chickpea crop. The result showed that application of P and Zn also improved the growth and yield. Phosphorus requirement of chickpea was found more.
Regional Variation in Chikungunya Viral Infection Prevalence in Meghalaya: A Study from Tertiary Teaching Center from North East India
Authors: Agarwal Sharat , Shadap Cleopatra K. , Lyngdoh W. Valarie , Lyngrah K. G. , Agarwal Manika
Published: January 2024

Aim: The aim of the study is to investigate the sero-prevalence of chikungunya presented within NEIGRIHMS (North Eastern Indira Gandhi Regional Institute of Health and Medical sciences), a regional institute located in Shillong, Meghalaya, India.

Study Design: This was a cross-sectional study.

Place and Duration of the Study: The study was carried out in NEIGRIHMS covering patients within Meghalaya apart from the Garo Hills, India, during the months of June to November,              2023.

Methodology: Blood samples from patients were collected and were subjected to CHIKV IgM ELISA for detection of chikungunya virus infection. A total of 100 samples (46 males and 54 females; age range: 18 above) from patientswith chikungunya-like symptoms commonly fever, arthralgia, myalgia and headache were recruited for the study.

Results: Out of 100 samples tested for CHIKV IgM Elisa, 10 samples came out positive.

Conclusion: An active surveillance of cases and identification of their sources can help to identify where the resources for chikungunya prevention program should be distributed within the state of Meghalaya for optimum utilization of resources and effective disease control.
Integrating Natural and Social Sciences for Urban Resilience and Sustainability
Authors: Edward Luo Ching-Ruey
Published: January 2024

Because of the differences in lifestyles, livelihoods, ecological conditions, natural environment, and social environment, etc., between urban areas and rural areas, the priorities for resilience and sustainability will also be different. Due to climate change, the economy under various conditions of development and cultural changes, urban areas or urbanized villages must face issues such as sustainability maintenance and resilience adjustment will be much more sensitive and with higher uncertainties. In fact, there are similarities and differences between sustainability and resilience, therefore, the response methods adopted to deal with issues such as the natural environment and social organizations will also vary depending on factors such as urgency and time competition, sometimes the two are positively correlated, sometimes they are negatively correlated, and sometimes they may be morphologically unrelated, therefore, some innovations will be necessary to be considered, and which will also be discussed in this article. Two applications are presented for the sustainability and resilience on urban area are expressed to show the applicability and the relationships between sustainability and resilience. The twins, sustainability and resilience, may initially proceed in opposite directions (negative correlation) on the timeline of plan execution.

Two applications on “The Catchment Management with Flood Control Infrastructure” and “The COVID-19 on the Management of Sustainability and Resilience in Taiwan” are presented for the sustainability and resilience on urban area are expressed to show the applicability and the relationships between sustainability and resilience.

During the execution process, there will be a period when the two pairs develop independently, but in the end, they will proceed in the same direction (positive correlation). This is something worthy of our attention.
Developing Biocontrol Strategies for the Management of Set rot Disease of Sugarcane under Wider Row Planting
Authors: Yamunarani K. , Sangeetha S. , Chitra K. , Dhanalakshmi K. , Dhanushkodi V.
Published: January 2024

Sugarcane (Saccharum officinarum L.) is one of the economically valuable agricultural crops grown worldwide in tropical and subtropical areas mainly for their sugar source. Among the 110 sugarcane cultivated countries, India and Brazil contribute half of global production [1]. During the period of last five decades the production, productivity and sugarcane recovery has also shown remarkable resilience in productivity growth rate. One of the reasons for the low productivity and recovery is increasing incidence of insect pests and diseases. An ecologically friendly alternative to these problems is biological control using rhizobacteria and their metabolic products [2]. In order to develop a technology capsule Surveys and surveillance were conducted in sugarcane fields both in plant and ratoon crops distributed in Orthanadu and Vallam block in New Cauvery delta area of Thanjavur dictrict during three consecutive years 2019- 22 with an objective to assess the incidence of sett rot, red rot and smut in New Cauvery delta area of Thanjavur dictrict.  Fortnightly fixed plot observation was taken.  The Maximium and minimum temperature, RH and quantity of rain and rainy days also recorded daily and consolidated on monthly basis and weather parameters were correlated with the incidence of disease. The results revealed that the maximum incidence sett rot negatively correlated with temperature. Similarly the number of rainy days and rainfall is positively correlated (r = 0.7523) with incidence of sett rot. For managing sett rot disease of sugarcane through biological approach, studies were conducted on biocontrol agents viz., Trichoderma asperellum (TNAU), Bacillus subtilis (TNAU), Chaetomium globosum (Cg6) with fungicide check propiconozole 0.1%. Among the treatment, highest millable cane (91,080/ha) and yield (91.39 tonnes / ha) and sugar yield ( 10.63 tonnes/ha) were recorded in M1- (Single bud treated with Trichoderma asperellum (TNAU)@ 4 g l-1 + soil application @ 2.5 kg  ha-1) followed by M2-  (Single bud treated with Bacillus subtilis (TNAU)@ 10 g l-1 + soil application @ 2.5 kg ha-1) in which, the cane yield of 88.54 tonnes/ha and sugar yield of 10.68 tonnes/ha were recorded. This study provides a technology capsule for the management of important disease of sugarcane.
On u-d Quark Coulomb Origin of Nuclear Force
Authors: Hoh F. C.
Published: January 2024

The origin of nuclear force is assigned to Coulomb interactions between quarks, u and d, in neighboring nucleons, replacing the current unspecified “residual” strong interaction assignment. The deuteron binding energy is correctly estimated using quasi-classical models for nucleons based upon SSI, the scalar strong interaction hadron theory. The next lightest nuclei are analogously treated. The Coulomb binding energies depend upon the small, in principle observable, internucleon distances between such u and d quarks whose positions in their respective host nucleons however depend upon intranucleon strong u - d potential that span over larger “hidden” distances.
Hubungan Sistem Adat dengan Tahapan Konstruksi dan Sistem Struktur pada Rumah Vernakular di NTT terhadap Gempa
Authors: Sundoro Edwin Hariadi , Trisna I Putu , Ranita Felicia , Griffith Princess , Hariyanto Agus Dwi
Published: January 2024

Indonesia merupakan negara yang memiliki keanekaragaman budaya dan adat istiadat serta sering mengalami gempa bumi, baik itu tektonik maupun vulkanik. Salah satu daerah yang sering terjadi gempa bumi adalah NTT. Di NTT, terdapat beberapa arsitektur vernakular yang memiliki bentuk yang unik. Arsitektur vernakular yang dipilih adalah Wae Rebo, Ammu Hawu dan Sao Ria. Ada beberapa penelitian yang melihat sistem adat dan konstruksinya, namun belum banyak yang melihat keterkaitan adat dengan respon gempa. Tujuan dari penelitian ini adalah untuk mencari hubungan sistem adat dengan tahapan konstruksi dan sistem struktur pada rumah vernakular di NTT terhadap gempa. Penelitian ini merupakan penelitian kualitatif dengan literatur review untuk menganalisis hubungan sistem adat dan respon gempa. Hasil dari analisis menyimpulkan bahwa tahapan konstruksi tidak ada kaitannya dengan respon gempa, melainkan sistem struktur dan detail konstruksi yang merespon terhadap konteks gempa.
Surface resistance measurement of superconducting thin film using probe‐coupling‐type microstrip line resonator
Authors: Okai Daisuke , Kusunoki Masanobu , Mukaida Masashi , Ohshima Shigetoshi
Published: March 2003

To design superconducting microwave receivers, the surface resistance of the superconducting thin film must be considered. Therefore, a highly accurate technique for measuring the surface resistance of superconducting thin films should be established. In this paper, we propose a probe‐coupled microstrip line resonator as a technique for measuring the surface resistance of superconducting thin films. In the resonator technique, the surface resistance is calculated from Qu, the unloaded Q, of the resonator. Since the microstrip line resonator searches for an accurate surface resistance of the superconducting thin film, establishing a technique that accurately determines the Qu of the resonator is crucial. We measure the Qu values of resonators fabricated from metal and superconducting thin film by a probe‐coupled microstrip line resonator and describe the accuracy of Qu measurement by the probe‐coupled micro‐strip line resonator and the repeatability of the surface resistance measurement of a superconducting thin film. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 86(4): 27–35, 2003; Published online in Wiley InterScience (www.interscience. wiley.com). DOI 10.1002/ecjb.10035
Numerical analysis of 1.55‐µm wavelength optical deflector using arrayed waveguide with staircase‐like refractive index distribution
Authors: Miki Kazunori , Kawakita Yasumasa , Kihara Tatsuya , Shimomura Kazuhiko
Published: March 2003

This paper proposes an optical deflector using an arrayed waveguide with a staircase‐like refractive index profile. This device is an optical deflector using an array waveguide with the refractive index different in each of the component waveguides. Optical deflection is accomplished by application of a voltage. In order to study the deflection properties, a theoretical analysis of the structure, device parameters, deflection angle, and number of resolution points is carried out. As a method of realizing an arrayed waveguide with built‐in refractive index steps, selective organometallic vapor phase epitaxial growth is used for fabrication of an array waveguide with multiple quantum well structures. Initial experimental results are reported here. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 86(4): 1–9, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10103
Photodynamic therapy with Pd‐bacteriopheophorbide (TOOKAD): Successful in vivo treatment of human prostatic small cell carcinoma xenografts
Authors: Koudinova Natalia V. , Pinthus Jehonathan H. , Brandis Alexander , Brenner Ori , Bendel Peter , Ramon Jacob , Eshhar Zelig , Scherz Avigdor , Salomon Yoram
Published: March 2003

Small cell carcinoma of the prostate (SCCP), although relatively rare, is the most aggressive variant of prostate cancer, currently with no successful treatment. It was therefore tempting to evaluate the response of this violent malignancy and its bone lesions to Pd‐Bacteriopheophorbide (TOOKAD)‐based photodynamic therapy (PDT), already proven by us to efficiently eradicate other aggressive non‐epithelial solid tumors. TOOKAD is a novel bacteriochlorophyll‐derived, second‐generation photosensitizer recently, developed by us for the treatment of bulky tumors. This photosensitizer is endowed with strong light absorbance (ϵ0 ∼ 105 mol−1 cm−1) in the near infrared region (λ=763nm), allowing deep tissue penetration. The TOOKAD‐PDT protocol targets the tumor vasculature leading to inflammation, hypoxia, necrosis and tumor eradication. The sensitizer clears rapidly from the circulation within a few hours and does not accumulate in tissues, which is compatible with the treatment of localized tumor and isolated metastases. Briefly, male CD1‐nude mice were grafted with the human SCCP (WISH‐PC2) in 3 relevant anatomic locations: subcutaneous (representing tumor mass), intraosseous (representing bone metastases) and orthotopically within the murine prostate microenvironment. The PDT protocol consisted of i.v. administration of TOOKAD (4 mg/kg), followed by immediate illumination (650–800 nm) from a xenon light source or a diode laser emitting at 770 nm. Controls included untreated animals or animals treated with light or TOOKAD alone. Tumor volume, human plasma chromogranin A levels, animal well being and survival were used as end points. In addition, histopathology and immunohistochemistry were used to define the tumor response. Subcutaneous tumors exhibited complete healing within 28–40 days, reaching an overall long‐term cure rate of 69%, followed for 90 days after PDT. Intratibial WISH‐PC2 lesions responded with complete tumor elimination in 50% of the treated mice at 70–90 days after PDT as documented histologically. The response of the orthotopic model was also analyzed histologically with similar results. The study with this model suggests that TOOKAD‐based PDT can reach large tumors and is a feasible, efficient and well‐tolerated approach for minimally invasive treatment of local and disseminated SCCP. © 2003 Wiley‐Liss, Inc.
Analysis of chromosomal instability in pulmonary or liver metastases and matched primary hepatocellular carcinoma after orthotopic liver transplantation
Authors: Gross‐Goupil Marine , Riou Philippe , Emile Jean‐François , Saffroy Raphaël , Azoulay Daniel , Lacherade Isabelle , Receveur Aline , Piatier‐Tonneau Dominique , Castaing Denis , Debuire Brigitte , Lemoine Antoinette
Published: March 2003

To investigate the genetic mechanism of metastatic spread in hepatocellular carcinoma (HCC), we analyzed genomic changes in lung or liver metastases and the corresponding primary tumors (83 tumor samples) in 18 patients who underwent orthotopic liver transplantation. We studied the incidence of microsatellite instability (MSI) and loss of heterozygosity (LOH) involving 8 highly polymorphic microsatellite markers and the polyA tract, Bat26. We also sought alterations of p53 and β‐catenin gene mutations. High MSI (>30–40% of the loci analyzed) was found only in primary tumors (11%), whereas LOH was observed in 50% of primary and in 39% of recurrent tumors. p53 mutations were found in 2 cases of primary HCC but not in the corresponding metastases. P53 was overexpressed in 4 primary HCC (22%) and 7 metastases (39%). The percentage of β‐catenin gene mutations was low (6%). Lung metastases retained the D16S402 microsatellite abnormalities observed in the primary tumors, whereas recurrent liver tumor did not (p = 0.02). In conclusion, LOH and P53 protein overexpression, rather than mutations in the p53 or β‐catenin genes or MSI, seem to be involved in the spreading of HCC, suggesting the presence of metastasis suppressor genes in the vicinity of the chromosomal loci in question. © 2003 Wiley‐Liss, Inc.
Refined mapping of 1q32 amplicons in malignant gliomas confirms MDM4 as the main amplification target
Authors: Riemenschneider Markus J. , Knobbe Christiane B. , Reifenberger Guido
Published: March 2003

We previously reported on the amplification and overexpression of the mouse double minute 4 homolog gene (MDM4) from 1q32 in a subset of malignant gliomas (Riemenschneider et al., Cancer Res 1999;59:6091–6). More recently, amplification and overexpression of the neighboring contactin 2 gene (CNTN2) was reported in individual malignant gliomas without MDM4 amplification (Rickman et al., Cancer Res 2001;61:2162–8). To address the question of whether 1q32 carries 2 independent amplification targets or a common target other than MDM4 and CNTN2, we analyzed primary malignant gliomas for amplification and overexpression of 17 different genes from this region. Our results indicate a single region of amplification that comprises the genes MDM4, GAC1, PIK3C2B and PEPP3, with only MDM4 amplification being invariably associated with overexpression. CNTN2 was found to be coamplified with MDM4 in 3 malignant gliomas but overexpressed in only 1 of these tumors. No CNTN2 amplification was detected in any of 102 malignant gliomas without MDM4 amplification. Our data therefore corroborate the notion that MDM4 is the main amplification target on 1q32 in malignant gliomas. However, coamplification and overexpression of adjacent genes may provide an additional growth advantage in some malignant gliomas with MDM4 amplification. © 2003 Wiley‐Liss, Inc.
Four new DP alleles identified in a study of 500 unrelated bone marrow donor‐recipient pairs
Authors: Steiner L.L. , Wu J. , Noreen H.J. , Moehlenkamp C. , Cavalli A. , Davidson M. , Johnson S. , Winden T. , Segall M. , Begovich A.B. , Williams T.M.
Published: March 2003

HLA‐DP genotyping of 500 donor recipient pairs in a retrospective analysis sponsored by the National Marrow Donor Program (NMDP) identified four new DP alleles, two DPB1 and two DPA1 1. DNA sequencing confirmed that DPB1*8001 and *8101, each found in a single individual, are novel combinations of previously described sequence motifs in the six variable regions of DPB1. DPA1*02014, found in two individuals, is identical to DPA1*02011 except for a novel silent substitution, a G to A transition at the third position of codon 14. DPA1*01032, found in one individual, is identical to DPB1*01031 except for a silent G to A transition at the third position of codon 20. The identification of these novel alleles brings the total number of reported DPB1 alleles to 85 and DPA1 alleles to 15.
CTLA4 polymorphisms in Spanish patients with rheumatoid arthritis
Authors: Gonzalez‐Escribano M.F. , Rodriguez R. , Valenzuela A. , Garcia A. , Garcia‐Lozano J. R. , Nuñez‐Roldan A.
Published: March 2003

Cytotoxic T‐lymphocyte antigen 4 (CTLA4) polymorphisms located in the promotor region at positions −318 (C/T) and in exon 1 (49 A/G) were investigated in 138 Spanish patients (37 men and 101 women) with rheumatoid arthritis and in 305 ethnically‐matched healthy controls. When the allelic and genotypic frequencies corresponding to the CTLA4 −318 position were compared, no significant differences between patients and controls were found. However, when the CTLA4 49 A/G polymorphism was analysed, a significant increase of A/G heterozygous individuals among female patients (48.5% vs. 33.8% in controls; P=0.008; OR=2.0) was observed. This increase was absent among males (37.8%, P=NS). Analysis of the CTLA4 49 polymorphism with respect to HLA‐DRB1 typing demonstrated a significant increase of A/G heterozygosity in the HLA‐DR3‐positive patient group compared with HLA‐DR3‐negative patient group (14/19, 74% vs. 49/119, 41%; P=0.009, OR=4.0). The increase of A/G genotype among HLA‐DR3‐positive patients was found in both males (4/6, 67%) and females (10/13, 77%), although statistical differences were only reached in the female group. These results provide new insight into this complex association, confirm previous data from other studies, and suggest that the CTLA4 gene could be involved in the pathogenesis of rheumatoid arthritis.
Identification, sequencing and serology of HLA‐B*3527
Authors: Guttridge M.G. , Thompson J. , Street J. , Darke C.
Published: March 2003

We describe a variant HLA‐B*35 allele (B*3527) that was detected by the polymerase chain reaction using sequence‐specific primers (PCR‐SSP) in an individual on the Welsh Bone Marrow Donor registry. B*3527 differs from B*3501 by a single base (G/A) at position 302 that encodes an amino acid change of Ser to Asn at position 77 in the Bw6 epitope. Serological studies using 38 B35‐, 4 Bw6‐ and 7 Bw4‐reactive sera indicated that the B*3527 product was indistinguishable from the B35 specificity, and that the substitution did not significantly affect the Bw6 epitope. A family study determined the B*3527 bearing haplotype as: HLA‐A*29, B*3527, Cw*0401, DRB1*0404, DRB4*0101/0103, DQA1*03, DQB1*0302, BFS, C4A3, C4B1. The phenotype and gene frequencies in the local Welsh population were<0.01% and <0.00005%, respectivelyNote.
The CBF.78 monoclonal antibody to human sialophorin has distinct properties giving new insights into the CD43 marker and its activation pathway
Authors: Tkaczuk J. , Al Saati T. , Escargueil‐Blanc I. , Salvayre A. , Horejsi V. , Durand M. , De Preval C. , Ohayon E. , Delsol G. , Abbal M.
Published: March 2003

We confirm here the CD43 specificity of the CBF.78 monoclonal antibody (mAb) and compare its phenotypic and functional capacities to classical group‐A mAbs (DFT1, MEM‐59) and to 2 other CD43 mAbs (RDP/AD9, 161–46). It reacts with stable human CD43 transfectants in a sialic acid independent way and blocks completely cell binding of RDP/AD9 or 161–46 more or less but not DFT1 and MEM‐59. Its distribution differs from all other CD43. B lymphocytes, but surprisingly the majority of granulocytes or monocytes are CBF.78 negative. CBF.78 is expressed on all T lymphocytes, but the number of CBF.78 molecules/cell is low and equally represented on resting T CD4 and CD8 cells. In comparison to naive T lymphocytes, CD45RO cells increase their CBF.78 epitopes much more than other CD43 epitopes. At a single cell level, confocal microscopy shows that CBF.78 can exist independently of other epitopes. CBF.78 is able to induce homotypic adhesion in different cell lines but not in peripheral blood lymphocytes and is unable to relocalise the targeted molecules. U937 cell line that is not agglutinated by CBF.78 (or RDP/AD9) undergoes a stronger adhesion with PMA when this reagent is combined with this mAb. By itself CBF.78 is unable to activate T lymphocytes and to costimulate CD3 mAbs but partially blocks PMA. The phosphorylation of the tyrosine kinase p59fyn and p56lck, driven by CBF.78, is weak and almost blocked by PMA. Altogether these data support the hypothesis that there are at least 3 modes of interaction between PKC and CD43 pathways: each pathway is inhibitory towards the other but the CD43 one can also be synergistic.
Molecular characterization of a novel human natural killer cell receptor homologous to mouse 2B4
Authors: Boles K.s. , Nakajima H. , Colonna M. , Chuang S.s. , Stepp S.e. , Bennett M. , Kumar V. , Mathew P.a.
Published: March 2003

Natural killer (NK) cells spontaneously detect and kill cancerous and virally infected cells through receptors that transduce either activating or inhibiting signals. The majority of well studied NK receptors are involved in inhibitory signaling. However, we have previously described an activating receptor, 2B4, expressed on all murine NK cells and a subset of T cells that mediate non‐major histocompatibility complex (MHC) restricted killing. Anti‐2B4 monoclonal antibodies directed against IL‐2‐activated NK cells enhanced their destruction of tumor cells. Recently, we determined binding of 2B4 to CD48 with a much higher affinity than CD2 to CD48. Here we describe the molecular characterization of a cDNA clone homologous to mouse 2B4, isolated from a human NK cell library. The cDNA clone contained an open reading frame encoding a polypeptide chain of 365 amino acid residues. The predicted protein sequence showed 70% similarity to murine 2B4. Additionally, it has 48, 45, and 43% similarity to human CD84, CDw150 (SLAM), and CD48, respectively. RNA blot analysis indicates the presence of 3 kb and 5 kb transcripts in T‐ and NK‐cell lines. A single transcript of 3 kb is identified in poly(A)+ RNA from human spleen, peripheral blood leukocytes, and lymph node, whereas, the level of expression in bone marrow and fetal liver was indeterminate. Preliminary functional data suggests that NK‐cell interaction with target cells via 2B4 modulates human NK‐cell cytolytic activity.
Polymorphism of human CD1 genes
Authors: Han M. , Hannick L.I. , DiBrino M. , Robinson M.A.
Published: March 2003

Human CD1 genes have been reported to be invariant or to show limited polymorphism. Recently, certain functions of CD1 antigens have been described to include the presentation lipid and glycolipid antigens. These observations prompted a thorough survey of the genetic polymorphism in the five human CD1 genes (CD1a–CD1e). Using polymerase chain reaction‐single stranded conformational polymorphism (PCR‐SSCP) combined with sequence analyses, exons 2 and 3 from CD1a–CD1e were characterized from a total of 110 unrelated healthy donors. Results showed that all five genes (CD1a–CD1e) are polymorphic in exon 2. Substitutions in CD1b and CD1c are silent, whereas, substitutions in CD1a, CD1d and CD1e result in amino acid replacements in the deduced protein products. CD1a and CD1e polymorphisms are prevalent in the population. The substitutions in CD1a have characteristics that may influence interactions with β2‐microglobulin (β2‐m) or accessory molecules. The substitution in CD1e is located in the region predicted to interact with ligands and may differentially impact the ability of CD1e alleles to bind antigen.
Polymorphisms in the 5′‐flanking region of tumor necrosis factor‐α gene in patients with rheumatoid arthritis
Authors: Seki N. , Kamizono S. , Yamada A. , Higuchi T. , Matsumoto H. , Niiya F. , Kimura A. , Tsuchiya K. , Suzuki R. , Date Y. , Tomita T. , Itoh K. , Ochi T.
Published: March 2003

Polymorphisms in the 5′‐flanking promoter/enhancer region of the tumor necrosis factor (TNF)‐α gene were examined to study the genetic background of rheumatoid arthritis (RA). Four variant alleles, −1,031C/−863A, −1,031C/−238A, −857T and −308A, were identified and examined in 387 RA patients and 575 healthy Japanese controls. The frequency of the −857T allele in RA patients was significantly higher than that in the controls. However, the HLA‐DRB1 analysis in the same subjects showed that the DRB1*0405 allele, which is in linkage disequilibrium with the −857T, was more strongly associated with the disease susceptibility than the −857T allele. These results suggest that the susceptible gene to RA is more closely linked to the HLA‐DRB1 locus than to the TNF‐α locus.
HLA in the Azores Archipelago: possible presence of Mongoloid genes
Authors: Bruges‐Armas J. , Martinez‐Laso J. , Martins B. , Allende L. , Gomez‐Casado E. , Longas J. , Varela P. , Gonzalez‐Granado M. , Arnaiz‐Villena A.
Published: March 2003

The HLA profile of the Azoreans has been compared with those of other world populations in order to provide additional information regarding the history of their origins. The allele frequencies, genetic distances between populations, correspondence analyses and most frequent haplotypes were calculated. Our results indicate that the Azorean population most likely contains an admixture of high‐frequency Caucasoid, Mongoloid and, to a lesser degree, Negroid HLA genes. The middle Atlantic Azores Archipelago was officially colonized by the Portuguese after 1439 and historical records are concordant with the existence of Caucasoid and Negroid population. However, Mongoloid genes were not suspected, but the Oriental HLA haplotypes A24‐B44‐DR6‐DQ1, A29‐B21‐DR7‐DQ2 and A2‐B50‐DR7‐DQ2 are the fourth, fifth and sixth most frequent ones in Azores. A correspondence analysis shows that the Azorean population is equidistant from Asian and European populations and genetic distances are in some cases closer to the Asian than to European ethnic groups, and never are significantly different; also, B*2707 subtype is found in Asians and Azoreans (but not in Europeans) and the same Machado‐Joseph Disease founder haplotypes (Chr 14) are found in both Japanese and Azoreans. It is proposed that a Mongoloid population exists in Azores; whether, the arrival occurred prior to discovery is undetermined.
Interleukin‐10 (IL‐10) genotypes in inflammatory bowel disease
Authors: Tagore A. , Gonsalkorale W.M. , Pravica V. , Hajeer A.H. , McMahon R. , Whorwell P.J. , Sinnott P.J. , Hutchinson I.V.
Published: March 2003

Interleukin‐10 (IL‐10) is an anti‐inflammatory cytokine. Its production in humans is under genetic control, and genotype defines high or low producers of this cytokine. This study addresses the hypothesis that idiopathic inflammatory bowel disease (IBD) patients are more likely to have the low IL‐10 producer genotype and phenotype. DNA was extracted from blood cells of patients with Crohn’s disease (CD) or with ulcerative colitis (UC) for IL‐10 genotyping. The frequency of the high IL‐10 producer allele (−1082*G) was decreased in the whole IBD group (41% vs. 51%, P=0.03) and in the UC patients compared with normal controls (37% vs. 51%; P=0.04). Hence, there appears to be an association between the IL‐10 genotypes and IBD. This suggests that individuals genetically predisposed to produce less IL‐10 are at a higher risk of developing IBD, in particular, UC.
Molecular modeling of the minor histocompatibility antigen HA‐1 peptides binding to HLA‐A alleles
Authors: Ren E.C. , Kangueane P. , Kolatkar P. , Lin M.T. , Tseng L.H. , Hansen J.A.
Published: March 2003

Mismatch of the minor histocompatibility antigen HA‐1 has been shown to correlate with graft‐versus‐host disease in HLA‐matched sibling marrow transplants. The HA‐1H peptide (VLHDDLLEA) that generates this response is known to be presented by HLA‐A*0201. In order to understand the interaction of HA‐1 peptides with other HLA‐A alleles, we have used the LOOK interface to construct molecular models of both HA‐1H peptide (VLHDDLLEA) and HA‐1R peptide (VLRDDLLEA) binding with 103 HLA‐A alleles. The results show that in addition to A*0201, 21/103 other HLA‐A alleles should be able to bind HA‐1H peptide but not HA‐1R peptide. Based on the modeled predictions, HLA alleles can be categorised into 4 groups with respect to their interaction with HA‐1 peptides: Group 1 – bind HA‐1H peptide but not HA‐1R peptide; Group 2 – bind HA‐1R peptide but not HA‐1H peptide; Group 3 – bind both HA‐1H and HA‐1R peptides; Group 4 – bind neither peptide. These predicted binding patterns of HA‐1 peptides will be useful as an aid for defining a wider pool of HLA‐A alleles in which HA‐1 disparities among donor‐recipient pairs can be investigated.
HLA DRB1*1501 and intrathecal inflammation in multiple sclerosis
Authors: Sellebjerg F. , Jensen J. , Madsen H.O. , Svejgaard A.
Published: March 2003

CD4 T cells are considered to be pivotal in the pathogenesis of multiple sclerosis (MS), and the human leukocyte antigen (HLA) haplotype associated with DRB1*1501 confers susceptibility to MS in patients of Northern European descent. Some previous studies have suggested an association of DRB1*1501 with T‐ and B‐cell reactivity to specific myelin protein peptides, other studies suggested an association with enhanced cytokine production or intrathecal immunoglobulin (Ig) synthesis. In order to further assess the role of DRB1*1501 in the pathogenesis of MS, we studied intrathecal inflammation and T‐cell phenotypes in patients with possible onset symptoms or clinically definite MS. Presence of DRB1*1501 was associated with higher levels of cerebrospinal fluid (CSF) inflammation as assessed by IgG synthesis levels and higher levels of matrix metalloproteinase‐9 activity. DRB1*1501‐positive patients also had a lower percentage of T cells in CSF expressing HLA‐DR without co‐expressing CD25. These findings suggest that enhanced intrathecal inflammation and an altered T‐cell activation status may be of importance in conferring the DRB1*1501‐associated susceptibility to MS.
Platelet endothelial cell adhesion molecule‐1 (PECAM‐1/CD31) is associated with a naïve B‐cell phenotype in human tonsils
Authors: Jackson D.E. , Gully L.M. , Henshall T.L. , Mardell C.E. , Macardle P.J.
Published: March 2003

In B cells, signaling through the B‐cell antigen receptor (BCR) is negatively modulated by the co‐ligation of immunoglobulin (Ig)‐immunoreceptor tyrosine‐based inhibitory motif (ITIM)‐bearing molecules such as FcγRIIB1, B‐cell transmembrane protein CD72, paired immunoglobulin‐like receptor PIR‐B, leukocyte‐associated immunoglobulin‐like receptor‐1 (LAIR‐1), Ig‐like transcript ILT2, biliary glycoprotein BGP‐1 and B‐cell co‐receptor CD22. The co‐expression of multiple Ig‐ITIM receptors may provide B cells with different mechanisms of regulating inhibitory pathways at different stages of differentiation. In this study, we have examined the expression of a newly defined Ig‐ITIM receptor, PECAM‐1 (CD31) on human B‐cells. Human tonsillar B cells were purified using negative selection by depleting T cells with a combination of monoclonal antibodies and magnetic bead separation. Following purification, the pattern of PECAM‐1 expression was analyzed in B‐cell subpopulations using two‐ and three‐colour fluorescence. To complement this work, PECAM‐1 localization in the context of distinct areas of human tonsil was defined by immunohistochemical analysis of tonsil sections. Finally to investigate somatic mutation, Ig variable (V) region genes belonging to the nonpolymorphic VH6 family were amplified by polymerase chain reaction (PCR), subcloned and sequenced from sort‐purified CD19+ PECAM‐1+ and CD19+ PECAM‐1− B cells. Our results demonstrate that PECAM‐1 is associated with an unstimulated resting B‐cell phenotype, localization to the follicular mantle and marginal zones of human tonsil and expression of unmutated Ig V region genes. These studies suggest that PECAM‐1 appears on the cell surface at the naïve B‐cell stage and is lost as B cells differentiate into memory cells, indicating that PECAM‐1 is primarily involved in naïve or immature B‐cell function.
Presence of a protective allele for achalasia on the central region of the major histocompatibility complex
Authors: De La Concha E.G. , Fernandez‐Arquero M. , Conejero L. , Lazaro F. , Mendoza J.L. , Sevilla M.C. , Diaz‐Rubio M. , Ruiz de Leon A.
Published: March 2003

Idiopathic achalasia is a motility disorder of the esophagus whose etiology is unknown. An association between HLA genes and susceptibility to achalasia which suggests a possible immunogenetic mechanism has been reported recently. This study was designed to examine the HLA class II association in a large group of achalasia patients further and to investigate the distribution of TNFa and TNFb microsatellites in these patients. The study population, all Spanish, white and unrelated, consisted of 115 consecutive patients and 339 healthy controls. All of the patients had been diagnosed with primary achalasia of the esophagus with manometric, radiographic and endoscopic studies. All studies were performed on DNA samples after locus‐specific amplification with the polymerase chain reaction: HLA‐DRB1, DQA1 and DQB1 were typed by dot‐blot hybridization and the size of the TNFa and TNFb microsatellites was measured using a semiautomatic method. The broad allele HLA‐DQ1 was seen to be weakly associated with achalasia. The TNFa11 allele and the DRB1*1501‐DQA1*0102‐DQB1*0602 haplotype were reduced in achalasia patients but the stratified analyses showed that this was true only when both were present in the same individual. These results confirm the association between achalasia and HLA‐DQ1 allele and suggest that TNFa11 is a marker for a protective allele for the disease, present on the B7‐DRB1*1501 (7.1) ancestral haplotype in our population.
DPB1*8501, a novel DPB1 variant in the US Black population
Authors: Rozemuller E.H. , Van Der Zwan A.W. , Voorter C.E.M. , Tilanus M.G.J.
Published: March 2003

We describe a new DPB1 allele, DPB1*8501, which was identified by sequencing‐based typing (SBT) in the UCLA exchange. DPB1*8501 is similar to DPB1*2701 with a difference at position 272, (G to A). This difference leads to an amino‐acid change of codon 91 from arginine (CGC) to histidine (CAC). Until now this position has been considered conserved. This substitution is located at the 3′ site of exon 2, and may interfere with typing strategies using primers or probes located in this region ( Note).
HLA class II allele distribution in the Gypsy community of Andalusia, southern Spain
Authors: Ramal L.M. , De Pablo R. , Guadix M.J. , Sánchez J. , Garrido A. , Garrido F. , Jiménez‐Alonso J. , López‐Nevot M.A.
Published: March 2003

Abstract: We have studied the allele distribution of DRB1, DQB1 and DPB1 loci in 80 unrelated Gypsies living in different eastern areas of the Andalusian province of Granada (southern Spain). The frequency distribution of HLA class II alleles and the genetic distance of Andalusian Gypsies from several Caucasian populations indicate a marked similarity – but not total – of the former with the Gypsy population previously studied in Madrid (central Spain), which suggests that both groups migrated together out of India. In terms of genetic distance, both Gypsy groups are more like the Czech Gypsies and the Northern Indian groups than their neighbouring Caucasian non‐Gypsy populations. In summary our data support the hypothesis of a common anthropological origin of all three European Gypsy groups, which probably split up after their arrival in Europe.