bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epitope-specific regulation. II. A bistable, Igh-restricted regulatory mechanism central to immunologic memory
Authors: Herzenberg LA , Tokuhisa T , Parks DR , Herzenberg LA 
Published: June 2004

Antibody responses to commonly used antigens are regulated by an epitope- specific system composed of Igh-restricted elements responsible for controlling the isotype and allotype responses mounted to each of the epitopes on the antigen. Because these elements can be independently induced to either suppress or support antibody production, this system as a whole provides an effector mechanism capable of selectively controlling the amount, affinity, isotype representation, and epitope-specificity of an antibody response.
Sequential immunizations with a carrier molecule and a hapten conjugated to that carrier (carrier/hapten-carrier immunization) induce suppression for IgG responses to the hapten. IgG(2a), IgG(2b), and IgG(3) responses are easily suppressed, whereas IgG(1) responses tend to be more resistant. Once induced, suppression tends to be maintained; however, repeated stimulation with the hapten (on any carrier) eventually induces antibody production, first for IgG(1) and later for the more suppressible isotypes (IgG(2a), IgG(2b), IgG(3)).
Antibody production, once initiated, also tends to be maintained. Ongoing IgG antihapten responses in animals primed with a hapten-carrier conjugate can be suppressed by subsequent carrier/hapten-carrier immunization (using a different carrier molecule); however, the suppression induced under these circumstances is substantially weaker, i.e., it mainly affects the more suppressible isotypes and is only strong enough to detect clearly in about one-half the immunized animals. Thus, the initiation of antibody production impairs the subsequent induction of suppression, and the initial induction of suppression tends to prevent subsequent initiation of antibody production.
This reciprocal relationship defines a bistable regulatory mechanism, i.e., one that tends to maintain its initially induced state but is capable of shifting to the alternate state when stimulatory conditions so dictate. The operation of such a mechanism permits conditions surrounding the first immunization with an epitope (hapten) to strongly influence but not absolutely determine which and how many of the anti-epitope memory B cells generated by that immunization will subsequently be expressed. Thus, epitope- specific regulation, although subordinate to mechanisms that control memory B cell development (as opposed to expression), plays a key role in determining the magnitude, affinity, and isotype representation of anamnestic (memory) responses produced in response to previously encountered epitopes.
Generation of antibody diversity in the immune response of BALB/c mice to influenza virus hemagglutinin. I. Significant variation in repertoire expression between individual mice
Authors: Staudt LM , Gerhard W 
Published: June 2004

The paratypic and idiotypic diversity of the BALB/c antibody response to the hemagglutinin (HA) of the influenza A/PR/8/34 virus (PR8) was investigated using a panel of 125 anti-HA hybridoma antibodies derived from 14 BALB/c mice. The paratypic diversity, as assessed by a fine specificity analysis using 51 related influenza viruses, was extensive: 104 distinct paratopes were observed. In three instances, antibodies with indistinguishable paratopes were isolated from two individual mice. A minimum estimate of the size of the adult BALB/c anti-HA paratypic repertoire, calculated from these data, is 1,500.
The generation of this diverse repertoire was studied by screening the anti-HA hybridoma panel for the presence of idiotypes (Id) that are markers for variable (V) region sequences derived from related germ line V genes. Three cross-reactive Id (IdX) that are markers for the V(k)21C, V(k)21B, and V(k)21A, D, E, or F L chain subgroups were found, respectively on 16, 1, and 10 anti-HA hybridoma antibodies derived from seven individual BALB/c mice. Thus, the V(k)21 IdX(+) hybridomas constitute 22 percent of the anti-HA hybridoma panel. The V(k)21 IdX are also present on 8.6 percent of K-bearing immunoglobulin in normal BALB/c serum. This suggests that the V(k)21 group is used preferentially in the BALB/c anti-HA immune response.
The generation of the anti-HA repertoire was further studied using large panels of anti-HA hybridomas derived from two individual adult BALB/c mice. Anti-idiotypic antisera were raised in rabbits against individual hybridomas from each mouse. One anti-Id serum defined a family of four idiotypically and paratypically related, but not identical, antibodies from mouse 36, which represented 31 percent of the hybridoma antibodies isolated from this mouse. None of the 112 anti-HA hybridoma antibodies derived from 13 other individual mice showed idiotypic cross-reactivity. Furthermore, this Id could not be detected in anti-PR8 antisera from 75 individual BALB/c mice. Another anti-Id serum defined a family of 27 idiotypically related antibodies from mouse 37, which represented 50 percent of the hybridoma antibodies isolated from this mouse. Only 1 of the 71 hybridoma antibodies isolated from 13 other individuals was idiotypically cross-reactive.
These results demonstrate that individual adult BALB/c mice express paratypically and idiotypically distinct antibody repertoires to the HA of influenza virus PR8. Based on these observations, we suggest that somatic mutation plays an important role in the generation of the adult anti-HA repertoire. Mechanisms that could account for differences in repertoire expression among individual mice are discussed.
Increasing Antibiotic Resistance of Streptococcus Species in New York City
Authors: Lin Karen , Tierno Philip M. , Komisar Arnold 
Published: June 2004

AbstractObjective:
Streptococcus species are common pathogens in head and neck infections and are leading causes of morbidity and mortality. Emerging penicillin‐resistant streptococcal pathogens have shifted empirical antibiotic therapy in favor of valuable alternatives, including erythromycin and clindamycin. This study was undertaken to determine the magnitude of antimicrobial resistance to these antibiotics.Study Design: Retrospective review.Methods: A retrospective study of two streptococcal species isolates, Streptococcus pyogenes (163 specimens) and Streptococcus pneumoniae (164 specimens), collected between January 1, 2001 and January 1, 2002 at two academic institutions. The antibiotic susceptibility patterns were analyzed for penicillin, erythromycin, and clindamycin according to the National Committee for Clinical Laboratory Standards.Results: Fourteen percent to 34% of S. pyogenes isolates were erythromycin‐resistant, and 0% to 28% were clindamycin‐resistant. None of the S. pyogenes isolates were resistant to penicillin. Of the S. pneumoniae isolates, 33% to 50% were resistant to erythromycin, and 18% to 33% were resistant to clindamycin. The penicillin resistance levels for S. pneumoniae were 0% to 45%.Conclusions: Our antimicrobial resistance levels for S. pyogenes and S. pneumoniae significantly exceeded national and worldwide levels of erythromycin and clindamycin resistance. With a diverse population of over 8 million residents and high physician supply, our model is a microcosm for the study of antimicrobial use and susceptibility patterns and of clinical failure.
New Method of Using Reconstructed Images for Assessment of Patency of Intracochlear Spaces for Cochlear Implant Candidates
Authors: Karino Shotaro , Hayashi Naoto , Aoki Shigeki , Ohtomo Kuni , Yamasoba Tatsuya 
Published: June 2004

AbstractObjective/Hypothesis: A new method of reconstruction using multidetector‐row helical computed tomography (MDCT) was applied for assessment of cochlear patency in cochlear implantation candidates.Study Design: Descriptive study comparing radiologic and surgical findings in eight radiologically normal cochleas and four abnormal cases.Methods: In unusual cases including cochlear ossification and misinsertion of electrodes, intracochlear space was evaluated on two types of reconstructed images: the “basal turn plane” that was vertical to the modiolus and contained whole basal turn was effective in the assessment of the lining of the inner bony wall of the otic capsule; “cochlear cross plane” images allowed evaluation of the patency of the intracochlear space and the location of inserted electrodes at the sections vertical to the direction of insertion of the electrodes.Results: Preoperative evaluation was useful for predicting possible problems in electrode insertion and therefore helped in decision‐making in regards to surgical strategies, especially in candidates with a high probability of cochlear ossification such as those with meningitis and otosclerosis. Furthermore, the new reconstruction method also provided useful information on the position of the cochlear implant electrodes after surgery.Conclusions: These unusual cases demonstrated that preoperative MDCT evaluation by our reconstruction method was useful for predicting possible problems in electrode insertion and decision‐making in regards to surgical strategies, especially in cochlear implantation candidates with a high probability of cochlear stenosis.
Office‐Based Endoscopic Procedure for Diagnosis in Conductive Hearing Loss Cases Using OtoScan Laser‐Assisted Myringotomy
Authors: Kakehata Seiji , Futai Kazunori , Kuroda Reiko , Shinkawa Hideichi 
Published: June 2004

AbstractObjectives/Hypothesis: In conductive hearing loss (HL), even though preoperative examinations including audiometry, tympanometry, and computed tomography (CT) scan are applied, exploratory tympanotomy is necessary to make an exact diagnosis of ossicular interruption and stapes fixation. Precise preoperative diagnosis would be useful for patient counseling, surgical indications, and planning. The advantages of office‐based OtoScan laser‐assisted myringotomy (LAM), which makes a circular and non‐hemorrhagic perforation, prompted us to investigate other uses of LAM in addition to ventilation and drainage of the tympanic cavity. To make presurgical diagnosis in conductive HL, endoscopes with an outer diameter of 1.7 or 1.9 mm were used to inspect the middle ear pathology through perforations with a diameter of 2 mm made by LAM.Methods: In the outpatient clinic, a circular perforation with a diameter of 2 mm was made in the tympanic membrane with LAM. An endoscopic view of the ossicular chain through a 70° angled tip endoscope held immediately to the outer side of the perforation was obtained to diagnose conduction disturbance loci in conductive HL cases.Results: Ossicular chain abnormalities were easily and safely detected by clean endoscopic views obtained through a nonhemorrhagic circular perforation. When necessary, insertion of the tip of the endoscope into the tympanic cavity provided additional views of epitympanum.Conclusion: We suggest that transtympanic endoscopy through the perforation made by LAM is an effective and safe office‐based procedure for diagnosis in conductive HL cases and could be an alternative procedure to replace exploratory tympanotomy.
Immunohistochemistry and Reverse Transcriptase–Polymerase Chain Reaction as Methods for Diagnostic Determination of Usher Syndrome Type IIa
Authors: Cohn Edward , Bhattacharya Gautam , Pearsall Nicole , Shendrik Igor , Kimberling William , Cosgrove Dominic 
Published: June 2004

AbstractObjectives/Hypothesis: Patients having null mutations in the USH2A gene do not produce usherin and therefore are not positive for immunohistochemical staining of the usherin protein. Thus, immunostaining for usherin can serve as a reliable diagnostic tool for Usher syndrome type IIa.Study Design: Prospective.Methods: Immunohistochemical staining for usherin was carried out in basement membrane of minor salivary gland tissue from subjects with confirmed Usher syndrome type IIa and from archival minor salivary gland tissue from patients without Usher syndrome as control samples. Quantitative usherin messenger RNA analysis was performed using minor salivary gland biopsy tissue.Results: Five subjects with Usher syndrome type IIa had no immunostaining in minor salivary gland tissue, whereas control minor salivary gland tissue did stain with usherin antibody. No usherin RNA was detected in biopsy specimens from patients with confirmed Usher syndrome IIa.Conclusion: The feasibility was confirmed of diagnosing Usher syndrome type IIa using purified usherin antibody in subjects having two null USH2A mutations.
The effects of nonnative interactions on protein folding rates: Theory and simulation
Authors: Clementi Cecilia , Plotkin Steven S. 
Published: June 2004

AbstractProteins are minimally frustrated polymers. However, for realistic protein models, nonnative interactions must be taken into account. In this paper, we analyze the effect of nonnative interactions on the folding rate and on the folding free energy barrier. We present an analytic theory to account for the modification on the free energy landscape upon introduction of nonnative contacts, added as a perturbation to the strong native interactions driving folding. Our theory predicts a rate‐enhancement regime at fixed temperature, under the introduction of weak, nonnative interactions. We have thoroughly tested this theoretical prediction with simulations of a coarse‐grained protein model, by using an off‐lattice Cαmodel of the src‐SH3 domain. The strong agreement between results from simulations and theory confirm the nontrivial result that a relatively small amount of nonnative interaction energy can actually assist the folding to the native structure.
Trapping a 96° domain rotation in two distinct conformations by engineered disulfide bridges
Authors: Schultz‐Heienbrok Robert , Maier Timm , Sträter Norbert 
Published: June 2004

AbstractEngineering disulfide bridges is a common technique to lock a protein movement in a defined conformational state. We have designed two double mutants of Escherichia coli 5′‐nucleotidase to trap the enzyme in both an open (S228C, P513C) and a closed (P90C, L424C) conformation by the formation of disulfide bridges. The mutant proteins have been expressed, purified, and crystallized, to structurally characterize the designed variants. The S228C, P513C is a double mutant crystallized in two different crystal forms with three independent conformers, which differ from each other by a rotation of up to 12° of the C‐terminal domain with respect to the N‐terminal domain. This finding, as well as an analysis of the domain motion in the crystal, indicates that the enzyme still exhibits considerable residual domain flexibility. In the double mutant that was designed to trap the enzyme in the closed conformation, the structure analysis reveals an unexpected intermediate conformation along the 96° rotation trajectory between the open and closed enzyme forms. A comparison of the five independent conformers analyzed in this study shows that the domain movement of the variant enzymes is characterized by a sliding movement of the residues of the domain interface along the interface, which is in contrast to a classical closure motion where the residues of the domain interface move perpendicular to the interface.
Observation of sequence specificity in the seeding of protein amyloid fibrils
Authors: Krebs Mark R.H. , Morozova‐Roche Ludmilla A. , Daniel Katie , Robinson Carol V. , Dobson Christopher M. 
Published: June 2004

AbstractIt is well established that the rate of formation of fibrils by amyloidogenic proteins is enhanced by the addition of preformed fibrils, a phenomenon known as seeding. We show that the efficiency of seeding fibril formation from solutions of hen lysozyme by a series of other proteins depends strongly on the similarity of their sequences. This observation is consistent with the importance of long‐range interactions in stabilizing the core structure of amyloid fibrils and may be associated with the existence of a species barrier observed in the transmissible spongiform encephalopathies. In addition, it is consistent with the observation of a single dominant type of protein in the deposits associated with each form of amyloid disease.
Determining the Causes and Durability of Transnational Labour Migration between Mexico and the United States: Some Empirical Findings
Authors: Pries Ludger 
Published: June 2004

AbstractWhile the field of transnational migration studies is expanding, one important challenge is to broaden research from a mainly qualitative approach proving the existence of transnational migration phenomena toward efforts to quantify transnational migration and pay more attention to analysing its internal dynamics and interrelationships with other (ideal) types of migration. Based on a qualitative and quantitative empirical study of (trans)migrants moving between Puebla (Mexico) and the New York City region focused on the life and work trajectories of 648 individuals and on biographical life history interviews with about 40 Mexican migrants, the article is focused on analysing and explaining the number of trips as an important indicator for transnational migration (even if transmigration could be predominantly a subjective perception and practice without constant physical movement between countries). In order to establish the empirical existence of the transmigration phenomenon, a typology for distinguishing between different types of migrants is advanced and applied to those migrants captured in the survey. The influence of personal, familial, time‐, job‐, and community‐related factors on their decision‐making processes and the number of country trips are analysed. The empirical findings will be complemented by qualitative interview material to present the case of a transnationally organized family. This case study serves, first, to demonstrate that research on transmigrant household decision‐making strategies is complicated by the complexity of social and family networks, which make it difficult to clearly identify household units; second, it helps address the issue of the durability of the transmigration phenomenon by showing that transnational strategies can be adopted by family members over several generations, depending on individuals' changing needs and desires.
Loving America and Longing for Home: Isma'il al‐Faruqi and the Emergence of the Muslim Diaspora in North America
Authors: Ghamari‐Tabrizi Behrooz 
Published: June 2004

AbstractIn this paper, I weave the experience of an emerging community of Muslim diaspora around a biographical narrative of the Muslim activist and scholar Isma'il al‐Faruqi. Through this narrative, I illustrate that the diasporic experience begins in the place of origin and it does not inevitably lead toward a perpetual hybridization. The latter point is particularly significant because notions of diaspora and hybridity are conceptually linked and are often understood as a unidirectional cutting and mixing between the West and the East, or between the modern and the traditional. Al‐Faruqi's experience shows that, in a Fanonian sense of colonialism, diasporic experience conveys living as a “stranger”, at and away from home.The postcolonial condition has made it possible for ethnically diverse communities of Muslims to reside in the West, but maintain strong connections with their place of origin. Adopting the allegory of the Prophet's migration or hijra, al‐Faruqi constructed a fantastic notion of the ummah and a normative homo islamicus subject. Although he was profoundly influenced by the diversity of the Muslim Student Associations' constituency, al‐Faruqi encouraged Muslims to transcend their differences and sought to conceive a discursively homogenous ummah. Ultimately, however, his project failed because it did not correspond to real life experiences of Muslims of the West. Historically, Muslim communities have negotiated the boundaries of Muslimhood and the social responsibilities it entails, both in their homelands and in their new home in the West — a new home that increasingly becomes hostile to their presence, and thereby further complicates their triangular diaspora/host society/homeland relationship.
The scientific status of metazoan cladistics: why current research practice must change
Authors: Jenner Ronald A. 
Published: June 2004

Jenner, R. A. (2004). The scientific status of metazoan cladistics: why current research practice must change. —Zoologica Scripta,33, 293–310.Metazoan phylogenetics is bustling with activity. The use of comprehensive morphological data sets in recent phylogenetic analyses of the Metazoa indicates that morphological evidence continues to play a key role in the reconstruction of metazoan deep history. In this paper I review the scientific status of morphological metazoan cladistics from the perspective of cladistic research cycles. Each research cycle consists of three main steps: (1) the compilation of a data matrix (2) the simultaneous evaluation of all possible cladograms in a character congruence test, and (3) the assessment of the relationship between evidence and hypothesis after finding the optimal tree. I identify a striking discrepancy between the sophistication of the analysis of given data sets (Step 2), and their compilation and the interpretation of the results (Steps 1 and 3). The latter two steps deserve far greater attention than is current practice. Uncritical and nonexplicit character selection, character coding, and character scoring seriously compromise Step 1. Careful comparative morphological study prior to data matrix construction is necessary to remedy this problem in future cladistic analyses. Step 2 is the locus of most recent advances in metazoan cladistics through the increasing availability of computing power, and the development of increasingly efficient phylogenetic software that allows analysis of large data sets. Failure to identify problems and errors generated in Step 1 of the research cycle is testament to the general failure of Step 3. Consequently, recent progress in metazoan cladistics is primarily analytical, while the only empirical anchor of the discipline receives surprisingly little attention. Not surprisingly, the first generation of modern metazoan phylogeneticists used computers principally as a relatively quick and easy means to generate abundant phylogenies from morphological data. The next phase should build on this foundation by critically testing these alternative hypotheses by a thorough qualitative reassessment and elaboration of morphological data matrices, and a more critical approach to data selection. A rigorous research program for metazoan cladistics can only be established when the cladistic research cycle is properly completed, and when subsequent research cycles are effectively linked to previous efforts.