Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

BACKGROUND/AIMS: Fibroblast growth factor signaling is involved in hepatocarcinogenesis. The aim of this study was to determine the fibroblast growth factor receptor (FGFR) isotype expression in hepatocellular carcinoma (HCC) and neighboring nonneoplastic liver tissue, and elucidate its prognostic implications. METHODS: Immunohistochemical staining of FGFR1, -2, -3, and -4 was performed in the HCCs and paired neighboring nonneoplastic liver tissue of 870 HCC patients who underwent hepatic resection. Of these, clinical data for 153 patients who underwent curative resection as a primary therapy were reviewed, and the relationship between FGFR isotype expression and overall survival was evaluated (development set). This association was also validated in 73 independent samples (validation set) by Western blot analysis. RESULTS: FGFR1, -2, -3, and -4 were expressed in 5.3%, 11.1%, 3.8%, and 52.7% of HCCs, respectively. Among the development set of 153 patients, FGFR2 positivity in HCC was associated with a significantly shorter overall survival (5-year survival rate, 35.3% vs. 61.8%; P=0.02). FGFR2 expression in HCC was an independent predictor of a poor postsurgical prognosis (hazard ratio, 2.10; P=0.02) in the development set. However, the corresponding findings were not statistically significant in the validation set. CONCLUSIONS: FGFR2 expression in HCC could be a prognostic indicator of postsurgical survival.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Blotting, Western ; Carcinoma, Hepatocellular/metabolism/mortality/*pathology ; Female ; Hepatectomy ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Neoplasms/metabolism/mortality/*pathology ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Protein Isoforms/metabolism ; Receptors, Fibroblast Growth Factor/*metabolism ; Young Adult

BACKGROUND/AIMS: Fabry disease is an X-linked recessive and progressive disease caused by alpha-galactosidase A (alpha-GaL A) deficiency. We sought to assess the prevalence of unrecognized Fabry disease in dialysis-dependent patients and the efficacy of serum globotriaosylceramide (GL3) screening. METHODS: A total of 480 patients of 1,230 patients among 17 clinics were enrolled. Serum GL3 levels were measured by tandem mass spectrometry. Additionally, we studied the association between increased GL3 levels and cardiovascular disease, cerebrovascular disease, or left ventricular hypertrophy. RESULTS: Twenty-nine patients had elevated serum GL3 levels. The alpha-GaL A activity was determined for the 26 patients with high GL3 levels. The mean alpha-GaL A activity was 64.6 nmol/hr/mg (reference range, 45 to 85), and no patient was identified with decreased alpha-GaL A activity. Among the group with high GL3 levels, 15 women had a alpha-GaL A genetics analysis. No point mutations were discovered among the women with high GL3 levels. No correlation was observed between serum GL3 levels and alpha-GaL A activity; the Pearson correlation coefficient was 0.01352 (p = 0.9478). No significant correlation was observed between increased GL3 levels and the frequency of cardiovascular disease or cerebrovascular disease. CONCLUSIONS: Fabry disease is very rare disease in patients with end-stage renal disease. Serum GL3 measurements as a screening method for Fabry disease showed a high false-positive rate. Thus, serum GL3 levels determined by tandem mass spectrometry may not be useful as a screening method for Fabry disease in patients with end stage renal disease.
Adult ; Aged ; Fabry Disease/blood/*diagnosis ; Female ; Humans ; Kidney Failure, Chronic/blood/*therapy ; Male ; Middle Aged ; *Renal Dialysis ; Trihexosylceramides/*blood ; alpha-Galactosidase/genetics/metabolism

OBJECTIVE: To evaluate the changes of gait patterns during crossing obstacles of different heights in hemiplegic stroke patients and to compare gait characteristics with those of healthy control subjects. METHOD: Subjects were 13 hemiplegic stroke patients and 9 age-matched healthy adults. Subjects stepped over obstacles with each height of 3, 8 and 13 cm. The three- dimensional gait analysis was performed. Temporospatial, kinematic and kinetic parameters were measured in both lead and trail limb. The pre- and post-obstacle distance, pre- and post-obstacle swing time and toe clearance were also measured. RESULTS: With increase in height of obstacles, ratio of single limb support time, angle of hip, knee flexion in swing phase and hip extensor moment increased in both lead and trail limbs. In the lead limb, post-obstacle distance and toe clearance also increased (p<0.05). Compared with control groups, the angle of knee flexion, hip extensor and hip flexor moment and pre- and post-obstacle distance decreased significantly in the lead limb of hemiplegic patients (p<0.05). In the trail limb of hemiplegic patients, the angle of hip flexion, hip flexor moment and post-obstacle distance decreased (p<0.05). CONCLUSION: Understanding strategies for adequate control and coordination of the swing limb during crossing obstacles may be the basis for the safe training of obstacle crossing in hemiplegic stroke patients.
Adult ; Extremities ; Gait ; Hip ; Humans ; Knee ; Stroke ; Toes

BACKGROUND: The optimal screening tools for hepat ocellular carcinoma are regular tests of alpha fetoprotein (aFP)and liver ultrasonography every 6 months in high risk group. To implement successful long-term project for reducing cancer-mortality,it is essential to know the reasons f or non-compliance among the high risk group. METHODS: A telephone survey was done a mong the hepatitis B surface antigen positive patient group who had not receiveda follow-up test of aFP and liver ultrasonography. This group was selected among the patients who had received health examinations from January,2002 to December,2002 at a university hospital center for health promotion, and the reasons for non-compliance were inquired. RESULTS: There were no stati stical di fferences i n educational level,economic status,age,and sex between the patient group who had taken appropriate follow-up tests and the group who had not. But there were statistically significant differences in the admission history and t ransf usi on hi st ory bet ween t he t wo groups. The reasons for non-compliance were as follows:1. ignorance to the significance of follow-up examination (41.7%),2.lack of time (27.8%),3.no specific signs of cancer (22.2%),4.high costs (5.6%),and 5.fear of discovering serious disease. CONCLUSION: It is important to have patients educated on the significance of screening and early diagnosis of hepatocellular carcinoma.
alpha-Fetoproteins ; Carcinoma, Hepatocellular* ; Compliance ; Early Diagnosis ; Follow-Up Studies ; Health Promotion ; Hepatitis B Surface Antigens* ; Hepatitis B* ; Hepatitis* ; Humans ; Liver ; Mass Screening* ; Telephone ; Ultrasonography

PURPOSE: Acute renal failure (ARF) is one of the common complications after liver transplantation (LT) and could be fatal unless promptly treated. Identification of risk factors is needed to prevent ARF and to attenuate the unfavorable outcomes of ARF after LT. The aim of this study was to analyze risk factors for development of postoperative ARF (between day 0 and day 30 after LT). METHODS: Total 72 LTs were performed between 1996 and 2005. Sixty six patients' records, excluding 6 patients with preoperative serum creatinine level more than 2.5 mg/dl, were reviewed retrospectively for preoperative, intraoperative, and postoperative variables to compare patients presenting ARF with the remaining patients. RESULTS: Postoperative ARF occurred in 36 transplants (54.5%) after LT. Preoperative serum sodium, bilirubin and BUN, creatinine level were higher in ARF group. ARF group had more child-pugh class C, and more episodes of preoperative hepatic encephalopathy. During intraoperative period, anhepatic time was longer and total doses of intraoperative furosemide was larger in ARF group. Also, postoperative blood immunosuppressant level was higher, and postoperative episodes of bleeding and hypotension were more common in ARF group. In multivariate analysis, preoperative child-pugh class C (P=0.041), preoperative serum creatinine level (> or =1.0 mg/dL, P=0.032), and postoperative episodes of hypotension and bleeding (P=0.045, P=0.03 respectively) were identified as risk factors for postoperative ARF. CONCLUSION: This study showed that preoperative renal and liver function, and postoperative hemodynamic condition were independent risk factors for development of ARF after LT.
Acute Kidney Injury* ; Bilirubin ; Creatinine ; Furosemide ; Hemodynamics ; Hemorrhage ; Hepatic Encephalopathy ; Humans ; Hypotension ; Intraoperative Period ; Liver Transplantation* ; Liver* ; Multivariate Analysis ; Retrospective Studies ; Risk Factors* ; Sodium

OBJECTIVE: To evaluate the level of depression, anxiety and quality of life in primary caregivers for the severe stroke patients. METHOD: We studied a sample of 44 severe stroke patients and their primary caregivers. Functional status of the severe stroke patients was evaluated by Modified Barthel Index (MBI). We collected the data through interviewing the caregivers and using the Beck Depression Inventory (BDI), State- Trait Anxiety Inventory (STAI), Ego-strength scale, Short Form Health Survey-36 (SF-36) and Family APGAR (Adaptation, Partnership, Growth, Affection and Resolve) score. RESULTS: The average level of depression in caregivers was low. The mean socres of STAI were 41.5 for state anxiety and 44.3 for trait anxiety, respectively. Ego-strength scale was significantly inversely related to BDI score and trait anxiety inventory score, but positively related to SF-36 score. The most influencing factor for the SF-36 score was the BDI score. CONCLUSION: Primary caregivers for the home-bound severe stroke patients demonstrated a lower level of quality of life, especially mental health, general health and vitality component. Community based rehabilitation should more focus on the evaluation and support for caregiver's psychologic status and their quality of life.
Anxiety ; Caregivers* ; Depression ; Humans ; Mental Health ; Quality of Life* ; Rehabilitation ; Stroke*

PURPOSE: we clinically measured the temperature rise in real time and analyzed the difference of albino rabbit and pigmented rabbit in use of the specially designed thermometer. METHODS: Specially designed thermometer was attached into the subretinal pigment epithealial and choroidal space through the suprachoroidal space in three pigment and three albino rabbits, with diode laser of 810 nm wave length, 3 mm spot size. We examined the retinal temperature according to laser irradiance power at each ten seconds during sixty seconds and the laser power setting was 200 mW, 300 mW, 400 mW in pigmeted rabbit and 300 mW, 600 mW, 800 mW in albino rabbit. We analyzed the results based on the measurements at least three times per each irradiance power. RESULTS: In albino rabbit, the maximal range of retinal temperature change was 1.2 degrees C and 1.7 degrees C in 300 mW and 600 mW, 14.1 degrees C in 800 mW power of 810 nm diode laser irradiance. In pigmented rabbit, the maximal range of retinal temperature change was 12.1 degrees C in 200 mW of laser irradiance power, 16.2 degrees C in 300 mW, 24.3 degrees C in 400 mW during sixty seconds in 810 nm diode laser. CONCLUSIONS: We investigated the ratinal temperature at transpupillary thermotherapy in 810 nm wavelength diode laser on rabbits. The difference of retinal temperature change was in accordance with the amount of chorioretinal melanin pigment. Therefore if the laser power setting used in caucasians would be attempted in orientals, it is the point to be considered during transpupillary thermotherapy.
Choroid ; Hyperthermia, Induced* ; Lasers, Semiconductor ; Melanins ; Rabbits* ; Retinaldehyde* ; Thermometers

BACKGROUND: Autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC), and autoimmune cholangiopathy (AIC) are major classes of liver diseases currently considered autoimmune. We investigated the clinical, biochemical, and immunologic findings in Korean patients with these disease entities. METHODS: We retrospectively analyzed 47 patients with AIH, 27 with PBC, 3 with Overlap syndrome, 15 with AIC, and 5 with PSC. RESULTS: About 90% of the patients were women, while 40% in PSC. The mean age of onset ranged from 47 to 57 years, while it was 28 years in PSC. Fatigue and jaundice were the most frequent manifestations at diagnosis. In AIH, 13% of patients had an acute onset and 1 died of fulminant hepatic failure. The serum level of IgG was elevated in 67.5%, and antinuclear antibody and anti-smooth muscle antibody were detected in 95.7% and 43.2%. Fifty eight per cent of the patients who received immunosuppressive therapy showed a complete response. In patients with PBC, the level of IgM was elevated in 75% and all of the patients were positive for anti-mitochondrial antibody. Biochemical remission was observed in 37% on ursodeoxycholic acid therapy. Except for the negative anti-mitochondrial antibody, the clinical and biochemical features in AIC were not different from those in PBC. CONCLUSION: Autoimmune liver diseases are not rare in Korea. Considering that these entities are potentially treatable diseases, a high index of suspicion is needed, especially in patients negative for the serologic markers of viral hepatitis.
Age of Onset ; Antibodies, Antinuclear ; Cholangitis ; Cholangitis, Sclerosing ; Diagnosis ; Fatigue ; Female ; Hepatitis ; Hepatitis, Autoimmune ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Jaundice ; Korea* ; Liver Cirrhosis ; Liver Cirrhosis, Biliary ; Liver Diseases* ; Liver Failure, Acute ; Liver* ; Retrospective Studies ; Ursodeoxycholic Acid

The number of diabetic ESRD patients has increased and death rates of diabetic patients on hemodialysis (HD), peritoneal dialysis (PD) and renal transplantation (RT) have remained higher than the death rate of non-diabetic patients. An attempt was made to compare the clinical characteristics, patients' cumulative survival, and technical survival among the three groups retrospectively according to the mode of renal replacement therapy (RRT), and to analyze the risk factors associated with mortality. A total of 229 diabetic ESRD patients diagnosed between 1986 and 1995 at the Severance Hospital who began dialysis or who underwent a kidney transplant were included and their medical charts were reviewed. Hypertension was the most common co-morbid disease in all study groups. The prevalence of cardiovascular disease was the only co-morbid condition that was significantly different among the three groups, which was highest in the PD group (24.4%) and lowest in the RT group (8%). In the analysis of a patient's cumulative survival rate not adjusted for age and sex, the RT group had the highest survival rate, and the cumulative survival rate of the HD and PD group were similar. The 5-year survival rate of the patients treated with HD, PD and RT was 28.8%, 19.8%, and 72.0%, respectively. No differences were observed in the patient's cumulative survival rate between the HD and PD patients even when it was adjusted for age. When adjusted for age, sex and risk factors, the relative death rate of the RT group was significantly lower in male patients younger than 60 years of age. With the exception of male patients younger than 60 years of age, the PD group showed a slightly lower relative death rate although it was not significant. The multiple Cox regression analysis of patient survival showed that age, serum albumin, BUN, mean hospital days, the presence of cardiovascular disease at the initiation of RRT were associated with mortality. The analysis of the technique survival rate revealed a better result in the HD group compared to PD group, but a limitation in being able to investigate the AVF function disturbed the accuracy of the analysis of technical survival rate. In conclusion, the survival rate between the PD and HD patients was not different and the RT group had the best survival rate. Therefore, kidney transplantation in diabetic ESRD patients should be considered positively if no other contraindicated condition for RT exit.
Aged ; Comparative Study ; Female ; Human ; Kidney Failure, Chronic/mortality/*therapy ; *Kidney Transplantation/adverse effects ; Korea ; Male ; Middle Aged ; *Peritoneal Dialysis/adverse effects ; *Renal Dialysis/adverse effects ; Retrospective Studies ; Survival Analysis