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The cortical bones of mammals, birds, and reptiles are composed of a complex of woven bone and lamellar bone (fibrolamellar bone) organized into a variety of different patterns; however, it remains unclear whether amphibians possess similar structures. Importantly, to understand the evolutionary process of limb bones in tetrapods, it is necessary to compare the bone structure of amphibians (aquatic to terrestrial) with that of amniotes (mostly terrestrial). Therefore, this study compared the cortical bones in the long bones of several frog species before and after metamorphosis. Using micro‐computed tomography (CT), we found that the cortical bones in the fibrolamellar bone of Xenopus tropicalis (Pipoidea superfamily) and Lithobates catesbeianus (Ranoidea superfamily) froglets are dense, whereas those of Ceratophrys cranwelli (Hyloidea superfamily) are porous. To clarify whether these features are common to their superfamily or sister group, four other frog species were examined. Histochemical analyses revealed porous cortical bones in C. ornata and Lepidobatrachus laevis (belonging to the same family, Ceratophryidae, as C. cranwelli). However, the cortical bones of Dryophytes japonicus (Hylidae, a sister group of Ceratophryidae in the Hyloidea superfamily), Microhyla okinavensis (Microhylidae, independent of the Hyloidea superfamily), and Pleurodeles waltl, a newt as an outgroup of anurans, are dense with no observed cavities. Our findings demonstrate that at least three members of the Ceratophryidae family have porous cortical bones similar to those of reptiles, birds, and mammals, suggesting that the process of fibrolamellar bone formation arose evolutionarily in amphibians and is conserved in the common ancestor of amniotes. [ABSTRACT FROM AUTHOR]

The urine-concentrating mechanism is one of the most fundamental functions of avian and mammalian kidneys. This particular function of the kidneys developed as a system to accumulate NaCl in birds and as a system to accumulate NaCl and urea in mammals. Based on phylogenetic evidence, the mammalian urine-concentrating mechanism may have evolved as a modification of the renal medulla's NaCl accumulating system that is observed in birds. This qualitative conversion of the urine-concentrating mechanism in the mammalian inner medulla of the kidneys may occur during the neonatal period. Human kidneys have several suboptimal features caused by the neonatal conversion of the urine-concentrating mechanism. The urine-concentrating mechanism is composed of various functional molecules, including water channels, solute transporters, and vasopressin receptors. Abnormalities in water channels aquaporin (AQP)1 and AQP2, as well as in the vasopressin receptor V2R, are known to cause nephrogenic diabetes insipidus. An analysis of the pathological mechanism involved in nephrogenic diabetes insipidus suggests that molecular chaperones may improve the intracellular trafficking of AQP2 and V2R, and, in the near future, such chaperones may become a new clinical tool for treating nephrogenic diabetes insipidus. [ABSTRACT FROM AUTHOR]

4-Aza-5α-androstanone(1α) and 4-aza-5β-androstanone(1β) were synthesized in order to obtain the NMR shielding parameters for the secondary amine group. A combination of the electric field effect and the anisotropy of the magnetic susceptibility of the C&z.sbnd;N bond can successfully reproduce the observed SIS values for these androstanes. Drastic chemical shift change of protons near-by nitrogen atom of ammonium salt was observed and shielding parameter for the secondary ammonium group was also obtained. [Copyright &y& Elsevier]

Evaluates the role of Ca2+ in insulin-stimulated NaCl transport in rabbit medullary thick ascending limb (MTAL) by in vitro microperfusion methods. Effect of extracellular Ca2+ on the actions of insulin; Measurements of transepithelial voltage; Effects of calmodulin inhibitors on the actions of insulin; Time course of the effects of insulin.

Presents a study of calcium dynamics in the ascending thin limb (ATL) of Henle's loop. Renal tubule; Microperfusion; Calcium ion channel; ATL cells as possessing a calmodulin-sensitive calcium pump.

Investigates the mechanisms of intracellular hydrogen ion concentration regulation in the in vitro microperfused hamster ascending thin limb (ATL) of Henle's loop. Relation of the transport of chloride to the function of the ATL cells; Role in sodium chloride reabsorption; Effect of ambient ion substitution on intracellular hydrogen ion concentration.

Reveals that insulin stimulates sodium chloride transport in isolated perfused medullary thick ascending limb (MTAL) of Henle's loop of rabbit kidney. Effect of insulin on transepithelial voltage; Blockage of Na+-K+-2Cl- cotransporter in the luminal membrane of the MTAL; Contribution of cyclic AMP to the action of insulin.

We simulate from first principles the energetic, structural, and electronic properties of ferroelectric (FE) ultrathin PbTi03 nanotubes. The nanotube possesses spontaneous polarization despite their sidewalls being thinner than the critical thickness at which the thin films lose ferroelectricity; this indicates the absence of an intrinsic critical size for ferroelectricity. The ground state of the nanotube is not purely FE since it primarily involves antiferrodistortive (AFD) rotations of oxygen atoms due to compression in the inner tube wall. The emergence of the AFD displacement plays a central role in stabilizing both the nanotubular structure and FE distortions due to direct AFD-FE coupling. Moreover, we predict intriguing rich phase transitions due to axial strains including polarization vortices as an important class of nanoscale FE ordering. [ABSTRACT FROM AUTHOR]

Abstract: A family with cerebrovascular dysfunctions and extensive white matter lesions was presented. The proband had suffered migraine. His brother showed syncopal episodes and migraine. His mother also suffered severe migraine with aura, and had transient hemiparesis during pregnancy. Their brain MRIs, being quite similar to each other, revealed diffuse bilateral deep white matter lesions, with no changes in serial follow-up. His grandmother showed similar white matter changes on CT, consistent with autosomal dominant inheritance. Lesions were considered to be due to chronic vasogenic edema based upon increased apparent diffusion coefficient (ADC) values on diffusion-weighted imaging, normal spectrum ratio of metabolites on 1H MR spectroscopy, and decreased regional cerebral blood flows on single-photon emission CT (SPECT). A deficiency of genetically determined factors contributing to the autoregulation of small blood vessels might possibly lead to both clinical symptoms and white matter lesions through the breakdown of the blood–brain barrier and resultant vasogenic edema. Although cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) was suspected, neither NOTCH3 mutation nor granular osmiphilic material (GOM) in the arteriole walls were detected. Further accumulation of similar cases is necessary to establish the possibility of a new familial leukoencephalopathy. [Copyright &y& Elsevier]

Abstract Background : Hypophosphatemia is observed in both genetic diseases and acquired disorders, although it has never been described in systemic lupus erythematosus (SLE). The present study reports hypophosphatemia observed in patients with SLE, and investigates whether serum phosphorus (P) concentration is associated with disease activity and some cytokines. Methods : Six girls with SLE (age 10 to 16 years) and seven age-matched controls were studied. Relationships between serum P and parameters that represented disease activity were evaluated. Interleukin (IL) 6 and tumor necrosis factor α (TNF-α) levels were measured by enzyme-linked immunosorbent assay (ELISA). Results : Two of the patients with SLE developed marked hypophosphatemia during active disease. Their serum P significantly correlated positively with serum complements, red blood cell (RBC) and platelet counts, and negatively with anti-double-stranded DNA antibody (dsDNAab). Three of the remaining four patients showed the same trend, in which their serum P significantly correlated with RBC, platelets, dsDNAab and/or serum complement concentrations. Serum and urinary IL-6 and serum TNF-α were higher in active SLE patients than those with inactive disease or in the control group. In addition, the concentrations of these cytokines significantly correlated inversely with serum P. Renal tubular reabsorption of P was significantly lower in patients with active disease both with and without lupus nephritis. Conclusions : Hypophosphatemia may be another sign of juvenile SLE, and serum P may represent disease activity. Both TNF-α and IL-6 may be related to hypophosphatemia in patients with SLE. Waste of P from renal tubules may be a possible mechanism of hypophosphatemia in SLE. [ABSTRACT FROM AUTHOR]

Analyzes the NaCl transport in thin ascending limb of Henle's loop in CLC-K1 null mice. Use of in vitro microperfusion of the tAL in the transport properties of sodium; Formation of concentrated urine by means of specific transport properties; Effects of protamine on the V[sub d] values in vitro microperfusion.

“Avian-type” renal medullary tubule organization causes immaturity of urine-concentrating ability in neonates. Background. While neonatal kidneys are not powerful in concentrating urine, they already dilute urine as efficiently as adult kidneys. To elucidate the basis for this paradoxical immaturity in urine-concentrating ability, we investigated the function of Henle's loop and collecting ducts (IMCDs) in the inner medulla of neonatal rat kidneys. Methods. Analyses of individual renal tubules in the inner medulla of neonatal and adult rat kidneys were performed by measuring mRNA expression of membrane transporters, transepithelial voltages, and isotopic water and ion fluxes. Immunofluorescent identification of the rCCC2 and rCLC-K1 using polyclonal antibodies was also performed in neonatal and adult kidney slices. Results. On day 1, the transepithelial voltages (VTs) in the thin ascending limbs (tALs) and IMCDs were 14.6 ± 1.1 mV (N = 27) and -42.7 ± 6.1 mV (N = 14), respectively. The VTs in the thin descending limbs (tDLs) were zero on day 1. The VTs in the tALs were strongly inhibited by luminal bumetanide or basolateral ouabain, suggesting the presence of a NaCl reabsorption mechanism similar to that in the thick ascending limb (TAL). The diffusional voltage (VD) of the tAL due to transepithelial NaCl gradient was almost insensitive to a chloride channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB). The VTs in the IMCDs were strongly inhibited by luminal amiloride. On day 1, both the tDL and tAL were impermeable to water, indicating the water impermeability of the entire loop. Diffusional water permeability (Pdw) and urea permeabilities (Purea) in the IMCDs indicated virtual impermeability to water and urea on day 1. Stimulation by vasopressin (1 nmol/L) revealed that only Pdw was sensitive to vasopressin by day 14. A partial isoosmolar replacement of luminal urea by NaCl evoked negligible water flux across the neonatal IMCDs, indicating the absence of urea-dependent volume flux in the neonatal IMCD. These transport characteristics in each neonatal tubule are similar to those in quail kidneys. Identification of mRNAs and immunofluorescent studies for specific transporters, including rAQP-1, rCCC2, rCLC-K1, rENaC β subunit, rAQP-2, and rUT-A1, supported these findings. Conclusion. We hypothesize that the renal medullary tubule organization of neonatal rats shares a tremendous similarity with avian renal medulla. The qualitative changes in the organization of medullary tubules may be primarily responsible for the immature urine-concentrating ability in mammalian neonates. [ABSTRACT FROM AUTHOR]

CLC-K1 is a kidney-specific chloride channel that mediates transepithelial chloride transport in the thin ascending limb of Henle's loop (tAL) in the inner medulla. Transport of NaCl in the tAL is thought to be a component of urinary concentration in a passive model of the countercurrent multiplication system, but there has been no direct evidence that CLC-K1 is involved in urine concentration. To analyse the physiological function of CLC-K1 in vivo, we generated mice lacking CLC-K1 by targeted gene disruption. Clcnk1?/? mice were physically normal appearance, but produced approximately five times more urine than Clcnk1+/? and Clcnk1+/+ mice. After 24 hours of water deprivation, Clcnk1?/? mice were severely dehydrated and lethargic, with a decrease of approximately 27% in body weight. Intraperitoneal injection of the V2 agonist 1-deamino-8-D-arginine vasopressin (dDAVP) induced a threefold increase in urine osmolarity in Clcnk1+/? and Clcnk1+/+ mice, whereas only a minimal increase was seen in Clcnk1?/? mice, indicating nephrogenic diabetes insipidus. After in vitro perfusion of the tAL, the lumen-to-bath chloride gradient did not produce a diffusion potential in Clcnk1?/? mice in contrast to Clcnk1+/+ and Clcnk1+/? mice. These results establish that CLC-K1 has a role in urine concentration, and that the countercurrent system in the inner medulla is involved in the generation and maintenance of hypertonic medullary interstitium. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to elucidate opinions regarding comprehensibility of audiometry display formats among otolaryngologists in Japan, and to identify the characteristics of otolaryngologists' cognitive processes for audiometry.Methods: We conducted a cross-sectional nationwide questionnaire-based mail survey regarding the comprehensibility of audiometry display formats among 543 Japanese otolaryngologists. Of 543 otolaryngologists to whom the questionnaires were mailed, 137 replied to the questions. For the analysis, the sample size used was 112 participants. The questionnaire contained questions regarding the otolaryngologists' occupational characteristics, and assessed their opinions of four comprehensibility aspects of five display formats.Results: Otolaryngologists in clinics indicated that the passage of time and changes in thresholds of each frequency in numeric tables were ordinary or incomprehensible. More than 60% of otolaryngologists with extensive experience in using electronic medical records indicated that both, the passage of time and change in the thresholds in overlaid thresholds on a chart were comprehensible.Conclusions: Display formats in audiometry influenced the comprehension of pure tone audiometry data. Our results suggest that overlaid thresholds on a chart rather than numeric table or multi-dimensional charts are the primary choice for computerized audiometry display formats in most aspects of audiometry. [ABSTRACT FROM AUTHOR]

In Japan, a range of patients with traumatic brain injury (TBI) has been recorded in a nationwide database (Japan Neurotrauma Data Bank; JNTDB). This study aimed to externally validate three international prediction models using JNTDB data: Trauma and Injury Severity Score (TRISS), Corticosteroid Randomization After Significant Head Injury (CRASH), and International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT). We also aimed to validate the applicability of these models in the Japanese population. Of 1,091 patients registered in the JNTDB from July 2009 to June 2011, we analyzed data for 635 patients. We examined factors associated with mortality in-hospital and unfavorable outcomes 6 months after TBI by applying the TRISS, CRASH, and IMPACT models. We also conducted an external validation of these models based on these data. The patients’ mean age was 60.1 ±21.1 years, and 342 were alive at the time of discharge (53.9%). Univariate analysis revealed eight major risk factors for mortality in-hospital: age, Glasgow Coma Scale (GCS), Injury Severity Score (ISS), systolic blood pressure, heart rate, mydriasis, acute epidural hematoma (AEDH), and traumatic subarachnoid hemorrhage. A similar analysis identified five risk factors for unfavorable outcomes at 6 months: age, GCS, ISS, mydriasis, and AEDH. For mortality in-hospital, the TRISS had a satisfactory area under the curve value (0.75). For unfavorable outcomes at 6 months, the CRASH (basic and computed tomography) and IMPACT (core and core extended) models had satisfactory area under the curve values (0.86, 0.86, 0.81, and 0.85, respectively). The TRISS, CRASH, and IMPACT models were suitable for application to the JNTDB population, indicating these models had high value in Japanese patients with neurotrauma. [ABSTRACT FROM AUTHOR]

C1C-5 is a chloride channel whose gene mutations have been reported to be associated with X-linked nephrolithiasis (XRN), X-linked recessive hypophosphatemic rickets (XLRH), Dent disease, and idiopathic lowmolecular-weight proteinuria (ILMWP) in Japanese children. To establish more efficient screening for CLCN5 abnormalities, we developed a new diagnostic method using reverse transcription and polymerase chain reaction (RT-PCR) of cultured renal tubular cells from the urine of patients. Using this new method, we successfully detected microdeletion of C1C-5 mRNA in a patient and splicing abnormality of the CLCN5 C1 channel. [ABSTRACT FROM AUTHOR]

Background: Sonographic assessment before congenital diaphragmatic hernia repair has rarely been studied.Objective: To evaluate the accuracy of preoperative ultrasound in measuring the defect size and in anticipating the presence of a rim and thereby to determine ultrasound's usefulness in informing the surgical approach for definitive repair of congenital diaphragmatic hernia.Materials and Methods: We performed a retrospective review of the medical records of seven children with left congenital diaphragmatic hernia who had undergone ultrasound and definitive repair between 2014 and 2017 at our institution.Results: The estimated defect size by ultrasound to the actual defect size measured intraoperatively for each case were as follows: 23 × 25 mm to 20 × 26 mm (case 1); 23 × 30 mm to 20 × 30 mm (case 2); 43 × 25 mm to 30 × 30 mm (case 3); 21 × 23 mm to 20 × 25 mm (case 4); 19 × 24 mm to 10 × 30 mm (case 5); 32 × 33 mm to 30 × 50 mm (case 6); and almost total absence to 40 × 50 mm (case 7). Presence or absence of each part of the diaphragm rim evaluated by ultrasound was almost identical with the actual intraoperative findings. According to the ultrasound findings, we performed a successful thoracoscopic repair in cases 1-5 with relatively small defects and presence of all parts of the rim or absence of only posterolateral rim.Conclusion: There was good concordance between ultrasound findings and operative findings regarding the size of the defect and presence or absence of the diaphragm rim. [ABSTRACT FROM AUTHOR]

Various studies have determined that the Great East Japan Earthquake (GEJE) caused mental distress among residents in affected areas. However, previous studies had not considered the prevalence of mental distress before the GEJE, and ignored the impact of an aged society on mental distress. Therefore, we aimed to describe the prevalence of mental distress before the GEJE in Miyagi Prefecture, Japan and elucidate the effect of an aged society on mental distress. We conducted an ecological study, using municipality in Miyagi Prefecture as the study unit. We used the cross-sectional mail survey data conducted in February 2011. We performed a correlation analysis in each of the 39 municipalities in Miyagi Prefecture. The prevalence of serious mental distress was 9.1%. The proportion of the population aged 65 years or older was related to the prevalence of serious mental distress in municipalities with a low proportion of all workers engaged in primary industry and with a high estimated number of inpatients with mental illness. We found that residents in Miyagi Prefecture suffered from poor mental health before the GEJE. Aged society was related to serious mental distress in the areas with advanced industrial structure and more patients with mental illness. We should approach mental health problems in the context of social structure, particularly in an aged society, based on facts about mental distress before the GEJE. [ABSTRACT FROM AUTHOR]

This study aims to use the conceptual framework of social determinants of health (SDH) to elucidate the social determinants that affect the use of complementary and alternative medicine (CAM) from the perspectives of both intermediary and structural determinants. Data were derived from a survey mailed to 1,500 randomly selected residents (20–69 years old; May–July 2009) of Sendai city in Japan. A generalized linear model was used in the analysis, with CAM use over the past one month as the dependent variable, SDH structural and intermediary determinants as independent variables, and demographic characteristics, indicators of health status, and the evaluation of health or healthcare systems as control variables. The prevalence of CAM usage was 62.1%. The generalized linear model showed that middle subjective social status (OR = 1.47; 95% CI: 1.04–2.07) as structural determinants was significantly associated with CAM usage. Adding the intermediary determinants, the same effect was observed. When demographic characteristics, indicators of health status, and the evaluation of health or healthcare systems were introduced as control variables, the associations of the structural determinants disappeared, revealing that hope (OR = 1.25; 95%CI: 1.04–1.50) as intermediary determinants was associated with the use of CAM. Female sex (OR = 1.47; 95% CI: 1.02–2.12) and health anxiety (OR = 1.68; 95% CI: 1.20–2.34) were associated with CAM usage. We found that intermediary rather than structural determinants were associated with CAM usage. Hope as an intermediary determinant was particularly associated with CAM usage. [ABSTRACT FROM AUTHOR]

Rationale, aims, and objectives Time is an important element in medical data. Physicians record and store information about patients' disease progress and treatment response in electronic medical records (EMRs). Because EMRs use timestamps, physicians can identify patterns over time regarding a patient's disease and treatment (eg, laboratory values and medications) . However, analyses of physicians' use and satisfaction with EMRs have focused on functionality, storage, and system operation rather than the use of time-oriented information. This study aimed to understand physicians' needs regarding time-oriented patient information in EMRs in clinical practice. Methods The reliability and validity of the items in the questionnaire were evaluated in 87 physicians at a national university hospital. Internal consistency was satisfactory (Cronbach alpha coefficient, 0.87). Results Four dimensions were identified in exploratory factor analysis. Correlations between the 4 dimensions supported the construct validity of the items. Scores of time-oriented patients' medical history in the 4 dimensions showed a significant association with physician age. Based on confirmatory factor analysis, associations were significant and positive ( P < .001). In terms of the needs of physicians regarding time-oriented patient information in EMRs, both time-oriented treatment results followed by time-oriented team information had significant positive associations. Conclusion Our study suggests that 4 specific time-oriented patient information factors in EMRs are needed by physicians. Exploring physicians' needs regarding patient-specific time-oriented information may provide a better understanding of the barriers facing the adoption and use of EMRs (eg, decision-making and practice safety concerns) and lead to better acceptance of EMRs in physicians' clinical practices. [ABSTRACT FROM AUTHOR]

Background Although several types of transfusion-related adverse reactions (TRARs) have been reported, one of the most important involves respiratory features during and after blood transfusion. Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are the most severe adverse events following blood transfusion, whereas transfusion-associated dyspnea　(TAD) is a less severe respiratory distress. However, there exists little evidence of these factors in pediatric populations. Case report Here, two cases of atypical TRARs with respiratory features, in pediatric patients with solid tumors, appearing after transfusion of platelet concentrate following autologous peripheral blood stem cell transplantation are reported. Both patients developed mild hypoxemia during PC transfusion, which continued for approximately 2 weeks. Chest radiography in either patient did not reveal any abnormalities that are included in the criteria of either TRALI or TACO. Both patients recovered following oxygen administration. Conclusion This complication of TRARs with respiratory features may occur more frequently in pediatric populations than realized because it may be under-recognized or under-reported. Accumulation of additional cases, including non-typical cases, is necessary to fully understand the pathology of TRARs, correctly classify these reactions, and improve care of patients receiving blood transfusions. [ABSTRACT FROM AUTHOR]

The article offers information on building a prototype hospital information system for clinicians to share institution-specific information. The system was developed with the help of medical knowledge units called Medical Cells. These units were created in a portal software architecture using an object-oriented Extensible Markup Language database system.

Barttin, a gene product of BSND, is one of four genes responsible for Bartter syndrome. Coexpression of barttin with ClC-K chloride channels dramatically induces the expression of ClC-K current via insertion of ClC-K-barttin complexes into plasma membranes. We previously showed that stably expressed R8L barttin, a disease-causing missense mutant, is retained in the endoplasmic reticulum (ER) of Madin-Darby canine kidney (MDCK) cells, with the barttin β-subunit remaining bound to ClC-K α-subunits (Hayama A, Rai T, Sasaki S, Uchida S. Histochem Cell Biol 119: 485-493, 2003). However, transient expression of R8L barttin in MDCK cells was reported to impair ClC-K channel function without affecting its subcellular localization. To investigate the pathogenesis in vivo, we generated a knockin mouse model of Bartter syndrome that carries the R8L mutation. These mice display disease-like phenotypes (hypokalemia, metabolic alkalosis, and decreased NaCl reabsorption in distal tubules) under a low-salt diet. Immunofluorescence and immunoelectron microscopy revealed that the plasma membrane localization of both R8L barttin and the ClC-K channel was impaired in these mice, and transepithelial chloride transport in the thin ascending limb of Henle's loop (tAL) as well as thiazide-sensitive chloride clearance were significantly reduced. This reduction in transepithelial chloride transport in tAL, which is totally dependent on ClC-K1/barttin, correlated well with the reduction in the amount of R8L barttin localized to plasma membranes. These results suggest that the major cause of Bartter syndrome type IV caused by R8L barttin mutation is its aberrant intracellular localization. [ABSTRACT FROM AUTHOR]

The effect of Ca2+ and calcimimetics on NaCl transport was investigated in the in vitro isolated microperfused mouse thin ascending limb of Henle’s loop. In the presence of a transmural NaCl gradient, the transepithelial diffusional potential was 13.7 ± 0.4 mV ( n = 17). When the Ca2+ in the bath was increased from 1.5 to 4.5 mM at 37°C, the relative permeability of Na+ to Cl− ( PNa /PCl) estimated from the diffusional voltage deflection due to the transepithelial NaCl gradient ( Vd) changed from 0.371 ± 0.017 to 0.341 ± 0.015 ( n = 10, P < 0.0001). When the Ca2+ in the lumen was increased from 1.5 to 4.5 mM, the PNa /PCl decreased from 0.349 ± 0.013 to 0.330 ± 0.013 ( n = 5, P < 0.002). The addition of 0.1 mM neomycin and 0.2 mM gentamicin to the bath or lumen also decreased the PNa /PCl. The same effect on PNa /PCl of Ca2+ and calcimimetics occurred in ClC-K1 (kidney-specific chloride channel) knockout mice. The addition of 300 μg/ml protamine to the bath strongly inhibited changes to PNa /PCl induced by basolateral Ca2+. These data indicate that ambient Ca2+ and calcimimetics inhibit Na+ transport in the thin ascending limb, which is known to occur via the paracellular shunt pathway. Our observations strongly suggest that Ca2+ is involved in the regulation of paracellular Na+ permeability in the thin ascending limbs. [ABSTRACT FROM AUTHOR]

Recently, disorders of the slit diaphragm have been considered as major causes of proteinuria in renal disease and the charge barrier function of the glomerular capillary wall has been given less attention. We evaluated the charge selectivity index (CSI) in 40 patients with podocyte disease (PD), 75 with chronic glomerulonephritis (CGN), and 8 with Dent disease, to reexamine the charge barrier function. We evaluated CSI in Dent disease because the urinary protein profile in Dent disease was assumed to be a concentrate of a normal glomerular filtrate. CSI was defined as the renal clearance ratio between IgA and IgG. CSI values (mean ± SD) in the CGN and PD groups and in Dent disease were 1.12 ± 0.25, 0.42 ± 0.31, and 0.16 ± 0.06, respectively, suggesting that the charge barrier function was defective in the CGN group and of reduced capacity in the PD group. The results suggest that functional interactions between the slit diaphragm and the glomerular basement membrane exist, and that a slit diaphragm disorder is accompanied by a decrease in the charge barrier function in PD, as argued by the conventional hypothesis. [ABSTRACT FROM AUTHOR]

Background: A novel purine synthesis inhibitor, mizoribine (MZR), with a similar activity to that of mycophenolate mofetil, was developed in Japan. We suspected that long-term oral MZR intermittent pulse therapy (MZR-P) might be more effective than the conventional daily MZR regimen due to the higher peak serum MZR levels that are achieved. Here, we examined the clinicopathologic efficacy of MZR-P treatment in 10 young patients with diffuse proliferative lupus nephritis (DPLN), including 3 patients who received MZR-P as their primary cytotoxic therapy. Methods: After their most recent renal flare-ups, all the patients were treated using MZR-P combined with oral prednisolone (PDN). MZR was administered as a single daily dose of 6–10 mg/kg per day (maximum dose of 500 mg) on 2 days of the week (Monday and Thursday) for at least 12 months or longer. The concomitantly administered PDN dose was gradually reduced. Results: The baseline characteristics of the patients were as follows: mean age 15 years; urinary protein/creatinine (Up/cr) ratio 1.57 ± 1.05 mg/mg; serum C3 level 50.3 ± 19.7 mg/dl; serum complement hemolytic activity (CH50) 18.1 ± 9.9 U/ml; serum anti-dsDNA antibody titer 177.5 ± 152.7 IU/ml; serum creatinine 0.6 ± 0.1 mg/dl, and European Consensus Lupus Activity Measurement (ECLAM) index 4.9 ± 2.6. Despite the gradual tapering of the PDN dose, marked improvements compared with the baseline values were observed at the last observation, mean interval of 29 months after the start of treatment: Up/cr ratio 0.19 ± 0.14; ECLAM index 1.3 ± 0.7 (p < 0.01); serum C3 level 76.5 ± 22.1 mg/dl; serum CH50 value 31.9 ± 8.7 U/ml, and anti-dsDNA antibody titer 34.2 ± 20.5 IU/ml (p < 0.05). The serum creatinine level remained within the normal range in all study participants. Post-treatment renal biopsies were performed in 5 of the patients; histology showed a marked attenuation of lesion progression. No serious adverse effects were observed. Conclusion: We believe that long-term MZR-P may prove to be a treatment of choice for young patients with DPLN. However, confirmation is needed as this preliminary study is limited by the small number of subjects, lack of controls, and its retrospective nature. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Although prenatal diagnosis of VACTERL (vertebral defects, anal atresia, cardiac anomaly, tracheal-esophageal fistula with esophageal atresia, renal defects, and radial limb dysplasia) association is not always possible, ultrasonography and magnetic resonance imaging can visualize some of the characteristic findings of this condition. Because infants with this condition usually require significant surgical treatment and care, prenatal detection with those imaging modalities should assist in proper planning for delivery and anticipated care of the neonate. In this report, we present dichorionic twin fetuses, both of whom were found postnatally to have this condition, and suggest the possible relationship between this disorder and intracytoplasmic sperm injection. As far as we know, this is the first report of twin fetuses affected by VACTERL association. [ABSTRACT FROM AUTHOR]

Abstract: Cystathionine β-synthase (CBS) deficiency is the most common cause of homocystinuria. More than 130 pathogenic mutations, mostly in the Caucasian populations, have been described. Recently, our group reported a mutation analysis of Japanese homocystinuric patients. In the present paper, we report an expression study of several mutant CBS enzymes in Escherichia coli, i.e., R121H, G148R, G151R, S217F, H232D, R266G, 1591delTTCG, and K441X. All of the mutants except K441X exhibited severely decreased activity, and the capability to form tetramers of most mutants was severely impaired. The K441X mutant, on the other hand, exhibited relatively high activity (63% of the wild type activity). This was probably due to two factors. First, the high abundance of the full-length CBS protein, a likely K441Q mutant, which was produced through suppression of the amber termination codon by glutamine tRNA in E. coli. And second, the presence of a C-terminally truncated protein, which was previously shown to be constitutively activated. Patient-derived lymphocytes, however, showed no detectable CBS subunits. As previously hypothesized, the increased aggregation of mutant CBS subunits might be a common pathogenic mechanism in CBS deficiency. [Copyright &y& Elsevier]

We present a case involving a giant hemangioma of the fetal neck, prenatal diagnosis of which was a teratoma. A 32-year-old pregnant woman was referred to our hospital at 31 weeks’ gestation owing to a giant solid mass of the fetal neck and excessive amniotic fluid. The mass seemed to be occupying the neck almost entirely, extending to the nasopharyngeal cavity, the mandible, the surface of the left orbit and the left shoulder. Based on sonographic and magnetic resonance imaging (MRI) findings, diagnosis of a giant teratoma was made. Cesarean section was performed at 35.5 weeks’ gestation, and a female infant weighing 2826 g was delivered. Purpurae were observed on the neck of the infant, and the tumor turned out to be a hemangioma. Postnatal MRI findings, in which the tumor's signal intensity differed from that of the prenatal findings, were quite compatible with the diagnosis of a typical hemangioma. Laser and corticosteroid treatment successfully decreased the volume of the mass. Although it may not always be possible to make a prenatal differential diagnosis between a hemangioma and a teratoma in the neck of the fetus, serial ultrasound and MRI examination are mandatory to evaluate the prognosis and to plan suitable treatment. Moreover, possible postnatal changes to the tumor characteristics have to be taken into consideration when evaluating the findings of prenatal diagnostic imaging. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the case of a four-year and seven-month old boy with nephrogenic diabetes insipidus due to mutaiton in the arginine vasopressin receptor 2 gene.