Restriction in the repertoire of the immunoglobulin light chain subgroup in pathological cold agglutinins with anti-Pr specificity

BACKGROUND AND OBJECTIVES: In cold agglutinin disease, monoclonal red blood cell autoantibodies, termed cold agglutinins, induce haemolysis in patients exposed to the cold. Commonly, these autoantibodies are directed against the developmentally regulated I/i blood groups. A second blood group system, the Pr system (located on glycophorins), is involved less frequently. Anti-Pr cold agglutinins recognize either alpha 2,3- or alpha 2,6-linked N-acetylneuraminic acid as the immunodominant group. Cold agglutinins of anti-I/i specificity show a remarkable restriction in their genomic repertoire of the immunoglobulin heavy and light-chain immunoglobulin-variable domain (i.e. exclusive use of VH4-34 in heavy chains). For anti-Pr cold agglutinins, preliminary data on the repertoire of the light-chain variable domain indicate a preference for the subgroup Vkappa IV. To elucidate restrictions in the light-chain variable-domain subgroup repertoire of anti-Pr cold agglutinins systematically, and to discuss these results in the context of their anti-Pr(1-3) subclassification and immunodominant sialic acid, light chains in 13 anti-Pr cold agglutinins were investigated. MATERIALS AND METHODS: The anti-Pr light chains were isolated using temperature-dependent absorption/elution techniques. Subsequently, they were subjected to N-terminal Edman degradation, and the light chain Vkappa subgroup was affiliated using the Kabat database. RESULTS: Five of 13 (38%) light chains belonged to Vkappa IV, five of 13 (38%) to Vkappa I and three of 13 (23%) to Vkappa III. Anti-Pr with Vkappa IV subgroup light chains exclusively recognized alpha 2,3-linked N-acetylneuraminic acid. CONCLUSIONS: Including data from the literature, the repertoire of the light-chain variable domain in pathological anti-Pr cold agglutinins exhibits a clear bias towards the use of the single germline gene-derived subgroup, Vkappa IV (eight of 17 or 47%). The association of Vkappa IV subgroup light chain-containing anti-Pr cold agglutinins with binding to alpha 2,3-, but not alpha 2,6-linked N-acetyneuraminic acid raises speculations about a possible role of subgroup-derived determinants in anti-Pr binding.     

Immunologic Identification of Tissue Factor (Thromboplastin) Synthesized by Cultured Fibroblasts

The proliferative capacity of bone marrowcells from thymus-deprived nude mice wasinvestigated in lethally irradiated recipients. Although the colony-forming capacityof these cells was found to be similar tothat of normal littermates, a reduction inthe number of nucleated cells was observed in the bone marrow of nude mice.Moreover when the radioprotective effectof such cells was studied, it was foundthat 5 x 10⁵ or 2 x 10⁶ bone marrowcells from nude mice were less effectivein restoring hemopoiesis and establishingpermanent chimerism than similaramounts of bone marrow cells of normalcontrols. In addition, irradiated animalssurviving after injection of bone marrowcells from nude mice were found to havelower immune responses to SRBC thannormal chimeras. The possibility that mortality of irradiated recipients injected withbone marrow of nude mice is due to thepresence of a latent infective agent or ofsome inhibitory factor of hematopoiesis inthe bone marrow of such nude mice isshown to be improbable. Alternatively it issuggested that nude mice suffer from anintrinsic defect in the proliferative capacityof their bone marrow colony-forming cells(CFUs).

Submitted on February 12, 1973 Revised on March 29, 1973 Accepted on April 20, 1973     

Usefulness of dipyridamole stress echocardiography for predicting graft patency after coronary artery bypass grafting

Noninvasive techniques often provide controversial results in patients who have coronary artery bypass grafts (CABGs). Vasodilator stress echocardiography allows semi-simultaneous imaging of CABG flow and segmental left ventricular wall motion. To assess the comparative and additive value of regional flow and function for noninvasive evaluation of graft patency status, we evaluated 110 consecutive patients who underwent CABG and who were scheduled for coronary angiography. All patients underwent stress echocardiography with dipyridamole (0.84 mg/kg) and atropine (1 mg), including wall motion analysis by 2-dimensional echocardiography and Doppler evaluation of flow reserve of each CABG. Echocardiographic findings were compared with angiographic data. Four patients had inadequate acoustic windows. The remaining 106 patients had 226 grafts performed. Stress echocardiography showed 67% sensitivity, 91% specificity, and 71% accuracy for identification of 50% to 100% stenosis in the graft or in the recipient coronary vessel. There was a fair agreement with angiography (kappa coefficient 0.60). Identification of impaired coronary bypass flow reserve (i.e., <1.9 for internal mammary grafts and <1.6 for saphenous vein grafts) by Doppler had 91% sensitivity, 88% specificity, and 89% accuracy for graft stenosis. There was good agreement with angiographic findings (kappa 0.77). The combination of the 2 techniques achieved 93% sensitivity, 93% specificity, and 93% accuracy, showing a very good agreement with the patency status of the grafts as evaluated at angiography (kappa 0.85). The combined assessment of wall motion and flow reserve in patients who underwent CABG is feasible and provides an accurate estimate of graft patency status by increasing sensitivity of stress echocardiography and specificity of Doppler flow reserve.     

ER-β expression in large bowel adenomas: Implications in colon carcinogenesis

BACKGROUND: A pivotal role of oestrogen receptor-beta has been suggested in colon carcinogenesis in humans. However, few data are available on oestrogen receptor-beta in colorectal pre-cancerous lesions. AIM: In the present study, we evaluated oestrogen receptor-beta expression and its possible correlation with proliferative activity and apoptosis in colorectal adenomas and normal colon tissue. PATIENTS/METHODS: Adenomatous tissue from 25 patients with colonic polyps, and normal tissue from 25 controls were used. Oestrogen receptor-beta expression, colonocyte proliferation (expressed as PCNA positivity) and apoptosis were evaluated. RESULTS: In adenomatous tissue, a significant reduction of oestrogen receptor-beta was observed compared to normal mucosa (10.1+/-5.5% vs. 44.2+/-13.7; p<0.03), while the expression of oestrogen receptor-alpha remained unvaried. Cell proliferative activity significantly increased in adenomatous tissue compared to normal mucosa (59.3+/-7.1 vs. 18.5+/-8.8; p<0.0001), doubling the PCNA/apoptosis ratio. An inverse correlation was found between oestrogen receptor-beta and PCNA expression in adenomas (r=-0.81), a datum confirmed by confocal microscopy evaluation. CONCLUSIONS: Our data demonstrate, for the first time, a significant reduction of oestrogen receptor-beta expression already in the pre-cancerous phase of colon carcinogenesis. This suggests a role of selective oestrogen receptor-beta agonists in the prevention of colorectal cancer.     

Low-level colonization and infection with ciprofloxacin-resistant gram-negative bacilli in a skilled nursing facility

Background: We report a 1-year surveillance study that evaluates colonization and infection with ciprofloxacin-resistant gram-negative bacilli (CR GNB) and the relation to quinolone use and other possible risk factors in a proprietary skilled nursing facility (SNF) with no history of outbreaks. Methods: Rectal swabs obtained quarterly were streaked on MacConkey agar with ciprofloxacin discs (5 μg) to screen for CR GNB and later were speciated and the antimicrobial susceptibilities were confirmed by standardized disc-diffusion tests. Results: The mean prevalence of CR GNB colonization was 2.6% (range 0.9% to 5.3%). The colonization frequency was higher in the last survey than it was in the first survey. CR GNB–colonized strains included Pseudomonas species (21%), but more than half were non-Pseudomonas enterics such as Acinetobacter baumannii (25%), Proteus mirabilis (17%), and Providencia stuartii (13%). None of the patients who had colonization with CR GNB had subsequent infections with the same species. Patients with colonization had more exposure to ciprofloxacin and they were more likely to have been recently admitted from an acute-care hospital and have decubitus ulcers. During the study period, of 336 patients surveyed, 98 (29%) patients developed suspected infections and cultures were done; the infection rate was 4.7 per 1000 patient days. Of these infected patients, 59 (60%) were infected by GNBs; the infection rate was 2.3 per 1000 patient days. Nineteen percent of the GNB infections were treated with a quinolone. (Overall, quinolones constituted about 17% of antibiotic usage in the SNF). Only 3 (5%) of the patients infected with GNB were infected with CR GNB, including Pseudomonas and Providenci a species. The CR GNB infections involved multiple sites, multiple organisms, and long length of stay in the SNF. Conclusions: The findings indicate that in this community SNF, a low frequency of colonization or infection with CR GNB existed. Whether continued moderate use of quinolones will lead to increasing levels of CR GNB will require further study. (AJIC Am J Infect Control 1998;26:552-7)     

Automated Algorithm for GI Spike Burst Detection and Demonstration of Efficacy in Ischemic Small Intestine

We present a novel, fully-automated gastrointestinal spike burst detection algorithm. Following pre-processing with SALPA (Wagenaar and Potter, J. Neurosci. Methods 120:113–120, 2002) and a Savitzky–Golay filter to remove unwanted low and high frequency components, candidate spike waveforms are detected utilizing the non-linear energy operator. Candidate waveforms are classified as spikes or artifact by a support vector machine. The new method achieves highly satisfactory performance with >90% sensitivity and positive prediction value. We also demonstrate an application of the new method to detect changes in spike rate and spatial propagation patterns upon induction of mesenteric ischemia in the small intestine. Spike rates were observed to transiently increase 10–20 fold for a duration of ≈600 s, relative to baseline conditions. In ischemic conditions, spike activity propagation patterns included retrograde-longitudinal wavefronts with occasional spontaneous conduction blocks, as well as self-terminating concentric-circumferential wavefronts. Longitudinal and circumferential velocities were 6.8–8.0 cm/s and 18.7 cm/s, respectively.