bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reductions of Rubisco Activase by Antisense RNA in the C4 Plant Flaveria bidentis Reduces Rubisco Carbamylation and Leaf Photosynthesis
Authors: von Caemmerer Susanne , Hendrickson L. , Quinn V. , Vella N. , Millgate A.G. , Furbank R.T. 
Published: January 2005

Abstract
To function, the catalytic sites of Rubisco (EC 4.1.1.39) need to be activated by the reversible carbamylation of a lysine residue within the sites followed by rapid binding of magnesium. The activation of Rubisco in vivo requires the presence of the regulatory protein Rubisco activase. This enzyme is thought to aid the release of sugar phosphate inhibitors from Rubisco's catalytic sites, thereby influencing carbamylation. In C3 species, Rubisco operates in a low CO2 environment, which is suboptimal for both catalysis and carbamylation. In C4 plants, Rubisco is located in the bundle sheath cells and operates in a high CO2 atmosphere close to saturation. To explore the role of Rubisco activase in C4 photosynthesis, activase levels were reduced in Flaveria bidentis, a C4 dicot, by transformation with an antisense gene directed against the mRNA for Rubisco activase. Four primary transformants with very low activase levels were recovered. These plants and several of their segregating T1 progeny required high CO2 (&gt;1 kPa) for growth. They had very low CO2 assimilation rates at high light and ambient CO2, and only 10% to 15% of Rubisco sites were carbamylated at both ambient and very high CO2. The amount of Rubisco was similar to that of wild-type plants. Experiments with the T1 progeny of these four primary transformants showed that CO2 assimilation rate and Rubisco carbamylation were severely reduced in plants with less than 30% of wild-type levels of activase. We conclude that activase activity is essential for the operation of the C4 photosynthetic pathway.
Tryptophan 64 → arginine polymorphism of β‐3‐adrenergic receptor in Chilean women with polycystic ovary syndrome
Authors: Pérez‐Bravo Francisco , Echiburú Bárbara , Maliqueo Manuel , Santos José Luis , Sir‐Petermann Teresa 
Published: January 2005

SummaryObjective  To establish the frequency of the Trp64Arg polymorphism of the β3 adrenergic receptor (ADRB3) in women with polycystic ovary syndrome (PCOS) from a Chilean population, focusing particularly on the interaction with body weight. In addition, we evaluated the relationship of the Trp64Arg variant with other metabolic components of this syndrome.Patients and Design  In a case–control design study, a total of 106 women with clinical and hormonal evidence of PCOS and 82 healthy women (HW) were evaluated.Measurements  An oral glucose tolerance test (OGTT) was performed and serum glucose and insulin were measured before the glucose load and 30, 60, 90 and 120 min after. Lipid profile was determined in the basal sample. Insulin resistance was assessed by the homeostatic model assessment (HOMAIR) and insulin sensitivity index (ISI) composite. A polymerase chain reaction restriction fragment length polymorphism (PCR‐RFLP) analysis was performed to determine the Trp64Arg polymorphism of ADRB3.Results  The frequency of the heterozygous condition was similar between PCOS and HW (39%vs. 35%). Only two subjects were homozygous for arginine, both belonging to the PCOS group and having a body mass index (BMI) > 30 kg/m2. In the crude analysis, hypothesis tests and odds ratios show that there is no evidence of association between the ADRB3 Trp64Arg variant and PCOS (P = 0·47). Moreover, when data were stratified by BMI categories, the statistical test for interaction between Trp64 carrier status and obesity was not significant (P = 0·29). This variant was present in 52% of the obese PCOS patients and 40% of the obese HW. In normal weight and obese PCOS carriers, the presence of the Trp64Arg variant was associated with high triglyceride (TG) levels. A major effect of the Trp64Arg variant on insulin resistance parameters could not be demonstrated.Conclusions  The frequency of the Trp64Arg polymorphism was similar in healthy women and PCOS women, and a possible interaction between the effect of this variant and obesity in PCOS could not be demonstrated. However, our results showed an association between triglyceride levels and the presence of this genetic variant in PCOS women.
Mutation analysis of POUF‐1, PROP‐1 and HESX‐1 show low frequency of mutations in children with sporadic forms of combined pituitary hormone deficiency and septo‐optic dysplasia
Authors: Rainbow L. A. , Rees S. A. , Shaikh M. G. , Shaw N. J. , Cole T. , Barrett T. G. , Kirk J. M. W. 
Published: January 2005

SummaryObjectives  Mutations in the genes encoding the transcription factors PROP1 and POUF‐1 (Pit‐1) have been reported as common causes of combined pituitary hormone deficiency (CPHD), and HESX1 mutations have been identified in children with septo‐optic dysplasia (SOD). There are few data on UK children. We have performed mutation analysis in a large cohort of affected children within the West Midlands region to assess the feasibility of a screening strategy for molecular diagnosis in CPHD and SOD.Design and Patients  The three coding exons of PROP1, and six exons of POUF‐1 in 27 children from 26 families with CPHD, and three exons of HESX1 in 23 children from 22 families with SOD were directly sequenced from a well‐characterized regional cohort.Results  We identified a C to T transition in exon 6 of POUF‐1, resulting in a known missense mutation (R271W) in a mother and daughter from one family with CPHD. We also found a novel homozygous T to C transition in exon 6 of POUF‐1, resulting in a missense mutation (F233L) in a twin with CPHD. This mutation was excluded in 100 ethnically matched control alleles. We did not identify any mutations in the PROP1 gene or HESX1. The median maternal age at delivery for the CPHD children was 27 years, compared to 21 years for the mothers of SOD children (P = 0·04).Conclusions  Mutations in POUF‐1, PROP1 and HESX1 are rare causes of CPHD and SOD, respectively, in children from the West Midlands. In particular, we did not confirm the reported ‘hotspot’ in PROP1. A screening strategy that targets familial cases is highly likely to increase the mutation yield. The young maternal age at conception of children with SOD and potential teratogen exposure indicate the predominance of environmental factors in this condition compared with CPHD.
High prevalence of long‐term cardiovascular, neurological and psychosocial morbidity after treatment for craniopharyngioma
Authors: Pereira Alberto M. , Schmid Eva M. , Schutte Pieter J. , Voormolen Joan H. C. , Biermasz Nienke R. , Van Thiel Sjoerd W. , Corssmit Eleonora P. M. , Smit Jan W. A. , Roelfsema Ferdinand , Romijn Johannes A. 
Published: January 2005

SummaryIntroduction  The treatment of craniopharyngiomas is associated with long‐term morbidity.Aim of the study  To assess the long‐term functional outcome and mortality rates after treatment for craniopharyngiomas, we audited our data with special focus on cardiovascular, neurological and psychosocial morbidity.Patients and methods  Between 1965 and 2002, 54 consecutive patients underwent surgery for craniopharyngiomas at the Leiden University Medical Centre (LUMC). Fifteen patients (25%) received additional postoperative radiation therapy. The median follow‐up period was 10 years (range 1–37 years).Results  Long‐term cure rate was 82% and long‐term recurrence rate 18%. Visual fields/visual acuity stabilized or improved in 74% of cases. The long‐term prevalence rate of hypopituitarism was 89%. In addition, long‐term cardiovascular, neurological and psychosocial morbidity rates were high: 22% (risk factors 57%), 49% and 47%, respectively. Female sex was an independent predictor of increased cardiovascular, neurological and psychosocial morbidity (odds ratio 3·78, P = 0·031). Ten patients (18%) died during an 828 person‐year follow‐up. The actuarial patient survival rates 5, 10 and 20 years after the initial operation were 95, 85 and 85%, respectively. The standardized mortality ratio (SMR) was 2·88 [95% confidence interval (CI) 1·35–4·99].Conclusion  Craniopharyngioma is associated with excessive long‐term multisystem morbidity and mortality, especially in female patients, despite a high cure rate. These observations indicate that dedicated long‐term follow‐up of these patients is required. The purpose of the follow‐up should be: first, to look for recurrences and to ensure appropriate endocrine replacement, especially oestrogen replacement in premenopausal females; and second, to achieve intensive control of glucose, lipids, blood pressure and weight, as in any other patient with increased risk for cardiovascular disease.
Evidence for increased ovarian follicular activity in girls with premature thelarche
Authors: Crofton Patricia M. , Evans Nancy E. M. , Wardhaugh Barbara , Groome Nigel P. , Kelnar Christopher J. H. 
Published: January 2005

SummaryObjective  Inhibin B is produced by granulosa cells in small antral follicles, under the influence of FSH, and has a paracrine role in oestradiol synthesis. To test the hypothesis that premature thelarche is associated with increased FSH‐driven follicular development, we measured inhibin B and FSH in girls with premature thelarche, girls with central precocious puberty (CPP) and controls matched either for age or breast stage.Patients  Blood samples were collected from 11 girls with premature thelarche (breast stage 2, aged 0·4–5·6 years), 11 prepubertal controls age‐matched to the thelarche girls (0·5–5·4 years), 13 girls with CPP (breast stage 2, 3·9–8·2 years) and nine normal pubertal controls (breast stage 2, 9·0–13·2 years).Measurements  Dimeric inhibin B was measured in plasma by double‐antibody enzyme‐linked immunoassay and FSH by immunoradiometric assay. Pelvic ultrasonography was performed on all girls with CPP and 10/11 girls with premature thelarche.Results  Seven of the 13 girls with CPP and three of the eight girls with premature thelarche whose ovaries could be visualized had visibly nonhomogeneous ovarian structure on ultrasonography. Girls with premature thelarche had inhibin B and FSH concentrations higher than those in their age‐matched controls (P < 0·01 and P < 0·05, respectively), and similar to those observed in girls with CPP and normal pubertal controls matched for breast stage. In thelarche girls, as in precocious puberty girls and normal pubertal controls, inhibin B and FSH were positively related (rs = 0·54–0·61).Conclusions  This study provides further evidence that premature thelarche is associated with enhanced follicular development, similar to that which occurs in early puberty, probably under the influence of FSH.
The long‐term efficacy of conventional radiotherapy in patients with GH‐secreting pituitary adenomas
Authors: Minniti Giuseppe , Jaffrain‐Rea Marie‐Lise , Osti Mattia , Esposito Vincenzo , Santoro Antonio , Solda Francesca , Gargiulo Patrizia , Tamburrano Guido , Enrici Riccardo Maurizi 
Published: January 2005

SummaryObjective  To assess the long‐term efficacy and safety of conventional radiotherapy (RT) in the control of acromegaly according to recent stringent criteria of cure.Design  A retrospective longitudinal study.Patients and Methods  Forty‐seven patients with active acromegaly were treated with conventional RT between 1982 and 1994. All patients were first operated on and successively irradiated at a dose of 45–50 Gy in 25–28 fractions for persistent (n = 40) or recurrent (n = 7) disease.Measurements  Long‐term GH/IGF‐I secretion and local tumour control were evaluated regularly, and possible side‐effects were searched for systematically, especially in terms of secondary endocrine dysfunction. Biochemical cure of acromegaly was defined by glucose‐suppressed plasma GH levels below 1 µg/l during an oral glucose tolerance test (OGTT) and normal age‐corrected IGF‐I values.Results  The 5‐, 10‐ and 15‐year overall survival rates were 98%, 95% and 93%, respectively. Suppression of GH during OGTT was seen in 9% of patients at 2 years, 29% at 5 years, 52% at 10 years, and 77% at 15 years. Age‐corrected IGF‐I levels were normal in 8% of patients 2 years after RT, and this proportion increased to 23%, 42% and 61% after 5, 10 and 15 years, respectively. Normalization of GH/IGF‐I mainly depended on pre‐RT levels. Local tumour control was 95% at 5, 10 and 15 years after treatment. Late toxicity was mainly represented by progressive hypopituitarism, which was present in 33% of patients at baseline and increased to 57%, 78% and in 85% of patients at 5 10 and 15 years after RT, respectively.Conclusion  Conventional RT is effective in the long‐term control of GH‐secreting pituitary adenomas, although with a high prevalence of progressive hypopituitarism. At present, it remains a suitable option in acromegalic patients uncontrolled by surgery or medical therapy.
Metastasis to the thyroid diagnosed by fine‐needle aspiration biopsy
Authors: Kim Tae Yong , Kim Won Bae , Gong Gyungyub , Hong Suck Joon , Shong Young Kee 
Published: January 2005

SummaryBackground  Metastasis to the thyroid is uncommon, but the number of cases seems to have increased in recent years. This increase may be related to more frequent use of fine‐needle aspiration biopsy (FNAB) in any suspected case.Design  A retrospective review of patients with thyroid metastasis diagnosed by FNAB at the Asan Medical Centre.Patients  Twenty‐two patients who were seen at the Asan Medical Centre between 1997 and 2003. Median age was 55 years with range between 34 and 74 years.Results  Fourteen patients presented with a palpable thyroid nodule. Eight patients had an impalpable thyroid nodule that was found incidentally during the various imaging studies. The breast (five patients) was the most common primary site followed by the kidney (three), colon (three) and lung (three). FNAB confirmed metastatic disease in 19 patients and raised suspicion in three patients. The suspicion of metastasis to the thyroid was confirmed by Tru‐cut needle core biopsy in one patient and surgery in two patients. Thyroid metastases were found during the initial work‐up for primary tumour in eight patients. In the remaining 14 patients, the interval from diagnosis of primary tumour to the detection of thyroid metastasis varied from 8 months to 15 years, with a median of 54 months. Fifteen patients had metastatic disease elsewhere at the time of presentation. Ten patients received chemotherapy. Radiotherapy was used in two patients. Seven patients are still alive, with one patient disease free for 16 months following resection of the thyroid metastasis.Conclusions  Thyroid metastases are uncommon but can be detected more frequently with routine use of FNAB. Breast cancer is the most common tumour that metastasizes to the thyroid. They usually occur when there are metastases elsewhere, sometimes many years after the diagnosis of the original primary tumour and show poor prognosis in general.
Changes in thyroid hormone state in children receiving chemotherapy
Authors: Van Santen H. M. , Thonissen N. M. , De Kraker J. , Vulsma T. 
Published: January 2005

SummaryObjective  The concentrations of thyroid function determinants may change during severe illness. Our goal was to quantify their changes in children with cancer during chemotherapy, and to correlate them to clinical condition and type of drugs.Design  During a 3‐month period all patients admitted for chemotherapy to the paediatric oncology ward were evaluated for inclusion. Patients with brain tumours, neuroblastoma (cranio)spinal irradiation and use of dexamethasone before the first blood sample were excluded.Measurements  Plasma concentrations of T4, T3, rT3, thyroxine‐binding globulin (TBG), thyroglobulin (Tg), TSH, IGF‐1, cortisol, PRL and physical well‐being by means of questionnaires were measured before and during chemotherapy.Results  In 19 children, 46 courses of chemotherapy and 123 plasma samples were analysed. During chemotherapy, mean concentrations of TSH, T3, Tg and cortisol decreased to 53, 67, 69 and 15% of the baseline value, respectively. Mean plasma rT3 increased to 217% of baseline. In 87% of all courses, one or more thyroid parameter(s) was aberrant. Furthermore, in 23 samples (19%) from 10 patients (53%), the concentration of IGF‐1 was below the reference value (adjusted for sex and age). Small changes were seen in scores for clinical condition but none was related to a change in thyroid function determinant. Most changes in thyroid hormones could be attributed to using dexamethasone.Conclusions  These results demonstrate that, in children, thyroid hormone state changes significantly during chemotherapy, apparently not related to physical well‐being but to the drugs administered. Future investigations should focus on the impact for patient care and possibilities of (preventive) intervention.
Is stimulation of thyroglobulin (Tg) useful in low‐risk patients with thyroid carcinoma and undetectable Tg on thyroxin and negative neck ultrasound?
Authors: Do Rosário Pedro Weslley Souza , Borges Michelle Aparecida Ribeiro , Fagundes Tales Alvarenga , Franco Ana Cristina Horta Messias , Purisch Saulo 
Published: January 2005

SummaryObjective  To determine the usefulness of thyroglobulin (Tg) stimulation in low‐risk patients with undetectable Tg on T4 and negative neck ultrasound (US) after initial therapy of thyroid carcinoma.Methods  We evaluated 122 consecutive patients classified as low risk 6 months to 1 year after total thyroidectomy and remnant ablation. All patients had a normal clinical exam, Tg ≤ 1 ng/ml during suppressive therapy (TSH < 0·1 mIU/l), and undetectable antithyroglobulin antibodies.Results  After T4 withdrawal and elevation of TSH to values > 30 mIU/l, 26 patients (21·3%) converted Tg to levels > 1 ng/ml. Metastases were detected in 10 patients, nine showing stimulated Tg levels > 1 ng/ml. Cervical metastases were observed in 9/10 patients and lung metastases in one patient. Neck US identified all cervical metastases. Seventeen patients with stimulated Tg levels > 1 ng/ml initially showed no apparent disease, with a reduction in Tg being observed upon subsequent measurements, and 13 patients presented undetectable Tg off T4 at the end of the study. Undetectable Tg on T4 showed a high negative predictive value (NPV; 91·8%), which increased to 99·1% when combined with neck US. Stimulated Tg levels < 1 ng/ml presented a 98·9% NPV. A total of 113 patients with undetectable Tg on T4 and negative US had to be exposed to hypothyroidism in order to diagnose one further case of metastases.Conclusion  Undetectable Tg on T4 combined with negative neck US presented a high NPV in low‐risk patients and Tg stimulation might be avoided in these patients.
LIGHT is involved in the pathogenesis of rheumatoid arthritis by inducing the expression of pro‐inflammatory cytokines and MMP‐9 in macrophages
Authors: Kim Won‐Jung , Kang Yoon‐Joong , Koh Eun‐Mi , Ahn Kwang‐Sung , Cha Hoon‐Suk , Lee Won‐Ha 
Published: January 2005

SummaryMacrophages play a crucial role in the perpetuation of inflammation and irreversible cartilage damage during the development of rheumatoid arthritis (RA). LIGHT (TNFSF14) and its receptor TR2 (TNFRSF14) are known to have pro‐inflammatory activities in foam cells of atherosclerotic plaques. We tested a hypothesis that LIGHT and TR2 are involved in activation of monocyte/macrophages in RA synovium. Immunohistochemical analysis of RA synovial tissue samples revealed that both LIGHT and TR2 are expressed in CD68 positive macrophages. In contrast, synovial tissue samples from osteoarthritis (OA) patients failed to reveal the expression of LIGHT. Expression of TR2 in RA synovial macrophages was also detected using flow cytometry analysis. To identify the role of LIGHT in the functioning of macrophages in RA, we isolated macrophage enriched cells from RA synovial fluid and stimulated them with LIGHT. LIGHT induced expression of matrix metalloproteinase‐9 and pro‐inflammatory cytokines such as tumor necrosis factor (TNF)‐α, interleukin (IL)‐6, and IL‐8. These data indicate that LIGHT and TR2 expressed in macrophages are involved in the pathogenesis of RA by inducing the expression pro‐inflammatory cytokines and matrix degrading enzymes.
Significance of Fas and Fas ligand in tuberculous lymphadenitis
Authors: Mustafa Tehmina , Mogga Stanley J. , Mfinanga Sayoki G. M. , Mørkve Odd , Sviland Lisbet 
Published: January 2005

SummaryThe Fas/Fas‐ligand (FasL) system plays an important role in regulation of apoptosis and the immune response, and is exploited by mycobacteria to evade the immune response. This study was performed to investigate the distribution and levels of FasL and Fas in lymph node granulomas and sera of tuberculous lymphadenitis patients by immunohistochemistry and enzyme‐linked immunosorbent assay. The validity of soluble Fas (sFas) or soluble FasL (sFasL) as a diagnostic tool was also examined. Levels of sFasL in serum were elevated among patients. The numbers of FasL stained cells in lymph node granulomas were higher than Fas. Children had significantly higher levels of sFasL as compared to adults. The human immunodeficiency virus (HIV)–tuberculosis (TB)‐coinfected patients displayed no differences in the levels of sFasL or sFas compared with HIV‐negative patients. The healthy controls from a high endemic tuberculosis country (having latent TB) had significantly higher levels of sFasL than from a country with no TB transmission. The sensitivity and specificity of the FasL and Fas test were low when compared with the culture results as the gold standard. However, by using histology as the gold standard, the sensitivity and specificity of the FasL test were increased to 66·7% and 100%, respectively, but for the Fas test remained low. In conclusion, sFasL and sFas cannot be used as diagnostic tests for tuberculous lymphadenitis. However, its utility in detecting latent TB and childhood tuberculous lymphadenitis remains to be evaluated. FasL seems to play a role in immune modulation and pathogenesis of TB. Modulators of Fas/FasL‐mediated apoptosis may therefore be clinically useful.
VH replacement in rearranged immunoglobulin genes
Authors: Darlow John M. , Stott David I. 
Published: January 2005

SummaryExamples suggesting that all or part of the VH segment of a rearranged VHDJH may be replaced by all or part of another VH have been appearing since the 1980s. Evidence has been presented of two rather different types of replacement. One of these has gained acceptance and has now been clearly demonstrated to occur. The other, proposed more recently, has not yet gained general acceptance because the same effect can be produced by polymerase chain reaction artefact. We review both types of replacement including a critical examination of evidence for the latter. The first type involves RAG proteins and recombination signal sequences (RSS) and occurs in immature B cells. The second was also thought to be brought about by RAG proteins and RSS. However, it has been reported in hypermutating cells which are not thought to express RAG proteins but in which activation‐induced cytidine deaminase (AID) has recently been shown to initiate homologous recombination. Re‐examination of the published sequences reveals AID target sites in VH‐VH junction regions and examples that resemble gene conversion.