Objective To determine whether all-trans retinoic acid (atR A) exerts an inhibitory effect on rats with pulmonary hypertension induced by monocrotaline.Methods All rats were given a single subcutaneous injection of ei...Objective To determine whether all-trans retinoic acid (atR A) exerts an inhibitory effect on rats with pulmonary hypertension induced by monocrotaline.Methods All rats were given a single subcutaneous injection of either monocrotaline (60 mg/kg) or saline.Monocrotaline-injected rats received either atRA (30 mg· kg-1· day-1) or saline through oral-gastro intubation. On Days 7, 14, 21, and 28 respectively after monocrotaline injection, cardiovascular catheters were inserted to examine the mean pulmonary artery pressure of rats in each group. Meanwhile, the matrix metalloproteinase-1 (MMP-1) mRNA expression and hydroxyproline content in the main pulmonary artery were determined by RT-PCR and chromornetry, respectively.Results The mean pulmonary artery pressure of rats in the model group increased significantly on day 21 and reached a peak on Day 28 compared with the control group (25.7+4.3 mm Hg vs 15.1 ± 1.5 mm Hg and 38.5 ± 6.4 mm Hg vs 16.4 ± 2.0 mm Hg, P ＜ 0.01 ). MMP-1 mRNA overexpression was present on Day 14 (0.72 ± 0.15 vs 0.39 ± 0.08, P ＜ 0.01 ) and was rapidly down-regulated on Day 21 and 28 compared with Day 14, but was still higher than that in the control. The hydroxyoroline content of the main pulmonary artery dropped significantly on Day 14 (4.01 ± 1.13 μg/mg vs 5.10 ± 0.91 μg/mg, P ＜ 0.05)and increased significantly on Days 21 and 28 compared with the control, atRA inhibited the MMP-1 mRNA overexpression from Day 14 to Day 28 and reduced the hydroxyproline content (5.59 ± 0.70 μg/mg vs 7.96 ± 1.13 μg/mg and 7.77 ± 0.96 μg/mg vs 9.93 ± 1.27μg/mg, P ＜ 0.01 ) and the mean pulmonary artery pressure compared with the model group ( 19.6 ± 3.2 mm Hg vs 25.7 ± 4.3 mm Hg and 26.3 ± 4.6 mm Hg vs 38.5±6.4 mm Hg, P＜0.01).Conclusion atRA inhibits MMP-1 overexpression and the accumulation of collagen, which might elicit favorable geometric remodeling in rat pulmonary hypertension induced by monocrotaline.展开更多
Objective To present a special case with the karyotype and molecular marker of acute myeloid leukemia (AML)-M 2 who was induced to complete remission by all-trans retinoic acid (ATRA) alone.Methods A recently hospi...Objective To present a special case with the karyotype and molecular marker of acute myeloid leukemia (AML)-M 2 who was induced to complete remission by all-trans retinoic acid (ATRA) alone.Methods A recently hospitalized young female patient with acute leukemia was initially diagnosed as M 3 subtype based on morphological French-American-British (FAB) classification. Karyotype analysis using standard G and R banding techniques and RT-PCR were applied to further define the diagnosis. After primarily cultured bone marrow cells from the iliac aspiration were tested for in vitro induced differentiation, the patient was treated with oral all-trans retinoic acid alone, 60?mg per day until complete remission was achieved. Peripheral blood and bone marrow changes were monitored over the whole treatment course.Results The characteristic chromosomal aberration for M 3, the t(15;17) reciprocal translocation, was not found while a t(8;21) translocation was verified. Furthermore, an amplified product of the AML-1/ETO fusion gene instead of the PML/RARα fusion gene was detected by RT-PCR and the diagnosis was corrected from M 3 to M 2. Primary cultured bone marrow cells can be fully induced to terminal differentiation after 4 days exposure to ATRA. A hematological complete remission was achieved after 40 days treatment with ATRA as a single therapeutic agent, suggesting an alternative pathway mediating ATRA-induced myeloid differentiation. Conclusion A leukemia patient with a subtype other than M 3, such as M 2 in this case, may also be induced to complete remission by the mechanism of ATRA-induced terminal differentiation. This implies that there may be a pathway other than PML/RARα fusion gene product which mediates ATRA-induced myeloid maturation in leukemia cells.展开更多
文摘Objective To determine whether all-trans retinoic acid (atR A) exerts an inhibitory effect on rats with pulmonary hypertension induced by monocrotaline.Methods All rats were given a single subcutaneous injection of either monocrotaline (60 mg/kg) or saline.Monocrotaline-injected rats received either atRA (30 mg· kg-1· day-1) or saline through oral-gastro intubation. On Days 7, 14, 21, and 28 respectively after monocrotaline injection, cardiovascular catheters were inserted to examine the mean pulmonary artery pressure of rats in each group. Meanwhile, the matrix metalloproteinase-1 (MMP-1) mRNA expression and hydroxyproline content in the main pulmonary artery were determined by RT-PCR and chromornetry, respectively.Results The mean pulmonary artery pressure of rats in the model group increased significantly on day 21 and reached a peak on Day 28 compared with the control group (25.7+4.3 mm Hg vs 15.1 ± 1.5 mm Hg and 38.5 ± 6.4 mm Hg vs 16.4 ± 2.0 mm Hg, P ＜ 0.01 ). MMP-1 mRNA overexpression was present on Day 14 (0.72 ± 0.15 vs 0.39 ± 0.08, P ＜ 0.01 ) and was rapidly down-regulated on Day 21 and 28 compared with Day 14, but was still higher than that in the control. The hydroxyoroline content of the main pulmonary artery dropped significantly on Day 14 (4.01 ± 1.13 μg/mg vs 5.10 ± 0.91 μg/mg, P ＜ 0.05)and increased significantly on Days 21 and 28 compared with the control, atRA inhibited the MMP-1 mRNA overexpression from Day 14 to Day 28 and reduced the hydroxyproline content (5.59 ± 0.70 μg/mg vs 7.96 ± 1.13 μg/mg and 7.77 ± 0.96 μg/mg vs 9.93 ± 1.27μg/mg, P ＜ 0.01 ) and the mean pulmonary artery pressure compared with the model group ( 19.6 ± 3.2 mm Hg vs 25.7 ± 4.3 mm Hg and 26.3 ± 4.6 mm Hg vs 38.5±6.4 mm Hg, P＜0.01).Conclusion atRA inhibits MMP-1 overexpression and the accumulation of collagen, which might elicit favorable geometric remodeling in rat pulmonary hypertension induced by monocrotaline.
文摘Objective To present a special case with the karyotype and molecular marker of acute myeloid leukemia (AML)-M 2 who was induced to complete remission by all-trans retinoic acid (ATRA) alone.Methods A recently hospitalized young female patient with acute leukemia was initially diagnosed as M 3 subtype based on morphological French-American-British (FAB) classification. Karyotype analysis using standard G and R banding techniques and RT-PCR were applied to further define the diagnosis. After primarily cultured bone marrow cells from the iliac aspiration were tested for in vitro induced differentiation, the patient was treated with oral all-trans retinoic acid alone, 60?mg per day until complete remission was achieved. Peripheral blood and bone marrow changes were monitored over the whole treatment course.Results The characteristic chromosomal aberration for M 3, the t(15;17) reciprocal translocation, was not found while a t(8;21) translocation was verified. Furthermore, an amplified product of the AML-1/ETO fusion gene instead of the PML/RARα fusion gene was detected by RT-PCR and the diagnosis was corrected from M 3 to M 2. Primary cultured bone marrow cells can be fully induced to terminal differentiation after 4 days exposure to ATRA. A hematological complete remission was achieved after 40 days treatment with ATRA as a single therapeutic agent, suggesting an alternative pathway mediating ATRA-induced myeloid differentiation. Conclusion A leukemia patient with a subtype other than M 3, such as M 2 in this case, may also be induced to complete remission by the mechanism of ATRA-induced terminal differentiation. This implies that there may be a pathway other than PML/RARα fusion gene product which mediates ATRA-induced myeloid maturation in leukemia cells.
