Tetrasomy 21 in megakaryoblastic leukemia

The precise localization of a membrane-bound, arginine-specific mono-ADP-ribosyltransferase (mADP-RT) was assessed in rabbit skeletal muscle by studying membrane fractions isolated by successive sucrose density gradient centrifugations. mADP-RT activity was 10-fold enriched in sarcolemmal and T-tubular membranes. The catalytic activity, determined in preparations with mainly right-side-out vesicles, was found to be on the cytoplasmic face. As revealed by SDS-PAGE and autoradiography endogenous mADP-RT activity labeled several proteins in the range between 15 kDa and 250 kDa. T-tubules contained the highest number of [32P]ADP-ribose-labeled proteins.     

Transient leukemia followed by megakaryoblastic leukemia in a child with mosaic Down syndrome

A case is presented of a child with mosaic Down syndrome, who presented at birth with a transient leukemia and later progressed to megakaryoblastic leukemia. Evidence is presented that both leukemias were of megakaryoblastic lineage and evolved from a trisomic hematopoietic precursor. This case is unique in the poor course of the initial transient neonatal leukemia with improvement following chemotherapy. It also highlights the form of leukemia and associated myelodysplasia that occurs in children with Down syndrome. This form of leukemia and transient leukemia are interrelated and are unique to children with Down syndrome.     

Paroxysmal nocturnal hemoglobinuria with myelofibrosis: progression to acute myeloblastic leukemia

Buccal hairy leucoplakia is associated with Epstein-Barr and HIV virus infections. The main symptom is the characteristic hairy lesion on side parts of the tongue without any other clinical sign. Histologically, there are hyperkeratosis, vacuolar degeneration, and presence of Candida, but no inflammatory infiltration. Antiviral drugs led to the regression of lesions, but there is a trend to relapse when treatment is interrupted.     

Myelodysplastic transformation in a case of essential thrombocythemia treated with pipobroman

A report of an 87-year-old Caucasian female with an extensive sebaceous carcinoma of the parotid gland is presented. The computed tomographic characteristics of this rare neoplasm are reported for the first time.     

A case of HTLV-I associated polyradiculoneuropathy and cerebral white matter lesions with smouldering type adult T cell leukemia

Chronic myelogenous leukemia (CML) is associated with an acquired karyotypic abnormality, the Philadelphia (Ph) chromosome, in 95% of cases. The Ph chromosome is the product of a balanced translocation that results in a hybrid gene that is considered essential for the pathogenesis of this disease. We have found a complex translocation involving chromosomes 9, 12, and 15 in a 42-year-old Haitian male with the clinical findings of CML. Complex translocations have been shown to result in the masking of the Ph chromosome. We used a mixture of two BCR-specific DNA probes for Southern blot analysis in order to test this hypothesis in our patient. High-molecular weight DNA was digested with the restriction enzymes BglII, BamHI and HindIII. The BglII digestion revealed the presence of two abnormal fragments of 3.9 and 3.0 kb and the BamHI digestion an abnormal 15-kb fragment. These data suggest there is a breakpoint in region 2 of M-bcr. The identification of this breakpoint confirms our hypothesis that a rearrangement involving 22q11 has occurred in the leukemic cells of our patient. A secondary translocation involving chromosomes 12 and 15 has hidden the effects of this translocation. Combined cytogenetic and molecular analysis establishes the karyotype of our patient as 46,XY,t(9;12;15;22)(q34;q12;q21;q11).     

Development of essential thrombocythemia in a patient treated with interferon alfa and pentostatin for hairy cell leukemia

A patient is reported who developed essential thrombocythemia after successful treatment for hairy cell leukemia. He was initially treated with interferon alfa and subsequently relapsed within one year of treatment. His diagnosis was reconfirmed and then treated with Pentostatin. Six years after treatment he had a progressive increase in the platelet count and was diagnosed as essential thrombocythemia. Second cancers including various types of hematological malignancy have been reported in patients with hairy cell leukemia treated with chemotherapy or interferon alfa. These malignancies may represent either a new clonal disorder or a complication of drug treatment. This is the first report of a chronic myeloproliferative disorder following successful treatment of hairy cell leukemia.     

Transformation of myelofibrosis into acute myelogenous leukemia (M0) with multiple tumor emboli

AIMS: To develop a DNA based plate hybridisation assay for the detection of polymerase chain reaction (PCR) products amplified from Aspergillus fumigatus DNA; and to determine the sensitivity of this technique and compare it with Southern blotting. METHODS: A half-log dilution series of DNA extracted from A fumigatus was amplified with specific primers, one of which was 5' end labelled with biotin. PCR products were subsequently detected by agarose gel electrophoresis, Southern blotting, and binding of the products to a streptavidin coated microtitre well, followed by non-radioactive colorimetric detection. Amplification was carried out 10 times for each DNA dilution and a plot of initial DNA concentration against signal intensity was made. RESULTS: A DNA concentration of 1.5 pg could be detected by agarose gel electrophoresis and Southern blotting with a non-radioactively labelled aspergillus specific probe; 1.5 pg was detectable by streptavidin binding of the PCR products to a microtitre plate. The signal from the microtitre plate detection was proportional to the amount of DNA in the PCR reaction on a log-log scale between 100 and 1 pg of DNA. CONCLUSIONS: A DNA based plate hybridisation assay for the detection of A fumigatus PCR products is as sensitive as Southern blotting. However, results are obtained in three hours rather than the three days required for agarose gel electrophoresis, blotting, hybridisation, and detection.     

Anesthesia in two patients with essential thrombocythemia

Case 1. The patient was a 69-year-old man with essential thrombocythemia (ET), who underwent urgent laparotomy. On admission he was dehydrated and the platelet count was more than 160 x 10(4).microliter-1, with hematocrit of 50%. Anesthesia was induced with ketamine i.v. and maintained with nitrous oxide and sevoflurane in oxygen. Postoperative care included the administration of gabexate mesilate (GM) which is an antiplatelet agent. Case 2. An 84-year-old woman with ET was diagnosed as gastric cancer and elective gastrectomy was scheduled. The platelet count was more than 100 x 10(4).microliter-1. The patient was anesthetized with nitrous oxide and oxygen supplemented with fentanyl and mepivacaine via epidural catheter. Intravenous infusion of GM was performed at a rate of 1 mg.kg-1.hr-1 during surgery. PF-4 and beta-TG were measured. These are platelet releasing factors. The level of PF-4 decreased to normal level during this procedure. In conclusions, it will be important to use GM during anesthesia in order to avoid the complications such as myocardial or pulmonary infarction caused by thrombocythemia.     

Thrombotic complications in essential thrombocythemia with relatively low platelet counts

The purpose of this prospective study was to determine the overall incidence and distribution of lumbo-sacral degenerative changes (i.e. disc protrusion or extrusion, facet degeneration, disc degeneration, nerve root canal stenosis and spinal stenosis) in patients with and without a lumbo-sacral transitional vertebra (LSTV). The study population consisted of 350 sequential patients with low back pain and/or sciatica, referred for medical imaging. In all cases CT scans of the lumbo-sacral region were obtained. In 53 subjects (15%) and LSTV was found. There was no difference in overall incidence of degenerative spine changes between the two groups. We did find, however, a different distribution pattern of degenerative changes between patients with and those without an LSTV. Disc protrusion and/or extrusion occurred more often at the level suprajacent to the LSTV than at the same level in patients without LSTV (45.3% vs 30.3%). This was also the case for disc degeneration (52.8% vs 28%), facet degeneration (60.4% vs 42.6%) and nerve root canal stenosis (52.8% vs 27.9%). For spinal canal stenosis there was no statistically significant difference between the two categories. In conclusion, our findings indicate that an LSTV does not in itself constitute a risk factor for degenerative spine changes, but when degeneration occurs, it is more likely to be found at the disc level above the LSTV.     

Chemical-viral co-carcinogenesis: requirement for leukemia virus expression in accelerated transformation

The essential role of Rauscher leukemia virus (RLV) multiplication in viral-chemical co-carcinogenesis was investigated by the use of ethidium bromide (EtBr) as an inhibitor of viral complementary DNA (cDNA) integration in the host genome. EtBr inhibited co-carcinogenic transformation when present at the time of RLV inoculation but was ineffective when added to preinfected cells. Inhibitors of protein synthesis, puromycin and cyclohexamide also inhibited co-carcinogenic transformation of chronically infected cells. Purified rat interferon used at a concentration which inhibited 85% of RLV production did not modify the course of co-carcinogenic transformation. The implications of these observations in terms of the possible role of the virus-specific protein (s) in the co-carcinogenic process are discussed.     

Origin of the Hodgkin/Reed-Sternberg cells in chronic lymphocytic leukemia with "Hodgkin's transformation"

A lymphoma with the characteristic features of Hodgkin's disease (HD) occasionally develops in patients with B-cell chronic lymphocytic leukemia (CLL), and has been called Richter's syndrome with HD features. In such cases, large tumor cells have the morphological and immunophenotypic features of classical Hodgkin and Reed-Sternberg (H-RS) cells. However, it is not known whether the H-RS cells arise from transformation of the underlying CLL cells or from a different pathological process. We report herein a study of the clonal relationship between the CLL cells and the H-RS cells in three cases of Richter's syndrome with HD features by using a single cell assay. We isolated single CLL cells and H-RS cells from immunostained tissue sections by micromanipulation. The immunoglobulin heavy chain gene (IgH) complementarity determining region (CDR) III of each cell was amplified by the polymerase chain reaction (PCR). The products were then compared by gel electrophoresis and nucleotide sequencing. The IgH CDRIII sequences from the H-RS cells were identical to those from the CLL cells in two cases. In one case, the clonal relationship between the two types of cells could not be determined because PCR products could not be obtained from any of the H-RS cells. This study shows that the H-RS cells and the CLL cells belong to the same clonal population in some cases of Richter's syndrome with HD features. Furthermore, our findings indicate that mature B cells can undergo transformation to cells with the features of H-RS cells, in association with a cellular background typical of HD. This study also supports recent findings suggesting that the H-RS cells in classical HD are derived from transformed B cells.     

A case of myelofibrosis that developed polycythemia vera following treatment with ranimustine and then acute myelogenous leukemia (M0)

Short latency somatosensory evoked potentials (SSEP) to median nerve stimulation recorded from post-Rolandic area and the surface of processus spinosus of Cvs at the same record time. To assess electrophysiologically functional status of central nervous system (CNS), SSEP were studied in 43 patients with ischemic heart disease (IHD); 18 cases of angina pectoris (AP group), 25 cases of old myocardial infarction (MI group), and 14 non-IHD controls (NC group). The N13, N20, P25 peak latencies (PLs) and the central conduction time (CCT, the peak latency between N13 and N20) in AP group or MI group were prolonged remarkably compared with NC group. Likewise, MI group showed significant prolongation of N20, P25 PLs and CCT compared to the AP group. Furthermore, in MI group, the N20 peak amplitude was significantly lowered; the subjects percentages of the N20 or P25 amplitude detraction more than 40 percent in one side and the P25 interextremital latency difference over 1 ms were significantly increased than those of the NC group. These results suggested the pathological changes of the somatosensory pathway from superior spinal cord or medulla oblongata to cerebral cortex primary sensory area in CNS in the IHD patients.     

Successful treatment of early secondary myelofibrosis in SLE with IVIG

With increasing demand for esthetics, dentists face the challenge of delivering definitive restorations that fulfill patients' expectations of esthetics, biocompatibility, and durability. Recent technical developments have encouraged fabrication of gold-reinforced porcelain inlays that meet these important criteria. This article describes a sequence to construct metal-reinforced porcelain inlay restorations.     

Outside-In signaling of soluble and solid-phase fibrinogen through integrin alphaIIbbeta3 is different and cooperative with each other in a megakaryoblastic leukemia cell line, CMK

The function and the outside-in signaling pathways of alphaIIbbeta3 were examined in relation to cell adhesion using a megakaryoblastic leukemia cell line, CMK. After 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment, the cells adhered to the culture plate and underwent megakaryocytic differentiation with expression of alphaIIbbeta3. Binding of soluble fibrinogen to the cells via alphaIIbbeta3 was dependent on cell adhesion. Cell detaching reduced the affinity of this integrin for soluble fibrinogen, although its surface expression was almost unchanged. In contrast, detached cells became tightly adherent to the fibrinogen-coated plate (solid-phase fibrinogen). The same ligand, fibrinogen, present either in soluble or solid-phase form, triggered differential signaling pathways mediated by alphaIIbbeta3. By the stimulation with soluble fibrinogen, Syk was tyrosine-phosphorylated but FAK was dephosphorylated, whereas solid-phase fibrinogen promptly caused tyrosine phosphorylation of FAK followed by delayed phosphorylation of Syk. In addition, the binding of soluble fibrinogen to the cells adherent to fibrinogen-coated plate resulted in tyrosine phosphorylation of integrin beta3 and a complex formation of integrin beta3 with Syk. This implies the cooperation of both soluble and solid-phase fibrinogen-mediated signaling pathways.     

Acute coronary occlusion and in-stent thrombosis in a patient with essential thrombocythemia

BACKGROUND: Physical activity in old age probably protects against hip fracture. However, very little is known about the impact of occupation during working life, in terms of its physical activity level and the socio-economic status (SES) it indicates, on the risk of hip fracture in later life. METHOD: A population-based case-control study was conducted on 416 subjects to investigate relationships between risk of hip fracture and occupational physical activity and occupation-related SES. Occupational physical activity was coded according to the proportion of the working day at ages 20 and 50 years that the subjects were likely to have spent sitting. The Australian Classification of Standard Occupations (ASCO) was used as the basis for the coding of SES, indicated by job titles. RESULTS: Compared with those in the intermediate category, women with a sedentary job at age 50 years (odds ratio (OR) 7.2, 95 per cent confidence interval (CI) 1.2-41.9) or a mainly weight-bearing job (OR 5.1, 95 per cent CI 1.1-23.2) had an increased risk of hip fracture. A decreasing hip fracture risk with increasing SES of the longest held job was also observed. CONCLUSION: The finding of a J-shaped relationship in women between occupational physical activity and risk of hip fracture supports the need for research into the most effective types of exercise for maintenance of bone strength. Furthermore, the protective effect of SES demonstrated in this study still need to be corroborated in other studies before establishing evidence of a causal relationship.     

Fatal myelofibrosis following fludarabine administration in a patient with indolent lymphoma

We report a case of fulminant myelofibrosis after administration of fludarabine in a patient diagnosed as having refractory low-grade lymphoma, progressing fatally. Myelofibrosis in the setting of an indolent lymphoma is very rare; this fact, and the short period between drug administration and fibrosis suggest an etiopathogenic link, although this potential and severe adverse effect of fludarabine has not been previously reported in the literature.