Thyroid hormones play crucial roles in normal neurodevelopment of fetus and child. Many chemicals can affect control and homeostasis of thyroid hormones, and eventually lead to various adverse health effects including neurodevelopmental disorders. Perfluoroalkyl substances (PFASs) are among the thyroid disrupting chemicals that can be encountered among general human population. Due to their unique physicochemical characteristics, PFASs have been used as surfactants and surface coating materials in many applications. Therefore, PFASs have been frequently detected in humans and environment worldwide. In cross-sectional studies using nationally representative general human populations of United States, several PFASs have shown significant associations with thyroid hormones. Moreover, among pregnant women and their infants, not only major PFASs such as perfluorooctane sulfonic acid and perfluorooctanoic acid, but also those with shorter or longer carbon chains showed significant associations with thyroid hormones. Often demographic characteristics such as sex, age, and disease status appear to influence the associations between PFASs exposure and thyroid hormones. In general, major PFASs showed hypothyroidism effects among pregnant women and infants. As 8 carbon based PFASs have been phased out, those with shorter or longer carbon chains have been used in growing amount as replacement. However, only limited information is available for their occurrences and toxicity among humans. Further investigations on these substituting PFASs are required. In addition, efforts are warranted to identify sources of and mitigate exposure to these thyroid disrupting chemicals especially during pregnancy and early stages of life.
Carbon ; Child ; Cross-Sectional Studies ; Environmental Monitoring ; Female ; Fetus ; Homeostasis ; Humans* ; Hypothyroidism ; Infant ; Neurodevelopmental Disorders ; Pregnancy ; Pregnant Women ; Surface-Active Agents ; Thyroid Gland* ; Thyroid Hormones* ; United States

Inflammatory skin diseases such as atopic dermatitis (AD) and rosacea were complicated by barrier abrogation and deficiency in innate immunity. The first defender of epidermal innate immune response is the antimicrobial peptides (AMPs) that exhibit a broad-spectrum antimicrobial activity against multiple pathogens, including Gram-positive and Gram-negative bacteria, viruses, and fungi. The deficiency of these AMPs in the skin of AD fails to protect our body against virulent pathogen infections. In contrast to AD where there is a suppression of AMPs, rosacea is characterized by overexpression of cathelicidin antimicrobial peptide (CAMP), the products of which result in chronic epidermal inflammation. In this regard, AMP generation that is controlled by a key ceramide metabolite S1P-dependent mechanism could be considered as alternate therapeutic approaches to treat these skin disorders, i.e., Increased S1P levels strongly stimulated the CAMP expression which elevated the antimicrobial activity against multiple pathogens resulting the improved AD patient skin.
Dermatitis, Atopic* ; Endoplasmic Reticulum Stress ; Fungi ; Gram-Negative Bacteria ; Humans ; Immunity, Innate ; Inflammation ; Peptides* ; Rosacea ; Skin ; Skin Diseases ; Sphingolipids*

BACKGROUND: Recently, the molecular pathologic investigation for clonality in lymphomas has been introduced and has gained a role in the diagnosis of lymphomas. In fact, the clonality test using TCRGR phenomenon has been done by Southern blot analysis (SBA) and polymerase chain reaction (PCR) for molecular pathologic diagnosis of T cell lymphomas. However, it is difficult to perform SBA with paraffin embedded specimens or with samples of small skin biopsies. OBJECTIVE: We investigated the efficacy of PCR amplification of TCR gene in paraffin em-bedded cutaneous T cell lymphomas. METHODS: Iii this study, the clonality was assessed by polymerase chain reaction (PCR) analysis of T cell receptor gamma (TCR) gene from the DNA extracts obtained from paraffin em-bedded tissues (PET) of malignant T cells, B cell lymphomas, and benign cutaneous T cell proliferative disorders. Heteroduple-x-analyses were also performed to rule out the false positives. RESULTS: Among the total of 62 cases analyzed, monoclonality was observed in 4 out of 10 mycosis fungoides, 7 out of 9 cutaneous T cell lymphomas excluding mycosis fungoides, 1 out of 3 angiocentric lymphomas, 2 out of 2 lymphomatosis papulosis, 1 out of 7 large plaque parapsoriasis, and 1 out of 2 T cell lymphomas in other organs. No monoclonality was observed in 9 inflammatory cutaneous diseases, 5 small plaque parapsoriasis, 4 cutaneous B cell lymphomas, and 11 B cell lymphomas in lymph nodes. CONCLUSION: The results suggest that the PCR method and heteroduplex analysis used in this study were not only practical but also efficacious for the diagnosis of cutaneous T cell lymphomas using tissues embedded in paraffins.
Biopsy ; Blotting, Southern ; Diagnosis ; DNA ; Gene Rearrangement* ; Genes, T-Cell Receptor ; Heteroduplex Analysis* ; Lymph Nodes ; Lymphoma ; Lymphoma, B-Cell ; Lymphoma, T-Cell ; Lymphoma, T-Cell, Cutaneous ; Mycosis Fungoides ; Paraffin ; Parapsoriasis ; Polymerase Chain Reaction* ; Receptors, Antigen, T-Cell* ; Skin ; T-Lymphocytes

This paper reviews the published literature that is concerned with color vision impairment from industrial and environmental exposure to neurotoxic substances, and we evaluated whether testing for color vision impairment could be an affordable procedure for assessing these neurotoxic effects. In general, most cases of congenital color vision impairment are red-green, and blue-yellow impairment is extremely rare. However, most of the acquired color vision impairment that is related to age, alcohol or environmental factors is blue-yellow impairment. Therefore, many studies have been performed to identify this relationship between exposure to neurotoxic substances, such as organic solvents and heavy metals, and the prevalence of blueyellow color vision impairment. The test for color vision impairment is known to be very sensitive to the early signs of nervous system dysfunction and this can be useful for making the early diagnosis of neurotoxic effects from exposure to very low concentrations of toxic substances.
*Color Perception Tests ; Color Vision Defects/*chemically induced/diagnosis ; Early Diagnosis ; Hazardous Substances/*toxicity ; Humans ; Neurotoxicity Syndromes/*diagnosis/pathology ; Solvents/adverse effects

PURPOSE: We aimed to investigate the gene expression of human gingival fibroblasts on microgroove surface using DNA microarray. MATERIALS AND METHODS: Microgrooves were applied on grade II titanium discs to have 0/0 µm (NE0, control group), 60/10 µm (E60/10, experimental group) of respective width/depth by photolithography. The entire surface of the microgrooved Ti substrata was further acid etched and used as the two experimental groups in this study. Human gingival fibroblasts were cultured in the experimental group and the control group, and total RNA was extracted. The oligonucleotide microarray was performed to confirm the changes of various gene expression levels between experimental group and control group. Changes of gene expression level were determined at the pathway level by mapping the expression results of DNA chips, using the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis. RESULTS: Gene expression levels on E60/10 and NE0 were analyzed, there were 123 genes showing significant differences in expression more than 1.5 times on E60/10 microgrooved surface compared to NE0 surface, and 19 genes showing significant differences in expression more than 2 times. The KEGG pathway analysis confirmed the changes in gene expression levels under experimental conditions. Cell signaling, proliferation, and activity among the various gene expression results were identified. CONCLUSION: Microgrooved surfaces induce gene expression changes and related cell signaling. According to the results of this study, microgrooves can be used as the surface of various biomaterials which need to improve cell activity through gene expression changes and activation of cell signaling.
Biocompatible Materials ; DNA* ; Fibroblasts* ; Gene Expression* ; Humans* ; Oligonucleotide Array Sequence Analysis* ; RNA ; Titanium

Estimation of biological profile for skeletal remains by forensic anthropological examination would be possible based on physical anthropological studies which were statistically analyzed. However, physical anthropological studies for Korean population are not enough to establish biological profile for Korean because there is lack of documented osteological specimens in Korea. Recent study suggested that physical anthropological examination could be possible on the three dimensional data which were reconstructed from computed tomography, instead of preparing skeletal specimen by defleshing bone. One of the aim of this study is to evaluate Digital Korean database which were composed of computed tomographic images of 100 cadavers. The other is to perform statistical analysis on morphometrics for segmented atlas whether the results could be helpful to estimate sex in Korean. We measured 100 segmentation atlases (male 51, female 49) from the Digital Korean database which were under the control of Catholic Institute for Applied Anatomy, The Catholic University of Korea. Measurements of segmented atlas were carried out by using Mimics software (Simulation module, Version 13.0, Materialise NV, Belgium), and values of measurement were performed statistical analysis by IBM(R) SPSS(R) (version 20.0, Armonk, New York). Among 19 measurements, the width of atlas showed most crucial element for estimating sex, which was consistent with the result using dried bones of atlas and hit ratio of discriminant functions was 88.0%. 76.7 was the cut-off score of discriminant functions. This results showed that morphometrics for segmented atlas could be helpful in estimating sex using the Digital Korean database. In the future, we expect that the other researchers could more actively use the Digital Korean database as a good specimen for physical and forensic anthropological study.
Cadaver ; Female ; Human Body* ; Humans ; Korea

OBJECTIVES: Corticotropin releasing factor (CRF) plays a primary role in coordinating the neuroendocrine, autonomic, immune and behavioral responses to stress. CRF exerts its action through two major receptors, corticotropin-releasing factor 1 Receptor (CRF-R1) and corticotropin-releasing factor 2 receptor (CRF-R2). Using two types of chronic stress models, we investigated the changes of CRF-R1 mRNA and CRF-R2A mRNA expressions and CRF mRNA in the stress related brain circuit areas. METHODS: Male Sprague-Dawley rats were exposed to either immobilization stress or variable intermittent unpredictable stress for 10 days and then in situ hybridization histochemistry was used to quantify CRF expression in the brain. RESULTS: 1) CRF1 receptor mRNA expressions were decreased in bed nucleus stria terminalis (BNST) following stressors. 2) CRF2A receptor mRNA expressions were increased in lateral septum following stressors. 3) CRF mRNA expressions were increased in central nucleus of amygdala (CeA) and BNST. CONCLUSION: The increased CRF mRNA of CeA and BNST may be related with anxiety response in the repeated stress. Down-regulation of CRF-R1 mRNA expression in BNST may represent a compensatory adaptation to chronic stress and may be involved in the anxiety response, whereas up-regulation of CRF-R2A mRNA expression in lateral septum may represent an anxiety response or impaired learning but the functional meaning is uncertain.
Adrenocorticotropic Hormone* ; Amygdala ; Anxiety ; Brain ; Corticotropin-Releasing Hormone* ; Down-Regulation ; Humans ; Immobilization ; In Situ Hybridization ; Learning ; Male ; Rats, Sprague-Dawley ; Receptors, Corticotropin-Releasing Hormone ; RNA, Messenger ; Up-Regulation

BACKGROUND: Emergence agitation after sevoflurane anesthesia in children can be prevented by midazolam. Alternative splicing of the GABAA receptor changes with age. Therefore, we hypothesized that alternative splicing of the gamma2 subunit affects the GABA current when applying sevoflurane and midazolam. METHODS: We performed the whole-cell patch clamp technique on human embryonic kidney 293 cells that were transfected with alpha1beta2gamma2L or alpha1beta2gamma2S. The concentration-response relations were recorded for midazolam and sevoflurane, and the co-application responses were measured at concentrations of 1.5 nM, 15 nM and 300 nM of midazolam and 0.5%, 2.0% and 4.0% of sevoflurane. Each GABA current was compared with that produced by 5 microM of GABA. RESULTS: The concentration-response relationships for midazolam and sevoflurane were dose-dependent without any differences between the alpha1beta2gamma2L and alpha1beta2gamma2S subtypes. 1.5 nM and 15 nM of midazolam did not significantly enhance the current after treatment with 0.5% sevoflurane for both subtypes. The current after treatment with 2.0% sevoflurane was enhanced by 1.5 nM midazolam for the alpha1beta2gamma2S subtype, but not for the alpha1beta2gamma2L subtype. In the case of 2.0% sevoflurane with 15 nM of midazolam, and 4.0% sevoflurane with 300 nM of midazolam, the GABA currents were significantly enhanced for both subtypes. CONCLUSIONS: These results show that the difference in the gamma2 subunit cannot explain the emergence agitation after sevoflurane anesthesia in children in vitro. This suggests that co-application of sevoflurane and midazolam enhances the GABA current according to the alternative splicing of the gamma2 subunit and the concentration of both drugs.
Alternative Splicing ; Anesthesia ; Child ; Dihydroergotamine ; gamma-Aminobutyric Acid ; Humans ; Kidney ; Methyl Ethers ; Midazolam

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPHTN) are complications of portal hypertension and cirrhosis. Their pathophysiological mechanisms clearly differ. HPS is characterized by a defect in arterial oxygenation induced by pulmonary vascular dilatation. In contrast, PPHTN is predominantly due to excessive pulmonary vasoconstriction and vascular remodeling, but is rarely associated with hypoxia. We report a case of a patient who had both HPS and PPHTN at the time of presentation. HPS was aggravated after sildenafil administration for the treatment of PPHTN. We demonstrated increased amount of intrapulmonay shunt after sildenafil challenge by using agitated saline contrast transthoracic echocardiography.
Anoxia ; Dihydroergotamine ; Dilatation ; Echocardiography ; Fibrosis ; Hepatopulmonary Syndrome* ; Humans ; Hypertension* ; Hypertension, Portal ; Oxygen ; Vasoconstriction ; Sildenafil Citrate

Ischemic acute kidney injury (AKI) is a common medical problem with significant mortality and morbidity, affecting a large number of patients globally. Ischemic AKI is associated with intrarenal inflammation as well as systemic inflammation; thus, the innate and adaptive immune systems are implicated in the pathogenesis of ischemic AKI. Among various intrarenal immune cells, T cells play major roles in the injury process and in the repair mechanism affecting AKI to chronic kidney disease transition. Importantly, T cells also participate in distant organ crosstalk during AKI, which affects the overall outcomes. Therefore, targeting T cell-mediated pathways and T cell-based therapies have therapeutic promise for ischemic AKI. Here, we review the major populations of kidney T cells and their roles in ischemic AKI.