Anaerobic NADH-fumarate reductase system is predominant in the respiratory chain of Echinococcus multilocularis, providing a novel target for the chemotherapy of alveolar echinococcosis

Alveolar echinococcosis, which is due to the massive growth of larval Echinococcus multilocularis, is a life-threatening parasitic zoonosis distributed widely across the northern hemisphere. Commercially available chemotherapeutic compounds have parasitostatic but not parasitocidal effects. Parasitic organisms use various energy metabolic pathways that differ greatly from those of their hosts and therefore could be promising targets for chemotherapy. The aim of this study was to characterize the mitochondrial respiratory chain of E. multilocularis, with the eventual goal of developing novel antiechinococcal compounds. Enzymatic analyses using enriched mitochondrial fractions from E. multilocularis protoscoleces revealed that the mitochondria exhibited NADH-fumarate reductase activity as the predominant enzyme activity, suggesting that the mitochondrial respiratory system of the parasite is highly adapted to anaerobic environments. High-performance liquid chromatography-mass spectrometry revealed that the primary quinone of the parasite mitochondria was rhodoquinone-10, which is commonly used as an electron mediator in anaerobic respiration by the NADH-fumarate reductase system of other eukaryotes. This also suggests that the mitochondria of E. multilocularis protoscoleces possess an anaerobic respiratory chain in which complex II of the parasite functions as a rhodoquinol-fumarate reductase. Furthermore, in vitro treatment assays using respiratory chain inhibitors against the NADH-quinone reductase activity of mitochondrial complex I demonstrated that they had a potent ability to kill protoscoleces. These results suggest that the mitochondrial respiratory chain of the parasite is a promising target for chemotherapy of alveolar echinococcosis.     

Dystonic frowning without blepharospasm

We report on two cases who presented with involuntary facial grimacing and frowning. Blepharospasm has never been documented in one, and the other case showed difficulty in lid opening only in the early phase of the disease. Botulinum toxin was effective for both. This is a hitherto unreported presentation of upper facial dystonia without interference of eyelid motor control.     

Correlation between adiponectin and reduction of cell adhesion molecules after pitavastatin treatment in hyperlipidemic patients with type 2 diabetes mellitus

The aim of this study was to determine whether pitavastatin may prevent the progression of atherosclerotic changes in hyperlipidemic patients. Seventy-five hyperlipidemic patients with and without type 2 diabetes were enrolled to receive pitavastatin 2 mg daily. Cell adhesion molecules (sCD40L, sP-selectin, sE-selectin, and sL-selectin), chemokines (MCP-1 and RANTES) and adiponectin were measured at baseline and after 3 and 6 months of pitavastatin treatment. Adiponectin levels prior to pitavastatin treatment in hyperlipidemic patients with and without diabetes were lower than levels in normolipidemic controls. Both total cholesterol and the LDL-cholesterol (LDL-C) decreased significantly after pitavastatin administration. Additionally, hyperlipidemic patients with type 2 diabetes exhibited a significant increase in adiponectin levels after pitavastatin treatment (before vs. 3 months, 6 months, 2.81 ± 0.95 vs. 3.84 ± 0.84 μg/ml (p < 0.01), 4.61 ± 1.15 μg/ml (p < 0.001)). Furthermore, hyperlipidemic diabetics exhibited significant decreases in sE-selectin and sL-selectin levels after 6 months of pitavastatin treatment (sE-selectin, before vs. 6 months, 74 ± 21 vs. 51 ± 10 ng/ml, p < 0.05; sL-selectin, before vs. 6 months, 896 ± 141 vs. 814 ± 129 ng/ml, p < 0.05). In addition, adiponectin showed significant correlation with sE-selectin and sL-selectin in diabetic hyperlipidemia. However, MCP-1, RANTES and sCD40L did not exhibit any differences before or after pitavastatin administration. These results suggest that pitavastatin possesses an adiponectin-dependent anti-atherosclerotic effect in hyperlipidemic patients with type 2 diabetes in addition to its lowering effects on total cholesterol and LDL-C.     

Generation of co-speech gestures based on spatial imagery from the right-hemisphere: evidence from split-brain patients

It has been claimed that the linguistically dominant (left) hemisphere is obligatorily involved in production of spontaneous speech-accompanying gestures (Kimura, 1973a, 1973b; Lavergne and Kimura, 1987). We examined this claim for the gestures that are based on spatial imagery: iconic gestures with observer viewpoint (McNeill, 1992) and abstract deictic gestures (McNeill, et al. 1993). We observed gesture production in three patients with complete section of the corpus callosum in commissurotomy or callosotomy (two with left-hemisphere language, and one with bilaterally represented language) and nine healthy control participants. All three patients produced spatial-imagery gestures with the left-hand as well as with the right-hand. However, unlike healthy controls and the split-brain patient with bilaterally represented language, the two patients with left-hemispheric language dominance coordinated speech and spatial-imagery gestures more poorly in the left-hand than in the right-hand. It is concluded that the linguistically non-dominant (right) hemisphere alone can generate co-speech gestures based on spatial imagery, just as the left-hemisphere can.     

Adult T-cell leukemia/lymphoma with multiple integration of HTLV-1 provirus presenting as an isolated paranasal sinus tumor: a case report

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive T-cell lymphoma and etiologically associated with human T-lymphotropic virus type 1 (HTLV-1). Patients with ATLL commonly present with leukemic changes, systemic lymphadenopathy, and/or extranodal lesion and have very poor prognosis. METHODS AND RESULTS: We describe a rare case of ATLL presenting as an isolated paranasal mass. Southern blot analysis of the biopsied specimens demonstrated multiple integration bands of HTLV-1 provirus of different intensities. Chemotherapy resulted in complete resolution of the paranasal mass. Thereafter, the patient showed an indolent clinical course with leukemic changes and pulmonary and cutaneous ATLL lesions and remains alive more than 5 years from diagnosis. CONCLUSION: ATLL should be included in the differential diagnosis of sinonasal lymphoma, although the event is rare. Multiple HTLV-1 provirus integrations of different intensities may be indicative of good prognosis for ATLL.     

Parents of childhood X-linked adrenoleukodystrophy: high risk for depression and neurosis

The purpose of this study was to assess mental health in parents of patients with the childhood cerebral form of X-linked adrenoleukodystrophy (CCALD) and to investigate factors relating to psychological problems in order to improve clinical management and quality of life. Sixteen fathers and 21 mothers of patients with CCALD completed a battery of psychological examinations including the Beck Depression Inventory second edition (BDI-II), the General Health Questionnaire 60 (GHQ60), and the State-Trait Anxiety Inventory (STAI). Three fathers and 11 mothers showed high scores on the BDI-II, suggesting that they were in a depressive state. Depression in the mothers was serious as compared with previous reports. Six fathers and 11 mothers were considered to be in a state of neurosis, according to the results of the GHQ60. Four fathers and 8 mothers showed high levels of anxiety on the STAI. Health and social status of the mothers correlated with their mental health, and younger mothers with young patients tended to be more depressed. Thus, parents of patients with CCALD have a high risk of depression and neurosis. Understanding the mental state of these parents and improvements in the social support system including mental counseling, home nursing care, supports in workplace and community are necessary to prevent and treat psychological problems. Especially, early intervention for mental health problems should be provided for younger mothers with few years since the child's diagnosis.     

Novel deletion mutation in GFAP gene in an infantile form of Alexander disease

Alexander disease is a rare, fatal neurologic disorder characterized by white-matter degeneration and cytoplasmic inclusions in astrocytes known as Rosenthal fibers, which are immunohistochemically positive to glial fibrillary acidic protein. Mutations in the glial fibrillary acidic protein gene were reported in patients with Alexander disease who had clinical and pathologic characteristics of the disease. All reported cases manifest heterozygous missense mutations, except for some insertions or deletions with no frame shift. Our patient had a heterozygous deletion of genomic sequence 1247-1249GGG>GG in exon 8 of the glial fibrillary acidic protein gene, which leads to a frame shift changing 16 amino acids and inducing a stop codon at codon 431 of 432 codons. The deletion mutation induces a structural conformation change in glial fibrillary acidic protein and their abnormal aggregation in astrocytes. This is the first report of a novel deletion mutation in the glial fibrillary acidic protein gene with a frame shift associated with Alexander disease.     

Vacuum-assisted closure for pediatric post-sternotomy mediastinitis: are low negative pressures sufficient?

We present 3 cases of pediatric post-sternotomy mediastinitis treated by a vacuum-assisted closure (VAC). The patients 2 girls, aged 6 months and 10 months, and a 2-year-old boy. The onset of infection was at 9, 14, and 32 postoperative days. The culture examination detected coagulase-negative Staphylococci strains in 2 cases, and Staphylococcus aureus in 1 case. A VAC was performed at -50 mm Hg for 10, 12, and 7 days. The wounds were closed without vascularized soft tissue. A VAC under a low negative pressure is a useful and safe procedure for the management of pediatric post-sternotomy mediastinitis.     

Clinical impact of body mass index on prostate biopsy in patients with intermediate PSA levels

From April 2005 to September 2007, 480 patients underwent transrectal prostate biopsy at our institution. The clinical data including age, serum prostate specific antigen (PSA) level, prostate volume and body mass index (BMI) were obtained, and the cancer detection rates and pathological findings were evaluated in 305 cases with a PSA concentration of 4.0 to 10.0 ng/ml. Prostate volume was calculated from magnetic resonance imaging (MRI) findings. The 305 patients were categorized according to their BMI into three groups (normal, less than 22 kg/m2 ; overweight, 22-25 kg/m2 ; and obese, more than 25 kg/m2). Cancer detection rates and histopathologic findings were compared between the groups. Multivariate logistic regression analysis was also performed. Prostate cancer was detected in 127 patients. No significant differences in BMI were observed between biopsy-positive and biopsy-negative cases (p = 0.965), and the detection rates of prostate cancer observed in the three groups were not significantly different. There was a significant association between BMI and the findings of high Gleason score (more than 4+3) (p = 0.048). BMI was not a contributory factor of prostate cancer detection for cases with intermediate PSA levels; however, patients with high BMI may have high-grade malignancy features.