Lack of Altered BECN1 Gene Expression in Iranian Patients with Acute Myeloid Leukemia

Acute myeloid leukemia (AML), one of the most prevalent leukemia types in adults, demonstrates great heterogeneity in molecular and clinical terms. Hence, there is a necessity to the mechanisms involved in AML generation in order to determine optimal treatment. This cross sectional study aimed to assess changes in BECN1 gene expression in with blood samples from 30 AML patients, compared with samples from 15 healthy persons. RNA was extracted and cDNA was synthesized and Real Time PCR applied to determine BECN1 gene expression. The results showed no significant differences in BECN1 gene expression between patients with AML and normal controls (P > 0.05). It appears that expression of BECN1 does not play a significant role in genesis of AML leukemia.     

The lower incisors as a predictor for the size of unerupted canine and premolars in the Iranian ethnicity

The purpose of this study was to find the correlation coefficients between the mesiodistal widths of the permanent mandibular incisors and the permanent canine and premolars for each quadrant and establish a regression equation for prediction of the sum of canine and premolars based on the dimension of the lower incisors. 90 patients 12–20 years old (45 females and 45 males) were selected. The mesiodistal crown diameters of the permanent teeth were measured. The correlation coefficients between the permanent mandibular incisors and the permanent canine and premolars sizes varied from 0.63 to 0.8. An Iranian mixed dentition analysis based on the Tanaka and Johnston method was constructed with linear regression equations; for maxillary arch y = 6.3 + 0.65x (SEE = 0.8 mm) and for mandibular arch y = 5.1 + 0.67x (SEE = 0.8 mm). No significant sexual dimorphism was found in tooth sizes. This study revealed that Iranian population has smaller teeth than white North American. We found that prediction equations of Tanaka and Johnston or Moyers charts cannot accurately predict the size of buccal segment in Iranian population.     

Glioblastoma recurrence after cediranib therapy in patients: lack of "rebound" revascularization as mode of escape

Recurrent glioblastomas (rGBM) invariably relapse after initial response to anti-VEGF therapy. There are 2 prevailing hypotheses on how these tumors escape antiangiogenic therapy: switch to VEGF-independent angiogenic pathways and vessel co-option. However, direct evidence in rGBM patients is lacking. Thus, we compared molecular, cellular, and vascular parameters in autopsy tissues from 5 rGBM patients who had been treated with the pan-VEGF receptor tyrosine kinase inhibitor cediranib versus 7 patients who received no therapy or chemoradiation but no antiangiogenic agents. After cediranib treatment, endothelial proliferation and glomeruloid vessels were decreased, and vessel diameters and perimeters were reduced to levels comparable to the unaffected contralateral brain hemisphere. In addition, tumor endothelial cells expressed molecular markers specific to the blood-brain barrier, indicative of a lack of revascularization despite the discontinuation of therapy. Surprisingly, in cediranib-treated GBM, cellular density in the central area of the tumor was lower than in control cases and gradually decreased toward the infiltrating edge, indicative of a change in growth pattern of rGBMs after cediranib treatment, unlike that after chemoradiation. Finally, cediranib-treated GBMs showed high levels of PDGF-C (platelet-derived growth factor C) and c-Met expression and infiltration by myeloid cells, which may potentially contribute to resistance to anti-VEGF therapy. In summary, we show that rGBMs switch their growth pattern after anti-VEGF therapy--characterized by lower tumor cellularity in the central area, decreased pseudopalisading necrosis, and blood vessels with normal molecular expression and morphology--without a second wave of angiogenesis.     

Effect of apolipoprotein E genotypes on incidence and development of coronary stenosis in Iranian patients with coronary artery disease

Background: Apolipoprotein (apo) E polymorphism plays a significant role in the development of coronary disease, but their involvement in coronary artery stenosis (CAS) is controversial. Therefore, the purpose of this study was to investigate the effects of this polymorphism on atherosclerosis, and severity and extent of CAS in unrelated Iranian population. Methods: DNA was isolated from 390 study participants and APOE genotypes were determined utilizing the polymerase chain reaction and restriction fragment length polymorphism. Results: The APOE‐ε4 and ‐ε2 allele frequencies were significantly higher in the CAS patients than in the control group (P<0.05). The association of Apo E polymorphism with the severity of stenosis was evaluated, which is according to the result that apolipoprotein E alleles were not significantly different when compared with the severity of stenosis (χ²=0.84, P>0.05). Conclusion: Our results suggest that APOE‐ε4 is a risk factor for stenosis but does not has any effect on the severity of this disease. J. Clin. Lab. Anal. 25:43–46, 2011. © 2011 Wiley‐Liss, Inc.     

Human trimodal perception follows optimal statistical inference

Our nervous system typically processes signals from multiple sensory modalities at any given moment and is therefore posed with two important problems: which of the signals are caused by a common event, and how to combine those signals. We investigated human perception in the presence of auditory, visual, and tactile stimulation in a numerosity judgment task. Observers were presented with stimuli in one, two, or three modalities simultaneously and were asked to report their percepts in each modality. The degree of congruency between the modalities varied across trials. For example, a single flash was paired in some trials with two beeps and two taps. Cross-modal illusions were observed in most conditions in which there was incongruence among the two or three stimuli, revealing robust interactions among the three modalities in all directions. The observers' bimodal and trimodal percepts were remarkably consistent with a Bayes-optimal strategy of combining the evidence in each modality with the prior probability of the events. These findings provide evidence that the combination of sensory information among three modalities follows optimal statistical inference for the entire spectrum of conditions.     

Outcomes of patients with renal monoclonal immunoglobulin deposition disease

Recent reports suggest that deep hematologic responses to chemotherapy are associated with improved renal outcomes in monoclonal immunoglobulin deposition disease (MIDD). Here we describe the long term outcomes and identify prognostic factors after first line treatment of the largest reported series of patients with MIDD. Between March 1992 and December 2014, 88 patients with MIDD were seen at Mayo Clinic, MN. Renal responses were defined using criteria used for light chain amyloidosis (AL) or those used by the IMWG. Sixty‐one (69%) patients had a GFR < 30 mL/min/1.73 m² and 16 (18%) were on renal replacement therapy at diagnosis. The interval between albuminuria or elevation in creatinine and MIDD diagnosis was 12 months suggesting a delay in diagnosis. Thirty‐seven patients (42%) had at least a hematologic CR/VGPR. Fifty‐three (60%) received an autologous stem cell transplant (ASCT) or proteasome inhibitor (PI)‐based treatments. Patients receiving ASCT or PI‐based therapies were more likely to achieve at least a hematologic CR/VGPR compared to those receiving other therapies: 66% vs 2%, p < 0.0001. Patients that achieved a hematologic CR were more likely to achieve a renal response (53% vs 24%, p = 0.001). Five year overall and renal survival for the entire cohort was 67% and 57%, respectively. In multivariate analyses, a baseline GFR < 20 mL/min/1.73 m² and a renal response (using AL or IMWG criteria) were independently predictive of progression to dialysis. This study confirms that deep hematologic responses, best achieved with ASCT or PI‐based therapies, are a prerequisite to achieving renal responses. Am. J. Hematol. 91:1123–1128, 2016. © 2016 Wiley Periodicals, Inc.