Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2009
Patients infected with human immunodeficiency virus (HIV) have a higher risk of developing major ... more Patients infected with human immunodeficiency virus (HIV) have a higher risk of developing major depressive disorder (MDD) than the general population. Immunophilins FKBP51 and FKBP52 are expressed in cortical neurons and regulate the function of the glucocorticoid receptor (GR). Previous reports have shown that genetic variants in the FKBP5 gene encoding FKBP51 are linked to psychiatric disorders. We sought to determine whether immunophilins are upregulated in HIV infection. To determine whether FKBP52 and FKBP51 are associated with MDD and/or HIV, we compared protein and gene expression in autopsy tissues from the frontal cortical gray matter. The study cases were divided into five groups: control, MDD, MDD with psychosis, HIV(+), and HIV(+) with MDD. Gene expression and protein levels were determined by real-time PCR and Western blot analysis of fresh frozen tissues. Genotyping of previously published alleles of the FKBP5 gene was also performed. We found correlation of upregulat...
... co.uk/lnw New mechanisms of neurodegeneration in HIV encephalitis: microglial associated neur... more ... co.uk/lnw New mechanisms of neurodegeneration in HIV encephalitis: microglial associated neurotrophic dysfunction CL Achim, Wanda Wang, RW Dorsey, CA Wiley and Virawudh Soontornniyomkij University of Pittsburgh ...
The pentanuclear, cyanide-bridged metal clusters with the general formula [M(tmphen)2]3[M'(CN... more The pentanuclear, cyanide-bridged metal clusters with the general formula [M(tmphen)2]3[M'(CN)6]2 (tmphen = 3, 4, 7, 8-tetramethyl-1, 10-phenanthroline) have a core with trigonal bipyramidal geometry with equatorial [M(tmphen)2(CN)2] and axial [M'(CN)6] ions and contain M-CN-M' or M-NC-M' units, depending on the relative preference of the M and M' ions for the C or N terminus of the cyanide bridge. Spin-crossover behavior
Journal of neuropathology and experimental neurology, 2003
Cellular mechanisms implicated in Parkinson disease (PD) include oxidative stress, inflammatory r... more Cellular mechanisms implicated in Parkinson disease (PD) include oxidative stress, inflammatory response, excess dopamine, DNA damage, and loss of trophic support. These stimuli have been observed to induce changes in cell cycle proteins in several cell types. One of the key regulators of cell cycle progression is the retinoblastoma protein (pRb); therefore, we assessed the staining for pRb and its inactive hyperphosphorylated isoform, ppRb, in autopsy tissue from patients with PD. In PD we found abundant pRb staining in neuronal cytoplasm of the substantia nigra, mid-frontal cortex, and hippocampus by immunohistochemistry. In controls, pRb weakly stained nucleoli of neurons in the substantia nigra and exhibited no detectable staining in mid-frontal cortex and hippocampus. Staining for ppRb resulted in a shift from weak cytoplasmic staining in neurons from control cases to strong nuclear staining in PD cases, especially within the substantia nigra, mid-frontal cortex, and hippocampu...
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 1998
This study investigated the sources of quinolinic acid, a neurotoxic tryptophan-kynurenine pathwa... more This study investigated the sources of quinolinic acid, a neurotoxic tryptophan-kynurenine pathway metabolite, in the brain and blood of HIV-infected patients and retrovirus-infected macaques. In brain, quinolinic acid concentrations in HIV-infected patients were elevated by > 300-fold to concentrations that exceeded cerebrospinal fluid (CSF) by 8.9-fold. There were no significant correlations between elevated serum quinolinic acid levels with those in CSF and brain parenchyma. Because nonretrovirus-induced encephalitis confounds the interpretation of human postmortem data, rhesus macaques infected with retrovirus were used to examine the mechanisms of increased quinolinic acid accumulations and determine the relationships of quinolinic acid to encephalitits and systemic responses. The largest kynurenine pathway responses in brain were associated with encephalitis and were independent of systemic responses. CSF quinolinic acid levels were also elevated in all infected macaques, b...
In the neurodevelopmental disorder autism, several neuroimmune abnormalities have been reported. ... more In the neurodevelopmental disorder autism, several neuroimmune abnormalities have been reported. However, it is unknown whether microglial somal volume or density are altered in the cortex and whether any alteration is associated with age or other potential covariates. Microglia in sections from the dorsolateral prefrontal cortex of nonmacrencephalic male cases with autism (n = 13) and control cases (n = 9) were visualized via ionized calcium binding adapter molecule 1 immunohistochemistry. In addition to a neuropathological assessment, microglial cell density was stereologically estimated via optical fractionator and average somal volume was quantified via isotropic nucleator. Microglia appeared markedly activated in 5 of 13 cases with autism, including 2 of 3 under age 6, and marginally activated in an additional 4 of 13 cases. Morphological alterations included somal enlargement, process retraction and thickening, and extension of filopodia from processes. Average microglial soma...
Neuronal damage and dementia are common sequelae of HIV encephalitis. The mechanism by which HIV ... more Neuronal damage and dementia are common sequelae of HIV encephalitis. The mechanism by which HIV infec- tion of CNS macrophages results in neuronal damage is not known. We examined the brains from 15 AIDS autopsies (8 with HIV encephalitis and 7 without) and 4 non-infected control autopsies for the presence of DNA strand breaks, for associated changes in the expression
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2009
Patients infected with human immunodeficiency virus (HIV) have a higher risk of developing major ... more Patients infected with human immunodeficiency virus (HIV) have a higher risk of developing major depressive disorder (MDD) than the general population. Immunophilins FKBP51 and FKBP52 are expressed in cortical neurons and regulate the function of the glucocorticoid receptor (GR). Previous reports have shown that genetic variants in the FKBP5 gene encoding FKBP51 are linked to psychiatric disorders. We sought to determine whether immunophilins are upregulated in HIV infection. To determine whether FKBP52 and FKBP51 are associated with MDD and/or HIV, we compared protein and gene expression in autopsy tissues from the frontal cortical gray matter. The study cases were divided into five groups: control, MDD, MDD with psychosis, HIV(+), and HIV(+) with MDD. Gene expression and protein levels were determined by real-time PCR and Western blot analysis of fresh frozen tissues. Genotyping of previously published alleles of the FKBP5 gene was also performed. We found correlation of upregulat...
... co.uk/lnw New mechanisms of neurodegeneration in HIV encephalitis: microglial associated neur... more ... co.uk/lnw New mechanisms of neurodegeneration in HIV encephalitis: microglial associated neurotrophic dysfunction CL Achim, Wanda Wang, RW Dorsey, CA Wiley and Virawudh Soontornniyomkij University of Pittsburgh ...
The pentanuclear, cyanide-bridged metal clusters with the general formula [M(tmphen)2]3[M'(CN... more The pentanuclear, cyanide-bridged metal clusters with the general formula [M(tmphen)2]3[M'(CN)6]2 (tmphen = 3, 4, 7, 8-tetramethyl-1, 10-phenanthroline) have a core with trigonal bipyramidal geometry with equatorial [M(tmphen)2(CN)2] and axial [M'(CN)6] ions and contain M-CN-M' or M-NC-M' units, depending on the relative preference of the M and M' ions for the C or N terminus of the cyanide bridge. Spin-crossover behavior
Journal of neuropathology and experimental neurology, 2003
Cellular mechanisms implicated in Parkinson disease (PD) include oxidative stress, inflammatory r... more Cellular mechanisms implicated in Parkinson disease (PD) include oxidative stress, inflammatory response, excess dopamine, DNA damage, and loss of trophic support. These stimuli have been observed to induce changes in cell cycle proteins in several cell types. One of the key regulators of cell cycle progression is the retinoblastoma protein (pRb); therefore, we assessed the staining for pRb and its inactive hyperphosphorylated isoform, ppRb, in autopsy tissue from patients with PD. In PD we found abundant pRb staining in neuronal cytoplasm of the substantia nigra, mid-frontal cortex, and hippocampus by immunohistochemistry. In controls, pRb weakly stained nucleoli of neurons in the substantia nigra and exhibited no detectable staining in mid-frontal cortex and hippocampus. Staining for ppRb resulted in a shift from weak cytoplasmic staining in neurons from control cases to strong nuclear staining in PD cases, especially within the substantia nigra, mid-frontal cortex, and hippocampu...
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 1998
This study investigated the sources of quinolinic acid, a neurotoxic tryptophan-kynurenine pathwa... more This study investigated the sources of quinolinic acid, a neurotoxic tryptophan-kynurenine pathway metabolite, in the brain and blood of HIV-infected patients and retrovirus-infected macaques. In brain, quinolinic acid concentrations in HIV-infected patients were elevated by > 300-fold to concentrations that exceeded cerebrospinal fluid (CSF) by 8.9-fold. There were no significant correlations between elevated serum quinolinic acid levels with those in CSF and brain parenchyma. Because nonretrovirus-induced encephalitis confounds the interpretation of human postmortem data, rhesus macaques infected with retrovirus were used to examine the mechanisms of increased quinolinic acid accumulations and determine the relationships of quinolinic acid to encephalitits and systemic responses. The largest kynurenine pathway responses in brain were associated with encephalitis and were independent of systemic responses. CSF quinolinic acid levels were also elevated in all infected macaques, b...
In the neurodevelopmental disorder autism, several neuroimmune abnormalities have been reported. ... more In the neurodevelopmental disorder autism, several neuroimmune abnormalities have been reported. However, it is unknown whether microglial somal volume or density are altered in the cortex and whether any alteration is associated with age or other potential covariates. Microglia in sections from the dorsolateral prefrontal cortex of nonmacrencephalic male cases with autism (n = 13) and control cases (n = 9) were visualized via ionized calcium binding adapter molecule 1 immunohistochemistry. In addition to a neuropathological assessment, microglial cell density was stereologically estimated via optical fractionator and average somal volume was quantified via isotropic nucleator. Microglia appeared markedly activated in 5 of 13 cases with autism, including 2 of 3 under age 6, and marginally activated in an additional 4 of 13 cases. Morphological alterations included somal enlargement, process retraction and thickening, and extension of filopodia from processes. Average microglial soma...
Neuronal damage and dementia are common sequelae of HIV encephalitis. The mechanism by which HIV ... more Neuronal damage and dementia are common sequelae of HIV encephalitis. The mechanism by which HIV infec- tion of CNS macrophages results in neuronal damage is not known. We examined the brains from 15 AIDS autopsies (8 with HIV encephalitis and 7 without) and 4 non-infected control autopsies for the presence of DNA strand breaks, for associated changes in the expression
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Papers by Cristian Achim