Miyeon Kim

Proinsulin Shares a Motif with Interleukin-1α (IL-1α) and Induces Inflammatory Cytokine via Interleukin-1 Receptor 1

Although it has been established that diabetes increases susceptibility to infections, the role of insulin (INS) in the immune response is unknown. Here, we investigated the immunological function of INS. Proinsulin dimer (pINSd) was a potent immune stimulus that induced inflammatory cytokines, but mature INS was unable to induce an immune response. An affinity-purified rabbit polyclonal antibody raised against mature IL-1α recognized IL-1α and pINS but failed to detect mature INS and IL-1β. Analysis of the pINS sequence revealed the existence of an INS/IL-1α motif in the C-peptide of pINS. Surprisingly, the INS/IL-1α motif was recognized by monoclonal antibody raised against IL-1α. Deleting the INS/IL-1α motif in pINSd and IL-1α changed their activities. To investigate the pINSd receptor, the reconstitution of IL-1 receptor 1 (IL-1R1) in Wish cells restored pINSd activity that was reversed by an IL-1R antagonist. These data suggested that pINSd needs IL-1R1 for inflammatory cytokine induction. Mouse embryo fibroblast cells of IL-1R1-deficient mice further confirmed that pINSd promotes immune responses through IL-1R1.

Cytokine-like Activity of Liver Type Fatty Acid Binding Protein (L-FABP) Inducing Inflammatory Cytokine Interleukin-6

It has been reported that fatty acid binding proteins (FABPs) do not act only as intracellular mediators of lipid responses but also have extracellular functions. This study aimed to investigate whether extracellular liver type (L)-FABP has a biological activity and to determined serum L-FABP levels in patients with end-stage renal disease (ESRD). We isolated L-FABP complementary deoxyribonucleic acid (cDNA) from the Huh7 human hepatocarcinoma cell line and expressed the recombinant L-FABP protein in Escherichia coli. A549 lung carcinoma and THP-1 monocytic cells were stimulated with the human recombinant L-FABP. Human whole blood cells were also treated with the human recombinant L-FABP or interleukin (IL)-1α. IL-6 levels were measured in cell culture supernatants using IL-6 enzyme-linked immunosorbent assay (ELISA). Human recombinant L-FABP induced IL-6 in a dose-dependent manner in A549, THP-1 cells, and whole blood cells. The blood samples of healthy volunteers and patients with ESRD were taken after an overnight fast. The serum levels of L-FABP in healthy volunteers and ESRD patients were quantified with L-FABP ELISA. The values of L-FABP in patients with ESRD were significantly lower than those in the control group. Our results demonstrated the biological activity of L-FABP in human cells suggesting L-FABP can be a mediator of inflammation.

Effectiveness of beraprost sodium in maintaining vascular access patency in patients on hemodialysis

PurposeHemodialysis vascular access dysfunction, mostly attributed to neointimal hyperplasia, is a major cause of morbidity and hospitalization in patients on hemodialysis. It has been reported that prostaglandin I2 has pleiotropic effects including anti-platelet, vasodilating, anti-inflammatory, and anti-atherogenic properties. In addition, several studies have shown that prostaglandin I2 can inhibit neointimal formation after vascular injury. This study aimed to investigate the effects of beraprost sodium, an oral synthetic analog of prostaglandin I2, on vascular access patency in patients on hemodialysis who experienced primary hemodialysis vascular access failure.MethodsFifty-five patients with end-stage renal disease who were on hemodialysis were prospectively selected for this study. Twenty-three patients were assigned to be treated with 120xa0µg/day of beraprost sodium, while remaining patients (nxa0=xa032) were assigned to a control group. The primary outcome was primary unassisted vascular access patency at 2xa0years.ResultsThe incidence of primary unassisted patency at 2xa0years was 83% in the beraprost sodium group and 38% in the control group (pxa0=xa00.001). Analysis of covariables indicated that this effect occurred mainly as a result of beraprost sodium administration. No life-threatening adverse event or severe bleeding was recorded in any of the groups.ConclusionsOur data indicated that an oral prostaglandin I2 analog, beraprost sodium, is effective and safe for the maintenance of vascular access patency in patients on hemodialysis with primary vascular access failure.

Dendritic Cell Dysfunction in Patients with End-stage Renal Disease.

End-stage renal disease (ESRD) with immune disorder involves complex interactions between the innate and adaptive immune responses. ESRD is associated with various alterations in immune function such as a reduction in polymorphonuclear leukocyte bactericidal activity, a suppression of lymphocyte proliferative response to stimuli, and a malfunction of cell-mediated immunity at the molecular level. ESRD also increases patients propensity for infections and malignancies as well as causing a diminished response to vaccination. Several factors influence the immunodeficiency in patients with ESRD, including uremic toxins, malnutrition, chronic inflammation, and the therapeutic dialysis modality. The alteration of T-cell function in ESRD has been considered to be a major factor underlying the impaired adaptive cellular immunity in these patients. However, cumulative evidence has suggested that the immune defect in ESRD can be caused by an Ag-presenting dendritic cell (DC) dysfunction in addition to a T-cell defect. It has been reported that ESRD has a deleterious effect on DCs both in terms of their number and function, although the precise mechanism by which DC function becomes altered in these patients is unclear. In this review, we discuss the effects of ESRD on the number and function of DCs and propose a possible molecular mechanism for DC dysfunction. We also address therapeutic approaches to improve immune function by optimally activating DCs in patients with ESRD.

The effect of zinc deficiency on salt taste acuity, preference, and dietary sodium intake in hemodialysis patients

Introduction High sodium intake is the main cause of fluid overload in hemodialysis (HD) patients, leading to increased cardiovascular mortality. High sodium intake is known to be associated with low salt taste acuity and/or high preference. As the zinc status could influence taste acuity, we analyzed the effect of zinc deficiency on salt taste acuity, preference, and dietary sodium intake in HD patients. Methods A total of 77 HD patients was enrolled in this cross‐sectional study. Zinc deficiency was defined as serum zinc level with below 70 µg/mL. The patients were divided into two groups based on serum zinc level. Salt taste acuity and preference were determined by a sensory test using varying concentrations of NaCl solution, and dietary sodium intake was estimated using 3‐day dietary recall surveys. Findings The mean salt recognition threshold and salt taste preference were significantly higher in the zinc deficient group than in the non‐zinc deficient group. And there was significant positive correlation between salt taste preference and dietary sodium intake in zinc deficient group (ru2009=u20090.43, Pu2009=u20090.002). Although, the dietary sodium intake showed a high tendency with no significance (Pu2009=u20090.052), interdialytic weight gain was significantly higher in the zinc deficient group than in the non‐zinc deficient group (2.68u2009±u20091.02 kg vs. 3.18u2009±u20091.02 kg; Pu2009=u20090.047). Discussion Zinc deficiency may be related to low salt taste acuity and high salt preference, leading to high dietary sodium intake in HD patients.

Prediction of hemodialysis vascular access failure using segmental bioimpedance analysis parameters

PurposeSegmental bioimpedance analysis (BIA) can identify fluid volume changes in the arms of patients on hemodialysis (HD) after vascular access surgery. We investigated whether the difference in fluid volumes between the arms of the patients using segmental BIA is associated with vascular access outcome.MethodsBody composition measurements were taken for 127 patients on HD with segmental, multi-frequency BIA equipment (InBody 1.0, Biospace Co. Ltd, Seoul, Korea). The difference in fluid volume between the arms of the patients was calculated from the fluid volume of the arm with the vascular access minus that of the other. The primary outcome was the loss of vascular access patency within 3xa0months of BIA measurement.ResultsThe median absolute and relative inter-arm fluid volume differences were 150xa0ml [interquartile range (IQR) 90–250xa0ml] and 9.6% (IQR 4.9–14.4%), respectively. Within 3xa0months of BIA measurement, 38 patients (30.0%) experienced vascular access failure. When the patients were divided into three groups based on the tertiles of relative inter-arm fluid volume differences (lowest tertile:xa0<xa06.8%; middle tertile: 6.8–12.7%; highest tertile:xa0>xa012.7%), greater difference in relative inter-arm fluid volume differences was associated with higher vascular access failure rates (14 vs. 28 vs. 48%, p value for trend across tertilesxa0=xa00.003).ConclusionsWe conclude that segmental BIA may be used as a tool that can predict vascular access failure in patients on HD by calculating the relative difference in fluid volume between the arms of the patients with and without vascular access.

Porphyromonas gingivalis causing brain abscess in patient with recurrent periodontitis.

We report an extremely rare case of Porphyromonas gingivalis causing brain abscess in a patient with recurrent periodontitis. The patient presented with right-sided homonymous hemianopsia and right hemiparesis. Emergent surgical drainage was performed and antibiotics were administered. P. gingivalis was identified from the anaerobic culture of the abscess. The clinical course of the patient improved with full recovery of the neurologic deficit.

Antineutrophil cytoplasmic antibody–negative pauci-immune glomerulonephritis with massive intestinal bleeding

A 61-year-old woman was admitted to hospital because of generalized edema and proteinuria. Her renal function deteriorated rapidly. Serum immunoglobulin and complement levels were within normal ranges. An autoantibody examination showed negative for antinuclear antibody and antineutrophil cytoplasmic antibody. Histologic examination of a renal biopsy specimen revealed that all of the glomeruli had severe crescent formations with no immune deposits. The patient was treated with steroid pulse therapy with cyclophosphamide followed by oral prednisolone. Fifteen days later, she experienced massive recurrent hematochezia. Angiography revealed an active contrast extravasation in a branch of the distal ileal artery. We selectively embolized with a permanent embolic agent. On the 45th hospital day, the patient suddenly lost consciousness. Brain computed tomography showed intracerebral hemorrhage. We report a case of antineutrophil cytoplasmic antibody–negative pauci-immune glomerulonephritis with massive intestinal bleeding and cerebral hemorrhage.

Arteriovenous fistula stent infection diagnosed with radiolabelled leucocyte scintigraphy

Abstract Infectious complications of haemodialysis in patients with arteriovenous fistula stent are rare. In addition, patients with low-grade infection are more difficult to diagnose. Here, we report the first case of low-grade infection of an arteriovenous fistula stent diagnosed using 99mTc-hexamethylpropylene amine oxime (HMPAO)-labelled leucocyte scintigraphy. A 62-year-old man with end-stage renal disease was referred for prolonged fever. We performed 99mTc-HMPAO-labelled leucocyte scintigraphy following a work-up according to fever of unknown origin. A focal uptake on the left forearm compatible with the arteriovenous fistula stent insertion site was shown, and the stent was removed. 99mTc-HMPAO-labelled leucocyte scintigraphy could be a suitable method for assessing vascular stent infection in low-grade fever.

A Case of Painful Hashimoto Thyroiditis that Mimicked Subacute Thyroiditis

Hashimoto thyroiditis (HT) is an autoimmune thyroid disorder that usually presents as a diffuse, nontender goiter, whereas subacute thyroiditis (SAT) is an uncommon disease that is characterized by tender thyroid enlargement, transient thyrotoxicosis, and an elevated erythrocyte sedimentation rate (ESR). Very rarely, patients with HT can present with painful, tender goiter or fever, a mimic of SAT. We report a case of painful HT in a 68-year-old woman who presented with pain and tenderness in a chronic goiter. Her ESR was definitely elevated and her thyroid laboratory tests suggested subclinical hypothyroidism of autoimmune origin. 99mTc pertechnetate uptake was markedly decreased. Fine needle aspiration biopsy revealed reactive and polymorphous lymphoid cells and occasional epithelial cells with Hürthle cell changes. Her clinical symptoms showed a dramatic response to glucocorticoid treatment. She became hypothyroid finally and is now on levothyroxine therapy.