Multisystem obstruction with cholestasis, pigmentary retinopathy, and cleft palate: a new syndrome?

A number of systemic abnormalities associated with cholestasis have been reported in the literature. This paper describes two unrelated patients with cholestasis and an unusual constellation of abnormalities including cleft palate/lip, hydronephrosis/hydroureter, retinal pigmentation, and intestinal septum.     

Efficiency of human rotavirus propagation in cell culture.

This study was designed to find methods to reproducibly propagate human rotaviruses from fecal specimens and to determine the relationship between particle numbers and infectivity. Growth of virus was initially compared in primary and continuous lines of monkey kidney cells. Primary cells (African green and cynomolgus monkey kidney) supported virus growth directly from fecal specimens much more efficiently than did continuous lines of African green (CV-1) or rhesus (MA104) monkey kidney cells. Rotaviruses were grown in primary cells from 14 of 14 fecal specimens of different individuals collected over a 3-year period. Although rotaviruses in fecal samples could not always be grown in the continuous cell lines, two passages in primary cells appeared to fully adapt the viruses for propagation in the continuous cell line tested (MA104). The efficiency of rotavirus growth was quantified with five of the fecal isolates. It was calculated that, on the average, 1 out of every 46,000 particles in fecal specimens infected monkey kidney cells. After three passages in primary cells, an average of 1 out of every 6,600 progeny virus particles appeared to be infectious. Thus, rotaviruses in fecal specimens were consistently grown in primary cells, and passage in these cells both increased virus infectivity and adapted the viruses for growth in continuous cell lines.     

Proliferative response of T lymphocytes to a proline-rich polypeptide (PRP): PRP mimics mitogenic activity of Il-1

Mitogenic properties of a proline-rich polypeptide were investigated. The mitogenic action of PRP was compared with the mitogenic action of Il-1. PRP was not mitogenic for thymocytes at doses 0.01-50 micrograms/ml. PRP, at doses 0.1-50 micrograms/ml, augmented the proliferative response of thymocytes to Con A in a similar fashion as Il-1. At doses higher than 10 micrograms/ml, PRP induced proliferation of lymph node cells and splenocytes as well as T cells from the lymph nodes. It did not, however, cause significant proliferation of B cells from the lymph nodes, at the doses used. PRP did not induce proliferation of an antigen specific Lyt 1+ T cell clone. Il-1 behaved in a similar way as PRP in all the tests described. We consider a possibility that under physiological conditions, at a very early stage of postneonatal life, PRP may replace some functions of Il-1.     

Microradiography with an x-ray image magnifier: application to dental hard tissue

The superior spatial resolution obtained with parallel-beam microradiography over conventional contact microradiography has allowed us to image microstructural features of dental hard tissue not previously reported. Our efforts to extend these techniques to provide a real-time capability for viewing in situ demineralization and remineralization effects, at and below the 1-micron level, have resulted in an instrument with several novel and unique features. Using a synchrotron radiation source of x rays and diffraction image magnification, we are now able to change magnification at will (x-ray zoom lens). In addition, the energy range over which the instrument operates gives one considerable flexibility in optimizing image contrast. The techniques of parallel-beam microradiography, and diffraction image magnification are applicable to problems in many other areas of science. Using examples within dental research, the uniqueness and versatility of these new techniques are discussed.     

Rapid and complete donor chimerism after unrelated mismatched cord blood transplantation in 5 children with beta-thalassemia major.

Hematopoietic stem cell transplantation is currently the only curative therapy for beta-thalassemia major. However, <30% of patients have unaffected HLA-identical siblings to serve as donors. We investigated the feasibility of using umbilical cord blood transplants from unrelated HLA mismatched donors and a myeloablative preparative regimen that did not involve total body irradiation. Between October 2003 and November 2004, 5 children with beta-thalassemia major received busulfan, cyclophosphamide, and antithymocyte globulin before cord blood transplantation (median dose, 8.8 x 10(7) cells per kilogram of body weight) from unrelated donors (1 or 2 of 6 HLA antigens were mismatched) and were then evaluated for engraftment, adverse effects, and treatment outcome. The median times to neutrophil engraftment, red blood cell transfusion independence, and platelet engraftment were 12, 34, and 46 days after transplantation, respectively. All patients showed grade II or III acute graft-versus-host disease; none developed extensive chronic graft-versus-host disease until the date of last contact. All patients were alive at a median follow-up of 303 days after transplantation, with complete donor chimerism and transfusion independence. These results are encouraging and clearly show the feasibility of unrelated mismatched umbilical cord blood transplantation in the treatment of children with beta-thalassemia major.     

Antigen presentation is a function of all B cell subpopulations separated on the basis of size

Purified splenic B cells from nonimmune mice were separated by counterflow centrifugal elutriation into 6 subpopulations containing cells of discrete sizes ranging from 119 to 200 μm³. B cells of each subpopulation were competent to process and present a native globular protein antigen, cytochrome c, to a cytochrome c-specific T cell hybrid. In all cases, the B cells' antigen-presenting function was radiation sensitive and did not require T cells or T cell products, since B cells fixed with paraformaldehyde effectively presented a carboxyl-terminal peptide fragment of cytochrome c containing the T cell determinant. Furthermore, the antigen-presenting function of B cells of each subpopulation was augmented by treatment with submitogenic doses of the F(ab')₂ fragment of rabbit anti-mouse Ig antibodies, in that 10-30-fold fewer B cells were required and higher maximal T cell responses were achieved, indicating that B cells of all sizes are capable of being regulated in their antigen presentation function through their surface Ig. In addition, B cells of each subpopulation responded to soluble factors present in the supernatants of activated T cells as evidenced by an increase in volume and by the uptake of [³H]thymidine. These results indicate that B cells, regardless of size, are able to participate in at least two essential phases of T cell-dependent antibody responses, initiating the interaction by processing and presenting antigen to helper T cells and responding to soluble helper factors secreted by activated T cells.     

Animal model of neutropenia suitable for the study of dual-phagocyte systems.

When two sets of phagocytic cells participate simultaneously in the inflammatory process and bacterial killing, the relative contribution of each cell type is difficult to ascertain. The use of cell-specific antibody will permit selective depletion of one phagocyte population. We describe an experimental model of granulocytopenia which utilizes the immunoglobulin G fraction of an antigranulocyte serum. This material markedly depleted circulating polymorphonuclear leukocytes (PMN); within 2 h after injection of antigranulocyte globulin, PMN counts were at 19% of original levels and remained significantly depressed for 24 h. Granulocyte recruitment was also impaired, with only 5 x 10(3) PMN appearing in the lungs in response to an aerosol of Klebsiella, compared to 4.17 x 10(5) PMN in control animals (P less than 0.01). Most importantly, alveolar macrophages retained normal viability (97% versus 94% for control value, P not significant) normal phagocytic function, and normal bactericidal capacity. Antigranulocyte globulin is thus a valuable tool for the study of bacterial defense mechanisms.