Most gastrointestinal stromal tumors (GISTs) carry activating mutations of the KIT gene encoding the receptor tyrosine kinase KIT. In a previous study we were able to show an association between the lack of KIT mutations (wild-type GISTs) and the presence of a significant epithelioid tumor component. A very recent study described the occurrence of PDGFRalpha mutations in KIT wt GISTS. Therefore, we studied a panel of 87 GISTs for mutations in the hot spot regions of the PDGFRalpha gene with single strand conformation polymorphism analysis and sequencing and correlated the PDGFRalpha status with pathomorphological data. We detected 20 cases with exon 18 mutations but none with exon 12 mutations. The mutations were located in the second kinase domain of PDGFRalpha with 16 point mutations, and four larger deletions of 9 to 12 bp. All cases with mutations in the PDGFRalpha gene revealed wild-type KIT in common regions of mutation, ie, exons 9 and 11. Most interestingly, the occurrence of PDGFRalpha mutations was significantly associated with a higher frequency of epithelioid or mixed morphology (18 of 20 cases, P < 0.0001) and gastric location (all cases, P = 0.0008). Our data indicate that GISTs represent distinctive entities, differing in genetic, biological, and morphological features.
The biological properties of latent or occult hepatitis B virus (HBV) have been poorly characterized as a result of the extremely low virus concentration. This report describes the phenotype of HBV reactivating in two patients after an HBsAg-negative latency period. One patient had latent HBV infection for at least 12 years without detectable viremia and symptoms of liver disease. Several full-length HBV genomes were cloned at reactivation, sequenced, and functionally tested by transfection into HuH7 cells. Genomes from both patients showed a low replication phenotype. It was caused at the level of RNA encapsidation or HBV DNA synthesis, but was not attributable to uncommon mutations in the terminal protein domain of P protein.
Gastrointestinal stromal tumors (GISTs) coexpress CD34 and the Kit tyrosine-kinase receptor (CD117). A subset of GISTs carry gain-of-function mutations
We describe 2 patients who were initially positive for antibodies to hepatitis B surface antigen and who experienced a strong and sudden increase of hepatitis B virus (HBV) replication during highly active antiretroviral therapy (HAART). We found that reactivation of HBV replication during HAART can occur independently of lamivudine resistance or withdrawal of lamivudine, and in spite of increasing CD4(+) cell counts.
The serum levels of procalcitonin (PCT) in Plasmodium falciparum malaria were evaluated for clinical significance in 66 nonimmune and semi-immune patients. Of the 66 patients, 36 had uncomplicated malaria, 24 had severe and complicated malaria, and 6 had fatal malaria (5 from previous studies). Pretreatment PCT concentrations were closely correlated with parasitemia. Concentrations were lowest in semi-immune patients with uncomplicated malaria, compared with those in nonimmune patients (geometric mean concentrations [GMCs], 1.07 and 2.37 ng/mL, respectively), and were highest in severe and complicated cases (GMC, 10.67 ng/mL; P<.001 among all subgroups). Six of 7 patients with PCT concentrations >25 ng/mL died. PCT concentrations decreased on day 2 of treatment in survivors but not in patients with fatal outcome. Thus, repeated PCT measurements may provide useful prognostic information, especially in medical centers that are not experienced in parasite density determination.
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