Collagenofibrotic glomerulopathy with a widespread expression of type-V collagen

Collagenofibrotic glomerulopathy is considered as a form of glomerulopathy in which organized collagen type III progressively deposits. We report a case of this disease with widespread expression of collagen type V. A 65-year-old woman was admitted to our hospital for further evaluation of nephrotic-range proteinuria. The patient had had anemia and hypertension for 9 years, and proteinuria for 3 years. A renal biopsy specimen showed a remarkable mesangial expansion with Congo red-negative and periodic acid-Schiff-positive deposits. At the ultrastructural level, two forms of bundling fibers were found in the mesangium and subendothelial side of the glomerular basement membranes (GBM). The GBM itself appeared normal. Immunohistochemical investigation showed that the glomerular lesions were strongly reactive with both anti-collagen type-III and -V antibodies. Immunoelectron microscopy demonstrated collagen type V in both forms of bundling fibers. Despite therapy, her renal function declined. The clinical course and renal pathology of this case were in accordance with collagenofibrotic glomerulopathy except for the widespread expression of collagen type V. Collagen type V is a fibrillar collagen capable of forming banding fibrils. This report poses the question whether collagen type V accumulates only in this particular case or whether it is a normal component in collagenofibrotic glomerulopathy.     

Six novel mutations detected in the GALC gene in 17 Japanese patients with Krabbe disease, and new genotype–phenotype correlation

Krabbe disease is an autosomal recessive leukodystrophy. It is pathologically characterized by demyelination of the central and peripheral nervous systems and the accumulation of globoid cells in brain white matter. It is caused by a deficiency of galactocerebrosidase (GALC) activity. We investigated mutations of the GALC gene in 17 Japanese patients with Krabbe disease, the largest subject number of Japanese patients to date, and found 27 mutations. Of these mutations, six were novel, including two nonsense mutations, W115X and R204X, two missense mutations, S257F and L364R, a small deletion, 393delT, and a small insertion, 1719-1720insT. Our findings, taken with the reported mutations in Japanese patients, confirm several mutations common to Japanese patients, the two most frequent being 12Del3Ins and I66M+I289V, which account for 37% of all mutant alleles. With two additional mutations, G270D and T652P, these account for up to 57% of genetic mutations in Japanese patients. Distribution of the mutations within the GALC gene indicated some genotype–phenotype correlation. I66M+I289M, G270D, and L618S contributed to a mild phenotype. Screening for these mutations may provide an effective method with which to predict the clinical phenotype.     

Temporal analysis of the flow from V1 to the extrastriate cortex in humans

We previously examined the cortical processing in response to somatosensory, auditory and noxious stimuli, using magnetoencephalography in humans. Here, we performed a similar analysis of the processing in the human visual cortex for comparative purposes. After flash stimuli applied to the right eye, activations were found in eight cortical areas: the left medial occipital area around the calcarine fissure (primary visual cortex, V1), the left dorsomedial area around the parietooccipital sulcus (DM), the ventral (MOv) and dorsal (MOd) parts of the middle occipital area of bilateral hemispheres, the left temporo-occipito-parietal cortex corresponding to human MT/V5 (hMT), and the ventral surface of the medial occipital area (VO) of the bilateral hemispheres. The mean onset latencies of each cortical activity were (in ms): 27.5 (V1), 31.8 (DM), 32.8 (left MOv), 32.2 (right MOv), 33.4 (left MOd), 32.3 (right MOv), 37.8 (hMT), 46.9 (left VO), and 46.4 (right VO). Therefore the cortico-cortical connection time of visual processing at the early stage was 4-6 ms, which is very similar to the time delay between sequential activations in somatosensory and auditory processing. In addition, the activities in V1, MOd, DM, and hMT showed a similar biphasic waveform with a reversal of polarity after 10 ms, which is a common activation profile of the cortical activity for somatosensory, auditory, and pain-evoked responses. These results suggest similar mechanisms of the serial cortico-cortical processing of sensory information among all sensory areas of the cortex.     

The relationship between anteroposterior stability and medial–lateral stability of the bi-cruciate stabilized total knee arthroplasty

Background

Acquisition of appropriate anteroposterior (AP) stability depends on the prosthetic design and intraoperative soft tissue handling. A bi-cruciate stabilized (BCS) total knee arthroplasty (TKA) has a two cam-post mechanism, which substitutes for the anterior cruciate ligament and posterior cruciate ligament (PCL). Therefore, appropriate AP stability is expected. Because the PCL is sacrificed during BCS TKA, medial stability and lateral stability are thought to be important factors to determine AP stability. However, no previous study has reported AP stability after BCS TKA and the relationship between AP and medial–lateral stability.

Acute liver failure in young children with systemic-onset juvenile idiopathic arthritis without macrophage activation syndrome: report of two cases

Acute liver failure (ALF) with macrophage activation syndrome (MAS) is well known as a complication of systemic-onset juvenile idiopathic arthritis (S-JIA). However, liver failure without overt MAS is rare in S-JIA. We encountered two Japanese children with S-JIA in whom ALF developed during the remission of clinical manifestations. ALF without MAS was improved with plasma exchange and cyclosporine A combined with pulse methylprednisolone.     

The role of medial meniscus posterior root tear and proximal tibial morphology in the development of spontaneous osteonecrosis and osteoarthritis of the knee

Background

Medial meniscus posterior root tear (MMPRT) has been reported to play a key role in the development of spontaneous osteonecrosis of the knee (SONK) and osteoarthritis (OA) of the knee. However, little is known about the differences in the development of SONK and OA after MMPRT. The purpose of this study was to investigate the factors contributing to the development of these conditions.

Mechanisms of Long-Latency Paired Pulse Suppression: MEG Study

Brain Topography - Paired pulse suppression is an electrophysiological method used to evaluate sensory suppression and often applied to patients with psychiatric disorders. However, it remains...     

Novel pathogenic mutations and copy number variations in the VPS13A Gene in patients with chorea‐acanthocytosis

Chorea‐acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disorder caused by loss of function mutations in the vacuolar protein sorting 13 homolog A (VPS13A) gene that encodes chorein. It is characterized by adult‐onset chorea, peripheral acanthocytes, and neuropsychiatric symptoms. In the present study, we performed a comprehensive mutation screen, including sequencing and copy number variation (CNV) analysis, of the VPS13A gene in ChAc patients. All 73 exons and flanking regions of VPS13A were sequenced in 35 patients diagnosed with ChAc. To detect CNVs, we also performed real‐time quantitative PCR and long‐range PCR analyses for the VPS13A gene on patients in whom only a single heterozygous mutation was detected. We identified 36 pathogenic mutations, 20 of which were previously unreported, including two novel CNVs. In addition, we investigated the expression of chorein in 16 patients by Western blotting of erythrocyte ghosts. This demonstrated the complete absence of chorein in patients with pathogenic mutations. This comprehensive screen provides an accurate and useful method for the molecular diagnosis of ChAc. © 2011 Wiley‐Liss, Inc.     

Analysis of daily energy,protein, fat,and carbohydrate intake in citrin-deficient patients: Towards prevention of adult-onset type II citrullinemia

Patients with citrin deficiency during the adaptation/compensation period exhibit diverse clinical features and have characteristic diet of high protein, high fat, and low carbohydrate. Japanese cuisine typically contains high carbohydrate but evaluation of diet of citrin-deficient patients in 2008 showed a low energy intake and a protein:fat:carbohydrate (PFC) ratio of 19:44:37, which indicates low carbohydrate consumption rate. These findings prompted the need for diet intervention to prevent the adult onset of type II citrullinemia (CTLN2). Since the publication of the report about 10 years ago, patients are generally advised to eat what they wish under active dietary consultation and intervention. In this study, citrin-deficient patients and control subjects living in the same household provided answers to a questionnaire, filled-up a maximum 6-day food diary, and supplied physical data and information on medications if any. To study the effects of the current diet, the survey collected data from 62 patients and 45 controls comparing daily intakes of energy, protein, fat, and carbohydrate. Food analysis showed that patient's energy intake was 115% compared to the Japanese standard. The confidence interval of the PFC ratio of patients was 20–22:47–51:28–32, indicating higher protein, higher fat and lower carbohydrate relative to previous reports. The mean PFC ratio of female patients (22:53:25) was significantly different from that of male patients (20:46:34), which may explain the lower frequency of CTLN2 in females. Comparison of the present data to those published 10 years ago, energy, protein, and fat intakes were significantly higher but the amount of carbohydrate consumption remained the same. Regardless of age, most patients (except for adolescents) consumed 100–200 g/day of carbohydrates, which met the estimated average requirement of 100 g/day for healthy individuals. Finally, patients were generally not overweight and some CTLN2 patients were underweight although their energy intake was higher compared with the control subjects. We speculate that high-energy of a low carbohydrate diet under dietary intervention may help citrin-deficient patients attain normal growth and prevent the onset of CTLN2.     

Intracerebroventricular administration of NPY stimulates resistin gene expression in mice

Resistin is thought to cause insulin resistance and link obesity to type 2 diabetes mellitus. However, little is known about the effects of neuropeptide Y (NPY) on resistin gene expression in white adipose tissue (WAT). Resistin gene expression was determined by northern blot analysis in food-deprived mice after NPY administration. Administered NPY (1 nmol/mouse) significantly increased resistin mRNA expression in WAT by 72% compared with artificial cerebrospinal fluid treated controls. These observations indicate that NPY might have a role in regulating resistin gene expression in WAT and that the novel brain-fat axis might be involved in the pathogenesis of obesity and related diseases.