Lactoferrin Induces Tolerogenic Bone Marrow-Derived Dendritic Cells

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that initiate both T-cell responses and tolerance. Tolerogenic DCs (tDCs) are regulatory DCs that suppress immune responses through the induction of T-cell anergy and Tregs. Because lactoferrin (LF) was demonstrated to induce functional Tregs and has a protective effect against inflammatory bowel disease, we explored the tolerogenic effects of LF on mouse bone marrow-derived DCs (BMDCs). The expression of CD80/86 and MHC class II was diminished in LF-treated BMDCs (LF-BMDCs). LF facilitated BMDCs to suppress proliferation and elevate Foxp3 +induced Treg (iTreg) differentiation in ovalbumin-specific CD4 + T-cell culture. Foxp3 expression was further increased by blockade of the B7 molecule using CTLA4-Ig but was diminished by additional CD28 stimulation using anti-CD28 Ab. On the other hand, the levels of arginase-1 and indoleamine 2,3-dioxygenase-1 (known as key T-cell suppressive molecules) were increased in LF-BMDCs. Consistently, the suppressive activity of LF-BMDCs was partially restored by inhibitors of these molecules. Collectively, these results suggest that LF effectively causes DCs to be tolerogenic by both the suppression of T-cell proliferation and enhancement of iTreg differentiation. This tolerogenic effect of LF is due to the reduction of costimulatory molecules and enhancement of suppressive molecules.

Lactoferrin Induces Tolerogenic Bone Marrow-Derived Dendritic Cells

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that initiate both T-cell responses and tolerance. Tolerogenic DCs (tDCs) are regulatory DCs that suppress immune responses through the induction of T-cell anergy and Tregs. Because lactoferrin (LF) was demonstrated to induce functional Tregs and has a protective effect against inflammatory bowel disease, we explored the tolerogenic effects of LF on mouse bone marrow-derived DCs (BMDCs). The expression of CD80/86 and MHC class II was diminished in LF-treated BMDCs (LF-BMDCs). LF facilitated BMDCs to suppress proliferation and elevate Foxp3 +induced Treg (iTreg) differentiation in ovalbumin-specific CD4 + T-cell culture. Foxp3 expression was further increased by blockade of the B7 molecule using CTLA4-Ig but was diminished by additional CD28 stimulation using anti-CD28 Ab. On the other hand, the levels of arginase-1 and indoleamine 2,3-dioxygenase-1 (known as key T-cell suppressive molecules) were increased in LF-BMDCs. Consistently, the suppressive activity of LF-BMDCs was partially restored by inhibitors of these molecules. Collectively, these results suggest that LF effectively causes DCs to be tolerogenic by both the suppression of T-cell proliferation and enhancement of iTreg differentiation. This tolerogenic effect of LF is due to the reduction of costimulatory molecules and enhancement of suppressive molecules.

Murine γδ T Cells Render B Cells Refractory to Commitment of IgA Isotype Switching

γδ T cells are abundant in the gut mucosa and play an important role in adaptive immunity as well as innate immunity. Although γδ T cells are supposed to be associated with the enhancement of Ab production, the status of γδ T cells, particularly in the synthesis of IgA isotype, remains unclear. We compared Ig expression in T cell receptor delta chain deficient (TCRδ⁻/⁻) mice with wild-type mice. The amount of IgA in fecal pellets was substantially elevated in TCRδ⁻/⁻ mice. This was paralleled by an increase in surface IgA expression and total IgA production by Peyer's patches (PPs) and mesenteric lymph node (MLN) cells. Likewise, the TCRδ⁻/⁻ mice produced much higher levels of serum IgA isotype. Here, surface IgA expression and number of IgA secreting cells were also elevated in the culture of spleen and bone marrow (BM) B cells. Germ-line α transcript, an indicator of IgA class switch recombination, higher in PP and MLN B cells from TCRδ⁻/⁻ mice, while it was not seen in inactivated B cells. Nevertheless, the frequency of IgA+ B cells was much higher in the spleen from TCRδ⁻/⁻ mice. These results suggest that γδ T cells control the early phase of B cells, in order to prevent unnecessary IgA isotype switching. Furthermore, this regulatory role of γδ T cells had lasting effects on the long-lived IgA-producing plasma cells in the BM.

MicroRNA-mediated Regulation of the Development and Functions of Follicular Helper T cells

The germinal center reaction is a key event of humoral immunity, providing long-lived immunological memory. Follicular helper T (T(FH)) cells are a specialized subset of CD4⁺ T cells located in the follicles, which help B cells and thus control the germinal center reaction. T(FH) cell development is achieved by multi-step processes of interactions with dendritic cells and B cells along with the coordination of various transcription factors. Since the T helper cell fate decision program is determined by subtle changes in regulatory molecules, fine tuning of these dynamic interactions is crucial for the generation functional T(FH) cells. MicroRNAs (miRNAs) have emerged as important post-transcriptional regulatory molecules for gene expression, which consequently modulate diverse biological functions. In the last decade, the miRNA-mediated regulation network for the germinal center reaction has been extensively explored in T cells and B cells, resulting in the identification of several key miRNA species and their target genes. Here, we review the current knowledge of the miRNA-mediated control of the germinal center reaction, focusing on the aspect of T cell regulation in particular. In addition, we highlight the most important issues related to defining the functional target genes of the relevant miRNAs. We believe that the studies that uncover the miRNA-mediated regulatory axis of T(FH) cell generation and functions by defining their functional target genes might provide additional opportunities to understand germinal center reactions.

Aquatide Activation of SIRT1 Reduces Cellular Senescence through a SIRT1-FOXO1-Autophagy Axis

Ultraviolet (UV) irradiation is a relevant environment factor to induce cellular senescence and photoaging. Both autophagy- and silent information regulator T1 (SIRT1)-dependent pathways are critical cellular processes of not only maintaining normal cellular functions, but also protecting cellular senescence in skin exposed to UV irradiation. In the present studies, we investigated whether modulation of autophagy induction using a novel synthetic SIRT1 activator, heptasodium hexacarboxymethyl dipeptide-12 (named as Aquatide), suppresses the UVB irradiation-induced skin aging. Treatment with Aquatide directly activates SIRT1 and stimulates autophagy induction in cultured human dermal fibroblasts. Next, we found that Aquatide-mediated activation of SIRT1 increases autophagy induction via deacetylation of forkhead box class O (FOXO) 1. Finally, UVB irradiation-induced cellular senescence measured by SA-β-gal staining was significantly decreased in cells treated with Aquatide in parallel to occurring SIRT1 activation-dependent autophagy. Together, Aquatide modulates autophagy through SIRT1 activation, contributing to suppression of skin aging caused by UV irradiation.

A comparative study of initial lateral cephalometric characteristics: mandibular setback surgery only versus mandibular setback surgery with advancement genioplasty / 대한치과교정학회지

OBJECTIVE: The aim of this study was to compare the initial lateral cephalometric characteristics in two groups of patients: those that had mandibular setback surgery only and those that had mandibular setback surgery with advancement genioplasty. METHODS: The lateral cephalograms of thirty-one patients were studied. Twenty-one Class III patients (group A) had only madibular setback surgery. Twelve Class III patients (group B) had mandibular setback surgery with advancement genioplasty. RESULTS: Differences between two groups were found in N-Me, ANS-Me, Occlusal Plane angle, Palatal Plane to U1, Mandibular Plane to L1, Mandibular Plane to L6, SN to U1, Sn-Stms, and Pog' projection. Compared to group A, group B showed more linguoversion and extrusion of upper incisors, more extrusion of lower incisors and lower first molar, and more steepness of the occlusal plane. N-Me, ANS-Me, and Sn-Stms were also longer in group B. But Pog' projection was shorter than group A. CONCLUSION: We conclude that certain initial lateral cephalometric characteristics may help indicate the inclusion of advancement genioplasty when mandibular setback surgery is planned in skeletal Class III patients.

Change in arch width in extraction vs nonextraction treatment / 대한치과교정학회지

OBJECTIVE: This study was performed to investigate the influences of extraction and nonextraction treatment on smile esthetics by measuring dental arch width changes. METHODS: Pretreatment and posttreatment study models of 30 first premolar extraction cases and 30 nonextraction cases were randomly selected to determine whether extraction treatment results in narrow dental arches, and a consequent unaesthetic smile. Arch widths were measured from the cusp tips of the canines and the first molars. Posterior arch widths were also measured at a constant arch depth derived by averaging randomly chosen nonextraction models. RESULTS: The intercanine widths increased significantly in the extraction sample, whereas the intermolar widths decreased significantly. The arch width at a standardized arch depth was significantly wider in the extraction subjects. CONCLUSION: These results elucidate that constriction in arch width is not a materialized consequence of extraction treatment. It leads to postulate that an esthetically compromising effect from narrow dental arches on smile is hardly anticipated with extraction treatment.

A comparative study of pre- and post-treatment cephalometric measurements: Upper premolar extraction only vs. upper/lower premolar extraction groups / 대한치과교정학회지

OBJECTIVE: The objective of this study was to provide guidelines for the diagnosis and successful treatment of orthodontic treatment with upper premolar extraction only. METHODS: The sample group consisted of 40 patients (20 with upper premolar extraction only, 20 with both upper and lower premolar extractions) who showed an overjet of more than 7 mm and were finished successfully. Lateral cephalographs were taken before and after orthodontic treatment. Landmarks showing the position of the upper and lower incisors and the position of the upper and lower lip were determined and angular measurement of these values were obtained for statistical analysis (Mann-Whitney test). RESULTS: At pre-treatment, the position of the lower incisor was less labially inclined and the convexity of the lower lip was smaller in the upper premolar extraction only group than in the upper/lower premolar extraction group. At post-treatment, there was no difference in all measurements except for the position of the lower incisor. A comparison of changes between pre- and post-treatment showed that the retraction of upper & lower incisors and the decrease in convexity of the lower lip were greater in the upper/lower premolar extraction group. CONCLUSIONS: Treatment by upper premolar extraction can be of benefit for patients whose lower incisor proclination and lower lip protrusion are not excessive.

A comparative study of soft tissue profile between Korean and Caucasian young adults under NHP / 대한치과교정학회지

This study was performed to establish Korean soft tissue cephalometric norms, to compare the norms between sexes and between races, and then to suggest a guideline to execute orthodontic diagnosis and treatment planning for dentofacial deformities in Korean. Young Korean adults were selected. They were 27 males (23.8 2.6-year-old) and 20 females (22.5 1.7-year-old) who had harmonious facial balance. After taking lateral cephalograms under the natural head position which is widely known as a highly reliable and reproducible reference position, films were traced and analysing factors were measured as introduced by Arnett et al. Comparisons were done between male and female groups and between Korean and Caucasian groups using unpaired t-test. From the results it was concluded that Korean male had generally thicker lower facial soft tissue and smaller nasolabial angle, longer facial height, deeper facial depth, and more protrusive lower face than Korean female. From the comparison with Caucasian norms adopted from the research of Arnett et al., both Korean male and female showed longer facial lengths generally except less exposed maxillary incisor, and shorter facial depth than Caucasian counterparts. Also, both races showed similar horizontal position of maxillary structures from TVL (true vertical line), but there were more significant anteroposterior differences of maxilla-mandible in Korean groups. These results mean Korean had relatively more retruded mandibular structures from the reference line, TVL. Individuals who had harmonious facial balance showed similar facial angle, more or less 170 degree, regardless of sexes or races.

Identification of a Variant Form of Cellular Inhibitor of Apoptosis Protein (c-IAP2) That Contains a Disrupted Ring Domain

Among the members of the inhibitor of apoptosis (IAP) protein family, only Livin and survivin have been reported to have variant forms. We have found a variant form of c-IAP2 through the interaction with the X protein of HBV using the yeast two-hybrid system. In contrast to the wild-type c-IAP2, the variant form has two stretches of sequence in the RING domain that are repeated in the C-terminus that would disrupt the RING domain. We demonstrate that the variant form has an inhibitory effect on TNF-mediated NF-kappaB activation unlike the wild-type c-IAP2, which increases TNF- mediated NF-kappaB activation. These results suggest that this variant form has different activities from the wild-type and the RING domain may be involved in the regulation of TNF-induced NF-kappaB activation.

Identification of a Variant Form of Cellular Inhibitor of Apoptosis Protein (c-IAP2) That Contains a Disrupted Ring Domain

Among the members of the inhibitor of apoptosis (IAP) protein family, only Livin and survivin have been reported to have variant forms. We have found a variant form of c-IAP2 through the interaction with the X protein of HBV using the yeast two-hybrid system. In contrast to the wild-type c-IAP2, the variant form has two stretches of sequence in the RING domain that are repeated in the C-terminus that would disrupt the RING domain. We demonstrate that the variant form has an inhibitory effect on TNF-mediated NF-kappaB activation unlike the wild-type c-IAP2, which increases TNF- mediated NF-kappaB activation. These results suggest that this variant form has different activities from the wild-type and the RING domain may be involved in the regulation of TNF-induced NF-kappaB activation.

In Vitro Susceptibility of the Herpes Simplex Virus to Acyclovir / 대한피부과학회지

BACKGROUND: Acyclovir is a highly effective antiviral agent specifically inhibiting the replication of members of the herpes virus group, in particular the has been used extensively herpes simplex virus types 1 and 2 and the varicella zoster virus. Although acyclovir it has not caused for the treatment or prevention of herpes simplex and varicella zoster virus infections, significant changes in virus sensitivity. OBJECTIVE: The purpose of this study was to evaluate the sensitivity of HSV to acyclovir. METHODS: A total of 80 strains were used 43 strains of non-genital herpes and 37 strains of genital gerpes. These were isolated from 80 patients and were studied to evaluate their sensitivities to acyclovir by the plaque reduction assay. The methods employed to monitor the sensitivity of virus isolates rely on simple dose-response experiments, looking at the effects of increasing concentrations of acyclovir on infected cell culture specimen. The assay is based on quantified plaque counting. The sensitivity of virus strains are then expressed as ID50(concentrations of drug reducing viral cytopathic effect by 50%) and MIC(minimum inhibitory concentration). RESULTS: The results were summarized as follows. 1. The ID50 values of acyclovir for HSV ranged between 0.0625 - 4.0 microgram / ml. For non-genital herpes isolates the mean and median values were 0.459 microgram / ml (SD = 0.624) and 0.250 microgram / ml ; for genital herpes isolates these values were 0.649 microgram / ml (SD = 0.746) and 0.50 microgram / ml . 2. The MIC values of acyclovir for HSV ranged between 0.250 - 32 microgram / ml . For non-genital herpes isolates the mean and median values were 2.605 microgram / ml (SD = 5.270) and 1.00 microgram / ml ; for genital herpes isolates these values were 2.716 microgram / ml (SD = 3.015) and 2.00 microgram / ml . 5. 93.75%(75 strains) of HSV isolates were within the ranges of sensitive HSV strains for acyclovir. CONCLUSION: We are concerned about the resistance of viruses to antiviral drugs, but so far, this has not been documented to be a big problem. With the increasing interest and ability to measure sensitivity of viruses to antiviral drugs we will find out more about viral resistance and its clinical significance.

A Case of CD3O-negative Large T-Cell Lymphoma Showing p53 and mdm-2 Expression / 대한피부과학회지

Primary cutaneous large cell lymphomas of the T-cell phenotype are relatively uncommon. Previous studies have revealed the following prognostic variables: the distribution of skin lesions, a history of pre-existing mycosis fungoides, CD30(Ki-1) antigen positivity and anaplastic morphology. CD30 antigen positivity has been associated with an indolent clinical course, in contrast to CD30-negative cases. However, a recent study revealed that multicentric skin lesions confer a worse prognosis on this subgroup of patients rather than the absence of CD30 antigen. p53 immunoreactivity also has been reported to be associated with high grade non-Hodgkin's lymphoma, although it is relatively uncommon. Herein, we report a case of a patient with EBV-related, CD30-negative primary cutaneous large cell lymphoma of the T-cell phenotype showing p53 and mdm-2 expression. She was initially diagnosed as having a benign-looking deep folliculitis or furunculosis, but treated successfully with radiation therapy without recurrence up to now.

Prevalence of Penicillinase-Producing Neisseria Gonorrhoeae (PPNG) in Seoul (1995)

BACKGROUND: In recent years gonorrhea has been pandemic and remains one of the most common sexually transmitted diseases(STD) in the world, especially in developing countries. OBJECTIVE & METHOD: For the detection of a more effective therapeutic regimen and to assess the prevalence of penicillinase-producing Neisseria gonorrhoeae (PPNG), we have been studying patients who have visited the VD Clinic of Choong-ku Public Health Center in Seoul since 1980 by means of the chromogenic cephalosporin method. RESULTS: In 1995, 97 strains of N. gonorrhoeae were isolated, among which 41(42.3%) were PPNG. CONCLUSION: Since the prevalence of PPNG was reported as 21.9% in 1981, the rate fluctuated. However, in 1993, there was an increase up to 74.3%. Thereafter, the prevalence rate decreased to 64.3% in 1994 and 42.3% in 1995. These changes will therefore need continuous observation.

Chronic Cutaneous Lupus Erythematosus in Two Sisters / 대한피부과학회지

Scalp involvements occur in 30-60% of patients with chronic cutaneous lupus erythematosus (CCLE), and may result in irreversible cicartricial alopecia due to follicular destructions. The pathogenesis of CCLE is consiclered to be multifactorial; relevant factors would be immunogenetic, hormonal, and environmental ir fluences. Perhaps, the immunogenetic factors may be more important. We report a case of two sisters who had superficial scarring alopecia on the scalp, in the constitutions of underlying mixed connective tissue disease (MCTD) and undifferentiated connective tissue syndrome (UCTS), respectively. This sister-CCLE case is regarded to be the first report among familial CCLE in Korea.