Localization of the KCC4 potassium-chloride cotransporter in the nervous system.

Potassium-chloride cotransporters (KCCs) collectively play a crucial role in the function and development of both the peripheral and central nervous systems. KCC4 is perhaps the least abundant KCC in the adult mammalian brain, where its localization is unknown. In the embryonic brain, KCC4 mRNA is found in the periventricular zone, cranial nerves and choroid plexus [Eur J Neurosci 16 (2002) 2358]. To investigate the distribution of KCC4 protein in the nervous system we developed a rabbit polyclonal antibody directed against a short N-terminal peptide. Western blot analysis of brain microsomal protein using purified antibody revealed the presence of a band at approximately 145 kDa, consistent with the size of a glycosylated K-Cl cotransporter. Western blot analysis of brain, spinal cord and peripheral nerves revealed high expression levels in peripheral nerves and spinal cord, with low levels in whole brain. Within the brain, the cerebral cortex, hippocampus, and cerebellum revealed minimal KCC4 expression, whereas midbrain and brainstem demonstrated higher levels. In the adult mouse brain, KCC4 staining was observed on the apical membrane of choroid plexus epithelial cells as well as in cranial nerves. All other brain structures, e.g. cortex, hippocampus, cerebellum showed no KCC4 immunoreactivity, suggesting very low or absent expression of the cotransporter in these regions. Co-staining of KCC4 with anti-MAP2, GFAP and CNPase revealed that KCC4 is expressed in peripheral neurons. Thus, KCC4 is expressed on the apical membrane of the choroid plexus, where it likely participates to K(+) reabsorption. KCC4 is also expressed in peripheral neurons, where its function remains to be determined.

Neuronal restrictive silencing element is found in the KCC2 gene: molecular basis for KCC2-specific expression in neurons.

KCC2 is one of four known isoforms of the K-Cl cotransporter with an expression pattern restricted to neurons. It mediates efflux of Cl- across neuronal membranes and plays an important role in GABAergic and glycinergic neurotransmission. To understand the molecular basis for neuronal specificity of KCC2 expression, we isolated and sequenced portions of the KCC2 gene, including some of its 5' flanking (control) region. We found a 21-bp sequence, within intron 1, that shares 80% homology to the consensus site for neuronal-restrictive silencing factor binding. We demonstrated that this specific sequence of the KCC2 gene promotes transcriptional regulation by showing that nuclear proteins isolated from a mouse neural progenitor cell line interact with this 21-bp element and by establishing that this element silences reporter gene expression in nonneuronal cells.

The characteristics of systemic lupus erythematosus. A study in a general hospital.

OBJECTIVE: There is a wide variation in the natural history of Systemic Lupus Erythematosus among different ethnic and geographical groups. Studies in Arabs are few. This study aims to demonstrate the clinical characteristics of Systemic Lupus Erythematosus patients in Jordanians. METHODS: A retrospective review of the records of the cases diagnosed as Systemic Lupus Erythematosus in a tertiary referral centre (King Hussein Medical Centre) over the years 1991-1997. The records were analyzed for age, sex, presentation, diagnostic criteria, investigations, complications and treatment. RESULTS: Seventy-six records were analyzed. The patients were from all parts of Jordan, with a mean age of 20 years. The female: male ratio was 24:1. The presentation was arthralgia-arthritis in 68 (89%) patients; skin manifestations in the form of malar rash in 32 (42%), photosensitivity in 19 (25%). Central nervous system manifestations were also noted in 21 (27%) of the patients. Anti-nuclear antibodies were positive in 71 (93%) patients, anti double stranded DNA (DsDNA) positive in 80%. Anemia and leukopenia or both were noted in 52 patients(69%). Erythrocyte Sedimentation Rate was more than 30mm in the first hour in 49 (88%) patients. Lupus anticoagulants were negative in 75% of patients, renal impairment was documented in 46% of the patients (35 patients) with positive correlation to DsDNA. All the patients received steroids, 95% (73) in the form of prednisolone and 5% in the form of methylprednisolone; cytotoxics either cyclophosphamide or azathioprine mainly for renal disease were prescribed to 25 patients, Complications were hypertension (18 patients), renal failure (7 patients), cerebral vascular disease (3 patients). Death was recorded in 3 subjects within 1-4 years of diagnosis CONCLUSION: This study demonstrates the presentations of Systemic Lupus Erythematosus patients with a high incidence of complications, which may be due to late presentation or late diagnosis. Further studies are needed on the natural history of this disease in Jordanians.

Gastric cancer in Jordan.

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