Frequent low-impact exposure to THC during adolescence causes persistent sexually dimorphic alterations in the response to viral infection in mice.

Adolescent exposure to Δ9-tetrahydrocannabinol (THC) has enduring effects on energy metabolism and immune function. Prior work showed that daily administration of a low-impact dose of THC (5 mg/kg, intraperitoneal) during adolescence alters transcription in adult microglia and disrupts their response to bacterial endotoxin or social stress. To explore the lasting impact of adolescent THC exposure on the brain's reaction to viral infection, we administered THC (5 mg/kg, intraperitoneal) in male and female mice once daily on postnatal day (PND) 30-43. When the mice reached adulthood (PND 70), we challenged them with the viral mimic, polyinosinic acid:polycytidylic acid [Poly(I:C)], and assessed sickness behavior (motor activity, body temperature) and whole brain gene transcription. Poly(I:C) caused an elevation in body temperature which was lessened by prior THC exposure in female but not male mice. Adolescent THC exposure did not affect the locomotor response to Poly(I:C) in either sex. Transcriptomic analyses showed that Poly(I:C) produced a substantial upregulation of immune-related genes in the brain, which was decreased by THC in females. Additionally, the viral mimic caused a male-selective downregulation in transcription of genes involved in neurodevelopment and synaptic transmission, which was abrogated by adolescent THC treatment. The results indicate that Poly(I:C) produces complex transcriptional alterations in the mouse brain, which are sexually dimorphic and differentially affected by early-life THC exposure. In particular, adolescent THC dampens the brain's antiviral response to Poly(I:C) in female mice and prevents the transcriptional downregulation of neuron-related genes caused by the viral mimic in male mice.

Prospective Comparative Study of Etoposide plus G-CSF versus G-CSF Alone, Followed by Risk-Adapted Plerixafor for Peripheral Blood Stem Cell Mobilization in Patients with Newly Diagnosed Multiple Myeloma: CAtholic REsearch Network for Multiple Myeloma Study (CAREMM-2001).

To explore the optimal mobilization for multiple myeloma (MM) patients, we conducted a prospective trial comparing single-dose etoposide (375 mg/m2 for one day) plus G-CSF versus G-CSF alone, followed by risk-adapted plerixafor. After randomization, 27 patients in the etoposide group and 29 patients in the G-CSF alone group received mobilizations. Six (22.2%) patients in the etoposide group and 15 (51.7%) patients in the G-CSF alone group received plerixafor based on a peripheral blood CD34+ cell count of < 15/mm3 (p = 0.045). The median count of CD34+ cells collected was significantly higher in the etoposide group (9.5 × 106/kg vs. 7.9 × 106/kg; p = 0.018), but the optimal collection rate (CD34+ cells ≥ 6 × 106/kg) was not significantly different between the two groups (96.3% vs. 82.8%; p = 0.195). The rate of CD34+ cells collected of ≥ 8.0 × 106/kg was significantly higher in the etoposide group (77.8% vs. 44.8%; p = 0.025). Although the rates of grade II-IV thrombocytopenia (63.0% vs. 31.0%; p = 0.031) and grade I-IV nausea (14.8% vs. 0%; p = 0.048) were significantly higher in the etoposide group, the rates of adverse events were low in both groups, with no neutropenic fever or septic shock. Thus, both single-dose etoposide plus G-CSF and G-CSF alone with risk-adapted plerixafor were effective and safe, but the former may be the better option for patients who are expected to receive two or more transplantations.

Self-assembled Nucleic Acid Nanostructures for Biomedical Applications.

Structural DNA nanotechnology has been developed into a powerful method for creating self-assembled nanomaterials. Their compatibility with biosystems, nanoscale addressability, and programmable dynamic features make them appealing candidates for biomedical research. This review paper focuses on DNA self-assembly strategies and designer nanostructures with custom functions for biomedical applications. Specifically, we review the development of DNA self-assembly methods, from simple DNA motifs consisting of a few DNA strands to complex DNA architectures assembled by DNA origami. Three advantages are discussed using structural DNA nanotechnology for biomedical applications: (1) precise spatial control, (2) molding and guiding other biomolecules, and (3) using reconfigurable DNA nanodevices to overcome biomedical challenges. Finally, we discuss the challenges and opportunities of employing DNA nanotechnology for biomedical applications, emphasizing diverse assembly strategies to create a custom DNA nanostructure with desired functions.

Effectiveness of the Infectious Disease (COVID-19) Simulation Module Program on Nursing Students: Disaster Nursing Scenarios.

PURPOSE: This study aimed to develop an emerging infectious disease (COVID-19) simulation module for nursing students and verify its effectiveness. METHODS: A one-group pretest-posttest quasi-experimental study was conducted with 78 under-graduate nursing students. A simulation module was developed based on the Jeffries simulation model. It consisted of pre-simulation lectures on disaster nursing including infectious disease pandemics, practice, and debriefings with serial tests. The scenarios contained pre-hospital settings, home visits, arrival to the emergency department, and follow-up home visits for rehabilitation. RESULTS: Disaster preparedness showed a statistically significant improvement, as did competencies in disaster nursing. Confidence in disaster nursing increased, as did willingness to participate in disaster response. However, critical thinking did not show significant differences between time points, and neither did triage scores. CONCLUSION: The developed simulation program targeting an infectious disease disaster positively impacts disaster preparedness, disaster nursing competency, and confidence in disaster nursing, among nursing students. Further studies are required to develop a high-fidelity module for nursing students and medical personnel. Based on the current pandemic, we suggest developing more scenarios with virtual reality simulations, as disaster simulation nursing education is required now more than ever.

Aptamer-Functionalized DNA Nanostructures for Biological Applications.

DNA nanostructures hold great promise for various applications due to their remarkable properties, including programmable assembly, nanometric positional precision, and dynamic structural control. The past few decades have seen the development of various kinds of DNA nanostructures that can be employed as useful tools in fields such as chemistry, materials, biology, and medicine. Aptamers are short single-stranded nucleic acids that bind to specific targets with excellent selectivity and high affinity and play critical roles in molecular recognition. Recently, many attempts have been made to integrate aptamers with DNA nanostructures for a range of biological applications. This review starts with an introduction to the features of aptamer-functionalized DNA nanostructures. The discussion then focuses on recent progress (particularly during the last five years) in the applications of these nanostructures in areas such as biosensing, bioimaging, cancer therapy, and biophysics. Finally, challenges involved in the practical application of aptamer-functionalized DNA nanostructures are discussed, and perspectives on future directions for research into and applications of aptamer-functionalized DNA nanostructures are provided.

Parity Differently Affects the Breast Cancer Specific Survival from Ductal Carcinoma In Situ to Invasive Cancer: A Registry-Based Retrospective Study from Korea.

PURPOSE: Multiparity might increase general mortality for women, but has inconclusive in patients with breast cancer. Here, we aim to discover their effect in terms of the breast cancer development hypothesis: from ductal carcinoma in situ to invasive carcinoma. METHODS: We included 37 947 patients from the web-based breast cancer registration program of the Korean Breast Cancer Society and analyzed survivals using multivariate Cox regression analysis and whether the associations of these factors displayed linear trends. They were divided into the following groups: (1) pure ductal carcinoma in situ (DCIS), (2) invasive ductal carcinoma (IDC) mixed with intraductal component (DCIS-IDC), and (3) node negative pure IDC. RESULTS: The mean age was 48.9 ± 9.9 years including premenopausal women was 61.8%. Although patients with parities of 1-3 had better prognosis compared with patients with nulliparous women, high parity (⩾4) increased the hazard ratio (HR) of overall survival (OS) (DCIS: HR, 1.52; 95% confidence interval [CI] 0.62-3.78; IDC: HR, 1.43, 95% CI 0.89-2.31; and DCIS-IDC: HR, 1.44, 95% CI 0.45-4.59) during 84.2 (±10.7) months. For breast cancer specific survival (BCSS), the HR of the IDC group (P-value for trend = .04) increased along with increasing parity and was worse than nulliparous patients, and the HR of the DCIS-IDC group increased but was better than nulliparous patients (P-value for trend = .02). Compared with nulliparous patients, any age at first birth (AFB) decreased HR of OS in the DCIS and IDC groups (DCIS: P = .01; IDC: P = .04). CONCLUSIONS: Parity show dual effects on OS of women with all ductal typed breast cancer but show different effects on BCSS in Korea.

Sanitary pads and diapers contain higher phthalate contents than those in common commercial plastic products.

Sanitary pads and diapers are made of synthetic plastic materials that can potentially be released while being used. This study measured the amounts of volatile organic compounds (VOCs) (methylene chloride, toluene, and xylene) and phthalates (DBP, DEHP, DEP, and BBP) contained in sanitary pads and diapers. In sanitary pads, 5,900- and 130-fold differences of VOC and phthalate concentrations were seen among the brands. In the diapers, 3- and 63-fold differences of VOC and phthalate concentrations were detected among the brands. VOC concentrations from the sanitary pads and diapers were similar to that of the residential air. However, phthalate concentrations of sanitary pads and diapers were significantly higher than those found in common commercial plastic products. As sanitary pads and diapers are in direct contact with external genitalia for an extended period, there is a probability that a considerable amount of VOCs or phthalates could be absorbed into the reproductive system.

Impact of Cigarette Smoke Exposure on the Lung Fibroblastic Response after Influenza Pneumonia.

Influenza viruses can result in significant lung injury with significant morbidity and mortality. In this study, we evaluated the impact of cigarette smoke (CS) exposure on the pulmonary fibroblastic response after influenza infection. We used a murine model in which animals were exposed to CS or room air and subsequently infected with H1N1 influenza virus. Inflammatory and fibrotic responses were measured at different time points after influenza infection. Primary fibroblasts were isolated from the lungs of mice and their characteristics were evaluated. Exposure to CS significantly increased the amount of collagen in the lungs of mice infected with influenza virus compared with the nonsmoking group at 30 days after infection. Furthermore, the presence of fibroblast-specific protein-positive cells increased in the lungs of influenza-infected mice that were exposed to CS compared with the infection-alone group. The smoking group also showed delays in weight recovery and higher cell counts in BAL fluid after infection. Active transforming growth factor ß1 levels in BAL fluid increased in both groups; however, CS-exposed mice had a later surge in active transforming growth factor ß1 (Day 24). Ex vivo cultures of lung-derived fibroblasts from CS-exposed mice with influenza infection showed rapid proliferation, increased expression of α-smooth muscle actin-stained stress fibers, and higher expression of growth factors compared with fibroblasts from room air-exposed lungs after infection. These results suggest that CS exposure changes the fibroblastic potential, leading to increased fibrosis after influenza infection.

Decitabine as a First-Line Treatment for Older Adults Newly Diagnosed with Acute Myeloid Leukemia.

PURPOSE: Decitabine, a DNA hypomethylating agent, was recently approved for use in Korea for older adults with acute myeloid leukemia (AML) who are not candidates for standard chemotherapy. This study aimed to evaluate the role of decitabine as a first-line treatment for older adults with AML. MATERIALS AND METHODS: Twenty-four patients with AML who received at least one course of decitabine (20 mg/m²/d intravenously for 5 days every 4 weeks) as a first-line therapy at Severance Hospital were evaluated retrospectively. RESULTS: The median age of the patients was 73.5 years. The longest follow-up duration was 502 days. A total of 113 cycles of treatment were given to 24 patients, and the median number of cycles was four (range, 1-14). Thirteen patients dropped out because of death, no or loss of response, patient refusal, or transfer to another hospital. Twenty-one (87.5%) and 12 (50%) patients completed the second and fourth cycles, respectively, and responses to treatment were evaluated in 17. A complete response (CR) or CR with incomplete blood-count recovery was achieved in six (35.3%) patients, and the estimated median overall survival was 502 days. Ten patients developed grade >2 hematologic or non-hematologic toxicities. In univariate analysis, bone marrow blasts, lactate dehydrogenase, serum ferritin level, and bone marrow iron were significantly associated with response to decitabine. CONCLUSION: Five-day decitabine treatment showed acceptable efficacy in older patients with AML who are unfit for conventional chemotherapy, with a CR rate 35.3% and about a median overall survival of 18 months.

Bronchomediastinal fistula detected accidently during palliative radiation therapy.

Bronchomediastinal fistula is an extremely rare complication resulting from diseases such as mediastinitis or mediastinal malignancies. In patients with lung cancer, bronchomediastinal fistula formation has rarely been reported, except during post-chemotherapy or post-radiation therapy complications. An 84-year-old visited our hospital to receive palliative radiation therapy for squamous cell carcinoma of the right main bronchus T4N2M1a. During an early course of radiation therapy, chest computed tomography (CT) scans revealed bronchomediastinal fistula between the right main bronchus and the enlarged sub-carinal lymph nodes. Radiation therapy was, therefore, discontinued and the patient received only supportive care.

Early experience of the compression anastomosis ring (CAR™ 27) in left-sided colon resection.

AIM: To evaluate clinical validity of the compression anastomosis ring (CAR™ 27) anastomosis in left-sided colonic resection. METHODS: A non-randomized prospective data collection was performed for patients undergoing an elective left-sided colon resection, followed by an anastomosis using the CAR™ 27 between November 2009 and January 2011. Eligibility criteria of the use of the CAR™ 27 were anastomoses between the colon and at or above the intraperitoneal rectum. The primary short-term clinical endpoint, rate of anastomotic leakage, and other clinical outcomes, including intra- and postoperative complications, length of operation time and hospital stay, and the ring elimination time were evaluated. RESULTS: A total of 79 patients (male, 43; median age, 64 years) underwent an elective left-sided colon resection, followed by an anastomosis using the CAR™ 27. Colectomy was performed laparoscopically in 70 patients, in whom two patients converted to open procedure (2.9%). There was no surgical mortality. As an intraoperative complication, total disruption of the anastomosis occurred by premature enforced tension on the proximal segment of the anastomosis in one patient. The ring was removed and another new CAR™ 27 anastomosis was constructed. One patient with sigmoid colon cancer showed postoperative anastomotic leakage after 6 d postoperatively and temporary diverting ileostomy was performed. Exact date of expulsion of the ring could not be recorded because most patients were not aware that the ring had been expelled. No patients manifested clinical symptoms of anastomotic stricture. CONCLUSION: Short-term evaluation of the CAR™ 27 anastomosis in elective left colectomy suggested it to be a safe and efficacious alternative to the standard hand-sewn or stapling technique.

A case of familial cutaneous collagenoma.

Familial cutaneous collagenoma is a rare hereditary disease that is inherited in an autosomal dominant pattern. It is characterized by early onset of multiple, skin-colored, sometimes hypopigmented cutaneous nodules, which initially show a symmetrical arrangement on the trunk, and later on the neck and upper limbs. We report on a case of a 45-year-old female who presented with multiple oval to round hypopigmented papules measuring 5~15 mm on her trunk. Histopathologically, the lesions showed an increased amount of collagen fibers and decreased, fragmented elastic fibers in the dermis. The skin lesions were diagnosed as familial cutaneous collagenoma and no treatment was administered. To the best of our knowledge, our case is the first reported case of familial cutaneous collagenoma (FCC) in the Korean literature.

The effects of platelet-rich plasma derived from human umbilical cord blood on the osteogenic differentiation of human dental stem cells.

Platelet-rich plasma (PRP) is an emerging therapeutic application because PRP contains various growth factors that have beneficial effects on tissue regeneration and engineering. Mesenchymal stem cells and PRP derived from peripheral blood have been well studied. In this study, we investigated the effects of PRP derived from human umbilical cord blood (UCB-PRP) on proliferation, alkaline phosphatase (ALP) activity, and osteogenic differentiation of stem cells from human exfoliated deciduous teeth (SHEDs), dental pulp stem cells (DPSCs), and periodontal ligament stem cells (PDLSCs). Three types of dental stem cells were primarily isolated and characterized by flow cytometric analysis. Dental stem cells were exposed to various concentrations of UCB-PRP, which resulted in the proliferation of dental stem cells. Treatment with 2% UCB-PRP resulted in the highest level of proliferation. The ALP activity of DPSCs and PDLSCs increased following treatment with UCB-PRP in a dose-dependent manner up to a concentration of 2%. ALP activity decreased with higher concentration of UCB-PRP. The effects of UCB-PRP on calcium deposition were similar to those on proliferation and ALP activity. Treatment with 2% UCB-PRP resulted in the highest calcium depositions in DPSCs and PDLSCs; however, treatment with 1% UCB-PRP resulted in the highest calcium deposition in SHEDs. The concentrations of platelet-derived growth factor-AB and transforming growth factor-ß1 in UCB-PRP were investigated and found to be comparable to the amounts in peripheral blood. Overall, UCB-PRP had beneficial effects on the proliferation and osteogenic differentiation of dental stem cells. Determination of the optimal concentration of UCB-PRP requires further investigation for clinical applications.

Regulation of polar peptidoglycan biosynthesis by Wag31 phosphorylation in mycobacteria.

BACKGROUND: Sensing and responding to environmental changes is a central aspect of cell division regulation. Mycobacterium tuberculosis contains eleven Ser/Thr kinases, two of which, PknA and PknB, are key signaling molecules that regulate cell division/morphology. One substrate of these kinases is Wag31, and we previously showed that partial depletion of Wag31 caused morphological changes indicative of cell wall defects, and that the phosphorylation state of Wag31 affected cell growth in mycobacteria. In the present study, we further characterized the role of the Wag31 phosphorylation in polar peptidoglycan biosynthesis. RESULTS: We demonstrate that the differential growth among cells expressing different wag31 alleles (wild-type, phosphoablative, or phosphomimetic) is caused by, at least in part, dissimilar nascent peptidoglycan biosynthesis. The phosphorylation state of Wag31 is found to be important for protein-protein interactions between the Wag31 molecules, and thus, for its polar localization. Consistent with these results, cells expressing a phosphomimetic wag31 allele have a higher enzymatic activity in the peptidoglycan biosynthetic pathway. CONCLUSIONS: The Wag31Mtb phosphorylation is a novel molecular mechanism by which Wag31Mtb regulates peptidoglycan synthesis and thus, optimal growth in mycobacteria.

A case of accessory tragus on the nasal vestibule.

We present a case of accessory tragus (AT) which developed at an unusual site, the nasal vestibule, of a 1-day-old girl. To our knowledge, this is the first report of an accessory tragus that appears on the nasal vestibule.

Novel diagnostic algorithm using tuf gene amplification and restriction fragment length polymorphism is promising tool for identification of nontuberculous mycobacteria.

Nontuberculous mycobacteria (NTM) are a major cause of opportunistic infections in immunocompromised patients, making the reliable and rapid identification of NTM to the species level very important for the treatment of such patients. Therefore, this study evaluated the usefulness of the novel target genes tuf and tmRNA for the identification of NTM to the species level, using a PCRrestriction fragment length polymorphism analysis (PRA). A total of 44 reference strains and 17 clinical isolates of the genus Mycobacterium were used. The 741 bp or 744 bp tuf genes were amplified, restricted with two restriction enzymes (HaeIII/MboI), and sequenced. The tuf gene-PRA patterns were compared with those for the tmRNA (AvaII), hsp65 (HaeIII/HphI), rpoB (MspI/HaeIII), and 16S rRNA (HaeIII) genes. For the reference strains, the tuf gene-PRA yielded 43 HaeIII patterns, of which 35 (81.4%) showed unique patterns on the species level, whereas the tmRNA, hsp65, rpoB, and 16S rRNA-PRAs only showed 10 (23.3%), 32 (74.4%), 19 (44.2%), and 3 (7%) unique patterns after single digestion, respectively. The tuf gene-PRA produced a clear distinction between closely related NTM species, such as M. abscessus (557-84- 58) and M. chelonae (477-84-80-58), and M. kansasii (141- 136-80-63-58-54-51) and M. gastri (141-136-117-80-58-51). No difference was observed between the tuf-PRA patterns for the reference strains and clinical isolates. Thus, a diagnostic algorithm using a tuf gene-targeting PRA is a promising tool with more advantages than the previously used hsp65, rpoB, and 16S rRNA genes for the identification of NTM to the species level.

Wag31, a homologue of the cell division protein DivIVA, regulates growth, morphology and polar cell wall synthesis in mycobacteria.

The Mycobacterium tuberculosis genome contains 11 serine/threonine kinase genes, and the products of two of these, PknA and PknB, are key components of a signal transduction pathway that regulates cell division and/or morphology. Previously, we have shown that one substrate of these kinases is Wag31, a homologue of the cell division protein DivIVA that is present, but not known to be phosphorylated, in other Gram-positive bacteria. Here, we investigate the localization and function of Wag31 and its phosphorylation. We demonstrate that Wag31 is localized to the cell poles. We further show that wag31 is an essential gene and that depletion of its product causes a dramatic morphological change in which one end of the cell becomes round rather than rod-shaped. This abnormal morphology appears to be caused by a defect in polar peptidoglycan synthesis. Finally, expression of M. tuberculosis wag31 in the wag31 conditional mutant of Mycobacterium smegmatis altered the growth rate in a manner that depended on the phospho-acceptor residue encoded by the allele being expressed. Taken together, these results indicate that Wag31 regulates cell shape and cell wall synthesis in M. tuberculosis through a molecular mechanism by which the activity of Wag31 can be modulated in response to environmental signals.

Anti-emetic effect of oculo-acupuncture on dogs with xylazine induced vomiting.

The present study was conducted in order to clarify the anti-emetic effect of oculo-acupuncture (OA) on dogs with xylazine-induced vomiting, and also to compare the anti-emetic effect of OA and body acupuncture (AP). Twelve dogs induced to vomit by xylazine were selected from total 29 mongrel dogs in preliminary experiment and were used as subjects in this study. This study was comprised of two experiments. In experiment 1, the anti-emetic effects of OA on dogs were examined in the stomach/spleen region (experimental group I), the zhongjiao region (experimental group II), and the stomach/spleen region plus the zhongjiao region (experimental group III) using 12 dogs induced to vomit for one week interval repeatedly. On the other hand, needle acupuncture (AP) (BL20 + BL21, experimental group A) and OA (stomach/spleen and zhong jiao regions) combined with needle AP (BL20 + BL21) (experimental group B) were examined using 6 vomiting dogs, for one week interval repeatedly in experiment 2. As a result, the vomiting rates of experimental group I (50%, p < 0.05), experimental group II (58.3%) and experimental group III (41.6%, p < 0.01) were lower than that of control (100%), respectively in experiment 1. The vomiting rates of both experimental group A (50%, p < 0.05) and experimental group B (50%, p < 0.05) were lower than that of control (100%) in experiment 2. The starting vomiting time in experimental groups was similar to that of the control groups in experiment 1 and 2. This study demonstrated that OA had anti-emetic effects on dogs with xylazine-induced vomiting and OA in the stomach/spleen region plus the zhongjiao region was the most effective in anti-emesis among the experimental groups. In addition, body AP and OA combined with body AP had a similar anti-emetic effect on dogs with xylazine-induced vomiting.

The comparison on changes of the body heats in electroacupuncture analgesia and anesthesia by ketamine hydrochloride in dogs.

This study was performed to clarify the differences of the body heats between electroacupuncture analgesia (EA) and anesthesia by ketamine hydrochloride (ketamine anesthesia) in dogs. Nine clinically healthy dogs were divided into ketamine anesthesia (control: 5 heads) and EA (experimental: 4 heads) groups, respectively. The acupoints GV-5 and Bai-Hui were used. The infrared thermographic system was used to determine the body heats. The body heats was determined at areas such as the dorsocranial (DCr), dorsocaudal (DCd), ventrocranial (VCr) and ventrocaudal (VCd) regions, on pretreatment, 10, 20, 30, 50 and 90 minutes after treatments, respectively in control and experimental groups. The body heats showed decreasing tendency until 30 minutes after ketamine injection, and then showed increasing pattern until 90 minutes after at all areas investigated in the control group. However, no significant differences of the body heats in the DCr, DCd, VCr and VCd regions were found in the control group. On the other hand, the body heats showed increasing tendency until 30 minutes, and then showed decreasing pattern until 90 minutes after EA, in the experimental group. The significant difference was observed at 30 minutes in the DCr region, and also at 10, 20 and 30 minutes in the DCd regions in the experimental group (p < 0.05). The significant differences of the body heats were detected at 20 minutes in the DCr region, at 30 minutes in the DCd region and at 30 minutes in the VCd region between the experimental and control groups (p < 0.05). In conclusion, EA increases of the body heat in the contrary to that of ketamine anesthesia.

The polycomb group gene product Mel-18 interacts with cyclin D2 and modulates its activity.

Considerable evidence supports the view that D-type cyclins play a role in G1-S progression. We found that cyclin D2 directly interacts with Mel-18, one of the polycomb group gene products in a yeast two hybrid screen. Further, we have determined the binding domains that are required for interaction between cyclin D2 and Mel-18. The proline/serine-rich domain (P/S domain) of Mel-18 is required to interact with cyclin D2, and the N-terminal region of cyclin D2 is necessary to interact with Mel-18. A co-localization study shows that cyclin D2 and Mel-18 interact within the nucleus. To determine whether Mel-18 affects cyclin D2 activity, we blocked Mel-18 expression using an anti-sense strand system in cyclin D2 over-expressing cells. The results indicate that cells with reduced Mel-18 expression levels show more proliferative activity than the controls. These findings are the first report that Mel-18 directly interacts with cyclin D2 and may inhibit cyclin D2 activity.