BACKGROUND: Toll like receptor (TLR), an element of innate immunity, is upregulated by Ischemia/reperfusion (IR) injury and may be involved in adaptive immune response. Immunosuppressive agents may increase or attenuate IR injury and TLR expression. To explore the involvement of TLRs in hypoxic tubular injury and modification by mycophenolic acid (MPA) rapamycin (RAP), this study examined TLR expression in hypoxia-induced human renal proximal tubular epithelial cells (HK-2). METHODS: HK-2 cells were cultured in keratinocyte-SFM media supplemented with epidermal growth factor and bovine pituitary extract. The Induction of hypoxia was achieved using GasPak pouch system. TLR 2, 3, and 4 mRNA expression was analyzed by real time RT-PCR using SYBR green and TLR 4 protein expression was evaluated by Western blot analysis. MPA at concentration of 100 nM and 1uM and RAP at concentration of 20, 50, and 100 nM were added to culture medium. RESULTS: TLR4 but noTLR2 or TLR3 mRNA expressions increased in hypoxic HK-2 cells at 24 and 48 hrs. TLR4 protein expression also increased in hypoxic HK-2 cells at 24 and 48 hrs. MPA (100 nM and 1uM) and RAP (20, 50, and 100 nM) decreased hypoxia-induced TLR4 mRNA expression in HK-2 cells compared to normoxia at 24 hrs. However, TLR4 protein expression was decreased only by RAP at 20 and 50 nM. CONCLUSIONS: The results suggest that RAP may modify hypoxic renal tubular damage by decreasing TLR4-mediated inflammatory and immune reactions.
Adaptive Immunity ; Anoxia ; Blotting, Western ; Epidermal Growth Factor ; Epithelial Cells ; Humans ; Immunity, Innate ; Immunosuppressive Agents ; Mycophenolic Acid ; RNA, Messenger ; Sirolimus ; Toll-Like Receptors

Amyotrophic lateral sclerosis is a rare disease. It is a fatal neurodegenerative disease characterized by progressive muscular paralysis reflecting degeneration of motor neurons which leads to muscle weakness and muscle wasting. Respiratory failure limits survival to 2-5 years after disease onset. Several clinical manifestations including dysphagia can result in reductions in both the quality of life and life expectancy. Dysphagia occurs at onset in about one third of case, although generally it occurs in later stage of the disease. Evaluation of dysphagia includes video-fluoroscopic swallow study, radiological esophagogram, flexible endoscopic examination, ultrasound examination, conventional manometry and electromyography. We report a case of amyotrophic lateral sclerosis in a 54-year-old man presenting oropharyngeal dysphagia which was diagnosed by high resolution esophageal manometry presenting abnormality of the upper esophageal sphincter.
Amyotrophic Lateral Sclerosis ; Deglutition Disorders ; Electromyography ; Esophageal Sphincter, Upper ; Humans ; Life Expectancy ; Manometry ; Middle Aged ; Motor Neurons ; Muscle Weakness ; Muscles ; Neurodegenerative Diseases ; Paralysis ; Quality of Life ; Rare Diseases ; Respiratory Insufficiency

A case of 42-year-oldI kidney transplant patient who developed invasive carcinama of the cervix after immunoauppresawe therepy is reported and the literature related to this diease is revuewed. The iatmgenic immunosuppresaionn renal transplantation recipients has been associated with increased incidence of malignancy in these patients. In particular, immunosuppressed women are al greater risk of developing cervical intraepithelial neoplasia and buman papillomavirus type 16 or 18 infection. So, all such individuals are required to receive periodic gynecologic examination before renal transplantation and at regular intervals thereafter so that the development of CIN may be diagnosed at an early Stage and treated effestively.
Allografts* ; Cervical Intraepithelial Neoplasia ; Cervix Uteri ; Female ; Humans ; Incidence ; Kidney ; Kidney Transplantation

Lymphangiomas are rare benign tumors of the lymphatic system. They usually occur in the neck or axillary region, whereas the retroperitoneum is one of the least frequent sites. The treatment of choice is complete surgical excision. We report a case of a 56-year-old man who had a retroperitoneal cystic lymphangioma in combination with bladder cancer. After complete surgical excision of the retroperitoneal lymphangioma with transurethral resection of the bladder tumor followed by intravesical BCG immunotherapy, the patient remained free of recurrence at 1 year after treatment.
Humans ; Immunotherapy ; Lymphangioma ; Lymphangioma, Cystic* ; Lymphatic System ; Middle Aged ; Mycobacterium bovis ; Neck ; Recurrence ; Urinary Bladder Neoplasms* ; Urinary Bladder*

No abstract available.
Veins*

Diffuse glomerular basement membrane (GBM) lamellation, reminiscent of Alport's syndrome, has rarely, and exclusively, been reported in renal allografts from pediatric donors to adult recipients. We report on a similar lesion, identified in a 42-year-old male, who received a kidney from an unrelated 21-year-old living male donor. The disease of the recipient was unknown. Renal allograft biopsies were performed 3.5 and 4.8 years after the renal transplantation, due to massive proteinuria and serum creatinine elevation. The histological features of both biopsies were similar, but more advanced in the second biopsy. Glomerular mesangium was widened and had an IgA deposit in the first biopsy. In addition to the presence of mesangial electron dense deposits, the GBM showed diffuse lamellation and splintering on the subepithelial side, but no definite deposits. In the second biopsy, IgA deposits were extended to the peripheral capillary walls, but electron microscopic examination was not available. Two months after the second biopsy, the patient returned for hemodialysis.
Adult ; Basement Membrane/*pathology ; Case Report ; Glomerulonephritis, IGA/*etiology/*pathology ; Human ; Kidney Glomerulus/*pathology ; *Kidney Transplantation/*adverse effects ; Male

Diffuse glomerular basement membrane (GBM) lamellation, reminiscent of Alport's syndrome, has rarely, and exclusively, been reported in renal allografts from pediatric donors to adult recipients. We report on a similar lesion, identified in a 42-year-old male, who received a kidney from an unrelated 21-year-old living male donor. The disease of the recipient was unknown. Renal allograft biopsies were performed 3.5 and 4.8 years after the renal transplantation, due to massive proteinuria and serum creatinine elevation. The histological features of both biopsies were similar, but more advanced in the second biopsy. Glomerular mesangium was widened and had an IgA deposit in the first biopsy. In addition to the presence of mesangial electron dense deposits, the GBM showed diffuse lamellation and splintering on the subepithelial side, but no definite deposits. In the second biopsy, IgA deposits were extended to the peripheral capillary walls, but electron microscopic examination was not available. Two months after the second biopsy, the patient returned for hemodialysis.
Adult ; Basement Membrane/*pathology ; Case Report ; Glomerulonephritis, IGA/*etiology/*pathology ; Human ; Kidney Glomerulus/*pathology ; *Kidney Transplantation/*adverse effects ; Male

Although active inflammation may be deleterious and indicate immunologic activation in chronically rejected grafts, the underlying mechanism of tissue destruction has been little studied. Twenty-four cases of chronic rejection (CR) with or without acute rejection (AR) were stained with antibodies against CD3, CD8, CD68, granzyme B and TIA-1, and the number of positive cells were counted. Eleven cases of AR served as controls. The number of CD3 and CD8 positive cells increased in the acute on CR group compared to the CR group. About a half of CD3 positive T cells were CD8 positive in both groups, however, the proportion of TIA-1 or granzyme B positive cells was higher in the acute on CR group. The numbers of CD3, CD68, granzyme B and TIA-1 positive cells were higher in the AR group than the acute on CR group, however, no significant difference was found between the two groups. Serum creatinine level and proteinuria at the time of biopsy and the percentages of late onset AR and graft failure rate were higher in the acute on CR group than the CR group. Summarizing, these results suggest that infiltration of activated T cells containing cytotoxic granules plays a role in graft destruction in acute on CR.
Adult ; Antigens, CD3/analysis ; Antigens, CD8/analysis ; Female ; Follow-Up Studies ; *Graft Rejection ; Human ; Immunohistochemistry ; *Kidney Transplantation ; Male ; Membrane Proteins/*analysis ; RNA-Binding Proteins/*analysis ; Serine Endopeptidases/*metabolism ; Transplantation, Homologous

An association between drug treatment for viral infections and severe cutaneous adverse reactions has been noted. We investigated six patients diagnosed with Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) after being prescribed acetaminophen for suspected viral illnesses. Multiplex analysis was performed to measure cytokine levels in sera before and after treatment. IL-2Rα levels significantly decreased during the convalescence phase. Although acetaminophen is relatively safe, the drug can trigger SJS/TEN in patients with suspected viral infections. T-cells and monocytes may be key components of the link between viral infection and acetaminophen-induced SJS/TEN.
Acetaminophen* ; Convalescence ; Humans ; Monocytes ; Stevens-Johnson Syndrome* ; T-Lymphocytes

Peritubular capillary (PTC) C4d staining represents a marker for acute humoral rejection, however, the impact of positive staining on chronic allograft dysfunction has received little attention. Ninety-three renal allograft biopsies from 93 patients were selected from a total of 174 renal allograft biopsies, which were obtained 6 months or more after transplantation (median: 89 months). Fresh frozen renal tissue was stained with monoclonal antibody against C4d. Sixteen of 93 biopsies showed C4d staining in PTC. C4d staining was positive in 40% of acute rejection cases (n=15) and 21% of chronic rejection cases (n=24). When the samples were divided according to C4d positivity, the C4d (+) group had a higher proportion of acute rejection than the C4d (-) group. However, no significant difference was observed between the two groups in terms of the prevalence of chronic rejection. Degrees of histological injury including tubulitis, interstitial inflammation and interstitial fibrosis were not significantly different between C4d (+) and C4d (-) groups. However, the 2-year graft survival rate after biopsy was lower in the C4d (+) group than in the C4d (-) group (24.8% versus 59.0%, p=0.1255). C4d staining in PTC is associated with late acute rejection, but not with chronic rejection based on conventional morphologic criteria in patients with chronic allograft dysfunction.
Adult ; Capillaries/metabolism ; Chronic Disease ; Complement 4b/*analysis ; Female ; Graft Rejection/*diagnosis ; Humans ; *Kidney Transplantation ; Male ; Middle Aged ; Peptide Fragments/*analysis ; Research Support, Non-U.S. Gov't ; Staining and Labeling ; Transplantation, Homologous