[COVID-19 in haemodialysis patients: result analysis of the first year of the pandemic].

BACKGROUND: Present concepts of the novel coronavirus infection prognosis in haemodialysis (HD) patients are rather controversial. There is little information on therapy efficiency and safety in such patients. We studied COVID-19 course specifics, prognostic factors associated with fatal outcomes, therapy efficiency and its transformation at different stages of the pandemic first year. MATERIALS AND METHODS: Single-centre retrospective uncontrolled study included 653 COVID-19 HD-patients treated at Moscow City Nephrology Centre from April 1 to December 31, 2020. RESULTS: This period mortality rate was 21.0%. Independent predictors of COVID-19 unfavourable outcome in HD patients were pulmonary lesion extension (CT grades 34), high comorbidity index, and mechanical ventilation. Approaches to COVID-19 treatment modified significantly at different periods. Immunomodulatory drugs (monoclonal antibodies to IL-6, corticosteroids) were used largely at later stages. With tocilizumab administration, mortality was 15.1%, tocilizumab together with dexamethasone 13.3%; without them 37.8% (р0,001). Tocilizumab administration in the first 3 days after hospitalization of patients with CT grades 12 was associated with more favourable outcomes: 1 out of 29 died vs 6 out of 20 (tocilizumab administered at later periods); p0.04. There was no significant difference in death frequency in patients with CT grades 34 depending on tocilizumab administration time. CONCLUSION: COVID-19 in HD patients can manifest in a severe course with unfavourable outcome. It is urgent to identify reliable disease outcome predictors and develop efficient treatment in this population.

Reuse of Living-Donor Liver Graft in Second Recipient with Long-Term Survival.

Brain death is a rare situation after living-donor liver transplantation. However, the recipient who suffers from brain death and has functional liver graft is a potential liver donor. We report the 1st case of successful reuse of extended right living-donor liver graft after brain death of the first recipient. The first recipient, who had acute liver failure caused by hepatitis A virus, experienced brain death on the 2nd day after the transplantation. The allograft had a favorable regeneration and functional recovery. On the 7th day, the allograft was procured with a patent hepatic artery, bile duct, portal vein, and reconstructed outflow (right hepatic vein and middle hepatic vein) and successfully implanted into the second recipient. The second recipient has experienced a long-term survival without any complications.

C3d-binding Donor-specific HLA Antibody Is Associated With a High Risk of Antibody-mediated Rejection and Graft Loss in Stable Kidney Transplant Recipients: A Single-center Cohort Study.

BACKGROUND: One risk factor for antibody-mediated rejection (ABMR) and poor outcome after kidney transplantation is donor-specific anti‒human leukocyte antigen (anti-HLA) antibodies (DSAs). In this study we sought to determine whether the presence of DSAs that bind complement component C3d could better predict ABMR and graft loss in stable kidney transplant recipients (KTRs). METHODS: We included 220 stable KTRs in this study and screened them for DSAs from July 2013 to July 2016. RESULTS: Of the 220 KTRs, DSAs were detected in 24 (10.9%). The incidence of ABMR was 3.6% (8 of 220) overall, and C3d-DSA‒positive KTRs had a significantly higher incidence than SA-DSA‒positive KTRs (63.3% vs 38.9%, P = .03). Most C3d-binding DSAs were anti-HLA class II antibodies (11 of 13, 84.6%). Class II C3d-binding DSA was also significantly associated with graft failure on multivariate analysis, as were ABMR, chronic ABMR, and high serum creatinine. Class II C3d-binding DSA was also significantly associated with lower graft survival after ABMR. CONCLUSION: C3d-binding DSA, especially class II, was significantly associated with the risk of ABMR and graft loss in stable KTRs. We suggest that monitoring of stable KTRs for C3d-binding DSA, followed by biopsy, could aid in early recognition of ABMR and prevention of graft loss.

Hanging Hepato-Atrial Anastomosis in Deceased-Donor Liver Transplantation for Budd-Chiari Syndrome With Extensive Vena Cava Obliteration: A Case Report.

INTRODUCTION: Although outcomes of liver transplantation (LT) have improved as the result of progress in surgical procedures, a failure to restore sufficient graft outflow may yield fatal consequences including graft dysfunction and even graft loss to date. In particular, patients with pre-existing obliterated venous drainage, such as those with Budd-Chiari syndrome (BCS), are at high risk of having venous complications followed by conventional LT. In selected cases, the transplant surgeons are compelled to modify the surgical procedures of LT from the conventional procedure. METHODS: We describe an LT performed in a BCS patient with complete inferior vena cava (IVC) obstruction. A procedure that we named "hanging hepato-atrial anastomosis" was performed, in which 2 major modifications were made. One modification was the dissection of the lower inlet of the right atrium by use of a trans-abdominal approach and hepato-atrial anastomosis. This was performed by exposing the thoracic IVC through a trans-abdominal approach. The other modification was the manufacture of a blind pouch from the graft's infra-hepatic IVC without anastomosis. RESULTS: Modifications were made possible as the result of meticulous examination of the patient's vascular anatomy before the operation. Fortunately, the patient had a heavy network of pre-vertebral veins that drained blood from the lower extremity and both kidneys to the azygos-hemi-azygos veins. CONCLUSIONS: We learned that a meticulous assessment of vascular anatomy and complete understanding of hemodynamics are the keys to the successful LT for BCS in patients with extensive IVC abnormality. Thoracotomy may not be necessary to explore thoracic IVC when performing hepato-atrial anastomosis in LT for BCS.

4-n-butylresorcinol enhances proteolytic degradation of tyrosinase in B16F10 melanoma cells.

OBJECTIVE: 4-n-butylresorcinol is a competitive inhibitor of tyrosinase and has been used as an antimelanogenic agent. However, its inhibition mechanism in intact cells is not fully understood. To elucidate the cellular mechanism, we compared in vitro and in vivo inhibitory effects of 4-n-butylresorcinol on tyrosinase activity. METHODS: B16F10 melanoma cells were cultured in media containing α-MSH in the presence or absence of 4-n-butylresorcinol. Tyrosinase mRNA levels, protein levels and activity in B16F10 cells were compared by real-time PCR, immunostaining combined with western blot and colorimetric analysis, respectively. Melanin concentration was measured by colorimetry both in the cells and in the media. Tyrosinase glycosylation and proteolytic degradation were analysed by immunoblotting after cells were treated with Endo H/PNGase F and E64/proteasome inhibitors, respectively. RESULTS: 4-n-butylresorcinol inhibited tyrosinase activity and melanin synthesis more effectively in intact cells than in cell lysates. Western blotting and real-time RT-PCR showed that 4-n-butylresorcinol reduced protein levels, but not mRNA levels, of tyrosinase in B16F10 cells. 4-n-butylresorcinol showed no effect on the processing of tyrosinase glycosylation or on trafficking to melanosomes. However, treatment of B16F10 cells with E64 or proteasome inhibitor abrogated the 4-n-butylresorcinol-induced decrease of tyrosinase. Moreover, 4-n-butylresorcinol activated p38 MAPK, resulting in increased ubiquitination of tyrosinase. CONCLUSION: 4-n-butylresorcinol inhibits melanogenesis by enhancing proteolytic degradation of tyrosinase as well as competitive binding to tyrosinase. These findings will help to develop new, effective and safe chemicals for the treatment of hyperpigmentation disorders.

Advanced remediation of uranium-contaminated soil.

The existing decontamination method using electrokinetic equipment after acidic washing for uranium-contaminated soil requires a long decontamination time and a significant amount of electric power. However, after soil washing, with a sulfuric acid solution and an oxidant at 65 °C, the removal of the muddy solution using a 100 mesh sieve can decrease the radioactivity of the remaining coarse soil to the clearance level. Therefore, only a small amount of fine soil collected from the muddy solution requires the electrokinetic process for its decontamination. Furthermore, it is found that the selective removal of uranium from the sulfuric washing solution is not obtained using an anion exchanger but rather using a cation exchanger, unexpectedly. More than 90% of the uranium in the soil washing solutions is adsorbed on the S-950 resin, and 87% of the uranium adsorbed on S-950 is desorbed by washing with a 0.5 M Na2CO3 solution at 60 °C.

The Study of Optical Properties as Glass Composition of Bi2O3-Based Glass/Phosphor Mixed Paste.

Recently, White light emitting diodes (WLEDs) have been studied because of many advantages such as lower energy consumption, fast response, high brightness. Glass frit has been interested in LED packages due to their superior properties such as long-term stability and permeability. To maximize the LED light emission characteristic, the glass frit was required a low firing temperature and high refractive index. We selected the bismuth-based glass due to their low melting and high refractive index. This study was investigated characteristics of glass according to the influence of the glass within Bi2O3 content and this glass characteristic change was studied the effects on the optical properties of LED package structure. The properties changes of the glass frit affect the optical property of the mixed paste. With higher contents of Bi203 glass composition, the transmittance and emission intensity of the mixed paste was increased. These results suggest that the difference in refractive index between the phosphor and glass frit is minimized, the loss of light is minimized.

PKCδ maintains phenotypes of tumor initiating cells through cytokine-mediated autocrine loop with positive feedback.

The existence of tumor initiating cells (TICs) has been emerged as a good therapeutic target for treatment of glioblastoma that is the most aggressive brain tumor with poor prognosis. However, the molecular mechanisms that regulate the phenotypes of TICs still remain obscure. In this study, we found that PKCδ, among PKC isoforms, is preferentially activated in TICs and acts as a critical regulator for the maintenance of TICs in glioblastoma. By modulating the expression levels or activity of PKCδ, we demonstrated that PKCδ promotes self-renewal and tumorigenic potentials of TICs. Importantly, we found that the activation of PKCδ persists in TICs through an autocrine loop with positive feedback that was driven by PKCδ/STAT3/IL-23/JAK signaling axis. Moreover, for phenotypes of TICs, we showed that PKCδ activates AKT signaling component by phosphorylation specifically on Ser473. Taken together, we proposed that TICs regulate their own population in glioblastoma through an autocrine loop with positive feedback that is driven by PKCδ-dependent secretion of cytokines.

Use of pericholedochal plexus for portal flow reconstruction in diffuse portal vein thrombosis: case report.

Portal vein thrombosis (PVT) remains a challenging issue for liver transplantation surgeons. Most patients who have PVT undergo eversion thrombectomy. When thrombectomy is not successful due to diffuse PVT, other modalities are adapted, such as the use of a venous jump graft or portal tributaries. Here, we report our successful experience with reconstruction of portal flow using collateral plexus for a patient with grade 4 PVT. Thrombectomy did not restore portal flow. A pericholedochal plexus was found on the lateral wall of common bile duct. Direct end-to-end anastomosis was performed between the donor's portal vein and patient's choledochal plexus. Postoperative color Doppler ultrasound revealed normal portal flow.

Fibulin-3-mediated inhibition of epithelial-to-mesenchymal transition and self-renewal of ALDH+ lung cancer stem cells through IGF1R signaling.

Fibulins (FBLNs), a family of extracellular matrix proteins, have recently been shown to act as tumor suppressors or activators in different cancers, and the underlying molecular mechanisms of their action in cancer remain unclear. We have previously shown that the expression of FBLN3 is suppressed by promoter hypermethylation and is associated with invasiveness in aggressive non-small cell lung cancer. In this study, we evaluated the roles and signaling mechanism of FBLN3 in lung cancer stem cells (CSCs). Forced expression of FBLN3 suppressed invasion and migration of lung adenocarcinoma cells and decreased the expression of epithelial-to-mesenchymal transition (EMT) activators, including N-cadherin and Snail. Stemness activities of lung adenocarcinoma cells were also suppressed by FBLN3 as indicated by a decrease in spheroid formation and the levels of stemness markers such as Sox2 and ß-catenin. These effects of FBLN3 were mediated by the glycogen synthase kinase-3ß, GSK3ß/ß-catenin pathway, and the upstream regulators of GSK3ß, including phosphoinositide 3-kinase (PI3K)/AKT and insulin-like growth factor-1 receptor (IGF1R), were inactivated by FBLN3. Moreover, IGF1R was shown to be a direct target of FBLN3, which competitively inhibited insulin-like growth factor (IGF) action. To confirm the effect of FBLN3 on lung CSCs, aldehyde dehydrogenase-positive (ALDH+) A549 lung CSCs were sorted and treated with recombinant FBLN3 protein. FBLN3 clearly suppressed EMT, stemness activity and the over-activated IGF1R/PI3K/AKT/GSK3ß pathway of the ALDH+ CSC subpopulation. In addition, injection of recombinant FBLN3 protein around subcutaneous xenografts established with ALDH+ CSCs in athymic nude mice significantly suppressed tumor growth and progression. Overall, our results show that FBLN3 suppresses both EMT and self-renewal of the lung CSCs by modulating the IGF1R/PI3K/AKT/GSK3ß pathway and that FBLN3 would be useful as an alternative CSC therapy.

Transglutaminase 2 suppresses apoptosis by modulating caspase 3 and NF-kappaB activity in hypoxic tumor cells.

The expression of hypoxia-inducible factor-1 (HIF-1) correlates with poor clinical outcomes and confers resistance to the apoptosis of the tumor cells that are exposed to hypoxia. Presently, the mechanism underlying this phenomenon is poorly understood. In this study we provide evidence that transglutaminase 2 (TG2), an enzyme that catalyses protein crosslinking reactions, is a transcriptional target of HIF-1 to enhance the survival of hypoxic cells. We found that hypoxia induces TG2 expression through an HIF-1 dependent pathway and concurrently activates intracellular TG2. The hypoxic cells overexpressing TG2 showed resistance to apoptosis. Conversely, the hypoxic cells treated with either TG2 inhibitor or small interfering RNA (siRNA) became sensitive to apoptosis. Activation of TG2 in response to hypoxic stress inhibited caspase-3 activity by forming crosslinked multimer, resulting in insoluble aggregates. TG2 also activates nuclear factor (NF)-kappaB pathway after hypoxic stress, and thereby induces the expression of cellular inhibitor of apoptosis 2. The anti-apoptotic role of TG2 was further confirmed in vivo using xenografts in athymic mice. Our results indicate that TG2 is an anti-apoptotic mediator of HIF-1 through modulating both apoptosis and survival pathways and may confer a selective growth advantage to tumor cells. These findings suggest that the inhibition of TG2 may offer a novel strategy for anticancer therapy.

[Risk factors and pathogenetic mechanisms of left ventricular hypertrophy in progressive chronic kidney disease and after transplantation of the kidney].

AIM: To specify the trend in the incidence of left ventricular hypertrophy (LVH) at a predialysis stage of chronic kidney disease (CKD) in the course of its progression from stage III to stage V and after transplantation of the kidney (TK); to study correlations between homeostatic disorders caused by CKD progression and myocardial remodeling; to define the role of some hemodynamic and nonhemodynamic factors in formation of LVH. MATERIAL AND METHODS: The study enrolled 128 patients (58 males and 70 females, age 18-55 years, mean age 42 +/- 11 years) at a predialysis stage of CKD (group 1) and 225 recipients of renal allotransplant--RRA (group 2, 140 males and 85 females, age 18-69 years, mean age 43 +/- 12 years). General clinical examination, biochemical and immunological blood tests, echocardiography were made. RESULTS: At a predialysis stage of CKD, LVH was diagnosed in 56% patients. Incidence of LVH was directly related with age of the patients (p = 0.001), blood pressure (p < 0.001), duration of arterial hypertension (p = 0.004), severity of anemia (p = 0.017), the level of C-reactive protein (p = 0.003), blood phosphorus concentration and inversely correlated with glomerular filtration rate--GFR (p = < 0.001), albumin level (p = 0.023) and blood Ca (p < 0.001). LVH was followed up for 12 months in 35 patients with predialysis CKD. Factors of LVH progression and factors hindering its regression were systolic blood pressure, Hb and Ca in the blood. In group 2 of RRA incidence of LVH was 53%. Significant factors of LVH risk after transplantation were age (p = 0.002), hypertension (p = 0.005) and anemia (p = 0.04). Moreover, LVH closely correlated with proteinuria (p < 0.03), transplant dysfunction (p = 0.002) and posttransplantation ischemic heart disease (p < 0.037). Changes in LVH were analysed in 30 RRA. Frequency of LVH decreased for 2 years after transplantation (from 56 to 32%) but 36-60 and more months after transplantation it increased (46 and 64%, respectively). Transplant dysfunction was the leading factor hindering LVH regression after transplantation. CONCLUSION: The same mechanisms are involved in LVH pathogenesis after transplantation and at a predialysis stage of CKD. The significance of initial renal lesion signs--minimal proteinuria and hypercreatininemia--was higher after renal transplantation than in patients with CKD.

[Transplantation of the kidney--optimal treatment of patients suffering from diabetes mellitus type 1 with terminal chronic renal failure].

AIM: To assess long-term results of renal transplantation in patients with diabetes mellitus of type 1 (DM-1) with terminal chronic renal failure (tCRF); to detect risk factors of low survival of the patients and development of dysfunction of renal transplant. MATERIAL AND METHODS: A retrospective comparative analysis of 418 recipients of the kidney with non-diabetic nephropathies (NDN) and 113 recipients with DM-1. RESULTS: Survival of DM-1 patients with tCRF after allotransplantation of the kidney was lower than in patients with NDN. Low survival risk factors for DM-1 patients after transplantation of the kidney are: DM-1 duration up to tCRF 25 years and more, minimum 3-year history of dialysis before transplantation, age at transplantation over 45 years, persistence of anemia (hemoglobin < 110 g/l) after operation. Survival of the transplanted kidney in DM-1 and NDN patients was the same. Risk factors of dysfunction of the transplanted kidney are the following: acute crises of rejection and delayed function of the transplant, arterial hypertension > 130/80 mmHg, proteinuria > 300 mg/day. Survival of the transplanted kidney is higher in transplantation from the relative donor, does not depend on the kind and duration of previous dialysis. Causes of a decline in the function of the transplanted kidney (by the data of puncture biopsy of 34 transplants) are the following: acute rejection crises (38%), chronic transplantation nephropathy (24%), toxic nephropathy (18%), recurrent diabetic nephropathy (6%), chronic pyelonephritis (6%). Lethality in DM-1 patients after renal transplantation is 2 times higher than in patients with NDN. Death was due to cardiovascular diseases, gangrene of the lower limbs, infectious complications (in 31%, 15% and 35% cases, respectively). CONCLUSION: Transplantation of the kidney is an optimal treatment in DM-1 patients with tCRF.

[Coronary artery disease after renal transplantation: epidemiology, risk factors, and surgical approaches to treatment].

Coronary artery disease (CAD) is the main cause of death in renal transplant recipients. The aim of the present study was to determine the frequency and risk factors of post-transplantation CAD and its influence on the long-term results of surgery, as well as to evaluate the efficiency of myocardial revascularization in patients with severe CAD. Analysis of the observation of 479 renal recipients (332 men and 147 women) aged 38.69 +/- 11.2 was performed. The mean follow-up period was 64.56 +/- 37.44 months. Sixty-eight patients had diabetes mellitus. CAD was diagnosed in 14.8% (71 out of 479) renal recipients; in 12.7% of patients it developed de novo and was revealed 32.4 +/- 18.6 months after the surgery. Ten-year survival of renal recipients with CAD was only 39%, while in the group of non-CAD patients it was 75% (p < 0.0001). Age more than 45, male gender, diabetes mellitus, hypercholesterolemia, infections, pre-existing left ventricular myocardial hypertrophy, and renal transplant dysfunction were defined as significant risk factors of CAD de novo. Multi-factor Cox model found only age more than 45 (p < 0.009), male gender (p < 0.00001), and hyperlipidemia (p < 0.0058) to be independent risk factors of CAD. Myocardial revascularization was performed in 29 patients with coronary lesions: 27 patients underwent percutaneous transluminal coronary angioplasty with stenting and 2 patients underwent coronary artery bypass grafting (5 and 52 months after renal transplantation). However, angioplasty had to be repeated in 6 out of 27 (22%) patients within 3 to 6 months. The average follow-up duration was 23 months (2 to 74 months) after revascularization. Prolonged effect (more than 12 months) was achieved in 17 out of 29 (58.6%) patients. None of the patients developed myocardial infarction after revascularization. Two patients died 28 and 35 months after angioplasty due to extracardial complications (hepatic cirrhosis and an oncological disease); one patient died 78 months after repeated revascularization from progressive cardiac insufficiency while receiving dialysis due to a relapse of renal transplant insufficiency. Thus, CAD develops in 14.8% of renal transplant recipients; in 12.7 of patients it develops de novo. There are conventional and nonconventional post-transplantation CAD risk factors, which include renal transplant dysfunction and post-transplantation infections. Association with myocardial hypertrophy, observed in a significant number of patients, is a feature of post-transplantation CAD. Coronary revascularization, angioplasty with stenting in particular, may be considered to be an effective method of CAD treatment in renal transplant recipients.

Polyamine depletion partially reduces the radiation-induced cell death via cell cycle delay mediated by thioredoxin.

In previous studies, polyamine depletion by DFMO (alpha-difluoromethylornithine)-treatment reduced H(2)O(2)-induced apoptotic cell death by reduction of ferric ion uptake. In the present study, we analyzed the reduction of radiation-induced cell death by polyamine depletion. Exposure of HT29 cells to radiation induced severe cell death, but when cells were pretreated with DFMO, a specific inhibitor of polyamine biosynthesis, radiation-induced cell death was reduced to 50-60% of control. Cell cycle analysis showed that, in these cells, the time to reach the G(2)/M phase arrest was delayed for 20-24 h compared to the control cells, at which stage the fate of cells exposed to ionizing radiation is determined. DFMO-treated cells also showed a low level of thioredoxin, which is a high-level determinant of the cellular fate. To investigate the relationship between the G(2)/M phase arrest and the reduction of thioredoxin caused by polyamine depletion, we also analyzed thioredoxin-antisensed (asTRX) HT29 cells as for DFMO-treated cells. In asTRX-transfected cells, the gamma-irradiation-induced G(2)/M phase arrest was also significantly delayed and radiation-induced cell death was profoundly reduced, as in the DFMO-treated cells. Both sets of cells showed a decrease of cyclin D1 and an increment of HSP25, which are involved in radiation-induced cell cycle progress. Overall, these results suggest that polyamines are essential for normal cell death of HT29 cells triggered by gamma-radiation and that this is partially mediated by the regulation of thioredoxin expression.

Alpha-difluoromethylornithine, ornithine decarboxylase inhibitor, antagonizes H2O2-induced cytotoxicity in HL-60 leukemia cells: regulation of iron-dependent lysosomal damage.

Recent studies indicate that reactive oxygen species, such as H2O2, can be generated by anti-cancer drugs, can damage cells, and then induce apoptotic cell death. In this study, we reported whether polyamines were capable of affecting apoptotic cell death triggered by H2O2 in leukemia cells or not. Alpha-difluoromethylornithine treatment (DFMO, 3 mmol/L, 48 h), which depletes intracellular putrescine by inhibiting ornithine decarboxylase, reduced H2O2-induced cell death in the HL-60 leukemia cells. Cytotoxicity caused by H2O2 in putrescine-depleted cells was 50% lower than that in the control cells, as determined by propidium iodide, the annexin V and DNA fragmentation assays. Following putrescine (1 mmol/L) supplement, cell death induction caused by H2O2 was restored to a similar level as the DFMO-untreated control cells. It seems that this partly resulted from the intralysosomal iron-dependent oxidation of the cells because DFMO did not significantly affect the increment of enzymes related to oxidative-stress resistance. Putrescine depletion by DFMO treatment reduced the cellular iron uptake of the cells by about 70%. In parallel to the reduction of iron uptake, lysosomal damage (assayed by acridine orange relocalization or uptake test) in the DFMO-treated cells was far less than that in the control cells. Moreover, putrescine supplement also restored the iron uptake to the control cell levels. Pre-incubation with desferrioxamine (DFO), which chelates iron and forms a non-reactive Fe-DFO complex that is localized in the lysosomal compartment, inhibited H2O2-induced cell death. This work suggests that polyamines may play a critical role in apoptotic cell death triggered by H2O2 via the regulation of the iron-dependent instability of the lysosome.

Polyamines reduce paraquat-induced soxS and its regulon expression in Escherichia coli.

Polyamines, ubiquitous polycationic compounds, are involved in many cellular responses and relieve paraquat-induced cytotoxicity in Escherichia coli. We constructed a new E. coli mutant strain, JIL528, which is deficient in the biosynthesis of both putrescine and spermidine, to examine the physiological role of polyamines under oxidative stress caused by paraquat. Putrescine and spermidine downregulate the expression of soxS induced by paraquat in a concentration-dependent manner. The product of SoxS is a key regulator governing cellular responses against oxidative stress in E. coli. The downregulation of soxS expression by polyamines was not shown in the soxR mutant background. Glucose-6-phosphate dehydrogenase (G6PDH; encoded by zwf) and manganese-containing superoxide dismutase (Mn-SOD; encoded by sodA) activities induced by paraquat were decreased by exogenous polyamines. The induction of the zwf expression by paraquat was also decreased by exogenous polyamines. The polyamine-deficient mutant strain JIL528 showed a higher soxS expression than its parent polyamine-proficient wild type BW1157, on exogenous supplementation of paraquat concentrations below 1 micromol/L. While the growth rate of the mutant was decreased, soxS expression was increased in a concentration-dependent manner above 0.01 micromol/L of paraquat. In contrast, growth inhibition of the mutant by paraquat was relieved, and soxS was no longer induced by exogenous putrescine (1 mmol/L). In conclusion, polyamines protect against paraquat-induced toxicity but downregulate soxS expression, suggesting that the protective role of polyamines against oxidative damage induced by paraquat results in soxS downregulation.

Personal experiences and algorithm of endoscopically assisted subperiosteal face lift in orientals for 5 years.

Orientals are anatomically distinct from Caucasians and are characterized by a thick dermis, a Mongoloid slant of the palpebral fissure, a relatively prominent zygoma and mandible angle, and a relatively flat nose. Given these characteristics, it was believed that the subperiosteal face lift was not suitable for Orientals. However, at our institution, endoscopically assisted subperiosteal face lifts were performed from May of 1994 to October of 1998 on 236 patients; variable pitfalls, as well as satisfying results, were reported. Patient ages ranged from 29 to 66 years (mean age, 55.2 years), and follow-up ranged from 6 to 44 months (mean follow-up, 23 months). All forehead and brow lifts were performed using an endoscopic guide, and routine corrugator resections and procerus myotomies were performed. Three slanted cortical tunnels were made at the corresponding locations on the outer table of the calvarium, and 1-0 nylon or screw suspension and fixation were performed after a 1-cm to 2-cm lift. Midface lifts were performed through lower blepharoplasty incisions and vertical temporal incisions instead of through conventional preauricular and postauricular incisions. Dissections were made subperiosteally and over the deep layers of deep temporal fascia. Malar fat pads were suspended with 1-0 nylon and affixed to deep temporal fascia. Most patients have been satisfied with their postoperative results, but unfavorable results and complications have been reported. Complications were classified as early or late complications or unfavorable results on the basis of the 3-week postoperative evaluation. There were 28 early complications (11.9 percent), consisting of ecchymosis with edema (persisting for up to 4 weeks), paresthesia, lagophthalmos, accentuated Mongoloid slant, small dimpling on the scalp, and scalp fold formation on the fixation site. There were 13 late complications/unfavorable results (5.5 percent), consisting of insufficient lift, exaggeration of sunken upper eyelids, intermittent headaches, itching sensations, and paresthesia on the scalp. The unfavorable results occurred in the patients who had previously undergone blepharoplasty and in those who had a history of foreign body injections into the face, fatty and thick faces, sunken upper eyelids, Mongoloid slants, and asymmetric facial expressions. Through understanding the anatomic characteristics of the Oriental face (i.e., thick dermis, Mongoloid slant of palpebral fissure, prominent zygoma and mandible angle, and flat nose), satisfying results were achieved by appropriate application of the modified procedures.

The Escherichia coli SOS gene sbmC is regulated by H-NS and RpoS during the SOS induction and stationary growth phase.

sbmC, an Escherichia coli gene, belongs to the SOS regulon, whose product is involved in cell susceptibility to microcin B17 and its expression is induced at the onset of the stationary growth phase. In the present work, we have investigated the regulation of sbmC expression during SOS induction and the stationary growth phase using a single-copy sbmC'-'lacZ fusion. The SOS induction of sbmC is profoundly diminished in the hns mutant and less diminished in the rpoS mutant. The strain with hns, rpoS double mutation, showed a similar level of sbmC induction to that of a strain with hns single mutation. Mutation in rpoS or hns causes the repression of the sbmC gene during the stationary growth phase. The sbmC expression in the rpoS mutant strain was approximately twofold lower than that in the hns mutant and the rpoS hns double mutant showed a similar level of sbmC expression to mutants deficient in rpoS alone. Interestingly, the sbmC'-'lacZ expression in the exponential growth phase was not derepressed in the hns mutant background. Transformation of hns and rpoS mutants with plasmids carrying histone-like nucleoid protein (H-NS) and RpoS effectively restored the sbmC expression to the wild-type level, respectively. The gel mobility shift assay showed that purified H-NS protein directly bound with a high affinity to a DNA fragment carrying the sbmC promoter region. These findings demonstrate that H-NS regulates the sbmC expression via H-NS's direct binding to the promoter region. In conclusion, our data suggest that H-NS and RpoS regulate a stationary phase-inducible sbmC gene in E. coli.

Dithiothreitol induces the sacrificial antioxidant property of human serum albumin in a metal-catalyzed oxidation and gamma-irradiation system.

The species *OH or H2O2 are produced by both metal-catalyzed oxidation (MCO) of reducing equivalents and gamma-irradiation. Intact or Cys-34-modified human serum albumin (HSA) was significantly degraded in the MCO system containing dithiothreitol (DTT) as electron donor, but as long as it lasted, HSA prohibited *OH or H2O2 from initiating molecular damage of DNA. However, in the GSH and ascorbate (nonthiol) MCO system, HSA was not sacrificially degraded, and indeed accelerated the formation of DNA strand breaks. In the y-irradiation system producing *OH from H2O, only DTT attenuated the generation of DNA strand breaks by HSA. It did not degrade more H2O2 in the presence of reduced GSH (thiol-linked peroxidase) than in its absence. Therefore it would seem that in an MCO system, the antioxidant activity of HSA depends on the effectiveness of reducing equivalents to induce exposure of a functional group scavenging the *OH or H2O2 species, by reduction of its disulfide-bonds. In the presence of DTT, disulfide bonds in HSA were quantitatively reduced to cysteinyl residues but not significantly reduced by ascorbate or GSH. In conclusion, the antioxidant activity of HSA in the D