Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Depo-Provera (medroxyprogesterone acetate), a long-acting derivative of progesterone, is utilized during many nonhuman primate microbicide studies to facilitate simian immunodeficiency virus (SIV) infection by thinning the vaginal epithelium. To date, the systemic effects of this steroid hormone in regard to SIV/HIV pathogenesis are not well understood, but an increase in infection rates and lymphoproliferation following progesterone application has been reported. Therefore, a proactive study using 20 Chinese rhesus macaques was designed to investigate the effect of a single Depo-Provera injection on SIV disease progression. Group 1 (n = 10) was treated with 30 mg Depo-Provera intramuscularly 30 days prior to intravenous challenge with 50 TCID(50) SIVmac251, while Group 2 (n = 10) remained untreated, but received the same amount of SIV. Blood samples were taken at predetermined intervals to measure RNA viral loads, CD4(+), CD8(+), and CD20(+) lymphocyte counts and percentages and absolute numbers of naive and memory T lymphocytes. Upon statistical endpoint data analysis, none of the parameters measured were shown to be significantly different between the groups. One animal in the Depo-Provera-treated group and two macaques in the control group were euthanized prior to study end due to the development of clinical signs (in weeks 43 and 51, respectively). All other animals were euthanized between weeks 68 and 71 post-SIV infection. Histopathological evaluations revealed that 5 of 10 animals in each group had developed simian AIDS (SAIDS). In summary, this prospective study demonstrated that a single injection of 30 mg Depo-Provera did not have a significant influence on SIV disease progression.
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PMID:Depo-Provera does not alter disease progression in SIVmac-infected female Chinese rhesus macaques. 2037 24

High levels of human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells (PBMCs), and specifically within CD14+ blood monocytes, have been found in HIV-infected individuals with neurocognitive impairment and dementia. The failure of highly active antiretroviral therapy (HAART) to eliminate cognitive dysfunction in HIV may be secondary to persistence of HIV-infected PBMCs which cross the blood-brain barrier, leading to perivascular inflammation and neuronal injury. This study assessed brain cortical thickness relative to HIV DNA levels and identified, we believe for the first time, a neuroimaging correlate of detectable PBMC HIV DNA in subjects with undetectable HIV RNA. Cortical thickness was compared between age- and education-matched groups of older (>40 years) HIV-seropositive subjects on HAART who had detectable (N = 9) and undetectable (N = 10) PBMC HIV DNA. Statistical testing revealed highly significant (P < 0.001) cortical thinning associated with detectable HIV DNA. The largest regions affected were in bilateral insula, orbitofrontal and temporal cortices, right superior frontal cortex, and right caudal anterior cingulate. Cortical thinning correlated significantly with a measure of psychomotor speed. The areas of reduced cortical thickness are key nodes in cognitive and emotional processing networks and may be etiologically important in HIV-related neurological deficits.
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PMID:Regional cortical thinning associated with detectable levels of HIV DNA. 2201 79

TAT peptide is one of the best-characterized cell penetrating peptides derived from the transactivator of transcription protein from the human immunodeficiency virus 1. The aim of this study was to investigate the interaction between TAT peptide and partially negatively-charged phospholipid bilayer by using lamellar neutron diffraction. The main findings are the existence of a contiguous water channel across the bilayer in the presence of TAT peptide. Taken in combination with other observations, including thinning of the lipid bilayer, this unambiguously locates the peptide within the lipid bilayer. The interaction of TAT peptide with anionic lipid bilayer, composed of an 80:20 mixture of DOPC and DOPS, takes place at two locations. One is in the peripheral aqueous phase between adjacent bilayers and the second is below the glycerol backbone region of bilayer. A membrane thinning above a peptide concentration threshold (1mol%) was found, as was a contiguous transbilayer water channel at the highest peptide concentration (10mol%). This evidence leads to the suggestion that the toroidal pore model might be involved in the transmembrane of TAT peptide. We interpret the surface peptide distribution in the peripheral aqueous phase to be a massive exclusion of TAT peptide from its intrinsic location below the glycerol backbone region of the bilayer, due to the electrostatic attraction between the negatively-charged headgroups of phospholipids and the positively charged TAT peptides. Finally, we propose that the role that negatively-charged headgroups of DOPS lipids play in the transmembrane of TAT peptide is less important than previously thought.
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PMID:Insertion of TAT peptide and perturbation of negatively charged model phospholipid bilayer revealed by neutron diffraction. 2364 91

Thickening of the corpus callosum is an important feature of development, whereas thinning of the corpus callosum can be the result of a number of diseases that affect development or cause destruction of the corpus callosum. Corpus callosum thickness reflects the volume of the hemispheres and responds to changes through direct effects or through Wallerian degeneration. It is therefore not only important to evaluate the morphology of the corpus callosum for congenital anomalies but also to evaluate the thickness of specific components or the whole corpus callosum in association with other findings. The goal of this pictorial review is raise awareness that the thickness of the corpus callosum can be a useful feature of pathology in pediatric central nervous system disease and must be considered in the context of the stage of development of a child. Thinning of the corpus callosum can be primary or secondary, and generalized or focal. Primary thinning is caused by abnormal or failed myelination related to the hypomyelinating leukoencephalopathies, metabolic disorders affecting white matter, and microcephaly. Secondary thinning of the corpus callosum can be caused by diffuse injury such as hypoxic-ischemic encephalopathy, human immunodeficiency virus (HIV) encephalopathy, hydrocephalus, dysmyelinating conditions and demyelinating conditions. Focal disturbance of formation or focal injury also causes localized thinning, e.g., callosal dysgenesis, metabolic disorders with localized effects, hypoglycemia, white matter injury of prematurity, HIV-related atrophy, infarction and vasculitis, trauma and toxins. The corpus callosum might be too thick because of a primary disorder in which the corpus callosum finding is essential to diagnosis; abnormal thickening can also be secondary to inflammation, infection and trauma.
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PMID:Corpus callosum thickness in children: an MR pattern-recognition approach on the midsagittal image. 2517 5

Currently, whether hormonal contraceptives affect male to female human immunodeficiency virus (HIV) transmission is being debated. In this study, we investigated whether the use of progesterone-based intrauterine devices (pIUDs) is associated with a thinning effect on the ectocervical squamous epithelium, down-regulation of epithelial junction proteins, and/or alteration of HIV target cell distribution in the human ectocervix. Ectocervical tissue biopsies from healthy premenopausal volunteers using pIUDs were collected and compared to biopsies obtained from two control groups, namely women using combined oral contraceptives (COCs) or who do not use hormonal contraceptives. In situ staining and image analysis were used to measure epithelial thickness and the presence of HIV receptors in tissue biopsies. Messenger RNA levels of epithelial junction markers were measured by quantitative PCR. The epithelial thickness displayed by women in the pIUD group was similar to those in the COC group, but significantly thinner as compared to women in the no hormonal contraceptive group. The thinner epithelial layer of the pIUD group was specific to the apical layer of the ectocervix. Furthermore, the pIUD group expressed significantly lower levels of the tight junction marker ZO-1 within the epithelium as compared to the COC group. Similar expression levels of HIV receptors and coreceptors CD4, CCR5, DC-SIGN, and Langerin were observed in the three study groups. Thus, women using pIUD displayed a thinner apical layer of the ectocervical epithelium and reduced ZO-1 expression as compared to control groups. These data suggest that pIUD use may weaken the ectocervical epithelial barrier against invading pathogens, including HIV.
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PMID:Progesterone-based intrauterine device use is associated with a thinner apical layer of the human ectocervical epithelium and a lower ZO-1 mRNA expression. 2558 10

Spinal muscular atrophy (SMA) has long been solely considered a neurodegenerative disorder. However, recent work has highlighted defects in many other cell types that could contribute to disease aetiology. Interestingly, the immune system has never been extensively studied in SMA. Defects in lymphoid organs could exacerbate disease progression by neuroinflammation or immunodeficiency. Smn depletion led to severe alterations in the thymus and spleen of two different mouse models of SMA. The spleen from Smn depleted mice was dramatically smaller at a very young age and its histological architecture was marked by mislocalization of immune cells in the Smn2B/- model mice. In comparison, the thymus was relatively spared in gross morphology but showed many histological alterations including cortex thinning in both mouse models at symptomatic ages. Thymocyte development was also impaired as evidenced by abnormal population frequencies in the Smn2B/- thymus. Cytokine profiling revealed major changes in different tissues of both mouse models. Consistent with our observations, we found that survival motor neuron (Smn) protein levels were relatively high in lymphoid organs compared to skeletal muscle and spinal cord during postnatal development in wild type mice. Genetic introduction of one copy of the human SMN2 transgene was enough to rescue splenic and thymic defects in Smn2B/- mice. Thus, Smn is required for the normal development of lymphoid organs, and altered immune function may contribute to SMA disease pathogenesis.
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PMID:Immune dysregulation may contribute to disease pathogenesis in spinal muscular atrophy mice. 2810 55

Enamel mineralization relies on Ca2+ availability provided by Ca2+ release activated Ca2+ (CRAC) channels. CRAC channels are modulated by the endoplasmic reticulum Ca2+ sensor STIM1 which gates the pore subunit of the channel known as ORAI1, found the in plasma membrane, to enable sustained Ca2+ influx. Mutations in the STIM1 and ORAI1 genes result in CRAC channelopathy, an ensemble of diseases including immunodeficiency, muscular hypotonia, ectodermal dysplasia with defects in sweat gland function and abnormal enamel mineralization similar to amelogenesis imperfecta (AI). In some reports, the chief medical complain has been the patient's dental health, highlighting the direct and important link between CRAC channels and enamel. The reported enamel defects are apparent in both the deciduous and in permanent teeth and often require extensive dental treatment to provide the patient with a functional dentition. Among the dental phenotypes observed in the patients, discoloration, increased wear, hypoplasias (thinning of enamel) and chipping has been reported. These findings are not universal in all patients. Here we review the mutations in STIM1 and ORAI1 causing AI-like phenotype, and evaluate the enamel defects in CRAC channel deficient mice. We also provide a brief overview of the role of CRAC channels in other mineralizing systems such as dentine and bone.
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PMID:CRAC channels in dental enamel cells. 3011 31

Purpose: The aim of this study was to investigate how human immunodeficiency virus (HIV) affects brain development in adolescents, what are susceptible brain regions, and how these brain structural changes correlate with cognitive abilities. Methods: We used structural magnetic resonance imaging to examine gray matter volume and cortical thickness in 16 HIV-infected children (mean age = 13.63 years) and 25 HIV-exposed uninfected children (mean age = 13.32 years), 12 of them were subjected to a 1-year repetitive magnetic resonance scan of the brain. Five neurocognitive tests were performed on each subject to assess cognitive performance in different areas. Results: Cross-sectional studies showed that the gray matter volume of HIV-infected children was widely reduced (mainly in the bilateral frontal, temporal, and insular regions, and cerebellum). The changes in cortical thickness were mainly due to thinning of the right temporal lobe and thickening of the left occipital lobe. Longitudinal studies showed that the gray matter volume reduction of HIV-infected children after 1 year mainly occurs in the advanced functional area of the right prefrontal, parietal lobe and the motor area, cortical thinning of brain regions were sensorimotor cortex and the limbic system. The gray matter volume of the bilateral cerebellum was positively correlated with the performance of the Wisconsin Card Sorting Test, while the cortical thickness of the right dorsolateral prefrontal cortex was negatively correlated with this test. Conclusion: This study found that HIV-infected pubertal children showed a delayed cortical maturation with atrophy. This abnormal pattern of cortical development may be the structural basis for cognitive impairment in HIV-infected children.
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PMID:Neuroanatomical Changes Underlying Vertical HIV Infection in Adolescents. 3111 Apr 99

Purpose: Overview of the evolving epidemiology of human immunodeficiency virus (HIV)-related ocular disease over time. Method: Narrative review. Results: HIV enhances susceptibility to opportunistic eye infections, has direct pathogenic effects, and places patients at risk of immune recovery inflammatory syndromes in previously infected eyes after starting highly-active antiretroviral therapy (HAART). Widespread availability of HAART has resulted in a decrease of infectious ocular conditions such as cytomegalovirus retinitis, toxoplasmic retinitis, squamous cell carcinoma of the conjunctiva, and microvascular retinopathy. However, large coexisting burdens of tuberculosis, herpesvirus infection and syphilis (among others) continue to contribute to the burden of ocular disease, especially in low-resource settings. Growing risks of cataract, retinopathy and retinal nerve fiber thinning can affect patients with chronic HIV on HAART; thought due to chronic inflammation and immune activation. Conclusion: The changing epidemic of ocular disease in HIV-infected patients warrants close monitoring and identification of interventions that can help reduce the imminent burden of disease.
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PMID:The Changing Global Epidemic of HIV and Ocular Disease. 3239 27


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