Xenogeneic bone marrow transplantation: II. Porcine-specific growth factors enhance porcine bone marrow engraftment in an in vitro primate microenvironment

Abstract: Establishment of mixed bone marrow chimerism in pig-to-primate transplantation, as a means of inducing specific immune tolerance, will require that both immune and nonimmune barriers be overcome. As a preliminary step in evaluating nonimmune barriers in this system, we have developed an in vitro model of engraftment in which long-term culture of porcine bone marrow-derived hematopoietic cells is supported on preformed primate bone marrow stromal layers. In the absence of cytokine supplementation, primate stromal cells were unable to support long-term porcine hematopoiesis in these cultures. Supplementation with porcine Steel Factor was required for long-term maintenance of hematopoietic progenitor cell content and total hematopoietic activity. Addition of porcine IL-3, in combination with porcine Steel Factor, increased long-term progenitor cell content and hematopoietic activity on primate stroma to levels comparable to that obtained in cultures on porcine stroma. The combination of porcine GM-CSF and Steel Factor increased progenitor cell content and hematopoietic activity early in the cultures, but had little effect in long-term cultures. The Steel Factor and IL-3 combination was species-specific in its action in these cultures, as the corresponding human cytokines were unable to effectively support long-term porcine hematopoiesis. Likewise, the combination of porcine cytokines had only minimal effects on long-term bone marrow culture of primate CD34+ cells I on primate stroma.     

TRH-induced reflex changes in patients with ALS

A trial of Thyrotropin Releasing Hormone (TRH) 5.0 mg/kg body weight subcutaneously every other day for two weeks produced transient increased tone in muscles, along with other (side-) effects in patients with Amyotrophic Lateral Sclerosis (ALS). One patient's extensor plantar transiently changed to a flexor plantar reflex after injection, probably due to disproportionate increase in tone of the calf muscles. No significant changes in F-waves or H-reflexes were seen. No increase in useful voluntary strength, or in strength measured by Medical Research Council (MRC) testing or strain gauge isometric strength testing was seen. However, dyspnea was seen within 10 minutes of TRH injection.     

Data sources for measuring colorectal endoscopy use among Medicare enrollees.

BACKGROUND: Estimates of colorectal cancer test use vary widely by data source. Medicare claims offer one source for monitoring test use, but their utility has not been validated. We compared ascertainment of sigmoidoscopy and colonoscopy between three data sources: self reports, Medicare claims, and medical records. MATERIALS AND METHODS: The study population included Medicare enrollees residing in North Carolina (n = 561) who had participated in a telephone survey on colorectal cancer tests. Medicare claims were obtained for the 5 years preceding the survey (January 1, 1998 to December 31, 2002). Information about sigmoidoscopy and colonoscopy procedures conducted in physician offices were abstracted from medical records. Sensitivity, specificity, positive predictive value, negative predictive value, agreement, and kappa statistics were calculated using the medical record as the gold standard. Agreement on specific procedure type and purpose was also assessed. RESULTS: Agreement between claim and medical record regarding whether an endoscopic procedure had been done was high (over 90%). Agreement between self report and medical record and between self report and claim was good (79% and 74%, respectively). All three data sources adequately distinguished the type of procedure done. None of the data sources showed reliable levels of agreement regarding procedure purpose (screening or diagnostic). CONCLUSION: Medicare claims can provide accurate information on whether a patient has undergone colorectal endoscopy and may be more complete than physician medical records. Medicare claims cannot be used to distinguish screening from diagnostic tests. Recognizing this limitation, researchers who use Medicare claims to assess rates of colorectal testing should include both screening and diagnostic endoscopy procedures in their analyses.     

A comparison study of dynamic visual acuity between athletes and nonathletes

A comparison study of dynamic visual acuity (DVA) was conducted using samples of nonathletic college students and college baseball players. The experimental population consisted of 17 male baseball players ranging in age from 19-24 years. The control population was made up of 25 male graduate students ranging in age from 23-29 years. Subjects reported the direction of a 20/25 "Landolt C" target exhibiting uniform angular motion produced by a projection system. Angular target velocities between 10 deg/sec and 110 deg/sec with an exposure time of 400 ms were used. The results showed a statistically significant difference between the two groups' DVA. The mean DVA for the baseball players was 82.35 deg/sec and 69.90 deg/sec for the control group.     

Natural immune response to the C-terminal 19-kilodalton domain of Plasmodium falciparum merozoite surface protein 1.

We have characterized the natural immune responses to the 19-kDa domain of merozoite surface protein 1 in individuals from an area of western Kenya in which malaria is holoendemic. We used the three known natural variant forms of the yeast-expressed recombinant 19-kDa fragment that are referred to as the E-KNG, Q-KNG, and E-TSR antigens. T-cell proliferative responses in individuals older than 15 years and the profile of immunoglobulin G (IgG) antibody isotypes in individuals from 2 to 74 years old were determined. Positive proliferative responses to the Q-KNG antigen were observed for 54% of the individuals, and 37 and 35% of the individuals responded to the E-KNG and E-TSR constructs, respectively. Considerable heterogeneity in the T-cell proliferative responses to these three variant antigens was observed in different individuals, suggesting that the 19-kDa antigen may contain variant-specific T epitopes. Among responses of the different isotypes of the IgG antibody, IgG1 and IgG3 isotype responses were predominant, and the prevalence and levels of the responses increased with age. We also found that a higher level of IgG1 antibody response correlated with lower parasite density among young age groups, suggesting that IgG1 antibody response may play a role in protection against malaria. However, there was no correlation between the IgG3 antibody level and protection. Furthermore, we observed that although the natural antibodies cross-reacted with all three variant 19-kDa antigens, IgG3 antibodies in 12 plasma samples recognized only the E-KNG and Q-KNG constructs and not the E-TSR antigen. This result suggests that the fine specificity of IgG3 antibodies differentiates among variant-specific natural B-cell determinants in the second epidermal growth factor domain (KNG and TSR) of the antigen.     

Histamine H1- and H2-receptor involvement in eosinophil infiltration and the microvascular changes associated with cutanneous anaphylaxis

Several substances alter eosinophil motility, but the relative importance of these putative mediators in immediate hypersensitivity remains unclear. The present study has reinvestigated the role of histamine in type I allergic eosinophil infiltration, and the temporally associated microvascular events, by examining the effect of H₁-and H₂-receptor antagonist pretreatment. A combination of cimetidine and pyrilamine significantly reduced eosinophil accumulation, whereas neither antagonist alone was effective. Similarly, cutaneous hyperemia, measured indirectly as ear surface temperature, was reduced only by the cimetidine-pyrilamine combination. Pyrilamine partially attenuated the increase in microvascular permeability, but the addition of cimetidine provided no further reduction.It appears that histamine participates significantly in mediating both the microvascular changes and the eosinophil infiltration evoked by cutaneous anaphylaxis. The histaminergic component of increased microvascular permeability appears to be an H₁-receptor mediated phenomenon. However, blockade of both H₁-and H₂-receptor subtypes is required to inhibit the hyperemia and eosinophil infiltration responses.