The interfoot process gap length was measured from electron microscopic images. Diabetic duration correlated best with the area ratio of podocin and CD2AP (r = 0.626), followed by other protein combinations, showing progressive change in the slit diaphragm structure. C-peptide-treatment did not alter area ratios. The interfoot process gap length was wider in diabetic rats (p < 0.05) and did not narrow with C-peptide-treatment in either control or diabetic rats (both p < 0.05). Diabetes widened the interfoot process gap length and distorted the slit diaphragm structure progressively and heterogeneously in rats with early diabetes; CP-673451 cost this was not altered by C-peptide-treatment. The nephroprotective effect

of C-peptide in decreasing Selleckchem Dinaciclib the glomerular filtration rate appears to be functional rather than

structural. This article is protected by copyright. All rights reserved. “
“The present study was designed to evaluate whether CP was beneficial in alleviating myocardial fibrosis following I/R injury. Sprague–Dawley rats were subjected to 30 minutes occlusion of the LADCA, followed by reperfusion. CP (0.4 or 0.8 g/kg) was daily administered starting from three hour after reperfusion until day 6. Coronary venular diameter, RBC velocity, albumin leakage, MBF, heart function, myocardial infarction and fibrosis size, myocardium ultrastructure, MPO activity, and MDA level Miconazole were evaluated. The expression of MCP-1, RP S19, TGF-β1, P-Smad3, Smad4, MMP-9 and α-SMA, and the infiltration of leukocytes were examined. CP post-treatment ameliorated I/R-induced myocardial RBC velocity reduction, MBF decrease, cardiac dysfunction, and albumin leakage increase. Moreover, myocardial infarction and fibrosis size, MPO activity, MDA level, the expression of RP S19, TGF-β1, P-Smad3, Smad4, MMP-9 and α-SMA, the number of CD68-positive cells increased significantly after I/R, and myocardium collagen deposition was observed on day 6 after reperfusion. All the alterations after

I/R were significantly ameliorated by CP. Post-treatment with CP ameliorates I/R-induced myocardial fibrosis, suggesting that CP may be applied as an option for preventing cardiac remodeling after I/R injury. “
“The aim of this study was to test the hypothesis that exercise training enhances sustained relaxation to persistent endothelium-dependent vasodilator exposure via increased nitric oxide contribution in small coronary arteries of control and ischemic hearts. Yucatan swine were designated to a control group or a group in which an ameroid constrictor was placed around the proximal LCX. Subsequently, pigs from both groups were assigned to exercise (five days/week; 16 weeks) or SED regimens. Coronary arteries (~100–350 μm) were isolated from control pigs and from both nonoccluded and collateral-dependent regions of chronically-occluded hearts.

Rats homozygous for IgM mutation generate truncated Cμ mRNA with a de novo stop codon and no Cγ mRNA. JH-deletion rats showed undetectable mRNA for all H-chain transcripts. No serum IgM, IgG, IgA and IgE were detected in these rat lines. In both lines, lymphoid B-cell numbers were reduced

>95% versus WT animals. In rats homozygous for IgM mutation, no Ab-mediated hyperacute allograft rejection was encountered. Similarities in B-cell differentiation seen in Ig KO rats and ES cell-derived Ig KO mice are discussed. These Ig and B-cell-deficient rats obtained using zinc-finger nucleases-technology should be useful as biomedical research models and a powerful platform for transgenic JNK inhibitor animals expressing a human Ab repertoire. The derivation of genetically engineered animals addresses basic biological problems, generates disease models and helps to develop new biotechnology tools 1, 2. Although ES-cell-derived mice carrying introduced gene mutations

have provided invaluable information, the availability of other species with engineered gene alterations is limited. For over 100 years, the rat has been an experimental species of choice in many biomedical research areas learn more and in biotechnological applications 3, 4. During the last 15 years, genetic engineering techniques have resulted in the generation of many transgenic and non-targeted mutated rats 1, 3, 4. This has confirmed and complemented disease studies but, as well as presenting biotechnological Lonafarnib order alternatives, also generated new paradigms. Nevertheless, the development of gene-targeted mutated rats was hampered by the absence of rat ES cells or robust cloning techniques. In 2008, rat ES cells were described 5, 6 but as yet there have been no reports on the generation of mutant rats from such cells. In 2009, we reported

for the first time the generation of IgM-specific alterations directly in rats using zinc-finger nucleases (ZFN) 7–9. ZFN are new versatile and efficient tools that have been used to generate several genetically modified organisms such as plants, Drosophila, zebra fish and rats as well as human ES cells 7. ZFN are hybrid molecules composed of a designed polymeric zinc finger domain specific for a DNA target sequence and a FokI nuclease cleavage domain 10. Since FokI requires dimerization to cut DNA, the binding of two heterodimers of designed ZFN-FokI hybrid molecules to two contiguous target sequences in each DNA strand separated by a 5–6 bp cleavage site results in FokI dimerization and subsequent DNA cleavage 10.

yuanmingense LPSs, and of 0.01 μg/mL in the case of B. elkanii,

Bradyrhizobium sp. (Lupinus), and B. liaoningense. These results indicate that Bradyrhizobium LPSs are 1000–10,000 times weaker endotoxins than are enterobacterial LPS. For M. huakuii and A. lipoferum LPSs, gelation was observed at 0.1 ng/mL, which indicates that these endotoxins are 10 times weaker than the standard LPSs. Thus, our studies lead to the conclusion that all the examined LPSs are weak endotoxins and probably have low lethality for animals (22). The differences between the examined strains and the standard endotoxin in biological activities of the LPS preparations were reflected in differences in the structure of lipid A, the centre of the endotoxic properties of the whole LPS molecule. The relationship between lipid A structure and its biological Small molecule library manufacturer activity has been extensively studied, and the factors regulating the immunological activity of LPS identified. Among them, phosphate residues and the number, type, and distribution of fatty acids in lipid A are the most important (40). For proinflammatory activity, an enterobacterial lipid A that contains six fatty acids, of

which two nonpolar ones are asymmetrically located creating two acyloxyacyl Y-27632 nmr moieties, is required. Lipid A deprived of one fatty acid residue is about 100-fold less toxic, whereas lipid A analogues carrying only four primary fatty oxyclozanide acids completely lack agonistic activity (16,41). M. huakuii produces a naturally heterogenic lipid A, in particular due to the occurrence of hexa-acyl, penta-acyl, and tetra-acyl subspecies (13). The monophosphorylated subfraction of this lipid A occurs mainly as penta-acyl and hexa-acyl,

containing, apart from 27-hydroxyoctacosanoic fatty acid, one eicosanoic moiety. The unphosphorylated subfraction of the lipid A is represented mainly as the hexa-acyl fraction. Thus, the presence of a large proportion of lipid A molecules with a lower degree of acylation might be a strong factor in the reduced biological activity of this LPS preparation. In addition, the presence of an unusual, very long chain hydroxylated fatty acyl (27-hydroxyoctacosanoic), which is typical of rhizobial lipids A, might affect toxicity, possibly by handicapping accommodation in the active site of the MD-2 receptor. The impaired toxicity of mesorhizobial lipid A may also result from reduced substitution by the ester-linked phosphate residue (50% of total). The C-1 position of the reducing end of the backbone in this lipid A is occupied by a galacturonic acid unit. The presence of two phosphate groups (at positions C-1 and C-4) in the lipid A greatly affects the endotoxic activity of enterobacterial LPS (40, 42). Removal of one of the phosphate groups reduces the biological activity of the enterobacterial endotoxin almost 100-fold, and monophosphoryl lipid A is a weak activator of the human innate immune response.

No patient in either group showed a 100% increase in serum creatinine from baseline or a 50% decrease in eGFR from baseline, or had indications for renal replacement therapy. No adverse effect related to tonsillectomy or general anesthesia was reported. One patient in Group A and 3 in Group B developed diabetes during the trial period, with 1 of these Group B patients requiring insulin therapy during the treatment with corticosteroid. At the end of the study, blood sugar levels of all four patients were restored to the normal range without any medications. No patient had a new onset of hypertension. Logistic regression analyses including the allocated treatment, eGFR,

mean blood pressure, urinary protein excretion, and the use of RAS inhibitors at

baseline as independent variables revealed the assigned treatment was R788 a significant, independent factor contributing to the disappearance of proteinuria (odds ratio 2.98, 95% CI 1.01–8.83, P = 0.049), but did not identify an independent factor in achieving the disappearance of hematuria or clinical remission. Conclusion: The results indicate tonsillectomy combined with steroid pulse therapy has no beneficial effect over steroid pulses alone to attenuate hematuria and to increase the incidence of clinical remission. Although the antiproteinuric effect was significantly greater in combined therapy, the difference was marginal, and its impact on the renal functional outcome remains to be clarified. YASUDA TAKASHI1, ifenprodil YASUDA YOSHINARI2, OHDE SACHIKO3, selleck TAKAHASHI OSAMU3, KAWAMURA TETSUYA4, MATSUO SEIICHI3 1Division of Nephrology & Hypertension, St. Marianna University School of Medicine, Japan; 2Department of Nephrology, Nagoya University Graduate School of Medicine, Japan; 3Center for Clinical Epidemiology, St. Luke’s Life Science Institute, St. Luke’s International Hospital, Japan; 4Division of Kidney & Hypertension, The Jikei University School of

Medicine, Japan We have started the Nationwide Retrospective Cohort Study in IgA nephropathy in Japan since Sep. 1, 2012. The main purpose is to clarify the choice of therapy, including tonsillectomy in combination with intravenous pulse methylprednisolone followed by oral prednisone (tonsillectomy with pulse methylprednisolone), in patients with IgA nephropathy under various clinical presentations. Adult patients with IgA nephropathy diagnosed by the first renal biopsy during the three years from 2002 to 2004 were eligible. Data at the time of renal biopsy and during the follow-up were collected, and total 1,174 cases from 49 facilities were registered. Among them, as an interim analysis, we analyzed 1082 cases which have sufficient data for the analysis upon registration.

Conclusion:  EETs are beneficial in AZD6244 supplier the setting of lung ischemia–reperfusion, when administered at reperfusion. However, further study will be needed to elucidate the mechanism of action. “
“Please cite this paper as: McGahon MK, McKee J, Dash DP, Brown E, Simpson DA, Curtis TM, McGeown JG, Scholfield CN. Pharmacological profiling of store-operated Ca2+ entry in retinal arteriolar smooth muscle. Microcirculation 19:

586–597, 2012. Objective:  Pharmacological profiling of SOCE and molecular profiling of ORAI and TRPC expression in arterioles. Methods:  Fura-2-based microfluorimetry was used to assess CPA-induced SOCE in rat retinal arteriolar myocytes. Arteriolar ORAI and TRP transcript expression was screened using RT-PCR. Results:  The SKF96365 and LOE908 blocked SOCE (IC50s of 1.2 and 1.4 μm, respectively). Gd3+ and La3+ potently inhibited SOCE (IC50s of 21 and 42 nm, respectively), but Ni2+ showed lower potency (IC50 = 11.6 μm). 2APB inhibited SOCE (IC50 = 3.7 μm) LY2109761 datasheet but enhanced

basal influx (>100 μm). Verapamil and nifedipine had no effect at concentrations that inhibit L-type Ca2+ channels, but diltiazem inhibited SOCE by approximately 40% (≥0.1 μm). The RT-PCR demonstrated transcript expression for ORAI 1, 2, and 3, and TRPC1, 3, 4, and 7. Transcripts for TRPV1 and 2, which are activated by 2APB, were also expressed. Conclusions:  The pharmacological profile of SOCE in retinal arteriolar smooth muscle appears unique when compared with other vascular Cytoskeletal Signaling inhibitor tissues.

This suggests that the molecular mechanisms underlying SOCE can differ, even in closely related tissues. Taken together, the pharmacological and molecular data are most consistent with involvement of TRPC1 in SOCE, although involvement of ORAI or other TRPC channels cannot be excluded. “
“Microcirculation (2010) 17, 69–78. doi: 10.1111/j.1549-8719.2010.00002.x Background:  This study was designed to explore the effect of transient inducible nitric oxide synthase (iNOS) overexpression via cationic liposome-mediated gene transfer on cardiac function, fibrosis, and microvascular perfusion in a porcine model of chronic ischemia. Methods and Results:  Chronic myocardial ischemia was induced using a minimally invasive model in 23 landrace pigs. Upon demonstration of heart failure, 10 animals were treated with liposome-mediated iNOS-gene-transfer by local intramyocardial injection and 13 animals received a sham procedure to serve as control. The efficacy of this iNOS-gene-transfer was demonstrated for up to 7 days by reverse transcriptase–polymerase chain reaction in preliminary studies. Four weeks after iNOS transfer, magnetic resonance imaging showed no effect of iNOS overexpression on cardiac contractility at rest and during dobutamine stress (resting ejection fraction: control 27%, iNOS 26%; P = ns). Late enhancement, infarct size, and the amount of fibrosis were similar between groups.

None of authors have financial support relevant to this study. “
“Objective: Cold stress can elicit increases in urinary urgency and frequency. We determined if there was a relationship between finger and toe temperatures and Ku-0059436 nmr lower urinary tract symptoms (LUTS). Methods: We studied 50 people who visited a public health management seminar. The participants were divided into

two groups according to self-described sensitivity to cold stress. The cold non-sensitive (CNS) group consisted of 3 males and 20 females (66.9 ± 10.8 years old), and the cold sensitive (CS) group consisted of 4 males and 23 females (65.8 ± 8.01 years old). Each participant was assessed to determine international prostate symptom score (IPSS), overactive bladder symptom score (OABSS), and quality of life (QOL) score. They were then instructed on lifestyle changes and exercises that could improve peripheral blood flow and provide relief for their LUTS. Next, the temperatures of their middle fingers and toes were measured before and after 5–10 min of the exercises. Two weeks later, the IPSS, OABSS, and QOL scores were reassessed. Results: Before exercise, the middle fingers were significantly warmer than the middle toes. Exercise had no significant effect on the middle finger temperature of either Z-VAD-FMK group; however, it did increase the middle toe temperature for both groups. The increase

was greatest for the CS group. The CS group had higher LUTS storage symptoms than the CNS group, and these improved after 2 weeks of lifestyle changes and exercise. Conclusion: Improvements in lifestyle and daily exercise may be

effective for LUTS in CS people. “
“Increasing evidence from clinical Ureohydrolase and epidemiological studies has shown associations between lower urinary tract symptoms (LUTS) and major chronic medical diseases. Recent epidemiological studies have revealed that, to a large extent, lifestyle factors associated with metabolism, such as obesity, physical activity, blood glucose, and diet, contribute substantially to the development of these conditions. Multiple studies have demonstrated strong independent associations between LUTS and components of metabolic syndrome. Therefore, modification of lifestyle factors may lower the risk of LUTS. Prevalence of MS is age-dependent with gender differences, and LUTS have different manifestations in men and women. LUTS-associated benign prostatic hyperplasia (BPH) have multiple evidence of correlation with MS factors; however, results were inconsistent in their correlation among prostate volume and prostate-specific antigen. There is limited data on female LUTS or other diseases such as urinary incontinence or overactive bladder and MS. Further research is required to understand their connection in the pathogenesis of LUTS and to establish a more effective prevention and a therapeutic model.

Because the factor ‘age’ has three levels (1, 6 and 20 weeks), post hoc testing was performed in case of significant main effects of age. When significant interaction effects were found, these instead of significant main effects were evaluated statistically by post hoc analyses. Outcomes of post hoc tests are shown on the figures. For clarity, only significant and relevant comparisons are presented,

for example, the 0.1-μg dose in 1-week-old mice is compared to the 0.1-μg dose, but not to the 10-μg dose, in older mice. The limit for statistical significance was set to P < 0.05. To investigate how sex, age and dose influenced sensitization and allergic inflammation in a standard airway allergy mouse model, female and male mice of

different age groups were sensitized and boosted i.p. with different Vemurafenib datasheet doses of OVA and challenged with three i.n. instillations of OVA. Significant main and interaction effects are given in Table 2, and results U0126 in vitro of the post hoc tests are displayed on the figures. OVA-specific IgE and IgG1 were measured in serum both before and after the airway challenges with OVA and statistical analyses revealed that dose, age and sex affected the antibody response in a similar way both before and after OVA challenges. This implies that the relationship between the groups was equivalent, and, therefore, only the antibody levels after allergen challenge are shown. Following the airway challenges, a significant interaction of sex, allergen dose and age was found for the OVA-specific IgE response (Table 2). For clarity, females and males are depicted in separate Florfenicol graphs (Fig. 1A, B). Overall, the IgE response in 1-week-old mice differed from the responses of older age groups. One-week-old females responded with significantly higher IgE production to sensitization with the 10-μg dose compared to the 0.1- and 0-μg dose (Fig. 1A). A comparable relationship

was observed for the 1-week-old males (Fig. 1B). The effect of dose was reversed in the older females with the highest IgE levels found following immunization with 0.1 μg OVA. The effect of the 0.1 and 10 μg doses did not differ in male mice (Fig. 1A, B). In 1-week-old mice, no effect of sex could be observed. After immunization with 0.1 μg OVA, the mean IgE response in 6- and 20-week-old females was higher compared with the males, but only statistically significant for 6-week-old mice (‘S’ in Fig. 1A, B). A significant effect of age on IgE production was only seen in female mice. At 6 and 20 weeks of age, females responded with significantly higher IgE levels to the 0.1-μg dose compared to 1-week-old females (* in Fig. 1A). No differences in IgE levels were observed between the oldest age groups. Interestingly, no effect of sex was seen on OVA-specific IgG1 production, and both sexes are therefore combined in Fig. 1C. A significant dose and age interaction effect was found (Table 2).

Lactic acid in vaginal secretions originates from the activity of both the vaginal mucosa (Gorodeski et al., 2005) and the action of Lactobacillus sp. and possibly also by other bacterial species (Zhou et al., 2004). Glucose LGK-974 in vivo in the intermediate vaginal epithelial cell layer under the influence of estrogen

is metabolized under anaerobic conditions to pyruvic acid and then to lactic acid. The lactic acid diffuses out of the cells and accumulates in the extracellular fluid. Similarly, Lactobacillus sp. convert extracellular glucose into lactic acid by anaerobic glycolysis. The activation of polymorphonuclear leukocytes and monocytes/macrophages is an energy-dependent process and stimulates the induction of glycolysis. Thus, inflammation is also associated with localized lactic acid release (Haji-Michael et al., 1999). Similarly, lactic acid is produced and released into the extracellular environment by many malignant tumors due to both accelerated aerobic glycolysis (the Warburg effect) (Warburg, 1961) and by anaerobic hypoxia-driven

glycolysis (Elson et al., 2000). The consequence of lactic acid release on immune system activities has not received much research attention. In a series of elegant experiments, Shime et al. (2008) demonstrated that a human lung adenocarcinoma cell line (CADO-LC10 cells) secreted lactic acid into the culture medium. While the lactic acid released by itself INK-128 had no effect on cytokine induction, in the concomitant presence of a Toll-like receptor (TLR) ligand, lactic acid stimulated the production of interleukin-23 (IL-23) by monocytes/macrophages. Conversely, there was no effect of lactic acid on

TLR-stimulated IL-12 transcription. IL-12 and IL-23 are heterodimeric cytokines that share a p40 subunit. In IL-12, p40 combines with a p35 subunit; in IL-23, p40 combines with p19 (Langrish et al., 2004). Thus, lactic acid enhanced p40 and p19 transcription drastically. The stimulation of IL-23 production required the presence Obatoclax Mesylate (GX15-070) of a lactate ion in its transportable form; the neutralized lactate anion or the presence of an equivalent proton concentration from a different acid did not enhance IL-23 release (Shime et al., 2008). IL-23 and IL-12 have unique effects on T helper lymphocyte subsets. IL-12 induces T cell differentiation into the Th1 CD4+ T cell subset. The release of interferon-γ (IFN-γ) by Th1 cells and natural killer cells activates macrophages to destroy intracellular microbial pathogens (Goriely et al., 2008). IFN-γ also acts on B lymphocytes to inhibit the synthesis of immunoglobulin G1 antibodies (Manetti et al., 1993). In contrast, IL-23 promotes the development of the newly recognized Th17 CD4+ T cell subset (Bettelli et al., 2007).

IL1-β was inhibited to its baseline in several, but not all experiments; IL-6 inhibition was always significant but almost never total. As indicated above, IL-10 secretion followed IL-1β and IL-6 secretion. We were surprised to observe that IL-10 was only mildly inhibited relative to IL-1β, and even to IL-6 (Fig. 3C). Inhibition of IL-1β was 75–100% in most experiments, and IL-6 was inhibited 40–70%, whereas IL-10 inhibition was only 20–35%. Thus, interaction with iC3b-opsonized apoptotic cells not only markedly inhibited the proinflammatory response to zymosan, but also changed the relative secretion of cytokines,

favoring a high anti-inflammatory-proinflammatory cytokine secretion ratio. Similar results were obtained while using LPS. IL-1β and IL-6 secretion were reduced from 160±25 to 31±14 and from 1820±188 to 555±88 pg/mL respectively, following one h exposure to opsonized apoptotic cells (p<0.001). In the same manner, selleck inhibitor interaction with iC3b-opsonized apoptotic cells downregulated MHC class II, CD86, CD83, CD40, and CCR7, as well IL-12 secretion (data not shown, see 5). In order to further Fulvestrant ic50 verify that the decrease in proinflammatory cytokines was not due to decreased ingestion of zymosan, we documented zymosan uptake following

macrophage−apoptotic cell interaction. As shown in Fig. 3D, zymosan uptake was not inhibited following apoptotic cell interaction, and was even augmented. Thus, the inhibitory pattern seen in secretion of proinflammatory cytokines was not due to decreased phagocytosis of zymosan. The specificity of the uptake was further shown by using fibrinogen-coated plates. Zymosan induced proinflammatory cytokines from macrophages differentiated on fibronectin-coated plates,

resulting in IL-1β and IL-6 secretion reaching 197±21 and 2120±118 pg/mL, respectively. Thus, no proinflammatory cytokine inhibition was shown using fibrinogen as a ligand. Furthermore, addition of opsonized apoptotic cells reduced cytokine secretion to 29±11 and 611±48, respectively, following 1 h exposure to opsonized apoptotic cells (p<0.001 and p<0.001). Taken together, the results indicate that CD11b/CD18 and CD11c/CD18 response to ligand is specific to iC3b-opsonized apoptotic cells, and not every ligand (i.e. fibronectin) will induce the same response. Since it has been proposed that inhibition of the proinflammtory response is an autocrine/paracrine process 2, 4, and Aprepitant we were able to detect IL-10 secretion, we examined the effect of anti-IL-10. As shown in Fig. 4A and B, anti-IL-10 had no effect, suggesting an alternative mode of inhibition. Although TGF-β was not detected, anti-TGF-β was also examined because TGF-β is sometimes hard to detect and can be released in the preformed mode. As shown in Fig. 4A and B, anti-TGF-β did not have any effect on inhibition. Thus, in this system we were not able to demonstrate a paracrine/autocrine effect of IL-10 or TGF-β that led to inhibition of the immune response to zymosan and LPS.

Mitochondrial DNA mutations were assessed in single muscle

fibres using Real-time PCR. We identified respiratory-deficient fibres at different stages of mitochondrial dysfunction, with downregulated expression of complex I of mitochondrial respiratory chain being the initial feature. We detected mitochondrial DNA rearrangements in the majority of individual respiratory-deficient muscle fibres. There was a strong correlation between number of T lymphocytes Palbociclib and macrophages residing in muscle tissue and the abundance of respiratory-deficient fibres. Moreover, we found that respiratory-deficient muscle fibres were more likely to be atrophic compared to respiratory-normal counterparts. Our findings suggest that mitochondrial dysfunction has a role in sIBM progression. A strong correlation between the severity of inflammation, degree of mitochondrial changes and atrophy implicated existence of a mechanistic link between these three parameters. We propose Kinase Inhibitor Library a role for inflammatory cells in the initiation of mitochondrial DNA damage, which when accumulated, causes respiratory dysfunction, fibre atrophy and ultimately degeneration

of muscle fibres. “
“While prion infection ultimately involves the entire brain, it has long been thought that the abrupt clinical onset and rapid neurological decline in laboratory rodents relates to involvement of specific critical neuroanatomical Sodium butyrate target areas. The severity and type of clinical signs, together with the rapid progression, suggest the brainstem as a candidate location for such critical areas. In this study we aimed to correlate prion pathology with clinical phenotype in order to identify clinical target areas. We conducted a comprehensive survey of brainstem pathology in mice infected with two distinct prion strains, which produce different patterns of pathology, in mice overexpressing prion protein (with accelerated clinical onset) and in mice in which neuronal expression was reduced by gene targeting (which greatly delays clinical onset).

We identified specific brainstem areas that are affected by prion pathology during the progression of the disease. In the early phase of disease the locus coeruleus, the nucleus of the solitary tract, and the pre-Bötzinger complex were affected by prion protein deposition. This was followed by involvement of the motor and autonomic centres of the brainstem. Neurodegeneration in the locus coeruleus, the nucleus of the solitary tract and the pre-Bötzinger complex predominated and corresponded to the manifestation of the clinical phenotype. Because of their fundamental role in controlling autonomic function and the overlap with clinical signs in sporadic CJD, we suggest that these nuclei represent key clinical target areas in prion diseases. “
“L. E. Taylor, Y. J. Kaminoh, C. K. Rodesch and K. M.