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Biomedical subjects

D de Jong

Publications and source records attributed to D de Jong.

At least 91 records · Page 5Linked to original sources

Unique combination of an ovarian gonadoblastoma, dysgerminoma, and mucinous cystadenoma in a patient with Turner's syndrome: a cytogenetic and molecular analysis.

Phenotypically female patients with a (mosaic) XY karyotype are at high risk to develop gonadoblastoma with potential progression to dysgerminoma. We studied a Turner's syndrome patient with a composite ovarian neoplasm of a gonadoblastoma, a dysgerminoma, and a mucinous cystadenoma. Nonradioactive in situ hybridization showed that the patient had a XO/XY genotype with deletion of part of Yq. Molecular analysis located the chromosomal breakpoint in deletion interval 6, indicating that potential genes responsible for the development of gonadoblastoma may be located on the short arm of the Y chromosome or on the long arm, centromeric of deletion interval 6. Moreover, using the XO/XY mosaicism as a clonal marker, the dysgerminoma and the mucinous cystadenoma were shown to be of independent origin. Therefore, in this case, we find support for the hypothesis that mucinous cysts with gastrointestinal epithelium can be of ovarian surface epithelial cell origin. This case also demonstrated that the occurrence of a composite tumor does not unequivocally imply that both components are of the same origin. Clonal analysis is required to determine the relation of the tumor constituents.

Adult↗

Laparoscopic rectopexy.

Laparoscopic rectopexy has been performed in four female patients with rectal prolapse. Four or five trocars were used in each case, with the same introduction places as for laparoscopic anterior resection. After dissecting the rectum free, a polypropylene mesh was introduced and fixed to the promontorium with an endoscopic stapler device, and then sutured to the rectum leaving a fourth of the anterior rectal wall free. The average operating time was three hours and the hospital stay six days. No constipation has been observed postoperatively in the patients with preoperative normal bowel habit. The introduction of laparoscopic rectopexy opens the possibility of performing different fixation techniques for various functional problems in the pelvis, offering a significant decrease in morbidity.

Aged↗

Essential differences in oncogene involvement between primary nodal and extranodal large cell lymphoma.

Large cell lymphomas (LCLs) are heterogeneous in morphology, clinical presentation, and behavior. We studied 52 de novo LCLs of B-cell type for rearrangements of the bcl-2 and c-myc oncogenes by Southern blot analysis and related these data to the primary site of presentation, stage, and cytomorphology. Thirteen tumors had comigrating rearrangements of JH and bcl-2, indicative of a t(14;18). Far more primary nodal lymphomas than extranodal lymphomas carried a t(14;18) (40% v less than 5%). Additionally, almost all lymphomas with a t(14;18) versus 41% of the tumors without a bcl-2 rearrangement presented with lymphadenopathy. c-myc rearrangements were seen in 35% of the extranodal lymphomas and 5% of the nodal lymphomas. No differences were observed in bone marrow involvement and staging according to Ann Arbor. bcl-2 rearrangements were found in 50% of the LCLs with cleaved nuclei, whereas c-myc rearrangements were relatively frequent (25%) in the noncleaved subtype. Our data support the hypothesis that primary nodal and extranodal lymphomas have a different genetic origin.

Blotting, Southern↗

[The usefulness of thoracic computerized tomography in patients in an intensive care unit].

Performing thoracic CT scanning in critically ill patients can be cumbersome and may have detrimental effects on the condition of the patient. We retrospectively analysed the clinical data of 46 patients who were examined over a period of 4.5 years. The thoracic CT scanning was judged useful in 40 patients (87%) and beneficial for 23 (50%) of these. The principal indications for the investigation are: suspected pulmonary abscess, suspected mediastinitis, precise localisation of an intrathoracic lesion prior to surgery, difficulty in the evaluation of the pulmonary parenchyma in patients with deforming thoracic kyphoscoliosis, suspected trapped pleural fluid and a suspected thoracic focus of sepsis. Transport had no detrimental effects on any of the patients. If the decision to undertake CT scanning is arrived at jointly by the radiologist and intensive care physicians, CT scanning is useful and can be performed safely if transport is undertaken by an experienced team.

Aged↗

De novo acute B-cell leukemia with translocation t(14;18): an entity with a poor prognosis.

Three cases of de novo acute B-cell lymphoblastic leukemia are presented, all with an unusual phenotype, involvement of translocation t(14;18) and additional chromosomal abnormalities, including translocation t(8;14) and deletion of chromosome 9. In contrast to normal FAB-L2 or FAB-L3 acute lymphoblastic leukemia (ALL), these leukemias did not express cytoplasmatic and membranous immunoglobulin. The combination of translocation t(14;18) and additional chromosomal events on the other chromosome 14 account for the lack of immunoglobulin expression. In one case a low grade follicular lymphoma was found next to a high grade Burkitt type ALL. The translocation t(14;18) takes place as a mistake in the VDJH joining in pre-B cells in the bone marrow. It is proposed that some cases of de novo ALL may arise as a blast crisis induced by genetic events, secondary to the primary t(14;18) translocation. This type of ALL seems to have a poor prognosis.

Adult↗

X-chromosome inactivation in patients who have pigmented villonodular synovitis.

We performed a histological examination and DNA analysis on samples of tissue from a forty-seven-year-old woman who had a clinical diagnosis of pigmented villonodular synovitis. The histological examination confirmed the diagnosis. The evaluation of the samples of tissue with preferential X-chromosome inactivation analysis (a molecular biological method for the study of clonality in tumors) showed that the lesion was polyclonal in origin. We concluded, therefore, that pigmented villonodular synovitis is more likely to be a reactive process than a true neoplasm.

Blotting, Southern↗

Bcl-2/JH rearrangements in benign lymphoid tissues with follicular hyperplasia.

The t(14; 18)(q32;q21) chromosomal translocation, characteristic of follicular lymphoma, couples the bcl-2 protooncogene on chromosome 18 to the immunoglobulin heavy-chain joining region (JH). This results in a deregulated transcription rate of bcl-2, suggesting a major role of the t(14;18) translocation in lymphomagenesis. By using a sensitive polymerase chain reaction technique specific for the major breakpoint region t(14;18), we now demonstrate the presence of bcl-2/JH rearrangements in lymph nodes and tonsils with follicular hyperplasia in 13 of 24 cases (54%). The approximate frequency was one translocation-positive cell in 10(5) cells. No bcl-2/JH rearrangements were detected in reactive lymph nodes without follicular hyperplasia or in bone marrow cells. Sequence analysis showed the amplified bcl-2/JH fragments to be unique to each individual sample and distinct from 24 sequenced follicular lymphoma-derived t(14;18) junctions, thus excluding contamination artifacts. The presence of random nucleotide insertions at the breakpoint junctions suggests a pre-B-cell origin of the t(14;18) translocation, in analogy with follicular lymphomas. We conclude that the t(14;18) translocation can occur in non-malignant tissue and will not, on its own, lead to malignancy.

Base Sequence↗

A new non-Hodgkin's B-cell line (DoHH2) with a chromosomal translocation t(14;18)(q32;q21).

A spontaneously growing EBV-negative B-cell line (DoHH2) was established from the pleural fluid cells of a 60-year-old man with centroblastic/centrocytic non-Hodgkin's lymphoma, that had transformed into an immunoblastic lymphoma. The pleural fluid cells and the DoHH2 cells expressed IgG lambda, were reactive with CD10 and CD19 monoclonal antibodies, and showed by cytogenetic analysis 48,XY, +7, +del(12)(q24), t(14;18)(q32;q21). Southern blot analysis of mini-satellite DNA patterns, and of rearrangements of the immunoglobulin genes and bcl-2, confirmed that the cell line was derived from the patient's clonal lymphoma cells. Direct nucleotide sequence analysis on polymerase chain reaction (PCR) products of the t(14;18) junction revealed an identical sequence for the JH-bcl-2 junction at JH6 and in the major breakpoint region of bcl-2 in both the original tumor cells and the DoHH2 cell line. The cell line was valuable as a standard quantification control for PCR analysis of the t(14;18) breakpoint. Titration experiments demonstrated the detection of up to one tumor cell in 10(5) normal blood lymphocytes.

Antigens, Viral↗

Clonal B-cell populations in patients with idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura (ITP) may be associated with other autoimmune diseases and the development of lymphoproliferative malignancies. In Sjögren's disease, Graves' disease, and essential mixed cryoglobulinemia, which are also associated with the development of B-cell neoplasia, clonal B-cell expansions have been detected. Eleven patients with ITP were investigated for the presence of a clonal excess (CE) using kappa-lambda flow cytometry and DNA analysis for rearrangement of immunoglobulin heavy and light chain genes in blood and/or spleen lymphocytes. In 10 of 11 patients, clonal B-cell populations were found by one or both tests. In three of these patients, oligoclonal B-cell populations were suggested by the combined findings. In all four patients with a small paraproteinemia, the isotype was confirmed by either flow cytometry or DNA rearrangement analysis. Our data suggest that the oligoclonal expansions are not restricted to CD5+ B cells, as in the majority of patients this subset was below the detection level of flow cytometry or DNA rearrangement analysis. None of the patients developed clinical manifestations of malignant lymphoma during a follow-up period of 10 to 44 months after sampling. We conclude that clonal excess populations of B cells are not a unique feature of malignant lymphoma, but may occur in autoimmune diseases, suggesting a benign (oligo)clonal B-cell proliferation.

Adult↗

Translocation t(14;18) in B cell lymphomas as a cause for defective immunoglobulin production.

Although follicle center cell (FCC) lymphomas represent mature B cells, a considerable percentage do not have detectable Ig production. We have used Southern blotting and the polymerase chain reaction (PCR) to study the involvement of translocations t(14;18) and t(8;14) in causing defective Ig production in 16 Ig- FCC-derived lymphomas and three Ig- B cell acute lymphoblastic leukemias. In 6 of 19 cases, a t(14;18) was present with the other allele either deleted or in germline. In two cases a t(14;18) and a t(8;14) affected both Ig alleles, as confirmed by karyotyping. In two other cases, rearrangement of both bcl-2 on chromosome 18 and c-myc on chromosome 8 were found as well. Although cytogenetic proof was not available, the latter was probably involved in t(8;14). Restriction map analysis of one more case showed rearrangement on the pseudo-JH3 gene on one allele and t(14;18) on the other. Thus, in 11 of 19 cases, defective Ig H chain production could be explained by the inactivation of both Ig H chain genes due to translocation of one allele, in combination with deletions or defective rearrangements of the other allele. In contrast, in 28 of 30 Ig+ lymphomas, one functional Ig H chain allele was found, either in, or not in, combination with t(14;18). In two cases a single rearranged Ig H chain allele was found in combination with rearrangement of bcl-2. No comigration of the single Ig rearrangement with bcl-2, however, was found both by Southern blotting and PCR, suggesting a variant bcl-2 translocation, which leaves the Ig H chain allele functionally intact.

Alleles↗

Alterations in immunoglobulin genes reveal the origin and evolution of monotypic and bitypic B cell lymphomas.

During progression of B-lymphoproliferative disorders (B-LPD), increasing divergence can be detected in histology, cytogenetics, and clinical behavior. To investigate genomic tumor cell heterogeneity, 50 biopsies of 21 patients with B-LPD of different histogenetic origin were studied for changes in the immunoglobulin gene structure during follow-up study. Ig-heavy chain (IgH) gene alterations were analyzed by Southern blotting using a panel of eight endonucleases. Ig-light chain (IgL) genes and the translocation of the bc 1-2 gene involved in t(14;18) were also studied. In seven of nine follicular lymphomas, most alterations suggested mutations in the IgH genes. Conservation of most restriction sites and of the t(14; 18) breakpoint confirmed the monoclonal origin in these tumors. Also, in two of three diffuse follicle center cell lymphomas (CLL) and in each of four immunocytomas, IgH alterations were found. In contrast, clonal changes were absent in three centrocytic lymphomas and two cases of CLL. In two follicular lymphomas with bitypic IgL expression, a common origin with subsequent divergence of the two constituents, rather than true biclonality, was indicated by the Ig gene structures. No relation was found between the frequency of somatic mutations and histologic signs of progression. These data indicate that somatic hypermutation in IgH genes is related to the histogenesis of the B-LPD and reflect the physiology of their benign counterparts in normal B cell development.

B-Lymphocytes↗

Computed tomography as an adjunct to chest x-rays of intensive care unit patients.

An analysis of 23 CT scans performed on 20 patients was carried out in an approximate 2-yr period. In 15 patients, CT scans were judged useful by subsequent clinical course when they indicated maintenance or alteration of existing treatment strategies. CT scans in five patients were not helpful. When judged by eventual outcome, the impact of CT scans remains uncertain. The influence of transportation is difficult to assess; it requires experienced team work and is contraindicated in cases where respiratory or circulatory stability might be seriously impaired.

Adult↗

Treatment of respiratory tract infections with pefloxacin in critically ill patients hospitalized in a surgical intensive care unit.

Respiratory tract infections were treated with pefloxacin in fifteen patients, who were hospitalized in the intensive care unit and required artificial ventilation. The treatment was successful in ten patients. Development of resistance was observed in Staphylococcus aureus (two times) and Pseudomonas aeruginosa (four times). No adverse reactions were seen.

Bacterial Infections↗

The value of 99mTc macroaggregated albumin lung perfusion scanning in the prediction of postpneumonectomy function and pulmonary artery pressure.

99mTc macroaggregated albumin lung perfusion scans were performed with assessment of pulmonary hemodynamics in 14 male patients with a centrally located lung tumor, subjected to pneumonectomy. In 7 patients perfusion of the affected lung was less than one third of total perfusion. However, all tumors were resectable. Results show that predictive value of the perfusion scan was significant (p less than 0.02) with regard to forced expiratory volume in the first second (FEV1, r = 0.80). A fair but not significant correlation existed in the prediction of vital capacity (VC, r = 0.64) and total lung capacity (TLC, r = 0.71). No correlation was found between perioperative change in mean pulmonary artery pressure (MPAP) and either relative radionuclide uptake of the affected lung or predicted FEV1. So, the lung perfusion scan cannot be used in preoperative estimation of postoperative MPAP.

Aged↗

Phytohemagglutinin skin testing in critically ill surgical patients.

Phytohemagglutinin (PHA) skin tests were performed in 225 critically ill surgical patients with respiratory failure. The study population was composed of 68 trauma patients who had suffered severe multiple injuries and 157 nontrauma patients who had a variety of surgical complications. The initial skin test response, obtained at the beginning of mechanical ventilation, was negative in 31% of the trauma patients and in 49% of the nontrauma patients. In the group of trauma patients, a higher mortality rate was noted in negative initial skin test responders compared with positive initial responders (38 and 15%, respectively; p less than 0.05). In the group of nontrauma patients, no association could be demonstrated between skin test unresponsiveness and mortality. With sequential testing, most (70%) of the patients were found to show at least one negative skin test reaction while in the intensive care unit. There was no difference in mortality between patients who remained reactive to PHA and patients with one or more negative skin test responses. These findings show that surgical intensive care patients frequently have an impaired cellular immunocompetence as indicated by a failed skin test response to PHA. However, PHA skin testing has little or no value in predicting outcome in these patients.

Adult↗