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Biomedical subjects

S Panzer

Publications and source records attributed to S Panzer.

At least 73 records · Page 4Linked to original sources
PubMed1998

Increase in endogenous thrombopoietin in healthy donors after automated plateletpheresis.

BACKGROUND: Thrombopoietin (TPO) is a key cytokine involved in the regulation of megakaryocytopoiesis and platelet production. The aim of the present study was to test whether platelet donation is associated with changes in the serum TPO levels in healthy donors undergoing plateletpheresis. STUDY DESIGN AND METHODS: The study group consisted of 23 healthy donors undergoing single-donor plateletpheresis for the first time. Serum TPO levels and platelet counts were determined before platelet collection, at the end of apheresis, and for 4 days thereafter. Serum TPO levels were determined by a TPO-specific enzyme-linked immunosorbent assay. RESULTS: In relationship to platelet donation, serum TPO levels showed a temporary increase from baseline levels of 69.2 +/- 7.1 pg per mL to 117 +/- 6.8 pg per mL 2 days after plateletpheresis (p < 0.05). Further evaluation revealed a decline in serum TPO levels as platelet counts increased. Female donors showed a delayed normalization of circulating platelet numbers and serum TPO levels as compared to male donors. There was no significant correlation between serum TPO levels and the absolute platelet number during normalization of the donors' platelet counts after plateletpheresis. CONCLUSION: Single-donor plateletpheresis results in a temporary increase in serum TPO levels in healthy platelet donors, which may be part of a compensatory response-boosting megakaryocytopoiesis after platelet collection.

Blood Donors↗
PubMed1998

Measurement of the levels of reticulated platelets after plateletpheresis to monitor activity of thrombopoiesis.

BACKGROUND: Little is known about the effects of long-term plateletpheresis on the donors' health. The aim of this study was to examine the effect of plateletpheresis on the time course of reticulated platelet counts as an estimate for thrombopoiesis. STUDY DESIGN AND METHODS: The effect of moderate platelet depletion on the thrombopoietic capacity was evaluated prospectively by the measurement of reticulated platelets before and after plateletpheresis and on the following 4 days. Donors undergoing plateletpheresis for the first time were compared to those donating platelets every other week for more than 18 months. RESULTS: The median levels of reticulated platelets were significantly lower in frequent donors than in new donors. In new donors, there was a transient increase in the median levels of reticulated platelets on Day 3 after apheresis, and baseline values were reached again on Day 4. On the contrary, in repeat donors, there was a sustained rise in the percentage of reticulated platelets from Days 1 through 4. However, this increase in reticulated platelet counts was still less than that seen in new donors. There was no difference in the peripheral blood platelet counts in the two groups at any time point. CONCLUSION: These findings suggest that repeat platelet donation might lead to a relative exhaustion of thrombopoiesis, as evidenced by the low levels of reticulated platelets exhibited by repeat donors. The reticulated platelet count can be used to monitor the thrombopoietic capacity of long-term platelet donors.

Adult↗
PubMed1997

Increased prevalence of a polymorphism in the gene coding for human prothrombin in patients with coronary heart disease.

A number of genetic risk factors for the development of coronary heart disease has been identified in the past. Some of these represent polymorphisms in genes of proteins which are associated with the process of blood clotting. We investigated the distribution of a recently described G/A polymorphism in the 3'untranslated region of the human prothrombin gene (nt 20210) in 98 patients (19 female age: 53 + 12 SD years and 79 male, age: 49 + 8.5 SD years) with coronary heart disease and in 102 healthy newborns by enzymatic amplification of the genomic DNA carrying the polymorphic site and by subsequent restriction digest. The diagnosis of coronary heart disease was established by coronary angiography in all patients. The frequency of the A allele in the healthy newborns was 0.98% (0.2%-3.5%; CI 0.95) with the G/A genotype occurring in 1.96% (0.24%-6.9%; CI 0.95). In the group of patients with coronary heart disease the G/A genotype was found in 5.1% (1.7%-11.4%; CI 0.95). 94.9% of the patients studied showed a G/G genotype. The A/A genotype was neither detected in the newborns nor in the patients with coronary heart disease. This preliminary study strongly suggest that the presence of the G/A polymorphism in the 3'untranslated region of the gene coding for human prothrombin is associated with the occurrence of coronary heart disease.

Adult↗
PubMed1997

Tumor-suppressive pathways in pancreatic carcinoma.

During tumorigenesis, positive selection is exerted upon those tumor cells that alter rate-limiting regulatory pathways. A corollary of this principle is that mutation of one gene abrogates the need for alteration of another gene in the same pathway and also that the coexistence in a single tumor of mutations in different genes implies their involvement in distinct tumor-suppressive pathways. We studied 42 pancreatic adenocarcinomas for genetic alterations in the K-ras oncogene and the p16, p53, and DPC4 tumor suppressor genes. All of them had the K-ras gene mutated. Thirty-eight % of the tumors had four altered genes, another 38% had three altered genes, 15% had two altered genes, and 8% of the tumors had one altered gene. Interestingly, we noted a high concordance of DPC4 and p16 inactivations (P = 0.007), suggesting that the genetic inactivation of p16 increases the selective advantage of subsequent mutation in DPC4. No statistically significant association was identified between the alteration of these cancer genes and pathological or clinical parameters. This type of multigenic analysis in human tumors may serve to substantiate experimental tumor models and thus increase our understanding of the truly physiologically relevant tumor-suppressive pathways that are abrogated during human tumorigenesis.

Adenocarcinoma↗
PubMed1997

Target platelet antigens of autoantibodies in patients with primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver, frequently associated with thrombocytopenia. As various immune abnormalities have been described in PBC, we hypothesized that thrombocytopenia is also an autoimmune phenomenon in these patients. We therefore assessed the frequency of platelet antibodies and their target platelet glycoprotein (GP) specificities. We investigated 66 PBC patients with a median disease duration of 25 months. Twenty-two patients with alcoholic liver disease and thrombocytopenia served as controls. Specificities of platelet antibodies were determined by the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay using monoclonal antibodies directed against GPIIb/IIIa and GPIb/IX. The notion that immunoglobulins are nonspecifically bound to platelets was further evaluated by the production of eluates from antibody-coated platelets. The specificities of antibodies in these eluates were again determined by the MAIPA assay. Twenty-six PBC patients had platelet antibodies, whereas antibodies were not detectable in control alcoholic patients. Seven of 13 thrombocytopenic PBC patients had detectable antibodies. Overall, GP Ib/IX and GP IIb/IIIa served in a similar frequency as target antigens. Antibody specificities were confirmed by the production of eluates from platelets. These studies provide evidence that antibodies are specifically bound to platelets in patients with PBC and that the development of immune phenomena in PBC may also involve immuno-mediated platelet destruction.

Adult↗
PubMed1997

Specificities of platelet autoantibodies in patients with lupus anticoagulants in primary antiphospholipid syndrome.

We have studied target platelet antigens in 22 patients with lupus anticoagulants and a primary antiphospholipid syndrome in order to determine whether any specificities of platelet autoantibodies are correlated with thromboembolism, and if these antibodies cross-react with phospholipids, which would suggest their role in the development of thromboembolic disease. Platelet counts were median 203 x 10(9)/l, range 100-298 x 10(9)/l. Platelet antibodies were found in six thrombocytopenic patients and in further nine patients. All these 15 patients had antibodies against GPIIb/ IIIa, five patients against GPIb/IX, and six patients against GPIV. Anti-GPIb/IX and -GPIV occurred only in combination with anti-GPIIb/IIIa antibodies. There was no correlation between the presence of detectable platelet antibodies or any of their glycoprotein specificity and thrombocytopenia or the history of a thromboembolic disease. Eluates from platelets contained only GPIIb/IIIa reactivities, but neither anti-GPIb/IX nor anti-GPIV. None of the eluates contained lupus anticoagulant activity. In one case, the platelet eluates contained anti-GPIIb/IIIa and anticardiolipin IgG antibodies. These results suggest that in patients with a primary antiphospholipid syndrome the presence of platelet autoantibodies neither indicate a risk for thromboembolic disorder nor have lupus anticoagulant activity.

Adolescent↗
PubMed1997

Acute leukemias express a functional receptor for the human growth hormone.

The potential influence of the human growth hormone (hGH) on the behavior of acute leukemias is a matter of controversy. We investigated primary childhood and adult leukemias (n = 44) and leukemic cell lines (n = 13) for the expression of the hGH receptor (hGHR) by immunohistochemistry and flow cytometry. All leukemias expressed the hGHR in the cytoplasm; expression on the surface was undetectable in some of the leukemias. In leukemic cell lines, hGHR expression on the surface was demonstrated in a dose-dependent manner after incubation with rhGH. Physiologic concentrations of hGH were more efficient than higher doses in increasing hGHR surface expression. A proliferative response to hGH was accomplished in cell lines REH, Molt4, and K562. However, only one of 19 primary leukemias (ALL, n = 12; AML, n = 7) showed increased cell counts after the addition of 50-800 ng/ml recombinant hGH (rhGH). These cells were of an immature T-cell phenotype. We thus conclude that acute leukemias can be stimulated by hGH to up-regulate its receptor, but that most primary leukemias may require additional signals for the induction of proliferation.

Adult↗
PubMed1997

Documented sudden onset of pseudothrombocytopenia.

A 66-year-old male patient was hospitalized for severe heart failure. Within 3 days after admission his platelet count dropped from 148 x 10(9)/l to 3 x 10(9)/l. Pseudothrombocytopenia was diagnosed based on the platelet count of 3 x 10(9)/l in K3-EDTA anticoagulated blood as opposed to 110 x 10(9)/l in sodium citrate. Platelet reactive antibodies were not detectable. To the best of our knowledge, this is the first report of a documented onset of pseudothrombocytopenia.

Aged↗
PubMed1997

Lupus anticoagulants: strong association with the major histocompatibility complex class II and platelet antibodies.

A relationship between the presence of platelet autoantibodies and major histocompatibilty complex class II alleles was determined in 27 patients with lupus anticoagulants. Twenty-two patients had a primary antiphospholipid syndrome' and five patients had lupus erythematosus (SLE). Platelet antibodies against the platelet glycoproteins (GP) IIb/IIIa were detectable in 20 patients. Anti-GPIb/IX or -GPIV antibodies were detectable only in patients with anti-GPIIb/IIIa antibodies. An increased frequency of HLA-DQB1*06 was demonstrable in the total patient population. The association between the lupus anticoagulants and HLA-DQB1*06 was even stronger if patients also had detectable platelet antibodies. This association was also seen if patients with a history of thromboembolic disease were considered separately. However, within the patient population there was no difference between frequencies of HLA alleles detectable platelet antibodies.

Adolescent↗
PubMed1997

Crosslineage TCR delta rearrangements occur shortly after the DJ joinings of the IgH genes in childhood precursor B ALL and display age-specific characteristics.

In order to test the hypothesis that the most immature T-cell receptor (TCR) rearrangements occur after the DJ joining of the immunoglobulin heavy chain genes (IgH), we analysed the TCR Vdelta2-Ddelta3 rearrangements in precursor B-cell leukaemias (PBC ALL) from 25 children younger than 3 years at disease onset and found that most of the junctional regions had N nucleotides inserted. We then selected 14 of these PCB ALLs for DJH (DJ joining of the IgH) characterization. These joining regions showed homology-directed recombination and lack of N regions, indicating absence of terminal deoxynucleotidyl transferase (TdT) activity during their rearrangement. Most leukaemias with a DJH rearrangement without N region have no, or only one, nucleotide in the joining regions of their Vdelta2-Ddelta3 rearrangements. The N regions of the TCR delta rearrangements displayed 'age-specific' differences: in children younger than 3 years of age the N regions were shorter than in those older than 3 years, and the rearrangements frequently contained complete segments. We conclude that the Vdelta2-Ddelta3 rearrangement in childhood PCB ALLs is an early event following DJH rearrangement and that it occurs shortly before or after the first hit, leading to malignant transformation.

Adolescent↗
PubMed1997

Spontaneous rise of fetal platelet counts despite increasing anti-HPA-5b antibodies.

BACKGROUND AND OBJECTIVES: Maternal anti-HPA alloantibodies are a rare cause of severe fetal thrombocytopenia. So far there have been no reports on the dynamics of maternal anti-HPA-5 during gestation and its effect on the fetus. MATERIALS AND METHODS: We monitored maternal anti-HPA-5b antibody titers and fetal platelet counts during gestation in a woman with known anti-HPA-5b alloimmunization. The patient was a 32-year-old woman in her third pregnancy. The 1st pregnancy and delivery of a healthy child had been uneventful. At delivery, anti-HPA-5b was detectable in the maternal serum. A 2nd pregnancy ended in early miscarriage. RESULTS: A steady rise in the alloantibody titer was recorded throughout the 3rd pregnancy. Therefore, cordocentesis was performed at 28 weeks of gestation (platelet count 76 x 10(9)/l). Serial platelet transfusions were administered to the fetus at 28, 32, and 37 weeks of gestation. The platelet counts rose spontaneously thereafter and were 220 x 10(9)/l at delivery, despite an increase in the anti-HPA-5b antibody titer. The child developed normally during the first year of life. CONCLUSIONS: This case illustrates the spontaneous recovery of fetal platelet counts in late pregnancy despite a rise in maternal alloantibody titer.

Adult↗
PubMed1997

Using explicitly represented biological relationships for database navigation and searching via the World-Wide Web.

MOTIVATION: The increasing availability of biological databases on the World-Wide Web and hypertext links between them has made a wealth of information easily accessible to biologists. Additional retrieval capabilities can be achieved by storing explicitly specified biological relationships between different entities as discrete database entries. RESULTS: We have built CySPID, a prototype database about the cytoskeleton that explores the approach of explicitly representing biological relationships. The stored relationships are displayed along with other retrieved information, can be used to make hyperlinks to related entities, and can be used to search for entities with specified properties. CySPID is extensible in that new types of relationships may be created without altering the database schema. AVAILABILITY: CySPID is available for public use (http://ycmi.med.yale.edu/cyspid/). The CGI scripts used by CySPID are available upon request.

Animals↗
PubMed1996

Genotypes of the vitamin-D-receptor gene and bone mineral density in Caucasoid postmenopausal females.

OBJECTIVE: To evaluate the relation of bone mineral density (BMD) to inherited polymorphisms within the gene coding for the vitamin D receptor (VDR) in postmenopausal women. METHODS: DNA samples from 163 post-menopausal women and from 112 controls were genotyped for common allelic determinants within the VDR gene as defined by the restriction enzyme sites for BsmI, ApaI, and TaqI. BMD was evaluated at the lumbar spine (L2-L4) by dual energy X-ray absorptiometry. Single restriction enzyme site polymorphisms as well as their joint genotypes were evaluated for their association with BMD in postmenopausal women. RESULTS: The three restriction site polymorphisms showed a close association indicating linkage disequilibrium (P < 0.0001). There was no relationship between any of the single restriction site polymorphisms and BMD. The distribution of the five most common joint genotypes among postmenopausal women and controls was similar. There was no relation of BMD and any of the five most common VDR genotype groups. Females more than 5 years after menopause had a significantly lower BMD than those less than 5 years after menopause (P < 0.001). This age-related decrease of BMD was also decernible within genotype groups. CONCLUSION: In our population, the postmenopausal period has a major influence on BMD, but BMD is not controlled significantly by any of the common allelic variations within the VDR gene.

Absorptiometry, Photon↗
PubMed1996

Specificities of anti-platelet antibodies in multitransfused patients with haemato-oncological disorders.

The clinical condition and the formation of platelet-reactive antibodies influence the post-transfusion platelet increment. We analysed the specificities of platelet-reactive antibodies in 81 multitransfused patients with haemato-oncological diseases refractory to platelet transfusions, or prior to a scheduled stem cell transplantation. In 17 additional patients we prospectively determined the development of platelet-reactive antibodies at the time of chemotherapy in weekly intervals. Sera were tested by the monoclonal antibody-specific immobilization of platelet antigens (MAIPA)-technique for antiplatelet antibodies against HLA class I antigens, the human platelet-specific alloantigens (HPA)-1, -2, -3, -5, and the platelet membrane glycoproteins (GP) Ia/IIa, Ib/IX, IIb/IIIa (panreactive). Platelet reactive antibodies were found in 54% of blood samples. They were frequent in patients with a history of possible previous immunization, particularly if patients were refractory to platelet transfusions. Platelet-reactive HLA antibodies were the most common antibodies. Even patients without a known risk of primary immunization who received exclusively leucocyte-depleted blood products formed antibodies. By the MAIPA technique, even LCT-negative sera were found to contain platelet-reactive antibodies.

Adolescent↗
PubMed1996

Rapid typing for human platelet antigen systems-1, -2, -3 and -5 by PCR amplification with sequence-specific primers.

Typing for human platelet antigens (HPA) is useful in a variety of clinical situations. We developed a method for genotyping for HPA-1, -2, -3 and -5 by means of the PCR amplification with sequence-specific primers (PCR-SSP) technique. Primer sets were designed to allow PCR amplification for all systems using the same assay conditions. Specificity and sensitivity of the method were assessed in a blind quality control study (n = 112). In 111 cases, results obtained by PCR-SSP were identical as compared with PCR-restriction fragment length polymorphism technique. One discrepancy was found to be due to a typing error in the data sheet. The results of the PCR-SSP technique were available within 3 h. We conclude that genotyping based on PCR-SSP enables rapid typing for HPA systems, which makes this technique feasible in most clinical settings where urgent HPA typing is required.

Antigens, Human Platelet↗
PubMed1996

Flow cytometric detection of platelet-reactive antibodies and application in platelet crossmatching.

BACKGROUND: Alloimmunization against HLA or platelet antigens can cause refractoriness to platelet transfusions in multiply transfused patients. Crossmatching of platelet concentrates is effective in overcoming this problem. STUDY DESIGN AND METHODS: A flow cytometric assay was used for simultaneous detection of lymphocyte-reactive and platelet-reactive antibodies in a single sample using fluorescein isothiocyanate-labeled anti-IgG. This assay was compared with the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay in selected sera containing HLA and platelet antibodies. In a further study, this assay was compared with lymphocytotoxicity test results from thrombocytopenic patients, for whom platelet concentrates were ordered. The results of both assays were then correlated with the 1-hour corrected count increment, with a corrected count increment greater then 7500 considered as an adequate transfusion response. RESULTS: The results of the MAIPA and flow cytometric assay in detecting platelet-reactive antibodies correlated well (p<0.0001, r = 0.84). The sensitivity and specificity of the flow cytometric assay in detecting platelet-reactive antibodies were 94.7 and 96.3 percent, when the MAIPA assay was taken as a reference. In unselected sera from patients, the sensitivity and specificity of the flow cytometric assays were, respectively, 72.7 and 91.7 percent in detecting lymphocyte-reactive antibodies and 70.6 and 77.7 percent in detecting platelet-reactive antibodies, when the lymphocytotoxicity test was used as a reference. With regard to an adequate transfusion response, the sensitivities and efficiencies were 20.0 and 82.1 percent, 33.3 and 84.3 percent, and 70.0 and 88.6 percent for the lymphocytotoxicity test and the lymphocyte-reactive and platelet-reactive flow cytometric assays, respectively. CONCLUSION: Flow cytometric crossmatching appears to be an effective method of detecting platelet-reactive antibodies that may affect the success of platelet transfusions. This procedure is well-suited for routine conditions and can be performed within 2 hours.

Antibodies, Monoclonal↗