bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring lake ecosystems: hierarchy responses to long‐term change?
Authors: WAGNER CAROLA , ADRIAN RITA
Published: December 2008

Shifts in climate regime have provoked substantial trophic‐ and species‐dependent changes within ecosystems. With growing concerns of present global warming, we examined potential lake ecosystem responses, natural hierarchy responses (i.e. immediate responses at lower system levels as opposed to delayed responses at higher system levels), and possible shifts among abiotic (physics, nutrients) and biotic (phytoplankton, zooplankton) system components. Specifically, we analyzed decadal data collected from Müggelsee, a lake in Berlin, Germany, for climate‐induced abiotic and biotic changes, their timing and type, and classified them as abrupt permanent, gradual permanent, abrupt temporary, or monotonic. We further categorized variable changes as a function of system hierarchy, including lake physics (ice, temperature, stratification), nutrients (phosphorus, nitrogen, silicate), plankton, and levels of integration (i.e. species, taxonomic groups, and total plankton). Contrary to current theory, data suggest abrupt responses did not occur in a hierarchy‐dependent manner, nor was a clear pattern observed among functional system‐based categories. Abrupt permanent changes were the most prominent response pattern observed, suggesting they may be driven by large‐scale climatic oscillations and by surpassed thresholds, as noted in previous case studies. Gradual changes coincided with affected abiotic parameters spanning an expansive time range; for example, climatic effects in spring preceded changes in nutrient limitation. Variables displaying no long‐term changes pointed to compensation processes caused by, e.g., simultaneously acting forces of warming trends and climate‐independent changes in trophic state. Nevertheless, the complexity of response patterns at the single system level manifested clear chronological regime shifts in abiotic and biotic parameters in spring and, to a lesser extent, in summer. With regard to projected global warming, the majority of currently unaffected system levels may face impending thermal thresholds, achievement of which would result in an accelerated shift in ecosystem state.
Little evidence for respiratory acclimation by microbial communities to short‐term shifts in temperature in red pine (Pinus resinosa) litter
Authors: MALCOLM GLENNA M. , LÓPEZ‐GUTIÉRREZ JUAN C. , KOIDE ROGER T.
Published: December 2008

Forest litter is a large reservoir of organic compounds that adds CO2to the atmospheric carbon pool when it decomposes. Predicting CO2efflux from litter decomposition is difficult because litter can undergo significant diurnal and day‐to‐day shifts in temperature. Moreover, the relationship between temperature and respiration may change if the decomposer microorganisms acclimate to short‐term temperature changes. Therefore, we studied the relationship between temperature and respiration by litter decomposer microorganisms in aPinus resinosa(Ait.) system and tested the hypothesis that their respiration acclimates to temperature. We found only limited evidence for acclimation following 6 °C shifts for 7 days. This suggests that increase in respiratory CO2loss associated with increased temperature would not be greatly ameliorated by physiological acclimation for periods of up to a week.
Complementary alternative medicine use in children with type 1 diabetes mellitus in Erzurum, Turkey
Authors: Arýkan Duygu , Sívríkaya Sibel Karaca , Olgun Nermin
Published: December 2008

Aim and objective.  The aims of this study were: (i) to determine the types of complementary and alternative medicine use among children with type I diabetes mellitus as reported by parents and (ii) to describe sociodemographic and medical factors associated with the use of such treatments in families residing in Eastern Turkey.

Background.  Type 1 diabetes mellitus is a tremendously challenging and complex disease for children and families to manage. Therefore, the use of complementary and alternative medicines among children with type 1 diabetes is becoming increasingly popular.

Design.  Survey.

Method.  Parents of 100 paediatric patients (who were diagnosed with type 1 diabetes at least 6 months prior to the study) who visited the participating paediatric endocrinology multidisciplinary centres and clinics for diabetes management were included in the study. Data were collected by using a semi‐structured questionnaire.

Results.  Fifty‐two per cent of the parents reported the use of one or more complementary alternative medicine therapies. Most such users (59·6%) were using oral herbal preparations; including morus alba (leaves) aloe vera and stinging nettle.

Conclusion.  Since we found that 78·6% of those using herbals were satisfied with their results and 69·2% were planning to continue use, it is important for healthcare providers to have relevant knowledge about complementary alternative medicine use and learn about its efficacy and effects (positive and adverse) of these treatments.

Relevance to clinical practice.  Botanical substitute for insulin seems unlikely, but complementary alternative treatments may provide valuable clues for the development of new oral hypoglycaemic agents and simple dietary agents. It is important for healthcare providers to have up‐to‐date knowledge about the use and effects of complementary alternative medicines in the outpatient clinical care setting.
Willingness to use respite care among family caregivers in Northern Taiwan
Authors: Huang Hsiu‐Li , Shyu Yea‐Ing Lotus , Chang Mei Yeh , Weng Li‐Chueh , Lee I
Published: December 2008

Aim and objectives.  Investigate the use of respite care among family caregivers and examine factors related to their willingness to use such care.

Background.  Respite care is a pivotal service for supporting family caregivers. Although research related to respite care is not a new field in western societies, such studies have rarely been done for Asian populations.

Design.  A cross‐sectional study.

Methods.  The study was conducted using a convenience sample of 100 family caregivers obtained through four home health care agencies in Northern Taiwan. Structured face‐to face interviews were conducted in home settings. Caregivers were divided into a willingness group and a non‐willingness group. The quantitative data were analysed using t‐test, chi‐square and multiple logistic regression.

Results.  Sixty‐five per cent of the caregivers interviewed did not know about respite care services. The prevalence of respite care use was 11%. Eighty‐nine per cent of the caregivers had never used respite care: 60·7% of them reported that they would never use it and 39·3% of the caregivers indicated that they were willing to use respite care in the future. This study showed that willingness to use respite care was higher when the respite services matched the needs of the caregivers as well as the caregivers perceived higher caregiving burden.

Conclusions.  These results suggest that respite care services should be explained more explicitly to family caregivers. Also, any respite care plan must consider the family caregivers burden, both perceived and realistically.

Relevance to clinical practice.  The willingness to use respite care is a culturally sensitive issue. Health care providers must act as advocates to improve respite care policy. They must ensure that respite care fits caregivers’ needs and they must help caregivers overcome the social or cultural barriers to respite care.
Emotional care experienced by hospitalised patients: development and testing of a measurement instrument
Authors: Williams Anne M , Kristjanson Linda J
Published: December 2008

Aims and objectives. This paper describes the development and preliminary psychometric testing of an instrument that evaluates the emotional care experienced by patients during hospitalisation.

Background. Previous qualitative work using the Grounded Theory method identified the characteristics of interpersonal interactions that hospitalised patients perceived to be therapeutic. Three conditions were associated with the patient’s experience of emotional comfort: the patient’s perceived Level of Security, Level of Knowing and Level of Personal Value. Questions relating to each of these conditions were included in this new instrument.

Design. Instrument development and psychometric testing.

Method. Preliminary psychometric testing was carried out in four phases: construction of the instrument; assessment of face and content validity; testing for clarity and feasibility for use with hospitalised patients; assessment of reliability, construct validity of the tool and assessment of the internal structure.

Conclusions. A hospital‐wide survey was carried out and the instrument was completed by a total sample of 132 patients. Two of the three sub‐scales achieved an internal consistency estimate of at least 0·70. The construct validity of the tool confirmed the previously identified characteristics of patients in need of additional emotional care. Exploratory factor analysis established two of the sub‐scales and identified a fourth sub‐scale which was named ‘Level of Connection’. Encouraging reliability and validity estimates were obtained and the instrument was improved. Further testing with larger samples is recommended.

Relevance to clinical practice. This questionnaire, which is completed by hospitalised patients, differs from other instruments because it evaluates the interactions of all hospital staff rather than only nursing staff. This instrument can be used to identify patients who may be in need of additional emotional care and to evaluate the effectiveness of interventions directed at improving the emotional well‐being of patients.
Ambulation after femoral sheath removal in percutaneous coronary intervention: a prospective comparison of early vs. late ambulation
Authors: Schiks Ingrid EJM , Schoonhoven Lisette , Aengevaeren Wim RM , Nogarede‐Hoekstra Coby , Van Achterberg Theo , Verheugt Freek WA
Published: December 2008

Aim and objectives.  To investigate if ambulation four hours after sheath removal can replace ambulation 10 hours or more after sheath removal with regard to puncture site complications after percutaneous coronary interventions and to examine patient comfort in both groups.

Background.  Early ambulation after percutaneous coronary intervention may facilitate earlier hospital discharge. Whether this approach is safe, is unknown.

Design.  A non‐randomised comparative study.

Methods.  Percutaneous coronary intervention was performed by femoral approach. Registered nurses of the ward removed the sheath and haemostasis was achieved by manual compression. After bed rest with a compression bandage for four hours, the patients in the early ambulation group were ambulated. The patients in the control group stayed in bed till the next morning. Primary study endpoint was the composition of puncture site complications: haematoma, bleeding, false aneurysm and arteriovenous fistula. Secondary endpoints were occurrence of vasovagal collapse after mobilisation, back pain and problems with voiding.

Results.  In the early ambulation group (n = 329) the total number of complications was nine (2·7%), vs. six (3·0%) in the control group (n = 202). The complication rate in the early ambulation group is not increased compared to the control group (test for non‐inferiority p = 0·002). Hence non‐inferiority is accepted and practical equivalence shown. There were no statistically significant differences concerning patient comfort between the groups.

Conclusions.  Early ambulation four hours after femoral sheath removal is feasible and safe. The incidence of puncture site complications in the early ambulation group is not increased in comparison with the group with prolonged bed rest.

Relevance to clinical practice.  Patients could possibly be discharged earlier after percutaneous coronary intervention, allowing percutaneous coronary intervention in an ambulant setting. Further research should confirm these findings and extend the research to the effect of various closure devices in early ambulation and on patients’ well‐being.
Incidence of pressure ulcers in intensive care unit patients at risk according to the Waterlow scale and factors influencing the development of pressure ulcers
Authors: Sayar Serap , Turgut Sibel , Doğan Havva , Ekici Aynur , Yurtsever Sabire , Demirkan Ferit , Doruk Nurcan , Taşdelen Bahar
Published: December 2008

Aims.  To determine incidence of pressure ulcers in patients at risk according to the Waterlow scale in intensive care units and to evaluate the effects of risk factors in critically ill patients.

Background.  Pressure ulcers continue to be an important health problem that increases the risk of illness and death, extends patients’ length of hospital stay and increases healthcare expenses.

Design.  The study was conducted as a descriptive and prospective study.

Method.  The sample consisted of 140 patients. Data were collected using a data collection form, the skin assessment instrument and the Waterlow scale.

Results.  The incidence of pressure ulcers in intensive care unit patients was found to be 14·3%. The majority of pressure ulcers (74%) were grade I. The mean length of time for pressure ulcer development was found to be 10·4 (SD 1·85) days. A statistically significant difference was found in the patients for pressure ulcer development according to their level of consciousness, activity, cooperation, length of stay, Waterlow scale score and C‐reactive protein level. In the multiple stepwise logistic regression analysis, the most influential factors for pressure ulcer development were determined to be length of stay and activity level.

Conclusions.  Extra care needs to be taken to prevent pressure ulcer development in intensive care unit patients who have an extended length of stay, are dependent for activities, have high Waterlow scores, are unconscious and are not cooperative.

Relevance to clinical practice.  This study determined the incidence of and factors that can affect the development of pressure ulcers in intensive care unit patients who are in a high risk group for the development of pressure ulcers and presented the importance of having Turkish nurses implement interventions directed at these factors.
Safety and security in acute admission psychiatric wards in Ireland and London: a comparative study
Authors: Cowman Seamus , Bowers Len
Published: December 2008

Aims and objectives.  The comparative element of this study is to describe safety and security measures in psychiatric acute admission wards in the Republic of Ireland and London; to describe differences and similarities in terms of safety and security patterns in the Republic of Ireland and London; and to make recommendations on safety and security to mental health services management and psychiatric nurses.

Background.  Violence is a serious problem in psychiatric services and staff experience significant psychological reactions to being assaulted. Health and Safety Authorities in the UK and Ireland have expressed concern about violence and assault in healthcare, however, there remains a lack of clarity on matters of procedure and policy pertaining to safety and security in psychiatric hospitals.

Design.  A descriptive survey research design was employed.

Methods.  Questionnaires were circulated to all acute wards in London and in Ireland and the resulting data compared.

Results.  A total of 124 psychiatric wards from London and 43 wards from Ireland were included in this study and response rates of 70% (London) and 86% (Ireland) were obtained. Differences and similarities in safety and security practices were identified between London and Ireland, with Irish wards having generally higher and more intensive levels of security.

Conclusions.  There is a lack of coherent policy and procedure in safety and security measures across psychiatric acute admission wards in the Republic of Ireland and London. Given the trends in European Union (EU) regulation, there is a strong argument for the publication of acceptable minimum guidelines for safety and security in mental health services across the EU.

Relevance to clinical practice.  There must be a concerted effort to ensure that all policy and procedure in safety and security is founded on evidence and best practice. Mental health managers must establish a review of work safety and security procedures and practices. Risk assessment and environmental audits of all mental health clinical environments should be mandatory.
Review: Role of developmental inflammation and blood–brain barrier dysfunction in neurodevelopmental and neurodegenerative diseases
Authors: Stolp H. B. , Dziegielewska K. M.
Published: December 2008

The causes of most neurological disorders are not fully understood. Inflammation and blood–brain barrier dysfunction appear to play major roles in the pathology of these diseases. Inflammatory insults that occur during brain development may have widespread effects later in life for a spectrum of neurological disorders. In this review, a new hypothesis suggesting a mechanistic link between inflammation and blood–brain barrier function (integrity), which is universally important in both neurodevelopmental and neurodegerative diseases, is proposed. The role of inflammation and the blood–brain barrier will be discussed in cerebral palsy, schizophrenia, Parkinson's disease, Alzheimer's disease and multiple sclerosis, conditions where both inflammation and blood–brain barrier dysfunction occur either during initiation and/or progression of the disease. We suggest that breakdown of normal blood–brain barrier function resulting in a short‐lasting influx of blood‐born molecules, in particular plasma proteins, may cause local damage, such as reduction of brain white matter observed in some newborn babies, but may also be the mechanism behind some neurodegenerative diseases related to underlying brain damage and long‐term changes in barrier properties.
Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain
Authors: Cosenza‐Nashat M. , Zhao M.‐L. , Suh H.‐S. , Morgan J. , Natividad R. , Morgello S. , Lee S. C.
Published: December 2008

Aims: Microglia are involved in neurodegeneration, are prime targets for anti‐inflammatory therapy and are potential biomarkers of disease progression. For example, positron emission tomography imaging employing radioligands for the mitochondrial translocator protein of 18 kDa (TSPO, formerly known as the peripheral benzodiazepine receptor) is being scrutinized to detect neuroinflammation in various diseases. TSPO is presumably present in activated microglia, but may be present in other neural cells. Methods: We sought to elucidate the protein expression in normal human central nervous system, several neurological diseases (HIV encephalitis, Alzheimer's disease, multiple sclerosis and stroke) and simian immunodeficiency virus encephalitis by performing immunohistochemistry with two anti‐TSPO antibodies. Results: Although the overall parenchymal staining was minimal in normal brain, endothelial and smooth muscle cells, subpial glia, intravascular monocytes and ependymal cells were TSPO‐positive. In disease states, elevated TSPO was present in parenchymal microglia, macrophages and some hypertrophic astrocytes, but the distribution of TSPO varied depending on the disease, disease stage and proximity to the lesion or relation to infection. Staining with the two antibodies correlated well in white matter, but one antibody also stained cortical neurones. Quantitative analysis demonstrated a significant increase in TSPO in the white matter of HIV encephalitis compared with brains without encephalitis. TSPO expression was also increased in simian immunodeficiency virus encephalitis. Conclusions: This report provides the first comprehensive immunohistochemical analysis of the expression of TSPO. The results are useful for informing the usage of positron emission tomography as an imaging modality and have an impact on the potential use of TSPO as an anti‐inflammatory pharmacological target.
Omalizumab therapy: patients who achieve greatest benefit for their asthma experience greatest benefit for rhinitis
Authors: Humbert M. , Boulet L. P. , Niven R. M. , Panahloo Z. , Blogg M , Ayre G.
Published: December 2008

Background:  Asthma and rhinitis are considered components of a single IgE‐mediated inflammatory disorder. However, despite being shown to often co‐exist, they are typically treated as independent conditions. Omalizumab, an anti‐IgE antibody, has proven effective in the treatment of both asthma and rhinitis.

Aims:  To examine whether a response to omalizumab in terms of asthma control predicts a higher likelihood of rhinitis response in patients with concomitant allergic asthma and rhinitis.

Methods:  This post hoc analysis was conducted on efficacy results from the SOLAR trial in which patients with moderate‐to‐severe asthma and rhinitis were randomized to receive omalizumab or placebo for 28 weeks. Patients were classified as asthma responders based on the physician’s overall assessment (complete control or marked improvement in a five‐level evaluation). Rhinitis responders were identified using the Rhinitis Quality of Life Questionnaire (RQLQ) questionnaire (≥ 1.0 point improvement in overall score).

Results:  Data were available for 207 omalizumab‐treated patients and 192 placebo patients. According to the physicians overall assessment, 123 (59.4%) of omalizumab‐treated patients were asthma responders, with the likelihood of a rhinitis response significantly (P < 0.001) greater in these patients than in the placebo group. The odds ratio for rhinitis response in omalizumab‐treated asthma responders vs nonresponders was 3.56 (95% CI: 1.94–6.54).

Conclusions:  A response in terms of asthma following omalizumab therapy is associated with a significantly increased probability of improvement in rhinitis.
Plasma biomarkers of acute attacks in patients with angioedema due to C1‐inhibitor deficiency
Authors: Cugno M. , Zanichelli A. , Bellatorre A. G. , Griffini S. , Cicardi M.
Published: December 2008

Background:  Cl‐inhibitor (C1‐INH) deficiency leads to recurrent attacks of mucocutaneous edema and may be inherited (hereditary angioedema [HAE]) or acquired (acquired angioedema [AAE]), which have the same clinical picture characterized by angioedema involving the skin, gastrointestinal tract, and larynx. Although cutaneous swelling is evident, abdominal angioedema is still a diagnostic challenge and attacks can mimic surgical emergencies. There is currently no laboratory marker for identifying angioedema attacks.

Objective:  As coagulation and fibrinolysis are activated during angioedema attacks, we assessed if plasma measurements of prothrombin fragment F1 + 2 (marker of thrombin generation) and D‐dimer (marker of fibrin degradation) can be useful for the diagnosis of angioedema because of C1‐INH deficiency, especially in case of hidden locations as abdominal attacks.

Methods:  In addition to complement, we measured plasma levels of F1 + 2 and D‐dimer in 28 patients with C1‐INH deficiency during acute attacks and remission, 35 patients without C1‐INH deficiency during abdominal colics, and 20 healthy subjects.

Results:  Plasma F1 + 2 levels were higher in patients with C1‐INH deficiency during remission than in healthy controls (P = 0.001), and further increased during cutaneous and abdominal attacks (P = 0.0001); patients without C1‐INH deficiency had normal F1 + 2 levels during abdominal colics. Plasma D‐dimer levels were higher in patients with C1‐INH deficiency during remission than in controls (P = 0.012) and increased during angioedema attacks, reaching higher levels than in patients without C1‐INH deficiency during colics (P = 0.002).

Conclusions:  During acute angioedema attacks, patients with C1‐INH deficiency have high prothrombin fragment F1 + 2 and D‐dimer levels, the measurement of which may have an important diagnostic value.
Activation of cytotoxic T lymphocytes in HLA‐A, ‐B and ‐C‐identical responder‐stimulator pairs II
Authors: Breuning Martijn H. , Breur Birgitta S. , Engelsma Marian Y. , Goulmy Els , Iványi Pavol
Published: December 2008

We compared five cytotoxic T lymphocytes raised by primary mixed lymphocyte cultures of HLA‐A, ‐B and ‐C serologically identical Bw35‐positive responder‐stimulator combinations. When tested on a panel of third‐party target cells, the reactivity pattern of these cytotoxic T lymphocytes allowed the distinction of three subtypes of HLA‐Bw35. Cold‐target inhibition experiments and analysis of CTL activity at the clonal level showed the existence of subsets of CTLs directed against distinct antigenic determinants associated with HLA‐Bw35.
Optimum cell numbers for mixed lymphocyte responses in hanging‐drop microcultures
Authors: Taylor G. Malcolm , Jones Helen , Hughes Gwyn , Harris R. , Dyer P. A.
Published: December 2008

The conditions required for optimum mixed lymphocyte culture (MLC) responses in hanging‐drop (HD) microcultures in Terasaki trays have been investigated. Compared with conventional (200 μl) MLC, HD‐MLC required 5–10 times fewer cells, and 10% of the amount of culture medium and 3H‐thymidine label. Peak uptake of label in HD‐MLC was mutually responder‐stimulator concentration dependent. Differences in response to related and unrelated lymphocytes indicate that HLA‐D determinants are detected in HD‐MLC.
Discontinuous expression of a membrane antigen (HB‐7) during B lymphocyte differentiation
Authors: Tedder Thomas F. , Clement Loran T. , Cooper Max D.
Published: December 2008

We have examined the expression of a cell surface antigen by B lineage cells in human fetuses, newborns and adults using a newly produced monoclonal antibody, HB‐7. The HB‐7 antigen was found to be a protease sensitive 45,000 MW molecule that appeared to be the same molecule recognized by the OKT‐10 antibody. The HB‐7 reactive molecule was expressed by all fetal pre‐B and B cells, and 50% of newborn blood and adult bone marrow B cells. In contrast, only a small minority of B cells (2–12%) from blood, spleen and tonsil of adults were weakly HB‐7+. The pokeweed mitogen‐responsive B cell precursors of plasma cells were also HB‐7−, but the HB‐7 antigen was re‐expressed during the plasma cell stage. We conclude that this antigen is unique among known B cell differentiation antigens in its intermittent pattern of expression during B cell development. The reactivity of the HB‐7 antibody with immature, but not mature, B cells makes it well suited for studies of B cell ontogeny.
Utilization of murine peripheral blood lymphocytes for H‐2 typing
Authors: Watson Ada L. M. , Mahoney Richard J. , D'Amico Sheryle A. , Coviello Linda J. , Flaherty Lorraine , Yunis Edmond J.
Published: December 2008

We adapted the NIH Standard Protocol for HLA‐A, B, C typing to perform murine H‐2 typing. The assay is direct, measuring the cytotoxicity of the antiserum/cell/complement reaction with a supravital dye. This method is advantageous because it: utilizes peripheral blood lymphocytes (PBL) obtained from the tail vein; uses μl volumes of antiserum; is practical because the formalin fixed reactions need not be read immediately; involves standard and inexpensive cytotoxicity techniques; is easily interpreted and is readily reproducible.
The use of cellular reagents as an adjunct to typing for HLA‐DRw10
Authors: Ball Edward J. , Stastny Peter
Published: December 2008

Two human T cell lines recognizing DRw10 were generated. One line was directly alloreactive, while a second cloned line recognized mumps virus in the context of a DRw10‐like determinant. In panel studies, the lines responded only to DRw10 cells, and not to DR1 (DRw10‐) cells. When compared to 5 anti‐DRw10 sera, the cellular reagents gave virtually identical results. The generation and use of such cellular reagents may be of particular value for the identification of HLA‐D‐region specificites that are rare, poorly defined, or for which serologic typing reagents are limited.
HLA antigens in South India: I. Major groups of Tamil Nadu
Authors: Pitchappan RM. , Kakkanaiah V. N. , Rajashekar R. , Arulraj N. , Muthukkaruppan VR.
Published: December 2008

HLA‐A, B profile of 385 normal healthy individuals living in Tamil Nadu, India was studied by microlymphocytotoxicity testing. Antigen, gene and haplotype frequencies of this population were calculated and compared to those already available in the literature. The sample was further divided into four major groups and the frequencies calculated. Genetic distances between the various major groups were also calculated: the analyses suggest that these different groups may differ by origin. The study further reveals that in any HLA genetic and disease association studies in India, one should give due consideration to the caste system of the sample studied.
HLA‐DR2 and DR4 further defined by two new HLA‐D specificities (HTC) derived from Israeli Jewish donors: comparative study in Caucasian, Korean, Eskimo and Israeli populations
Authors: Mickelson Eric , Brautbar Chaim , Nisperos Brenda , Cohen Nadine , Amar Avraham , Kim Se Jong , Lanier Anne , Hansen John A.
Published: December 2008

Two newly‐identified HLA‐D antigens were characterized by testing selected homozygous typing cells (HTC) against responder panels derived from Caucasian. Korean, Alaskan Eskimo and Israeli Jewish populations. The first specificity, defined by typing cell “AZH”, is associated with DR2 haplotypes and is detected primarily in Israelis. The second specificity, defined by HTC “TAS”, is associated with DR4 haplotypes and is detected with relatively high frequency in Koreans and Alaskan Eskimos. The data indicate that HTC‐AZH and ‐TAS can be used to identify previously undefined splits or variants of lymphocyte‐defined (LD) determinants associated with DR2 and DR4 haplotypes. Further, the study demonstrates the utility of comparative population analysis in identifying and characterizing alleles encoded by the HLA‐D region and provides additional evidence of heterogeneity within the family of serologically‐defined HLA‐DR haplotypes.
The new HLA‐DRw6‐ and 8‐ associated HLA‐Dw HAG specificity defined by homozygous typing cell 9W 1802
Authors: Pawelec G. , Müller C. , Rehbein A. , Balko I. , Schunter F. , Wernet P.
Published: December 2008

Intrafamilial primary mixed lymphocyte culture (MLC) typing established that an HLA‐A, B, C homozygous, DP heterozygous donor HAG was homozygous for HLA‐Dw and behaved as a homozygous typing cell (HTC). Both haplotypes of the HTC were HLA‐DR identical, but could not be assigned a clear DR specificity, giving reactions with sera containing antibodies against DRw6, DRw8 and TA10. MLC checkerboard studies failed to assign the HTC HAG specificity to any established or provisional cluster, suggesting that it defined a new Dw specificity. Primed lymphocyte typing (PLT) clones derived from intra‐familial priming against either HAG haplotype displayed heterogeneous reactivity patterns. One clone was restimulated only by family members and unrelated donors positive for Dw HAG. Other clones were restimulated by determinants associated with either Dw8 or Dw6. Blocking of stimulation with monoclonal antibodies against different class II molecules suggested that while stimulatory determinants associated with Dw HAG and Dw8 were classifiable as HLA‐D related, those associated with Dw6 were of a DP‐like nature.
Automated reading of Propidium Iodide lymphocytotoxicity tests for HLA‐DR, MB, MT typing
Authors: Naipal A. M. I. H. , D'Amaro J. , Bruning J. W. , Leeuwen A. van , Rood J. J. van
Published: December 2008

The combination of the Propidium Iodide method and automatic reading and scoring with a microscope fluorimeter is an accurate, reproducible and stable procedure for HLA‐DR, MB and MT typing
HLA‐DP antigen and Takayasu arteritis
Authors: Dong Rui‐Ping , Kimura Akinori , Numano Fujio , Yajima Michiyoshi , Hashimoto Yuji , Kishi Yukio , Nishimura Yasuharu , Sasazuki Takehiko
Published: December 2008

Abstract: Sixty‐four patients with Takayasu arteritis and 317 healthy individuals in the Japanese population were examined for HLA‐A, ‐B and ‐C alleles by serological typing and for HLA‐DRY DQ and DP alleles by DNA typing using PCR/SSOP analysis. The frequencies of HLA‐Bw52, DRB1*1502, DRB5*0102, DQA1*0103. DQB1*0601 and DPB 1*0901 alleles were significantly increased and the frequencies of HLA‐Bw54, DRB1*0405, DRB4*0101, DQA1*0301, DQB1*0401 alleles were significantly decreased. Strong linkage disequilibria among the increased alleles and among the decreased alleles were evident in the Japanese population. Therefore, the combination or haplotype of HLA‐Bw52‐DRB1 *1502‐DRB5*0102‐DQA 1*0103‐DQB 1*0601‐DPA 1*02‐DPB 1*0901 may confer susceptibility to Takayasu arteritis while another combination or haplotype of HLA‐Bw54‐DRB1*0405‐DRB4*0101‐DQA1*0301‐DQB1 *0401 may confer resistance to the disease. Because this is the first evidence for the association between an HLA‐DP allele and Takayasu arteritis, we examined the nucleotide sequences of the DPB 1*0901 allele from a patient and her healthy relatives and found no difference. The disease is therefore not caused by a mutated DPB1 gene.
Sequence differences between HLA‐B and TNF distinguish different MHC ancestral haplotypes
Authors: Abraham L. J. , Leelayuwat C. , Grimsley G. , Degli‐Esposti M. A. , Mann A. , Zhang W. J. , Christiansen F. T. , Dawkins R. L.
Published: December 2008

Abstract: The HLA‐B locus is extremely polymorphic. We have sequenced a region, CL, telomeric of HLA‐B that also shows a high degree of allelic variation which we have shown previously by RFLP analysis. The polymorphism can be accounted for by sequence variation in duplicated, reiterated sequence elements called geometric elements. Comparison of the CL1 and CL2 sequences from the 57.1, 8.1, 18.2 and 7.1 ancestral haplotypes revealed that the lengths of the elements vary, both between the duplicated loci within a haplotype and between haplotypes, apparently because certain sequences are inserted or deleted. It is possible, using the polymerase chain reaction, to amplify these elements in genomic DNA from ancestral haplotypes for which sequence data of the CL region are not available and to obtain gel patterns which are characteristic of different ancestral haplotypes. The most striking feature of the data is the fact that the majority of the CL patterns are haplospecific; i.e. have a particular pattern that is unique for a particular ancestral haplotype and can be used to type these ancestral haplotypes. At least 12 different allelic patterns have been identified within a panel of 29 cell lines representing 16 ancestral haplotypes. For these 16 ancestral haplotypes, all examples of each haplotype have the same CL pattern. The haplotypic nature of the patterns confirms that ancestral haplotypes are conserved chromosomal segments and that coding and non‐coding sequences are identical by descent from a remote ancestor.
Development and characterization of a human monoclonal antibody probably detecting the leukocyte differentiation antigen CD39
Authors: Ikewakl Nobunao , Takabe Sachiko , Tsuji Kimiyoshi
Published: December 2008

Abstract: A human monoclonal IgM antibody, referred to as TU223, has been produced. The reactivity of TU223 was tested in various cells and cell lines by complement‐dependent microcytotoxicity test and fluorescence‐activated cell sorter analysis. The antigen defined by TU223 was expressed on Epstein‐Barr virus‐transformed B‐cell lines and on some Burkitt's lymphoma cell lines, but was not expressed on normal T cells, B cells or erythrocytes. In addition, expression of the antigen defined by TU223 was also induced on B cells activated by Epstein‐Barr virus or pokeweed mitogen, and on T cells activated by phytohemagglutinin, concanavalin A, pokeweed mitogen or recombinant interleukin‐2. However, no expression of the antigen detected by TU223 was induced at all on recombinant interleukin‐4‐treated B cells or macrophage‐like cell line U937. When the ability of TU223 and various mouse monoclonal antibodies to bind to human differentiation antigens was compared, interestingly, the reactivity of TU223 was found to be very similar to that of mouse monoclonal antibody CD23 (H107), which reacts with Fcs receptor 11. Two‐color analysis revealed that the antigen defined by TU223 is expressed on the cell surface of certain lymphoid cells expressing CD23 antigen. However, it can be concluded that the antigen defined by TU223 is clearly distinct from Fcs receptor 11, based on assay of cross‐blocking between HI07 and TU223. The surface antigen on B85 cells recognized by TU223 had the molecular size of 80–82 kiloDaltons as determined by immunoblotting analysis. In biological function, TU223 inhibited the generation of plaque‐forming cells when added to a pokeweed mitogen‐derived IgG‐secreting system on days 0 to 4. These findings suggest that TU223 recognizes a novel and functional antigen expressed on certain activated lymphoid cells.
Genetic exchange in the evolution of the human MHC class II loci
Authors: Kuhner Mary K. , Peterson Michael J.
Published: December 2008

Abstract: A total of 61 DNA sequences from human major histocompatibility class II loci were searched for statistical evidence of past genetic exchange (gene conversion or recombination). Among the 12 A‐locus sequences (derived from DPA1 and DQA1), 4 clusters indicating potential exchange events were found. Among the 49 B‐locus sequences (derived from DOB, DPB1, DPB2, DQB1, DRB1, DRB3, DRB4 and DRB5), 15 clusters were found. The clusters suggested short exchanges (less than 100 bp) within and between loci, and were concentrated in exon 2 (coding for the antigen binding site). The most striking feature of the results was the presence of an approximately 200‐bp region in the middle of B‐locus exon 2 which contained almost no locus‐specific substitutions, which were abundant elsewhere. This suggests either strong selection for locus specificity in the other regions of the gene or a history of frequent between‐locus exchange in this part of exon 2, which is involved in forming the antigen binding site.
HLA structure of the Sardinian population: A haplotype study of 551 families
Authors: Contu L. , Arras M. , Carcassi C. , Nasa G. La , Mulargia M.
Published: December 2008

A study on the HLA structure of the Sardinian population was carried out on 551 healthy unrelated,families representing all of the island districts. Altogether 2202 HLA‐A, B, Cw, DR individual haplotypes and 853 different haplotypes were determined. Cavalli‐Sforza and Edwards’genetic distance index for the total of 62 tested alleles showed a modest heterogeneity between one district and another (0.09–0.16). The genetic distance between Sardinians and the rest of the Italian population was 0.23 (0.22–0.26) and progressively increased in comparisons with cauca‐soids (0.26), negroids (0.34) and mongoloids (0.41). Sixty‐three two‐locus haplotypes with a high positive linkage disequilibrium were observed in our family sample. The percentages of two‐locus haplotypes in LD shared with other populations turned out to be 45% with caucasoids, 20% with negroids and 10% with mongoloids. The distribution of the A, B, Cw, DR haplotypes is shown with 673 of them represented only once or twice, and 10 (1.2%) 14–322 times each. Of the latter, 8 are extended haplotypes. 6 of which characterize the Sardinian population. The analysis of our data suggests that the present‐day Sardinian population is the result of a superposition of different populations, mainly consisting of caucasoids on a pre‐caucasoid paleo‐Mediterranean substratum.
HLA‐DPB typing using co‐digestion of amplified fragments allows efficient identification of heterozygous genotypes
Authors: Sawitzke Allen D. , Sawitzke Arleen L. , Ward R. H.
Published: December 2008

Twenty‐four alleles have been defined for HLA‐DPB based on their second exon sequences. This paper describes a novel method, co‐digested amplified fragment length polymorphisms (CAFLP), for assigning these alleles to heterozygous patients, as well as to homozygous cell lines. The method depends on co‐digestion of amplified DNA by restriction endonucleases and separation of the resultant fragments with polyacrylamide gel electrophoresis. Co‐digestion by selected restriction enzymes produces a set of readily discernible fragments that are unique for a given haplotype because the selected restriction sites occur in cis. Consequently, this method provides haplotype information not available from independent digests and allows all known heterozygous genotypes to be identified. Analysis of 103 trios of mother, father, and child, plus 120 normal caucasians, demonstrates the reliability and simplicity of this procedure. This simple typing method results in unambiguous assignment of all current HLA‐DPB genotypes in random samples with a high proportion of heterozygous individuals.
Analysis of HLA‐DR types of unexplained recurrent spontaneous aborters in the Japanese population by oligonucleotide‐DNA typing
Authors: Ito Koichi , Obata Fumiya , Tanaka Tadao , Tsutsumi Norio , Kashiwagi Noboru
Published: December 2008

To examine whether unexplained recurrent spontaneous abortion (URSA), defined as 2 or more consecutive spontaneous abortions, is correlated with a particular DR type in the Japanese population, we determined the HLA‐DR types of 82 primary aborters and 21 secondary aborters by DNA typing utilizing the polymerase chain reaction (PCR) and hybridization with sequence‐specific oligonucleotides (SSOs). The DR gene frequencies of the patient group were compared with those of a normal group at three different levels of DR‐definition (27, 13 and 11 DR types). At none of the three levels of comparison was any particular DR type with a frequency differing significantly between the patient and normal groups detected in Japanese URSA patients. Furthermore, we examined whether URSA was correlated with the degree of compatibility of HLA‐DR antigen within patients and their husbands. Comparison of the DR compatibility between patients and normal couples was made in two different ways, i.e., comparison of the numbers of couples with mismatches and comparison of the average number of mismatches. For either of these two comparisons, we observed no difference in DR compatibility between patients and normal couples. Our results suggest that URSA is not correlated with any particular DR type and that the condition cannot be explained simply by DR compatibility between husband and wife.
Analysis of HLA class II allogenotyping in Australian Aborigines and Papua New Guinea populations
Authors: Trejaut J. , Dunckley H. , Sullivan J. , Kennedy C. , Crane G.
Published: December 2008

Abstract: Human leukocyte antigen (HLA) class II allogenotyping has been applied to investigate the polymorphism of the DRB, DQB1, DQB2, DQA1, and DQA2 genes in Aborigines from the East Coast of Australia and in Melanesians from the Papua New Guinea North‐East Coast and Highlands. Three new DR/DQ arrangements were observed, DRw14/DQB1‐2b/DQA1‐1a and DRw5Nauru/DQB1‐3a/DQA1‐2 (in Australian Aborigines), and DR wSNauru/DQB1‐1a/DQA1‐1b (in Madang). DQA2 and DQB2 allogenotyping with TaqI and PstI digested genomic DNA revealed little polymorphism among the Papua New Guineans, with DQA2‐Xa1 and DQB2‐Xb1 the most common alleles in all the groups. However, the presence of DQA2‐Xa2 in Papuans and Australian Aborigines reflects the degree of admixture with Caucasoids while the DQA2‐Xa4 allele in Madang is probably a marker of Mongoloid origin.
HLA‐linked heat‐shock protein 70 (HSP70–2) gene polymorphism and celiac disease
Authors: Partanen Jukka , Milner Caroline , Campbell R. Duncan , Mäki Markku , Lipsanen Virpi , Koskimies Saija
Published: December 2008

The restriction enzyme Pstl showed a two‐allele restriction fragment length polymorphism (RFLP) marker when DNA polymorphism of the gene G8, a novel major histocompatibility complex (MHC) class III gene, was screened. The gene G8 is located ca. 4 kb centromeric of the heat‐shock protein 70 (HSP70) gene cluster. A more detailed mapping indicated that the polymorphic restriction site is actually located in the coding region of the adjacent HSP70–2 gene, where it has been earlier reported to cause a silent mutation. To estimate the frequency of this polymorphism in the normal population, 95 blood donors were analyzed: The gene frequency of the 8.5 kb (designated‘L’) allele was 0.45 and that of the 8.65 kb (‘U’) allele 0.55. However, when 19 families with patients suffering from celiac disease were studied, the gene frequencies in the affected haplotypes (L = 0.76, U = 0.24) significantly deviated from those observed in the normal population and in the non‐affected MHC haplotypes of these families (L = 0.48, U = 0.52). However, the association results from a strong association between the allele ‘L’and the MHC haplotype HLA B8 DR3, a known suspectibility marker of celiac disease. Only one patient, in fact, was negative for the well‐established class II haplotype markers DR3 or DR7. The data therefore confirm the crucial role of MHC class II in suspectibility to celiac disease, but due to a strong linkage disequilibrium within MHC the role of MHC class III genes in disease associations can not be ruled out.
HLA class I expression and HPV‐16 sequences in premalignant and malignant lesions of the cervix
Authors: Torres Luis Manuel , Cabrera Teresa , Concha Angel , Oliva Maria Rosario , Ruiz‐Cabello Francisco , Garrido Federico
Published: December 2008

A series of 10 normal cervix epithelia, 38 condylomas, 17 CIN (cervical intraepithelial neoplasm) I/II (low‐grade CIN), 10 CIN III (high‐grade CIN), 27 squamous cell carcinomas and 7 adenocarcinomas of the cervix were studied in paraffin‐embedded sections for the expression of MHC class I antigens, using antibodies against HLA antigens and the immunoperoxidase technique. A PCR technique was also used to evaluate the presence of HPV‐16 DNA. All samples from normal tissue, benign, premalignant and CIN III lesions expressed HLA class I antigens. However, 15% of the invasive carcinomas completely lacked HLA‐B and HLA‐C antigen expression, 20% presented a heterogeneous pattern and 2 cases lacked HLA‐B and HLA‐C heavy chain but retained β,‐microglobulin. MHC class I antigen expression on tumors was compared with clinicalpathological parameters. The absence of expression of HLA class I molecules was significantly associated with the Glanz histoprognostic index of malignancy. HPV‐16 sequences were detected in 60% of the condylomas, 88% of the CIN I/II, 80% of the CIN III and 82% of the cervical carcinomas. Eight‐six per cent of the tumors expressing HLA class I antigen presented HPV‐16, whereas only 40% of the nonexpressing tumors did. Our results lead us to the following conclusions: a) HLA class I losses occurred when the tumor became invasive, and in tumors of a more aggressive histological type; b) The presence of HPV‐16 was associated with tumors expressing HLA class I antigens.