bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumour cell killing using chemically engineered antibody constructs specific for tumour cells and the complement inhibitor CD59
Authors: HARRIS C L , KAN K S , STEVENSON G T , MORGAN B P 
Published: December 2003

SUMMARY
Immunotherapy using MoAbs is inefficient due to limited activation of human effectors by mouse antibodies and multiple protective mechanisms available to host cells against autologous complement. We have used chemically engineered antibody constructs and human complement in vitro to specifically target and kill neoplastic B lymphoid cells (Raji). Fab′γFcγ2 chimaeric antibody (specific for human CD37) was used to activate the classical pathway of human complement on Raji cells, whilst CD59 was neutralized using one of two different bispecific F(ab′γ)2 antibody constructs which contained both cell-targeting (anti-CD19 or anti-CD38) and CD59-neutralizing moieties. When either bispecific construct was used to neutralize CD59, 15–25% of cells were lysed. If CD55 was also neutralized using specific antibody, Raji cells were efficiently killed (70% lysis). When added to a mixture of target (Raji) and bystander (K562) cells, one bispecific antibody (anti-CD38 × anti-CD59) could be specifically delivered to Raji, avoiding significant uptake on CD59-expressing bystander cells (K562). The second bispecific antibody (anti-CD19 × anti-CD59) bound equally well to either cell type. Cell-specific targeting was dependent upon combination of a low-affinity anti-CD59 Fab′γ with a high-affinity anti-tumour cell Fab′γ. When Raji and K562 cells were mixed and incubated with a combination of the engineered constructs and anti-CD55 antibodies, Raji cell lysis (30–40%) was observed in the absence of K562 killing. We propose that combinations of these constructs may be of use for treatments such as ex vivo purging of autologous bone marrow or in vivo targeting of tumour cells.
Role of γδ T lymphocytes in the development of Behc¸et's disease
Authors: YAMASHITA N , KANEOKA H , KANEKO S , TAKENO M , ONEDA K , KOIZUMI H , KOGURE M , INABA G , SAKANE T 
Published: December 2003

SUMMARY
Phenotypic and functional properties of γδ T cells, which play an important role in mucocutaneous immunity, were examined to elucidate whether immunological abnormality in Behc¸et's disease may be related to a specific T cell population. We found that CD45RA+Vγ9+Vδ2+γδ T cells, which constitute a minor population of γδ T cells in healthy individuals, were increased in number in Behc¸et's disease irrespective of disease activity. This CD45RA+ subset of γδ T cells in the active, but not inactive, phase of this disease expressed IL-2Rβ and HLA-DR, suggesting that they are activated in vivo in active Behc¸et's disease. In addition, the CD45RA+γδ T cells produced extreme amounts of tumour necrosis factor and contained perforin granules. These data indicate that a phenotypically distinct subset of γδ T cells, CD45RA+CD45RO−Vγ9+Vδ2+, may contribute to immunological abnormalities which may lead to complexity of pathophysiology in Behc¸et's disease.
Proliferation and production of interferon-gamma (IFN-γ) and IL-4 in response to Staphylococcus aureus and Staphylococcal superantigen in childhood atopic dermatitis
Authors: CAMPBELL D E , KEMP A S 
Published: December 2003

SUMMARY
We have examined the cell-mediated immunity (CMI) to Staphylococcus aureus (S. aureus) and Staphylococcal enterotoxin B (SEB) in peripheral blood mononuclear cells (PBMC) from children with atopic dermatitis (AD) and from non-atopic child controls by measurement of proliferative responses and production of the cytokines IFN-γ and IL-4. PBMC from children with AD showed significantly higher proliferative responses to both S. aureus (P &lt;0.01) and SEB (P &lt; 0.05). Despite this enhanced proliferation, production of IFN-γ in response to S. aureus (P &lt;0.001) and SEB (P &lt; 0.01) from these PBMC was significantly diminished. In contrast, PBMC from children with AD were significantly more likely to produce IL-4 in response to S. aureus (P &lt; 0.01). These findings demonstrate in vitro heightened CMI to S. aureus in children with AD, and implicate S. aureus as a potent inflammatory stimulant. Impaired IFN-γ production to S. aureus in vivo may result in failure to eradicate S. aureus from skin. The organism's persistence on skin would contribute to inflammation by causing continued T cell activation and release of pro-inflammatory mediators.
Analysis of rearranged immunoglobulin heavy chain variable region genes obtained from a bone marrow transplant (BMT) recipient
Authors: GLAS A M , NOTTENBURG C , MILNER E C B 
Published: December 2003

SUMMARY
Haematopoietic stem cell transplantation has been used for the treatment of many different malignant and non-malignant diseases. The immune system of transplant recipients must be regenerated from the transplant inoculum, and it is not surprising that many transplant recipients are deficient in generating specific antibody responses to exogenous stimuli. This B cell immunodeficiency in these patients is associated with clinically significant infections, although the underlying mechanism remains unknown. We have previously shown that the pattern of usage of VH genes was similar between healthy subjects and BMT recipients, indicating that the immunodeficiency was not due to a dramatic imbalance in VH utilization. However, motif-specific hybridization analysis indicated that the accumulation of somatic mutations was much greater among rearrangements in controls than in BMT recipients. The failure of BMT recipients to accumulate somatic mutations in rearranged VH genes correlates with an absence of IgD− B cells, and is consistent with a defect in antigen-driven B cell responses. In the current study, which extends those findings, we have determined the nucleotide sequences of 68 heavy chain rearrangements from one patient as well as 39 rearrangements from a healthy control. Analysis of these sequences made possible a more precise definition of variable region configuration and of the status of somatic mutation in this BMT recipient. The results validate the hybridization data and support the conclusion that, although somatic hypermutation and, by inference, antigen-driven responses are detected in BMT recipients, they are deficient compared with healthy subjects as late as 1 year after transplant.
A bias in the αβ T cell receptor variable region gene usage in Takayasu's arteritis
Authors: NITYANAND S , GISCOMBE R , SRIVASTAVA S , HJELMSTRO¨M P , SANJEEVI C B , SINHA N , GRUNEWALD J , LEFVERT A K 
Published: December 2003

SUMMARY
Takayasu's arteritis (TA) is a chronic large vessel vasculitis with a predilection for the aortic arch and its branches. T lymphocytes may be important in the pathogenesis, as they have been found to infiltrate the vascular lesions. To elucidate further the role of T cells in the disease, we studied circulating CD4+ and CD8+ T cells, expression of the activation marker (HLA-DR), marker for naive (CD45RA) and primed (CD45RO) cells and the different variable α/β (AV/BV) gene segments on them. The TCR AV/BV repertoire was studied using a panel of 15 T cell receptor (TCR) V-specific MoAbs by flow cytometry in 18 patients and 23 age- and sex-matched controls. Patients had a higher percentage of AV12S1 (P &lt; 0.05), BV6S7 (P &lt; 0.05) and BV9 (P &lt; 0.001)-bearing CD4+ cells. Patients also had a higher frequency of expansions, i.e. of T cell populations with an abnormally high TCR AV/BV gene usage. In patients' CD4+ subset of cells, there were 22 expansions out of 231 analyses (9.5%), whereas in controls, four were expanded out of 310 analyses (1%) (P &lt; 0.001). For CD8+ cells, the frequency of expansions was 32 in 231 analyses (14%) in patients and nine out of 304 analyses in controls (3%) (P &lt; 0.01). In addition, there was a correlation between CD4+ expansions and disease activity; nine out of 10 patients with active disease in comparison with two out of eight patients with inactive disease (P &lt; 0.01) had an expansion. Some of the expanded populations in patients were phenotypically characterized and observed to be HLA-DR&lt;, CD28&lt;, CD45RA&lt; and CD45RO+, with a greater proportion being CD45RO+. Patients had a higher percentage of expression of HLA-DR on both CD4+ and CD8+ T cells (P &lt; 0.01). The percentages of naive and primed CD4+ and CD8+ T cells, γδ+ T cells and natural killer cells were comparable to those in the control group.
High intratumoural level of cytokines mediates efficient regression of a rat histiocytoma
Authors: KHAR A , MURALIKRISHNA K , VARALAKSHMI C H 
Published: December 2003

SUMMARY
We have studied the role of cytokines in the spontaneous regression of AK-5 histiocytoma in syngeneic rats. Animals in which the tumour regresses show high levels of cytokines in the serum compared with animals which succumb to the tumour, and levels of IL-2, IL-4, IL-12, interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α) are significantly higher in tumour tissue of the former. Thus there is an association between rejection of the tumour and the levels of cytokines present in the tumour mass. Our results also suggest a predominant Th1-type of response in those rats that display early tumour rejection.
Altered sialylation of alveolar macrophages in HIV-1-infected individuals
Authors: PERRIN C , GIORDANENGO V , BANNWARTH S , BLAIVE B , LEFEBVRE J-C 
Published: December 2003

SUMMARY
In previous studies, we have demonstrated that O-glycans at the surface of HIV-1-infected cell lines were hyposialylated. Moreover, we and others have shown that HIV+ individuals produced autoantibodies that react with hyposialylated CD43, on T cell lines. Since the autoantigen responsible for this abnormal immune response was not easily found in the peripheral blood cells of corresponding patients, we searched for its possible presence in other sites. Using fluorescence staining of alveolar macrophages with various lectins, we show that the binding of the PNA lectin specific for asialo O-glycans is much more efficient on cells from HIV-1-infected individuals. Moreover, the degree of reactivity of PNA is correlated with the clinical stage of the illness.
Blood gases in pregnancy at sea level and at high altitude
Authors: McAuliffe Fionnuala , Kametas Nikos , Krampl Elisabeth , Ernsting John , Nicolaides Kypros 
Published: December 2003

Objective
1. To measure blood gases and minute ventilation in healthy women with normal pregnancies, compare with non‐pregnant women both at sea level and at high altitude; 2. to relate the results at altitude with duration of residence there.Design
Cross‐sectional study.Setting
Antenatal clinics at sea level in Lima, Peru and at high altitude 4300m in Cerro de Pasco, Peru.Population
A total of 304 normal pregnant women between 7 and 41 weeks of gestation were studied, including 112 who lived at sea level and 192 at high altitude (4300m). For comparison 38 non‐pregnant women (19 at sea level and 19 at high altitude) were also studied.Methods
Arterialised blood gases, haemoglobin, pulse oximetry and minute ventilation were measured once in each woman.Main
outcome measures
PO2, PCO2, pH, haemoglobin, oxygen saturation, arterial oxygen content and minute ventilation and their relationship to gestation.Results
PO2, PCO2, bicarbonate, base excess and oxygen saturation were lower in pregnancies at high altitude compared with sea level; pH, haemoglobin, arterial oxygen content and minute ventilation were higher. At high altitude oxygen saturation and haemoglobin decreased towards term resulting in a fall in arterial oxygen content at the end of pregnancy. Women whose family had lived at high altitude for at least three generations maintained their oxygenation throughout pregnancy better than women whose family had lived there for less than three generations.Conclusions
In pregnancy at high altitude maternal adaptation appeared adequate in the first trimester but declined towards term. However, maternal oxygenation was maintained in those whose family had lived longest at high altitude suggesting a beneficial adaptation to a hypoxic environment, occurring over generations.
Outcome for children born after in utero laser ablation therapy for severe twin‐to‐twin transfusion syndrome
Authors: Sutcliffe A.G. , Sebire N.J. , Pigott A.J. , Taylor B. , Edwards P.R. , Nicolaides K.H. 
Published: December 2003

Objective
To examine the postnatal development of a group of children born after in utero laser ablation therapy for severe twin‐to‐twin transfusion syndrome.Design
Retrospective cohort outcome study involving assessment of neurodevelopment and physical well being.Setting
Harris Birthright Centre, King's College Hospital, London.Participants
Twins and singleton survivors treated via laser ablation therapy for twin‐to‐twin transfusion syndrome over a four‐year period.Methods
Of 54 families contacted to participate in the study, who had been treated for twin‐to‐twin transfusion syndrome during a four‐year period, 24 families attended for paediatric assessment; 12 pairs of twins and 12 singleton survivors were assessed for perinatal, neurological and neurodevelopmental outcome using the Griffiths scales of mental development. A further 20 families were assessed via a proforma after contact with their general practitioner. A comparison of these groups showed no significant differences in sociodemographic factors or severity of disease between responders (44 families, 81.5%) and non‐responders (10 families).Results
The group of children assessed by a paediatrician had low birthweight (1619g donor, 1814g recipient, 1877g singleton) and had been born preterm (33 weeks twins, 31.2 weeks singleton) with attendant increased resuscitation, neonatal unit admission (mean 40 days) and instrumental delivery. Mean Griffiths scores were within the normal range of ability (91.2 donor vs 97.7 recipient and 101.6 singletons) with the only significant difference being in the locomotor subscale where donor (82.6) and recipient (85.3) were less than singletons: ‐99.1 (P<0.05). There was no cerebral palsy in the singleton survivors, but there were five cases in the twin group. All except one affected child (with quadriplegia) had mean Griffiths scores in the normal range. In the GP proforma group there was one case, in a twin, of cerebral palsy.Conclusion
The overall cerebral palsy rate was 9%: 0% in the singleton survivors group and 13.3% in the twin survivors group. This pilot data highlights the need for careful long term follow up of children affected by twin‐to‐twin transfusion syndrome.
Clinical, provider and sociodemographic predictors of late initiation of antenatal care in England and Wales
Authors: Kupek Emil , Petrou Stavros , Vause Sarah , Maresh Michael 
Published: December 2003

Objective
To identify factors that are predictive of late initiation of antenatal care in England and Wales.Design
A multivariate binomial regression model was constructed to examine the association between clinical, provider and sociodemographic characteristics and late initiation of antenatal care.Setting
Nine maternity units in Northern England and North Wales.Population
A total of 20,771 women with a singleton pregnancy who delivered a liveborn or stillborn baby between 1 August 1994 and 31 July 1995. All analyses were based on the 17,765 (85.5%) women for whom information on gestational age at initial presentation for antenatal care and other variables incorporated into the regression model was retrievable from the case recordsResults
Primiparous women of high obstetric risk were 13.4% more likely to initiate antenatal care after 10 weeks of gestation than a low risk reference group (adjusted OR 1.134, 95% CI 1.011, 1.272; P= 0.0312), and 34.3% more likely to initiate antenatal care after 18 weeks of gestation (adjusted OR 1.343, 95% CI 1.046, 1.724; P= 0.0208). This association between high obstetric risk status and late initiation of antenatal care was not replicated among multiparous women. When the effects of other independent variables on gestational age at booking were examined, the following characteristics were associated with failure to initiate antenatal care by 10 weeks of gestation (P≤ 0.05): maternal age at booking, smoking status, ethnicity, type of hospital at booking, the planned pattern of antenatal care and the planned place of delivery. Adopting a criterion of 18 weeks of gestation exacerbated the association between clinical and sociodemographic characteristics and late initiation of antenatal care, but appeared to dilute the association between provider characteristics and late initiation of antenatal care.Conclusions
There is a pressing need for further research to identify the specific concerns of late bookers, to identify areas where new interventions might encourage the uptake of services and to gauge the likely impact of increased dissemination of information about the availability of antenatal care services.
Combined ultrasound and biochemical screening for Down's Syndrome in the first trimester: a Scottish multicentre study
Authors: Crossley Jennifer A. , Aitken David A. , Cameron Alan D. , McBride Elizabeth , Connor J. Michael 
Published: December 2003

Objective
To evaluate the use of ultrasound measurements of fetal nuchal translucency (NT) obtained in a routine antenatal clinic setting in combination with appropriate biochemical markers as a first trimester screening test for Down's Syndrome.Design
Multicentre observational study.Setting
Fifteen Scottish maternity units.Population
Pregnant women (n= 17,229) attending routine antenatal clinics at 10–14 weeks of gestation.Methods
NT measurements were attempted in all women along with the measurement of maternal serum free beta human chorionic gonadotrophin (FβhCG) and pregnancy‐associated plasma protein‐A (PAPP‐A). All results were converted to multiples of the appropriate gestational median (MoM) and using a statistical model the risk of an affected pregnancy was derived. No results were given to participating women but all were offered routine second trimester biochemical screening. All cases of Down's Syndrome within the study group were ascertained and the detection rate for each marker was estimated.Main outcome measures
Success rate of obtaining NT measurements and overall effectiveness of ultrasound and biochemical markers individually and in combination for the detection of Down's Syndrome pregnancies.Results
NT measurements were obtained in 72.9% of women and blood samples in 98.4%. Forty‐five cases of Down's Syndrome were ascertained (2.6/1000). NT measurements were obtained in 37 cases (median NT 1.65 MoM), blood samples in 42 cases and both NT and blood in 34 cases. In combination with the a priori maternal age risk, observed detection rates at a 5% false positive rate were 20/37 (54%) for NT, 23/42 (55%) for FβhCG and PAPP‐A and 28/34 (82%) for a combination of NT, FβhCG and PAPP‐A using a cutoff risk of 1:250. The effect of failing to obtain NT measurements in all cases reduces the overall detection rate to 62% (i.e. 28/45) if the entire series of affected pregnancies within the study group is considered.Conclusions
NT in combination with appropriate serum markers has the potential to detect over 80% of Down's Syndrome fetuses in early pregnancy. However, NT measurement is highly operator‐dependent. It requires training, external quality control and adequate time to allow accurate measurement, otherwise suboptimal performance will result.
Sterilisation during unplanned caesarean sections for women likely to have a completed family—should they be offered? Experience in a country with limited health resources
Authors: Verkuyl D.A.A. 
Published: December 2003

Objective
To determine if it is proper to give a woman of higher parity who needs at short notice a caesarean section the option of a tubal ligation.Design
Retrospective study.Setting
Maternity unit of a tertiary hospital in Bulawayo, Zimbabwe.Population
Women of higher parity who were delivered by an emergency caesarean section, by an elective caesarean section or vaginally and who had been asked or not asked whether they wanted a tubal ligation.Methods
A postal questionnaire and visits to the participants.Main outcome measures
Satisfaction with (in)fertility after having had, or not had, the option of a tubal ligation with the last delivery.Results
In women who had an emergency caesarean section and who were successfully followed up, 301/418 (72.0%) had been offered a tubal ligation and 241/301 (80.1%) accepted. Of the 301 women, 269 (89.4%) were happy with the outcome. Thirty‐two women were unhappy (of whom 6 had tubal ligation, 24 had declined a sterilisation and in 2 cases the doctor forgot to do the sterilisation). Of the 117/418 women not offered a tubal ligation, 75/117 (64.1%) regretted not having had one. The relative risk of being unhappy with the consequences of not being offered tubal ligation compared with being given this option was 6.0 (95% CI 4.2–8.6, P < 0.001). Tubal ligations performed during emergency caesarean sections had no higher regret rate (2.5%) in this setting than those performed during elective caesarean sections (3.2%) and not much higher than postpartum sterilisations (0.5%). Women who did not have a tubal ligation during an emergency caesarean section regretted this (56.4%) significantly more often than women who did not have a tubal ligation with an elective caesarean section (34.6%) or after vaginal delivery (45.0%) (P < 0.01 and P < 0.02, respectively).Conclusions
We found no evidence that the need to take an urgent decision resulted in more regret following tubal ligation. Women were far more likely to regret declining a tubal ligation (40%) than regret accepting one (2.5%). In this setting, some women are more likely to die of the next pregnancy than to regret an emergency tubal ligation.
The association between maternal HIV‐1 infection and pregnancy outcomes in Dar es Salaam, Tanzania
Authors: Coley Jenny L. , Msamanga Gernard I. , Fawzi Mary C. Smith , Kaaya Sylvia , Hertzmark Ellen , Kapiga Saidi , Spiegelman Donna , Hunter David , Fawzi Wafaie W. 
Published: December 2003

Objective To examine the association between maternal HIV infection and pregnancy outcomes controlling for potential confounding factors among a cohort of HIV‐uninfected and HIV‐infected pregnant women in Dar es Salaam, Tanzania.Design Prospective cohort study.Methods A cohort of 1078 HIV‐infected and 502 HIV‐uninfected pregnant women between 12 and 27 weeks of gestation were enrolled and followed up until delivery. Multiple regression models were used to compare the risk of adverse pregnancy outcomes among HIV‐uninfected women with those among HIV‐infected women overall, and separately among asymptomatic or symptomatic HIV‐infected women.Results No significant differences between HIV‐uninfected women and HIV‐infected women were observed in risks of fetal loss or low birthweight or in the weight, head circumference and gestational age of infants at birth. HIV‐infected women were more likely to have severe immature infants (<34 weeks) than HIV‐uninfected women (multivariate RR 1.54 [95% CI 0.90–2.48]; P=0.05). There was a significantly higher risk of low birthweight (RR 2.29, 95% CI 1.34–3.92; P=0.03) and prematurity (<37 weeks) (RR 1.93, 95% CI 1.35–2.77; P=0.0003) among symptomatic HIV‐infected women when compared with HIV‐uninfected women.Conclusion HIV‐infected women, particularly those who are symptomatic, are at a higher risk of adverse pregnancy outcomes.