LATERAL TORSIONAL BUCKLING OF MONOSYMMETRIC DOUBLY STEPPED I-BEAM SUBJECTED TO UNIFORM MOMENT

Kathleen G. M,Kang Hyo Gi(강효기),Park Jong Sup(박종섭),Choi Snag Hyun(최상현) 대한토목학회 2009 대한토목학회 학술대회 Vol.2009 No.10

Cutaneous mucormycosis of the lower extremity leading amputation in two diabetic patients

Coerdt, Kathleen M.,Zolper, Elizabeth G.,Starr, Amy G.,Fan, Kenneth L.,Attinger, Christopher E.,Evans, Karen K. Korean Society of Plastic and Reconstructive Surge 2021 Archives of Plastic Surgery Vol.48 No.2

Mucormycosis is an invasive, rapidly progressive, life-threatening fungal infection, with a propensity for diabetic, immunosuppressed, and trauma patients. The classic rhinocerebral variation is most common in diabetic patients. While the cutaneous form is usually caused by direct inoculation in immunocompetent patients. Cutaneous mucormycosis manifests in soft tissue and risks involvement of underlying structures. Tibial osteomyelitis can also occur secondary to cutaneous mucormycosis but is rare. Limb salvage is typically successful after lower extremity cutaneous mucormycosis even when the bone is involved. Herein, we report two cases of lower extremity cutaneous mucormycosis in diabetic patients that presented as acute worsening of chronic pretibial ulcers. Despite aggressive antifungal therapy and surgical debridement, both ultimately required amputation. Such aggressive presentation has not been reported in the absence of major penetrating trauma, recent surgery, or burns.

Human bone marrow-derived mesenchymal stromal cells expressing S-TRAIL as a cellular delivery vehicle for human glioma therapy.

Menon, Lata G,Kelly, Kathleen,Yang, Hong Wei,Kim, Seung-Ki,Black, Peter M,Carroll, Rona S AlphaMed Press 2009 Stem Cells Vol.27 No.9

<P>Glioblastoma is among the most aggressive and treatment resistant of all human cancers. Conventional therapeutic approaches are unsuccessful because of diffuse infiltrative invasion of glioma tumor cells into normal brain parenchyma. Stem cell-based therapies provide a promising approach for the treatment of malignant gliomas because of their migratory ability to invasive tumor cells. Our therapeutic strategy was to use human bone marrow-derived mesenchymal stromal cells (hMSCs) as a cellular vehicle for the targeted delivery and local production of the biologic agent tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) at the glioma tumor site. hMSCs were transduced with a lentivirus expressing secretable TRAIL (S-TRAIL) and mCherry (red fluorescent protein). Our results clearly demonstrate the retention of tumor tropic ability of hMSC S-TRAIL cells by in vitro and in vivo migration assays. In vitro assays confirmed the expression, release, and biological activity of S-TRAIL produced by hMSC S-TRAIL cells. For the in vivo assessment of therapeutic efficacy, hMSCs were injected ipsilateral to an established intracranial glioma tumor in a mouse xenograft model. Genetically engineered hMSC S-TRAIL cells were effective in inhibiting intracranial U87 glioma tumor growth (81.6%) in vivo and resulted in significantly longer animal survival. Immunohistochemical studies demonstrated significant, eight fold greater tumor cell apoptosis in the hMSC S-TRAIL-treated group than in controls. Our study demonstrates the therapeutic efficacy of hMSC S-TRAIL cells and confirms that hMSCs can serve as a powerful cell-based delivery vehicle for the site-specific release of therapeutic proteins.</P>

Cinnamyl alcohol attenuates vasoconstriction by activation of K+ channels via NO-cGMP-protein kinase G pathway and inhibition of Rho-kinase

강윤환,양인준,Kathleen G. Morgan,신흥묵 생화학분자생물학회 2012 Experimental and molecular medicine Vol.44 No.12

Cinnamyl alcohol (CAL) is known as an antipyretic, and a recent study showed its vasodilatory activity without explaining the mechanism. Here we demonstrate the vasodilatory effect and the mechanism of action of CAL in rat thoracic aorta. The change of tension in aortic strips treated with CAL was measured in an organ bath system. In addition, vascular strips or human umbilical vein endothelial cells (HUVECs) were used for biochemical experiments such as Western blot and nitrite and cyclic guanosine monophosphate (cGMP)measurements. CAL attenuated the vasoconstriction of phenylephrine (PE, 1 μM)-precontracted aortic strips in an endothelium-dependent manner. CAL-induced vasorelaxation was inhibited by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME; 10-4 M),methylene blue (MB; 10-5 M) and 1 H-[1,2,4]-oxadiazolole-[4,3-a] quinoxalin-10one, (ODQ; 10-6 or 10-7M) in the endothelium-intact aortic strips. Atrial natriuretic peptide (ANP; 10-8 or 10-9 M) did not affect the vasodilatory effect of CAL. The phosphorylation of endothelial nitric oxide synthase (eNOS) and generation of nitric oxide (NO) were stimulated by CAL treatment in HUVECs and inhibited by treatment with L-NAME. In addition,cGMP and PKG1 activation in aortic strips treated with CAL were also significantly inhibited by L-NAME. Furthermore, CAL relaxed Rho-kinase activator calpeptin-precontracted aortic strips, and the vasodilatory effect of CAL was inhibited by the ATP-sensitive K+ channel inhibitor glibenclamide (Gli; 10-5 M) and the voltage-dependent K+ channel inhibitor 4-aminopyridine (4-AP; 2 × 10-4 M). These results suggest that CAL induces vasorelaxation by activating K+ channels via the NO-cGMP-PKG pathway and the inhibition of Rho-kinase.

Anti-Inflammatory Properties of a Dried Fermentate In Vitro and In Vivo

Gitte S. Jensen,Steve G. Carter,Stuart G. Reeves,Larry E. Robinson,Kathleen F. Benson 한국식품영양과학회 2015 Journal of medicinal food Vol.18 No.3

The aim of this study was to document anti-inflammatory properties of a dried fermentate derived from Saccharomyces cerevisiae (EpiCor® ), hereafter referred to as dried fermentate in vitro using cell-based bioassays, and in vivo using a skin irritation model in healthy humans. In vitro testing involved parallel assessment of primary human polymorphonuclear (PMN) cell formation of reactive oxygen species (ROS) and migration toward the inflammatory mediator Leukotriene B4. In vivo evaluation used a single-blind placebo-controlled design, where dermal histamine-induced inflammation was used as a model for the complex intercellular signals involved in the initiation, escalation, and resolution of the inflammatory response. Microvascular blood perfusion was evaluated using noninvasive laser Doppler probes applied to the inner forearms of 12 healthy human subjects, where parallel sites were treated with either dried fermentate or saline (placebo). Subjective scores of dermal irritation were also collected. Treatment of PMN cells in vitro resulted in reduced ROS formation and migratory activity toward Leukotriene B4. Clinical results demonstrated significantly reduced microvascular inflammatory responses to histamine-induced skin inflammation, and significantly reduced subjective scores of irritation at the inflamed sites treated with dried fermentate compared with the sites treated with placebo (P < .05). Treatment of inflammatory cells in vitro with dried fermentate resulted in reduced inflammatory responses. This was confirmed in vivo, suggesting that the dried fermentate facilitates the resolution of inflammatory responses. The effects using a topical skin model suggest that similar events may happen when the dried fermentate is introduced across mucosal membranes after consumption.

Weight Gain during Early Adulthood, Trajectory of Body Shape and the Risk of Non-Alcoholic Fatty Liver Disease Among Women : A Prospective Cohort Study

( Mi Na Kim ),( Chun-han Lo ),( Kathleen E. Corey ),( Mingyang Song ),( Tracey G. Simon ),( Andrew T. Chan ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Obesity is established as a major risk factor for the development of nonalcoholic fatty liver disease (NAFLD). However, the influence of changes in adiposity over the life course on NAFLD risk remains poorly understood. Methods: This study included 110,054 women in the Nurses’ Health Study II cohort without NAFLD at baseline (in 1995), who were followed prospectively through 2015. Early adulthood weight change was defined as the difference between early adulthood weight (at age 18 years) and the weight reported in the current questionnaire cycle. We used a group-based modeling approach to identify five trajectories of body shape from age 5 years up to 50. Results: We documented 3,798 incident cases of NAFLD over 20 years of follow-up (1,842,560 person-years). An elevated early adulthood body mass index (BMI) and weight gain since early adulthood were significantly and positively associated with the risk of incident NAFLD (all P trend <0.0001). Compared to women who maintained stable weight (+/-2 kg), women with ≥20 kg of early adulthood weight gain had the multivariable adjusted hazard ratio (aHR) of 6.96 (95% confidence interval [CI], 5.27-9.18), and this remained significant after further adjusting for updated BMI (P trend <0.0001). Compared to women with a medium-stable body shape trajectory, the multivariable aHRs for NAFLD risk were, 2.84 (95% CI, 2.50-3.22) for lean-marked increase, 2.60 (95% CI, 2.27-2.98) for medium-moderate increase, and 3.39 (95% CI, 2.95-3.89) for medium-marked increase. Conclusions: Both early adulthood weight gain and lifetime body shape trajectory were significantly and independently associated with excess risk of developing NAFLD. Maintaining both lean and stable weight throughout life may offer the greatest benefit for the prevention of NAFLD.

Poster Session 5 : Tumor Biology Developmental Biology Plant Biology Molecular Medicine and Gene Therapy Procaryotic Genetics Biotechnology ; Vasodilation by Banhabackchulchunmatang, a chinese medicine, is associated with negative modulation of PKCα activ

( Heung Mook Shin ),( Soo Young Jun ),( Kathleen G. Morgan ) 한국생화학분자생물학회 (구 한국생화학회) 2003 생화학분자생물학회 춘계학술발표논문집 Vol.2003 No.-

Long-Term Use of Antibiotics and the Risk of Non-Alcoholic Fatty Liver Disease: A Prospective Cohort Study among Women

( Mi Na Kim ),( Chun-han Lo ),( Kathleen E. Corey ),( Xuehong Zhang ),( Andrew T. Chan ),( Tracey G. Simon ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Gut microbial dysbiosis is associated with the development of nonalcoholic fatty liver disease (NAFLD). Antibiotics can alter the composition of the gut microbiota. However, the association of antibiotic use with the risk of NAFLD has not been clarified in a population at usual risk. We investigated the association of the duration of antibiotic use in different phases of adulthood with the risk of NAFLD. Methods: This study included 68,644 women in the Nurses’ Health Study II cohort without NAFLD at baseline (in 2005). Participants were followed prospectively through 2015. In the 2005 questionnaire, women were asked to indicate the cumulative amount of antibiotic use at age 20-39 years (young adulthood) or 40-49 years (middle adulthood). Cox proportional hazard models were used to estimate multivariable adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Results: Over a total of 534,644 person-years, we documented 1,944 incident cases of NAFLD. Compared to women with no antibiotic use during young adulthood, use of long-term antibiotics for ≥2 months was associated with significantly increased risk of incident NAFLD (multivariable aHR 1.48, 95% CI 1.03- 2.11). In analyses focused on middle adulthood, compared to women who did not use antibiotics during middle adulthood, those with both short-term (<2 months) and long-term (≥2 months) antibiotics use had significantly increased risk of incident NAFLD (multivariable aHRs, 1.32 [95% CI 1.01-1.72] and 1.83 [95% CI 1.37-2.45], respectively). Conclusions: In conclusion, long-term antibiotic use in both young and middle adulthood was associated with a significantly increased risk of developing incident NAFLD. These findings support the potential role of the gut microbiota in the pathogenesis of NAFLD.

A Prospective Cohort Study of Red Meat Consumption and Non-Alcoholic Fatty Liver Disease Risk Among Women

( Mi Na Kim ),( Chun-han Lo ),( Kathleen E. Corey ),( Xiao Luo ),( Xuehong Zhang ),( Andrew T. Chan ),( Tracey G. Simon ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Previous studies have suggested consumption of red meat might be associated with an increased risk of developing nonalcoholic fatty liver disease (NAFLD). However, large-scale, prospective data regarding red meat consumption in relation to the incidence of NAFLD are lacking, nor is it known whether this association is mediated by obesity. Methods: This prospective cohort study included 77,795 women in the Nurses’ Health Study II cohort without NAFLD at baseline (in 1995), who provided detailed, validated information regarding diet, including consumption of red meat, every 4 years, through 2015. Lifestyle factors, clinical comorbidities and body mass index (BMI), were updated biennially. Cox proportional hazard models were used to estimate multivariable adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Results: Over 1,444,637 person years of follow-up, we documented 3,130 cases of incident NAFLD. Women consuming ≥2 servings of red meat per day had a 56% higher risk of developing incident NAFLD compared to women consuming ≤1 serving per week (95% CI, 1.26-1.93), after multivariable adjustment. Similarly, significant and positive associations were observed for both unprocessed and processed red meat (both P-trend< 0.0001). However, after further adjustment for BMI, all associations for red meat, including unprocessed and processed red meat, were attenuated and not statistically significant (all P-trend >0.05). BMI was estimated to mediate 66% (95% CI, 41.9%-83.9%; P<0.0001) of the association between red meat consumption and NAFLD risk. Conclusions: Red meat consumption, including both unprocessed and processed red meat, was associated with significantly increased risk of developing NAFLD. This association was mediated largely by obesity.

EphrinB1 interacts with the transcriptional co-repressor Groucho/xTLE4

( Teddy Kamata ),( Yong Sik Bong ),( Kathleen Mood ),( Mae Ja Park ),( Tagvor G. Nishanian ),( Hyun Shik Lee ) 생화학분자생물학회(구 한국생화학분자생물학회) 2011 BMB Reports Vol.44 No.3

Ephrin signaling is involved in various morphogenetic events, such as axon guidance, hindbrain segmentation, and angiogenesis. We conducted a yeast two-hybrid screen using the intracellular domain (ICD) of EphrinB1 to gain biochemical insight into the function of the EphrinB1 ICD. We identified the transcriptional co-repressor xTLE1/Groucho as an EphrinB1 interacting protein. Whole-mount in situ hybridization of Xenopus embryos confirmed the co-localization of EphrinB1 and a Xenopus counterpart to TLE1, xTLE4, during various stages of development. The EphrinB1/xTLE4 interaction was confirmed by co-immunoprecipitation experiments. Further characterization of the interaction revealed that the carboxy-terminal PDZ binding motif of EphrinB1 and the SP domain of xTLE4 are required for binding. Additionally, phosphorylation of EphrinB1 by a constitutively activated fibroblast growth factor receptor resulted in loss of the interaction, suggesting that the interaction is modulated by tyrosine phosphorylation of the EphrinB1 ICD. [BMB reports 2011; 44(3): 199-204]