... differences of four children with single mitochondrial DNA deletions Hanna Mierzewska1, Macie... more ... differences of four children with single mitochondrial DNA deletions Hanna Mierzewska1, Maciej Pronicki2, Massoud Houshmand 4, Katarzyna Tońska5, Elżbieta ... Hum Genet 95: 75–81 4. Bohm M, Pronicka E, Karczmarewicz E, et al (2006) Retrospective, multicen-tric study of ...
... Powieści: Joanna Kulmowa Wio, Leokadio; Astrid Lindgren Dzieci z Bullerbyn; Alan Aleksander M... more ... Powieści: Joanna Kulmowa Wio, Leokadio; Astrid Lindgren Dzieci z Bullerbyn; Alan Aleksander Milne Kubuś Puchatek. Wymagania 1. Komunikacja językowa i jej składniki 1.1. Nawiązać rozmowę z innymi ludźmi. 1.2. Nazwać uczucia wpisane do tekstu. 1.3. ...
Many models of tumour formation have been put forth so far. In general they involve mutations in ... more Many models of tumour formation have been put forth so far. In general they involve mutations in at least three elements within the cell: oncogenes, tumour suppressors and regulators of telomere replication. Recently numerous mutations in mitochondria have been found in many ...
... czterech jonów wodorowych z macie-rzy mitochondrialnej (zostają zużyte do utworzenia dwóch cz... more ... czterech jonów wodorowych z macie-rzy mitochondrialnej (zostają zużyte do utworzenia dwóch cząsteczek wody) oraz jednoczesne przeniesienie czterech protonów w poprzek wewnętrznej błony mitochondrialnej [1]. Protony przenoszone są poprzez trzy kanały (D, K i H ...
To describe a patient with genetically confirmed POLG mutation and partially treatment-responsive... more To describe a patient with genetically confirmed POLG mutation and partially treatment-responsive chronic immune demyelinating polyneuropathy. Patient and methods: A 16Â years old girl with predominantly sensory neuropathy, dysarthria and ataxia. Case description together with nerve conduction study, evoked potentials and MRI results are presented. She had history of 1.5Â years of slowly progressive walking difficulties. Developmental milestones were normal, but she was never good at sports. On admission she had ataxic gait, proprioceptive sensation disturbances, high arched feet, dysarthria, pansensory loss in lower extremities up to her knees, areflexia, positive Romberg sign. Nerve conduction studies demonstrated sensory-motor polyneuropathy of lower limbs. Evoked potentials studies confirmed disturbances of visual, brain stem and somatosensory pathways. Magnetic resonance imaging (MRI) of lumbar spine revealed gadolinium enhancement of spinal roots She had elevated CSF protein with normal leukocyte count. Preliminary diagnosis of chronic immune demyelinating neuropathy was made. Immunomodulatory treatment with methylprednisolone and IVIG led to marked improvement of gait, resolution of abnormalities of touch, temperature sensation, improved proprioception. Several weeks later she developed action-exacerbated myoclonus of her left lower extremity, partially responsive to treatment with clonazepam and levetiracetam. Myoclonus limited her ability to walk. MR Spectroscopy with voxel placed in lateral ventricle demonstrated increased lactate in CSF. DNA testing revealed heterozygous mutation of POLG, with paternally inherited W748S, and maternally inherited V1106A mutation of an evolutionary conserved POLG region. The case raises the question if mitochondrial disease triggered additional immune disease, or autoimmune polyneuropathy affected the clinical course of this rare hereditary disorder.
We have analysed the heteroplasmy level in 11 individuals from 3 families harbouring the mitochon... more We have analysed the heteroplasmy level in 11 individuals from 3 families harbouring the mitochondrial 11778A mutation responsible for Leber hereditary optic neuropathy using last cycle hot PCR. The mutation level exceeded 90 % both in affected and in unaffected individuals. We also checked whether any of the families belonged to the J haplogroup of mitochondrial DNA and obtained a negative result. Human mitochondrial DNA (mtDNA) is a small circular molecule coding for 13 respiratory chain proteins, 22 tRNAs and 2 rRNAs used in mitochondrial translation and is maternally inherited. In one cell a few hundred to a few thousand mtDNA molecules are present — from 1 to about 10 in one mitochondrion. Divisions of these molecules are not correlated with the cell cycle and during mitosis or meiosis mitochondria with mtDNA are randomly
We have analysed the heteroplasmy level in 11 individuals from 3 families harbouring the mitochon... more We have analysed the heteroplasmy level in 11 individuals from 3 families harbouring the mitochondrial 11778A mutation responsible for Leber hereditary optic neuropathy using last cycle hot PCR. The mutation level exceeded 90% both in affected and in unaffected individuals. We also checked whether any of the families belonged to the J haplogroup of mitochondrial DNA and obtained a negative result.
Numerous studies of mitochondrial DNA (mtDNA) in cancer have shown differences between mtDNA sequ... more Numerous studies of mitochondrial DNA (mtDNA) in cancer have shown differences between mtDNA sequences in tumor and normal tissue and at various stages of cancer treatment in the same patient. However, there is little data on acute lymphoblastic leukemia (ALL), the most common type of leukemia in children. In this study we compared mitochondrial sequence variation in the D-loop region and in 5 genes of mtDNA in bone marrow samples of 6 pediatric patients with ALL at various stages of therapy. We found several common polymorphisms and one variant at position 3688 whose level varied during leukemia treatment. Our results suggest that mitochondrial DNA mutations, whose levels change during patient treatment, could be potential biomarkers for monitoring treatment efficacy and disease progression.
Leber hereditary optic neuropathy is a maternally inherited type of blindness caused by degenerat... more Leber hereditary optic neuropathy is a maternally inherited type of blindness caused by degeneration of the optic nerve. It is caused by point mutations in mitochondrial DNA. Like in other mitochondrial diseases, its penetrance and inheritance is complicated by heteroplasmy, tissue distribution, and the bottleneck phenomenon in oocyte maturation. On the cellular level, the mechanism of the disease development is still mysterious. Currently three theories of pathomechanism of LHON are considered: biochemical, ROS (reactive oxygen species) and apoptotic.
Simple Summary Treatment of osteosarcoma, apart from chemotherapy modifications, has not changed ... more Simple Summary Treatment of osteosarcoma, apart from chemotherapy modifications, has not changed for approximately 30 years. Similarly, as in other tumors, mutations in the TP53 gene are often observed in osteosarcoma. In this article, we highlight the possibility of targeting p53 in the treatment of osteosarcoma. We collected data on mutations in this gene founded in patients-derived samples. We describe animals with TP53 dysfunction, which may constitute preclinical models. We put emphasis on several molecules which act on p53 protein or its activity. We also highlight gene therapy approaches. Although many of the therapies are at an early stage, they offer hope for a change in the approach to osteosarcoma treatment based on TP53 targeting in the future. Abstract The TP53 gene is mutated in 50% of human tumors. Oncogenic functions of mutant TP53 maintain tumor cell proliferation and tumor growth also in osteosarcomas. We collected data on TP53 mutations in patients to indicate whi...
... differences of four children with single mitochondrial DNA deletions Hanna Mierzewska1, Macie... more ... differences of four children with single mitochondrial DNA deletions Hanna Mierzewska1, Maciej Pronicki2, Massoud Houshmand 4, Katarzyna Tońska5, Elżbieta ... Hum Genet 95: 75–81 4. Bohm M, Pronicka E, Karczmarewicz E, et al (2006) Retrospective, multicen-tric study of ...
... Powieści: Joanna Kulmowa Wio, Leokadio; Astrid Lindgren Dzieci z Bullerbyn; Alan Aleksander M... more ... Powieści: Joanna Kulmowa Wio, Leokadio; Astrid Lindgren Dzieci z Bullerbyn; Alan Aleksander Milne Kubuś Puchatek. Wymagania 1. Komunikacja językowa i jej składniki 1.1. Nawiązać rozmowę z innymi ludźmi. 1.2. Nazwać uczucia wpisane do tekstu. 1.3. ...
Many models of tumour formation have been put forth so far. In general they involve mutations in ... more Many models of tumour formation have been put forth so far. In general they involve mutations in at least three elements within the cell: oncogenes, tumour suppressors and regulators of telomere replication. Recently numerous mutations in mitochondria have been found in many ...
... czterech jonów wodorowych z macie-rzy mitochondrialnej (zostają zużyte do utworzenia dwóch cz... more ... czterech jonów wodorowych z macie-rzy mitochondrialnej (zostają zużyte do utworzenia dwóch cząsteczek wody) oraz jednoczesne przeniesienie czterech protonów w poprzek wewnętrznej błony mitochondrialnej [1]. Protony przenoszone są poprzez trzy kanały (D, K i H ...
To describe a patient with genetically confirmed POLG mutation and partially treatment-responsive... more To describe a patient with genetically confirmed POLG mutation and partially treatment-responsive chronic immune demyelinating polyneuropathy. Patient and methods: A 16Â years old girl with predominantly sensory neuropathy, dysarthria and ataxia. Case description together with nerve conduction study, evoked potentials and MRI results are presented. She had history of 1.5Â years of slowly progressive walking difficulties. Developmental milestones were normal, but she was never good at sports. On admission she had ataxic gait, proprioceptive sensation disturbances, high arched feet, dysarthria, pansensory loss in lower extremities up to her knees, areflexia, positive Romberg sign. Nerve conduction studies demonstrated sensory-motor polyneuropathy of lower limbs. Evoked potentials studies confirmed disturbances of visual, brain stem and somatosensory pathways. Magnetic resonance imaging (MRI) of lumbar spine revealed gadolinium enhancement of spinal roots She had elevated CSF protein with normal leukocyte count. Preliminary diagnosis of chronic immune demyelinating neuropathy was made. Immunomodulatory treatment with methylprednisolone and IVIG led to marked improvement of gait, resolution of abnormalities of touch, temperature sensation, improved proprioception. Several weeks later she developed action-exacerbated myoclonus of her left lower extremity, partially responsive to treatment with clonazepam and levetiracetam. Myoclonus limited her ability to walk. MR Spectroscopy with voxel placed in lateral ventricle demonstrated increased lactate in CSF. DNA testing revealed heterozygous mutation of POLG, with paternally inherited W748S, and maternally inherited V1106A mutation of an evolutionary conserved POLG region. The case raises the question if mitochondrial disease triggered additional immune disease, or autoimmune polyneuropathy affected the clinical course of this rare hereditary disorder.
We have analysed the heteroplasmy level in 11 individuals from 3 families harbouring the mitochon... more We have analysed the heteroplasmy level in 11 individuals from 3 families harbouring the mitochondrial 11778A mutation responsible for Leber hereditary optic neuropathy using last cycle hot PCR. The mutation level exceeded 90 % both in affected and in unaffected individuals. We also checked whether any of the families belonged to the J haplogroup of mitochondrial DNA and obtained a negative result. Human mitochondrial DNA (mtDNA) is a small circular molecule coding for 13 respiratory chain proteins, 22 tRNAs and 2 rRNAs used in mitochondrial translation and is maternally inherited. In one cell a few hundred to a few thousand mtDNA molecules are present — from 1 to about 10 in one mitochondrion. Divisions of these molecules are not correlated with the cell cycle and during mitosis or meiosis mitochondria with mtDNA are randomly
We have analysed the heteroplasmy level in 11 individuals from 3 families harbouring the mitochon... more We have analysed the heteroplasmy level in 11 individuals from 3 families harbouring the mitochondrial 11778A mutation responsible for Leber hereditary optic neuropathy using last cycle hot PCR. The mutation level exceeded 90% both in affected and in unaffected individuals. We also checked whether any of the families belonged to the J haplogroup of mitochondrial DNA and obtained a negative result.
Numerous studies of mitochondrial DNA (mtDNA) in cancer have shown differences between mtDNA sequ... more Numerous studies of mitochondrial DNA (mtDNA) in cancer have shown differences between mtDNA sequences in tumor and normal tissue and at various stages of cancer treatment in the same patient. However, there is little data on acute lymphoblastic leukemia (ALL), the most common type of leukemia in children. In this study we compared mitochondrial sequence variation in the D-loop region and in 5 genes of mtDNA in bone marrow samples of 6 pediatric patients with ALL at various stages of therapy. We found several common polymorphisms and one variant at position 3688 whose level varied during leukemia treatment. Our results suggest that mitochondrial DNA mutations, whose levels change during patient treatment, could be potential biomarkers for monitoring treatment efficacy and disease progression.
Leber hereditary optic neuropathy is a maternally inherited type of blindness caused by degenerat... more Leber hereditary optic neuropathy is a maternally inherited type of blindness caused by degeneration of the optic nerve. It is caused by point mutations in mitochondrial DNA. Like in other mitochondrial diseases, its penetrance and inheritance is complicated by heteroplasmy, tissue distribution, and the bottleneck phenomenon in oocyte maturation. On the cellular level, the mechanism of the disease development is still mysterious. Currently three theories of pathomechanism of LHON are considered: biochemical, ROS (reactive oxygen species) and apoptotic.
Simple Summary Treatment of osteosarcoma, apart from chemotherapy modifications, has not changed ... more Simple Summary Treatment of osteosarcoma, apart from chemotherapy modifications, has not changed for approximately 30 years. Similarly, as in other tumors, mutations in the TP53 gene are often observed in osteosarcoma. In this article, we highlight the possibility of targeting p53 in the treatment of osteosarcoma. We collected data on mutations in this gene founded in patients-derived samples. We describe animals with TP53 dysfunction, which may constitute preclinical models. We put emphasis on several molecules which act on p53 protein or its activity. We also highlight gene therapy approaches. Although many of the therapies are at an early stage, they offer hope for a change in the approach to osteosarcoma treatment based on TP53 targeting in the future. Abstract The TP53 gene is mutated in 50% of human tumors. Oncogenic functions of mutant TP53 maintain tumor cell proliferation and tumor growth also in osteosarcomas. We collected data on TP53 mutations in patients to indicate whi...
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