Clinical Trial Protocol for Porcine Islet Xenotransplantation in South Korea.

Background: Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. Methods: A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. Conclusion: A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Patch formation on diblock copolymer micelles confined in templates for inducing patch orientation and cyclic colloidal molecules.

HYPOTHESIS: Chemically or physically distinct patches can be induced on the micelles of amphiphilic block copolymers, which facilitate directional binding for the creation of hierarchical structures. Hence, control over the direction of patches on the micelles is a crucial factor to attain the directionality on the interactions between the micelles, particularly for generating colloidal molecules mimicking the symmetry of molecular structures. We hypothesized that direction and combination of the patches could be controlled by physical confinement of the micelles. EXPERIMENTS: We first confined spherical micelles of diblock copolymers in topographic templates fabricated from nanopatterns of block copolymers by adjusting the coating conditions. Then, patch formation was conducted on the confined micelles by exposing them with a core-favorable solvent. Microscopic techniques of SEM, TEM, and AFM were employed to investigate directions of patches and structures of combined micelles in the template. FINDINGS: The orientation of the patches on the micelles was guided by the physical confinement of the micelles in linear trenches. In addition, by confining the micelles in a circular hole, we obtained a specific polygon arrangement of the micelles depending on the number of micelles in the hole, which enabled the formation of cyclic colloidal molecules consisting of micelles.

Porous self-supporting film of semi-flexible supracolloidal chains of diblock copolymer micelles.

Patchy micelles of diblock copolymers can be polymerized into a linear supracolloidal chain. We measure the persistence and contour lengths of supracolloidal chains coated on a solid substrate to evaluate their flexibility. Based on the analysis, the chain is semi-flexible, and the conformation is suitably explained by the worm-like chain model. In addition, utilizing a spin-coating technique with the semi-flexible nature of the chains, we produce a self-supporting film of supracolloidal chains having nanoscale pores essentially from colloidal constituents that tend to form dense packing if there is no prior organization of them into a semi-flexible chain.

Long-term control of diabetes in a nonhuman primate by two separate transplantations of porcine adult islets under immunosuppression.

Porcine islet transplantation is an alternative to allo-islet transplantation. Retransplantation of islets is a routine clinical practice in islet allotransplantation in immunosuppressed recipients and will most likely be required in islet xenotransplantation in immunosuppressed recipients. We examined whether a second infusion of porcine islets could restore normoglycemia and further evaluated the efficacy of a clinically available immunosuppression regimen including anti-thymocyte globulin for induction; belimumab, sirolimus, and tofacitinib for maintenance and adalimumab, anakinra, IVIg, and tocilizumab for inflammation control in a pig to nonhuman primate transplantation setting. Of note, all nonhuman primates were normoglycemic after the retransplantation of porcine islets without induction therapy. Graft survival was >100 days for all 3 recipients, and 1 of the 3 monkeys showed insulin independence for >237 days. Serious lymphodepletion was not observed, and rhesus cytomegalovirus reactivation was controlled without any serious adverse effects throughout the observation period in all recipients. These results support the clinical applicability of additional infusions of porcine islets. The maintenance immunosuppression regimen we used could protect the reinfused islets from acute rejection.

Long-term porcine islet graft survival in diabetic non-human primates treated with clinically available immunosuppressants.

BACKGROUND: Although pancreatic islet transplantation is becoming an effective therapeutic option for patients with type 1 diabetes (T1D) who suffer from a substantially impaired awareness of hypoglycemia, its application is limited due to the lack of donors. Thus, pig-to-human islet xenotransplantation has been regarded as a promising alternative due to the unlimited number of "donor organs." Long-term xenogeneic islet graft survival in pig-to-non-human primate (NHP) models has mainly been achieved by administering the anti-CD154 mAb-based immunosuppressant regimen. Since the anti-CD154 mAb treatment has been associated with unexpected fatal thromboembolic complications in clinical trials, the establishment of a new immunosuppressant regimen that is able to be directly applied in clinical trials is an urgent need. METHODS: We assessed an immunosuppressant regimen composed of clinically available agents at porcine islet transplantation in consecutive diabetic NHPs. RESULTS: Porcine islet graft survival in consecutive diabetic NHPs (n = 7; >222, >200, 181, 89, 62, 55, and 34 days) without severe adverse events. CONCLUSION: We believe that our study could contribute greatly to the initiation of islet xenotransplantation clinical trials.

Shearing with solvent vapor annealing on block copolymer thin films for templates with macroscopically aligned nanodomains.

A template with macroscopically aligned nanopatterns can be an effective vehicle for arranging nanoscale particles or rods in a particular orientation to achieve their anisotropic properties. A room-temperature process is also desirable for nanoscale patterning of heat-sensitive functional molecules such as organic fluorophores. Here, large-area orientation of nanodomains of block copolymers is demonstrated by simultaneous shearing and solvent vapor annealing at room temperature. The shear-aligned nanodomains are applied to a chemical template for nanoscale patterning of green fluorescent molecules. In addition, the grooved nanochannels obtained from the macroscopically aligned nanodomains work as a physical template for guiding Au nanorods to end-to-end assemblies which exhibit the polarization-dependent plasmonic extinction.

Radial Artery Tonometry to Monitor Blood Pressure and Hemodynamics in Ambulatory Left Ventricular Assist Device Patients in Comparison With Doppler Ultrasound and Transthoracic Echocardiography: A Pilot Study.

Noninvasive measurements of blood pressure (BP) and cardiac output (CO) are crucial in the follow-up of continuous-flow left ventricular assist device (CF-LVAD) patients. For our pilot study, we sought to compare BP measurements between a tonometry blood pressure pulse analyzer (BPPA) (DMP-Life, DAEYOMEDI Co., Ltd., Gyeonggi-do, South Korea) and Doppler ultrasound in CF-LVAD patients, as well as to compare the BPPA estimated CO to LVAD calculated blood flow and to the patient's intrinsic CO estimated with transthoracic echocardiography (TTE). Ambulatory CF-LVAD patients (6 HeartMate, 26 HeartMate II), were included. According to TTE findings, patients were then subdivided in two groups: patients with an opening aortic valve (OAV) [n = 21] and those with an intermittent opening aortic valve (IOAV) [n = 11]. We found a very good correlation of systolic BP (SBP) measurements between the two methods, BPPA and Doppler ultrasound (r = 0.87, P < 0.0001). Bland-Altman plots for SBP revealed a low bias of -4.6 mm Hg and SD of ±4.7 mm Hg. In CF-LVAD patients with IOAV, the BPPA-CO had a good correlation with the LVAD-flow (r = 0.78, P < 0.0001), but in OAV patients, there was no correlation. After adding the patient's intrinsic CO, estimated from TTE in patients with OAV to the LVAD-flow, we found a very good correlation between the BPPA-CO and LVAD-flow + TTE-CO (r = 0.81, P = 0.002). Our study demonstrated that compared with the standard clinical method, Doppler ultrasound, the BPPA measured BP noninvasively with good accuracy and precision of agreement. In addition, tonometry BPPA provided further valuable information regarding the CF-LVAD patient's intrinsic CO.

Pre-clinical results in pig-to-non-human primate islet xenotransplantation using anti-CD40 antibody (2C10R4)-based immunosuppression.

BACKGROUND: Islet transplantation is an effective therapy for selected patients with type 1 diabetes with labile glycemic control and hypoglycemic unawareness, but donor organs are limited. Islet xenotransplantation using porcine islets will potentially solve this problem. Although successful proof of concept studies using clinically inapplicable anti-CD154 monoclonal antibody (mAb) in pig-to-non-human primate (NHP) islet xenotransplantation has been demonstrated by several groups worldwide, potentially clinically applicable anti-CD40 (2C10R4) mAb-based studies have not been reported. METHODS: Nine streptozotocin (STZ)-induced diabetic rhesus monkeys were transplanted with adult porcine islets isolated from designated pathogen-free (DPF) miniature pigs. They were treated with anti-CD40 mAb-based immunosuppressive regimen and were divided into 3 groups: anti-CD40 only group (n = 2), belatacept group (anti-CD40 mAb+belatacept, n = 2), and tacrolimus group (anti-CD40 mAb+tacrolimus, n = 5). All monkeys received anti-thymocyte globulin (ATG), cobra venom factor (CVF), adalimumab, and sirolimus. Blood glucose levels (BGL) and serum porcine C-peptide concentrations were measured. Humoral and cellular immune responses were assessed by ELISA and ELISPOT, respectively. Liver biopsy and subsequent immunohistochemistry were conducted. RESULTS: All animals restored normoglycemia immediately after porcine islet transplantation and finished the follow-up without any severe adverse effects except for one animal (R092). Most animals maintained their body weight. Median survival, as defined by a serum porcine C-peptide concentration of >0.15 ng/mL, was 31, 27, and 60 days for anti-CD40 only, belatacept, and tacrolimus groups, respectively. Anti-αGal IgG levels in serum and the number of interferon-γ secreting T cells in peripheral blood mononuclear cells did not increase in most animals. CONCLUSION: These results showed that anti-CD40 mAb combined with tacrolimus was effective in prolonging porcine islet graft survival, but anti-CD40 mAb was not as effective as anti-CD154 mAb in terms of preventing early islet loss.

Comparison between radial artery tonometry pulse analyzer and pulsed-Doppler echocardiography derived hemodynamic parameters in cardiac surgery patients: a pilot study.

BACKGROUND: Bedside non-invasive techniques, such as radial artery tonometry, to estimate hemodynamic parameters have gained increased relevance as an attractive alternative and efficient method to measure hemodynamics in outpatient departments. For our pilot study, we sought to compare cardiac output (CO), and stroke volume (SV) estimated from a radial artery tonometry blood pressure pulse analyzer (BPPA) (DMP-Life, DAEYOMEDI Co., Gyeonggi-do, South Korea) to pulsed-wave Doppler (PWD) echocardiography derived parameters. METHODS: From January 2015 to December 2016, all patients scheduled for coronary artery bypass (CABG) surgery at our department were screened. Exclusion criteria were, inter alia, moderate to severe aortic- or Mitral valve disease and peripheral arterial disease (PAD) > stage II. One hundred and seven patients were included (mean age 66.1 ± 9.9, 15 females, mean BMI 27.2 ± 4.1 kg/m2). All patients had pre-operative transthoracic echocardiography (TTE). We measured the hemodynamic parameters with the BPPA from the radial artery, randomly before or after TTE. For the comparison between the measurement methods we used the Bland-Altman test and Pearson correlation. RESULTS: Mean TTE-CO was 5.1 ± 0.96 L/min, and the mean BPPA-CO was 5.2 ± 0.85 L/min. The Bland-Altman analysis for CO revealed a bias of -0.13 L/min and SD of 0.90 L/min with upper and lower limits of agreement of -1.91 and +1.64 L/min. The correlation of CO measurements between DMP-life and TTE was poor (r = 0.501, p < 0.0001). The mean TTE-SV was 71.3 ± 16.2 mL and the mean BPPA-SV was 73.8 ± 19.2 mL. SV measurements correlated very well between the two methods (r = 0.900, p < 0.0001). The Bland-Altman analysis for SV revealed a bias of -2.54 mL and SD of ±8.42 mL and upper and lower limits of agreement of -19.05 and +13.96 mL, respectively. CONCLUSION: Our study shows for the first time that the DMP-life tonometry device measures SV and CO with reasonable accuracy and precision of agreement compared with TTE in preoperative cardiothoracic surgery patients. Tonometry BPPA are relatively quick and simple measuring devices, which facilitate the collection of cardiac and hemodynamic information. Further studies with a larger number of patients and with repeated measurements are in progress to test the reliability and repeatability of DMP-Life system.

Transferrable superhydrophobic TiO2 nanorods on reduced graphene oxide films using block copolymer templates.

Superhydrophobic surfaces are normally fixed on the chosen materials. Here, we report transferrable superhydrophobicity which was enabled by fabricating TiO2 nanorods on a reduced graphene oxide (rGO) film. Superhydrophobic TiO2 nanorods were first synthesized from a nanoporous template of block copolymers (BCPs). The controllability over the dimension and shape of nanopores of the BCP template allowed for the adjustment of TiO2 nanostructures for superhydrophobicity. Since the rGO film provided effective transferring, TiO2 nanorods were conveyed onto a flexible polymer film and a metal substrate. Thus, the surface of the designated substrate was successfully changed to a superhydrophobic surface without alteration of its inherent characteristics.

HMOX1 gene promoter polymorphism is not associated with coronary artery disease in Koreans.

BACKGROUND: The heme oxygenase-1 gene (HMOX1) promoter polymorphisms modulate its transcription in response to oxidative stress. This study screened for HMOX1 polymorphisms and investigated the association between HMOX1 polymorphisms and coronary artery disease (CAD) in the Korean population. METHODS: The study population consisted of patients with CAD with obstructive lesions (n=110), CAD with minimal or no lesions (n=40), and controls (n=107). Thirty-nine patients with CAD with obstructive lesions underwent follow-up coronary angiography after six months for the presence of restenosis. The 5'-flanking region containing (GT)n repeats of the HMOX1 gene was analyzed by PCR. RESULTS: The numbers of (GT)n repeats in the HMOX1 promoter showed a bimodal distribution. The alleles were divided into two subclasses, S25 and L25, depending on whether there were less than or equal to and more than 25 (GT)n repeats, respectively. The allele and genotype frequencies among groups were statistically not different. More subjects in the S25-carrier group had the low risk levels of high sensitivity C-reactive protein (hsCRP) for the CAD than those in the non-S25 carrier group (P=0.034). Multivariate logistic regression analysis revealed that the genotypes of (GT)n repeats were not related to CAD status. The restenosis group in the coronary angiography follow-up did not show any significant difference in HMOX1 genotype frequency. CONCLUSIONS: The HMOX1 genotypes were not found to be associated with CAD, but the short allele carrier group contained more individuals with hsCRP values reflecting low risk of cardiovascular disease in the Korean population.

Evidence for involvement of medium chain acyl-CoA dehydrogenase in the metabolism of phenylbutyrate.

Sodium phenylbutyrate is used for treating urea cycle disorders, providing an alternative for ammonia excretion. Following conversion to its CoA ester, phenylbutyryl-CoA is postulated to undergo one round of ß-oxidation to phenylacetyl-CoA, the active metabolite. Molecular modeling suggests that medium chain acyl-CoA dehydrogenase (MCAD; EC 1.3.99.3), a key enzyme in straight chain fatty acid ß-oxidation, could utilize phenylbutyryl-CoA as substrate. Moreover, phenylpropionyl-CoA has been shown to be a substrate for MCAD and its intermediates accumulate in patients with MCAD deficiency. We have examined the involvement of MCAD and other acyl-CoA dehydrogenases (ACADs) in the metabolism of phenylbutyryl-CoA. Anaerobic titration of purified recombinant human MCAD with phenylbutyryl-CoA caused changes in the MCAD spectrum that are similar to those induced by octanoyl-CoA, its bona fide substrate, and unique to the development of the charge transfer ternary complex. The calculated apparent dissociation constant (K(D app)) for these substrates was 2.16 µM and 0.12 µM, respectively. The MCAD reductive and oxidative half reactions were monitored using the electron transfer flavoprotein (ETF) fluorescence reduction assay. The catalytic efficiency and the K(m) for phenylbutyryl-CoA were 0.2 mM 34(-1)·sec(-1) and 5.3 µM compared to 4.0 mM(-1)·sec(-1) and 2.8 µM for octanoyl-CoA. Extracts of wild type and MCAD-deficient lymphoblast cells were tested for the ability to reduce ETF using phenylbutyryl-CoA as substrate. While ETF reduction activity was detected in extracts of wild type cells, it was undetectable in extracts of cells deficient in MCAD. The results are consistent with MCAD playing a key role in phenylbutyrate metabolism.

Knowledge and attitudes of Korean dentists towards human immunodeficiency virus/acquired immune deficiency syndrome.

PURPOSE: Infection with human immunodeficiency virus (HIV) remains a major global threat, and although the prevalence is comparatively still very low, the number of HIV-positive Koreans is increasing. However, there are no official guidelines as to how to treat people living with HIV/acquired immunodeficiency syndrome (AIDS) (PLWHA) or how to screen for potentially infectious people. This study assessed the level of knowledge and attitudes of dentists in Korea toward PLWHA, and their attitudes to screening patients for HIV infections. METHODS: A cross-sectional prospective survey targeting dentists working in Korea was conducted using a self-administered questionnaire. RESULTS: A satisfactory level of knowledge about HIV/AIDS and a relatively positive attitude toward PLWHA was found. Most of the respondents preferred rapid HIV testing using oral fluid as a specimen. The general attitude of dentists toward HIV/AIDS is sufficiently positive to enable provision of the best treatment to the patients in need. CONCLUSIONS: Most of the dentists require HIV testing in dental clinics. In spite of their needs, there are several obstacles. It is hoped that financial considerations and official legal requirements related to HIV testing strategies will be considered.

Concerns of South Korean patients and family members affected with genetic conditions: a content analysis of internet website messages.

The genetic counseling profession is expanding globally, and many countries, such as South Korea, are in the early stages of developing programs to prepare healthcare professionals specifically trained as genetic counselors. However, little research has investigated the concerns of South Korean patients and family members that have genetic conditions. The present study assessed their concerns by accessing and analyzing messages posted to websites devoted to genetic conditions. Eighteen websites were accessed-1 website concerns general genetic conditions, and 17 concern specific conditions. A sample of 700 messages was translated into English and analyzed using grounded theory analysis. Three major themes and 30 categories were extracted. The themes are: 1) Medical Concerns (e.g., clinical symptoms, diagnosis, prognosis, recurrence risk, prevention, inheritance); 2) Psychosocial Concerns (e.g., emotions, social stigma, social support); and 3) Management Concerns (e.g., therapy and alternative treatments, education, financial support, nutrition, medical facilities, folk remedies). The findings provide insight into the types of information and genetic counseling services that might benefit South Korean individuals and family members.

Cuffless and noninvasive measurement of systolic blood pressure, diastolic blood pressure, mean arterial pressure and pulse pressure using radial artery tonometry pressure sensor with concept of Korean traditional medicine.

Parameters for noninvasive diagnosis and monitoring of cardiovascular disease. We developed a new method to measure blood pressure (BP) noninvasively without cuff. In Korean traditional medicine, the degree of the pulse depth is one of the important criteria to diagnosis. We combined this concept with pulse wave analysis. With clinical data obtained from 163 subjects, we selected APm (applied pressure which has a maximum value of pulse wave), elasticity of wrist tissue, depth of blood vessel, cardiac output and h1 as parameters to estimate blood pressure. And with the parameters, we induced multi regression equation of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP). And the probabilities of these parameters to explain SBP, DBP, and MAP were 89.5%, 91.1% and 94.6%, respectively. To estimate PP, we added h1 to the parameters to explain PP was 97.5%. We compared the estimated SBP, DBP, MAP and PP through the multiple regression equations to the actual measured SBP, DBP, MAP and PP through the wrist type BP meter. Differences were (+/- SD) 0.38 +/- 9.95, -1.0 +/- 8.2, 0.02 +/- 6.9 and 0.05 +/- 5.9mmHg for SBP, DBP, MAP and PP, respectively. According to the American National Standard for Electronic or Automated Sphygmomanometers, the mean difference (MD) should be +/- 5mmHg or less with a standard deviation (SD) of +/- 8mmHg or less. Hence, the results of MAP and PP were within the limits for the AAMI SP 10 criteria and the results of SBP and DBP were not within the limits for the AAMI SP 10 criteria. The preliminary results indicate the results are quite reliable and promising.

Evaluation of a new fourth generation enzyme-linked immunosorbent assay, the LG HIV Ag-Ab Plus, with a combined HIV p24 antigen and anti-HIV-1/2/O screening test.

The LG HIV Ag-Ab Plus, a new fourth generation diagnostic assay for HIV infection, was evaluated in comparison to the Enzygnost HIV Integral, an established fourth generation HIV assay. The LG assay showed 100% sensitivity with 109 samples with anti-HIV-1, anti-HIV-2 or anti-HIV-1 group O reactivity. It also detected correctly all 51 positives on three BBI performance panels, slightly outperforming the Enzygnost HIV Integral, which detected 50. The specificity of the LG HIV Ag-Ab Plus was 99.9% with 999 sera from healthy blood donors, which was slightly inferior to the performance of the Enzygnost HIV Integral, which had 100% specificity. The LG assay showed 100% specificity with 81 specimens with underlying diseases including hepatitis B, demonstrating a low risk of cross-reactivity with other infections. The reduction of the diagnostic window by the LG HIV Ag-Ab Plus, compared to a third generation HIV assay, was 6.3 days. The LG assay also showed sufficiently high intra-person and inter-person reproducibility. The overall performance of this new fourth generation HIV assay was adequate for screening and diagnosis of HIV infection.

Inhibition of SUMO-independent PML oligomerization by the human cytomegalovirus IE1 protein.

In human cytomegalovirus-infected cells, the immediate-early IE1 protein disrupts the subnuclear structures known as the PML oncogenic domains or PODs, via the induction of PML desumoylation. This activity correlates with the functions of IE1 in transcriptional regulation and in the stimulation of lytic infection. Here, the effects of IE1 in induction of desumoylation of PML were characterized. IE1 did not interfere with the formation of sumoylated forms of PML in vitro. In in vitro assays using the sumoylated proteins, a SUMO-specific protease SENP1 desumoylated both PML and IE1. However, the IE1 proteins generated from bacteria or insect cells were unable to desumoylate PML in the same conditions. Although both IE1 and SUMO proteases such as SENP1, Axam and SuPr-1 efficiently desumoylated PML in co-transfection assays, they exerted different effects on the localization of PML. In cells transfected with either SENP1 or SuPr-1, the number of PML foci was reduced significantly and these remnant PML foci were devoid of SUMO-1 signals. However, in cells co-transfected with both SUMO proteases and IE1, these SUMO-independent PML foci were also completely disrupted. Furthermore, IE1, but not SENP1, was shown to disrupt the PML foci generated via transfection of a sumoylation-deficient mutant of PML. These data suggest that IE1 exhibits neither an inhibitory effect on sumoylation of PML nor intrinsic SUMO protease activity against PML in vitro. The finding that IE1 is capable of disrupting SUMO-independent PML aggregates suggests that inhibition of PML oligomerization by IE1 may play an important role in inducing PML desumoylation in vivo.

Evaluation of a new third-generation ELISA for the detection of HIV infection.

The purpose of this study was to assess whether the LG Anti-HIV 1/2 Plus ELISA (LG Life Sciences, Seoul, Korea), a new third-generation enzyme-linked immunosorbent assay for the detection of HIV infection, has improved sensitivity and specificity in comparison to the other licensed third-generation assays. The sensitivity of the LG Anti-HIV 1/2 Plus ELISA was comparable to the Enzygnost Anti-HIV 1/2 Plus ELISA (Dade Behring, Marburg, Germany) (100% vs 100%), and it was capable of detecting highly divergent subtypes including HIV-1 group O. The specificity of the LG Anti-HIV 1/2 Plus ELISA was 100%. The concordance of the LG Anti-HIV 1/2 Plus ELISA and the Enzygnost Anti-HIV 1/2 Plus was found to be 1. The LG Anti-HIV 1/2 Plus ELISA has a short window period among the third-generation ELISA assays and this test showed satisfactory reproducibility.

Cuffless and noninvasive tonometry mean arterial pressure measurement by physiological characteristics and applied pressure.

We developed a cuffless and noninvasive measurement technique of blood pressure using tonometric pressure sensor. With observation that the maximum value of a pulse pressure is not obtained at mean arterial pressure (MAP), we have figured out MAP based on the physiological characteristic including the elasticity of wrist tissue, the depth of blood vessel. Through an analysis of 198 clinic data, we have induced the regression equation of the MAP. The probability of the elasticity, depth and AP(M) to explain MAP was 92.1%. The mean difference and the standard deviation between the MAP predicted from the regression equation and the MAP measured by commercial cuff type BP meter were Z-3.183 mmHg and 5.133 mmHg respectively. Comparing the results with the American national standard for electronic or automated sphygmomanometers, we can conclude that the results are quite reliable and promising. Detecting only one part of the body and using only one device are quite advantageous over other BP measurement technique. Our technique makes new way for the cuffless BP measurement.

PIAS1 enhances SUMO-1 modification and the transactivation activity of the major immediate-early IE2 protein of human cytomegalovirus.

The protein inhibitor of activated STAT1 (PIAS1), known to be a small ubiquitin-like modifier (SUMO) E3 ligase, was found to interact with the human cytomegalovirus IE2 protein. We found that the sumoylation of IE2 was markedly enhanced by wild-type PIAS1 but not by a mutant containing a Cys to Ser substitution at position 351 (C351S) within the RING finger-like domain. In target reporter gene assays, wild-type PIAS1, but not the C351S mutant, enhanced the IE2-mediated transactivations of viral polymerase promoter and cellular cyclin E promoter and this augmentation required the intact sumoylation sites of IE2. Our results suggest that PIAS1 acts as a SUMO E3 ligase toward IE2 and that it may regulate the transactivation function of IE2. To our knowledge, IE2 is the first viral target found to be regulated by a SUMO E3 ligase.