Translocation t(5;12)(q31-q33;p12-p13): a non-random translocation associated with a myeloid disorder with eosinophilia

SUMMARY. To investigate the clinical significance of determination of plasma tissue factor (TF) antigen, we have developed a highly sensitive enzyme-linked immunosorbent assay (ELISA) for plasma TF, using two different monoclonal antibodies against TF apoprotein, 6B4 (catching antibody) and 5G9 (detecting antibody), and tetramethyl benzidine/H₂O₂ as substrates. Titration curves of recombinant human TF in buffer containing Triton X-100 were linear within the range from 50 to 2000pg/ml. The total assay time was 3h. Ultracentrifugation and immunoblot analysis indicated that human plasma and urine contained 50 000 g sedimentable and non-sedimentable forms of TF, both of which were detected by our ELISA method.
Plasma and urine concentrations of TF in healthy subjects and patients with various diseases were measured by the ELISA method. In healthy subjects, plasma and urinary TF levels were found to be 149± 72pg/ml (n = 30) and 175±60pg TF/urine creatinine mg (n = 95). respectively. TF was increased in plasma of patients with disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura, vasculitis associated with collagen diseases, diabetic microangiopathy and chronic renal failure receiving haemodialysis, but not in the plasma of endotoxaemic patients without DIC. The plasma TF/serum creatinine ratio did not show a positive correlation. Measurement of TF antigen in plasma may be useful for evaluating the endothelial damage and cell destruction in TF-containing tissues.     

Distinct surrogate markers for protection against Plasmodium falciparum infection and clinical malaria identified in a Senegalese community after radical drug cure

Plasmodium falciparum expresses many antigens, which elicit various immune responses in exposed individuals, but no simple surrogate marker for protection has yet been developed. In this prospective survey, we looked for immune responses predictive of protection at various stages of progression from parasite inoculation to onset of disease. We studied 110 Senegalese volunteers from an area in which malaria is mesoendemic after they had received eradication therapy. We evaluated 4 protection-related outcomes (reappearance of parasitemia, duration of asymptomatic carriage, time to first clinical episode, and incidence of clinical episodes) in terms of levels of immunoglobulin G (IgG) against 3 crude parasite extracts and 5 conserved antigens during a 5-month period. Kaplan-Meier estimates and age-adjusted regression models showed these 4 outcomes to be associated with different patterns of IgG response to PfEMP3-cl5 (derived from P. falciparum erythrocyte membrane protein 3), PfEB200, MSP-1(19) (derived from merozoite surface protein-1), [NANP]10, infected red blood cell membrane, and merozoite and schizont extracts. It should, therefore, be possible to develop surrogate markers for each end point on the basis of IgG response to a limited number of conserved antigens.     

Polymorphism of HLA-DMA and DMB alleles in patients with systemic lupus erythematosus

OBJECTIVE: To evaluate the contribution of HLA-DM alleles to susceptibility to systemic lupus erythematosus (SLE) in a Caucasian population. METHODS: HLA-DMA and DMB alleles were studied in 73 patients with SLE, 147 randomly selected controls, and 86 HLA-DRB1 genotype matched controls by oligotyping of polymerase chain reaction amplified genomic DNA with sequence-specific oligonucleotide probes. RESULTS: There was a significant presence of HLA-DMA*0103, DMA*0104, and DMB*0102 in the SLE patients compared with the randomly selected controls. After stratification of patients and matched controls according to DRB1 genotypes, only HLA-DMA*0104 was increased in SLE patients negative for the SLE susceptibility HLA-DR alleles. For the patients and controls positive for HLA-DR allele-susceptibility for SLE, HLA-DMA*0103, DMA*0104, DMB*0102, and DMB*0103 alleles tended to be more frequent, but without reaching statistical significance. No correlation was found between HLA-DM phenotype frequencies and any clinical or biological manifestations of SLE. CONCLUSION: This is the first study evaluating the influence of HLA-DM in a Caucasian SLE population. Our results suggest that HLA-DMA*0104 may represent a novel allele of susceptibility to SLE.     

Insuficiencia respiratoria hipercápnica aguda en pacientes con apneas del sueño

Introduction

Acute hypercapnic respiratory failure (AHRF) is a serious condition observed in some patients with sleep apnea-hypopnea syndrome (SAHS). The objective of the present study was to study the clinical characteristics of SAHS patients who develop AHRF and their prognosis.

Patients and method

A total of 70 consecutive SAHS patients who survived an AHRF episode and 70 SAHS patients paired by age with no previous history of AHRF were prospectively studied and followed up for 3 years.

Results

The deterioration of lung function due to obesity or concomitant chronic obstructive pulmonary diseases (COPD) was common in SAHS patients with AHRF. In the multivariate analysis, the risk factors associated with AHRF were baseline PaO_2, the theoretical percentage value of the forced vital capacity, alcohol consumption, and benzodiazepines. The mortality during follow up was higher among patients who had AHRF than in the control group. The main cause of death was respiratory, and the coexistence of COPD was identified as a mortality risk factor.

Conclusions

The development of AHRF in SAHS patients is associated with a deterioration in lung function and with alcohol and benzodiazepine consumption. The patients had a higher mortality after the AHRF episode, mainly a respiratory cause. New studies are required that evaluate the different available therapeutic options in these patients.     

Long-term complete haematological and molecular remission after allogeneic bone marrow transplantation in a patient with a stem cell myeloproliferative disorder associated with t(8;13)(p12;q12)

A rare atypical myeloproliferative disorder (aMPD) associated with chromosomal translocations involving the short arm of chromosome 8, region p11-p12 has been described. In most patients, the cytogenetic abnormality is a t(8;13)(p12;q12) that fuses fibroblast growth factor receptor 1, the 8p12 key gene, to FIM/ZNF198 gene. Prognosis is poor with frequent evolution to acute myeloid leukaemia within 1 year of diagnosis. We report a new patient with aMPD with a t(8;13) translocation. Complete haematological, cytogenetic and molecular remission was demonstrated 39 months after allogeneic bone marrow transplantation. This is the first report to demonstrate a molecular remission in this disorder.     

Cumulative Marijuana Use and Carotid Intima-Media Thickness at Middle Age: The CARDIA Study

BackgroundLong-term cardiovascular health effects of marijuana are understudied. Future cardiovascular disease is often indicated by subclinical atherosclerosis for which carotid intima-media thickness is an established parameter.MethodsUsing the data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort of 5115 Black and white women and men at Year 20 visit, we studied the association between carotid intima-media thickness in midlife and lifetime exposure to marijuana (1 marijuana year = 365 days of use) and tobacco smoking (1 pack-year = 20 cigarettes/day for 365 days). We measured carotid intima-media thickness by ultrasound and defined high carotid intima-media thickness at the threshold of the 75th percentile of all examined participants. We fit logistic regression models stratified by tobacco smoking exposure, adjusting for demographics, cardiovascular risk factors, and other drug exposures.ResultsData was complete for 3257 participants; 2722 (84%) reported ever marijuana use; 374 (11%) were current users; 1539 (47%) reported ever tobacco smoking; 610 (19%) were current smokers. Multivariable adjusted models showed no association between cumulative marijuana exposure and high carotid intima-media thickness in never or ever tobacco smokers, odds ratio (OR) 0.87 (95% confidence interval [CI]: 0.63-1.21) at 1 marijuana-year among never smokers and OR 1.11 (95% CI: 0.85-1.45) among ever tobacco smokers. Cumulative exposure to tobacco was strongly associated with high carotid intima-media thickness, OR 1.88 (95%CI: 1.20-2.94) for 20 pack-years of exposure.ConclusionsThis study adds to the growing body of evidence that there might be no association between the average population level of marijuana use and subclinical atherosclerosis.     

Successive transformation of chronic myelomonocytic leukaemia into acute myeloblastic then lymphoblastic leukaemia, both with minor-bcr rearrangement

We report a case of chronic myelomonocytic leukaemia (CMML), which transformed first into acute myeloblastic leukaemia (AML) and then into acute lymphoblastic leukaemia (ALL). In the AML and ALL phases, chromosome analysis showed a classic Philadelphia chromosome (Ph) t(9;22)(q34;q11). Molecular studies showed breakpoint cluster region rearrangement between exons e1 and a2 compatible with a p190^bcr/abl breakpoint as observed in Ph-positive lymphoblastic acute leukaemia. The minor (m-bcr) rearrangement was also detected during complete remission.
This observation supports a multistep pathogenesis of leukaemias, and that the p190^bcr/abl breakpoint may influence the course of the disease.     

IgG4 serology of loiasis in three villages in an endemic area of south-eastern Gabon

Human filariasis due to Loa loa differs from other filariasis in that the majority of infected subjects are without circulating microfilariae (occult loiasis). In search for alternative diagnostic methods, which do not depend on circulating microfilariae or the (rather infrequent) eye-passage of adult worms, it was shown earlier that IgG4 antibodies directed against Loa loa adult worm antigen are apparently a good marker of occult loiasis and specific with regard to the sympatrically occurring Mansonella perstans . In this study we evaluated an IgG4 antibody-based ELISA using crude extract of Loa loa microfilariae (which is easier to obtain than adult worm) to estimate the prevalence of loiasis in 3 villages in South-East Gabon. Of 222 examined individuals (80 children < 16 years, 142 adults) 44 (20%) carried Loa loa microfilariae and 170 (77%) M. perstans . Using the mean OD-value + 1 standard deviation of 9 sera from patients solely infected with M. perstans (from the Gambia, where Loa loa is not endemic) as a cut-off, 35 of the 44 microfilaraemic Loa loa patients and 2 of the 9 Gambian controls were positive. This shows that our method had a sensitivity of 80% and a specificity of 78%. Among the remaining 178 subjects who had no microfilariae of Loa loa , as many as 97 (55%) had significant levels of specific IgG4 antibodies against Loa loa , suggesting that they carried occult loiasis. The mean IgG4 level in these putatively occult loiasis patients was slightly but significantly lower than in microfilaraemic subjects ( P < 0.03). In conclusion, despite the limited sensitivity and specificity of our method, IgG4- ELISA at present is a very useful tool in estimating the real prevalence of loiasis in epidemiological surveys and at the individual level can confirm the diagnosis of L. loa amicrofilaraemic subjects with clinical signs suggesting loiasis.