Severe combined immunodeficiency due to a specific defect in the production of interleukin-2.
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Biomedical subjects
Publications and source records attributed to K Weinberg.
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Deferoxamine has been extensively used as chelation therapy in iron-overloaded states. Recently, some investigators have explored the potential usefulness of deferoxamine as an antiproliferative, antiinflammatory, and immunosuppressive agent. The studies of deferoxamine have indicated that the drug blocks DNA synthesis by inhibition of ribonucleotide reductase. Deferoxamine has also shown antiinflammatory properties, possibly by inhibition of polymorphonuclear neutrophil function. Analysis of possible antiinflammatory effects of deferoxamine has been complicated by concomitant immunosuppressive effects of the drug. Deferoxamine inhibits T lymphocyte proliferation, both by ribonucleotide reductase inhibition and by preventing the expression of interleukin 2 receptor-alpha chain. The use of iron-chelating agents in non-iron-overloaded patients carries the risk of neurologic, metabolic, and infectious complications. The clinical usefulness of deferoxamine in these novel applications will require careful study of both efficacy and any toxic effects.
Serious infections caused by the Mycobacterium avium-intracellulare (MAI) complex have been increasingly recognized in patients with acquired immunodeficiency syndrome (AIDS). Allogeneic bone marrow transplant recipients are prone to infections caused by a wide spectrum of organisms. However, infection with MAI has been reported only once in an allogeneic bone marrow transplant setting. We describe two allogeneic bone marrow transplant recipients with severe combined immunodeficiency syndrome (SCID) in whom MAI infections occurred. Thus, MAI must be added to the list of infectious pathogens that can infect allogeneic bone marrow transplantation (BMT) recipients. Aggressive multidrug antituberculosis therapy may be of benefit in such patients.
Although autologous bone marrow transplantation (ABMT) following purging with 4-hydroperoxycyclophosphamide (4HC) has been effective for some adults with acute non-lymphoblastic leukemia (ANLL), there are few data on ABMT for children. We have performed ABMT for 13 patients (median age, 5 years) with ANLL in second remission. Bone marrow was treated ex vivo with 4HC to kill residual leukemic cells. In order to enhance the anti-leukemic effect of 4HC, exogenous red blood cells were eliminated from the marrow/4HC mixture. All patients were conditioned for transplantation with busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg), followed by infusion of the 4HC treated marrow. Eleven of 13 patients had complete hematologic reconstitution; there were no transplant-related deaths. Five patients relapsed at 2, 4, 5, 6 and 6 months post-BMT. Eight patients are disease-free survivors; the median time for survival is 24 months, with a projected disease-free survival of 61%. ABMT is a safe and efficacious treatment modality for children with ANLL in second remission. Our results suggest that the disease-free survival for pediatric patients may be superior to that seen in adults.
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It is estimated that in 1985 about 1,560 fewer drivers were involved in fatal crashes because of three types of drinking-driving laws. The laws studied were per se laws that define driving under the influence using blood alcohol concentration (BAC) thresholds; laws that provide for administrative license suspension or revocation prior to conviction for driving under the influence (often referred to as "administrative per se" laws); and laws that mandate jail or community service for first convictions of driving under the influence. It is estimated that if all 48 of the contiguous states adopted laws similar to those studied here, and if these new laws had effects comparable to those reported here, another 2,600 fatal driver involvements could be prevented each year. During hours when typically at least half of all fatally injured drivers have a BAC over 0.10 percent, administrative suspension/revocation is estimated to reduce the involvement of drivers in fatal crashes by about 9 percent; during the same hours, first offense mandatory jail/community service laws are estimated to have reduced driver involvement by about 6 percent. The effect of per se laws was estimated to be a 6 percent reduction during hours when fatal crashes typically are less likely to involve alcohol. These results are based on analyses of drivers involved in fatal crashes in the 48 contiguous states of the United States during the years 1978 to 1985.
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In chronic myelogenous leukemia (CML) and in a percentage of childhood and adult acute lymphoblastic leukemia (ALL) the Philadelphia (Ph') chromosome is present in the leukemic cells of patients. This chromosome is the result of a reciprocal translocation between chromosomes 9 and 22. In CML the break on chromosome 22 occurs within the major breakpoint cluster region (Mbcr) of the bcr gene. In this study, we report on the examination of DNAs from nine Ph'-chromosome positive ALL patients for rearrangements within the bcr gene using Southern blot analysis. Of nine patients having a karyotypically identifiable Ph'-chromosome, only five exhibited rearrangements of the bcr gene. This could indicate that in ALL, chromosome 22 sequences other than the bcr gene are involved in the Ph'-translocation. Within the group of Ph'-positive ALL patients having a bcr gene breakpoint, a correlation appears to exist between the age of the patient and the location of the breakpoint within the gene: all or the vast majority of pediatric patients analyzed to date do not have a Mbcr breakpoint as found in CML and in adult ALL.
Subpopulations of normal bronchial epithelial cells were identified using a series of murine monoclonal antibodies. These antibodies were used to stain intact bronchial epithelial cells in culture by indirect immunofluorescence. LAM 2 reacted with 80%, LAM 6 with 75%, LAM 7 with 60%, and LAM 8 with 5% of these cells. Sections of human bronchial epithelium were also stained with these antibodies by immunoperoxidase methods. LAM 2 was found to bind with 80%, LAM 6 with 65%, LAM 7 with 50%, and LAM 8 with less than 1% of bronchial epithelial cells. LAM 2 stained both columnar epithelial cells and basal cells; LAM 6 stained mainly basal cells and only a small proportion of columnar cells; LAM 7 showed specificity for basal cells; LAM 8 distinctly stained single cells in the basal cell layer. These antibodies were previously shown to react with the surface membrane of human lung carcinomas, ranging from the broad reactivity of LAM 2 with small cell and non-small cell lung cancers to the highly restricted reactivity of LAM 8 with small cell carcinomas of the lung. Thus, membrane antigens have been identified in bronchial epithelial cells by monoclonal antibodies which exhibit a similar range of cellular reactivity in vitro as in vivo. Inasmuch as these antibodies recognize subsets of cells which could not be easily distinguished by morphologic characteristics, these reagents may be useful in classifying bronchial epithelial cells.
Constitutional pure red cell aplasia (CPRCA) is a syndrome of failed erythropoiesis usually diagnosed within the first year of life. Four patients with CPRCA received transplants with marrow from their HLA-identical, mixed lymphocyte culture-nonreactive siblings. All patients were resistant to corticosteroid therapy and were dependent on regular red cell transfusions for at least 5 years. Three patients were conditioned with procarbazine, antithymocyte globulin, cyclophosphamide, and busulfan, and one was conditioned with antithymocyte serum, cyclophosphamide, and busulfan. Three patients promptly had successful engraftments with establishment of donor hematopoiesis. One patient initially rejected his graft but received a successful retransplant. All patients are currently alive with Karnofsky performance scores of 100 and normal erythropoiesis of donor origin. Despite a history of multiple transfusions, bone marrow transplantation is a potentially curative therapy for patients with CPRCA.
Studies on immunoglobulin gene rearrangement in lymphoid lesions are an increasingly important application of molecular biology in diagnostic medicine. The authors have therefore examined the possibility of detecting such rearrangements in formalin-fixed, paraffin-embedded pathology specimens. Southern blots of DNA obtained from optimally fixed tissues were very similar to blots of unfixed material, except that the electrophoretic mobility of the fixed DNA fragments was sometimes slightly reduced. High-molecular-weight DNA was not recovered from suboptimally fixed partially autolysed samples. Increasing the time of exposure to formalin resulted in loss of hybridizable DNA. Monoclonal rearrangements of heavy and light chain immunoglobulin genes could be detected in formalin-fixed specimens provided that these fixation artifacts were taken into consideration. This technique expands the pool of material available for studies on gene rearrangement and should facilitate the use of such studies in clinical medicine.
The human T cell receptor-T3 antigen complex is composed of at least five polypeptide chains. In addition to the 45-kDa/50-kDa heterodimer (alpha and beta chains) of the T cell receptor, the complex includes 25-kDa (T3-gamma) and 20-kDa (T3-delta) glycoproteins and a nonglycosylated 20-kDa (T3-epsilon) protein. Here we report that in pulse-chase biosynthetic labeling experiments we detect a new polypeptide chain (T3-p28) which is associated with the T3-delta and T3-epsilon chains during biosynthesis but not on the cell surface. T3-p28, which is not recognized by anti-T3 antibodies, can be chemically distinguished from the previously described T3-gamma chain. The carboxylic ionophore monensin blocks the apparent dissociation of T3-p28 from the T3-delta and T3-epsilon chains. Peripheral blood lymphocytes as well as all T cell leukemic lines tested contain T3-p28, except one HPB-ALL subline. Since the T3-p28 protein is only observed early in biosynthesis of T3-delta and T3-epsilon, it may function in intracellular transport or assembly of the T cell receptor-T3 complex.
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Burn prevention lectures instituted in early childhood education is believed to have decreased burn-related injuries in children. Validation of retention of information to verify effectiveness of school lectures is needed. A pretest and posttest were developed to measure the retention of burn prevention methods taught to students. The pretests were administered by the teachers to fourth and fifth graders (n = 500) one day before the prevention lecture. Programs were taught assembly style. The teachers were asked to reissue the posttest within 2 days after the program. The tests were then returned to the community educator. The test included 15 multiple choice questions. Questions addressed escaping a burning building and burn prevention items such as cooking, first aid tips, and other general prevention ideas. Test results showed overall improvement of scores. Additional analysis showed that though test scores improved, there was less improvement in scores of inner-city students. Pretesting and posttesting has provided valuable information regarding student learning. It has also identified target groups and areas where increased efforts of prevention programs must be directed.
Pain and anxiety are integral parts of burn dressing care. Descriptions of pain and anxiety from the patients' perspectives enhance our understanding of their experiences. This descriptive study measured relationships between self-reported pain and anxiety. Twenty-four patients who had an uncomplicated flame or scald wound reported scores immediately before, immediately after, and 1/2 hour after dressing changes. Results indicated that pain and anxiety increased until day 4. Pain correlated with anxiety. Self-report scores showed that pain and anxiety are perceived by patients in a similar manner. Self-report scores are of great value because they indicate the degree of relief achieved with medication. Through the descriptive study, we found that the pain score immediately after dressing changes was greater than 3 on all study days. This finding indicates a need to further examine the way pain is managed with dressing changes.
A total of 222 burn nurses from 30 burn centers completed a questionnaire about how and when a burn patient looks at their burn wound for the first time. The registered nurse is most frequently with the patient when the patient sees the wound for the first time (n = 187; 84%). Looking at the wound is not usually a planned event, and it is not documented in the patient record. Nurses use verbal and nonverbal patient cues to determine when it is appropriate for the patient to look initially at the wound and combine this initial look with an opportunity to teach wound healing. The patient asks the nurse for an opinion about the way the wound looks (n = 181; 81.5%). The nurse uses silence, presence-of-self, and gentle encouragement with the patient while remaining positive and honest. Respondents reported that the patient wants the truth but also needs reassurance and some degree of optimism when viewing the wound for the first time.