Pathological examination revealed that the resection edge of the extradural component consisted of a spinal nerve with thickened epineurium and was free of neoplastic cells. No schwannoma component was evident in the intradural tumor. No obvious transition thus existed between the extra- and intradural tumors. Distinguishing these tumors prior to surgery is critical for determining

an optimal surgical plan, as schwannoma and meningioma require different surgical procedures. We therefore recommend a careful review of preoperative imaging with the possibility of concurrent tumors in mind. “
“M. Paradisi, M. Fernández, G. Del Vecchio, G. Lizzo, G. Marucci, M. Giulioni, Napabucasin supplier E. Pozzati, T. Antonelli, G. Lanzoni, G. P. Bagnara, selleck inhibitor L. Giardino and L. Calzà

(2010) Neuropathology and Applied Neurobiology36, 535–550 Ex vivo study of dentate gyrus neurogenesis in human pharmacoresistant temporal lobe epilepsy Aims: Neurogenesis in adult humans occurs in at least two areas of the brain, the subventricular zone of the telencephalon and the subgranular layer of the dentate gyrus in the hippocampal formation. We studied dentate gyrus subgranular layer neurogenesis in patients subjected to tailored antero-mesial temporal resection including amygdalohippocampectomy due to pharmacoresistant temporal lobe epilepsy (TLE) using the in vitro neurosphere assay. Methods: Sixteen patients were enrolled in the study; mesial temporal sclerosis (MTS) was present in eight patients. Neurogenesis was investigated by ex vivo neurosphere expansion in the presence (-)-p-Bromotetramisole Oxalate of mitogens (epidermal growth factor + basic fibroblast growth factor) and spontaneous differentiation after mitogen withdrawal. Growth factor synthesis was investigated by qRT-PCR in neurospheres. Results: We demonstrate that in vitro proliferation of cells derived from dentate gyrus of TLE patients is dependent on disease duration.

Moreover, the presence of MTS impairs proliferation. As long as in vitro proliferation occurs, neurogenesis is maintained, and cells expressing a mature neurone phenotype (TuJ1, MAP2, GAD) are spontaneously formed after mitogen withdrawal. Finally, formed neurospheres express mRNAs encoding for growth (vascular endothelial growth factor) as well as neurotrophic factors (brain-derived neurotrophic factor, ciliary neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor). Conclusion: We demonstrated that residual neurogenesis in the subgranular layer of the dentate gyrus in TLE is dependent on diseases duration and absent in MTS. “
“A polymorphous variant of oligodendroglioma was described by K.J. Zülch half a century ago, and is only very sporadically referred to in the subsequent literature. In particular, no comprehensive analysis with respect to clinical or genetic features of these tumors is available.

Exogenous BM-MSCs were detected in their kidneys. These data suggest a modulatory effect of BM-MSCs on albumin-induced tubular inflammation and fibrosis and underscore a therapeutic potential of BM-MSCs in proteinuric CKD. OSAFUNE KENJI Center for iPS Cell Research and Application (CiRA), Ivacaftor Kyoto University, Japan Chronic kidney disease (CKD) causes both medical and medicoeconomical problems worldwide. Regenerative medicine strategies using stem cells are considered candidates

to solve these problems. Cell replacement therapy and disease modeling with patient-derived stem cells should be applied for CKD. However, the methods to regenerate fully differentiated renal cells and tissues from stem cells remain to be developed. The mechanisms of kidney morphogenesis and cell fate determination of renal lineage cells have been elucidated by experimental animal

models. By mimicking in vivo kidney development, we are aiming to develop stepwise differentiation methods for adult renal cells and tissues from human pluripotent stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). We established highly efficient differentiation methods from human iPSCs/ESCs into intermediate mesoderm (IM), an early embryonic germ layer that gives rise to most cells constituting adult kidneys. CX-4945 purchase These human IM cells show the developmental Selleckchem Rucaparib potential to differentiate into multiple renal lineage cells and to form three-dimensional renal tubular structures (Mae S, 2013). A recent report has demonstrated that IM are divided into two domains, anterior and posterior IMs (Taguchi A, 2013). The anterior IM gives rise to ureteric bud, an embryonic progenitor tissue that elaborates collecting ducts

and lower urinary tract, while the posterior IM gives rise to metanephric mesenchyme, another progenitor tissue that differentiate into nephron and interstitium. We are currently establishing the induction protocols to selectively generate each of anterior and posterior IMs from human iPSCs/ESCs in order to generate the two renal progenitors, ureteric bud and metanephric mesenchyme, and adult renal cell types. I would like to summarize the current status of regenerative medicine research for kidney diseases including our results and describe the future perspectives. NISHINAKAMURA RYUICHI, TAGUCHI ATSUHIRO Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Japan Recapitulating three-dimensional structures of the kidney in vitro is a major challenge for developmental biology and regenerative medicine. Adult kidney derives from embryonic metanephros, which develops by the reciprocal interaction between the metanephric mesenchyme and the ureteric bud.

Moreover, FGF-23 is emerging as the most potent phosphate-regulating hormone and, like phosphate, could be a promising novel therapeutic target in the CKD-MBD pathway. However, it

is not known whether elevated levels of phosphate and FGF-23 are mere biomarkers of CVD and mortality or play a causative role Stem Cell Compound Library nmr in the pathogenesis. The epidemiological data are bolstered by many laboratory studies that show a role of phosphate to induce vascular calcification and endothelial dysfunction. These data make a compelling argument for testing whether phosphate reduction strategies can mitigate renal and non-renal risk in patients with CKD, although there is limited evidence on the effects of phosphate-lowering therapy on clinical outcomes and study design is complicated by the multiple mechanisms that are aimed to maintain phosphate homeostasis when GFR is normal or minimally compromised. Large randomized controlled trials are urgently needed to prove or disprove the benefits, risks and potential

economic impact of introducing phosphate-lowering therapy before patients develop ESKD. NT is the recipient of a National Health and Medical Research Council (NHMRC) PLX4032 manufacturer National Institute of Clinical Studies (NICS) Fellowship. Although this Fellowship is supported by NHMRC the views expressed herein are those of the authors and are not necessarily those of the NHMRC. “
“Aim:  Chronic nephrotoxicity of long-term cyclosporine A (CsA) treatment is a matter of concern in patients with steroid-dependent nephrotic syndrome (SDNS). Methods:  Twenty-eight adult NS patients

(25, minimal-change nephrotic syndrome (NS); three, focal-segmental glomerulosclerosis) were divided into three groups. Group A was continuously treated with CsA for more than 5 years (143 ± 40 months, 1.3 ± 0.4 mg/kg per day at final analysis, n = 12); group B had been previously treated with CsA (70 ± 27 months, n = 6); and group C had been treated with corticosteroids alone (n = 10). The clinical variables related to chronic CsA nephrotoxicity were examined. Results:  In groups A and B, estimated glomerular filtration rate decreased from 86 ± 22 and 107 ± 17 to 83 ± 23 and 88 ± 13 mL/min per 1.73 m2, respectively, at final analysis (both P < 0.05). Serum magnesium levels in group A were significantly lower than those in group B or C (A, 1.78 ± 0.16 mg/dL; Baf-A1 B, 2.00 ± 0.14 mg/dL; C, 2.03 ± 0.10 mg/dL; A vs B, C, P < 0.01), and a significant correlation between these and the duration of CsA treatment was found (r = −0.68, P < 0.001). There was a trend towards a correlation between the duration of CsA administration and urinary α1-microglobulin (r = 0.38, P = 0.07). Conclusion:  Mild decrease in renal function and hypomagnesemia were found in adult SDNS patients with long-term CsA treatment. Careful monitoring of renal function, blood pressure and serum magnesium levels is necessary.

Similarly, pyrosequencing analysis of microbes resident in diabetic selleck chemicals llc foot ulcers identified 38 distinct genera and again yielded a subset of sequences unmatched to any recognized microbial sequences (Dowd et al., 2008b). The microbiome of the healthy oral cavity when examined by cloning and sequencing comprises more than 1000 distinct taxa with over half of them yet to be cultured (Dewhirst et al., 2010). This heretofore unappreciated microbial diversity raises significant questions about the relative importance of the component

organisms, individually and in communities, to health and disease. Much progress has also been made in the examination of bacterial gene expression patterns associated with biofilm formation, including whole transcriptomic studies on multiple microbial species. The vast majority of these studies have been on in vitro biofilms and employ a range of technologies. DNA microarray analysis of microbial transcriptomes has now been accomplished for a variety of organisms associated with human disease, including EPZ-6438 molecular weight Escherichia coli (Reshamwala & Noronha, 2011), Streptococcus mutans (Shemesh et al., 2010), Streptococcus pyogenes (Kreth et al., 2011), and

Candida (Sellam et al., 2009). Direct RNA sequencing (RNA Seq) has also been undertaken to distinguish biofilm-specific patterns of gene expression. Dotsch et al. used RNA Seq to compare planktonic cultures of P. aeruginosa with stationary phase cultures and bacteria grown as a biofilm. They found that although there was substantial similarity in the gene expression profiles of stationary phase and biofilm cells, there were also significant differences, indicating that the physiology of biofilm bacteria was not simply surface-attached stationary phase cells. Some studies have begun to examine the transcriptomes of bacteria in vivo. Bielecki et al. (2011) Bay 11-7085 investigated the expression profiles of three distinct clonal isolates of P. aeruginosa from burn wounds in five different conditions: directly from a burn wound sample, in a plant infection, in a murine tumor infection, and as planktonic and biofilm cultures. They found distinct patterns of

gene expression in each condition, indicating distinct adaptive responses of P. aeruginosa to different environments. Immunohistochemical or immunofluorescent techniques represent another targeted approach to identifying pathogens in host tissue. Polyclonal or monoclonal sera specific to pathogens are routinely used to detect encapsulated pathogens in fluids such as S. pneumoniae, Neisseria meningiditis, and Haemophilus influenzae. These antibodies have not been consistently applied for the detection of bacteria in biofilms often because it is thought the matrix may bind antibodies nonspecifically. However, antibodies can be used by performing parallel controls and careful testing of sera, as well as using blocking steps to reduce nonspecific interactions (Fig. 2) (Hall-Stoodley et al., 2006).

One-ml fractions were collected and analysed by SDS–PAGE. The fractions that contained the desired proteins at the expected size were combined and desalted using PD-10 columns (Amersham-Pharmacia) equilibrated in PBS. Purification of recombinant Rv3619c protein.  The induction of expression and preparation of cell-free

extract from E. coli BL-21 cells carrying the plasmid pGES-TH/Rv3619c was carried out as described above for Rv3874 and Rv3875. The GST-Rv3619c fusion protein was recovered in the inclusion bodies as pellet, and therefore it was solubilized in successively higher concentrations Ulixertinib supplier of urea in phosphate-buffered saline (PBS), as described previously [20, 25]. Most of the fusion protein was recovered www.selleckchem.com/products/Rapamycin.html in 4 m urea and was purified by affinity chromatography on glutathione-Sepharose column after proteolytic digestion of the column-bound

fusion protein with thrombin protease, as described previously [16, 25]. The fractions that contained the desired protein at the expected size were combined and analysed for purity by 15% SDS–PAGE gels, as described previously [24]. Raising polyclonal antibodies against recombinant proteins in rabbits.  Polyclonal antibodies were raised in rabbits against the purified and GST-free Rv3874, Rv3875 and Rv3619c recombinant proteins according to standard procedures [26]. In brief, purified proteins (50 μg/ml) were emulsified with an equal volume of incomplete Freund’s PRKACG adjuvant (Sigma) and injected intramuscularly in the right and left thigh. The rabbits were boosted twice with the same amount of protein at 2 weeks intervals. The animals were bled from the ear before the immunization and 2 weeks after the last immunization. The sera were tested for antigen-specific antibodies using 15% SDS–PAGE gels, as described previously [26]. Enzyme-linked immunosorbent assay (ELISA).  ELISA was performed to detect antibodies in rabbit

sera against full-length purified recombinant proteins and overlapping synthetic peptides corresponding to each protein using standard procedures [32]. In brief, wells of 96-well PolySorb plates (Nunc, Rochester, NY, USA) were coated with antigens/peptides (10 μg/ml), blocked with the blocking buffer, incubated with the primary antibody (rabbit sera at 1:100) followed by secondary antibody (alkaline phosphatase-conjugated anti-rabbit immunoglobulin G) and addition of substrate for colour development, as described previously [33]. The colour intensity was measured by determining the optical density (OD) at 405 nm. Antigen-/peptide-coated wells in the presence of secondary antibody alone, i.e. without adding primary antibody, were used as negative controls. The results were expressed as E/C, which is defined as: E/C = OD in antigen-coated wells having primary and secondary antibodies/OD in antigen-/peptide-coated wells having secondary antibody alone. The values of E/C > 2 were considered positive. PCR using gene-specific primers and genomic DNA from M.

Results presented in Supporting Information Fig. 3 show that the polyclonal anti-EBI3 Ab is specific for EBI3. The monoclonal Ab against p35 (clone27537), IL-12p40 (mAb609), IL-12p70 (mAb611), IL-27 (mAb25261), and TGF-β (mAb240) were purchased from R&D Systems. The neutralizing polyclonal anti–IL-10 Ab (PAL-hIL10) was obtained from Strathmann Biotech (Hannover, Germany). MAb EB-I against IFN-α

was kindly provided by G. Adolf (Boehringer Ingelheim). PBMC were isolated from buffy coats obtained from the Red Cross in Austria. Heparinized whole blood of healthy donors was separated by standard density gradient centrifugation with Ficoll-PaqueTM Plus (GE Healthcare Chalfont St. Giles, UK). Subsequently, T cells (total-CD3+ T cells used unless stated otherwise), CD4+, CD8+ Tigecycline purchase and CD25– T cells, and monocytes were separated by magnetic sorting using the MACS technique (Miltenyi Biotec, Bergisch Gladbach, Germany) as described previously JAK assay 34. Naïve T cells were isolated from CB. CB samples from healthy

donors were collected during healthy full-term deliveries. Approval was obtained from the Medical University of Vienna institutional review board for these studies. CB-T cells used in this study were CD45RA+ (92±3%) and CD45RO−. DC were generated by culturing purified blood monocytes for 7 days with a combination of GM-CSF (50 ng/mL) and IL-4 (100 U/mL). Preparation and purification of rhinoviruses were performed as described 34. DC were treated with HRV14 for 1 day (R-DC) at a titer of 1 TCID50 (50% tissue culture infectious

dose) per cell. To examine the suppressor activity of the SN of R-DC-induced Treg, T cells were added to R-DC or DC in a 10:1 or 5:1/T-cell:DC ratio. These SN were harvested after 1–3 days of coculture and 100 μL/well were added to different MLR. Centricon YM-50 filters (Millipore, Bedford, MA, USA) were used for size fractionation of the SN. The fraction containing molecules >50 kDa was compared to the fraction containing molecules <50 kDa in an allogeneic MLR. The T cells of the coculture were also investigated by intracellular staining or analyzed via real-time PCR. For the MLR, allogeneic, purified T cells (1×105) were incubated with graded numbers of DC. Experiments were performed in Interleukin-2 receptor 96-well round bottom cell culture plates in RPMI 1640 medium supplemented with 10% FBS. Proliferation of T cells was monitored by measuring (methyl-3H)TdR (ICN Pharmaceuticals, Irvine, CA, USA) incorporation on day 5 of culture. Cells were harvested 18 h later, and radioactivity was determined on a microplate scintillation counter (Packard Instruments, Meriden, CT, USA). Assays were performed in triplicates. For Fig. 1 preactivated T cells were harvested, irradiated (30 Gy, 137Cs source) and tested for their suppressive function, for Supporting Information Fig. 1 and 4A preactivated T cells were not irradiated.

Retinal microvascular changes are known to be affected by inflammatory factors [26], and may be another biologic mechanism through which diet mediates microvascular caliber.

RO4929097 nmr Although the mechanisms underlying the above associations may not be completely understood, this data supports the vascular-protective effects of increased dietary fish, fiber, and low GI food consumption. Sedentary behavior, low levels of physical activity, and low cardiorespiratory fitness are all well-established risk factors for atherosclerosis and CVD [34]. Recent research has also shown that the adverse effects of lack of physical activity and low fitness extends to changes in microvascular structure [3,4,15,16,55]. Sedentary behavior, indicated by time spent watching TV and lower levels of physical activity, assessed via self-report, were found to be associated with retinal venular caliber [3,4,55], suggesting a possible deleterious

effect of decreased levels of physical activity and increased sedentary behavior on the microvasculature. In addition, the impact of physical activity on the retinal microvasculature was also observed in a cohort of 6-year children. In the study by Gopinath et al., children who spent more time in outdoor sporting activities had wider mean retinal arteriolar caliber [15], but those who spent more time watching TV had narrower mean retinal arteriolar JQ1 concentration caliber. More importantly, for each hour of daily television viewing time, PRKACG similar retinal arteriolar changes are associated with a 10 mmHg increase in systolic blood pressure [15]. Recently, there is also evidence showing the relationship between higher levels of physical fitness and retinal microvascular structure [16]. Higher cardiovascular fitness, as assessed by individual anaerobic threshold, was found to be related to retinal arteriolar dilation and higher retinal

AVR [16]. Moreover, 10 weeks of exercise training was also shown to induce arteriolar dilatation in obese individuals and increased AVR in both obese and lean individuals [16]. Conflicting results were found in a study of older women with type 2 diabetes in which no training-induced improvements in retinal vessel caliber were found after 12-weeks of moderate-intensity exercise. In this cohort, however, increased retinal microvascular density, shown by increased Df was associated with increased time to exhaustion during peak exercise testing, a measure of physical fitness. Observed associations between physical activity and changes in the retinal microvasculature may provide in vivo evidence regarding the effect of physical activity on the systemic circulation. Although the exact pathophysiologic mechanisms behind these relationships is not know, recent research suggests that moderators of vascular tone, specifically NO and ADMA, may play a significant role.

1). This process begins in the nucleolus and the preribosomal units are exported into the cytoplasm for final steps in the maturation of

ribosomes [8]. The exact functions of many of these proteins remain unknown. Some ribosomal proteins are now known to have extraribosomal functions; for example, the SBDS protein has a role in stabilizing the mitotic spindle. Immunological abnormalities in ribosomopathies may therefore provide clues as to how ribosomal proteins can shape the ICG-001 datasheet immune system. According to internationally accepted criteria, the diagnosis of CVID remains one of exclusion. The currently identified four genetic mutations (ICOS, CD19, TACI, BAFFR) account for fewer than a fifth of cases, with no consensus on which genetic testing should be undertaken in most cases [1]. The current European Society of Immunodeficiency (ESID)/Pan-American Group for Immunodeficiency (PAGID) criteria for PD0325901 research buy CVID include: ‘probable’ CVID in those aged > 2 years with low immunoglobulin (Ig)G and another low isotype level (IgA or IgM)

with absent vaccine responses; and ‘possible’ CVID in those with low immunoglobulin of any isotype with absent vaccine responses where other causes of hypogammaglobulinaemia have been excluded [2]. Additional similarities with ribosomopathies and CVID patients include heterogeneous presentations with T cell defects, cytopenias and malignancies [1–3]. The initial description of DBA was of a congenital erythroblastopenia characterized by an early arrest of pre-erythroblast differentiation. The first

report of loss-of-function mutations in a gene coding for a ribosomal protein in this disease (non-sense, missense, frameshift, splice-site, complete deletion of one RPS19 allele) generated enormous interest in the clinical effects of disordered ribosome biosynthesis [8,9]. Mutations in the RPS19 gene prevent assembly of the 40S ribosomal subunit, but account for only 25% of DBA patients [9]. However, to our knowledge, there have been no reports of failure of antibody production in DBA. We present our clinical experience with the report of the first case of DBA who subsequently developed antibody deficiency, consistent Ibrutinib ic50 with a new diagnosis of CVID, with complications of bronchiectasis and managed on immunoglobulin therapy. The previous case of CVID with mutation in the SBDS gene of SDS has been discussed briefly with additional data, as a detailed report was published in a previous issue of this Journal [10]. In the final part of this perspective paper, we review the immunological abnormalities beginning to emerge in ribosomopathy syndromes. Clinical synopsis including investigations.  A 22-year-old female presented with bronchiectasis and hypogammaglobulinemia. DBA had been diagnosed at 1 year of age and required treatment with corticosteroids and blood transfusions until the age of 6 years.

To investigate the co-stimulatory role of CD277 in T-cell signaling, CD3 mAb versus CD3+CD277 mAb coated beads were used to stimulate CD4+ T cells and phosphoflow analysis was performed. CD4+ T cells were stimulated with mAb coated beads for various periods of time (Fig. 2). Induction of Akt and ERK-1/2 phosphorylation using CD3 mAb coated beads was detected specially at late time points such as 30 min (Fig. 2A and B). These TCR-induced phosphorylation events were enhanced when a combination of CD3 plus CD277 mAbs were used. Moreover, this CD277 co-stimulation revealed phosphorylation events as early as 2 min after stimulation

(Fig. 2B). These results show that CD277 stimulation is involved in the regulation of T-cell signaling induced by the TCR-CD3 complex. As the CD28 molecule is known to be a potent co-stimulator of TCR-induced signaling events in primary T cells 15, the role of CD277 was analyzed in the modulation check details of an optimal (CD3+CD28)-induced T-cell stimulation. Purified CD4+ T cells were stimulated with various concentrations of mAbs against CD277 (from 5 to 17 μg/mL) or isotype control IgG1, together with anti-CD3 plus anti-CD28 for different periods of time (2, 5, 10 and 30 min) (Fig. 2). The CD277 cross-linking strongly increases the phosphorylation of Akt and ERK-1/2 induced by CD3+CD28 stimulation (Fig. 3A and B). This effect was dose

and time dependent (Fig. 3B). Hence, we thus demonstrated that CD277 triggering potentialize the TCR signal as expected for a co-stimulatory signal and that it further enhanced the cosignals provided by CD28. Imatinib We next decided to investigate the functional consequences of the activation of these signaling pathways. To investigate the CD277 cosignaling effects on T-cell proliferation and cytokine production induced by CD3+CD28 co-stimulation, CD4+ T cells were stimulated with various concentrations of CD277 mAb (from 5 to 17 μg/mL), together with CD3 plus CD28 mAbs Molecular motor (Fig. 4). The amount of mAbs able to bind on the beads stays

equal along the stimulation conditions by adding IgG1 isotype control and anti-MHC class I (MHC I). The proliferation was evaluated by measuring the dilution of CFSE cytosolic dye in stimulated CD4+ T cells (Fig. 4A). The CD277 cross-linking on CD4+ T cells strongly activates CD4+ T-cell proliferation mediated by CD3 plus CD28 mAbs in a dose-dependent manner. Among the CD3+CD28 stimulated, only 60% of these cells are divided at day 5 (Fig. 4C). The CD277 mAb cross-linking strongly enhances CD4+ T-cell division already induced by CD3 plus CD28 mAbs in a dose-dependent manner, such as 90% of cells are divided (Fig. 4C). In parallel, our results also showed that the engagement of CD277 increased the proliferation (Fig. 4B) and the secretion of cytokines induced by CD3+CD28 stimulation in a dose-dependent manner (Fig. 4D).

At the age of 33 years, the patient suffered a pathological fracture in the right femoral neck and could no longer walk. As for psychological symptoms, the patient was apathetic and exhibited behavioral Quizartinib cost abnormalities. At the age of 34 years, the patient had an epileptiform seizure, and although the seizures gradually subsided,

voluntary upper limb movements and speech became difficult. In response to external stimulation, the patient could move his eyeballs and swallow a liquid substance placed in the mouth. At the age of 38 years, he could not move or speak and subsequently died. Systemic emaciation and subcutaneous fat tissue degeneration were marked, the liver, spleen, and lymph nodes were severely atrophied, and abnormal lipid deposition was not seen at all. In long bones, such as the femur, tibia, fibula, and ribs, the medullary cavity at both ends was filled with yellow opaque gelatinous substances,

matching the translucent cystic lesions seen on X-rays, the bone substance was highly resorbed, and the bone cortex was so thin that it could be damaged when pressed by a finger. In the substances, numerous membranocystic changes were widely distributed on light microscopy, and surrounding fat cells and other cell components were markedly reduced (Fig. 1). I-BET-762 mw Membranocystic lesions were also seen in the bone fatty marrow, subepicardium, mediastinum, mesentery, thymus, systemic adipose tissue around the kidney and lymph nodes, adrenal glands, testes, hepatic sinusoids, and pulmonary vascular lumina. Membranous structures were positive for Sudan III, stained blue Ureohydrolase with Nile blue, and most were positively stained by Luxol fast blue. The brain weighed 1050 g. As for macroscopic findings, symmetric systemic atrophy of the brain, in particular severe atrophy of the occipital and temporal white matters, was seen. The gyrus was narrow, the cerebral sulcus was somewhat broad and deep, and the meninx was smooth. On cross-sections, marked white matter atrophy was confirmed. The boundary between the white and gray matters was slightly unclear. The basal ganglia were mildly atrophied,

and the ventricles were severely enlarged in a symmetrical manner. Bleeding or softening was not confirmed. No notable findings were seen in the cerebellum, pons or medulla oblongata. The spinal cord was not examined. As for histological findings, the white matter was broadly degenerated, and diffuse sclerosis accompanied by astroglial proliferation was confirmed (Fig. 2). Gemistocytic astrocyte was the major component, and fibrillary gliosis was mild. Inflammatory cellular infiltration was absent. Myelin sheath staining confirmed severe demyelination, but U-fibers were relatively conserved. Axonal degeneration and destruction were marked, and the axons were bloated in a balloon fashion and ruptured (Fig. 3), and positively stained using Sudan III or PAS.