A prospective study on the long-term storage of sputum and the recovery of nontuberculous mycobacteria.

BACKGROUND: There is little information on the optimal storage conditions for recovery of nontuberculous Mycobacterium spp. (NTM) from refrigerated sputum. OBJECTIVES: We investigated the storage duration that could increase the culture-positive rate of NTM isolates. DESIGN: In this prospective study, we collected NTM isolates and clinical data from patients with repeated culture-positive NTM pulmonary disease (NTM-PD). METHODS: From June 2020 to July 2021, the participants were instructed to randomly collect six sputum samples and immediately store them in a refrigerator at 4°C until the date of their clinic visit. At the outpatient visits, expectorated spot sputum samples were collected. RESULTS: A total of 226 sputum samples were collected from 35 patients. The median duration of refrigeration was 6 days (maximum duration: 36 days). The overall culture-positive rate was 81.6%. While there was a trend for a higher culture positivity rate when stored for ⩽3 weeks, this was not significant compared with those stored for >3 weeks (p = 0.610). According to sputum microscopy, smear-positive sputum was 100% isolated, but smear-negative samples had a culture-positive rate of 77.5%. Similarly, there was no significant association between sputum storage duration and culture positivity (p = 0.511). In addition, the recovery rate of the refrigerated sputum was comparable with the collected spot expectorated sputum (82.6% versus 80.6%, p = 0.795), which is suggestive of the long-term viability of NTM in refrigerated sputum. CONCLUSION: Our data demonstrated the long-term viability of refrigerated NTM, and the culture positivity rate of these samples was comparable with the spot expectorated sputum. These results suggest that implementing sputum refrigeration would enhance convenience in diagnosing and following patients with NTM-PD. PLAIN LANGUAGE SUMMARY: Easy way to diagnose NTM lung diseasesUnder usual circumstances, most patients with suspected NTM submit spontaneously expectorated sputum rather than induced sputum for the purpose of testing the causative organism. By collecting and storing sputum specimens for a longer period than before, it is expected that more sufficient and adequate collection of sputum specimens will be possible.

Recovery of dopaminergic amacrine cells after strobe light stimulation in the developing rat retina.

Concerns regarding the impact of strobe light on human health and life have recently been raised. Sources of strobe light include visual display terminals, light-emitting diodes, and computer monitors. Strobe light exposure leads to visual discomfort, headaches, and poor visual performance and affects the number of dopaminergic amacrine cells (DACs) in the developing retina, as well as retinal dopamine levels in animals. DACs serve as the sole source of retinal dopamine, and dopamine release from the retina is activated by light exposure following a circadian rhythm. Using a Sprague-Dawley rat model, this study sought to determine whether changes in DACs caused by strobe light are recoverable after ceasing strobe light exposure during retinal development. From eye opening (postnatal 2 weeks), rats in the control group were reared under normal light (an unflickering 150 lux incandescent lamp with a 12 h light/dark cycle), whereas those in the experimental group (i.e., strobe-recovery group) were reared under strobe light (2 Hz for 12 h/day) exposure for 2 weeks. After postnatal week 4, normal light was provided to all animals to observe the reversibility of the effect of strobe light. Immunohistochemistry and immunoblot analysis for the rate limiting enzyme for dopamine synthesis, tyrosine hydroxylase (TH), as well as high-pressure liquid chromatography for measuring dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) were performed at postnatal weeks 4, 6, 8, and 10. The number of type I and type II TH-immunoreactive (TH-IR) cells across the entire retina was counted to evaluate whether changes in DACs induced by strobe light could recover after ceasing strobe light exposure. The number of type I TH-IR cells slightly decreased but remained at a constant level in the control group. In contrast, the number of type I TH-IR cells rapidly decreased up to postnatal week 6, but then increased after postnatal week 8 in the strobe-recovery group. Subsequently, the number of type I TH-IR cells eventually reached a number similar to that in the control group. In addition, the number of intermediate-sized TH-IR cells were increased at postnatal weeks 8 and 10 and the dopamine level was decreased at postnatal week 8 in the strobe-recovery group. However, the levels of DOPAC and TH proteins did not differ between the two groups. This suggests that changes in DACs caused by strobe light are reversible and that type II TH-IR cells may play a key role in this recovery.

Increased Caveolin-2 Expression in Brain Endothelial Cells Promotes Age-Related Neuroinflammation.

Aging is a major risk factor for common neurodegenerative diseases. Although multiple molecular, cellular, structural, and functional changes occur in the brain during aging, the involvement of caveolin-2 (Cav-2) in brain ageing remains unknown. We investigated Cav-2 expression in brains of aged mice and its effects on endothelial cells. The human umbilical vein endothelial cells (HUVECs) showed decreased THP-1 adhesion and infiltration when treated with Cav-2 siRNA compared to control siRNA. In contrast, Cav-2 overexpression increased THP-1 adhesion and infiltration in HUVECs. Increased expression of Cav-2 and iba-1 was observed in brains of old mice. Moreover, there were fewer iba-1-positive cells in the brains of aged Cav-2 knockout (KO) mice than of wild-type aged mice. The levels of several chemokines were higher in brains of aged wild-type mice than in young wild-type mice; moreover, chemokine levels were significantly lower in brains of young mice as well as aged Cav-2 KO mice than in their wild-type counterparts. Expression of PECAM1 and VE-cadherin proteins increased in brains of old wild-type mice but was barely detected in brains of young wild-type and Cav-2 KO mice. Collectively, our results suggest that Cav-2 expression increases in the endothelial cells of aged brain, and promotes leukocyte infiltration and age-associated neuroinflammation.

The impacts of three-dimensional anatomical atlas on learning anatomy.

Gross anatomy has traditionally been the foundation of medical education. Medical students have learned the structure of the human body through dissection, lecture, and textbooks. As tablets and three-dimensional (3D) applications are developed, 3D atlas applications are utilized in learning anatomy by medical students. The purpose of this research is to investigate the impacts of 3D atlas applications on students' understanding of gross anatomy. This research was targeted at medical students taking the Anatomy and Embryology class in 2017 and 2018, at Ewha Womans University. The correlation between use of 3D atlas and student's results on the Anatomy and Embryology test was analyzed. An open-book anatomy quiz was also carried out to analyze the correlation between the type of atlas each student refers to and the results of the quiz. Independent t test between groups did not show statistically significant difference in the results of the Anatomy and Embryology test. However, the group referring to 3D atlas showed significantly higher results on the simple questions of the open-book anatomy quiz (P<0.05). In conclusion, 3D atlas is not very helpful in acquiring deep anatomical knowledge or memorizing the location of anatomical structures, but it can simply aid in the rapid identification of anatomical structures. Additionally, the 3D atlas will show good synergy with the two-dimensional atlas if used properly in anatomy education, because most students think it is useful to use the 3D atlas.

Extracellular matrix-derived extracellular vesicles promote cardiomyocyte growth and electrical activity in engineered cardiac atria.

Extracellular matrix (ECM) plays a critical role in the provision of the necessary microenvironment for the proper regeneration of the cardiac tissue. However, specific mechanisms that lead to ECM-mediated cardiac regeneration are not well understood. To elucidate the potential mechanisms, we investigated ultra-structures of the cardiac ECM using electron microscopy. Intriguingly, we observed large quantities of micro-vesicles from decellularized right atria. RNA and protein analyses revealed that these contained exosomal proteins and microRNAs (miRNAs), which we referred to herein as ECM-derived extracellular vesicles (ECM-EVs). One particular miRNA from ECM-EVs, miR-199a-3p, promoted cell growth of isolated neonatal cardiomyocytes and sinus nodal cells by repressing homeodomain-only protein (HOPX) expression and increasing GATA-binding 4 (Gata4) acetylation. To determine the mechanisms, we knocked down Gata4 and showed that miR-199a-3p actions required Gata4 for cell proliferation in isolated neonatal cardiomyocytes and sinus nodal cells. To further explore the role of this miRNA, we isolated neonatal cardiac cells and recellularized into atrial ECM, referred here has engineered atria. Remarkably, miR-199a-3p mediated the enrichment of cardiomyocyte and sinus nodal cell population, and enhanced electrocardiographic signal activity of sinus nodal cells in the engineered atria. Importantly, antisense of miRNA (antagomir) against miR-199a-3p was capable of abolishing these actions of miR-199a-3p in the engineered atria. We further showed in Ang II-infused animal model of sinus nodal dysfunction that miR-199-3p-treated cardiac cells remarkably ameliorated and restored the electrical activity as shown by normalization of the ECG, in contrast to untreated cells, which did not show electrical recovery. In conclusion, these results provide clear evidence of the critical role of ECM, in not only providing a scaffold for cardiac tissue growth, but also in promoting atrial electrical function through ECM-derived miR-199a-3p.

The Impact of Patient Education with a Smartphone Application on the Quality of Bowel Preparation for Screening Colonoscopy.

BACKGROUND/AIMS: Few studies have evaluated the use of a smartphone application (app) for educating people undergoing colonoscopy and optimizing bowel preparation. Therefore, this study was designed to develop a smartphone app for people to use as a preparation guide and to evaluate the efficacy of this app when used prior to colonoscopy. METHODS: In total, 142 patients (male:female=84:58, mean age=43.5±9.3 years), who were scheduled to undergo a colonoscopy at Myongji Hospital, were enrolled in this study. Seventy-one patients were asked to use a smartphone app that we had recently developed to prepare for the colonoscopy, while the 71 patients of the sex and age-matched control group were educated via written and verbal instructions. RESULTS: The quality of bowel cleansing, evaluated using the Boston Bowel Preparation Scale, was significantly higher in the smartphone app group than in the control group (7.70±1.1 vs. 7.24±0.8, respectively, p=0.007 by t-test). No significant differences were found between the two groups regarding work-up time and the number of patients with polyps. CONCLUSIONS: In this study, targeting young adults (≤50 years), the bowel preparation achieved by patients using the smartphone app showed significantly better quality than that of the control group.

Bacterial Ulcerative Esophagitis in an Immunocompetent Patient.

Bacterial esophagitis is a very rare condition usually occurring in patients with immunosuppression. To our best knowledge, bacterial esophagitis without underlying immunosuppressive disease has not been reported. We report an immunocompetent patient with bacterial esophagitis caused by B-hemolytic Streptococcus which resulted in an esophageal stricture. A 68-year-old female was admitted for odynophagia which had developed several days before. Upper endoscopy revealed extensive ulceration covered by whitish exudates with submucosal edema at the proximal esophagus. She was treated with steroids and empirical broad-spectrum antibiotics. Within 14 days the symptoms improved. Since growth of B-hemolytic Streptococcus was detected in nasal smear culture, bacterial esophagitis was suspected. Gram staining was carried out on the already obtained tissue that had been fixed with formalin. There was heavy infiltration with gram-positive cocci morphologically consistent with Streptococcus. Since the bacterial colony was demonstrated histologically, the diagnosis of bacterial esophagitis caused by B-hemolytic Streptococcus was confirmed. In addition, complete resolution of the inflammation following antibiotics therapy was further evidence of the bacterial cause of the esophagitis.

Inhibition of Matrix Metalloproteinase 9 Enhances Rod Survival in the S334ter-line3 Retinitis Pigmentosa Model.

Retinitis Pigmentosa (RP) is one of the most common forms of inherited visual loss with the initial degeneration of rod photoreceptors, followed by a progressive cone photoreceptor deterioration. Coinciding with this visual loss, the extracellular matrix (ECM) is reorganized, which alters matrix metalloproteinase (MMP) activity levels. A potential pathological role of MMPs, MMP-9 in particular, involves an excitotoxicity-mediated physiological response. In the current study, we examine the MMP-9 and MMP-2 expression levels in the rhodopsin S334ter-line3 RP rat model and investigate the impact of treatment with SB-3CT, a specific MMP-9 and MMP-2 inhibitor, on rod cell survival was tested. Retinal MMP-9 and MMP-2 expression levels were quantified by immunoblot analysis from S334ter-line3 rats compared to controls. Gelatinolytic activities of MMP-9 and MMP-2 by zymography were examined. The geometry of rod death was further evaluated using Voronoi analysis. Our results revealed that MMP-9 was elevated while MMP-2 was relatively unchanged when S334ter-line 3 retinas were compared to controls. With SB-3CT treatment, we observed gelatinolytic activity of both MMPs was decreased and diminished clustering associated with rod death, in addition to a robust preservation of rod photoreceptors. These results demonstrate that up-regulation of MMP-9 in retinas of S334ter-line3 are associated with rod death. The application of SB-3CT dramatically interferes with mechanisms leading to apoptosis in an MMP-9-dependent manner. Future studies will determine the feasibility of using SB-3CT as a potential therapeutic strategy to slow progression of vision loss in genetic inherited forms of human RP.

Reshaping the Cone-Mosaic in a Rat Model of Retinitis Pigmentosa: Modulatory Role of ZO-1 Expression in DL-Alpha-Aminoadipic Acid Reshaping.

In S334ter-line-3 rat model of Retinitis Pigmentosa (RP), rod cell death induces the rearrangement of cones into mosaics of rings while the fibrotic processes of Müller cells remodel to fill the center of the rings. In contrast, previous work established that DL-alpha-aminoadipic-acid (AAA), a compound that transiently blocks Müller cell metabolism, abolishes these highly structured cone rings. Simultaneously, adherens-junction associated protein, Zonula occludens-1 (ZO-1) expression forms in a network between the photoreceptor segments and Müller cells processes. Thus, we hypothesized that AAA treatment alters the cone mosaic rings by disrupting the distal sealing formed by these fibrotic processes, either directly or indirectly, by down regulating the expression of ZO-1. Therefore, we examined these processes and ZO-1 expression at the outer retina after intravitreal injection of AAA and observed that AAA treatment transiently disrupts the distal glial sealing in RP retina, plus induces cones in rings to become more homogeneous. Moreover, ZO-1 expression is actively suppressed after 3 days of AAA treatment, which coincided with cone ring disruption. Similar modifications of glial sealing and cone distribution were observed after injection of siRNA to inhibit ZO-1 expression. These findings support our hypothesis and provide additional information about the critical role played by ZO-1 in glial sealing and shaping the ring mosaic in RP retina. These studies represent important advancements in the understanding of retinal degeneration's etiology and pathophysiology.

Effect of Acylglycerol Composition and Fatty Acyl Chain Length on Lipid Digestion in pH-Stat Digestion Model and Simulated In Vitro Digestion Model.

In this study, a pH-stat digestion model and a simulated in vitro digestion model were employed to evaluate the digestion degree of lipids depending on different acylglycerols and acyl chain length (that is, diacylglycerol [DAG] compared with soybean oil representing long-chain triacylglycerol compared with medium-chain triacylglycerol [MCT]). In the pH-stat digestion model, differences were observed among the digestion degrees of 3 oils using digestion rate (k), digestion half-time (t1/2 ), and digestion extent (Φmax). The results showed the digestion rate order was MCT > soybean oil > DAG. Accordingly, the order of digestion half-times was MCT < soybean oil < DAG. In simulated in vitro digestion model, digestion rates (k') and digestion half-times (t'1/2 ) were also obtained and the results showed a digestion rate order of MCT (k' = 0.068 min(-1) ) > soybean oil (k' = 0.037 min(-1) ) > DAG (k' = 0.024 min(-1) ). Consequently, the order of digestion half-times was MCT (t'1/2 = 10.20 min) < soybean oil (t'1/2 = 18.74 min) < DAG (t'1/2 = 29.08 min). The parameters obtained using the 2 models showed MCT was digested faster than soybean oil, and that soybean oil was digested faster than DAG.

Arrestin 1 and Cone Arrestin 4 Have Unique Roles in Visual Function in an All-Cone Mouse Retina.

PURPOSE: Previous studies discovered cone phototransduction shutoff occurs normally for Arr1-/- and Arr4-/-; however, it is defective when both visual arrestins are simultaneously not expressed (Arr1-/-Arr4-/-). We investigated the roles of visual arrestins in an all-cone retina (Nrl-/-) since each arrestin has differential effects on visual function, including ARR1 for normal light adaptation, and ARR4 for normal contrast sensitivity and visual acuity. METHODS: We examined Nrl-/-, Nrl-/-Arr1-/-, Nrl-/-Arr4-/-, and Nrl-/-Arr1-/-Arr4-/- mice with photopic electroretinography (ERG) to assess light adaptation and retinal responses, immunoblot and immunohistochemical localization analysis to measure retinal expression levels of M- and S-opsin, and optokinetic tracking (OKT) to measure the visual acuity and contrast sensitivity. RESULTS: Study results indicated that Nrl-/- and Nrl-/-Arr4-/- mice light adapted normally, while Nrl-/-Arr1-/- and Nrl-/-Arr1-/-Arr4-/- mice did not. Photopic ERG a-wave, b-wave, and flicker amplitudes followed a general pattern in which Nrl-/-Arr4-/- amplitudes were higher than the amplitudes of Nrl-/-, while the amplitudes of Nrl-/-Arr1-/- and Nrl-/-Arr1-/-Arr4-/- were lower. All three visual arrestin knockouts had faster implicit times than Nrl-/- mice. M-opsin expression is lower when ARR1 is not expressed, while S-opsin expression is lower when ARR4 is not expressed. Although M-opsin expression is mislocalized throughout the photoreceptor cells, S-opsin is confined to the outer segments in all genotypes. Contrast sensitivity is decreased when ARR4 is not expressed, while visual acuity was normal except in Nrl-/-Arr1-/-Arr4-/-. CONCLUSIONS: Based on the opposite visual phenotypes in an all-cone retina in the Nrl-/-Arr1-/- and Nrl-/-Arr4-/- mice, we conclude that ARR1 and ARR4 perform unique modulatory roles in cone photoreceptors.

TIMP-1 affects the spatial distribution of dendritic processes of second-order neurons in a rat model of Retinitis Pigmentosa.

Retinitis Pigmentosa (RP) is an inherited disorder that may lead to blindness. In the rhodopsin S334ter-line-3 rat model of RP, the death of rods induces spatial rearrangement of cones into regular ring mosaics. Using this model, we discovered that the ring mosaics are restored to a homogeneous distribution upon application of tissue inhibitor of metalloproteinase-1 (TIMP-1). In this study, we further investigated the cone migration and spatial distribution of second-order neurons and their connections to cones in the presence or absence of TIMP-1 using immunohistochemistry to identify retinal neurons and their connections with cones. M-opsin cell bodies and their outer segments were evaluated to determine whether TIMP-1 delays the degeneration of outer segments of cones. We observed that during cone rearrangement into ring mosaics in RP retina, dendritic processes of second-order neurons undergo remodeling to maintain their synaptic connections with the cones in the rings. TIMP-1 treatment induced the cones to rearrange and dendritic processes of second-order neurons to return to a more homogeneous spatial distribution. In addition, TIMP-1 treatment protected the outer segments of cones at later stages of retinal degeneration. Our findings clearly demonstrate that despite their dramatic spatial rearrangement, cones and second-order neuron processes maintain their synaptic connections before and after TIMP-1 treatment.

Visual Cone Arrestin 4 Contributes to Visual Function and Cone Health.

PURPOSE: Visual arrestins (ARR) play a critical role in shutoff of rod and cone phototransduction. When electrophysiological responses are measured for a single mouse cone photoreceptor, ARR1 expression can substitute for ARR4 in cone pigment desensitization; however, each arrestin may also contribute its own, unique role to modulate other cellular functions. METHODS: A combination of ERG, optokinetic tracking, immunohistochemistry, and immunoblot analysis was used to investigate the retinal phenotypes of Arr4 null mice (Arr4-/-) compared with age-matched control, wild-type mice. RESULTS: When 2-month-old Arr4-/- mice were compared with wild-type mice, they had diminished visual acuity and contrast sensitivity, yet enhanced ERG flicker response and higher photopic ERG b-wave amplitudes. In contrast, in older Arr4-/- mice, all ERG amplitudes were significantly reduced in magnitude compared with age-matched controls. Furthermore, in older Arr4-/- mice, the total cone numbers decreased and cone opsin protein immunoreactive expression levels were significantly reduced, while overall photoreceptor outer nuclear layer thickness was unchanged. CONCLUSIONS: Our study demonstrates that Arr4-/- mice display distinct phenotypic differences when compared to controls, suggesting that ARR4 modulates essential functions in high acuity vision and downstream cellular signaling pathways that are not fulfilled or substituted by the coexpression of ARR1, despite its high expression levels in all mouse cones. Without normal ARR4 expression levels, cones slowly degenerate with increasing age, making this a new model to study age-related cone dystrophy.

Dopamine receptor D4 internalization requires a beta-arrestin and a visual arrestin.

PURPOSE: The G-protein coupled receptor (GPCR) Dopamine Receptor D4 (DRD4) plays an essential role in cAMP regulation and gap junctional coupling in the photoreceptors, where DRD4 expression is under circadian control. Previous in vitro transfection studies of human DRD4 desensitization have reported that DRD4 is not internalized upon dopamine stimulation when beta-arrestin is co-transfected with DRD4. We hypothesized that the visual arrestins, ARR1 and ARR4, play a modulatory role in DRD4 desensitization in the photoreceptors. METHODS: To test this hypothesis, immunohistochemistry analysis of mouse retinas was used to determine the cellular localization of beta-arrestins and DRD4 in photoreceptors. In vitro studies were performed in HEK293T cells transiently transfected with human DRD4 and arrestins. First, co-immunoprecipitation experiments were executed to test protein-protein interactions and to investigate the effect of dopamine stimulation. Second, immunohistochemistry analysis was implemented to study DRD4 internalization and translocation of ARR4. RESULTS: Immunohistochemistry studies of mouse retinas confirmed the expression of beta-arrestin 2, ARR1 and ARR4, as well as DRD4 in mouse cone photoreceptor inner segments. Co-immunoprecipitation experiments revealed a dopamine-dependent protein-protein interaction between human DRD4 and ARR4. In vitro internalization experiments showed that no detectable internalization of DRD4 was observed with any single arrestin co-transfected. However, a dopamine-dependent internalization of DRD4 was observed with three out of six sets of two arrestins co-transfected with DRD4. Each of these pairs of arrestins contained one visual arrestin and one beta-arrestin, and no internalization was observed with either two visual arrestins or two beta-arrestins. Additional time-course experiments revealed that in vitro, ARR4 translocates to co-localize with DRD4 at the plasma membrane in response to 30min of dopamine stimulation. CONCLUSIONS: The results have functional implications and we hypothesize that the desensitization and internalization of DRD4 in photoreceptors are synergistically mediated by both visual and beta-arrestins. These results are additionally unique because they demonstrate for the first time that at least one G-protein coupled receptor, DRD4, requires two arrestins for desensitization and internalization, and opens up the possibility that other G-protein coupled receptors may require more than one arrestin for desensitization and/or internalization.

A Case of Metastatic Low-Grade Endometrial Stromal Sarcoma Treated with Letrozole after Ovarian Ablation by Radiotherapy.

A 50-year-old woman was admitted to our hospital due to multiple lung nodules detected incidentally on a chest X-ray. A video-assisted thoracoscopic lung biopsy revealed low-grade endometrial stromal sarcoma (LG-ESS). She had undergone a simple hysterectomy 1 year earlier owing to a diagnosis of adenomyosis. A review of her previous hysterectomy specimen showed not endometriosis but LG-ESS. According to the patient's levels of serum follicle stimulating hormone and estradiol, she was in the premenopausal state with retained and normally functioning ovaries. She then underwent ovarian ablation by radiotherapy, after which she was administered 2.5 mg of letrozole once per day. Three months later, the size of the metastatic nodules in both lungs had decreased. The patient was followed up for 24 months while continuing on letrozole, and maintained a partial remission. We report herein on a case of metastatic LG-ESS treated with letrozole after ovarian ablation by radiotherapy.

Effect of maternal excessive sodium intake on postnatal brain development in rat offspring.

OBJECTIVES: Postnatal brain development is affected by the in utero environment. Modern people usually have a high sodium intake. The aim of this study was to investigate the effect of sodium hyperingestion during pregnancy on the postnatal brain development of rat offspring. METHODS: The sodium-overloaded rats received 1.8% NaCl in their drinking water for 7 days during the last week of gestation. Their body weight, urine, and blood levels of sodium and other parameters were measured. Some rats were sacrificed at pregnancy day 22 and the weight and length of the placenta and foetus were measured. The cerebral cortex and hippocampus were obtained from their offspring at postnatal day 1 and at postnatal weeks 1, 2, 4, and 8. Western blot analyses were conducted with brain tissue lysates. RESULTS: The sodium-overloaded animals had decreased weight gain in the last week of gestation as well as decreased food intake, increased water intake, urine volume, urine sodium, and serum sodium. There were no differences in placental weight and length. The foetuses of sodium-overloaded rats showed decreased body weight and size, and this difference was maintained postnatally for 2 weeks. In the cerebral cortex and hippocampus of the offspring, the protein levels of myelin basic protein, calmodulin/calcium-dependent protein kinase II, and brain-derived neurotrophic factor were decreased or aberrantly expressed. DISCUSSION: The present data suggest that increased sodium intake during pregnancy affects the brain development of the offspring.

Localization of folate metabolic enzymes, methionine synthase and 5,10-methylenetetrahydrofolate reductase in human placenta.

BACKGROUND: Normal fetal development requires adequate folate levels during pregnancy. Although folate metabolic enzymes have important roles in the maintenance of normal fetal development, the location of folate metabolic enzymes, methionine synthase (MTR) and 5,10-methylenetetrahydrofolate reductase (MTHFR), has not been previously examined. METHODS: We investigated the expression of MTR and MTHFR in human term placenta obtained from normal and pregnancy-induced hypertension (PIH) patients. RESULTS: MTR is expressed in the villous syncytiotrophoblast and MTHFR is expressed in the extravillous trophoblast. There was no difference in the quantity and location of these enzymes between control and PIH patients. CONCLUSION: These results suggest that MTR in the villous trophoblast participates in the metabolism of homocysteine by using folate, and MTHFR in the extravillous trophoblast is associated with extratrophoblast invasion.

Sarcoidosis associated with oxaliplatin-based chemotherapy for colorectal cancer.

Acute lung injury occasionally occurs after chemotherapy, but pulmonary toxicities by oxaliplatin-based chemotherapy have rarely been identified. A 76-year-old female with rectosigmoid colon cancer presented with ongoing dyspnea after the eighth cycle of standard chemotherapy (5-fluorouracil, sodium folinic acid, and oxaliplatin: FOLFOX). Nodular consolidation progressed despite antibiotics and BAL fluid analysis was compatible with the diagnosis of sarcoidosis. Corticosteroid therapy rapidly improved the symptoms and radiographic findings. We report this first case of secondary sarcoidosis related to FOLFOX therapy with review of references.

Effects of strobe light stimulation on postnatal developing rat retina.

The nature and intensity of visual stimuli have changed in recent years because of television and other dynamic light sources. Although light stimuli accompanied by contrast and strength changes are thought to have an influence on visual system development, little information is available on the effects of dynamic light stimuli such as a strobe light on visual system development. Thus, this study was designed to evaluate changes caused by dynamic light stimuli during retinal development. This study used 80 Sprague-Dawley rats. From eye opening (postnatal day 14), half of the rats were maintained on a daily 12-h light/dark cycle (control group) and the remaining animals were raised under a 12-h strobe light (2 Hz)/dark cycle (strobe light-reared group). Morphological analyses and electroretinogram (ERG) were performed at postnatal weeks 3, 4, 6, 8, and 10. Among retinal neurons, tyrosine hydroxylase-immunoreactive (TH-IR, dopaminergic amacrine cells) cells showed marked plastic changes, such as variations in numbers and soma sizes. In whole-mount preparations at 6, 8, and 10 weeks, type I TH-IR cells showed a decreased number and larger somata, while type II TH-IR cells showed an increased number in strobe-reared animals. Functional assessment by scotopic ERG showed that a-wave and b-wave amplitudes increased at 6 and 8 weeks in strobe-reared animals. These results show that exposure to a strobe light during development causes changes in TH-IR cell number and morphology, leading to a disturbance in normal visual functions.

Neurolymphomatosis of Brachial Plexus in Patients with Non-Hodgkin's Lymphoma.

Neurolymphomatosis (NL) is a rare clinical disease where neoplastic cells invade the cranial nerves and peripheral nerve roots, plexus, or other nerves in patients with hematologic malignancy. Most NL cases are caused by B-cell non-Hodgkin's lymphoma (NHL). Diagnosis can be made by imaging with positron emission tomography (PET) and magnetic resonance imaging (MRI). We experienced two cases of NL involving the brachial plexus in patients with NHL. One patient, who had NHL with central nervous system (CNS) involvement, experienced complete remission after 8 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy but relapsed into NL of the brachial plexus 5 months later. The other patient, who suffered from primary central nervous system lymphoma (PCNSL), had been undergoing chemoradiotherapy but progressed to NL of the brachial plexus.