Molecular characterisation and infectivity of a “Legumovirus” (genus Begomovirus: family Geminiviridae) infecting the leguminous weed Rhynchosia minima in Pakistan

The legume yellow mosaic viruses (LYMVs) that cause extensive losses to grain legumes across southern Asia are an evolutionarily unusual group of begomoviruses (genus Begomovirus; family Geminiviridae) with bipartite genomes. All previously identified LYMVs were isolated from leguminous crop species. Here we have identified a virus related to the LYMVs in a common weed, the legume Rhynchosia minima originating from Pakistan. Analysis of the sequence of the virus shows it to be a typical bipartite begomovirus. Sequence comparisons to all other begomovirus sequences available in the databases show the virus from R. minima to be distinct, with the highest level of sequence identity (69.5%) to an isolate of Mungbean yellow mosaic virus. This indicates that the virus identified here is a new species in the genus Begomovirus for which we propose the name Rhynchosia yellow mosaic virus (RhYMV). By Agrobacterium-mediated inoculation we show that, in common with the other LYMVs, the clones of RhYMV are not infectious to the experimental host Nicotiana benthamiana. In soybean, the results of inoculation depended upon the variety. In soybean var. Ig6 the symptoms were mild and plants recovered from infection. However, in var. FS-85, symptoms were severe and progressed to necrosis, indicative of a hypersensitive response. These results indicate that there is resistance to RhYMV in the soybean germplasm. The significance of these results is discussed.     

Analysis of humoral immune responses to LM1 ganglioside in guinea pigs

Guillain-Barré syndrome (GBS) is an autoimmune-mediated disease triggered by a preceding infection. A substantial body of evidence implicates antibodies to various gangliosides in subtypes of GBS. A significant proportion of patients with acute demyelinating subset of GBS have IgG antibodies against peripheral nervous system myelin specific neolactogangliosides such as LM1 and Hex-LM1. Although anti-neolactoganglioside antibodies in GBS were described more than two decades ago, their pathogenic role in neuropathy remains unknown due to the lack of suitable experimental models. In this study, we immunized ten guinea pigs with purified LM1 ganglioside mixed with keyhole limpet hemocyanin (KLH) and emulsified in complete Freund's adjuvant (CFA). Control guinea pigs were injected with KLH emulsified in CFA only. The animals were bled every four week intervals. The animals were boosted 3 times every four weeks. Experiments were terminated four months after initial immunization. Nine of 10 guinea pigs immunized with LM1 exhibited antibody responses to LM1. Anti-LM1 IgG titers in nine guinea pigs ranged from 1:400 to 1:12,800 at 16-weeks after initial immunization. Anti-LM1 antibodies were predominantly of IgG2 subclass. One guinea pig with the highest levels of IgG antibodies exhibited mild signs of neuropathy. There was no evidence of demyelination or inflammation in the sciatic nerves of LM1-immunized guinea pigs. Anti-LM1 antibodies bound to rat sciatic nerve myelin and to isolated rat Schwann cells. In summary, our findings suggest that relatively high levels of anti-LM1 IgG antibodies can be induced in guinea pigs and that LM1 is localized in peripheral nerve myelin and in Schwann cells. Further studies are needed to determine the pathogenic potential of anti-neolactoganglioside antibodies in neuropathy.     

Amino acid concentrations in the hamster central auditory system and long-term effects of intense tone exposure

Exposure to intense sounds often leads to loss of hearing of environmental sounds and hearing of a monotonous tonal sound not actually present, a condition known as tinnitus. Chronic physiological effects of exposure to intense tones have been reported for animals and should be accompanied by chemical changes present at long times after the intense sound exposure. By using a microdissection mapping procedure combined with high‐performance liquid chromatography (HPLC), we have measured concentrations of nine amino acids, including those used as neurotransmitters, in the cochlear nucleus, inferior colliculus, medial geniculate, and auditory cortex of hamsters 5 months after exposure to an intense tone, compared with control hamsters of the same age. No very large differences in amino acid concentrations were found between exposed and control hamsters. However, increases of glutamate and γ‐aminobutyrate (GABA) in some parts of the inferior colliculus of exposed hamsters were statistically significant. The most consistent differences between exposed and control hamsters were higher aspartate and lower taurine concentrations in virtually all regions of exposed hamsters, which reached statistical significance in many cases. Although these amino acids are not considered likely neurotransmitters, they indirectly have roles in excitatory and inhibitory neurotransmission, respectively. Thus, there is evidence for small, widespread, long‐term increases in excitatory transmission and decreases in inhibitory transmission after a level of acoustic trauma previously shown to produce hearing loss and tinnitus. © 2012 Wiley Periodicals, Inc.     

Segmental neurofibromatosis of the hand and upper extremity: a case report

A case of segmental neurofibromatosis of the upper extremity is presented. Multiple neurofibromas involving different peripheral nerves limited to a single body part or limb is a rare form of neurofibromatosis. The clinical, genetic, and histologic findings of segmental neurofibromatosis are described. The criteria for segmental neurofibromatosis are reviewed, and the differentiation of neurofibromatosis types 1 and 2 and schwannomatosis is also briefly reviewed.     

Strategy for reversing resistance to a single anticancer agent in human prostate and pancreatic carcinomas

Effective therapies for most solid cancers, especially those that have progressed to metastasis, remain elusive because of inherent and acquired resistance of tumor cells to conventional treatments. Additionally, the effective therapeutic window for many protocols can be very narrow, frequently resulting in toxicity. The present study explores an anticancer strategy that effectively eliminates resistant cancer cells without exerting deleterious effects on normal cells. This approach employs melanoma differentiation-induced gene-7/interleukin-24 (mda-7/IL-24), a cancer-specific, apoptosis-inducing cytokine, in combination with nontoxic doses of a chemical compound from the endoperoxide class that decomposes in water generating singlet oxygen. This combinatorial regimen specifically induced in vitro apoptosis in prostate carcinoma cells, with innate resistance to chemotherapy or engineered resistance to mda-7/IL-24, as well as pancreatic carcinoma cells inherently resistant to any treatment modality, including mda-7/IL-24. Apoptosis induction correlated with increased cellular reactive oxygen species production and was prevented by general antioxidants, such as N-acetyl-l-cysteine or Tiron. Induction of apoptosis in combination-treated cancer cells correlated with a reduction in the antiapoptotic protein BCL-x(L). In contrast, both normal prostate and pancreatic epithelial cells were unaffected by the single or combination treatment. These provocative findings suggest that this combinatorial strategy might provide a platform for developing effective treatments for therapy-resistant cancers.     

Frequency of atrial fibrillation and factors related to its development in dialysis patients

BACKGROUND: The frequency of atrial fibrillation is increased in patients with end-stage renal disease. In this study, we sought to determine the incidence of persistent and paroxysmal atrial fibrillation in patients with end-stage renal disease and to identify the risk factors associated with this arrhythmia. METHODS: Two hundred seventy-five patients with end-stage renal disease who were in a hemodialysis program for at least 4 months were included in the study. Patients with permanent, persistent, or paroxysmal atrial fibrillation were identified and recorded. All patients were evaluated for cardiac risk factors and arrhythmias. RESULTS: Thirty (10.9%) of the 275 patients were found to have atrial fibrillation. Ten (33.3%) of these patients had permanent or persistent atrial fibrillation, and 20 (66.6%) of these patients had paroxysmal atrial fibrillation. Patients with atrial fibrillation were older. Incidences of hypertension, coronary artery disease, left ventricular systolic dysfunction, right atrial diameters, and mitral and/or aortic calcification were significantly higher in patients with atrial fibrillation. Serum albumin and high-density lipoprotein levels were significantly lower in patients with atrial fibrillation. CONCLUSIONS: Our data indicate that atrial fibrillation is a frequent arrhythmia in patients with end-stage renal disease, and the most frequently encountered form is paroxysmal atrial fibrillation. In this patient group, presence of coronary artery disease, age, and right atrial diameter are independent factors for determination of the risk of development of atrial fibrillation.     

Evaluation by magnetic resonance imaging of aortic dilatation and coarctation in adult Turner syndrome patients

OBJECTIVE: Turner syndrome has well-recognized cardiovascular complications that appear in up to 40% of the patients and are more common in monosomy X. Left-sided obstructive lesions are relatively more frequent and predispose to aortic root dilatation and life-threatening aortic dissection. However, bicuspid aortic valves, hypertension, coarctation and aortic stenosis are also at risk of aortic dissection. Currently there is no clear guideline regarding the best single test for detection or monitoring aortic disease progression. DESIGN: Routine thoracic aortic magnetic resonance imaging (MRI) was introduced to the dedicated Turner syndrome clinic, with repeated MRI examination every 2 years to detect or assess progression of aortic lesions. RESULTS: Seven out of a total of 17 patients developed aortic anomalies during the course of surveillance, which included coarctation as well as aortic dilatation. None of these patients had any cardiovascular symptoms and the vascular abnormalities were detected on MRI at presentation or during the course of their follow-up. In patients with previously normal aortic imaging, the time interval for the lesion to be detectable varied between 2 and 6 years. In one patient there was progression of an established lesion over the 2-year period. CONCLUSION: In the few patients presented here, regular imaging at first consultation followed by every 2 years would appear to be warranted, although the exact frequency of imaging and by what modality still need to be ascertained definitively.     

Knowledge and practice of help-seeking for treatment of mental disorders in Pemba Island, Zanzibar

The objective of this study was to describe how people explain mental disorders and its treatment in Pemba Island, Zanzibar. Eight hundred and twenty-one participants (users, carers, health professionals, traditional healers, community members and leaders) were interviewed as part of a cross-sectional survey. Most people viewed mental disorder as arising within their internal or supernatural world. Although they thought that they could be helped both by primary health care and alternative healing, the majority described going to the traditional healers when things went wrong. This provides evidence that there is considerable reliance on traditional care for the treatment of mental disorders. It is therefore important for the health services to be in dialogue with the traditional healers.