Immunoglobulin isotypes: structure, function, and genetics.
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Biomedical subjects
Publications and source records attributed to N Miller.
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BACKGROUND: The precision of intraocular lens (IOL) calculation is essentially determined by the accuracy of the measurement of axial length. In addition to classical ultrasound biometry, partial coherence interferometry serves as a new optical method for axial length determination. A functional prototype from Carl Zeiss Jena implementing this principle was compared with immersion ultrasound biometry in our laboratory. PATIENTS AND METHODS: In 108 patients attending the biometry laboratory for planning of cataract surgery, axial lengths were additionally measured optically. Whereas surgical decisions were based on ultrasound data, we used postoperative refraction measurements to calculate retrospectively what results would have been obtained if optical axial length data had been used for IOL calculation. For the translation of optical to geometrical lengths, five different conversion formulas were used, among them the relation which is built into the Zeiss IOL-Master. IOL calculation was carried out according to Haigis with and without optimization of constants. RESULTS: On the basis of ultrasound immersion data from our Grieshaber Biometric System (GBS), postoperative refraction after implantation of a Rayner IOL type 755 U was predicted correctly within +/- 1 D in 85.7% and within +/- 2 D in 99% of all cases. An analogous result was achieved with optical axial length data after suitable transformation of optical path lengths into geometrical distances. CONCLUSIONS: Partial coherence interferometry is a noncontact, user- and patient-friendly method for axial length determination and IOL planning with an accuracy comparable to that of high-precision immersion ultrasound.
A case-control study was undertaken to determine if asymptomatic carotid artery stenosis (ACS) is independently associated with ipsilateral hemispheric stroke following cardiac surgery (CS). All CS patients (3069) who were at two hospitals between 1989 and 1994 were reviewed. Cases (31) selected for this study were those with hemispheric stroke within 30 days following CS. Controls (69) were taken from those without hemispheric stroke. Case-control analysis demonstrated that ACS of 50-90% and of 80-90% increased the risk of ipsilateral stroke 5.2-fold (95% confidence interval [CI] = 1.5-16.3, p = 0.01) and 24.3-fold (CI = 2.6-114.9, p = 0.002), respectively. Other variables with significant odds ratios (OR) were age > or =65 years (OR = 4.0, CI = 1.3-10.5, p = 0.01), peripheral vascular disease (OR = 3.4, CI = 1.3-8.8, p = 0.02), hypertension (OR = 3.0, CI = 1.2-7.0, p = 0.02), and female gender (OR = 3.0, CI = 1.2-7.1, p = 0.04). A second conservative analysis for missing data demonstrated a significant association for ACS of 80-90% alone (OR = 13.1, CI = 1.5-60.9, p = 0.01). This association remained significant after multivariate adjustment with propensity score stratification. ACS (80-90%) appears to be independently associated with ipsilateral hemispheric stroke following CS when evaluated against the present study variables. This finding supports the need for a properly conducted prospective natural history study, including an evaluation of aortic arch atherosclerosis, to determine the clinical relevance of this observation.
Four studies examined the effect of positive versus neutral affect on preference among potential discussion partners who were members of two in-groups, two out-groups, or both an in-group and an out-group (crossed targets). The importance of targets' category memberships was manipulated by idiographically based selection. Positive affect elevated evaluation of crossed targets with a dominant (differentially important) in-group (Study 1). When categories were made equally important, positive affect had no impact (Studies 2 and 3). Study 4 presented crossed targets with both equally and differentially important group memberships and showed that differential category importance (dominance) is necessary for positive affect to influence judgments about them. These results are explained by the broadened categorization induced by positive affect.
Content analysis of 122 social psychology textbooks confirmed that displaced aggression received a surge of attention immediately following J. Dollard, L. W. Doob, N. E. Miller, O. H. Mowrer, and R. R. Sears (1939), but subsequent interest sharply declined. Contemporary texts give it little attention. By contrast, meta-analysis of the experimental literature confirms that it is a robust effect (mean effect size = +0.54). Additionally, moderator analyses showed that: (a) The more negative the setting in which the participant and target interacted, the greater the magnitude of displaced aggression; (b) in accord with N. E. Miller's (1948) stimulus generalization principle, the more similar the provocateur and target, the more displaced aggression; and (c) consistent with the contrast effect (L. Berkowitz & D. A. Knurek, 1969), the intensity of initial provocation is inversely related to the magnitude of displaced aggression.
Two studies examined the interaction between the presence or absence of (a) an initial provocation and (b) a subsequent minor triggering action on the part of the target of displaced aggression. Consistent with the triggering event being seen by participants as indeed trivial when administered by itself without prior provocation, exposure to it literally had no impact on aggression toward its source. When previously provoked, however, this subsequent triggering event strongly increased displaced aggression, causing it to reliably exceed both that displayed when there was no antecedent provocation and that elicited by provocation alone. Mediation analyses showed that for participants who had been provoked, subjective feelings of displeasure concerning the triggering event mediated the effect of the trigger on aggression.
Purge-and-trap, solid-phase extraction, and solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) sample preparation techniques for the analysis of odor impact chemicals in fermented cucumber brine are compared. SPME-GC-MS is coupled with detection frequency olfactometry experiments to determine key impact odor compounds in the brine. The most potent odorants that define the typical characteristic brine aroma are trans-4-hexenoic acid and cis-4-hexenoic acid. Confirmation of key impact odorants in brine is confirmed by recombination experiments.
PURPOSE: The study examined trends and predictors of state Medicaid home and community based waiver participants and expenditures from 1992 to 1997 to identify factors of interest to policy makers and clinicians. DESIGN AND METHODS: HCFA Form 372 data were collected from state officials for each waiver for each year. Two separate regression analyses were conducted to examine the effects of sociodemographic, economic, political, policy, and health services on state waiver participants and expenditures. RESULTS: State waiver participants were positively associated with those aged 85 and over, personal income, residential care beds, and inpatient users and negatively with home health regulation and nursing home beds. State waiver expenditures were positively associated with democratic governors, personal income, home health reimbursement methods, Medicaid eligibility, home health agencies, and Medicare home health users. IMPLICATIONS: The factors policy makers might consider changing include increasing the number of residential care beds and home health agencies, removing certificate of need for home health care, using Medicare home health reimbursement methods for Medicaid, and raising the Medicaid eligibility criteria. In some states with low nursing home occupancy rates, reducing the supply of nursing home beds may also be considered. All of these approaches would be controversial and should be based on additional cost-effectiveness analysis.
Campath-1H, a humanized mAb undergoing clinical trials for treatment of leukemia, transplantation and autoimmune diseases, produces substantial lymphocyte depletion in vivo. The antibody binds to CD52, a highly glycosylated molecule attached to the membrane by a glycosylphosphatidylinositol anchor. Cross-linked Campath-1H is known to activate T cells in vitro. We have investigated the molecular basis for these effects by comparing the protein tyrosine phosphorylation signals induced by Campath-1H and the CD3 mAb OKT3 in primary T cells, and in CD45(+)TCR(+), CD45(-)TCR(+) and CD45(+)TCR(-) Jurkat subclones transfected with CD52. Our results show that Campath-1H triggers similar tyrosine phosphorylation events as OKT3 in both primary T cells and in the CD45(+)TCR(+) Jurkat sub-clone, albeit at quantitatively lower levels. However, no phospholipase C gamma 1 activation nor calcium signals were detected in response to CD52 ligation. The CD52-mediated induction of protein tyrosine phosphorylation was absolutely dependent upon the expression of both the TCR and the CD45 phosphotyrosine phosphatase at the cell surface. Cross-linking of Campath-1H was essential for signal transduction in all cells investigated. Fluorescence resonance energy transfer was used to demonstrate CD52 homo-association at the cell surface in Jurkat T cells in a TCR- and CD45-independent manner, and CD52-TCR association in CD45(+)TCR(+) cells. We propose a model to explain the activating effects of Campath-1H in which CD52 mAb cross-linking causes the trapping of TCR polypeptides within molecular complexes at the cell surface, thereby inducing signals via the TCR by a process which depends on the CD45-mediated regulation of the p56(lck) and p59(fyn) tyrosine kinases.
The LiPA MYCOBACTERIA (Innogenetics NV, Ghent, Belgium) assay was used to identify mycobacterial isolates using culture fluid from positive BACTEC 12B bottles. The LiPA method involves reverse hybridization of a biotinylated mycobacterial PCR fragment, a 16 to 23S rRNA spacer region, to oligonucleotide probes arranged in lines on a membrane strip, with detection via biotin-streptavidin coupling by a colorimetric system. This system identifies Mycobacterium species and differentiates M. tuberculosis complex, M. avium-M. intracellulare complex, and the following mycobacterial species: M. avium, M. intracellulare, M. kansasii, M. chelonae group, M. gordonae, M. xenopi, and M. scrofulaceum. The mycobacteria were identified in the laboratory by a series of tests, including the Roche AMPLICOR Mycobacterium tuberculosis (MTB) test, the Gen-Probe ACCUPROBE, and a PCR-restriction fragment length polymorphism (PCR-RFLP) analysis of the 65-kDa heat shock protein gene. The LiPA MYCOBACTERIA assay detected 60 mycobacterium isolates from 59 patients. There was complete agreement between LiPA and the laboratory identification tests for 26 M. tuberculosis complex, 9 M. avium, 3 M. intracellulare complex, 3 M. kansasii, 4 M. gordonae, and 5 M. chelonae group (all were M. abscessus) isolates. Three patient samples were LiPA positive for M. avium-M. intracellulare complex, and all were identified as M. intracellulare by the PCR-RFLP analysis. Seven additional mycobacterial species were LiPA positive for Mycobacterium spp. (six were M. fortuitum, and one was M. szulgai). The LiPA MYCOBACTERIA assay was easy to perform, and the interpretation of the positive bands was clear-cut. Following PCR amplification and gel electrophoresis, the LiPA assay was completed within 3 h.
Five adolescents with autism, 5 adult control participants, and 4 child controls received rewards for varying their sequences of responses while playing a computer game. In preceding and following phases, rewards were provided at approximately the same rate but were independent of variability. The most important finding was that, when reinforced, variability increased significantly in all groups. Reinforced variability could provide the necessary behavioral substrate for individuals with autism to learn new responses.
MEDLINEplus is a Web-based consumer health information resource, made available by the National Library of Medicine (NLM). MEDLINEplus has been designed to provide consumers with a well-organized, selective Web site facilitating access to reliable full-text health information. In addition to full-text resources, MEDLINEplus directs consumers to dictionaries, organizations, directories, libraries, and clearinghouses for answers to health questions. For each health topic, MEDLINEplus includes a preformulated MEDLINE search created by librarians. The site has been designed to match consumer language to medical terminology. NLM has used advances in database and Web technologies to build and maintain MEDLINEplus, allowing health sciences librarians to contribute remotely to the resource. This article describes the development and implementation of MEDLINEplus, its supporting technology, and plans for future development.
PURPOSE: This trial was designed to identify factors affecting patency rates of primary prosthetic above-knee femoropopliteal bypass grafts at 5 years. METHODS: A multi-institutional, prospective trial randomized 240 patients to compare patency rates of Gore-tex and Hemashield above-knee femoropopliteal bypass grafts at 5 years. Univariate comparisons of patency between levels of each prognostic variable were made with the Kaplan-Meier method. Variables that had a univariate P value less than.25 or those known to be important were submitted to a Cox regression analysis. RESULTS: The patient survival rate at 5 years was 59.4%. There were no differences in primary or secondary patency rates at 5 years between the two graft materials (primary, 45% vs 43% and secondary, 68% vs 68%). The risk for graft occlusion was significantly increased for patients younger than 65 years (2.1; P =.001) and for grafts with a diameter less than 7 mm (1.65; P =.0219). Variables with no apparent independent effect on patency rates were smoking status, runoff, diabetes mellitus, sex, presenting symptoms, and postoperative treatment with aspirin or Coumadin. Noninvasive test results were not predictive of subsequent graft function. CONCLUSION: Although the type of prosthetic used for above-knee femoropopliteal bypass grafts does not affect 5-year patency rates, age and graft size do influence results. These factors should be considered before a prosthetic bypass grafting procedure. Furthermore, these data should serve as a contemporary standard, with which evolving and conventional procedures can be compared.
This study examines the mortality trends for chronic obstructive pulmonary disease (COPD) among whites and African Americans in Missouri from 1980-1996. Data from the Missouri Center for Health Information Management and Epidemiology were used to calculate mortality rates. Missouri's COPD deaths rose 40.6% from 1980-1996. Projections through the year 2006 predict continued escalation in rates. Much of the growth in COPD can be attributed to heavy tobacco use in the population.
This study presents the histologic analysis of an implant retrieved 14 months after loading because of a fracture in the collar region. The implant (Biovent) was removed with part of the periimplant tissues, and the block was prepared using cutting and grinding equipment to obtain 3 sections approximately 30 microns thick. The examination evidenced a high degree of osseointegration, with a bone-to-implant contact of 74% +/- 13%. The lamellar bone was dense and in close relation with the hydroxyapatite coating of the implant. The connection between the 0.4-mm hydroxyapatite coating and the metal was always very tight. The thickness of the metal at the break point was assessed to be 1.6 mm. Besides the relative weakness of the metal at the neck of the implant, other possible causes of failure are discussed.
The human PEG1 gene is a newly identified imprinted gene on 7q32. Genetic aberrations of this chromosomal region are often detected in invasive breast carcinomas. In this study, we show monoallelic PEG1 expression in normal breast tissue, indicating the presence of a functional imprint, and more importantly, we demonstrate loss of imprinting (LOI) in all of seven informative invasive breast carcinomas. In contrast to this, in one case of atypical ductal hyperplasia (ADH) found in residual breast, imprinting was maintained. This raises the possibility that aberrant imprinting of PEG1 may be involved in the progression from hyperplasia to invasive breast cancer.
The ribosome-inactivating protein, Shiga-like toxin-1 (SLT-1), targets cells that express the glycolipid globotriaosylceramide (CD77) on their surface. CD77 and/or SLT-1 binding was detected by flow cytometry and immunocytochemistry on lymphoma and breast cancer cells recovered from biopsies of primary human cancers as well as on B cells or plasma cells present in blood/bone marrow samples of multiple myeloma patients. Breast cancer cell lines also expressed receptors for the toxin and were sensitive to SLT-1. Treatment of primary B lymphoma, B-cell chronic lymphocytic leukemia, and myeloma B or plasma cells with SLT-1-depleted malignant B cells by 3- to 28-fold, as measured by flow cytometry. Depletion of myeloma plasma cells was confirmed using a cellular limiting dilution assay followed by reverse transcriptase-polymerase chain reaction analysis of clonotypic IgH transcripts, which showed a greater than 3 log reduction in clonotypic myeloma cells after SLT-1 treatment. Receptors for the toxin were not detected on human CD34(+) hematopoietic progenitor cells (HPC). HPC were pretreated with a concentration of SLT-1 known to purge primary malignant B cells and cultured for 6 days. The number of HPC was comparable in toxin-treated and untreated cultures. HPC were functionally intact as well. Colony-forming units (CFU) were present at an identical frequency in untreated and SLT-1 pretreated cultures, confirming that CFU escape SLT-1 toxicity. The results suggest the ex vivo use of SLT-1 in purging SLT-1 receptor-expressing malignant cells from autologous stem cell grafts of breast cancer, lymphoma, and myeloma patients.
BACKGROUND: A single-institution review of clinical presentation, treatment, and outcome of male breast carcinoma was conducted. METHODS: Data obtained by chart review of 229 cases were analyzed with respect to clinical presentation, treatment choice, significant prognostic factors, and survival. The patients were analyzed both as a single cohort and as four cohorts grouped according to decade of diagnosis. RESULTS: Presentation occurred at a median age of 63 years, most often with a self-detected lump. Pathology consisted of subtypes similar to those of female breast carcinoma. The majority of tumors were larger than 2 cm in greatest dimension. Lymph node status, hormone receptors, and histologic and nuclear grade were underreported. Primary, adjuvant, and advanced disease treatment practices were reviewed over time. The 5-year disease free survival (DFS), overall survival (OS), and local control were 47%, 53%, and 91%, respectively. No difference in outcome by decade of diagnosis was observed. Negative lymph nodes and adjuvant hormone treatment predicted for better DFS and OS. Younger age and Stage 0 also predicted for better OS. CONCLUSIONS: Compared with data from female breast carcinoma patients, 5-year OS for this series was low; however, when these patients were separated by lymph node status, survival was similar for those with axillary lymph node metastases. Despite a change in standard primary surgical treatment and an increased use of chemotherapy and hormone therapy over the study period, no difference in outcome was observed among these males. In the absence of prospective, randomized clinical trials, collection of comprehensive data on the presentation and management of male breast carcinoma may help to optimize clinical care.