Emetic Potentials of Newly Identified Staphylococcal Enterotoxin-Like Toxins

Staphylococcal enterotoxins (SEs) are a common causative agent of food poisoning. Recently, many new SE-like (SEl) toxins have been reported, although the role of SEls in food poisoning remains unclear. In this study, the emetic potentials of SElK, SElL, SElM, SElN, SElO, SElP, and SElQ were assessed using a monkey-feeding assay. All the SEls that were tested induced emetic reactions in monkeys at a dose of 100 μg/kg, although the numbers of affected monkeys were significantly smaller than the numbers that were affected after consuming SEA or SEB. This result suggests that these new SEs may play some role in staphylococcal food poisoning.     

Prevalence and persistence of depression in patients with implantable cardioverter defibrillator: a 2-year longitudinal study

Background: It is unclear whether depression persists in patients with implantable cardioverter defibrillators (ICDs). We evaluated the prevalence and persistence of depression in ICD patients over a 2‐year period. Methods: The study included 90 consecutively hospitalized patients. Patients underlying heart disease was 24% coronary artery disease, 29% idiopathic dilated cardiomyopathy, 24% hypertrophic cardiomyopathy, 13% idiopathic VF/long QT syndrome and miscellaneous conditions 11%. A secondary indication for ICD implantation was present in 20 patients. All patients completed the Zung Self‐Rating Depression Scale (SDS) at study baseline and at the their routine follow‐up visit 2 years after the baseline questionnaire. Delivery of ICD therapies was tracked throughout the 2 years. Results: Depression, indicated by a Zung SDS index score exceeding 60, was present in 29 (32%) of patients at study baseline. Depression was present in 11/51 (21%) patients scheduled to undergo ICD implantation, 2/2 (100%) patients whose device was upgraded to a CRT‐D, 3/14 (21%) patients who had undergone pulse generator replacement, 7/14 (50%) patients who experienced electrical storm and 6/9 (66%) patients hospitalized with acute decompensated heart failure. NYHA functional class III was significantly associated with depression at baseline (HR 6.7, 95% CI 1.68–27.2, p = 0.0007). No differences were noted for female gender, demographics, β‐blocker use, or LVEF ≤35% (p = ns). Depression was present in 25 (28%) of patients at 2 years follow‐up, persisting in 21 (72%) of patients whose Zung SDS scores were elevated at baseline. The median time from ICD shock therapy to completion of the 2 year questionnaire was 9 months (range, 1–22). Patients who were depressed (9/25, 36%) experienced more shocks than non‐depressed patients (6/65, 9%) after 2 years (p = 0.002). Conclusions: Depression is not uncommon among patients who meet criteria for ICD implantation and persists over time particularly when functional status is impaired. Depression is associated with a higher incidence shock therapy. (PACE 2010; 33:1455–1461)     

Formation and distribution of the sural nerve based on nerve fascicle and nerve fiber analyses

The formation and distribution of the sural nerve are presented on the basis of an investigation of 31 legs of Japanese cadavers using nerve fascicle and fiber analyses. Nerve fibers constituting the medial sural cutaneous nerve were designated as 'T', whereas those constituting the peroneal communicating branch were designated as 'F'. In 74.2% of cases (23/31), the T and F fibers joined each other in the leg, whereas in 9.7% of cases (3/31) they descended separately. In 16.1% of cases (5/31), the sural nerve was formed of only the T fibers. The sural nerve gave off lateral calcaneal branches and medial and lateral branches at the ankle. The lateral calcaneal branches always contained T fibers. The medial branches consisted of only T fibers, whereas most of the lateral branches consisted of only F fibers (71.0%; 22/31). In addition to the T and F fibers, P fibers, which derived from the superficial and deep peroneal nerves, formed the dorsal digital nerves. The P fibers were entirely supplied to the medial four and one-half toes. However, they were gradually replaced by the T and F fibers in the lateral direction. The 10th proper dorsal digital nerve consisted of T fibers only (38.7%; 12/31), of F fibers only (19.4%; 6/31) or of both T and F fibers (38.7%; 12/31). These findings suggest that the T fibers are essential nerve components for the skin and deep structures of the ankle and heel rather than the skin of the lateral side of the fifth toe. The designation of the medial sural cutaneous nerve should be avoided and only the T fibers are appropriate components for naming as the sural nerve.     

Induction and activation of the aryl hydrocarbon receptor by IL-4 in B cells

It is widely known that IL-4 and IL-13 act on various kinds of cells, including B cells, resulting in enhancement of proliferation, class switching to IgE and expression of several surface proteins. These functions are important for the recognition of the various antigens in B cells and are known to be involved in the pathogenesis of allergic diseases. However, it has not been known whether IL-4/IL-13 is involved in the metabolism of various kinds of xenobiotics including 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD), and it remains undetermined whether TCDD, an environmental pollutant, influences IgE production in B cells, exaggerating allergic reactions. We identified IL-4- or IL-13-inducible genes in a human Burkitt lymphoma cell line, DND-39, using microarray technology, in which the AHR gene was included. The AHR gene product, the aryl hydrocarbon receptor (AhR), was induced by IL-4 in both mouse and human B cells in a STAT6-dependent manner. IL-4 alone had the ability to translocate the induced AhR to the nuclei. TCDD, a ligand for AhR, rapidly degraded the induced AhR by the proteasomal pathway, although IL-4-activated AhR sustained its expression. AhR activated by IL-4 caused expression of a xenobiotic-metabolizing gene, CYP1A1, and TCDD synergistically acted on the induction of this gene by IL-4. However, the induction of AhR had no effect on IgE synthesis or CD23 expression. These results indicate that the metabolism of xenobiotics would be a novel biological function of IL-4 and IL-13 in B cells, whereas TCDD is not involved in IgE synthesis in B cells.     

Efficacy and immunologic responses to influenza vaccine in HIV-1-infected patients

Influenza vaccine is recommended for HIV-1-infected patients. The present prospective study was conducted to evaluate the clinical efficacy and immunologic responses to the vaccine. From November 1 to December 27, 2002, 262 HIV-1-infected patients received a trivalent influenza subunit vaccine, whereas 66 did not. Influenza illness occurred in 16 vaccinated and 14 nonvaccinated patients (incidence = 6.1% [95% confidence interval (CI): 4%-10%] in vaccinated vs. 21.2% [CI: 13%-35%] in nonvaccinated persons, P < 0.001; relative risk = 0.29 [CI: 0.14-0.55]). Influenza vaccine provided clinically effective protection against influenza illness in HIV-1-infected patients. In baseline antibody-negative patients, anti-H1 and anti-H3 antibody responses to the vaccination were significant in those patients with a CD4 count >200 cells/muL compared with those with a CD4 count <200 cells/muL (P < 0.05). In contrast, in baseline antibody-positive patients, good antibody responses were observed irrespective of CD4 counts, like the healthy controls. Based on these results, annual vaccination is recommended. Specific CD4 responses correlated with HIV-1 viral load (VL), especially in patients treated with highly active antiretroviral therapy (HAART) compared with those without HAART (P < 0.01), although the clinical efficacy did not correlate with HIV-1 VL. HAART may enhance the immunologic efficacy of influenza vaccine.     

Functional overlap between RecA and MgsA (RarA) in the rescue of stalled replication forks in Escherichia coli

Escherichia coli RecA protein plays a role in DNA homologous recombination, recombination repair, and the rescue of stalled or collapsed replication forks. The mgsA (rarA) gene encodes a highly conserved DNA-dependent ATPase, whose yeast orthologue, MGS1, plays a role in maintaining genomic stability. In this study, we show a functional relationship between mgsA and recA during DNA replication. The mgsA recA double mutant grows more slowly and has lower viability than a recA single mutant, but they are equally sensitive to UV-induced DNA damage. Mutations in mgsA and recA cause lethality in DNA polymerase I deficient cells, and suppress the temperature-dependent growth defect of dnaE486 (Pol III alpha-catalytic subunit). Moreover, recAS25P, a novel recA allele identified in this work, does not complement the slow growth of DeltamgsA DeltarecA cells or the lethality of polA12 DeltarecA, but is proficient in DNA repair, homologous recombination, SOS mutagenesis and SOS induction. These results suggest that RecA and MgsA are functionally redundant in rescuing stalled replication forks, and that the DNA repair and homologous recombination functions of RecA are separated from its function to maintain progression of replication fork.     

Nerve fiber analysis of ansa cervicalis-vagus communications

Communications between the ansa cervicalis and the vagus nerve, although described only as variations in many textbooks, can be observed frequently in the dissection room. Following macroscopic observation, some of such cases were subsequently dissected under surgical microscope to determine the nature of such communications. As a result, two broad categories of communications between the ansa cervicalis complex and the vagus nerve could be recognized: (i) false (pseudo) communications, where the two nerves were attached only by the connective tissue with no fiber exchange; and (ii) true communications, with nerve fiber involvement. Fiber analysis showed that the majority of the ansa–vagal communications observed during gross dissection were of the first category. True communications, when present, were only scanty contributions and always directed towards the side of the vagus. In addition, the vagus (region of the inferior ganglion) and hypoglossal nerves were found to be in close contact at the base of the skull and usually could not be separated by gross dissection. But such attachments, too, were shown to be almost entirely of false nature except for the possible presence of a few fine nerve filaments. It seems that the ansa–vagal communications are merely a result of the close physical relationship between the two structures and serve no significant functional purpose, but at the same time may hinder the prospects of using ansa cervicalis in surgical procedures such as re-innervation of laryngeal and facial muscles, following damage to recurrent laryngeal and facial nerves, respectively.     

Neural-specific ablation of the scaffold protein JSAP1 in mice causes neonatal death

We previously identified c-Jun NH₂-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1, also known as JNK-interacting protein 3) as a scaffolding factor for JNK intracellular signaling pathways. Targeted gene-disruption studies have shown that JSAP1-null mice are unable to breathe and die shortly after birth. Although neural defects might be responsible for their death, there has been no convincing evidence for this. Here we first generated genetically engineered mice carrying a loxP-flanked (floxed) jsap1 gene. To evaluate the validity of this deletion as a jsap1 conditional knockout (KO), we created mice in which the same exon was deleted in all cell lineages, and compared their phenotypes with those of the jsap1 conventional KO mice reported previously. The two KO lines showed indistinguishable phenotypes, i.e., neonatal death and morphological defects in the telencephalon, indicating that the conditional deletion was a true null mutation. We then introduced the floxed jsap1 deletion mutant specifically into the neural lineage, and found that the jsap1 conditional KO mice showed essentially the same phenotypes as the JSAP1-null mice. These results strongly suggest that the neonatal death of jsap1-deficient mice is caused by defects in the nervous system.     

Hemilaminectomy for removal of extramedullary or extradural spinal cord tumors: medium to long-term clinical outcomes

Purpose

Laminectomy is generally the treatment of choice for removal of spinal tumors. However, it has been shown that laminectomy may cause instability due to damage of posterior elements of the spinal column, which may induce subsequent kyphosis in the future. Therefore, to reduce the risk of deformity and spinal instability after laminectomy, hemilaminectomy has been used. However, the medium to long-term effects of hemilaminectomy on spinal sagittal alignment is not well understood. The present study was performed to evaluate the clinical outcomes, including spinal sagittal alignment of patients, associated with spinal cord tumors treated by surgical excision using hemilaminectomy.

Materials and Methods

Twenty hemilaminectomy operations at our institute for extramedullary or extradural spinal cord tumors in 19 patients were evaluated retrospectively with an average follow-up of 85 months (range, 40-131 months). Neurological condition was evaluated using the improvement ratio of the Japanese Orthopaedic Association Score (JOA score) for cervical, thoracic myelopathy, or back pain, and sagittal alignment by sagittal Cobb angle of the hemilaminectomied area.

Results

The mean improvement ratio of neurological results was 56.7% in the cervical spine (p < 0.01, n = 10), 26.3% in the thoracic spine (not significant, n = 5), and 48.6% in the lumbar spine (NS, n = 5). The sagittal Cobb angle was 4.3 ± 18.0° in the preoperative period and 5.4 ± 17.6° at the latest follow-up, indicating no significant deterioration.

Conclusion

Hemilaminectomy is useful for extramedullary or extradural spinal cord tumors in providing fair neurological status and restoration of spinal sagittal alignment in medium to long-term follow-up.     

Genotype–Phenotype Correlations of Malignant Hyperthermia and Central Core Disease Mutations in the Central Region of the RYR1 Channel

Type 1 ryanodine receptor (RYR1) is a Ca²⁺ release channel in the sarcoplasmic reticulum of skeletal muscle and is mutated in some muscle diseases, including malignant hyperthermia (MH) and central core disease (CCD). Over 200 mutations associated with these diseases have been identified, and most mutations accelerate Ca²⁺‐induced Ca²⁺ release (CICR), resulting in abnormal Ca²⁺ homeostasis in skeletal muscle. However, it remains largely unknown how specific mutations cause different phenotypes. In this study, we investigated the CICR activity of 14 mutations at 10 different positions in the central region of RYR1 (10 MH and four MH/CCD mutations) using a heterologous expression system in HEK293 cells. In live‐cell Ca²⁺ imaging, the mutant channels exhibited an enhanced sensitivity to caffeine, a reduced endoplasmic reticulum Ca²⁺ content, and an increased resting cytoplasmic Ca²⁺ level. The three parameters for CICR (Ca²⁺ sensitivity for activation, Ca²⁺ sensitivity for inactivation, and attainable maximum activity, i.e., gain) were obtained by [³H]ryanodine binding and fitting analysis. The mutant channels showed increased gain and Ca²⁺ sensitivity for activation in a site‐specific manner. Genotype–phenotype correlations were explained well by the near‐atomic structure of RYR1. Our data suggest that divergent CICR activity may cause various disease phenotypes by specific mutations.