Waves of B-lymphopoiesis in the establishment of the mouse B-cell compartment.
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Animals↗
Biomedical subjects
C Martinez
Publications and source records attributed to C Martinez.
Treatment with IL2/vaccinia recombinant virus leads to serologic, histologic and phenotypic normalization of autoimmune MRL/lpr-lpr mice.
We have analyzed the effect of IL2 administered in vivo on both the lymphoproliferation and autoimmune disease progression of MRL/lpr mice. Human IL2 was delivered by infecting MRL/lpr mice with vaccinia virus recombinants at different stages of lpr disease. The results reported here showed that treatment of lpr mice with IL2 mediated: (1) restored normal thymic differentiation illustrated by an expansion of the double positive population accompanied by increased numbers of mature thymocytes; (2) depletion of the peripheral CD3+ CD4- CD8- (DN) T-cell population; (3) normalization in the pattern of TcRV beta gene expression displayed by mature T cells; (4) decreased urine-protein levels and immune complex deposition in the kidney, with a resultant absence of glomerulonephritis; and (5) an increased longevity (from 195 to more than 400 days). We speculate that the dramatic reduction in the abnormally expanded CD3+ DN T-cell population following IL2 therapy might be directly related to the amelioration and/or prevention of autoimmune disease in these mice. Collectively, these results suggest that diseases showing a selective expansion of DN cells should be envisaged as possible targets for the treatment described here.
Animals↗
Gluten challenge in patients with celiac disease: evaluation of alpha 1-antitrypsin clearance.
Our aim in this study was to monitor changes of the intestinal structure by alpha 1-antitrypsin clearance (alpha 1-ATCL) in order to offer an alternative to the gluten challenge biopsy. In addition, we evaluated the possibility of reducing the time of gluten challenge. Twelve patients had a presumptive diagnosis of celiac disease based on clinical and histological grounds. They were studied when the jejunal histology was normal after gluten-free diet and an alpha 1-ATCL was normal. The gluten was introduced by returning to a normal diet. The challenge lasted 4 wk. We measured alpha 1-ATCL at the end of the 1st and 4th wk, and a new jejunal biopsy was obtained at the end of the 4th wk. By wk 1, alpha 1-ATCL was abnormal in 11 patients but normal in one. By wk 4, alpha 1-ATCL was abnormal in 10 patients and still normal in one. The post-challenge biopsies showed atrophy in 11 and was normal only in the patient with normal alpha 1-ATCL at wk 1 and 4. One patient with abnormal alpha 1-ATCL had to stop the challenge at the first week. The patient with normal clearance at wk 1 and 4 and normal biopsy at wk 4 had abnormal results at 6 months. These data support our hypothesis that alpha 1-ATCL can be used as evidence of gluten toxicity after gluten challenge, and that this test can be abnormal as early as 1 wk after gluten is reintroduced.
Adolescent↗
Anatomy of the gonadal veins: a reappraisal.
Variations in anatomy were found quite frequently during bilateral gonadal vein dissection and resection for pelvic varices in the past 5 years (120 cases). In about one fourth of the cases, routine gonadal phlebography was not technically feasible or did not correlate exactly with the operative findings. Some cases of male varicocele showed recurrence after surgery. These facts, in addition to the scarce information provided by anatomy textbooks, induced us to study thoroughly the gonadal veins. One hundred cadaver dissections (200 veins) were done for length, diameter, number, and location of valves and collaterals, number of trunks in each side, and mode of termination in the renal vein and vena cava. Topographic division of the veins by thirds facilitated the information. Variations from the classic anatomic description were encountered frequently. As to the number of trunks, at the middle third, where the vein is usually divided, only 60% have one trunk on the left and only 75% have one on the right side. The rest are multiple; as many as four and six trunks in the lower third were found. The knowledge of these anatomic variations, not clearly described before, is of great importance to both surgeons and invasive radiologists and conducive to successful results.
Adolescent↗
Crystallization and preliminary X-ray study of a recombinant cutinase from Fusarium solani pisi.
Recombinant cutinase from Fusarium solani pisi is expressed and excreted with very high yields in Escherichia coli cultures. Cutinase was crystallized at 20 degrees C using the vapour diffusion technique, with polyethylene glycol 6000 as precipitant. Best crystals were obtained at pH 7.0 with polyethylene glycol 6000 as precipitant. Best crystals were obtained at pH 7.0 with polyethylene glycol at 15 to 20%. They are monoclinic, with space group P2(1) and cell dimensions a = 35.1 A, b = 67.4 A, c = 37.05 A and beta = 94.0 degrees; they diffract beyond 1.5 A resolution. The asymmetric unit contains one molecule of 22,000 Da (Vm = 1.98 A3/Da; 38% water).
Carboxylic Ester Hydrolases↗
Recovery from autoimmunity of MRL/lpr mice after infection with an interleukin-2/vaccinia recombinant virus.
Interleukin-2 (IL-2) is a T-cell derived molecule implicated in the clonal expansion of antigen-activated T cells and in T-cell development. IL-2 is also implicated in autoimmune disease, although its role is still controversial. Murine systemic lupus erythematosus (SLE) is a good model for human SLE as most of the immunological abnormalities in the human disease also seem to be operative in the mouse. Among SLE mice, the MRL/lpr strain develops early in life autoimmune diseases such as immune complex-mediated glomerulonephritis, arthritis and arteritis. Lymphoid abnormalities associated with those diseases in this strain are thymic atrophy and abnormal proliferation of CD3+ CD4- CD8- 'double-negative' T cells, resulting in massive generalized lymph node enlargement. We have therefore now examined the effects of IL-2 on the disease progression in MRL/lpr mice using live vaccinia recombinant viruses expressing the human IL-2 gene. Vaccinated mice showed prolonged survival, decreased autoantibody and rheumatoid factor titres, marked attenuation of kidney interstitial infiltration and intraglomerular proliferation, as well as clearance of synovial mononuclear infiltrates. Inoculation with the IL-2/vaccinia recombinant virus led, in addition, to drastic reduction of the double-negative T-cell population, improved thymic differentiation and restoration of normal values of mature cells in peripheral lymphoid organs.
Animals↗
Low IgG2 and polysaccharide response in a T cell receptor expression defect.
B lymphocytes require appropriate T lymphocyte cooperation to synthesize immunoglobulins (Ig). Such interaction presumably takes place after engagement of the T cell receptor (TcR) by antigen. The present work addresses B lymphocyte function (and phenotype) in a novel type of immunodeficiency which is characterized by a TcR expression defect. In contrast to expectations, the two affected siblings that were studied displayed normal in vivo antibody responses to both endogenous and exogenous protein antigens. However, they showed impaired responses to certain polysaccharide antigens together with a selective IgG2 deficiency. These results suggest that some polysaccharide responses may be more T cell dependent than previously suspected, and support the notion that T cell dysfunctions (of this or other kind), rather than Ig gene deletions, may be the molecular basis of certain IgG2 deficiencies. To rule out a concomitant gross B cell dysfunction in these individuals, B lymphocyte phenotype and function were assayed in vitro, and found to be normal. A T cell line derived from one of the siblings displayed an abnormal TcR on the cell surface, but it showed several normal TcR-mediated functions. This suggests that the low number of peripheral T lymphocytes that have been found to express low TcR levels in these immunodeficiencies may be operational, and supplying sufficient "help" for the observed normal antibody responses to all tested protein, but not polysaccharide, antigens.
B-Lymphocytes↗
The development and function of gamma delta T cells.
In June of this year, a small group of researchers came together at the inspiring location of Segovia, Spain to exchange information and opinions on gamma delta T cells. In this report the new, unpublished findings presented, and the ideas that germinated during the meeting are discussed in the context of recent gamma delta literature.
Animals↗
Malaria in the Amazon. Prevalence of Plasmodium falciparum antibodies in Amerindians inhabiting the Venezuelan Amazon.
The acquisition of antibodies to Plasmodium falciparum in various age groups was studied in 511 Amerindians inhabiting the north of the Venezuelan Amazon. The overall prevalence by ELISA was 91.2% and antibodies were acquired early in life. Seropositivity was 69.6% in the group aged two to five years and reached 86% at 10 years of age; 96.9% of the adults aged 31-40 years exhibited high ELISA values to P. falciparum. The high prevalence of malaria antibodies among Amazonians, from early on in life, reflects the high level of malaria transmission in that part of the world.
Adult↗
Multicenter prospective study of treatment of Brucella melitensis brucellosis with doxycycline for 6 weeks plus streptomycin for 2 weeks.
The effectiveness of treating human brucellosis caused by Brucella melitensis with a 6-week course of doxcycline plus streptomycin for 2 of those weeks was analyzed by a multicenter prospective study of 139 patients. Subjects with central nervous system involvement, endocarditis, or spondylitis were excluded from the study. All but 5 of the 139 patients completed the full treatment schedule and became afebrile in the first week of therapy. Four patients suffered relapses during the follow-up period. Of the five patients who did not complete the treatment, two left because of adverse secondary effects (1.4%), another two left for noncomplicance with the treatment (1.4%), and the remaining patient was considered a therapeutic failure because his symptoms persisted after the first week of therapy (0.7%). We concluded that the combination of doxycycline and streptomycin is an effective treatment for the types of brucellosis included in our study.
Adolescent↗
Oxidative polymorphism of debrisoquine in Parkinson's disease.
Oxidative phenotype and metabolic ratio (MR) of debrisoquine (DBQ) have been determined in 87 patients with Parkinson's disease and in 556 healthy control subjects. Three patients (3.45%) and 34 control subjects (6.12%), having an MR greater than 12.6, were classified as poor metabolisers (PM) of DBQ (ns). The distribution of MR values in the 84 Parkinsonian patients classified as extensive metabolisers (EM) showed a less efficient oxidative rate when compared with controls of the same phenotype (p less than 0.001). This difference may be due to enzymatic inhibition caused by drug treatment in 40 of these patients. As in patients not taking any drug known to inhibit the oxidation of DBQ, distribution of MR values was not different from that in controls. A negative correlation (r = -0.36, p less than 0.02) was found between MR of DBQ and age at onset of disease in patients free of drugs known to interact with DBQ metabolism. A higher rate of DBQ oxidation could be a genetic factor that delays the clinical onset of Parkinson's disease in predisposed people.
Adult↗
Squamous cell carcinoma arising on a congenital fissure of the lower lip.
In this study we document a case of squamous cell carcinoma in a young man arising on a fissure of the lower lip. The fissure, which existed since birth, could be considered congenital. We report here the clinical and pathological aspects; the pathogenesis is discussed.
Adult↗
Insights into autoimmunity: from classical models to current perspectives.
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Animals↗
Personal experience with a transplant.
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Adult↗
Early image acquisition after administration of indium-111 platelets in clinically suspected deep venous thrombosis.
Indium-111 platelet scintigraphy accurately detects acute deep venous thrombosis in asymptomatic high-risk patients and may be used as a surveillance test. However, its value in symptomatic patients and its accuracy early after platelet injection are not satisfactorily established. The latter is important for timely institution of therapy. Accordingly, 65 patients (67 limbs) with suspected deep venous thrombosis (symptom duration 8 +/- 10 days, mean +/- standard deviation) were prospectively studied with platelet scintigraphy and contrast venography. Platelets were labeled with 405 +/- 101 mCi indium-111 oxine. The labeling efficiency was 80 +/- 10%. All images were acquired within 120 minutes after intravenous administration of the platelet suspension. Both platelet scintigraphy and venography were interpreted independently by 2 blinded observers (for each technique). Five separate analyses were performed. Each scintigraphic reader was compared to each venographic reader. A fifth analysis--consisting of readings with blinded agreement of both readings of the platelet scans and both readings of the venograms--was performed. Interobserver agreement was 92% for venography and 79% for scintigraphy. Excluding anticoagulated patients, the sensitivity of platelet scintigraphy was between 38 and 46% and the specificity was between 92 and 100%. Thus, early imaging of labeled platelets for the diagnosis of symptomatic deep venous thrombosis carries a high specificity but a much lower sensitivity. It is speculated that the low sensitivity is related to the inactivity of the thrombus. This may suggest that early imaging will only be useful in patients whose symptoms are of recent onset.
Blood Platelets↗
Expression of alkaline phosphatase in murine B lymphocytes. Correlation with B cell differentiation into Ig secretion.
Alkaline phosphatases (ALPase) (orthophosphoric-monoester phosphohydrolase, EC 3.1.3.1) are implicated in many biologic phenomena including ossification and differentiation of human neutrophils and choriocarcinoma cells. Another trait, demonstrated by microinjection into Xenopus oocytes, is their ability to block the first mitotic division. Previous work in our laboratory has established that ALPase is also present on murine B lymphocytes activated by either polyclonal mitogens or Th cells. We have now characterized the ALPase present on murine B cells as belonging to the liver-bone-kidney isoenzyme and found it to be implicated in B cell differentiation into antibody secretion. Thus, B cell proliferative responses, elicited either by high concentrations of rabbit anti-IgM antibodies or by LPS in the presence of PMA, are characterized by the lack of both antibody secretion and expression of ALPase activity. In contrast, B cells stimulated to differentiate into Ig-secreting cells by B cell differentiation factors, nearly in the absence of a proliferative response, express high levels of ALPase activity, as did those that were LPS-stimulated. These data showing the association of the ALPase expression with the process of B cell differentiation into antibody-secreting cells are discussed in the context of the possible role that phosphorylation-dephosphorylation mechanism may play in controlling the growth/differentiation rate in the B cell lineage.
Alkaline Phosphatase↗
Differential L chain expression in the antibody responses to phosphorylcholine of adult bone marrow or peritoneum-derived B lymphocytes.
Lethal irradiation of adult BALB/c mice followed by reconstitution with autologous bone marrow results in loss of T15 Id and IdX expression in the responses to phosphorylcholine (PC) and alpha(1-3)-dextran, respectively. T15 Id, but not IdX expression can be reconstituted with low numbers of syngeneic, T cell-depleted peritoneal resident cells. All three groups of mice produce comparable titers of specific anti-PC and anti-dextran antibodies. The inability of adult bone marrow-reconstituted BALB/c mice to produce T15 Id+ antibodies is not due to differential VH-gene expression in bone marrow or peritoneum-derived B cells. Thus, the levels of T15 VH in total serum Ig and in anti-PC antibodies are similar in all groups of mice. Furthermore, IEF patterns of T15 VH-associated L chains directly demonstrate differential Vk repertoire expression in bone marrow and peritoneum-derived B cells.
Aging↗
The frequency of complement receptor type 1 (CR1) gene polymorphisms in nine families with multiple cases of systemic lupus erythematosus.
Low levels of complement receptor type 1 (CR1) on the erythrocytes of patients with systemic lupus erythematosus (SLE) may be acquired or genetically determined. Nine families with multiple cases of SLE were studied using a CR1 probe and restriction fragment length polymorphism analysis, to address this question. The absence of a significant increase in the frequency of a 6.9-kb band (previously shown to be associated with low-level CR1 on erythrocytes) suggests that this genetic marker does not play a major role in determining SLE, either in these families or in SLE patients in general.
DNA Probes↗