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1.  Clinical utilization of cord blood over human health: experience of stem cell transplantation and cell therapy using cord blood in Korea 
Korean Journal of Pediatrics  2014;57(3):110-116.
Cord blood (CB) has been used as an important and ethical source for hematopoietic stem cell transplantation (SCT) as well as cell therapy by manufacturing mesenchymal stem cell, induced pleuripotential stem cell or just isolating mononuclear cell from CB. Recently, the application of cell-based therapy using CB has expanded its clinical utility, particularly, by using autologous CB in children with refractory diseases. For these purposes, CB has been stored worldwide since mid-1990. In this review, I would like to briefly present the historical development of clinical uses of CB in the fields of SCT and cell therapy, particularly to review the experiences in Korea. Furthermore, I would touch the recent banking status of CB.
PMCID: PMC4000756  PMID: 24778692
Cord blood; Transplantation; Cell therapy
2.  Meta-analysis of randomized controlled trials of bosentan for treatment of pulmonary arterial hypertension 
We assessed the efficacy and safety of bosentan in patients with pulmonary arterial hypertension (PAH).
We surveyed randomized controlled trials (RCTs) of the efficacy and safety of bosentan in patients with PAH using MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and manual searches. Meta-analysis of RCTs was performed to determine treatment efficacy and safety outcomes. Results are presented as odds ratios (ORs) or weighted mean differences (WMDs).
Meta-analysis of seven RCTs including a total of 410 patients and 296 controls revealed that the 6-minute work distance was significantly higher in the bosentan group than in the placebo group (WMD, 46.19; 95% confidence interval [CI], 21.20 to 71.19; p = 2.9 × 10-5). Compared with the placebo, bosentan significantly reduced the mean pulmonary arterial pressure in patients with PAH (WMD, -6.026; 95% CI, -8.785 to -3.268, p = 1.8 × 10-6). The bosentan therapy group worsened less clinically than the placebo group (OR, 0.252; 95% CI, 0.140 to 0.454; p = 4.6 × 10-7). The incidence of serious adverse events did not differ between the bosentan and placebo groups (OR, 0.948; 95% CI, 0.556 to 1.614; p = 0.843). However, the results of the abnormal liver function test (LFT) were significantly higher in the bosentan group than in the placebo group (OR, 2.312; 95% CI, 1.020 to 5.241; p = 0.045).
This meta-analysis shows that bosentan can treat PAH effectively. However, bosentan increased the incidence of abnormal LFT results compared with the placebo.
PMCID: PMC3846996  PMID: 24307846
Bosentan; Efficacy; Safety; Hypertension, pulmonary
3.  Responsiveness of the Korean Version of the Michigan Hand Outcomes Questionnaire after Carpal Tunnel Release 
Clinics in Orthopedic Surgery  2014;6(2):203-207.
The Korean version of the Michigan Hand Outcomes Questionnaire (K-MHQ) was recently validated; however, the questionnaire's responsiveness as well as the degree to which the instrument is sensitive to change has not been thoroughly evaluated in a specific condition in Koreans. We evaluated the responsiveness of the K-MHQ in a homogenous cohort of patients with carpal tunnel syndrome (CTS) and we compared it with that of the Korean version of the Disability of the Arm, Shoulder, and Hand Questionnaire (K-DASH), which was found to have a large degree of responsiveness after carpal tunnel release for Korean patients with CTS.
Thirty-seven patients with CTS prospectively completed the K-MHQ and the K-DASH before and 6 months after surgery. The responsiveness statistics were assessed for both the K-MHQ and the K-DASH by using the standardized response mean (SRM), which was defined as the mean change of the original scores after surgery divided by the standard deviation of the change.
All domains of the K-MHQ significantly improved after carpal tunnel release (p < 0.001). The SRM for all scales but one (the aesthetics scale) showed large responsiveness of ≥ 0.8. The aesthetics scale showed medium responsiveness of 0.6. The combined function/symptom scale of the K-DASH significantly improved after surgery (p < 0.001). The SRM of the K-DASH revealed large responsiveness of 0.9.
The K-MHQ was found to have a large degree of responsiveness after carpal tunnel release for Korean patients with CTS, which is comparable not only to the K-DASH, but also to the original version of the MHQ. The region-specific K-MHQ can be useful for outcomes research related to carpal tunnel surgery, especially for research comparing CTS with various other hand and wrist health conditions.
PMCID: PMC4040382  PMID: 24900903
Responsiveness; K-MHQ; K-DASH; Carpal tunnel syndrome
4.  Thromboembolic events identified during diagnosis of germ cell tumors in 2 children 
The Korean Journal of Hematology  2012;47(3):233-236.
We describe 2 cases in which radiographic evidence of thromboembolic events was obtained during germ cell tumor diagnosis. There was no evidence of coagulation factor abnormalities or contributory procedures or drugs in either patient. We used anticoagulation therapy for thrombolysis in one patient, but in the other, the thromboembolism resolved spontaneously.
PMCID: PMC3464343  PMID: 23071481
Thromboembolism; Germ cell tumor; Chemotherapy
5.  Enactment of a Law for Governmental Support of the Use of Cord Blood, and Ethical Issues 
In Korea, cord blood banking projects have been developed since 1996, and the 1st successful cord blood transplant was performed in 1998. Recently, “Cord Blood Management and Research Act” was legislated in 2010, and has been come into effect on July 1st, 2011. This review focuses the backgrounds, aims, and legislation process as well as principal articles in this act.
PMCID: PMC3840985  PMID: 24298360
Cord blood; Act
6.  Roles of protein arginine methylation in DNA damage signaling pathways 
Cell Cycle  2011;10(9):1343-1344.
PMCID: PMC3117038  PMID: 21445011
BRCA1; p300; CARM1; DNA damage; protein methylation; p21; Gadd45; cell cycle; apoptosis; cancer
7.  Triple disruption of the superior shoulder suspensory complex 
The superior shoulder suspensory complex (SSSC) is an extremely important structure composed of a ring of bone and soft tissues at the superior aspect of the shoulder. Double disruption leads to instability of the construct and usually requires operative treatment. Triple disruption of the SSSC is extremely rare and is encountered in high-energy trauma cases often in association with other injuries. The authors experienced a case of triple disruption involving the acromion, coracoid process, and acromioclavicular separation. This type of SSSC disruption is unlikely to have been caused by a single impact and is rather caused by multiple impacts during one traumatic event.
PMCID: PMC3391788  PMID: 22787337
Superior shoulder suspensory complex; SSSC; triple disruption
8.  A Multi-Classifier Based Guideline Sentence Classification System 
Healthcare Informatics Research  2011;17(4):224-231.
An efficient clinical process guideline (CPG) modeling service was designed that uses an enhanced intelligent search protocol. The need for a search system arises from the requirement for CPG models to be able to adapt to dynamic patient contexts, allowing them to be updated based on new evidence that arises from medical guidelines and papers.
A sentence category classifier combined with the AdaBoost.M1 algorithm was used to evaluate the contribution of the CPG to the quality of the search mechanism. Three annotators each tagged 340 sentences hand-chosen from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) clinical guideline. The three annotators then carried out cross-validations of the tagged corpus. A transformation function is also used that extracts a predefined set of structural feature vectors determined by analyzing the sentential instance in terms of the underlying syntactic structures and phrase-level co-occurrences that lie beneath the surface of the lexical generation event.
The additional sub-filtering using a combination of multi-classifiers was found to be more effective than a single conventional Term Frequency-Inverse Document Frequency (TF-IDF)-based search system in pinpointing the page containing or adjacent to the guideline information.
We found that transformation has the advantage of exploiting the structural and underlying features which go unseen by the bag-of-words (BOW) model. We also realized that integrating a sentential classifier with a TF-IDF-based search engine enhances the search process by maximizing the probability of the automatically presented relevant information required in the context generated by the guideline authoring environment.
PMCID: PMC3259557  PMID: 22259724
Knowledge Bases; Data Mining; Natural Language Processing
9.  Efficacy and Safety of Monthly 150 mg Oral Ibandronate in Women with Postmenopausal Osteoporosis: A Systematic Review and Meta-analysis of Randomized Controlled Trials 
The aim of this study was to assess the efficacy and safety of monthly oral 150 mg ibandronate in women with postmenopausal osteoporosis (PMO).
A systematic review and meta-analysis were performed to determine treatment efficacy and safety outcomes between monthly oral 150 mg ibandronate and weekly 70 mg alendronate, daily 2.5 mg ibandronate, and a placebo.
Eight randomized controlled trials were included in this systematic review and meta-analysis. Once-monthly 150 mg ibandronate therapy was clinically comparable to weekly 70 mg alendronate, showing increased bone mineral density (BMD) in both the lumbar spine and total hip. Pooled data from two cross-over trials showed that significantly more women with PMO preferred once-monthly ibandronate therapy to once-weekly alendronate therapy (relative risk [RR], 2.422; 95% confidence interval [CI], 2.111 to 2.825; p < 1 × 10-8) and found the monthly ibandronate regimen more convenient than the weekly alendronate regimen (RR, 3.096; 95% CI, 2.622 to 3.622; p < 1 × 10-8). Monthly 150 mg ibandronate therapy resulted in a significantly higher change in BMD of the lumbar spine than with the placebo. A once monthly 150 mg regimen produced greater increases in lumbar spine, total hip, femoral neck, and trochanter BMD than daily treatment, with a similar incidence of adverse events between the groups.
Once monthly 150 mg ibandronate therapy was clinically comparable to weekly 70 mg alendronate, and patients strongly preferred the convenience of monthly ibandronate over weekly alendronate. Monthly 150 mg ibandronate was superior to, and as well tolerated as, the daily treatment.
PMCID: PMC3192207  PMID: 22016595
Ibandronic acid; Efficacy; Safety; Osteoporosis; Review
10.  Virilizing Adrenocortical Oncocytoma in a Child: A Case Report 
Journal of Korean Medical Science  2010;25(7):1077-1079.
Functioning adrenocortical oncocytomas are extremely rare and most reported patients are 40-60 yr of age. To our knowledge, only 2 cases of functioning adrenocortical oncocytomas have been reported in childhood. We report a case of functioning adrenocortical oncocytoma in a 14-yr-old female child presenting with virilization. She presented with deepening of the voice and excessive hair growth, and elevation of plasma testosterone and dehydroepiandrosterone sulfate. She had an adrenalectomy. The completely resected tumor composed predominantly of oncocytes without atypical mitosis and necrosis. A discussion of this case and a review of the literature on this entity are presented.
PMCID: PMC2890887  PMID: 20592902
Adrenal Cortex Neoplasms; Adenoma, Oxyphilic; Virilism; Child
11.  Implication of Cord Blood for Cell-Based Therapy in Refractory Childhood Diseases 
Since cord blood (CB) contains hematopoietic stem cells as well as a mixture of multipotent stem cells, CB has the ability to give rise to hematopoietic, epithelial, endothelial and neural tissues. Recently, the application of cell-based therapy using CB has expanded its clinical utility, particularly, by using autologous CB in children with refractory diseases. This review focuses clinical and pre-clinical application of CB cell-based therapy for inherited metabolic diseases as well as tissue regenerations in neonatal hypoxic-ischemic encephalopathy, cerebral palsy, and juvenile diabetes.
PMCID: PMC4022686  PMID: 24855537
Cord blood; Stem cells; Regenerative medicine
12.  Role of Endogenous ENaC and TRP Channels in the Myogenic Response of Rat Posterior Cerebral Arteries 
PLoS ONE  2013;8(12):e84194.
Mechanogated ion channels are predicted to mediate pressure-induced myogenic vasoconstriction in small resistance arteries. Recent findings have indicated that transient receptor potential (TRP) channels and epithelial sodium channels (ENaC) are involved in mechanotransduction. The purpose of this study was to investigate the role of TRP channels and ENaC in the myogenic response. Our previous study suggested that ENaC could be a component of the mechanosensitive ion channels in rat posterior cerebral arteries (PCA). However, the specific ion channel proteins mediating myogenic constriction are unknown. Here we found, for the first time, that ENaC interacted with TRPM4 but not with TRPC6 using immunoprecipitation and confocal microscopy.
Methods and Results
Treatment with a specific βENaC inhibitor, amiloride, a specific TRPM4 inhibitor, 9-phenanthrol, and a TRPC6 inhibitor, SKF96365, resulted in inhibition of the pressure-induced myogenic response. Moreover, the myogenic response was inhibited in rat PCA transfected with small interfering RNA of βENaC, TRPM4, and TRPC6. Co-treatment with amiloride and 9-phenanthrol showed a similar inhibitory effect on myogenic contraction compared to single treatment with amiloride or 9-phenanthrol. The myogenic response was not affected by 9-phenanthrol or amiloride treatment in PCA transfected with βENaC or TRPM4 siRNA, respectively. However, pressure-induced myogenic response was fully inhibited by co-treatment with amiloride, 9-phenanthrol, and SKF96365, and by treatment with SKF96365 in PCA transfected with βENaC siRNA.
Our results suggest that ENaC, TRPM4, and TRPC6 play important roles in the pressure-induced myogenic response, and that ENaC and TRPM4 interact in rat PCA.
PMCID: PMC3877230  PMID: 24391909
14.  Antibiotic-induced Severe Neutropenia with Multidrug-Dependent Antineutrophil Antibodies Developed in A Child with Streptococcus pneumoniae Infection 
Journal of Korean Medical Science  2009;24(5):975-978.
Drug-induced neutropenia (DIN), particularly that in which antibiotic-dependent antineutrophil antibodies have been detected, is a rare disorder. We report the case of a child with pneumococcal pneumonia, who experienced severe neutropenia during various antibiotic treatments. We detected 4 kinds (cefotaxim, augmentin, vancomycin, and tobramycin) of antibiotic-dependent antineutrophil antibodies by using the mixed passive hemagglutination assay (MPHA) technique with this child.
PMCID: PMC2752789  PMID: 19795004
Neutropenia; Antineutrophil Antibody; Anti-Bacterial Agents
15.  Role of T-type Ca2+ Channels in the Spontaneous Phasic Contraction of Pregnant Rat Uterine Smooth Muscle 
Although extracellular Ca2+ entry through the voltage-dependent Ca2+ channels plays an important role in the spontaneous phasic contractions of the pregnant rat myometrium, the role of the T-type Ca2+ channels has yet to be fully identified. The aim of this study was to investigate the role of the T-type Ca2+ channel in the spontaneous phasic contractions of the rat myometrium. Spontaneous phasic contractions and [Ca2+]i were measured simultaneously in the longitudinal strips of female Sprague-Dawley rats late in their pregnancy (on day 18~20 of gestation: term=22 days). The expression of T-type Ca2+ channel mRNAs or protein levels was measured. Cumulative addition of low concentrations (<1 µM) of nifedipine, a L-type Ca2+ channel blocker, produced a decrease in the amplitude of the spontaneous Ca2+ transients and contractions with no significant change in frequency. The mRNAs and proteins encoding two subunits (α1G, α1H) of the T-type Ca2+ channels were expressed in longitudinal muscle layer of rat myometrium. Cumulative addition of mibefradil, NNC 55-0396 or nickel induced a concentration-dependent inhibition of the amplitude and frequency of the spontaneous Ca2+ transients and contractions. Mibefradil, NNC 55-0396 or nickel also attenuated the slope of rising phase of spontaneous Ca2+ transients consistent with the reduction of the frequency. It is concluded that T-type Ca2+ channels are expressed in the pregnant rat myometrium and may play a key role for the regulation of the frequency of spontaneous phasic contractions.
PMCID: PMC2766731  PMID: 19885043
Calcium channels; Nickel; Mibefradil; NNC 55-0396; Spontaneous contractility
16.  Clinical characteristics of hemophagocytic lymphohistiocytosis following Kawasaki disease: differentiation from recurrent Kawasaki disease 
Blood research  2013;48(4):254-257.
Our aim was to investigate the clinical pattern of hemophagocytic lymphohistiocytosis following Kawasaki disease (HLH-KD), to enable differentiation of HLH from recurrent or refractory KD and facilitate early diagnosis.
We performed a nationwide retrospective survey and reviewed the clinical characteristics of patients with HLH-KD, including the interval between KD and HLH, clinical and laboratory findings, treatment responses, and outcomes, and compared them with historical data for both diseases.
Twelve patients with HLH-KD, including 5 previously reported cases, were recruited. The median age was 6.5 years (range, 9 months-14.7 years). Eight patients were male and 4 were female. The median interval between the first episode of KD and the second visit with recurrent fever was 12 days (3-22 days). Of the 12 children, 2 were initially treated with intravenous IgG (IVIG) for recurrent KD when they presented at the hospital with recurrent fever. Eventually, 10 children received chemotherapy under an HLH protocol and 2 received supportive treatment. Two patients died of combined infections during chemotherapy, 1 was lost to follow up, and 9 remain alive. The overall survival rate at 4 years was 81.1% with a median follow up of 45.1 months.
A diagnosis of HLH-KD should be considered when symptoms similar to recurrent KD develop within 1 month of the first episode of KD. Our findings will help physicians differentiate between HLH and the recurrent form of KD.
PMCID: PMC3894383  PMID: 24466549
Hemophagocytic lymphohistiocytosis; Kawasaki disease; Recurrent
17.  Lateral Calcaneal Artery Adipofascial Flap for Reconstruction of the Posterior Heel of the Foot 
Soft tissue defects of the posterior heel of the foot present difficult reconstructive problems. This paper reports the authors' early experience of five patients treated with a lateral calcaneal artery adipofascial flap.
Between 2003 and 2007, five patients (3 males and 2 females) with soft-tissue defects over the posterior heel underwent a reconstruction using a lateral calcaneal artery adipofascial flap and a full-thickness skin graft. The flap sizes ranged from 3.5 × 2.5 cm to 5.5 × 4.0 cm.
All five flaps survived completely with no subsequent breakdown of the grafted skin, even after regularly wearing normal shoes. The adipofascial flap donor sites were closed primarily in all patients.
Lateral calcaneal artery adipofascial flaps should be included in the surgical armamentarium to cover difficult wounds of the posterior heel of the foot. These flaps do not require the sacrifice of a major artery to the leg or foot, they are relatively thin with minimal morbidity at the donor site, and leave a simple linear scar over the lateral aspect of the foot.
PMCID: PMC2766687  PMID: 19884990
Foot; Posterior heel; Soft tissue defect; Lateral calcaneal artery adipofascial flap
18.  Pre-engraftment Syndrome in Hematopoietic Stem Cell Transplantation 
The clinical findings of fever and skin rash with or without evidence of fluid retention, which mimic engraftment syndrome, have been observed during the pre-engraftment period in patients undergoing hematopoietic stem cell transplantation. In order to characterize this newly observed clinical syndrome called pre-engraftment syndrome (pES), we retrospectively analyzed the clinical records of 50 patients. Three out of 14 patients (23.1%) who underwent cord blood stem cell transplantation developed non-infectious fever, skin rash, and tachypnea 4-15 days prior to neutrophil engraftment. Two patients spontaneously recovered with fluid restriction and oxygen inhalation. One patient died of a complicated pulmonary hemorrhage in spite of aggressive supportive therapy and steroid treatment. Four out of 23 patients (17.4%) who underwent allogeneic bone marrow transplantation developed non-infectious fever and skin rash 4 to 5 days prior to neutrophil engraftment. All four of these patients recovered with only steroid treatment. These characteristic findings were not observed in patients who had undergone autologous peripheral blood stem cell transplantation. Interestingly, the speed of neutrophil engraftment was significantly faster for the patients suffering from pre-engraftment syndrome. The close observation and further pathophysiological research are required to better understand this syndrome.
PMCID: PMC2526496  PMID: 18303207
Engraftment Syndrome; Hematopoietic Stem Cell Transplantation
19.  Inflammatory Responses in the Muscle Coat of Stomach and Small Bowel in the Postoperative Ileus Model of Guinea Pig 
Yonsei Medical Journal  2013;54(6):1336-1341.
Small intestinal function returns first after surgery, and then the function of the stomach returns to normal after postoperative ileus (POI). The aim of this study was to investigate inflammatory responses in the muscle coat of stomach and small intestine in guinea pig POI model.
Materials and Methods
The distance of charcoal migration from pylorus to the distal intestine was measured. Hematoxylin and eosin (H&E) and immunohistochemical stain for calprotectin were done from the histologic sections of stomach, jejunum and ileum obtained at 3 and 6 hour after operation. Data were compared between sham operation and POI groups.
The distance of charcoal migration was significantly reduced in the 3 and 6 hour POI groups compared with sham operated groups (p<0.05). On H&E staining, the degree of inflammation was significantly higher in the stomach of 3 hour POI groups compared with jejunum and ileum of POI groups or sham operated groups (p<0.05). Calprotectin positive cells were significantly increased in the muscle coat of stomach of 3 hour POI groups compared with jejunum and ileum of POI groups or sham operated groups (p<0.05). There was strong association between the degree of inflammation and calprotectin positive cells in stomach.
Postoperative ileus induced by cecal manipulation significantly increased the degree of inflammation and calprotectin positive cells in the muscle coat of stomach as a remote organ. The relevance of degree of inflammation and the recovery time of ileus should be pursued in the future research.
PMCID: PMC3809856  PMID: 24142636
Postoperative ileus; stomach; small intestine; calprotectin
20.  Roles of TLR7 in Activation of NF-κB Signaling of Keratinocytes by Imiquimod 
PLoS ONE  2013;8(10):e77159.
Imiquimod is known to exert its effects through Toll-like receptor 7 (TLR7) and/or TLR8, resulting in expression of proinflammatory cytokines and chemokines. Keratinocytes have not been reported to constitutively express TLR7 and TLR8, and the action of imiquimod is thought to be mediated by the adenine receptor, not TLR7 or TLR8. In this study, we revealed the expression of TLR7 in keratinocytes after calcium-induced differentiation. After addition of calcium to cultured keratinocytes, the immunological responses induced by imiquimod, such as activation of NF-κB and induction of TNF-α and IL-8, were more rapid and stronger. In addition, imiquimod induced the expression TLR7, and acted synergistically with calcium to induce proinflammatory cytokines. We confirmed that the responses induced by imiquimod were significantly inhibited by microRNAs suppressing TLR7 expression. These results suggest that TLR7 expressed in keratinocytes play key roles in the activation of NF-κB signaling by imiquimod, and that their modulation in keratinocytes could provide therapeutic potential for many inflammatory skin diseases.
PMCID: PMC3795621  PMID: 24146965
21.  Stem Cells Expressing Homing Receptors Could be Expanded From Cryopreserved and Unselected Cord Blood 
Journal of Korean Medical Science  2004;19(5):635-639.
We assessed the cytokine combinations that are best for ex vivo expansion of cord blood (CB) and the increment for cell numbers of nucleated cells, as well as stem cells expressing homing receptors, by an ex vivo expansion of cryopreserved and unselected CB. Frozen leukocyte concentrates (LC) from CB were thawed and cultured at a concentration of 1×105/mL in media supplemented with a combination of SCF (20 ng/mL)+TPO (50 ng/mL)+FL (50 ng/mL)±IL-6 (20 ng/mL)±G-CSF (20 ng/mL). After culturing for 14 days, the expansion folds of cell numbers were as follows: TNC 22.3±7.8~26.3±4.9, CFU-GM 4.7±5.1~11.7±2.6, CD34+CD38- cell 214.0±251.9~464.1±566.1, CD34+CXCR4+ cell 4384.5±1664.7~7087.2±4669.3, CD34+VLA4+ cell 1444.3±1264.0~2074.9±1537.0, CD34+VLA5+ cell 86.2±50.9~113.2±57.1. These results revealed that the number of stem cells expressing homing receptors could be increased by an ex vivo expansion of cryopreserved and unselected CB using 3 cytokines (SCF, TPO, FL) only. Further in vivo studies regarding the engraftment after expansion of the nucleated cells, as well as the stem cells expressing homing receptors will be required.
PMCID: PMC2816322  PMID: 15483335
Receptors, Lymphocyte Homing; Ex Vivo Expansion; Cryopreservation; Fetal Blood; Cytokines; Granulocyte Colong-Stimulating Factor; Thrombopoietin; Interleukin-6: Antigen, CD34
22.  Homing-Associated Cell Adhesion Molecules and Cell Cycle Status on the Nucleated Cells in the Bone Marrow, Mobilized Peripheral Blood and Cord Blood 
Journal of Korean Medical Science  2004;19(4):523-528.
Homing-associated cell adhesion molecules (H-CAM) on the CD34+ cells play an important role for the engraftment process following hematopoietic stem cell transplantation (HSCT). However, it seems that not only CD34+ cells but also other nucleated cells (NCs) with H-CAM could be implicated in the engraftment process and the proliferation of hematopoietic stem cells. We investigated the differences of H-CAM and cell cycle status on the NCs in cord blood (CB), bone marrow (BM), and mobilized peripheral blood (PB). The proportions of CXCR4+ cells within the NC populations were greater in CB than in PB or BM (p=0.0493), although the proportions of CXCR4+, CD44+, and CD49d+ cells within the CB CD34+ cell populations were same within BM or PB. A lower proportion of CD34+CD49d+ cells within the CD34+ cell populations was more noted in CB than in PB or BM (p=0.0085). There were no differences in cell cycle status between CB and BM or PB. Our results suggest that the migrating potential of CB would be enhanced with increased CXCR4 expression on the NCs, but the adhesion potential of CB CD34+ cells would be less than that of PB and BM. These findings may help explain why the lower cell dose is required and engraftment is delayed in cord blood stem cell transplantation.
PMCID: PMC2816885  PMID: 15308842
Cell Adhesion Molecules; Nucleated Cells; Erythrocytes; Bone Marrow; Peripheral Blood; Fetal Blood
23.  Structure, Folding Dynamics, and Amyloidogenesis of D76N β2-Microglobulin 
The Journal of Biological Chemistry  2013;288(43):30917-30930.
Background: We recently discovered the first natural human β2-microglobulin variant, D76N, as an amyloidogenic protein.
Results: Fluid flow on hydrophobic surfaces triggers its amyloid fibrillogenesis. The α-crystallin chaperone inhibits variant-mediated co-aggregation of wild type β2-microglobulin.
Conclusion: These mechanisms likely reflect in vivo amyloidogenesis by globular proteins in general.
Significance: Our results elucidate the molecular pathophysiology of amyloid deposition.
Systemic amyloidosis is a fatal disease caused by misfolding of native globular proteins, which then aggregate extracellularly as insoluble fibrils, damaging the structure and function of affected organs. The formation of amyloid fibrils in vivo is poorly understood. We recently identified the first naturally occurring structural variant, D76N, of human β2-microglobulin (β2m), the ubiquitous light chain of class I major histocompatibility antigens, as the amyloid fibril protein in a family with a new phenotype of late onset fatal hereditary systemic amyloidosis. Here we show that, uniquely, D76N β2m readily forms amyloid fibrils in vitro under physiological extracellular conditions. The globular native fold transition to the fibrillar state is primed by exposure to a hydrophobic-hydrophilic interface under physiological intensity shear flow. Wild type β2m is recruited by the variant into amyloid fibrils in vitro but is absent from amyloid deposited in vivo. This may be because, as we show here, such recruitment is inhibited by chaperone activity. Our results suggest general mechanistic principles of in vivo amyloid fibrillogenesis by globular proteins, a previously obscure process. Elucidation of this crucial causative event in clinical amyloidosis should also help to explain the hitherto mysterious timing and location of amyloid deposition.
PMCID: PMC3829406  PMID: 24014031
Amyloid; Protein Aggregation; Protein Misfolding; Protein Stability; Shear Stress; D76N β2-Microglobulin; Chaperones; Systemic Amyloidosis
24.  Marked Acceleration of Atherosclerosis following Lactobacillus casei induced Coronary Arteritis in a Mouse Model of Kawasaki Disease 
To investigate if Lactobacillus casei cell wall extract (LCWE)-induced Kawasaki Disease (KD) accelerates atherosclerosis in hypercholesterolemic mice.
Method and Resuslts
Apoe−/− or Ldlr−/− mice were injected with LCWE (KD mice) or PBS, fed high fat diet for 8 weeks, and atherosclerotic lesions in aortic sinuses (AS), arch (AC) and whole aorta were assessed. KD mice had larger, more complex aortic lesions with abundant collagen, and both extracellular and intracellular lipid and foam cells, compared to lesions in control mice despite similar cholesterol levels. Both Apoe−/− KD and Ldlr−/− KD mice showed dramatic acceleration in atherosclerosis vs. controls, with increases in en face aortic atherosclerosis and plaque size in both the AS and AC plaques. Accelerated atherosclerosis was associated with increased circulating IL-12p40, IFN-γ, TNF-α, and increased macrophage, DC, and T cell recruitment in lesions. Furthermore, daily injections of the IL-1Ra, which inhibits LCWE induced KD vasculitis, prevented the acceleration of atherosclerosis.
Our results suggest an important pathophysiologic link between coronary arteritis/vasculitis in the KD mouse model and subsequent atherosclerotic acceleration, supporting the concept that a similar relation may also be present in KD patients. These results also suggest that KD in childhood may predispose to accelerated and early atherosclerosis as adults.
PMCID: PMC3480341  PMID: 22628430
atherosclerosis; coronary disease; Kawasaki Disease; Interleukin 1 beta; IL-1 Receptor antagonist; mouse model of Kawasaki; vasculitis
25.  Proteomic Evaluation of Acquired Enamel Pellicle during In Vivo Formation 
PLoS ONE  2013;8(7):e67919.
Acquired enamel pellicle (AEP) is a protein film that forms on the enamel surface of teeth by selective adsorption of proteins and peptides present in the mouth. This protein film forms the interface between enamel and the damage oral biofilm, which modulates the attachment of bacteria found in oral biofilm. The overall goal of this study was to gain insight into the biological formation of the human in vivo AEP. This study hypothesized that AEP is created by the formation of successive protein layers, which consist of initial binding to enamel and subsequent protein-protein interactions. This hypothesis was examined by observing quantitative and qualitative changes in pellicle composition during the first two hours of AEP formation in the oral cavity. Quantitative mass spectrometry approaches were used to generate an AEP protein profile for each time-point studied. Relative proteomic quantification was carried out for the 50 proteins observed in all four time-points. Notably, the abundance of important salivary proteins, such as histatin 1, decrease with increasing of the AEP formation, while other essential proteins such as statherin showed constant relative abundance in all time-points. In summary, this is the first study that investigates the dynamic process to the AEP formation by using proteomic approaches. Our data demonstrated that there are significant qualitative and quantitative proteome changes during the AEP formation, which in turn will likely impact the development of oral biofilms.
PMCID: PMC3700865  PMID: 23844127

Results 1-25 (91)