Levels of serum chemokines discriminate clinical myelopathy associated with human T lymphotropic virus type 1 (HTLV-1)/tropical spastic paraparesis (HAM/TSP) disease from HTLV-1 carrier state

Approximately 5% of people infected with human T lymphotropic virus type 1 (HTLV-1) develop clinical myelopathy or tropical spastic paraparesis (HAM/TSP) that is associated with high-levels of Th1 cytokines, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha. Chemokines are known to induce cytokine secretion and direct the trafficking of immune cells to sites of disease. The present study measured serum chemokines correlated with autonomously released IFN-gamma in cell cultures. HTLV-1 infection was defined by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blot. Subjects included HTLV-1 carriers (n = 56), patients with HAM/TSP (n = 31) and healthy HTLV-1 seronegative volunteer controls (n = 20). Serum chemokines and IFN-gamma autonomously released by mononuclear cells in culture were quantified by ELISA. Compared to HTLV-1 carriers, serum chemokines in HAM/TSP patients showed significantly increased levels of CXCL9 and CXCL10, significantly diminished levels of CCL2 and similar amounts of CCL11 and CCL24. In contrast, CCL11 and CCL24 were significantly lower in serum of HAM/TSP patients than either control. IFN-gamma was positively correlated with CXCL9 and CXCL10 when HAM/TSP and HTLV-1 carriers were used as a combined group. However, despite a large proportion of HTLV-1 carriers having high IFN-gamma levels, these chemokines were not increased in carriers. This study showed that high levels of CXCL9 and CXCL10 in the systemic circulation and low serum CCL2 levels are features of HAM/TSP. HTLV-1 infection and Tax and/or additional viral encoded factor-mediated pathological processes triggering T cell activation with autogenous IFN-gamma release are probably involved in regulating chemokine release.     

Focal adhesion kinase is a blood–testis barrier regulator

In mammalian testes, such as rats, the mechanism(s) that regulate blood–testis barrier (BTB) restructuring at stages VIII–IX of the seminiferous epithelial cycle of spermatogenesis to facilitate the transit of preleptotene/leptotene spermatocytes is not known. This is due to the lack of information on the regulatory proteins at the BTB. Herein, focal adhesion kinase (FAK), a nonreceptor protein tyrosine kinase, is shown to structurally interact with occludin and ZO-1 to form a functional protein complex at the BTB. Its expression at the BTB in the seminiferous epithelium is stage specific, being lowest at stage VIII–IX tubules, analogous to the expression pattern of occludin. Using primary Sertoli cells cultured in vitro with an established tight junction (TJ) permeability barrier that mimics the BTB in vivo, the knockdown of FAK by RNAi led to a transient disruption of the TJ barrier. This was accompanied by a loss of association between occludin and ZO-1, likely the result of reduced occludin phosphorylation at Tyr and Ser residues, but not Thr, which in turn led to a redistribution of occludin at the Sertoli–Sertoli cell interface, moving from cell membrane into cell cytosol, thereby disrupting the BTB. These findings suggest that a similar mechanism is in place in the testis in vivo to regulate BTB restructuring to facilitate the transit of primary spermatocytes. Furthermore, FAK was shown to be a molecular target of cadmium because its knockdown would desensitize Sertoli cells to cadmium-induced TJ barrier disruption. In summary, FAK is a unique regulator of BTB dynamics in the testis.     

Liver transplantation in tyrosinaemia type 1: the dilemma of timing the operation

Four children with tyrosinaemia type 1 received liver transplants. The metabolic disorder was corrected and all four had normal liver function on an unrestricted diet. Two children, transplanted at age five and seven years, proved to have occult hepatocellular carcinoma and both subsequently developed pulmonary metastases. One child was well 32 months after removal of a single pulmonary metastasis but the other child died with multiple metastases. The two younger children, transplanted at age 19 and 21 months, were well 28 and 44 months after operation, one after a second liver transplant. Our experience confirms the high risk of hepatocellular carcinoma in this disease and the potential value of early liver transplantation.     

Alkaloids,amides and antispasmodic activity of Zanthoxylum hyemale

Two quinoline alkaloids, (-)-R-geilbalansine (1) and hyemaline (2), as well as aromatic amide, N-[2-(3,4-dimethoxyphenyl)-2-methoxyethyl)-2-methoxyethyl]benzamide (O-methylbalsamide) (3), were isolated as new natural products from the stem barks of Zanthoxylum hyemale, together with seven known compounds. Their structures were determined on the basis of spectroscopic data (IR, (1)H- and (13)C-NMR, MS). In addition, the antispasmodic activity of the crude extract of Z. hyemale and three other more abundant isolated compounds (4, 5 and 10) were studied in two different antispasmodic test models on isolated rat ileum and only the crude ethanolic extract presented antispasmodic activity.     

Spinal subdural haematoma mimicking tethered cord after posterior fossa open surgery

We report the MRI findings in a girl aged 3 years and 10 months who developed a spinal subdural haematoma after posterior fossa open surgery for cerebellar malignant rhabdoid tumour. Emergency surgery was performed immediately because of increased intracranial pressure. Control MRI 48 h after surgery showed a spinal subdural haematoma without clinical signs of paresis or bladder dysfunction. Spinal subdural haematoma is rare, and only few cases have been reported, especially in children. This report suggests that "silent" (without clinical symptoms) postoperative spinal acute subdural haemorrhage can occur after posterior fossa surgery.     

Primary lumbar epidural Ewing's sarcoma: case report

We report a case of a 15-years old female with an acute paraparesis secondary of an epidural mass and histopathological diagnosis was consistent with an Ewing's sarcoma without bone compromise. An exaustive literature review showed only 17 cases of primary lumbar epidural extraosseus Ewing's sarcoma.     

Eye-hand preference dissociation in obsessive-compulsive disorder and dyslexia

Dyslexia may be a development disturbance in which there are alterations in visual-spatial and visual-motor processing, while obsessive-compulsive disorder (OCD) is a psychiatric disease in which there are alterations in memory, executive function, and visual-spatial processing. Our hypothesis is that these disturbances may be, at least partially, the result of a crossed eye and hand preference. In the present study 16 controls, 20 OCD (DSM-IV criteria) and 13 dyslexic adults (Brazilian Dyslexia Association criteria) were included. All had a neurological examination, the Yale-Brown scale for obsessive-compulsive symptoms application and the Zazzó evaluation for laterality, abridged by Granjon. Results showed a right hand preference for 100% of controls, 84.6% of dyslexics, and 75% of OCD patients and a right eye preference for 73.3% of controls, 69.2% of dyslexics, and 35% of OCD patients. The left eye preference was significantly higher in OCD when compared with the two other groups (p = 0.01) and the left hand preference of OCD patients (25%) was also significant when compared to Brazilian population (4%) or British population (4.5%). It is possible that this crossed preference may be partially the reason for visual-spatial and constructive disturbances observed in OCD.