Journal of embryology and experimental morphology, 1975
The growth of hair from the mystacial vibrissal follicles of C3H mice and Wistar rats has been me... more The growth of hair from the mystacial vibrissal follicles of C3H mice and Wistar rats has been measured for up to seven cycles. Normally growth in length and thickness was regular and little affected by age or sex. Plucking vibrissae at any stage during the growing period was followed by the appearance of a new vibrissa 8-11 days later. Plucking when growth had ceased had no effect on the time of appearance of the subsequent cycle. New whiskers emerging after plucking grew at the normal rate. Withholding food slowed the growth of vibrissae within 1 day. Normal growth was re-established 3 days after return to full diet.
Journal of embryology and experimental morphology, 1982
SUMMARY The volumes of the dermal papilla, matrix and fully grown hair of vibrissal follicles of ... more SUMMARY The volumes of the dermal papilla, matrix and fully grown hair of vibrissal follicles of rats and mice were measured. Dermal papillae were surgically removed from rats' vibrissal follicles and a small new dermal papilla was always reformed. The lower third of rats and mice follicles, containing the whole of the dermal papilla was amputated and very small dermal papillae were reformed. Follicles containing small dermal papillae produced small hairs and a constant positive linear relationship of 7-0 was found between the volume of the dermal papilla and the volume of the full-grown hair for all cases studied.
Background. Deregulation of the Wnt signaling pathway had a role in haematological malignancies. ... more Background. Deregulation of the Wnt signaling pathway had a role in haematological malignancies. Previous studies reported that lymphoid enhancer factor 1 (LEF1) expression and serum Galectin-3 level could affect clinical parameters and outcome in acute myeloid leukemia patients, but as far as we know, no study has addressed their combined effect on AML patients. Aim. We studied the expression of LEF1 by real-time qPCR and measured serum level of Gal.3 by ELISA technique in peripheral blood of 69 AML patients and correlated it with different clinicopathological criteria of patients, response, PFS and OS. Results. We found high expression (LEF1high) was associated with better OS (p=0.02) and EFS (p=0.019) compared to LEF1low, low serum Gal.3 level had better OS (p=0.014) and EFS (p=0.02) compared to high serum Gal.3 level. LEF1high less likely to carry a FLT3-ITD (p=0.047) compared to LEF1low patient, also LEF1high characterized by favorable risk (p=0.02) than LEF1low patients. While...
Recent success in identifying gene regulatory elements in the context of recombinant adeno-associ... more Recent success in identifying gene regulatory elements in the context of recombinant adeno-associated virus vectors have enabled cell type-restricted gene expression. However, within the cerebral cortex these tools are presently limited to broad classes of neurons. To overcome this limitation, we developed a strategy that led to the identification of multiple novel enhancers to target functionally distinct neuronal subtypes. By investigating the regulatory landscape of the disease gene Scn1a, we identified enhancers that target the breadth of its expression, including two selective for parvalbumin and vasoactive intestinal peptide cortical interneurons. Demonstrating the functional utility of these elements, we found that the PV-specific enhancer allowed for the selective targeting and manipulation of fast-spiking cortical interneurons across species, from mice to humans.
Multiple lines of evidence support a role for the glutamatergic system in the pathophysiology of ... more Multiple lines of evidence support a role for the glutamatergic system in the pathophysiology of major depressive disorder (MDD). Ketamine, an N-methyl-D-aspartate antagonist, rapidly improves depressive symptoms in individuals with treatment-resistant depression. The neural mechanisms underlying this effect remain unknown. In this preliminary study, 20 unmedicated participants with treatment-resistant MDD underwent positron emission tomography to measure regional cerebral glucose metabolism at baseline and following ketamine infusion (single dose of .5mg/kg intravenous over 40minutes). Metabolic data were compared between conditions using a combination of region-of-interest and voxelwise analyses, and differences were correlated with the associated antidepressant response. Whole-brain metabolism did not change significantly following ketamine. Regional metabolism decreased significantly under ketamine in the habenula, insula, and ventrolateral and dorsolateral prefrontal cortices of the right hemisphere. Metabolism increased postketamine in bilateral occipital, right sensorimotor, left parahippocampal, and left inferior parietal cortices. Improvement in depression ratings correlated directly with change in metabolism in right superior and middle temporal gyri. Conversely, clinical improvement correlated inversely with metabolic changes in right parahippocampal gyrus and temporoparietal cortex. Although preliminary, these results indicate that treatment-resistant MDD subjects showed decreased metabolism in the right habenula and the extended medial and orbital prefrontal networks in association with rapid antidepressant response to ketamine. Conversely, metabolism increased in sensory association cortices, conceivably related to the illusory phenomena sometimes experienced with ketamine. Further studies are needed to elucidate how these functional anatomical changes relate to the molecular mechanisms underlying ketamine's rapid antidepressant effects.
Objective: Suicidal ideation is a medical emergency, especially when severe. Little research has ... more Objective: Suicidal ideation is a medical emergency, especially when severe. Little research has been done on pharmacologic interventions that could address this problem. Ketamine, an N-methyl-D-aspartate antagonist, has been reported to have antidepressant effects within ...
Mood disorders such as bipolar disorder and major depressive disorder are common, chronic, and re... more Mood disorders such as bipolar disorder and major depressive disorder are common, chronic, and recurrent conditions affecting millions of individuals worldwide. Existing antidepressants and mood stabilizers used to treat these disorders are insufficient for many. Patients ...
There have been no recent advances in drug development for mood disorders in terms of identifying... more There have been no recent advances in drug development for mood disorders in terms of identifying drug targets that are mechanistically distinct from existing ones. As a result, existing antidepressants are based on decades-old notions of which targets are relevant to the mechanisms of ...
Existing pharmacological treatments for bipolar disorder (BPD) and major depressive disorder (MDD... more Existing pharmacological treatments for bipolar disorder (BPD) and major depressive disorder (MDD) are often insufficient for many patients. Here we describe a number of targets/compounds that clinical and preclinical studies suggest could result in putative novel treatments for mood disorders. These include: (1) glycogen synthase kinase-3 (GSK-3) and protein kinase C (PKC), (2) the purinergic system, (3) histone deacetylases (HDACs), (4) the melatonergic system, (5) the tachykinin neuropeptides system, (6) the glutamatergic system, and (7) oxidative stress and bioenergetics. The paper reviews data on new compounds that have shown antimanic or antidepressant effects in subjects with mood disorders, or similar effects in preclinical animal models. Overall, an improved understanding of the neurobiological underpinnings of mood disorders is critical in order to develop targeted treatments that are more effective, act more rapidly, and are better tolerated than currently available therapies.
Leaching and solvent extraction of total iron and titanium has been studied. A detailed investiga... more Leaching and solvent extraction of total iron and titanium has been studied. A detailed investigation on quantitative leaching of the mineral and separation by solvent extraction were also carried out. The effect of some parameters such as acid concentrations and temperature has been investigated. Experimental results indicate that the dissolution rate is by diffusion control. With 2.0 M HCl solution, about 85.4% of the ore was dissolved within 120 min. using solid: liquid ratio of 10g/L at optimal conditions.
Higher order feedback projections to sensory cortical areas converge on layer 1 (L1), the primary... more Higher order feedback projections to sensory cortical areas converge on layer 1 (L1), the primary site for integration of top-down information via the apical dendrites of pyramidal neurons and L1 GABAergic interneurons. Here, we investigated the contribution of early thalamic inputs onto L1 interneurons for the establishment of top-down inputs in the primary visual cortex. We find that bottom-up thalamic inputs predominate during early L1 development and preferentially target neurogliaform cells. We find that these projections are critical for the subsequent strengthening of feedback inputs from the anterior cingulate cortex. Enucleation or selective removal of thalamic afferents blocked this phenomenon. Notably, while early activation of anterior cingulate afferents resulted in a premature strengthening of these top-down inputs to neurogliaform cells, this was also dependent on thalamic inputs. Our results demonstrate that the proper establishment of top-down feedback inputs critic...
Journal of embryology and experimental morphology, 1975
The growth of hair from the mystacial vibrissal follicles of C3H mice and Wistar rats has been me... more The growth of hair from the mystacial vibrissal follicles of C3H mice and Wistar rats has been measured for up to seven cycles. Normally growth in length and thickness was regular and little affected by age or sex. Plucking vibrissae at any stage during the growing period was followed by the appearance of a new vibrissa 8-11 days later. Plucking when growth had ceased had no effect on the time of appearance of the subsequent cycle. New whiskers emerging after plucking grew at the normal rate. Withholding food slowed the growth of vibrissae within 1 day. Normal growth was re-established 3 days after return to full diet.
Journal of embryology and experimental morphology, 1982
SUMMARY The volumes of the dermal papilla, matrix and fully grown hair of vibrissal follicles of ... more SUMMARY The volumes of the dermal papilla, matrix and fully grown hair of vibrissal follicles of rats and mice were measured. Dermal papillae were surgically removed from rats' vibrissal follicles and a small new dermal papilla was always reformed. The lower third of rats and mice follicles, containing the whole of the dermal papilla was amputated and very small dermal papillae were reformed. Follicles containing small dermal papillae produced small hairs and a constant positive linear relationship of 7-0 was found between the volume of the dermal papilla and the volume of the full-grown hair for all cases studied.
Background. Deregulation of the Wnt signaling pathway had a role in haematological malignancies. ... more Background. Deregulation of the Wnt signaling pathway had a role in haematological malignancies. Previous studies reported that lymphoid enhancer factor 1 (LEF1) expression and serum Galectin-3 level could affect clinical parameters and outcome in acute myeloid leukemia patients, but as far as we know, no study has addressed their combined effect on AML patients. Aim. We studied the expression of LEF1 by real-time qPCR and measured serum level of Gal.3 by ELISA technique in peripheral blood of 69 AML patients and correlated it with different clinicopathological criteria of patients, response, PFS and OS. Results. We found high expression (LEF1high) was associated with better OS (p=0.02) and EFS (p=0.019) compared to LEF1low, low serum Gal.3 level had better OS (p=0.014) and EFS (p=0.02) compared to high serum Gal.3 level. LEF1high less likely to carry a FLT3-ITD (p=0.047) compared to LEF1low patient, also LEF1high characterized by favorable risk (p=0.02) than LEF1low patients. While...
Recent success in identifying gene regulatory elements in the context of recombinant adeno-associ... more Recent success in identifying gene regulatory elements in the context of recombinant adeno-associated virus vectors have enabled cell type-restricted gene expression. However, within the cerebral cortex these tools are presently limited to broad classes of neurons. To overcome this limitation, we developed a strategy that led to the identification of multiple novel enhancers to target functionally distinct neuronal subtypes. By investigating the regulatory landscape of the disease gene Scn1a, we identified enhancers that target the breadth of its expression, including two selective for parvalbumin and vasoactive intestinal peptide cortical interneurons. Demonstrating the functional utility of these elements, we found that the PV-specific enhancer allowed for the selective targeting and manipulation of fast-spiking cortical interneurons across species, from mice to humans.
Multiple lines of evidence support a role for the glutamatergic system in the pathophysiology of ... more Multiple lines of evidence support a role for the glutamatergic system in the pathophysiology of major depressive disorder (MDD). Ketamine, an N-methyl-D-aspartate antagonist, rapidly improves depressive symptoms in individuals with treatment-resistant depression. The neural mechanisms underlying this effect remain unknown. In this preliminary study, 20 unmedicated participants with treatment-resistant MDD underwent positron emission tomography to measure regional cerebral glucose metabolism at baseline and following ketamine infusion (single dose of .5mg/kg intravenous over 40minutes). Metabolic data were compared between conditions using a combination of region-of-interest and voxelwise analyses, and differences were correlated with the associated antidepressant response. Whole-brain metabolism did not change significantly following ketamine. Regional metabolism decreased significantly under ketamine in the habenula, insula, and ventrolateral and dorsolateral prefrontal cortices of the right hemisphere. Metabolism increased postketamine in bilateral occipital, right sensorimotor, left parahippocampal, and left inferior parietal cortices. Improvement in depression ratings correlated directly with change in metabolism in right superior and middle temporal gyri. Conversely, clinical improvement correlated inversely with metabolic changes in right parahippocampal gyrus and temporoparietal cortex. Although preliminary, these results indicate that treatment-resistant MDD subjects showed decreased metabolism in the right habenula and the extended medial and orbital prefrontal networks in association with rapid antidepressant response to ketamine. Conversely, metabolism increased in sensory association cortices, conceivably related to the illusory phenomena sometimes experienced with ketamine. Further studies are needed to elucidate how these functional anatomical changes relate to the molecular mechanisms underlying ketamine's rapid antidepressant effects.
Objective: Suicidal ideation is a medical emergency, especially when severe. Little research has ... more Objective: Suicidal ideation is a medical emergency, especially when severe. Little research has been done on pharmacologic interventions that could address this problem. Ketamine, an N-methyl-D-aspartate antagonist, has been reported to have antidepressant effects within ...
Mood disorders such as bipolar disorder and major depressive disorder are common, chronic, and re... more Mood disorders such as bipolar disorder and major depressive disorder are common, chronic, and recurrent conditions affecting millions of individuals worldwide. Existing antidepressants and mood stabilizers used to treat these disorders are insufficient for many. Patients ...
There have been no recent advances in drug development for mood disorders in terms of identifying... more There have been no recent advances in drug development for mood disorders in terms of identifying drug targets that are mechanistically distinct from existing ones. As a result, existing antidepressants are based on decades-old notions of which targets are relevant to the mechanisms of ...
Existing pharmacological treatments for bipolar disorder (BPD) and major depressive disorder (MDD... more Existing pharmacological treatments for bipolar disorder (BPD) and major depressive disorder (MDD) are often insufficient for many patients. Here we describe a number of targets/compounds that clinical and preclinical studies suggest could result in putative novel treatments for mood disorders. These include: (1) glycogen synthase kinase-3 (GSK-3) and protein kinase C (PKC), (2) the purinergic system, (3) histone deacetylases (HDACs), (4) the melatonergic system, (5) the tachykinin neuropeptides system, (6) the glutamatergic system, and (7) oxidative stress and bioenergetics. The paper reviews data on new compounds that have shown antimanic or antidepressant effects in subjects with mood disorders, or similar effects in preclinical animal models. Overall, an improved understanding of the neurobiological underpinnings of mood disorders is critical in order to develop targeted treatments that are more effective, act more rapidly, and are better tolerated than currently available therapies.
Leaching and solvent extraction of total iron and titanium has been studied. A detailed investiga... more Leaching and solvent extraction of total iron and titanium has been studied. A detailed investigation on quantitative leaching of the mineral and separation by solvent extraction were also carried out. The effect of some parameters such as acid concentrations and temperature has been investigated. Experimental results indicate that the dissolution rate is by diffusion control. With 2.0 M HCl solution, about 85.4% of the ore was dissolved within 120 min. using solid: liquid ratio of 10g/L at optimal conditions.
Higher order feedback projections to sensory cortical areas converge on layer 1 (L1), the primary... more Higher order feedback projections to sensory cortical areas converge on layer 1 (L1), the primary site for integration of top-down information via the apical dendrites of pyramidal neurons and L1 GABAergic interneurons. Here, we investigated the contribution of early thalamic inputs onto L1 interneurons for the establishment of top-down inputs in the primary visual cortex. We find that bottom-up thalamic inputs predominate during early L1 development and preferentially target neurogliaform cells. We find that these projections are critical for the subsequent strengthening of feedback inputs from the anterior cingulate cortex. Enucleation or selective removal of thalamic afferents blocked this phenomenon. Notably, while early activation of anterior cingulate afferents resulted in a premature strengthening of these top-down inputs to neurogliaform cells, this was also dependent on thalamic inputs. Our results demonstrate that the proper establishment of top-down feedback inputs critic...
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