bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological treatment of asthma today: Table 1
Authors: Rabe K.F. , Schmidt D.T. 
Published: January 2003

The current concept of asthma therapy is based on a stepwise approach, depending on disease severity, and the aim is to reduce the symptoms that result from airway obstruction and inflammation, to prevent exacerbations and to maintain normal lung function.β2‐Adrenoceptor agonists and glucocorticoids are at present the most effective drugs for the treatment of airway obstruction and inflammation, with theophylline, leukotriene receptor antagonists and anticholinergics as second- or third-line therapy. There are, to date, no additional or newly developed drugs available that add substantially to the current strategies or even replace β2‐adrenoceptor agonists or glucocorticoids. New approaches in asthma therapy recommend drug combinations of inhaled steroids, primarily with long-acting β2‐adrenoceptor agonists, based on their improved efficacy and the potential for a steroid-sparing effect.Although existing drug entities are able to control the vast majority of patients with mild and moderate asthma, patients' (and doctors') adherence to guidelines and treatment strategies falls well short of the desired standards.Treatment choices, however, differ between countries and should take into account convenience to the patient and the occurrence of side-effects. Additionally, the cost of therapy and reimbursement policies also influences therapeutic strategies.
Cytokines and the lung
Authors: Toews G.B. 
Published: January 2003

Cytokines are signal molecules that induce movement, differentiation, growth and death of many cell types. Cytokines generate these effects through interactions with receptors, which relay a signal into the cell triggering a response.Cytokine-receptor interactions are promiscuous; a combining site of any receptor can bind many ligands. Promiscuity allows for the generation of agonists, alternative ligands that activate a receptor in a way similar to the normal ligands and antagonists, ligands that bind to a receptor, but neutralize the effects of an agonist. Cytokine-receptor interactions induce many diverse (pleiotropic) effects. Cytokine-receptor interactions are redundant; several cytokines can perform the same function.Mammalian hosts use cytokines to maintain homeostasis and to provide signals crucial to host responses to invading microbes and other injurious agents. Cytokines are the molecular messages, which: 1) initiate and amplify inflammatory and immune responses by recruiting and activating cells; 2) regulate the activation and differentiation of T‐ and B‐lymphocytes, whose functions are crucial to specific cell-mediated immunity; and 3) initiate and regulate local repair processes critical to the resolution of inflammatory responses.Further studies of cytokines and their receptors should provide a framework for therapeutic interventions in patients with dysregulated inflammatory responses.
A PIT-1 Homeodomain Mutant Blocks the Intranuclear Recruitment Of the CCAAT/Enhancer Binding Protein α Required for Prolactin Gene Transcription
Authors: Enwright John F. , Kawecki-Crook Margaret A. , Voss Ty C. , Schaufele Fred , Day Richard N. 
Published: January 2003

AbstractThe pituitary-specific homeodomain protein Pit-1 cooperates with other transcription factors, including CCAAT/enhancer binding protein α (C/EBPα), in the regulation of pituitary lactotrope gene transcription. Here, we correlate cooperative activation of prolactin (PRL) gene transcription by Pit-1 and C/EBPα with changes in the subnuclear localization of these factors in living pituitary cells. Transiently expressed C/EBPα induced PRL gene transcription in pituitary GHFT1–5 cells, whereas the coexpression of Pit-1 and C/EBPα in HeLa cells demonstrated their cooperativity at the PRL promoter. Individually expressed Pit-1 or C/EBPα, fused to color variants of fluorescent proteins, occupied different subnuclear compartments in living pituitary cells. When coexpressed, Pit-1 recruited C/EBPα from regions of transcriptionally quiescent centromeric heterochromatin to the nuclear regions occupied by Pit-1. The homeodomain region of Pit-1 was necessary for the recruitment of C/EBPα. A point mutation in the Pit-1 homeodomain associated with the syndrome of combined pituitary hormone deficiency in humans also failed to recruit C/EBPα. This Pit-1 mutant functioned as a dominant inhibitor of PRL gene transcription and, instead of recruiting C/EBPα, was itself recruited by C/EBPα to centromeric heterochromatin. Together our results suggest that the intranuclear positioning of these factors determines whether they activate or silence PRL promoter activity.
Determination of Nuclear Receptor Corepressor Interactions with the Thyroid Hormone Receptor
Authors: Makowski Anita , Brzostek Sabrina , Cohen Ronald N. , Hollenberg Anthony N. 
Published: January 2003

AbstractThe thyroid hormone receptor (TR) recruits the nuclear corepressors, nuclear receptor corepressor (NCoR) and silencing mediator of retinoid and thyroid hormone receptors (SMRT), to target DNA elements in the absence of ligand. While the TR preferentially recruits NCoR, the mechanism remains unclear. The corepressors interact with the TR via interacting domains (IDs) present in their C terminus which contain a conserved motif termed a CoRNR box. Despite their similarity, the corepressor IDs allow for nuclear receptor specificity. Here we demonstrate that NCoR stabilizes the TR homodimer when bound to DNA by preventing its dissociation from thyroid hormone response elements. This suggests that NCoR acts to hold the repression complex in place on target elements. The TR homodimer recruits NCoR through two of its three IDs, one of which is not present in SMRT. This unique ID, N3, contains a CoRNR box but lacks the extended helical motif present in each of the other IDs. Instead, N3 contains an isoleucine just proximal to this motif. This isoleucine is also conserved in N2 but not in the corresponding S2 domain in SMRT. On thyroid hormone response elements and in mammalian cells this residue is critical in both N3 and N2 for high-affinity TR binding. In addition, this residue also controls specificity for the interactions of TR with NCoR. Together these data suggest that the specific recruitment of NCoR by the TR through a unique motif allows for stabilization of the repression complex on target elements.
Molecular Basis for the Subtype Discrimination of the Estrogen Receptor-β-Selective Ligand, Diarylpropionitrile
Authors: Sun Jun , Baudry Jerome , Katzenellenbogen John A. , Katzenellenbogen Benita S. 
Published: January 2003

AbstractAlthough the two subtypes of the human estrogen receptor (ER), ERα and ERβ, share only 56% amino acid sequence identity in their ligand binding domain (LBD), the residues that surround the ligand are nearly identical; nevertheless, subtype-selective ligands are known. To understand the molecular basis by which diarylpropionitrile (DPN), an ERβ-selective ligand, is able to discriminate between the two ERs, we examined its activity on ER mutants and chimeric constructs generated by DNA shuffling. The N-terminal region of the ERβ LBD (through helix 6) appears to be fully responsible for the ERβ selectivity of DPN. In fact, a single ERα point mutation (L384M) was largely sufficient to switch the DPN response of this ER to that of the ERβ type, but residues in helix 3 are also important in achieving the full ERβ selectivity of DPN. Using molecular modeling, we found an energetically favorable fit for the S-DPN enantiomer in ERβ, in which the proximal phenol mimics the A ring of estradiol, and the nitrile engages in stabilizing interactions with residues in the ligand-binding pocket of ERβ. Our findings highlight that a limited number of critical interactions of DPN with the ERβ ligand-binding pocket underlie its ER subtype-selective character.
Revision surgery for chronic otitis media: recurrent-residual disease and hearing
Authors: O’Leary Stephen , Veldman Jan E. 
Published: January 2003

The aim of this study was to determine the effect of surgical approach, intact canal wall (ICW) or canal wall down (CWD), upon the success of revision surgery for chronicotitis media (COM). A retrospective analysis of 367 patients (including 65 children aged <15years) who underwent revision tympanoplasty because of persistent disease was performed. Single-staged tympanoplasty was performed, preserving the canal wall when present. Hearing was reconstructed with allograft incus. Follow-up ranged from one to 15 years. Hearing was determined by pre- and post-operative air-bone gaps.Post-operative re-perforation, aural discharge and/or cholesteatoma rates were similar for CWD and ICW. Cholesteatoma could present following the revision, even though it was not apparentat surgery. Following tympanoplasty, the final hearing was not significantly affected by the surgical approach or presence of cholesteatoma. Improvement in hearing was adversely affected by cholesteatoma or an absent stapes suprastructure.Revision ICW and CWD operations were both successful in controlling signs of COM. Cholesteatoma is a peripheral risk in COM and may become apparent after revision surgery.
Computer imaging and patient satisfaction in rhinoplasty surgery
Authors: Sharp H. R. , Tingay R. S. , Coman S. , Mills V. , Roberts D. N. 
Published: January 2003

The measurement and achievement of improved patient benefit following a particular medical or surgical intervention has become an increasingly relevant part of the provision of effective healthcare.We have retrospectively analysed patient satisfaction in 56 patients following rhinoplasty via the Glasgow Benefit Inventory (GBI), 25 of whom underwent pre-operative computer imaging planning. We have also audited patient reaction to this technique via a concurrent questionnaire in those subjects who underwent imaging, and correlated this with overall patient outcome.Patient satisfaction with cosmetic rhinoplasty following computer imaging was significantly improved compared to those patients who did not receive imaging.
Endoscopic laser treatment in pre-malignant and malignant vocal fold epithelial lesions
Authors: Remijn E. E. G. , Marres H. A. M. , van den Hoogen F. J. A. 
Published: January 2003

Endoscopic laser treatment was performed in 43 patients with pre-malignant or malignant vocal fold epithelial lesions, 10 were treated with endoscopic laser surgery for dysplasia, 12 for carcinoma in situ (CIS), five for verrucous carcinoma and 16 patients for squamous cell carcinoma (SCC). Thirty-two patients received laser therapy as their first therapy, whereas 11 patients had had previous radiation therapy for laryngeal carcinoma (n = 9) or CIS (n = 2).Recurrence after initial laser therapy necessitating re-treatment (a second laser treatment or radiotherapy) occurred in nine out of 32 patients (28 per cent), thus 23 (72 per cent) were maintained free of disease during the follow-up period.Besides the 32 patients without previous therapy, patients who had already undergone radiat on therapy were also included in this study. In this group there were nine patients with SCC, one patient with CIS and one with dysplasia. They all underwent laser therapy. Four were free ofdisease during follow-up (36 per cent) and seven developed recurrences. Six (58 per cent of allpatients with previous radiation therapy) underwent total laryngectomy.
A case of rhinolithiasis in Botswana: a mineralogical, microscopic and chemical study
Authors: Vink Bernard W. , van Hasselt Piet , Wormald Richard 
Published: January 2003

A case of rhinolithiasis in Southeast Botswana was treated and after removal in hospital, the rhinolith was subjected to macroscopic and microscopic examination, X-ray diffraction analysis, electron microscope analysis and partial botanical analysis.The rhinolith consists of a strongly elliptical core of calcium stearate (C36H70CaO4.H2O), surrounded by approximately 30 elongated concentric growth rings, consisting of sodium-containing whitlockite (Ca18Mg2(Na,H)(PO4)14). The different layers have various degrees of porosity and red staining, probably due to traces of amorphous iron oxide. The origin of the rhinolith started with a piece of plant material, lodged in the nose, which was replaced by calcium stearate, leaving some remnants of resistant epidermal plant tissue. During subsequent years, thin layers of whitlockite were deposited periodically around the core with the reddish brown bands representingdeposition during the dry season when atmospheric dust rich in amorphous iron oxide is at its highest in Botswana.
Heritability and anthropometric influences on human fertility
Authors: Madrigal Lorena , Relethford John H. , Crawford Michael H. 
Published: January 2003

AbstractThis study researched the impact of anthropometrics and size‐of‐family of orientation on women's fertility by using path analysis. The data were collected as part of the anthropological study conducted in Ireland by Harvard University personnel before the Second World War. The women included in this analysis were all over age 49 and were either married or widowed at the time of the survey. Our results indicate that the heritability of fertility is moderate in this sample and that there is a tendency for heavy women to have a higher fertility. However, when anthropometrics and size‐of‐family of orientation were entered as independent variables in a path diagram, an insignificant portion of the variation of fertility was explained. In this Irish population, the main cause of differential fertility was cultural rather than biological. A large portion of women never married and no unmarried woman reported producing a child. Am. J. Hum. Biol. 15:16–22, 2003. © 2002 Wiley‐Liss, Inc.
Effect of the bubonic plague epidemic on inbreeding in 14th century Britain
Authors: Pattison John E. 
Published: January 2003

AbstractThe purpose of the study reported here was to further investigate a new method of estimating inbreeding in large, relatively isolated populations over historic times, as reported by Pattison (1999, 2001). The method is based on modeling the genealogical “paradox” and produces values of Pearl's coefficients of inbreeding as a function of time for any given population curve. In particular, this study demonstrates that the new method of estimating inbreeding may be used to examine the effect of unusual features in population curves on levels of inbreeding in that population. As an example, the medieval population “bump” that spans the 13th and 14th centuries in the population of Britain, which terminated abruptly with the outbreak of bubonic plague in 1348 AD, is examined. It is first assumed that the whole population was the adult (breeding) population, corresponding to minimum inbreeding. For this case it is found that, for distant generations, about 90% of the whole population occurs in any present‐day British pedigree. This value compares favorably with the values of 85% and 80% reported by Wachter (1980) and Derrida et al. (1999, 2000), respectively. The population bump causes the curves for Pearl's coefficient, for minimum inbreeding, to have a plateau of about 96% over the period from about 1220 AD to 1380 AD. The effect of introducing a single known estimate of inbreeding into the model is to produce a more realistic situation where the adult (breeding) population is considerably less than the whole population. It is found that the maximum number of different ancestors in any generation, in the average British pedigree, is about 22,900 individuals and occurs about 1220 AD. More importantly, and possibly contrary to expectation, it is now found that the population bump had virtually no effect on the level of inbreeding. Am. J. Hum. Biol. 15:101–111, 2003. © 2002 Wiley‐Liss, Inc.
Facial dysgenesis: A novel facial syndrome with chromosome 7 deletion p15.1‐21.1
Authors: Hoover‐Fong Julie E. , Cai J. , Cargile C.B. , Thomas G.H. , Patel A. , Griffin C.A. , Jabs E.W. , Hamosh A. 
Published: January 2003

AbstractWe describe a female neonate with a unique constellation of features including anophthalmia and cryptophthalmos, temporal remnant “eye tags,” bilateral cleft lip, unilateral cleft palate, a proboscis with absent nasal septum, choanal atresia, micrognathia, square stoma, and bilateral external auditory canal atresia. Gross brain structure, pituitary function, limbs, trunk, and genitalia were normal. Skeletal survey, echocardiogram and abdominal viscera were unremarkable except for a split central sinus of the right kidney. BAER exam indicated she could hear and temporal CT confirmed the presence of cochlea and possible ossicles. Cytogenetic evaluation revealed an interstitial deletion at chromosome 7p15.1‐21.1. TWIST, a gene encoding a transcription factor involved in craniofacial development, is deleted by FISH analysis. The absence of a mutation on the non‐deleted allele of TWIST as determined by sequencing virtually eliminates complete loss of the TWIST gene as the cause of this patient's severe phenotype. The HOXA gene cluster also encodes transcription factors that are crucial for directing cephalad to caudad somatic fetal development. HOXA1, the most telomeric of the 13 members of the HOXA gene cluster, is located at the centromeric boundary of the patient's chromosome 7 deletion. By FISH analysis, neither allele of HOXA1 is deleted and sequencing reveals no mutations. Haploinsufficiency or complete loss of the HOXA1 gene also does not appear to cause this patient's severe phenotype. Previous reports of chromosome 7p15‐21 deletions do not have phenotypes similar to this patient. © 2003 Wiley‐Liss, Inc.
Recombinants of intrachromosomal transposition of subtelomeres in chromosomes 1 and 2: A cause of minute terminal chromosomal imbalances
Authors: Daniel Art , Baker Elizabeth , Chia Nicole , Haan Eric , Malafiej Paul , Hinton Lyn , Clarke Nigel , Adès Lesley , Darmanian Artur , Callen David 
Published: January 2003

AbstractTwo cases of submicroscopic recombinants of intrachromosomal transposition of telomeres, one each from chromosome 1 and 2 are described. Meiotic crossing‐over would generate the recombinants from these reciprocal rearrangements. In both cases, which were detected by FISH with subtelomeric probes, there is a minute deletion of the qter region and a second presence of the pter subtelomeric region on the respective qter, i.e., a duplication of 1pter or 2pter respectively. The deletion on 2qter (case 2) was confirmed by microsatellite inheritance and was of paternal origin, but in case 1 there was no detectable 1q deletion other than of the subtelomeric probe, and parental origin could not be determined. The present case 2 with del(2qter)/dup(2pter) shares many features with reported cases of simple deletion (2qter) but did not have features of Albright hereditary osteodystrophy, which are seen in half of such deletion patients. The clinical features present in case 1 were similar to those of the previously reported case of a submicroscopic 1qter deletion but also to cases with microscopically visible 1qter deletions, presumably because of gene enrichment in subtelomeric regions. Recombinants of such intrachromosomal subtelomere transpositions detected by subtelomeric probes may comprise up to 10% of submicroscopic pter or qter deletion cases. Other cases of this unusual mechanism may be detected with more common use of subtelomeric probes. It is suggested the bouquet associations of telomeres in early meiosis may facilitate such unusual rearrangements. © 2003 Wiley‐Liss, Inc.
Cryptic t(1;12)(q44;p13.3) translocation in a previously described syndrome with polymicrogyria, segregating as an apparently X‐linked trait
Authors: Zollino Marcella , Colosimo Cesare , Zuffardi Orsetta , Rossi Elena , Tosolini Alessandra , Walsh Christopher A. , Neri Giovanni 
Published: January 2003

AbstractWe report on the multistep progression to the correct genetic diagnosis in an apparently new syndrome of mental retardation and multiple congenital anomalies, including hypogenitalism and polymicrogyria. We had previously reported it as an X‐linked condition affecting four members (three males and one female) of a family [Zollino et al., 1992: Am J Med Genet 43:452–457]. Two of the four patients, both males, presented with a brain abnormality that was initially described as pachygyria, while the remaining two (one male and one female) did not. Our present study includes a clinical follow‐up on the patients, neuroradiological reexamination of one patient, X linkage studies and X inactivation analyses, and finally molecular cytogenetics, which allowed us to establish definitely the genetic causes of the condition. After the detection of a subtle t(1;12)(q44;p13.3) balanced translocation in healthy carriers, two unbalanced segregation products were observed in different patients, resulting in 1q44qter monosomy and 12p13.3pter trisomy in patients with polymicrogyria and severe psychomotor delay, 12p13.3pter monosomy and 1q44qter trisomy in the other two patients without polymicrogyria, with less severe mental retardation and less distinctive physical anomalies. Thus, this condition is no longer to be considered X‐linked, but the result of cryptic autosomal imbalance. Furthermore, this study identified an approximately 14 Mb interval in 1q44qter pathogenetically related to polymicrogyria. © 2003 Wiley‐Liss, Inc.
Bilateral microphthalmia with cyst, facial clefts, and limb anomalies: A new syndrome with features of Waardenburg syndrome, cerebro‐oculo‐nasal syndrome, and craniotelencephalic dysplasia
Authors: Gupta P.C. , Peralta D. , Parker M. , Crowe C. , Clark B. , Traboulsi E.I. 
Published: January 2003

AbstractWe report a patient with bilateral microphthalmia with cyst, limb anomalies, and multiple facial malformations. This patient has clinical features similar to Waardenburg ophthalmo‐acromelic syndrome, cerebro‐oculo‐nasal syndrome, and craniotelencephalic dysplasia. Although all of these syndromes are characterized by microphthalmia, the presently reported patient does not have the complete pattern of any of these syndromes, It is possible that he has a previously undescribed syndrome, most closely related to the cerebro‐oculo‐nasal syndrome with malformations outside the craniofacial region. More case reports are needed to further delineate this possibly new syndrome. © 2003 Wiley‐Liss, Inc.
Biological and environmental contributions to adaptive behavior in fragile X syndrome
Authors: Glaser Bronwyn , Hessl David , Dyer‐Friedman Jennifer , Johnston Cindy , Wisbeck Jacob , Taylor Annette , Reiss Allan 
Published: January 2003

AbstractFragile X syndrome is the most common cause of inherited developmental disability. The purpose of the present study is to understand how both biological and environmental influences affect the development of adaptive behavior in children with fragile X. In‐home assessments were conducted on 120 children (80 boys and 40 girls) with the fragile X full mutation and their unaffected siblings (58 boys and 62 girls). Hierarchical multiple regression analyses were utilized. Independent variables included biological or demographic variables specific to the child (age, gender, full‐scale IQ, and FMRP percentage), as well as factors specific to his/her environment (household income, home environment, maternal psychopathology, and effectiveness of educational/therapeutic services). Results of these analyses showed that for both boys with fragile X and the control sibling group, adaptive behavior was predicted by IQ, age, gender, and home environment. For girls with fragile X, adaptive behavior was most strongly associated with IQ. Adaptive behavior was not significantly associated with FMRP in boys or girls with fragile X. By examining the relative influences of biological and environmental factors on adaptive behavior in children with fragile X, we begin to lay the foundation for the development of more specific treatment studies in children with this disorder. © 2002 Wiley‐Liss, Inc.