Substance-P Ameliorates Dextran Sodium Sulfate-Induced Intestinal Damage by Preserving Tissue Barrier Function

Intestinal inflammation alters immune responses in the mucosa and destroys colon architecture, leading to serious diseases such as inflammatory bowel disease. Thus, the modulation of intestinal integrity and immune responses in IBD can be the critical factor to be considered to reduce the severity of damages. Substance-P (SP), endogenous peptide to be involved in cell proliferation, migration and immune modulation, can exert the therapeutic effect on diverse diseases including cornea damage, rheumatoid arthritis and diabetic complications. SP was found to elevate expression of junctional molecule. Considering the function of SP reported previously, it was inferred that SP is capable of exert the beneficial effect of SP on intestinal diseases by controlling intestinal structure as well as immune responses. In this study, we explored the therapeutic effect of SP on dextran sodium sulfate-induced intestine damage by injecting SP. The effects of SP were evaluated by analyzing crypt structures, proliferating cell pool and infiltration of immune cells. DSS treatment provoked abnormal immune response and disruption of intestine epithelial barrier. However, co-treatment of SP obviously blocked the development of intestinal damages by declining inflammatory responses and sustaining intestinal structure more intact. The treatment of SP to chronic damages also promoted intestinal regeneration by preserving the integrity of colon tissue. Moreover, DSS-induced reduction of epithelial junctional molecule was obviously inhibited by SP treatment in vitro. Taken together, our data indicate that SP can reduce intestinal damages, possibly by modulating barrier structure and immune response. Our results propose SP as candidate therapeutics in intestinal damages.

Associations between Breast Density on Mammography and Lifestyle Related Disease

BACKGROUND: Dense breast reduced the sensitivity of mammography in breast cancer screening and known as an independent risk factor of breast cancer. The relationship between breast density and age, body mass index has studied. However, there are few studies on the relationship between breast density and lifestyle related disease. In this study, we investigated the relationship between mammographic breast density and lifestyle related disease. METHODS: Retrospective cross sectional research was carried out from people who visited a single health screening center in Busan from January 2015 to December 2015. We investigated age, past history of the subjects and measured their height, weight, blood pressure and waist circumference. The biochemical test was carried out using their blood. All patients underwent mammography. The breast density on mammography determined by the basis of American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS) breast composition and 996 people was recruited. RESULTS: In the distribution of breast density, 16.3% of women (n=160) had dense breast. Age (under 49), body mass index (BMI) (underweight) were positively correlated with the BI-RADS composition category 3, 4 but the number of lifestyle related disease were negatively correlated (age ρ=0.17, BMI ρ=0.39, the number of lifestyle related disease ρ=-0.21). The odds ratio (OR) of dense breast increased with decreasing lifestyle related disease severity (OR=3.06, 95% confidence interval: 1.13-8.22, P=0.027). CONCLUSIONS: This study showed that the number of lifestyle related disease was negatively correlated with mammographic density. The OR of dense breast increased with decreasing lifestyle related disease severity. Therefore, primary physicians should consider negative correlation between breast density and lifestyle related disease in breast cancer screening.

Spontaneous Renal Artery Dissection in a Patient with Protein C and S Deficiency / 대한내과학회지

Spontaneous renal artery dissection without aortic dissection in normotensive patients is rarely reported. Spontaneous renal artery dissection is also an uncommon cause of renal infarction that occurs, though rarely, in patients with hypercoagulable states such as protein C and S deficiency. We report here a case of spontaneous renal artery dissection and renal infarction associated with protein C and S deficiency.

Erythropoietin Antibody-Positive Pure Red Cell Aplasia Diagnosed after Surgical Intervention for Malignant Gastric Ulcer Bleeding / 대한내과학회지

Rarely, patients on erythropoietin stimulating agent (ESA) therapy develop antibodies that neutralize both ESA and endogenous erythropoietin, resulting in antibody-mediated pure red cell aplasia (PRCA). The sudden development of severe transfusion-dependent anemia requires rapid recognition, the evaluation of PRCA, and prompt intervention after differentiating other causes of anemia, such as iron deficiency, occult bleeding, and infection. Here, we report the case of a 67-year-old male undergoing hemodialysis who presented with the anemia of chronic blood loss from a malignant gastric ulcer. Even after surgical intervention for stomach cancer and increasing the erythropoietin dosage, the anemia was not correctable and required monthly packed red blood cell transfusions. Further evaluation revealed positive erythropoietin antibody, and a bone marrow biopsy showed no red blood cell precursors, supporting the diagnosis of PRCA.

Basic data on the hematology, serum biochemistry, urology, and organ weights of beagle dogs / 한국실험동물학회지

This study was conducted to provide basic data on physiological and hematological characteristics, and organ weights of beagle dogs. A total of 237 beagle dogs were used to determine differences in physiological and hematological parameters, and organ weights depending on sex and age. The respiratory rate of both sexes tended to increase as they grew older and the female heart rate was slightly higher than that of males. Male and female body weights increased rapidly to 33 weeks old followed by a gradual increase to 41-weeks-old. The relative weight of the brain was negatively correlated with body weight, whereas the weight of reproductive organs was positively correlated with body weight. The platelet count of female dogs was slightly higher than that of males. The red blood cell, hemoglobin, and hematocrit of both sexes increased non-significantly with age. In the leukocyte differential count, the neutrophils, and eosinophils of both sexes tended to increase as they grew older, whereas basophils, lymphocytes, and monocytes decreased. In the serum biochemical profiles, alkaline phosphatase was slightly higher in males than females, while the total cholesterol of female dogs at 9-months-old was higher than that of males at the same age. Other biochemical components, including alanine aminotransferase, blood urea nitrogen, creatinine, triglyceride, and total protein increased non-significantly with age in both sexes. To conclude, we observe no significant physiological or hematological differences with sex or age, although decreasing and increasing trends were detected with some parameters. These data provide valuable reference indices of the normal physiological and hematological characteristics of beagle dogs, which should prove useful in toxicological and pharmacological studies.

A Case of Hemicranial Pneumocephalus Secondary to Removal of a Central Venous Catheter / 대한내과학회지

The presence of pneumocephalus associated with insertion, maintenance, and removal of intravenous catheters is a rare radiographic finding, but may be clinically relevant. Various pathways have been proposed to explain the development of pneumocephalus, but none are well understood. We present a patient with hemicranial pneumocephalus secondary to removal of a central venous catheter as determined by computed tomography, and we propose a possible mechanism of the pneumocephalus.

No Association of TGF-beta Gene Polymorphism with the Progression of Autosomal Dominant Polycystic Kidney Disease(ADPKD) in Korean Patients / 대한신장학회잡지

BACKGROUND: Two genetic loci, PKD1 and PKD2, have been identified as being responsible for ADPKD, and PKD1 is known to be associated with poor prognosis. However, the presence of intrafamilial clinical diversity suggests the presence of disease-modifying loci. Because the mechanism of renal failure in ADPKD includes cystic growth and tubulointerstitial atrophy and fibrosis, we studied the associations between two cytokine gene polymorphisms in the TGF-beta gene, which are known to be related with chronic tubulointerstitial inflammation, and ADPKD progression in Korean patients. METHODS: 47 normal controls and 114 individuals with ADPKD were genotyped by PCR-RFLP, and the TGF-beta gene leader sequence of T869C(Leu10Pro) variant was compared with MspA1I and G915C (Arg25Pro) with BglI. Statistic significances were determined using the Chi-square test. RESULTS: The distribution of alleles for the TGF-beta Leu10Pro polymorphism in ADPKD was : T 52%, C 48%, which was similar to the Korean(56 : 44, p= 0.670) and Western controls(65 : 35), and in addition, no differences were found between the CRF and the non-CRF groups(p=0.571) or the early hypertension and the normotension groups(p=0.252). The distribution of alleles for the TGF-beta Arg25Pro polymorphism was all GG type, which was different from Western controls(90 : 10, p=0.000). CONCLUSION: Our results suggest that the polymorphism at Arg25Pro of TGF-beta in Korean population has different allele distribution from Western, and the polymorphism at Leu10Pro of TGF-beta has no association with the renal progression of Korean ADPKD patients.

Sclerotherapy of Renal Cysts in Korean ADPKD Patients / 대한신장학회잡지

BACKGROUND: Autosomal dominant polycystic kidney disease(ADPKD) is the most common hereditary renal disease in adults, and its major complaints include pain and abdominal fullness due to cyst expansion. So far, for the control of these symptoms, cyst ablation with ethanol or tetracycline, laparoscopic manipulations and surgical marsupialization have been used. METHODS: We used conventional ethanol(n=9) or n-butyl cyanoacrylate(NBCA) plus lipiodol solution (n=18) or both(n=3) for separate cysts as the sclerosing agent in 24 adult Korean ADPKD patients. And their clinical courses after treatment were evaluated. RESULTS: The male to female ratio was 8 : 16 and the mean age at the treatment was 50 yrs(S.D. 13.1). Causes for aspiration were pain in 14 and abdominal fullness in 7 patients and the range for the cyst diameters aspirated were 5-16 cm. Flank pain or discomfort were decreased subjectively in most cases except two. Mean arterial pressures(S.D.) (mmHg) before and after procedure were as follows 112(11.1)(basal), 96(9.6)(1 month) and 98(9.7)(6 month)(p < 0.05, paired-t test). Blood urea nitrogen levels(mg/dL) were not changed 6 month later[24 (12.1) vs. 22(14.6)]. There was no major complication such as bleeding or infection and no death and associated with procedure. There was no difference of therapeutic effect according to sclerosing agent. CONCLUSION: NBCA was as effective as conventional ethanol for sclerotherapy in ADPKD and cyst ablation therapy showed a BP-lowering effect in short-term period.

Clinical Characteristics of End-stage Renal Disease in Korean Autosomal Dominant Polycystic Kidney Disease / 대한신장학회잡지

End stage renal disease(ESRD) is a well-known major complication of autosomal polycystic kidney disease(ADPKD). Several risk factors of renal progression in ADPKD were identified, such as PKD1 gene, male gender and earlier age of onset. In Korea, ADPKD is a cause of ESRD in 2% of hemodialysis patients. Until now, only a few detailed studies have been performed in regarding to evaluate the risk factor for ESRD especially in the Asian population. 148 ADPKD patients were registered to PKD clinic in our hospital(Mar. 1996-Dec. 1999). Among them, 34 patients(male : female = 14 : 20) who had started renal replacement therapy were studied to elucidate clinical characteristics including the nature of progression of renal failure. These data were compared with 14 patients(male : female = 3 : 11) who did not develop renal failure(serum creatinine 1g/24h), urolithiasis, upper urinary tract infection, hypertension and liver cysts were 69, 54, 16, 29, 85 % and 85%, respectively. 84% of these patients had family members with ADPKD and 10% of them had ESRD family members. PKD1 vs. PKD2 was 7 : 1 in 8 patients with ESRD and 1 : 1 in 2 patients of control group. Gross hematuria and proteinuria were more prevalent in ESRD patients than the control group(p=0.001 and p=0.0008, respectively). In 18 patients with ESRD, rates of renal progression were traced using a reciprocal of serum creatinine(1/Cr) curve. Once azotemia(serum creatinine value > OR =1.5 mg/dL) developed, the median rate of decline of 1/Cr was -0.073dL/mg/year(range : -0.046--0.114dL/mg/year), which was constant irrespective of either the age of onset or sex. In summary, in 34 patients, the renal function seemed to be maintained to a certain age. But, once azotemia developed, the renal function was rapidly declining with similar rate, ended up ESRD in 8.2 years. Presence of gross hematuria and proteinuria were associated with poor prognosis.

The Expression Patterns of CD44 and CD45RB on Peripheral Blood T Lymphocytes in the Rejection of Allogeneic Skin Transplantation in Mice / 대한이식학회지

PURPOSE: Until now, the rejection was diagnosed through a biopsy, but this method of diagnosis reflected the advanced tissue damage of the transplanted organ and contained the innate problem of being invasive. Activation of T lymphocytes, which occurs before the overt tissue damage has a pivotal role in rejection. In relation, our research attempted to evaluate the viability of analyzing the surface antigens of the peripheral blood activated T lymphocytes in mice after skin transplantation as a noninvasive and early diagnostic tool for diagnosis of rejection. METHODS: After the mouse's skin was transplanted, the expression patterns of activated T lymphocyte markers, CD44 and CD45RB were analyzed along with T lymphocyte markers, CD3, CD4, and CD8 using flow cytometry. The skins from the tails of allogeneic Balb/c (H2(d)) mice and syngeneic C57BL/6J mice were transplanted to C57BL/6J (H2(b)) mice as test and control groups, respectively. Peripheral blood, which was sampled from the tail every other day from day 3 to day 15 was stained with anti-CD44 (or CD45RB), anti-CD4 (or CD8) and anti-CD3 monoclonal antibodies simultaneously, and analyzed by 3-color FACS. Repeated ANOVA test and Mann-Whitey test were used to analyze the differences between the expression patterns of peripheral blood T lymphocyte surface antigen in the control and test groups (SPSS 8.0). RESULTS: Rejection occurred only in the test group from day 8 to day 13 (median: day 10). Although the proportions of CD3(+)lymphocytes (CD3(+)%), CD4(+)lymphocytes (CD4(+) %), and CD8 lymphocytes (CD8(+)%) showed no difference between the control and test groups, the total number of peripheral blood lymphocytes and the number of CD3(+)lymphocytes (CD3(+)) and CD8(+)lymphocytes (CD8(+)) decreased more sharply in the control group after day 7. The proportion and the number of CD44 CD3(+)lymphocytes, CD44 CD4(+)lymphocytes, and CD44(+) CD4(+) CD3(+)lymphocytes began to increase after day 7, to peak on day 11, and then to decrease, showing a significant difference from those of the control group. The proportion and number of CD44(+) CD3(+)lymphocytes, in particular, showed the most significant difference among these significant markers. The proportion and number of CD44(+) CD8(+) lymphocytes and CD44(+) CD8(+) CD3(+)lymphocytes showed similar trends to those of CD44(+) CD3(+) or CD44(+) CD4(+), but the differences between the subset proportions in control and test groups were statistically insignificant. No significant difference was observed in any subsets of the CD45RB antigen. CONCLUSION: CD44(+)CD3(+) lymphocytes representing activated T lymphocytes increased significantly compared to the control group during the rejection period of skin transplantation. The analysis of the expression patterns of surface antigen CD44 on peripheral blood T lymphocytes using flow cytometry is sensitive, safe, easily repeatable, and controllable, and, therefore, can be considered a promising tool for the diagnosis of rejection. However, the clear change in CD44 occurred between day 9 and day 13, when rejection was observed grossly. Therefore, it is regarded more useful as a screening test or follow-up indicator rather than as an early diagnostic tool.

Genotype Analysis in Korean Families with Autosomal Dominant Polycystic Kidney Disease(ADPKD) / 대한신장학회잡지

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease in adults, and its major morbidities are renal failure and cerebrovascular accident. The prevalence of this disease in the chronic haemodialysis patient population is known to be approximately 2% in Korea. So far, three genetic loci have been identified as being responsible for ADPKD, and approximately 85% of the cases in Western countries are related to the PKD1 gene. However, little information is available concerning the pattern of linkage analysis or the mutations present in Asian populations. For this study, 35 families with hereditary renal cysts were recruited from our ADPKD clinic from 1993 to the present, and their molecular genetic characteristics were studied. Subjects were chosen according to the criteria of Ravine et al. Linkage analysis was done with microsatellite markers(PKD1:SM7, UT581, AC2.5, KG8, D16S418, PKD2 : D4S423, D4S1534, D4S1542, D4S1544, D4S2460). Genomic DNA PCR and PAGE gel run were done, and the allele patterns were compared with sonographic findings. The results of this study showed that the ratio of PKD1 to PKD2 was 23 : 3, and PKD2 families showed the tendency of milder renal prognosis than PKD1 families. In conclusion, we confirmed the usefulness of linkage analysis for ADPKD in Korean population, and our data shows a similar percentage of PKD1(88%) and PKD2(12%) in Korean patients as in the Western population.

Cerebrovascular complications in autosomal dominant polycystic kidney disease(ADPKD) / 대한내과학회지

BACKGROUND: ADPKD is one of the most common hereditary renal disease in adult and is a systemic disorder with a variety of cardiovascular manifestations. To elucidate the clinical characteristics of cerebrovascular complications in Korean ADPKD patients, we reviewed the medical records of ADPKD patients who was registered in ADPKD clinic of Seoul National University Hospital. METHODS: A total of 18 adult patients were included and their sex ratio was 8:10. The median age of ADPKD diagnosis was 45.5 year (range 19-85), and age at cerebrovascular accident(CVA) was 52 years(22-82). The median duration from hypertension to CVA was 8 years(0-30). RESULTS: There were 5 cases of infarction, 4 cases of intracerebral hemorrhage, 4 cases of subarachnoid hemorrhage, and 4 cases of transient ischemic attack. Other clinical parameters of ADPKD were not different from patients who were not complicated with CVA. Intracranial aneurysms were detected in 6 patients and their median age at diagnosis was 47.5 years(33-66). Four cases were manifested as subarachnoid hemorrhage. Five cases were diagnosed through TFCA, and two of them were revealed as multiple aneurysms. Five cases received surgical treatment and five of six cases improved without any neurologic sequeale. MR angiography(MRA) were taken in 16 asymptomatic patients, and multiple aneurysms were newly detected in one of them. CONCLUSION: Cerebrovascular complications in Korean ADPKD patients were not significantly different from western patients. Intracranial aneurysms must be included in differential diagnosis in ADPKD patients who manifest an acute neurologic symptoms, and high-risk group need to be screened selectively with MRA.

Serial Changes in Plasma Cytokine Levels in Hemorrhagic Fever with Renal Syndrome / 대한신장학회잡지

Hemorrhagic fever with renal syndrome (HFRS) in Korea is caused by 2 serotypes of hantavirus, Hantaan and Seoul. Even though the number of peripheral CD8' T-lymphocytes is markedly elevated in the acute phase of HFRS, the pathogenetic role of this phenomena is not clear. To elucidate the role of cell-mediated immune response in HFRS, we measured concentrations of cytokines, such as IL-1, IL-2, IL-4, IL-6, IL-10 and IFN-r in plasma samples obtained from 15 patients (15 men, 20-24 years old) at various phase of illness. Cytokines were measured by ELISA in plasma samples. The plasma concentration of IL-10 was elevated in 13/15 patients. The median maximum value, during days 4-8, was 23 ng/L (range, 0-70.2). The maximum values were significantly higher(p=0.005) than the baseline. IL-1 and IL-6 was detected in 6 patients. Other cytokine responses (IL-2, IL-4, IFN-r ) were negligible. There was no significant correlation between maximum levels of IL-10 and maximum serum concentration of creatinine (r=0.118, p=0.675), and lowest plate#let count (r=-0.088, p=0.765). Kinetics of IL-10 were quite similar in HFRS patients with maximum creatinine values >3 mg/dL and in those with values <3 mg/dL. In conclusion, plasma IL-10 levels, but not IL-2, IL-4 or INF-r were elevated in acute phase of HFRS, and it suggests that the systemic immunosuppressive activities of IL-10 might have some pathogenetic role in HFRS.

Clinical and Genetic Characteristics of 49 Probands of Autosomal Dominant Polycystic Kidney Disease in Korea / 대한신장학회잡지

We analysed the 49 probands of autosomal dominant polycystic kidney disease (ADPKD) in Korea to elucidate clinical and genetic characteristics. 1) Family history of renal disease or ADPKD was taken from 44% of probands; hypertension 88%, cerebrovascular attack 64%, end stage renal disease 16%. 2) From the family screening with renal ultrasonography, we have confirmed dominant trait in 24 families. We found 2 families which have suspicious new mutations. 3) We performed linkage analysis of 15 families. The PKD-1 to non PKD-1 ratio was 13 : 2. 4) The male to femal ratio was 17 : 32 and age at diagnosis was 41 (24-65)years (mean (range)) in male, 45 (26-68) years in female. 5) The factors leading to the diagnosis of ADPKD were flank pain (23%), incidental finding (17%), palpable abdominal mass (11%), headache (9%) and gross hematuria (9%) 3) Hypertension (80%), azotemia (43%), flank pain (42%), renal calcification (42%), gross hematuria (33%) and cyst hemorrhage (25%) were renal complications. There were 2 renal cell carcinoma cases. 4)Liver cyst (82%) was the most common extrarenal manifestations. There were colonic diverticulosis (13%), cerebral artery aneurysm (7%), adrenal cyst (4%) and pancreatic cyst (2%). Results of our study revealed the clinical and genetic characteristics of ADPKD in Korea. We found only 44% of family history of renal disease, variable initial manifestations, variable renal and extrarenal complications. And we also found the similar percentage of PKD-2 (13%) to that (5-15%) of western countries, but it is necessary to study with more patients and families.

Clinicopathological Study on Adult Nephrotic Syndrome / 대한신장학회잡지

We investigated the clinical features of nephrotic syndrome in Korea according to sex, age and pathologic diagnosis under the classification system supported by WHO. Adult nephrotic patients who underwent renal biopsy from 1979 to 1993 at the Department of Internal Medicine, Seoul National University Hospital, with the exception of diabetic nephropathy and multiple myeloma, were analyzed in terms of their clinical manifestations, laboratory data, and pathologic features. 1) The number of our total nephrotic patients was 956 and their mean age was 32.6. Male to female ratio was 1.96:1. 2) Among total nephrotic syndrome patients, there were 736 (77%) primary NS and 220 (23%) secondary NS patients. 3) The pathologic diagnoses of the primary NS were minimal change nephrotic syndrome (41.6%), membraneous nephropathy (20.9%), focal glomerulosclerosis (17.3%), IgA nephropathy (9%), membranoproliferative GN (4.5%), sclerosing GN (2.4%), and mesangial proliferative GN (2.2%). 4) Among primary NS patients with ages between 15 and 40, the percentage of minimal change nephrotic syndrome was highest(47.7%), while among those above 40 of age, membraneous nephropathy was most common(42.1%). 5) The pathologic diagnoses of the secondary NS were hepatitis B virus associated GN (46.8%), lupus nephritis (39.5%), amyloidosis (5.9%), post-infectious GN (2.7%), Henoch-Schoenlein nephritis (2.7%). We had one each case of thrombotic thrombocytopenic purpura, Fabry's disease, mixed essential cryoglobulinemia, light chain disease, and Alport's syndrome. In conclusion, minimal change nephrotic syndrome was the most common disease among the primary NS and hepatitis B virus associated GN was the most common among the secondary NS.