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Biomedical subjects

S Panzer

Publications and source records attributed to S Panzer.

At least 109 records · Page 6Linked to original sources
PubMed1992

Organogenesis in Drosophila melanogaster: embryonic salivary gland determination is controlled by homeotic and dorsoventral patterning genes.

We have investigated Drosophila salivary gland determination by examining the effects of mutations in pattern forming genes on the salivary gland primordium. We find that the anterior-posterior extent of the primordium, a placode of columnar epithelial cells derived from parasegment 2, is established by the positive action of the homeotic gene Sex combs reduced (Scr). Embryos mutant for Scr lack a detectable placode, while ectopic Scr expression leads to the formation of ectopic salivary glands. In contrast, the dorsal-ventral extent of the placode is regulated negatively. Functions dependent on the decapentaplegic product place a dorsal limit on the placode, while dorsal-dependent genes act to limit the placode ventrally. We propose a model in which these pattern forming genes act early to determine the salivary gland anlage by regulating the expression of salivary gland determining genes, which in turn control genes that are involved in salivary gland morphogenesis.

Animals↗
PubMed1990

Childhood acute lymphoblastic leukemia: results of the Austrian Cooperative Study Group with the ALL A 84 protocol.

We prospectively treated 127 children with ALL with a risk-adapted regimen. All patients received the identical induction-consolidation therapy. The early maintenance included intermediate dose methotrexate in patients with standard risk (n = 79) and medium risk (n = 39). In addition patients with high risk (n = 6) received high dose ARA-C followed by L-asparaginase. Intensification treatment and prophylactic cranial irradiation was also tailored according to the risk group. Treatment duration was 2 years. Complete remission was achieved in 97.6% of all patients. Treatment-related toxicity accounted for one death in complete remission. The probability of event-free survival (pEFS) for the combined group was 72% at a median follow-up of 42 months. The pEFS was higher in patients with standard risk (SR) than in patients with medium risk (MR) (80% versus 65%; p less than 0.05) at 30 months, but attenuated in the follow-up evaluation at 42 months (76% versus 63%; p less than 0.1). The number of high-risk patients was too small for statistical evaluation. Relapse within the first 18 months after diagnosis indicated a poor prognosis and was more common in patients with MR than in patients with SR. The immunophenotype of the leukemic cells was not found to constitute an independent risk factor after treatment has been risk-adapted. Patients with an initial white blood cell count of more than 50 X 10(9)/l had a worse prognosis than patients with a lower white blood cell count (p less than 0.01).

Adolescent↗
PubMed1990

Identification of the platelet glycoprotein IIb/IIIa complex as a target antigen in primary biliary cirrhosis-associated autoimmune thrombocytopenia. Evidence that platelet-reactive autoantibodies can also bind to the mitochondrial antigen M2.

A 67-year-old woman with a 4-year history of primary biliary cirrhosis (PBC) unexpectedly developed autoimmune thrombocytopenia. The platelet-bound IgG antibody was eluted from the patient's platelets to determine the platelet target antigen. The autoantibodies were found to precipitate the platelet glycoprotein complex IIb/IIIa of autologous and allogeneic platelets. A further precipitate of 70 kDa was detectable under reducing conditions. In addition, platelet-reactive antibodies bound to the 70 kDa mitochondrial antigen M2. No cross-absorption studies were performed to confirm that a single antibody reacted with both antigens. Computer analysis of published peptide sequences of the mitochondrial protein and the platelet GPIIb/IIIa complex showed partial amino acid sequence homology suggesting the possibility of a common antibody binding site. These findings suggest a relationship between the development of autoimmune thrombocytopenia in PBC and the underlying liver disease.

Aged↗
PubMed1990

Purified human T cells stimulated with cross-linked anti-CD3 monoclonal antibody OKT3: rIL-1 is a co-stimulatory factor for CD4+CD29+CD45RA- T cells.

Accessory cells (AC) are believed to play two major roles in T-cell activation: they cross-link certain stimuli such as monoclonal antibodies, and they provide needed cytokines. To differentiate between these roles, we cross-linked OKT3 on highly purified T cells by means of Fc-specific goat anti-mouse IgG-coated polystyrene beads and studied T-cell activation after exogenously added cytokines. Following addition of AC, rIL-2, or rIL-1, CD25 was up-regulated, and the cells proliferated and became cytotoxic. Both CD4+ and CD8+ cells were activated in the presence of AC or rIL-2. In contrast, only CD4+CD29+CD45RA- cells responded in the presence of rIL-1. Anti-IL-2R p55 (anti-TAC) monoclonal antibody inhibited the proliferative response supported by rIL-2 or rIL-1. To inhibit proliferation of cells stimulated in the presence of AC, anti-TAC needed to be supplemented with anti-IL-6 antibodies, or to be added in a 10-fold higher concentration. Cultures with AC produced larger amounts of IL-2 than those supplemented with rIL-1. Only AC-containing cultures also produced detectable amounts of IL-6. These findings combined with the observation that none of 2000 purified T cells counted in each of six independent experiments expressed MHC class II antigens strongly suggest that rIL-1 can activate T cells directly, rather than indirectly by potentiating the function of contaminating AC.

Antibodies, Monoclonal↗
PubMed1990

Platelets in hyperthyroidism: studies on platelet counts, mean platelet volume, 111-indium-labeled platelet kinetics, and platelet-associated immunoglobulins G and M.

We compared in 15 patients with hyperthyroidism (11 with Graves' disease, 3 with toxic adenoma, and 1 with multinodular goiter) platelet counts (PC) and mean platelet volume (MPV) before and 3 weeks after initiation of antithyroid drug therapy when the patients were euthyroid. In addition, platelet kinetic studies of autologous 111-indium-labeled platelets and platelet-associated immunoglobulins G and M (PAIgG and PAIgM, respectively) were investigated. The control group for the platelet kinetic studies consisted of 2 patients with diffuse nontoxic goiter and 86 patients who were studied for evaluation of their arteriosclerotic vascular disease. After 3 weeks of antithyroid drug therapy there was a significant increase in PC and a decrease in MPV compared with the pretreatment values (pretreatment PC median, 215 X 10(9)/L; range, 96-350 X 10(9)/L; PC median 3 weeks later, 248 X 10(9)/L; range, 157-384 X 10(9)/L; P less than 0.005; pretreatment MPV median, 10.6 fL; range, 9.1-13.2 fL; MPV 3 weeks later, 9.9 fL; range, 8.4-11.0 fL; P less than 0.005). 111-Indium platelet recovery was normal in all subjects. Platelet lifespan was significantly shortened in the patients with hyperthyroidism compared with the control group (median, 163.8 h; range, 128.5-206 h; vs. 180.0 h; range, 138.3-231.5 h; P less than 0.05). Platelet turnover averaged 45.6 (range, 25.6-71.9) X 10(9)/L.day; values above the limit of normal were found in 7 of 15 patients with hyperthyroidism. Three patients with Graves' disease had elevated levels of PAIgG; 1 of these patients had elevated levels of PAIgM and was the only patient with thrombocytopenia (PC, 96 X 10(9)/L). Various combinations of statistical correlations between the degree of hyperthyroidism, pretreatment PC and MPV, platelet kinetic studies, levels of PAIg, and serum levels of antithyroid antibodies revealed no significant differences. These findings suggest that the platelet changes observed in hyperthyroidism, such as lower PC and increased MPV, together with the shortened platelet lifespan reflect metabolically rather than immunologically mediated phenomena, although these may be involved in cases with marked thrombocytopenia.

Adolescent↗
PubMed1990

[Preoperative autologous blood donation, effect of hydroxyethyl starch on the reticuloendothelial system and opsonins].

The effect of 6% low molecular weight (LMW) HES (MW 270,000) on reticuloendothelial function was studied in 9 male patients, median of age 50 years, who were scheduled for vascular surgery. An erythrocyte clearance test (Anti Rh) labeled with 99 mTc, evaluating primarily the splenic section of the RES, showed a considerable variation (37-87%) prior to hemodilution. 24 hours after replacement of 15 ml/kg body weight of blood, there was no significant change of the clearance rate, a follow up weeks later approached the base line values. Plasma opsonins like fibronectin, complement fraction 3, complement fraction 4 and immunoglobulin G showed a proportional decrease following hemodilution, and after 24 hours approached control levels. Changes at this time seemed to be independent from the course of the hematocrit. It is concluded that LMW HES does not adversely influence the spleen dependent phagocytic capacity of the RES system.

Blood Transfusion, Autologous↗
PubMed1990

Fatal encephalitis in a patient with chronic graft-versus-host disease.

A 32-year-old male patient with chronic myelocytic leukemia in accelerated phase received a bone marrow allograft from his 42-year-old HLA/MLC-identical sister. He recovered from acute graft-versus-host disease (GVHD) grade III-IV of skin, liver and gut, but chronic GVHD of progressive onset developed. On day 556 post-graft severe thrombocytopenia was resistant to prednisolone, cyclophosphamide and high dose immunoglobulin. Splenectomy was followed by a normalization of platelet counts. The subsequent clinical course was characterized by progressive muscular atrophy and weight loss. Dysphagia, dysarthria, cachexia and ultimately recurrent pneumonic episodes ensued. The cachectic patient developed a highly abnormal breathing pattern with hypoventilation and intermittent apnea requiring mechanical ventilation. Auditory evoked potentials revealed a considerable dysfunction of the brainstem. The patient died on day 1120 post-graft from pneumonia, aggravated by thoracic muscular insufficiency. Postmortem examination revealed diffuse predominantly lymphoid perivascular infiltration in meninges and CNS tissue; proliferation of activated microglial cells expressing the HLA-DR antigen was prominent in the brainstem. These histologic changes are similar to those observed in the CNS in experimental GVHD. We suggest that this case represents the first documentation of CNS involvement in chronic GVHD.

Adult↗
PubMed1989

Regulatory studies on the promoter for a gene governing synthesis and assembly of the spore coat in Bacillus subtilis.

gerE is a regulatory gene of Bacillus subtilis that governs the synthesis and assembly of the spore coat and is required for the production of spores that are lysozyme-resistant and germination-proficient. We report the identification of the promoter for gerE and studies on the regulation of its expression. We show that gerE is switched on at the fourth hour of sporulation (stage-V) and that this expression is restricted to the mother-cell chamber of the sporangium. Dependency studies in which the level of gerE expression was measured in 36 different developmental mutants indicate that efficient expression of gerE requires the products of almost all spo0-IV genes tested as well as certain spoV genes. On the basis of its time of induction, compartmentalization of expression and pattern of dependence on other spo genes, gerE is inferred to be regulated co-ordinately with the previously studied spore coat protein gene cotA. gerE and cotA may be members of a developmental regulon of genes whose products are involved in the assembly of the spore coat.

Bacillus subtilis↗
PubMed1989

Anticardiolipin antibodies are elevated in HIV-1 infected haemophiliacs but do not predict for disease progression.

Levels of anticardiolipin antibodies (ACA) were measured in 55 patients with haemophilia A in serum samples obtained in 1983 and in 1987. Twenty-one patients were negative for anti HIV-1 antibodies in 1983 and remained negative in 1987; 34 patients had anti HIV-1 antibodies in 1983; 17 of these latter patients remained asymptomatic, whereas 17 patients developed ARC or AIDS during the 4 years follow-up. Thirteen anti HIV-1 negative patients had elevated ACA levels in 1983; subsequently, a significant decrease was observed in all these subjects (p less than 0.001). All anti HIV-1 positive patients had elevated ACA levels in 1983; normal values were found in 9 patients in 1987. Yet, these changes were not significant (p greater than 0.05). ACA levels were significantly higher in HIV-1 infected patients than in those without anti HIV-1 antibodies (p less than 0.05). There was no difference of ACA levels between the two anti HIV-1 positive patient groups, be it in 1983 or be it in 1987 (p greater than 0.05). There was no correlation of ACA levels with serum IgG concentrations, CD4+ lymphocytes, or the consumption of factor VIII concentrates.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Antinuclear antibodies in patients with chronic idiopathic autoimmune thrombocytopenia followed 2-30 years.

We determined whether serological investigations can assist to distinguish between chronic idiopathic autoimmune thrombocytopenia (cAITP) and immune-mediated thrombocytopenia in patients at risk to develop systemic lupus erythematosus (SLE); 82 patients were seen in this institution for the evaluation of immune thrombocytopenia. In nine of these patients a diagnosis of SLE was made at presentation or shortly thereafter. In the remaining 73 patients with an established diagnosis of cAITP we obtained serum samples at a median disease duration of 7 years; 45 patients were investigated again 2 years later. cAITP patients suffered from their disease for up to 30 years (median 7 years, range 2-30 years) without developing clinical features of SLE. Elevated antinuclear antibodies were found in all patients with a diagnosis of SLE but also in seven patients with established cAITP. All patients who had thrombocytopenia in association with SLE had additional antibodies to anti-nDNA and/or antibodies to soluble cellular antigens. Neither in the initial, nor in the follow-up investigation, such antibodies were discernible in patients with cAITP. We conclude that patients with cAITP do not develop SLE and do not form antibodies to defined cellular antigens, even if suffering from the disease for many years. The ANA titer does not help to differentiate cAITP from thrombocytopenia of SLE. A differentiation, however, between the two diseases is possible by the combined screening for antinuclear antibodies, anti-nDNA, and antibodies to defined soluble cellular antigens.

Adult↗
PubMed1989

Identification of the target platelet glycoprotein in autoimmune thrombocytopenia occurring after allogeneic bone marrow transplantation.

We report the case of a patient who developed autoimmune thrombocytopenia after allogeneic bone marrow transplantation from her HLA-identical sister. An IgG autoantibody was detected that bound to the platelet glycoprotein IIb/IIIa and to the HLA class I proteins. Immunoprecipitation studies with radiolabeled platelets revealed additional antibody binding sites on proteins of 214 kDa molecular weight under nonreduced conditions and 65 and 56 kDa molecular weight under reduced conditions.

Adult↗
PubMed1989

Recurrence of hepatitis B in children with serologic evidence of past hepatitis B virus infection undergoing antileukemic chemotherapy.

Two patients showed an unusual serologic response to hepatitis B virus infection during intensive chemotherapy for acute lymphoblastic leukemia. Before treatment, one patient was anti-HBs- and anti-HBc-positive. During intensive chemotherapy these antibodies disappeared and HBsAg and HBeAg became detectable. Twenty months later, still on maintenance chemotherapy, active viral replication with high DNA polymerase levels was present. The second patient developed anti-HBc during the first course of intensive chemotherapy for acute lymphoblastic leukemia. She had anti-HBc and anti-HBe when a bone marrow relapse of the leukemia was diagnosed 3 years later and became HBsAg-positive together with high DNA polymerase levels in the serum while receiving intensive chemotherapy. Clinically no signs of active hepatitis were noted in these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Immune thrombocytopenia more than a year after allogeneic marrow transplantation due to antibodies against donor platelets with anti-PlA1 specificity: evidence for a host-derived immune reaction.

We report on a male patient transplanted from his HLA-matched sister for Ph1-chromosome positive chronic myelogenous leukaemia who developed immune thrombocytopenia more than 1 year after transplantation. The platelet antibody reacted with the platelet specific antigen PlA1 on donor platelets, and also on recipient platelets after engraftment. A presumed host-versus-donor induced thrombocytopenia was supported by Southern blot analysis using a Y-chromosome specific probe demonstrating residual host-origin cells in the patient's excised spleen.

Adult↗
PubMed1989

Effects of 3-azidothymidine on platelet counts, indium-111-labelled platelet kinetics, and antiplatelet antibodies.

Treatment of the acquired immunodeficiency syndrome with 3-azidothymidine (zidovudine; AZT) can induce severe neutropenia and anemia, while platelet counts increase. In order to understand the mechanism by which this favorable effect on platelets is induced, we prospectively studied platelet kinetics and platelet serology in 8 hemophiliacs receiving the drug. All patients underwent a second investigation after 3 months of treatment. Four patients were thrombocytopenic before treatment. Platelet counts increased significantly already after 1 week of treatment (p = 0.03), when only 3 patients remained thrombocytopenic. In these latter patients a further increase of platelet counts was noticed during the following 3 months. Platelet life-span was shortened in all patients at the initial investigation and a significant prolongation was measurable at the second evaluation (p = 0.015). Platelet-associated immunoglobulin G was increased in 3 patients at the first investigation and in 4 patients at the follow-up. Platelet-associated complement (PAC3d) was elevated in all subjects at the first determination. It decreased in 6, but increased in 2 patients thereafter; thus these changes did not become significant (p = 0.078). Immunofluorescence studies revealed antiplatelet antibodies in 7 patients' sera before treatment, and in 5 sera during drug therapy. At both investigations, the antibodies bound to the platelet glycoprotein IIIa as was demonstrated by immunoprecipitation of radiolabeled platelet proteins. We conclude, that AZT treatment improves platelet counts in HIV-infected hemophiliacs primarily by a prolongation of platelet survival without having a significant influence on antiplatelet antibody binding.

Autoantibodies↗
PubMed1989

Evidence for an additional temporal class of gene expression in the forespore compartment of sporulating Bacillus subtilis.

We present evidence indicating that the previously studied, sporulation-induced gene 0.3 kb, which encodes a stable RNA present at late developmental stages, is transcribed in the forespore chamber of sporulating cells of Bacillus subtilis. Compartmentalized gene expression was demonstrated on the basis of subcellular fractionation experiments in which severalfold-higher levels of 0.3 kb-directed beta-galactosidase specific activity were observed in forespore extracts than in extracts from the mother cell and dependence studies in which 0.3 kb transcription was found to be blocked in mutants bearing mutations in spoIIIA, spoIIIE, and spoIIIG, genes which are known to govern forespore gene expression. Also, 0.3 kb transcription could be switched on during growth in cells in which transcription of the forespore regulatory gene spoIIIG was engineered to be activated in response to the lac inducer IPTG (isopropyl-beta-D-thiogalactopyranoside). Although it is transcribed in the forespore, 0.3 kb is switched on at a later developmental stage than other previously studied forespore-expressed genes, and hence it appears to be representative of an additional temporal class of compartmentalized gene expression.

Bacillus subtilis↗
PubMed1988

Functional asplenia after bone marrow transplantation. A late complication related to extensive chronic graft-versus-host disease.

STUDY OBJECTIVE: To evaluate splenic function in bone marrow transplant recipients, with relation to chronic graft-versus-host disease and infections. DESIGN: Survey, outpatients geographically accessible for voluntary participation. SETTING: Bone marrow transplantation referral center. PATIENTS: Fifteen bone marrow graft recipients (13 allogeneic, 2 autologous), out of a total of 33 patients who received transplants at the center and survived more than 6 months after grafting. MEASUREMENTS AND MAIN RESULTS: In 6 of 15 patients impaired splenic function (functional asplenia) was indicated by the presence of Howell-Jolly bodies in peripheral blood smears, reduced spleen size (P less than 0.001), higher platelet counts (P less than 0.01), higher indium-111 labeled autologous platelet recovery (P less than 0.005), reduced splenic blood flow (P less than 0.001), and reduced accumulation of radioactivity at the splenic site (P less than 0.001). All patients with functional asplenia but only 2 patients without functional asplenia had extensive chronic graft-versus-host disease. The incidence of bacterial infections was four times higher in patients with impaired splenic function. CONCLUSIONS: Functional asplenia is a late complication after allogeneic bone marrow transplantation and contributes to the high susceptibility to bacterial infections in patients with extensive chronic graft-versus-host disease.

Adolescent↗