A pilot study assessing sphingolipids and glycolipids dysmetabolism in idiopathic normal pressure hydrocephalus.

Idiopathic normal pressure hydrocephalus usually exhibits triad of symptoms including gait disturbance, urinary incontinence, and dementia with ventriculomegaly. Currently, its pathogenesis remains to be fully elucidated. To provide a better understanding of this order, we examined whether dysmetabolism of sphingolipids as major lipid components in the brain present in cerebrospinal fluid (CSF) of the patients. Here, we measured various sphingolipidsincluding ceramide and sphingomyelin and glycolipids by electrospray ionization-tandem mass spectrometry in the cerebrospinal fluid of 19 consecutive idiopathic normal pressure hydrocephalus patients, 49 Parkinson's disease patients, and 17 neurologically normal controls. The data showed that there was a significant and specific reduction of all galactosylceramide subspecies levels in idiopathic normal pressure hydrocephalus patients compared with other groups, whereas ceramide and sphingomyelin levels as well as other neutral glycolipids such as glucosylceramide and lactosylceramide were similar in both disease states. Multiple regression analysis of sex and age did not show any correlation with galactosylceramide levels. We also examined whether MMSE scores are correlated with sphingolipid levels in iNPH patients. A specific subspecies of sphingomyelin (d18:1/18:0) only exhibited a statistically significant negative correlation (p = 0.0473, R = -0.4604) with MMSE scores but no other sphingolipids in iNPH patients. These data strongly suggest that myelin-rich galactosylceramide metabolism is severely impaired in idiopathic normal pressure hydrocephalus patients and might serve as the basis of biomarker for this disorder.

Reduction of severe acute respiratory syndrome coronavirus-2 infectivity by admissible concentration of ozone gas and water.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the global coronavirus disease 2019 (COVID-19) pandemic. Because complete elimination of SARS-CoV-2 appears difficult, decreasing the risk of transmission is important. Treatment with 0.1 and 0.05 ppm ozone gas for 10 and 20 hr, respectively, decreased SARS-CoV-2 infectivity by about 95%. The magnitude of the effect was dependent on humidity. Treatment with 1 and 2 mg/L ozone water for 10 s reduced SARS-CoV-2 infectivity by about 2 and 3 logs, respectively. Our results suggest that low-dose ozone, in the form of gas and water, is effective against SARS-CoV-2.

Warm ischemic time as a critical risk factor of graft failure from donors after cardiac death: A single-center experience over three decades in the Kidney Donor Profile Index/Kidney Donor Risk Index era in Japan.

OBJECTIVES: To evaluate the prognostic value of the warm ischemic time and the validity of the Kidney Donor Profile Index/Kidney Donor Risk Index for predicting the survival of donors after cardiac death grafts. METHODS: We retrospectively assessed 315 kidneys retrieved from donors after cardiac death at Fujita Health University Hospital, Toyoake, Aichi, Japan. The Kidney Donor Profile Index/Kidney Donor Risk Index was calculated and the grafts were enrolled. RESULTS: The median follow-up period was 11.9 years. The Kidney Donor Profile Index had a markedly asymmetric distribution (median 94%), and the Kidney Donor Risk Index had high index rates (0.79-2.94, median 1.70). The overall 5-, 10- and 15-year graft survival rates were 67.5%, 52.1% and 38.9%, respectively. The Kidney Donor Profile Index correlated with graft survival. The 5-, 10- and 15-year graft survival rates for the Kidney Donor Profile Index <1.2 were 87.7%, 73.5% and 59.2%; those for the Kidney Donor Risk Index >2.0 were 55.0%, 34.7% and 22.1%, respectively. A Cox multivariate analysis identified the Kidney Donor Risk Index (hazard ratio 2.06, 95% confidence interval 1.48-2.86, P < 0.0001) and warm ischemic time (hazard ratio 1.21, 95% confidence interval 1.09-1.34, P = 0.0010) as independent risk factors for graft loss. The addition of warm ischemic time >30 min had a significant effect, as measured by the C-index (0.708-0.731, P = 0.032), improving the net reclassification improvement score (0.256, P = 0.0039) and integrated discrimination improvement score (0.042, P = 0.0022). CONCLUSIONS: The Kidney Donor Profile Index/Kidney Donor Risk Index is a good prognostic tool for determining the outcomes of donors after cardiac death grafts. However, the warm ischemic time should also be included in the allocation system for donors after cardiac death grafts.

Combined predictive value of the expanded donor criteria for long-term graft survival of kidneys from donors after cardiac death: A single-center experience over three decades.

OBJECTIVES: Kidneys procured from the deceased hold great potential for expanding the donor pool. The aims of the present study were to investigate the post-transplant outcomes of renal allografts recovered from donors after cardiac death, to identify risk factors affecting the renal prognosis and to compare the long-term survival from donors after cardiac death according to the number of risk factors shown by expanded criteria donors. METHODS: A total of 443 grafts recovered using an in situ regional cooling technique from 1983 to 2011 were assessed. To assess the combined predictive value of the significant expanded criteria donor risk criteria, the patients were divided into three groups: those with no expanded criteria donor risk factors (no risk), one expanded criteria donor risk factor (single-risk) and two or more expanded criteria donor risk factors (multiple-risk). RESULTS: Among the donor factors, age ≥50 years, hypertension, maximum serum creatinine level ≥1.5 mg/dL and a warm ischemia time ≥30 min were identified as independent predictors of long-term graft failure on multivariate analysis. Regarding the expanded criteria donors criteria for marginal donors, cerebrovascular disease, hypertension and maximum serum creatinine level ≥1.5 mg/dL were identified as significant predictors on univariate analysis. The single- and multiple-risk groups showed 2.01- and 2.40-fold higher risks of graft loss, respectively. CONCLUSIONS: Renal grafts recovered from donors after cardiac death donors have a good renal function with an excellent long-term graft survival. However, an increased number of expanded criteria donors risk factors increase the risk of graft loss.

[A Case of Localized Amyloidosis of the Ureter Diagnosed by Ureter Biopsy Using a Ureteroscope].

A 42-year-old female visited our hospital with the chief complaint of macrohematuria and left lateroabdominal pain. Computed tomography and retrograde pyelogram showed left hydronephroureter and obstructive uropathy which was 20 mm in diameter in the middle ureter. Urine cytology was negative. Ureter biopsy revealed amyloidosis. Our diagnosis was localized amyloidosis of the ureter, because amyloid was not found in other places in her whole body inspection. Partial ureterectomy was performed. Left renal function was preserved. The patient has been free of recurrence for 18 months after surgery.

Serum liver-type fatty acid-binding protein predicts recovery of graft function after kidney transplantation from donors after cardiac death.

Kidneys procured by donation after cardiac death (DCD) may increase the donor pool but are associated with high incidence of delayed graft function (DGF). Urinary liver-type fatty acid-binding protein (L-FABP) level is an early biomarker of renal injury after kidney transplantation (KTx); however, its utility is limited in DGF cases owing to urine sample unavailability. We examined whether serum L-FABP level predicts functional recovery of transplanted DCD kidneys. Consecutive patients undergoing KTx from living related donors (LD), brain-dead donors (BD), or DCD were retrospectively enrolled. Serum L-FABP levels were measured from samples collected before and after KTx. Serum L-FABP decreased rapidly in patients with immediate function, slowly in DGF patients, and somewhat increased in DGF patients requiring hemodialysis (HD) for >1 wk. Receiver-operating characteristic curve analysis demonstrated that DGF was predicted with 84% sensitivity (SE) and 86% specificity (SP) at cutoff of 9.0 ng/mL on post-operative day (POD) 1 and 68% SE and 90% SP at 6.0 on POD 2. DGF >7 d was predicted with 83% SE and 78% SP at 11.0 on POD 1 and 67% SE and 78% SP at 6.5 on POD 2. Serum L-FABP levels may predict graft recovery and need for HD after DCD KTx.

Occurrence of infection following prostate biopsy procedures in Japan: Japanese Research Group for Urinary Tract Infection (JRGU) - a multi-center retrospective study.

We retrospectively investigated the incidence of genitourinary tract infection in 5895 patients who underwent transrectal and/or transperineal prostate biopsy procedure between January and December 2011 at 46 institutions belonging to Japanese Research Group for Urinary Tract Infection (JRGU). The total rate of genitourinary tract infection after prostate biopsy was 0.76%, while that following transrectal procedure was 0.83% and following transperineal procedure was 0.57%, which were not significantly different. In contrast, febrile infection associated with a fever (≥38 °C) occurred significantly more frequently after transrectal (0.71%) than transperineal (0.16%) approach (P = 0.04). Notably, in infectious cases, Escherichia coli was most frequently isolated. Of the 9 E. coli strains isolated by urine culture, 6 (66.7%) produced extended spectrum ß-lactamase (ESBL) and 7 (77.8%) showed levofloxacin resistance. Similarly, of 6 E. coli strains isolated by blood culture, 4 (66.7%) produced ESBL and 6 (100%) showed levofloxacin resistance. When the efficacy of antimicrobial prophylaxis (AMP) with levofloxacin for the patients undergoing transrectal or transperineal biopsy was compared between a single dose (500 mg) and that given for 2 or more days, no significant difference was observed for the rate of infection (transrectal: 0.82% vs. 1.04%, p = 0.94; transperineal: 0.30% vs. 0.46%, p = 0.68). Although a single dose of levofloxacin for AMP is sufficient to prevent genitourinary infection after transrectal or transperineal prostate biopsy, and recommended in this era of increased multi-drug resistant pathogens, the increase in fluoroquinolone-resistant E. coli and ESBL-producing E. coli has emerged as a profound problem for surveillance.

Oral alendronate can suppress bone turnover but not fracture in kidney transplantation recipients with hyperparathyroidism and chronic kidney disease.

Post-transplantation bone diseases negatively affect the quality of life of solid organ recipients. Secondary or tertiary hyperparathyroidism is a frequent complication in kidney transplantation (KTx) recipients. Treatment with immunosuppressive agents including glucocorticoids can lead to deterioration in bone metabolism in these patients. In the present study, we explored the effects of a three-year treatment period with oral alendronate (ALN) in long-term KTx recipients. Post-KTx recipients were recruited (n = 24, M/F = 12/12, mean age 52.0 ± 7.8 years) into this study. All patients were prescribed methylprednisolone (4.07 ± 0.86 mg/day) with various immunosuppressive agents. Before treatment with oral ALN (35 mg/week), the mean concentrations of intact parathyroid hormone (iPTH) and 25-hydroxyvitamin D were 139.2 ± 71.4 pg/mL and 20.8 ± 4.1 ng/mL, respectively. After 36 months of ALN treatment, mean iPTH levels increased slightly (+20.9 %). Treatment with ALN reduced bone-specific alkaline phosphatase (-35.4 %), serum type I collagen N-terminal telopeptide (-31.2 %) and osteocalcin (-55.6 %) levels. ALN did not increase bone mass after 24 months. Four patients with the highest baseline iPTH levels suffered a clinical osteoporotic fracture during the 36-month ALN treatment period. Higher iPTH levels with chronic kidney disease (CKD) at baseline were associated with the incidence of new clinical fractures during ALN treatment. In conclusion, anti-resorptive therapy with ALN can suppress bone turnover even when iPTH concentration is elevated in long-term KTx recipients. However, hyperparathyroidism with CKD seems to be associated with new clinical fractures during ALN treatment.

[A questionnaire survey of antimicrobial prophylaxis to prevent perioperative infection in urological field in Japan].

PURPOSE: To survey the present condition of administration method of the antimicrobial prophylactic (AMP) agents for the perioperative infection in Japan on revising "The Japanese guidelines for prevention of perioperative infections in urologic field (2006)". PATIENTS AND METHODS: With the approval of the Japanese Urological Association (JUA) in 2011, all of the principal urological training institutions certified by JUA (n = 836) were encouraged to participate to survey their adherence to the JUA guidelines (published in 2006) for AMP to prevent perioperative infection in urological field, and 446 (53.3%) institutions responded to the questionnaire. RESULTS: The rates of following the JUA guidelines of, "completely", "mainly", "not too much", and "not at all" were 6.5%, 69.7%, 22.0% and 1.6%, respectively. The guidelines were followed for open clean operations in 48.5%, open clean-contaminated operations in 66.4%, open contaminated operations in 61.8%, laparoscopic clean operations in 54.1%, laparoscopic clean-contaminated operations in 61.2%, transurethral resection of bladder tumor in 71.5%, transurethral resection of prostate in 68.9%, ureteroscopy and transurethral ureterolithotomy in 68.2%, prostate biopsy in 43.2%, and cystoscopy were in 42.2%, respectively. However, in terms of duration of AMP administration, the longer duration than those recommended by the guidelines were observed for clean surgery, transurethral resection of bladder tumor, ureteroscopy and transurethral ureterolithotomy, prostate biopsy, and cystoscopy. CONCLUSIONS: In terms of kinds of AMP, the guidelines were almostly followed in all operative procedures. However, the duration of AMP administration were longer than those recommended by the guidelines. On revision of "Japanese guidelines for prevention of perioperative infections in urologic field (2006)", these data would be taken into consideration to avoid dissociation between the guidelines and the practical side in the urologists.

Serum neutrophil gelatinase associated lipocalin during the early postoperative period predicts the recovery of graft function after kidney transplantation from donors after cardiac death.

PURPOSE: Kidneys procured from donors after cardiac death hold great potential to expand the donor pool. However, they have not yet been fully used, in part due to the high incidence of delayed graft function. Although urine neutrophil gelatinase-associated lipocalin is a well-known early biomarker for renal injury after kidney transplantation, its usefulness is limited in cases with delayed graft function because of the unavailability of a urine sample. We evaluated serum neutrophil gelatinase-associated lipocalin as a potential biomarker to predict the functional recovery of kidneys transplanted from donors after cardiac death. MATERIALS AND METHODS: Consecutive patients transplanted with a kidney from a living related (39), brain dead (1) or post-cardiac death (27) donor were retrospectively enrolled in the study. Serum samples were collected serially before and after kidney transplantation. Serum neutrophil gelatinase-associated lipocalin was measured using the ARCHITECT® assay. RESULTS: Average serum neutrophil gelatinase-associated lipocalin was markedly high during the pre transplantation period. It decreased rapidly after transplantation. The slope of the decrease correlated well with the recovery period. By analyzing ROC curves we determined cutoffs to predict immediate, slow or delayed graft function requiring hemodialysis for longer than 1 week with high sensitivity and specificity. CONCLUSIONS: These data suggest that serial monitoring of serum neutrophil gelatinase-associated lipocalin may allow us to predict graft recovery and the need for hemodialysis after kidney transplantation from a donor after cardiac death.

Photoselective vaporization of the prostate: pursuing good indications based on the results of 400 Japanese patients.

OBJECTIVE: To investigate good indications of photoselective vaporization of the prostate (PVP) by retrospective evaluation of its efficacy in relation to prostate volume. PATIENTS AND METHODS: A cohort of 400 patients had International Prostate Symptoms Score (IPSS), Quality of Life (QoL) score, urinary peak flow (Q(max) ), and prostate volume (P(vol) ), assessed before and after surgery. Changes of outcome variables were compared among four groups classified according to preoperative prostate volume: <30 mL (group A), ≥30 and <50 mL (group B), ≥50 and <70 mL (group C), and >70 mL (group D). RESULTS: Operating times and amounts of energy applied were 44.2 min and 159 kJ, 67.7 min and 268 kJ, 111 min and 409 kJ, and 171 min and 604 kJ in groups A, B, C, and D, respectively. All variables improved significantly and immediately, and remained for more than 12 months. Investigation of groups classified by prostate size demonstrated that IPSS and QoL score decreased and improvement rate of Q(max) rose as prostate volume increased. Changes of P(vol) were from 24.5 mL to 13.2 mL (-46.1%), from 39.8 mL to 22.9 mL (-42.4%), from 58.4 mL to 32.8 mL (-43.8%), and from 92.1 mL to 53.8 mL (-41.5%) in groups A, B, C, and D, respectively. Overall the P(vol) reduction rate was 43.2%, and no significant differences were observed in reduction ratios among the groups. Complications were minimal, but bladder neck contracture arose in 16 cases with a smaller prostate. CONCLUSION: Whilst the percentage reduction in volume was similar across the groups, the larger absolute volume reduction in patients with larger prostates was associated with greater improvement in objective urinary function variables, and with symptom score reduction.

Selection and analysis of anti-cancer antibodies for cancer therapy obtained from antibody phage library.

The search for effective antibodies (Ab) for curable cancer immunotherapy has been a quest of many research groups in order to find an effective target that exists on the cancer cell surface. So far there have been no conclusive answers to shed light on the search. This study therefore aimed to bridge the gap of cancer therapy. Screening against 49 kinds of cell lines belonging to 11 kinds of solids cancers was performed. Isolation and characterization for approximately 4200 monoclonal antibodies (mAb) was also performed thereafter. Of those mAb 488 clones that turned out to bind to 29 tumor-associated antigens (TAA) were subjected to immunohistochemical (IHC) analyses. Selection of target antigens (Ag) and a potential antibody for cancer therapy was conducted prior to clinical examinations. In order to find predictably effective targets for therapeutic Ab against solid cancers, expression of the Ag on the surface of cancer and normal cells was extensively examined by IHC analyses using fresh cancer specimens resected from patients. In this study, the tendencies of all staining patterns and distribution of the Ab are reported. While all of the TAA appeared to be involved in tumorigenesis, their expression was not restricted to some specific tumor types but rather randomly distributed among various cancers. Some kinds of Ab including anti-epidermal growth factor receptor (EGFR) and anti-human epidermal growth factor receptor 2 (HER2) indicated the frequency of expression in normal cells was generally low. We concluded that identification of 488 mAb and the accumulated results of IHC analyses in this study could be the key for further therapeutic Ab against cancers. The targets that showed cancer-specific expression are expected to be better for therapeutic Ab than the other Ab. Moreover, further investigation into the growth of cancer cell lines using full human IgG form of Ab shows available efficacy in specific cases.

Neurotrophin levels in cerebrospinal fluid of adult patients with meningitis and encephalitis.

BACKGROUND: The data on cerebrospinal fluid (CSF) levels of neurotrophins (NTs) in patients with meningoencephalitis are scarce, especially in adult patients. METHODS: We measured CSF levels of NTs such as nerve growth factor (NGF), brain-derived neurotrophic factor, and neurotrophin-3 (NT-3) in adult patients with various meningitis (n = 10) and encephalitis (n = 10) in both acute phase and recovery phase and adult control subjects (n = 21) by the enzyme-linked immunosorbent assay for NTs. RESULTS: Data show that NGF and NT-3 CSF levels were markedly elevated in the patient group in the acute phase compared with non-neurological controls (p < 0.001 and p < 0.05, respectively) and later returned to the levels of controls. Most intriguingly, we only recognized a significant correlation between NGF and NT-3 CSF levels in the patients in the acute phase. CONCLUSION: Such strong correlation of NGF and NT-3 CSF levels strongly suggests that in adult patients, some common regulatory mechanism(s) might be present among various kinds of NTs to cope with central nervous system infection.

Comprehensive screening for antigens overexpressed on carcinomas via isolation of human mAbs that may be therapeutic.

Although several murine mAbs that have been humanized became useful therapeutic agents against a few malignancies, therapeutic Abs are not yet available for the majority of the human cancers because of our lack of knowledge of which antigens (Ags) can become useful targets. In the present study we established a procedure for comprehensive identification of such Ags through the extensive isolation of human mAbs that may become therapeutic. Using the phage-display Ab library we isolated a large number of human mAbs that bind to the surface of tumor cells. They were individually screened by immunostaining, and clones that preferentially and strongly stained the malignant cells were chosen. The Ags recognized by those clones were isolated by immunoprecipitation and identified by MS. We isolated 2,114 mAbs with unique sequences and identified 21 distinct Ags highly expressed on several carcinomas. Of those 2,114 mAbs 356 bound specifically to one of the 21 Ags. After preparing complete IgG(1) Abs the in vitro assay for Ab-dependent cell-mediated cytotoxicity (ADCC) and the in vivo assay in cancer-bearing athymic mice were performed to examine antitumor activity. The mAbs converted to IgG(1) revealed effective ADCC as well as antitumor activity in vivo. Because half of the 21 Ags showed distinct tumor-specific expression pattern and the mAbs isolated showed various characteristics with strong affinity to the Ag, it is likely that some of the Ags detected will become useful targets for the corresponding carcinoma therapy and that several mAbs will become therapeutic agents.

[The state of antimicrobial prophylaxis for holmium laser enucleation of the prostate : HoLEP and the results of a questionnaire survey].

Holmium laser enucleation of the prostate (HoLEP) has been established as a procedure for the treatment of patients with benign prostate hyperplasia, instead of transurethral resection of prostate (TURP). To determine the appropriate antimicrobial prophylaxis for the prevention of perioperative urinary tract infection following HoLEP we sent a questionnaire to 79 institutes belonging to the Japanese Urological Association. We surveyed 1) the performance of HoLEP, 2) number of HoLEP performed in 2009, 3) antimicrobial agents and the term of the administration for prophylaxis, 4) rate of perioperative infections, and 5) usage of other antimicrobial prophylaxis in HoLEP, as compared with in TUR-P. We received answers from 59 institutes (74. 9%). We examined 43 responses, which were obtained from executive members who performed more than eleven cases of HoLEP in 2009. Thirty-one of these institutes (72.1%) indicated parenteral antibiotics ; three of them adopted oral antibiotics, and nine of them added oral antibiotics following parenteral antibiotics. In 40 of them (93.0%), the rate of perioperative infections was reported to be fewer than 5%. Twenty-seven of them (62. 7%) adopted the same schedule for the prophylaxis in both HoLEP and TUR-P. Eleven of them indicated shorter antimicrobial usage in HoLEP than in TUR-P. Ten of the eleven institutes reported that the rate of perioperative infections in HoLEP had been lower than in TUR-P. Our questionnaire survey demonstrated that shorter antimicrobial prophylaxis might be possible in HoLEP than in TUR-P.

[Robot-assisted laparoscopic partial nephrectomy using daVinci S-surgical system for localized renal tumor: report of initial five cases].

OBJECTIVES: For the management of patients with small renal tumor, laparoscopic partial nephrectomy (LPN) provides similar oncological control as radical nephrectomy (RN) and is superior to RN with respect to preserving renal function and preventing chronic kidney disease (CKD). The challenge of LPN is to resect a tumor in a bloodless field within a limited warm ischemia time (WIT) , followed by hemostatic renorrhaphy under restricted movement of laparoscopic forceps. Therefore, LPN still remains challenging to even experienced laparoscopic surgeon. DaVinci device improved the movability of forceps in LPN and provided three-dimensional visualization. We evaluated outcome and safety of our first series of robot-assisted laparoscopic partial nephrectomy (RALPN) for localized kidney tumor. There was no previous report of RALPN undertaken in our country. PATIENTS AND METHODS: Since August 2010, our team carried out RALPN for a total of five cases of renal tumor. There were four males and one female with an age range of 41 to 65 years-old. Size of tumor ranged from 15 to 28 mm, located in exophytic region, and four cases in right side and one in left. RALPN was undertaken by single surgeon through transperitoneal approach in two cases and retroperitoneal in tree. RESULTS: RALPN was completed in all patients without conversion to open or hand-assisted surgery. The median operative time and the estimated blood loss were 189 minutes, ranged from 150 to 264, and 29 ml, from 10 to 50, respectively. The median volume of removed tumor and the length of WIT were 7 g, ranged from 4 to 13 g, and 18 minutes, from 13 to 26 minutes, respectively. No complications or reoperations were associated during or post our RALPN cases. Pathological examination of removed tumor showed renal cell carcinoma with negative surgical margin in all cases. CONCLUSIONS: Introduction of daVinci device to LPN made this procedure, RALPN, a secured and promising one, which leading to shorten the WIT and to achieve satisfied renorrhaphy. Even for the complex and technically challenging renal tumors, robotic assistance is expected to provide patients the benefit of minimally invasive surgery with safety and satisfactory renal function.

Cerebrospinal Fluid Profiles in Parkinson's Disease: No Accumulation of Glucosylceramide, but Significant Downregulation of Active Complement C5 Fragment.

BACKGROUND: As mutations in glucocerebrosidase 1 (GBA1) are a major risk factor for Parkinson's disease (PD), decreased GBA1 activity might play an important role in the pathogenesis of the disease. However, there are currently no reports on glucosylceramide levels in the cerebrospinal fluid (CSF) in PD. OBJECTIVE: We investigated whether glucosylceramide accumulation and abnormal immune status in the brain are associated with PD. METHODS: We measured glucosylceramide by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) as well as levels of the active fragment of complement C5, C5a, in the CSF of 33 PD, 15 amyotrophic lateral sclerosis (ALS) and 22 neurologically normal control (NNC) subjects. Serum C5a levels in all PD and ALS cases and in a limited number of NNC subjects (n = 8) were also measured. RESULTS: C5a levels in CSF were significantly downregulated in PD compared with NNC. Moreover, CSF C5a/serum C5a ratio showed pronounced perturbations in PD and ALS patients. LC-ESI-MS/MS revealed a statistically significant accumulation of a specific subspecies of glucosylceramide (d18 : 1/C23 : 0 acyl chain fatty acid) in ALS, but not in PD. Interestingly, CSF glucosylceramide (d18 : 1/C23 : 0) exhibited a significant correlation with CSF C5a levels in PD, but not ALS. No correlation was observed between C5a levels or glucosylceramide subspecies content and disease duration, levodopa equivalent daily dose or Hoehn & Yahr staging in PD. CONCLUSION: Our findings demonstrate complement dysregulation without glucosylceramide accumulation in PD CSF. Furthermore, we found an association between a specific glucosylceramide subspecies and immune status in PD.

Urinary neutrophil-gelatinase associated lipocalin is a potential noninvasive marker for renal scarring in patients with vesicoureteral reflux.

PURPOSE: Renal scarring is a serious complication that often occurs with chronic pyelonephritis in the presence of vesicoureteral reflux. In a previous study we established a rat model of renal scarring in which we found the up-regulation of neutrophil-gelatinase associated lipocalin at the mRNA and protein levels. In this study we evaluated urinary neutrophil-gelatinase associated lipocalin as a potential biomarker for progression of renal scarring in patients with vesicoureteral reflux. MATERIALS AND METHODS: A total of 34 patients diagnosed with vesicoureteral reflux without evidence of current urinary tract infection and 28 normal healthy children were enrolled in this study. Renal scars were evaluated by (99m)technetium dimercapto-succinic acid renal scan in 24 of the reflux cases. Urinary neutrophil-gelatinase associated lipocalin levels were monitored by ELISA. RESULTS: In normal subjects urinary neutrophil-gelatinase associated lipocalin was high during infancy, decreased rapidly within the following year and reached a low stable level from age 3 years onward. Urinary neutrophil-gelatinase associated lipocalin levels, normalized to age matched standards, were significantly increased in patients with vesicoureteral reflux compared to controls. These levels did not correlate with reflux grade, but were significantly higher in patients with radiological evidence of renal scarring irrespective of reflux grade. CONCLUSIONS: Estimation of urinary neutrophil-gelatinase associated lipocalin may be useful as a noninvasive diagnostic or prognostic biomarker for renal scarring.

[Current situation of pancreas transplantation in Japan].

Pancreas transplantation has been recognized as the best treatment for advanced type 1 diabetic patients. In Japan, we have performed 64 SPK, PAK or PTA from 62 brain-dead donors and two non-heart beating donors since the enforcement of Organ Transplant Act in 1997. In addition, 18 cases have been performed from living related donors. The patient survival, pancreas graft survival and kidney graft survival rate of the cadaveric transplantation at five years are 97.5%, 73.9% and 71.0%, respectively. The QOL of the recipients in both mental and physical aspects has been wonderfully improved leading to the happy second life. In front of the revised low in this year, the number of the donor and the transplantation are expected to increase.

Increased urinary neutrophil gelatinase associated lipocalin levels in a rat model of upper urinary tract infection.

PURPOSE: Recurrent upper urinary tract infection is a common complication of vesicoureteral reflux that often leads to irreversible renal scarring. In our previous study of a rat model of renal bacterial infection we performed global gene expression profiling of the kidney during the onset of renal scarring. We have further investigated the product of an up-regulated gene product, NGAL, in this animal model to evaluate its potential usefulness as a biomarker of renal scarring. MATERIALS AND METHODS: Renal NGAL mRNA and protein levels were examined by real-time polymerase chain reaction, Western blot and immunohistochemistry. Urinary NGAL levels were monitored by direct enzyme-linked immunosorbent assay. RESULTS: Rat renal NGAL mRNA and protein levels were found to be increased soon after bacterial injection. They then decreased rapidly but subsequently persisted at high levels until the 6-week time point after injection. On histological analysis we found that NGAL protein was overproduced in macrophages and renal tubular cells 2 weeks after injection. However, renal tubular cells continued to produce NGAL 6 weeks after injection, whereas this expression was lost in infiltrating cells. Rat urinary NGAL levels were also markedly increased at the early stages of infection and they persisted at high levels throughout the latter stages of the experiment. CONCLUSIONS: Urinary NGAL may be a potential noninvasive diagnostic biomarker of renal scarring.