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Biomedical subjects

J McCullough

Publications and source records attributed to J McCullough.

At least 19 recordsLinked to original sources

Cyclosporine therapy for psoriasis: a cell cycle-derived dosing schedule.

BACKGROUND: Cyclosporine is effective in the treatment of psoriasis; however, potentially serious side effects limit its long-term use. On the basis of the 36-hour psoriatic keratinocyte cell cycle, a new dosing regimen was investigated. OBJECTIVE: The purpose of this study was to evaluate a 36-hour weekly dosing schedule with cyclosporine for the treatment of psoriasis, in an attempt to decrease side effects while maintaining efficacy. METHODS: Fifteen patients were studied by means of oral doses of cyclosporine taken at 12-hour intervals for three doses per week during a 10-week period. The initial dose, 2.5 mg/kg/dose (7.5 mg/kg/wk), was increased every 2 weeks by 2.5 mg/kg/dose to a maximum of 10 mg/kg/dose. RESULTS: The average improvement as assessed by the Psoriasis Area and Severity Index for all 15 patients was 61%. Six patients had a more than 75% improvement, three patients improved 50% to 74%, and six patients improved less than 50%. Three patients dropped out because of adverse side effects, and three others completed the study at a reduced dose. CONCLUSION: It is concluded that, although effective, this dosing regimen may not have an advantage over daily dosing, given its side effect profile and the need to go to relatively high doses every 24 hours.

Adult

Evidence of cross-reactivity between olive, ash, privet, and Russian olive tree pollen allergens.

In a clinical investigation, 103 Michigan residents with symptoms suggestive of allergic rhinitis or asthma were skin tested with olive (Olea europaea) pollen extract. Nineteen had positive reactions. Since the olive tree is not native to nor grown in Michigan, this study was undertaken to determine whether the skin test reactivity was the result of cross-reactivity among tree pollen allergens. ELISAs were developed to measure olive, ash (Fraxinus americana), privet (Ligustrum vulgare), and Russian olive (Elaeagnus angustifolia) specific IgE antibodies. Inhibition studies were performed to determine whether pollen extracts from each of these tree species could inhibit IgE antibody binding to olive extracts. Eleven of the 19 skin test-positive patients were olive-ELISA positive, eight either were ELISA-positive to ash, seven to privet and ten to Russian olive. There were significant correlations between the ELISA results to olive and each of the other three pollens. The inhibition studies demonstrated that all three of the tree pollens were capable of inhibiting the binding of IgE to olive extract in a dose-response fashion. IgE-immunoblot studies demonstrated several proteins common to olive, ash, and privet. Twelve of the olive skin test-positive patients were contacted and 75% were exposed to one or more of the studied trees in their yards. Five patients had traveled to areas where olive trees are grown. We conclude that there is a high degree of cross-reactivity among allergens from native Michigan trees and from olive trees. This cross-reactivity is the most likely reason for skin test reactivity to olive pollen extract in Michigan.

Allergens

Alloimmune neonatal neutropenia due to an antibody to the neutrophil Fc-gamma receptor III with maternal deficiency of CD16 antigen.

Antibodies to the neutrophil-specific antigens NA1 and NA2 are associated with alloimmune neonatal neutropenia (ANN), autoimmune neutropenia of childhood, and acute pulmonary transfusion reactions. These antigens have been found to be located on the neutrophil Fc-gamma receptor III (FcRIII). The mother of a child with ANN was found to lack both NA antigens and to produce an antibody that reacted with all normal neutrophils tested. We used maternal antibody and a CD16 monoclonal antibody (MoAb) that has specificity for FcRIII to immunoblot and immunoprecipitate neutrophil membranes of various NA phenotypes. Both antibodies immunoblotted an approximately 40- to 70-Kd glycoprotein (GP) on NA1, NA2-positive membrane, an approximately 40- to 55-Kd GP on NA1-homozygous membranes, and an approximately 55- to 70-Kd GP on NA2-homozygous membranes. Both antibodies also immunoprecipitated a 50- to 80-Kd GP from NA1, NA2-positive cells, a 50- to 60-Kd GP from NA1-homozygous cells, and a 55- to 80-Kd GP from NA2-homozygous cells. To further examine the specificity of the maternal antibody, sequential immunoprecipitation studies were performed using maternal antisera and a CD16 MoAb. After extracts of 125I surface-labeled neutrophils were precleared with maternal serum, CD16 MoAbs no longer immunoprecipitated any GP. Neither the CD16 MoAb nor a rabbit polyclonal antibody specific for FcRIII detected any GP in maternal neutrophil membranes by immunoblotting. Neutrophil FcRIII is a glycosyl-phosphatidylinositol anchored membrane GP as is decay accelerating factor and both are absent from neutrophils of patients with paroxysmal nocturnal hemoglobinuria (PNH). Maternal neutrophil membranes were probed with antibody specific for DAF and an 80-Kd GP was detected. This woman also has had no clinical evidence of PNH. These studies provide further evidence that the NA1 and NA2 antigens are on FcRIII and identify a healthy person whose neutrophils lack not only the neutrophil specific antigens NA1 and NA2 but multiple other epitopes of FcRIII and, therefore, likely lack FcRIII entirely.

Antibodies, Monoclonal

Comparison of the effectiveness of potential marrow donors recruited from apheresis donors or whole blood donors and through appeals to the general public.

Marrow transplants with phenotypically HLA-matched, unrelated donors have been used effectively to treat a number of diseases. Many blood centers have recruited HLA-typed apheresis blood donors into marrow donor registries. However, to build larger registries so that more patients may be treated with unrelated donor marrow transplants, whole blood donors and people who do not donate blood have been added to the registries. The marrow donor program at our blood center had 2844 potential donors, of whom 1725 were also apheresis donors, 608 were whole blood donors, and 511 were recruited from the general public as a result of community appeals for marrow donors for a specific patient. Over a 9-month period, 297 potential donors were asked to donate blood samples for HLA-DR typing or mixed lymphocyte culture (MLC) testing or to participate in an informational session, undergo a medical evaluation, and sign a statement indicating an intention to donate marrow for a specific patient. Overall, these requests were successfully completed by 75.5 percent of apheresis donors, 87.2 percent of whole blood donors, and 78.1 percent of the potential donors recruited through community appeals. Furthermore, there was no difference among the three groups in the portion of people who donated blood samples for HLA-DR typing or MLC testing. Fifteen of 18 apheresis donors who were found to match a specific donor signed a statement of intent to donate marrow, 2 apheresis donors were deferred for medical reasons, and 1 decided not to donate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Fatal Yersinia enterocolitica (serotype 0:5,27) sepsis after blood transfusion.

Septicemia is a rare complication of blood transfusion. This is probably primarily due to the use of sealed disposable containers for blood collection and the storage of red cell-containing components at 4 degrees C. However, despite these measures, septicemia due to blood transfusion continues to occur. We report here a fatal case of Yersinia enterocolitica septicemia due to a contaminated unit of red cells which was collected from an apparently healthy, asymptomatic blood donor. The organism grows at cold temperature and multiplies during storage of red blood cell-containing components. Contaminated components do not show any visible abnormalities. The possibility of transfusion-transmitted Y. enterocolitica should be considered in patients who have symptoms of sepsis or shock following transfusion.

Female

Anaphylaxis associated with latex allergy during barium enema examinations.

During the interval from January 1989 to March 1990, signs and symptoms of anaphylaxis developed in six patients during barium enema examinations in our institution. In all six cases the symptoms of anaphylaxis began during the procedure, usually within 10 min of starting the examination. The principal manifestation of anaphylaxis was severe hypotension, usually accompanied by edema and urticaria. The symptoms were considered potentially life threatening in all patients, and one patient died despite prompt recognition of the anaphylactic nature of the reaction and resuscitative efforts. Serum samples were obtained within a few hours of the reaction in two patients and at autopsy in the fatal case: all three samples showed elevated concentrations of mast cell tryptase, demonstrating the systemic release of anaphylactic mediators. In vitro tests demonstrated the presence of immunoglobulin E antibodies specific for latex allergens in five of the six cases. Further in vitro inhibition tests confirmed the specificity of the antibodies for latex allergens and demonstrated that similar allergens were found in both raw latex, latex gloves, and catheter balloons. Only one patient was willing to undergo a skin test, and her skin test was positive for extracts of latex products. After considering multiple possibilities, we conclude that the reactions associated with barium enemas observed in these six patients are most probably the result of latex allergy.

Adult

The use of beta-galactosidase gene fusions to screen for antibacterial antibiotics.

The desirable features for a screening assay to detect antibacterial antibiotics include 1) high specificity for the desired antibiotic type 2) high sensitivity 3) lack of interference by other compounds likely to be associated with the antibiotic of interest and 4) ease of operation to allow a large number of samples to be tested. These characteristics are largely found in screens employing strains carrying fusions between antibiotic induced promoters and the structural genes for Escherichia coli beta-galactosidase. Screens were designed based upon fusions with three antibiotic induced promoters: the tetracycline induced tetA/tetR promoter from transposon Tn10, the erythromycin induced promoter from the Staphylococcus aureus ermC erythromycin-resistance gene and the chloramphenicol induced promoter from the S. aureus cat86 chloramphenicol-resistance gene. Because there have been no reports of vancomycin induced resistance determinants, a Tn903 random gene fusion pool was screened to isolate a vancomycin induced gene fusion. This gene fusion was induced fairly specifically by glycopeptide antibiotics and the fusion was used as the basis for a glycopeptide screen.

Anti-Bacterial Agents

Prevention of cytomegalovirus infection following bone marrow transplantation: a randomized trial of blood product screening.

From 1983 to 1987, cytomegalovirus seronegative allogeneic bone marrow recipients were randomized to receive screened cytomegalovirus (CMV) seronegative or unscreened blood products and 125 patients were available for analysis. CMV infection occurred in 18% of patients in the screened versus 38% in the unscreened blood product group. However, only two of 64 patients in the screened group and seven of 61 in the unscreened group developed culture or biopsy-proven CMV infections. Bone marrow donor CMV seropositivity was associated with an increased risk of developing CMV infection (21% with seronegative and 46% with seropositive donor), and CMV infection was not prevented by blood product screening if the bone marrow donor was sero = positive (62% for screened, 42% for unscreened group, p = 0.80). One year survival censored for relapse was 52% in the screened group versus 68% in the unscreened group (p = 0.08). Gram negative bacteremia complicated bone marrow transplantation (BMT) in 35% of patients receiving screened and 15% of those receiving unscreened blood products (p = 0.02). Relapse did not differ in the screened and unscreened groups. By multivariate analysis, high risk disease (p = 0.0002), CMV infection (p = 0.004), screened blood products group (p = 0.011), recipient age greater than 17 (p = 0.027), chronic graft-versus-host disease (p = 0.014) and gram negative bacteremia (p = 0.004) independently had a negative influence on survival. We conclude that blood product screening was effective in preventing CMV infections following BMT if both the recipient and bone marrow donor were CMV seronegative.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

The role of the blood bank in transplantation.

Blood transfusion supportive care is essential to successful organ, tissue, and bone marrow transplantation, thus making the blood bank an integral part of these programs. The impact of clinical transplantation on the blood bank can be considered in the following categories: (1) use of blood and blood components for transfusion support; (2) special blood component needs; (3) red blood cell serologic needs; (4) collection, processing, and preservation of bone marrow and peripheral blood stem cells; (5) hemotherapy for bone marrow donors, (6) recruitment of bone marrow donors; and (7) the special procedures that must be available for managing patients undergoing transplantation therapy.

Blood

Transfusion-related acute lung injury caused by an NB2 granulocyte-specific antibody in a patient with thrombotic thrombocytopenic purpura.

HLA and granulocyte-specific antibodies have been implicated in the production of transfusion-related acute lung injury (TRALI). Reported here is a case that suggests that the patient's preexisting condition may play an important role in determining whether TRALI develops upon transfusion of blood products containing anti-white cell (WBC) antibodies. A 29-year-old woman with thrombotic thrombocytopenic purpura (TTP) underwent an uneventful 1.5-volume plasma exchange, which was followed by the transfusion of 2 red cell (RBC) units. At the end of the second RBC transfusion, the patient developed clinical signs and symptoms of noncardiogenic pulmonary edema. Serologic studies demonstrated that the serum from the second RBC donor had no HLA antibodies but did have a granulocyte-specific antibody (anti-NB2) that caused the agglutination of the recipient's granulocytes, which were NB2 positive. Serum from the donor of the first RBC unit and serum from the donors of units used in the exchange had no HLA or granulocyte-specific antibodies that reacted with the recipient's WBCs. Because the donor implicated in this reaction had a history of 21 blood donations, none of which had been associated with a transfusion reaction, we suggest that the patient's preexisting condition played a significant role in this episode of TRALI, owing to the granulocyte-specific antibody.

Acute Disease

Janthinocins A, B and C, novel peptide lactone antibiotics produced by Janthinobacterium lividum. I. Taxonomy, fermentation, isolation, physico-chemical and biological characterization.

Janthinocins A, B and C are novel antibacterial agents produced by Janthinobacterium lividum. They were isolated from fermentation broths and characterized by UV, IR, NMR and mass spectroscopy. They are cyclic decapeptide lactones with marked activity against aerobic and anaerobic Gram-positive bacteria and are 2 to 4 times more potent in vitro than vancomycin. Janthinocins A and B were also found to be effective in a Staphylococcus aureus systemic infection in mice.

Animals

Successful allogeneic cryopreserved marrow transplantation.

Cryopreservation has been used extensively in autologous marrow transplantation (BMT), but there has been limited use in allogeneic BMT. We describe here 6 cases of successful engraftment following allogeneic BMT with cryopreserved marrow. Patients suffered from Wiscott-Aldrich syndrome, osteopetrosis, aplastic anemia, and acute lymphocytic, acute non-lymphocytic, and chronic myelogenous leukemia, and ranged in age from 5 mos to 35 yrs. Marrow was collected using standard techniques. In one case T-cells were removed to prevent graft-vs-host disease. Marrow was frozen for a variety of reasons. Buffy coat cells were frozen at controlled rate in 10% DMSO, and stored in liquid nitrogen for 6 to 49 d. Engraftment (WBC greater than 1000/uL x 3 d) occurred from 13 to 37 d post BMT. In 4 of 4 cases in which data are available, donor origin of engraftment was documented, 1 with cytogenetics, 2 with red cell typing, and 4 with restriction fragment length polymorphisms. 3 patients are alive and well 21, 21, and 42 months post BMT. These results suggest frozen marrow can be successfully used for allogeneic BMT.

Adolescent