Monitoring Twenty-Six Chronic Myeloid Leukemia Patients by BCR-ABL mRNA Level in Bone Marrow: A Single Hospital Experience

Chronic myeloid leukemia (CML) is caused by the BCR-ABL oncogene. The Philadelphia chromosome (Ph) from a reciprocal translocation, t(9;22) (q34;q11) causes a fusion gene, BCR-ABL, that encodes a constitutively active tyrosine kinase. Treatment of CML by imatinib is effective to control the tyrosyl phosphorylation of the protein related to the cell signaling. BCR-ABL mRNA is overexpressed in the minimal residual disease (MRD), known as an early sign of relapse. Between December 2005 and June 2008, we measured BCR-ABL mRNA levels in the bone marrow (BM) from patients by quantitative real-time polymerase chain reaction (RQ-PCR) in Aomori Prefectural Central Hospital. Eighty-six samples from 26 patients were collected. Among the 26 CML patients, 11 patients (42%) were in the pretreatment group. Seven (64%) of the 11 patients achieved complete molecular response (CMR). In the post-treatment group consisting of the remaining 15 patients, 9 (60%) patients achieved CMR. The patients receiving imatinib at a dose over 300mg per day required 13 (6-77) months [median (range)] to achieve CMR. On the other hand, the patients receiving a dose below 300mg per day required 29.5 (11-84) months [median (range)]. When BCR-ABL mRNA was detected during the treatment course of patients with CMR, careful observation of BCR-ABL mRNA was useful for tracking the clinical course of patients. In conclusion, the BCR-ABL mRNA level was useful for monitoring the clinical course in 26 patients with CML

Relationship between Fluorescein Pooling and Optical Coherence Tomographic Reflectivity of Cystoid Spaces in Diabetic Macular Edema.

[Objective]: To study the characteristics of the reflectivity of the cystoid spaces and serous retinal detachment (SRD) on spectral-domain optical coherence tomography (SD-OCT) and the correlation with fluorescein findings in diabetic macular edema (DME). [Design]: Retrospective, observational, cross-sectional study. [Participants]: Consecutive 134 eyes of 114 patients with clinically significant macular edema for whom SD-OCT and fluorescein angiography (FA) were performed on the same day. [Methods]: Fluorescein angiography using Heidelberg Retina Angiograph 2 (Heidelberg Engineering, Heidelberg, Germany) and OCT images using Spectralis OCT (Heidelberg Engineering) were obtained. The reflectivity of the cystoid spaces and SRD on the OCT images was evaluated qualitatively and quantitatively and compared with the fluorescein pooling intensity on FA images. [Main Outcome Measures]: The relationship between the fluorescein pooling and the reflectivity characteristics of the cystoid spaces on SD-OCT images. [Results]: A total of 141 cystoid spaces in 101 eyes were delineated on OCT images, and 138 spaces (97.9%) had fluorescein pooling. Fifty-five cystoid spaces (39.9%) with marked fluorescein pooling intensity had lower reflectivity on OCT images than those with modest pooling (12.1±10.4 vs. 22.0±15.4, P < 0.001). The heterogeneity of the reflectivity of the cystoid spaces on the OCT images was associated significantly (P < 0.001) with modest fluorescein pooling. The hyperreflective foci in the cystoid spaces were correlated significantly with modest fluorescein pooling and higher or heterogeneous reflectivity on OCT images (P < 0.001, P < 0.001, and P=0.005, respectively). In addition, the cystoid spaces with microaneurysms had higher or heterogeneous reflectivity on OCT images more frequently than those without microaneurysms (P < 0.001 and P=0.019, respectively). The reflectivity levels in the SRD were significantly (P=0.005) lower than in the cystoid spaces, and only 1 eye (3.3%) had heterogeneous reflectivity on OCT images. [Conclusions]: The results provided a novel interpretation of fluorescein pooling and OCT characteristics of cystoid spaces and SRD in DME and suggested several mechanisms by which the blood–retinal barrier is disrupted and concomitant edematous changes develop

Subfoveal serous retinal detachment associated with extramacular branch retinal vein occlusion.

[Purpose]: To study the pathophysiology of subfoveal serous retinal detachment (SRD) observed in eyes with extramacular branch retinal vein occlusion (BRVO). [Methods]: We retrospectively reviewed the medical records of nine patients (nine eyes) with extramacular BRVO with macular complications that were examined using optical coherence tomography (OCT). [Results]: Extramacular BRVO was observed in the inferior area in three eyes, in the superior area in five eyes, and in the nasal area in one eye. Visual acuity was moderately disturbed (median, 0.6; range, 0.2–0.9, measured using the Landolt chart). One eye showed extensive SRD that was connected to the area affected by BRVO through the subretinal space. In eight of the eyes, focal SRD was observed beneath the fovea without subretinal connections to the area affected by BRVO. However, all these eyes showed marked retinal swelling in the outer retina, particularly in the outer plexiform layer. In two of the eyes, detailed OCT examinations showed a small break on the external surface of the retina connecting the swollen outer retina with the underlying SRD. All eyes showed hyperreflective foci in the outer retina, most frequently along the inner boundary of the outer plexiform layer and external limiting membrane. [Conclusion]: Extramacular BRVO is often accompanied by focal SRD beneath the fovea. Leakage from the retinal capillaries affected by BRVO travelled via the outer plexiform layer and caused SRD under the fovea

Retinal sensitivity after resolution of the macular edema associated with retinal vein occlusion.

[Purpose]To study the correlation of retinal sensitivity with both morphologic changes in the macula and status of retinal capillary perfusion, after resolution of the macular edema associated with retinal vein occlusion (RVO). [Methods]Retinal sensitivity in the macular area was examined with the Micro Perimeter 1 in 24 eyes after resolution of the macular edema associated with RVO. Using spectral-domain optical coherence tomography, 6 mm × 6 mm areas of macula were examined with 256 sequential horizontal scans. Condition of the photoreceptor layer was evaluated depending upon detection of the junctions between inner and outer segments of the photoreceptors (IS/OS). Fluorescein angiography was performed in 19 eyes. [Results ]Mean retinal sensitivity on the affected side of the retina was significantly decreased (p < 0.001). On the affected side, the mean retinal sensitivity within the area of deteriorated IS/OS was significantly less (3.8 ± 4.8 dB) than that within areas with complete IS/OS (10.1 ± 6.4 dB, p < 0.001). Mean retinal sensitivity within nonperfused areas was extremely low (0.3 ± 1.3 dB), compared with that in perfused retina (10.9 ± 5.9 dB, p < 0.001). In eyes with a broken foveal capillary ring (FCR), the marked decline in retinal sensitivity was seen within the area where the FCR was broken; this was not seen in eyes with an intact FCR. [Conclusion ]Retinal function was decreased markedly in areas with a damaged photoreceptor layer due to RVO, and was lethally decreased within nonperfused areas. Due to the various limitations of the current study, including implementation of fluorescein angiography in limited number of eyes, wide range of follow-up, and heterogeneity of pretreatments, further prospective studies are necessary to confirm the current findings

Age- and hypertension-dependent changes in retinal vessel diameter and wall thickness: an optical coherence tomography study.

[Purpose]To validate and evaluate the reliability of retinal vessel diameter measurements by optical coherence tomography (OCT). The effects of age and hypertension on vessel diameter were also examined. [Design]Prospective, cross-sectional study. [Methods]Two hundred thirty-eight eyes (238 subjects) with no ocular disease were included. Hypertension was present in 106 subjects and absent in 132 subjects. Spectralis HRA+OCT was used to scan a circular region around the optic disc. Outer and inner diameters of the 4 largest retinal arteries and veins were measured using OCT vascular wall reflections, and vessel wall thickness was calculated. [Results]Intervisit, interexaminer, and interevaluator intraclass correlation coefficients of randomly selected vessel measurements were all greater than 0.90. Mean inner arterial and venous diameters were 87.8 ± 9.4 μm and 113.7 ± 12.5 μm, respectively. The OCT-measured mean inner arterial and venous diameters were significantly correlated to fundus photography caliber measurements (P = .005 and P = .001, respectively). Arterial and venous wall thicknesses were 17.4 ± 2.4 μm and 13.7 ± 2.1 μm, respectively, both of which were highly correlated with subject age (arterial: r = 0.612, P < .001, venous: r = 0.455, P < .001). Additionally, both mean arterial and venous wall thicknesses were significantly greater in subjects with hypertension than in age-matched subjects without hypertension (P = .020 and P = .015, respectively). [Conclusions]Retinal vessel diameter measurements obtained with OCT were highly reproducible and vessel wall thicknesses, calculated using outer and inner diameter measurements, were significantly thickened by both aging and systemic hypertension

Safety and feasibility of MEAM therapy followed by auto-HSCT for malignant lymphoma

第73回日本血液学会学術集

Platelet-derived growth factor-C functions as a growth factor in mouse embryonic stem cells and human fibrosarcoma cells

Abstract Background Platelet-derived growth factor-C (PDGF-C) has been shown to be involved in several biological processes, such as embryonic development, wound healing and angiogenesis, as well as in diseases including tumor formation and fibrotic diseases. However, its role in fibrosarcoma and embryonic stem (ES) cells has not been elucidated. Methods The expression level of PDGF-C was measured using RT-PCR. The activity of PDGF-C was suppressed using RNA interference or a neutralizing antibody and the effect on cell growth was examined using the WST and soft agar assays. Results In the tumor cell lines studied, the highest level of PDGF-C expression was in human HT1080 fibrosarcoma cells. In ES cells, it was highly expressed in the self-renewal state but not in the differentiated state. PDGF-C knockdown suppressed anchorage-dependent and -independent growth of HT1080 and ES cells. In addition, the suppression of PDGF-C activity by a neutralizing antibody retarded ES cell growth. Conclusion Our results suggest that PDGF-C plays an important role in the proliferation of fibrosarcoma and ES cells