Biomedical subjects
Publications and source records attributed to D Greer.
The marrow hematopoietic stem cell is currently being redefined as to all aspects of its phenotype and its total differentiation capacity. This redefinition now includes its plasticity as to production of nonhematopoietic and hematopoietic cell types, the determinants of its in vivo engraftment potential and its expression of stem cell functional characteristics.
Long-term multilineage allochimerism can be obtained in H2-mismatched B6.SJL to BALB/c transplants with host irradiation of 100 cGy, donor spleen cell pre-exposure and costimulator blockade with anti-CD40 ligand (CD40L) antibody. We evaluated this allochimerism approach in murine marrow transplants with different degrees of major histocompatibility complexe (MHC) mismatching; these include: (1) H2-mismatched transplant H2Kk to H2Kb, (2) full haplo-identical transplant H2Kbd to H2Kbk, (3) a partial haplo-identical transplant H2Kd to H2Kbd and (4) an MHC class II mismatch. Levels of chimerism increased up to 12 weeks and then stayed relatively stable up to 1 year after transplant. At 18 weeks post-transplant, the H2-mismatched, haplo-identical, partial haplo-identical and class II-mismatch transplants evidenced 17.9+/-4.4, 40.7+/-0.9, 25.1+/-4.19 and 33.7+/-3.5% donor chimerism, respectively. Dropping the anti-CD40 antibody treatment and spleen cells or changing the schedule of antibody to one injection, in haplo-identical or full-mismatched transplants resulted in no donor-derived chimerism. On the other hand, these still resulted in minor chimerism in class II-mismatched transplants. Lineage analysis of peripheral blood at 6 and 12 months post-transplant demonstrated a significant shift toward increased chimeric lymphocytes and decreased chimeric granulocytes in the full H2 as compared with haplo-identical or class II transplants. Transplantation with anti-CD40L antibody eliminated both graft-versus-leukemia and graft-versus-host disease (GVHD) and delayed lymphocyte infusion did not rescue animals from fatal leukemia. In conclusion, under the conditions of our tolerization regimen, a haplo transplant gives higher engraftment levels than a full H2 mismatch, and despite lower engraftment levels, a class II-mismatched transplant can be successfully accomplished with only 100 cGy and no CD40L blockade.
On the basis of our studies of the fluctuation of the hematopoietic stem cell phenotype with cell cycle trnsit, we hypothesize that the ability of marrow stem cells to convert to nonhematopoietic cells will also vary at different points in the cell cycle. The new biology of stem cells has an impact on many fields including developmental biology and stem cell biology and the clinical potential is enormous.
Two experiments were conducted to study the effects of six processing techniques for barley grain in a 3 x 2 factorial arrangement of grain conditions and roller settings on ruminal degradation of the grain (Exp. 1) and on growth performance by 138 feedlot steers (n = 23 per treatment; Exp. 2). Dry barley (11% moisture, D barley), barley tempered to 20% moisture (M barley), and barley tempered with 60 mL/t of surfactant-based tempering agent (GrainPrep, Agrichem, Inc., Anoka, MN; MS barley), were each rolled at two roller settings selected from preliminary tests. The settings selected for the study were RD, the roller position that had yielded optimally processed D barley, and RMS, the setting that had yielded optimally processed MS barley. Setting RMS was tighter than RD. Barley rolled at the RMS setting was more extensively processed (i.e., had a lower [P < 0.001] processing index, PI), had lighter (P < 0.001) volume weight, thinner (P < 0.001) kernels, and fewer (P < 0.001) whole kernels compared with setting RD. Tempering did not affect (P > 0.05) PI, percentage of whole kernels, or kernel thickness at either roller setting. The processing characteristics of tempered barley were unaffected (P > 0.05) by surfactant. The extent of in situ DM disappearance (ISDMD) was higher (P < 0.01) in grain rolled at setting RMS compared with RD. At both roller settings, tempering reduced (P < 0.05) ISDMD between 4 and 24 h of ruminal incubation. Steers fed RMS-rolled barley had lower (P < 0.001) DMI, slightly lower (P = 0.084) ADG, but increased (P < 0.05) gain:feed (G:F) compared with steers fed RD-rolled barley. Tempering did not affect (P > 0.05) ADG, DMI, or G:F during backgrounding, but improved (P < 0.01) these variables during finishing. Surfactant improved (P < 0.05) G:F but not DMI or ADG. The improvement in G:F was most pronounced when setting RMS was used. The optimal PI values calculated from performance data were numerically greater for the backgrounding diet than for the finishing diet. Steers fed M or MS barley had heavier (P < 0.01) hot carcasses and thicker (P < 0.05) fat cover but lower (P < 0.05) dressing percentages than steers fed D. When the feed barley was rolled at setting RMS, steers fed MS barley produced heavier (P < 0.05) carcasses than those fed M. Tempering with or without surfactant increased performance by feedlot steers compared with not tempering. Diet composition and degree of barley processing mediated this effect.
The armamentarium available for treating acute stroke patients is growing as clinical trials show benefit of intravenous thrombolysis, intra-arterial clot lysis, and antiplatelet agents. Patients with dissection or severe atheromatous stenosis of major cerebrovascular vessels are commonly treated with anticoagulation to prevent recurrent artery-to-artery embolus or arterial thrombosis. These advances in acute stroke treatments demand an accurate means to quickly identify those patients most likely to benefit (or not benefit) from a specific therapy. Fortunately, advances in imaging cerebrovascular lesions, decreased brain perfusion, and even ischemic tissue injury now make it possible to consider tailoring therapy to the individual patient's cerebrovascular problem. Experience and controlled clinical data in this endeavor is meager. Here we describe the ability of various emergency neuroimaging tools to provide information on the state of brain blood flow, metabolism, and vascular anatomy. Most importantly, we present the rationale and limited available evidence relevant to how the neuroimaging information might be used to select optimal treatments for individual patients.
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To learn if there are brain asymmetries for image generation we asked 50 right-handed normal subjects to image one-half of an object and to report which half (right or left) they saw. We found that these subjects were more likely to image the right half of objects than the left. We also found that right hemi-imagers demonstrated a greater degree of right-handedness than did left hemi-imagers. Our results suggest that in strongly right-handed subjects the left hemisphere is more adept at object image generation than is the right hemisphere.
Several nucleic acid amplification techniques (NAAT) have been developed for rapid and direct detection of Mycobacterium tuberculosis (MTB) from clinical specimens. This study compared the performances of the Gen-Probe Amplified MTB Direct Test (AMDT), Roche Amplicor MTB PCR test, and an IS6110-PCR assay with acid-fast smear and culture in the detection of MTB from 428 respiratory specimens from 259 patients. Patients' charts were reviewed for clinical correlation. Of 98 specimens that were clinically positive for MTB, acid-fast smear was positive in 50% of cases, culture in 93%, IS6110-PCR in 83%, AMDT in 84%, and Amplicor MTB PCR in 80%. Of 337 specimens that were negative for MTB, 117 (35%) were positive for nontuberculous mycobacteria. Specificities were as follows: smear, 89%; culture, 100%; IS6110-PCR, 99%; AMDT, 98%; and Amplicor MTB PCR, 96%. The accuracies of the tests were 80%, 98%, 96%, and 92%, respectively. MTB culture-positive specimens that were smear-negative were detected by AMDT and IS6110-PCR in 77% of cases and by Amplicor MTB PCR in 70%. NAAT was less sensitive than was culture for detection of MTB, but all these techniques had acceptable accuracy and were completed within hours. NAAT may be useful for rapid screening of respiratory specimens to distinguish MTB from nontuberculous mycobacteria infection in order to isolate patients.
Back pain among nurses is a common problem. Prior studies of this problem have been based on cross-sectional or retrospective data. This 18-month prospective study involving nurses newly graduated from nursing school investigated personal, worksite, and training factors associated with future risk of back pain. Each nurse underwent a preliminary interview and periodic follow-ups to identify those with back injuries. Contingency tables and logistic regression analyses demonstrated that prior significant back pain episodes (evidenced by previous job changes because of back pain, frequent medication use, etc.) were associated with increased future risk. Training at nursing school or on the job did not have a protective effect. This pilot study therefore suggests factors useful in placement and counseling of new nurses and indicates the need for further implementation of mechanical lift assist device use.
Supermarket checkers are known to be at risk of upper-extremity cumulative trauma disorders. Forty-two experienced checkers checked a standard "market basket" of items on an experimental checkstand. The counter height could be adjusted (high = 35.5, low = 31.5 inches), and the pre-scan queuing area length (between conveyor belt and laser scanner) could be set to "near" or "far" lengths. Each subject scanned under the high-near, high-far, low-near, and low-far conditions in random order. Seven ordinal symptom scales were used to describe comfort. Analysis showed that both counter height and queuing length had significant effects on symptoms. Furthermore, the height of the subject affected the degree and direction of the impact of the checkstand configuration differences. The study suggests that optimization of design may be experimentally evaluated, that modification of postural as well as frequency loading may be beneficial, and that adjustability for the individual may be advisable.
The use of the N-acetyl-beta-D-glucosaminidase (NAGase) test for detecting subclinical mastitis was investigated in surveys of milk samples from 20 farms. A milk sample was considered to be mastitic if it had a milk cell count above 400,000 cells/ml, and the NAGase test results were graded accordingly. The test gave an average of 16.6 per cent false positives and 2.0 per cent false negatives per herd. It was concluded that the NAGase test could be used as a rapid screening method for selecting suspect samples for further analysis by standard methods.
Milk samples collected from normal and experimentally infected quarters of five heifers throughout their first lactation were examined by bacterial culture, milk cell count (MCC), N-acetyl-beta-D-glucosaminidase (NAGase) test and a monoclonal antibody based antigen-capture ELISA. The results were analysed according to the presence (mastitis positive) or absence (mastitis negative) of bacteria on culture, and the numbers of false negative and false positive results of the other three tests defined in relation to this. Similar numbers of false negative results were observed with the MCC (20), NAGase (18) and ELISA (13). False positive results due to the physiological factors present in early lactation were evident in the MCC, prominent in the NAGase test and absent from the ELISA. The major difference in false positive results associated with experimental infection between the three tests was the more rapid return to negative values of the ELISA following resolution of infection, compared with MCC and NAGase.
A new enzyme immunoassay (EIA), PREMIER Cryptococcal Antigen, was compared with latex agglutination (LA) for the detection and quantitation of circulating capsular polysaccharide antigen from Cryptococcus neoformans. The clinical evaluation of PREMIER EIA as a screening assay, including 475 specimens with 120 LA and EIA positives, resulted in 99% sensitivity and 97% specificity. The clinical specimens included sera and cerebrospinal fluids as well as 10 rheumatoid factor-positive and 20 anti-nuclear antibody-positive serum samples. This monoclonal antibody-based assay detects serotypes A to D at 0.63, 0.63, 7.8, and 62 ng/ml, respectively. With three different known positive specimens, the assay was found to yield coefficients of variation of 2 to 12% for intra- and interassay comparisons of precision and reproducibility. The primary use for semiquantitative values derived with the LA or EIA is to follow the course of disease and monitor drug therapies. The present data suggest that the PREMIER EIA will be a valuable method for this purpose. We conclude that the PREMIER Cryptococcal Antigen EIA provides a rapid, convenient, and reliable antigen detection method for screening and semiquantitative determination of antigen levels.
A monoclonal antibody to a 23.5-kDa bovine inflammatory antigen present in high levels in mastitic milk has been used in an antigen-capture enzyme-linked immunosorbent assay (ELISA) to screen milk samples from herds of cattle for subclinical mastitis. The results from 20 herds with a total of 2,612 quarter samples are presented. Good correlation was observed between the ELISA level and the milk cell count (MCC). The results demonstrated an average of 5% false negatives (1.8% associated with isolates of Staphylococcus aureus and/or Streptococcus spp.) and 7.7% false positives for each herd in relation to mastitic (greater than 400,000 cells per ml) or nonmastitic (less than 400,000 cells per ml) MCCs.
An artificial intelligence expert-based system for facilitating the clinical recognition of occupational and environmental factors in lung disease has been developed in a pilot fashion. It utilizes a knowledge representation scheme to capture relevant clinical knowledge into structures about specific objects (jobs, diseases, etc) and pairwise relations between objects. Quantifiers describe both the closeness of association and risk, as well as the degree of belief in the validity of a fact. An independent inference engine utilizes the knowledge, combining likelihoods and uncertainties to achieve estimates of likelihood factors for specific paths from work to illness. The system creates a series of "paths," linking work activities to disease outcomes. One path links a single period of work to a single possible disease outcome. In a preliminary trial, the number of "paths" from job to possible disease averaged 18 per subject in a general population and averaged 25 per subject in an asthmatic population. Artificial intelligence methods hold promise in the future to facilitate diagnosis in pulmonary and occupational medicine.
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Active lifestyles may delay the onset of the functional consequences of chronic disease, potentially increasing active life expectancy. We analyzed the Longitudinal Study of Aging (LSOA) to test the hypothesis that elders participation in an active lifestyle prevents loss of function. Focusing on the cohort aged 70-74 who reported being able to carry 25 lb, walk 1/4 mile, climb 10 steps and do heavy housework without help and without difficulty at baseline, decline was defined as no longer being able to perform these tasks independently and without difficulty 2 years later. Using multivariate logistic regression, results reveal that those who did not report regularly exercising or walking a mile were 1.5 times more likely to decline than those who did, controlling for reported medical conditions and demographic factors. Similar findings (with different models) were observed for both men and women. Findings suggest the potential value of programs oriented toward the primary prevention of functional decline.