In dexamethasone-treated thymocyte cultures an increase in nuclear proteolytic activity parallele... more In dexamethasone-treated thymocyte cultures an increase in nuclear proteolytic activity paralleled chromatin fragmentation and the appearance of small apoptotic cells. The elevation of nuclear proteolytic activity was accompanied by site-specific degradation of nuclear mitotic apparatus protein and lamin B, two essential components of the nuclear matrix. Nuclear mitotic apparatus protein phosphorylation and cleavage into 200 and 48 kDa fragments occurred within 30 minutes of dexamethasone treatment. Cleavage of lamin B, which generated a fragment of 46 kDa consistent with the central rod domain of the protein, was also detected after 30 minutes of exposure to the steroid hormone. The level of lamin B phosphorylation did not change as a result of the dexamethasone treatment and the lamina did not solubilize until the later stages of apoptosis. Initial DNA breaks, detected by the terminal transferase-mediated dUTP-biotin nick end labeling assay, occurred throughout the nuclei and solu...
Folia neuropathologica / Association of Polish Neuropathologists and Medical Research Centre, Polish Academy of Sciences, 2007
We describe a granular cell tumour developing in clear cell meningioma of the falx. Granular and ... more We describe a granular cell tumour developing in clear cell meningioma of the falx. Granular and clear cells showed immunoreactivity for vimentin, epithelial membrane antigen and progesterone receptors. This is the first case documenting arachnoid origin of neoplastic granular cells in meningioma.
The expression of Bcl-2, Bcl-X, Mcl-1, and Bax was examined by immunohistochemical methods in 93 ... more The expression of Bcl-2, Bcl-X, Mcl-1, and Bax was examined by immunohistochemical methods in 93 tumors of nervous system origin, including 49 gliomas (30 astrocytomas and 19 glioblastoma multiforme (GMs)), 16 medulloblastomas (MBs), 19 neuroblastomas (NBs; 9 undifferentiated and 10 differentiated), and 9 miscellaneous neuroectodermal neoplasms. Among the 49 gliomas, immunopositivity (defined as > or = 10%) was observed for Bcl-2 in 45 (92%), Bcl-X in 48 (98%), Mcl-1 in 49 (100%), and Bax in 48 (98%) of 49 specimens. In 11 (37%) of 30 astrocytomas (WHO grades I to III), the tumor specimens were composed predominantly of malignant cells with strong-intensity Bcl-2 immunostaining, whereas none of the 19 GMs (WHO grade IV) exhibited strong-intensity Bcl-2 immunoreactivity (P = 0.001). Similarly, Mcl-1 immunointensity was strong in 15 (50%) of 30 astrocytomas, compared with only 2 (11%) of 19 GMs (P = 0.005). The percentage of Mcl-1-immunopositive tumor cells was also higher in astro...
Alzheimer's disease (AD) is a complex disorder that involves multiple biological processes. M... more Alzheimer's disease (AD) is a complex disorder that involves multiple biological processes. Many genes implicated in these processes may be present in low abundance in the human brain. DNA microarray analysis identifies changed genes that are expressed at high or moderate levels. Complementary to this approach, we described here a novel technology designed specifically to isolate rare and novel genes previously undetectable by other methods. We have used this method to identify differentially expressed genes in brains affected by AD. Our method, termed Subtractive Transcription-based Amplification of mRNA (STAR), is a combination of subtractive RNA/DNA hybridization and RNA amplification, which allows the removal of non-differentially expressed transcripts and the linear amplification of the differentially expressed genes. Using the STAR technology we have identified over 800 differentially expressed sequences in AD brains, both up- and down- regulated, compared to age-matched c...
Hemangiomas are customarily described as low-grade vascular tumors most often located in the head... more Hemangiomas are customarily described as low-grade vascular tumors most often located in the head and neck, but on rare occasions occurring in the intradural space of the spine. The different subtypes of hemangiomas can be distinguished histologically as capillary, cavernous, or mixed types. We describe a rare case of a mixed capillary-cavernous extramedullary intradural hemangioma of the thoracic spinal cord, mimicking meningioma radiologically.
Macrophagic myofasciitis is a novel, "inflammatory myopathy&... more Macrophagic myofasciitis is a novel, "inflammatory myopathy" described after a variety of vaccinations, almost exclusively in adults. We examined the relevance of histological findings of this myopathy to the clinical presentation in pediatric patients. Muscle biopsies from 8 children (7 months to 6 years old) with histological features of macrophagic myofasciitis were reviewed and correlated with the clinical manifestations. Patients underwent quadriceps muscle biopsy for suspected mitochondrial disease (4 patients), spinal muscular atrophy (2 patients), myoglobinuria (1 patient), and hypotonia with motor delay (1 patient). All biopsies showed identical granulomas composed of periodic acid-Schiff-positive and CD68-positive macrophages. Characteristic aluminum hydroxide crystals were identified by electron microscopy in 2 cases. The biopsy established diagnoses other than macrophagic myofasciitis in 5 patients: spinal muscular atrophy (2), Duchenne muscular dystrophy (1), phospho-glycerate kinase deficiency (1), and cytochrome c oxidase deficiency (1). Three children with manifestations and/or a family history of mitochondrial disease had otherwise morphologically normal muscle. All children had routine vaccinations between 2 months and 1 year before the biopsy, with up to 11 intramuscular injections, including the biopsy sites. There was no correlation between histological findings of macrophagic myofasciitis in biopsies and the clinical symptoms. We believe that macrophagic myofasciitis represents a localized histological hallmark of previous immunization with the aluminum hydroxide adjuvants contained in vaccines, rather than a primary or distinct inflammatory muscle disease.
The brain of a 5-year-old boy with Schinzel-Giedion syndrome displayed a cobblestone appearance o... more The brain of a 5-year-old boy with Schinzel-Giedion syndrome displayed a cobblestone appearance of orbital and lateral aspects of frontal lobes due to widespread glioneuronal meningeal heterotopia. Meningeal heterotopia consisted of scattered neurons, neurofilament positive axons, and myelinated fibers accompanied by striking astrocytic gliosis. The underlying cortex showed gaps in the pial basal lamina, distorted neuronal layering, and focal polymicrogyria. The number of capillaries appeared increased throughout the brain. Mild hydrocephalus was associated with a slight atrophy of corpus callosum as well as villous hyperplasia and marked stromal degeneration of the choroid plexus. Our findings suggest that Schinzel-Giedion syndrome may represent One more entity within enlarging spectrum of lissencephalic cortical dysplasia syndromes.
Suspensions of rat thymocytes were given 0.09-100 Gy using 60Co gamma-rays. The radiation-induced... more Suspensions of rat thymocytes were given 0.09-100 Gy using 60Co gamma-rays. The radiation-induced changes in the thymocytes were examined from minutes to hours post-irradiation using electron microscopy, agarose gel electrophoresis, staining and Coulter Counter sizing. Sizing by Coulter Counter showed, for the first time, that thymocytes which undergo apoptosis shrink in two distinct stages, first by a sudden decrease from an original volume of 99 microns 3 to a volume of 76 microns 3, followed by a gradual decrease to 57 microns 3 over the space of a few hours. The oxygen enhancement ratio for apoptosis was measured to be about 3.5, similar to the value for reproductive death for many mammalian cells.
The differentiation pattern of two related human neuroblastoma cell lines, SK-N-SHF and SK-N-SHN,... more The differentiation pattern of two related human neuroblastoma cell lines, SK-N-SHF and SK-N-SHN, induced by retinoic acid and staurosporine was studied. Immunohistochemical and electron microscopic examination of the cells indicated that the SHF variant could undergo differentiation along a melanocytic route when treated with retinoic acid and to neuronal cells when treated with retionic acid and staurosporine together. Treatment of SHN cells with either or both these agents caused neuronal differentiation. The melanocytic pathway was characterized in part by the flattening of the cells, the appearance of melanocytic antigens and various forms of melanosomes, an increase in tyrosinase activity, and the absence of neuronal marker proteins. The neuronal route was typified by the development of long neuritic processes containing microtubules and numerous neurosecretory granules as well as by immunohistochemical reactions for neural cell adhesion molecule, synaptophysin, and neurofilament proteins. The significance of these results is discussed in terms of the differentiation responses of neuroblastoma cells to chemical agents as well as some of the factors involved in the regulation of phenotype expressions of these cells.
Morphometric analysis of transmission electron micrographs of blood vessel, skin and dura mater c... more Morphometric analysis of transmission electron micrographs of blood vessel, skin and dura mater collagen fibers were performed on postmortem tissues taken from 28-year-old female with Ehlers-Danlos type IV syndrome (EDS IV). Vascular tissue from this patient was compared to 5 age- and sex-matched controls (age range 26-28 years). Our study revealed significant variation in collagen fibril diameter in the walls of almost all the vessels studied. In general, the EDS IV tissue showed a net decrease in average collagen fibril cross sectional area in arterial wall samples. This decrease was significant (p less than .05) across the entire wall of the renal artery, in the media of the carotid artery, and in the media and adventitia of the common iliac artery. Samples from the vena cava show significant increases in collagen fibril cross sectional area across the vessel wall (p less than .005). The only areas studied which did not show significant changes were the intimal and adventitial regions of the common carotid artery. The observed changes may be contributory to the decreased arterial wall strength typical of the syndrome.
In dexamethasone-treated thymocyte cultures an increase in nuclear proteolytic activity parallele... more In dexamethasone-treated thymocyte cultures an increase in nuclear proteolytic activity paralleled chromatin fragmentation and the appearance of small apoptotic cells. The elevation of nuclear proteolytic activity was accompanied by site-specific degradation of nuclear mitotic apparatus protein and lamin B, two essential components of the nuclear matrix. Nuclear mitotic apparatus protein phosphorylation and cleavage into 200 and 48 kDa fragments occurred within 30 minutes of dexamethasone treatment. Cleavage of lamin B, which generated a fragment of 46 kDa consistent with the central rod domain of the protein, was also detected after 30 minutes of exposure to the steroid hormone. The level of lamin B phosphorylation did not change as a result of the dexamethasone treatment and the lamina did not solubilize until the later stages of apoptosis. Initial DNA breaks, detected by the terminal transferase-mediated dUTP-biotin nick end labeling assay, occurred throughout the nuclei and solu...
Folia neuropathologica / Association of Polish Neuropathologists and Medical Research Centre, Polish Academy of Sciences, 2007
We describe a granular cell tumour developing in clear cell meningioma of the falx. Granular and ... more We describe a granular cell tumour developing in clear cell meningioma of the falx. Granular and clear cells showed immunoreactivity for vimentin, epithelial membrane antigen and progesterone receptors. This is the first case documenting arachnoid origin of neoplastic granular cells in meningioma.
The expression of Bcl-2, Bcl-X, Mcl-1, and Bax was examined by immunohistochemical methods in 93 ... more The expression of Bcl-2, Bcl-X, Mcl-1, and Bax was examined by immunohistochemical methods in 93 tumors of nervous system origin, including 49 gliomas (30 astrocytomas and 19 glioblastoma multiforme (GMs)), 16 medulloblastomas (MBs), 19 neuroblastomas (NBs; 9 undifferentiated and 10 differentiated), and 9 miscellaneous neuroectodermal neoplasms. Among the 49 gliomas, immunopositivity (defined as > or = 10%) was observed for Bcl-2 in 45 (92%), Bcl-X in 48 (98%), Mcl-1 in 49 (100%), and Bax in 48 (98%) of 49 specimens. In 11 (37%) of 30 astrocytomas (WHO grades I to III), the tumor specimens were composed predominantly of malignant cells with strong-intensity Bcl-2 immunostaining, whereas none of the 19 GMs (WHO grade IV) exhibited strong-intensity Bcl-2 immunoreactivity (P = 0.001). Similarly, Mcl-1 immunointensity was strong in 15 (50%) of 30 astrocytomas, compared with only 2 (11%) of 19 GMs (P = 0.005). The percentage of Mcl-1-immunopositive tumor cells was also higher in astro...
Alzheimer's disease (AD) is a complex disorder that involves multiple biological processes. M... more Alzheimer's disease (AD) is a complex disorder that involves multiple biological processes. Many genes implicated in these processes may be present in low abundance in the human brain. DNA microarray analysis identifies changed genes that are expressed at high or moderate levels. Complementary to this approach, we described here a novel technology designed specifically to isolate rare and novel genes previously undetectable by other methods. We have used this method to identify differentially expressed genes in brains affected by AD. Our method, termed Subtractive Transcription-based Amplification of mRNA (STAR), is a combination of subtractive RNA/DNA hybridization and RNA amplification, which allows the removal of non-differentially expressed transcripts and the linear amplification of the differentially expressed genes. Using the STAR technology we have identified over 800 differentially expressed sequences in AD brains, both up- and down- regulated, compared to age-matched c...
Hemangiomas are customarily described as low-grade vascular tumors most often located in the head... more Hemangiomas are customarily described as low-grade vascular tumors most often located in the head and neck, but on rare occasions occurring in the intradural space of the spine. The different subtypes of hemangiomas can be distinguished histologically as capillary, cavernous, or mixed types. We describe a rare case of a mixed capillary-cavernous extramedullary intradural hemangioma of the thoracic spinal cord, mimicking meningioma radiologically.
Macrophagic myofasciitis is a novel, "inflammatory myopathy&... more Macrophagic myofasciitis is a novel, "inflammatory myopathy" described after a variety of vaccinations, almost exclusively in adults. We examined the relevance of histological findings of this myopathy to the clinical presentation in pediatric patients. Muscle biopsies from 8 children (7 months to 6 years old) with histological features of macrophagic myofasciitis were reviewed and correlated with the clinical manifestations. Patients underwent quadriceps muscle biopsy for suspected mitochondrial disease (4 patients), spinal muscular atrophy (2 patients), myoglobinuria (1 patient), and hypotonia with motor delay (1 patient). All biopsies showed identical granulomas composed of periodic acid-Schiff-positive and CD68-positive macrophages. Characteristic aluminum hydroxide crystals were identified by electron microscopy in 2 cases. The biopsy established diagnoses other than macrophagic myofasciitis in 5 patients: spinal muscular atrophy (2), Duchenne muscular dystrophy (1), phospho-glycerate kinase deficiency (1), and cytochrome c oxidase deficiency (1). Three children with manifestations and/or a family history of mitochondrial disease had otherwise morphologically normal muscle. All children had routine vaccinations between 2 months and 1 year before the biopsy, with up to 11 intramuscular injections, including the biopsy sites. There was no correlation between histological findings of macrophagic myofasciitis in biopsies and the clinical symptoms. We believe that macrophagic myofasciitis represents a localized histological hallmark of previous immunization with the aluminum hydroxide adjuvants contained in vaccines, rather than a primary or distinct inflammatory muscle disease.
The brain of a 5-year-old boy with Schinzel-Giedion syndrome displayed a cobblestone appearance o... more The brain of a 5-year-old boy with Schinzel-Giedion syndrome displayed a cobblestone appearance of orbital and lateral aspects of frontal lobes due to widespread glioneuronal meningeal heterotopia. Meningeal heterotopia consisted of scattered neurons, neurofilament positive axons, and myelinated fibers accompanied by striking astrocytic gliosis. The underlying cortex showed gaps in the pial basal lamina, distorted neuronal layering, and focal polymicrogyria. The number of capillaries appeared increased throughout the brain. Mild hydrocephalus was associated with a slight atrophy of corpus callosum as well as villous hyperplasia and marked stromal degeneration of the choroid plexus. Our findings suggest that Schinzel-Giedion syndrome may represent One more entity within enlarging spectrum of lissencephalic cortical dysplasia syndromes.
Suspensions of rat thymocytes were given 0.09-100 Gy using 60Co gamma-rays. The radiation-induced... more Suspensions of rat thymocytes were given 0.09-100 Gy using 60Co gamma-rays. The radiation-induced changes in the thymocytes were examined from minutes to hours post-irradiation using electron microscopy, agarose gel electrophoresis, staining and Coulter Counter sizing. Sizing by Coulter Counter showed, for the first time, that thymocytes which undergo apoptosis shrink in two distinct stages, first by a sudden decrease from an original volume of 99 microns 3 to a volume of 76 microns 3, followed by a gradual decrease to 57 microns 3 over the space of a few hours. The oxygen enhancement ratio for apoptosis was measured to be about 3.5, similar to the value for reproductive death for many mammalian cells.
The differentiation pattern of two related human neuroblastoma cell lines, SK-N-SHF and SK-N-SHN,... more The differentiation pattern of two related human neuroblastoma cell lines, SK-N-SHF and SK-N-SHN, induced by retinoic acid and staurosporine was studied. Immunohistochemical and electron microscopic examination of the cells indicated that the SHF variant could undergo differentiation along a melanocytic route when treated with retinoic acid and to neuronal cells when treated with retionic acid and staurosporine together. Treatment of SHN cells with either or both these agents caused neuronal differentiation. The melanocytic pathway was characterized in part by the flattening of the cells, the appearance of melanocytic antigens and various forms of melanosomes, an increase in tyrosinase activity, and the absence of neuronal marker proteins. The neuronal route was typified by the development of long neuritic processes containing microtubules and numerous neurosecretory granules as well as by immunohistochemical reactions for neural cell adhesion molecule, synaptophysin, and neurofilament proteins. The significance of these results is discussed in terms of the differentiation responses of neuroblastoma cells to chemical agents as well as some of the factors involved in the regulation of phenotype expressions of these cells.
Morphometric analysis of transmission electron micrographs of blood vessel, skin and dura mater c... more Morphometric analysis of transmission electron micrographs of blood vessel, skin and dura mater collagen fibers were performed on postmortem tissues taken from 28-year-old female with Ehlers-Danlos type IV syndrome (EDS IV). Vascular tissue from this patient was compared to 5 age- and sex-matched controls (age range 26-28 years). Our study revealed significant variation in collagen fibril diameter in the walls of almost all the vessels studied. In general, the EDS IV tissue showed a net decrease in average collagen fibril cross sectional area in arterial wall samples. This decrease was significant (p less than .05) across the entire wall of the renal artery, in the media of the carotid artery, and in the media and adventitia of the common iliac artery. Samples from the vena cava show significant increases in collagen fibril cross sectional area across the vessel wall (p less than .005). The only areas studied which did not show significant changes were the intimal and adventitial regions of the common carotid artery. The observed changes may be contributory to the decreased arterial wall strength typical of the syndrome.
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