NGF prevents the changes induced by monocular deprivation during the critical period in rats

Photic evoked responses were recorded from the striate cortex of Long-Evans hooded intact, monocular visual deprivation (MD) and MD treated with NGF rats. The averaged visual evoked responses (AVER) were obtained from both hemispheres and provided comparison after binocular photic stimuli between the contralateral and the ipsilateral striate cortex with relation to the MD eye. One month of monocular visual deprivation at the critical period of development resulted in marked reduction of the amplitudes of AVER components as compared to the control recordings (P < 0.001). These changes of the AVER could be prevented by NGF infusion to lateral ventricle at the dosage of 2.0–2.4 μg/day for four weeks during the monocular deprivation. In conclusion, the change of AVER amplitudes induced by monocular visual deprivation during the critical period of development can be prevented by NGF infusion to lateral ventricle.     

Mapping the Von Hippel -- Lindau disease tumour suppressor gene: identification of germline deletions by pulsed field gel electrophoresis

Von Hlppel—Lindau (VHL) disease is a dominantly Inheritedfamillal cancer syndrome In which affected individuals havea greatly increased predisposition to the development of haemangloblastomasof the central nervous system and retina, renal cell carcinomaand phaeochromocytoma. The VHL gene has been mapped to chromosome3p25 -p26 by genetic linkage studies and we have previouslydemonstrated that the VHL gene is tightly linked to the D3S601locus (Zmax = 18.86 at     

Renal clearance and protein binding of melphalan in patients with cancer

Summary The renal clearance of melphalan and the fraction unbound in plasma were determined after intravenous infusion of 5 mg/m² over 5 min in nine patients with cancer to obtain information regarding the mechanism of renal handling of melphalan. Four of the patients underwent bone marrow transplantation and also received an IV dose of 220 mg/m². Total melphalan clearance after the 5 mg/m² dose ranged from 66.0 to 272 ml/min per m²; the percentage of the dose excreted unchanged in urine, from 2.5% to 92.8%; renal clearance, from 4.1 to 188 ml/min per m²; the fraction unbound in plasma, from 0.0598 to 0.460; and t_1/2, from 39.4 to 84.3 min. Unbound melphalan clearance and renal clearance calculated from the unbound fraction in plasma for each patient ranged from 441 to 3356 ml/min per m² and 15 to 961 ml/min per m² respectively and were not related to serum albumin, serum creatinine or creatinine clearance. The percentage of the dose exctreted and melphalan renal clearance were not related to urine flow. There was evidence of active secretion of melphalan in the kidney an possible reabsorption. There were no significant paired differences in melphalan disposition between the high- and low-dose studies. Highly variable renal clearance involving active secretion may contribute in part to large interpatient differences in the total plasma clearance of melphalan in patients with cancer.This study was supported by a grant from The Queen Elizabeth Hospital Research Foundation     

The role of genetics in the development of asthma and atopy

PURPOSE OF REVIEW: The mapping of complex traits such as asthma and atopy is one of the most important and central areas of human genetics. This article will present an overview of the current status of genetic studies of asthma and atopy using genome screens and association studies that have occurred in the literature since January 2003. RECENT FINDINGS: Many regions of the genome have been found to have linkage with the phenotypes of asthma and atopy. Over 70 variants in candidate genes have been reported to be associated with these phenotypes. The main regions these variants have been found are on chromosomes 2q, 5q, 6p, 11q, 12q, 16q and 17q. Five potential asthma susceptibility genes or complexes have been identified using a positional approach. These are ADAM33, DPP10, PHF11 and SETDB2, GPRA and SPINK5. It is evident that environmental factors will influence the expression of genes and the ultimate clinical phenotype of asthma and atopy. SUMMARY: The development of asthma and atopy involves many genes and environmental factors. An understanding of their genetic basis has great implications for their management.     

Role for mannose binding lectin in the prevention of Mycoplasma infection

Polymorphisms in exon 1 of the MBL-2 gene, resulting in reduced plasma levels of mannose binding lectin, were significantly overrepresented in 23 patients with primary antibody deficiency and culture-proven mycoplasma infections (P = 0.0038). This association persisted with the inclusion of a further nine suspected (doxycycline-responsive) cases (P = 0.0087). The lectin was shown to bind to three strains of mycoplasma.     

Listeria monocytogenes intragastric and intraperitoneal approximate 50% lethal doses for mice are comparable, but death occurs earlier by intragastric feeding.

The intraperitoneal (i.p.) and intragastric (i.g.) mouse approximate 50% lethal dose values (ALD50S) were determined for 15 food and clinical isolates of Listeria monocytogenes. Although all strains gave i.g. ALD50S comparable to or less than their i.p. ALD50S, the i.g. feeding of most strains produced more deaths within the first 3 days of the 6-day test than did i.p. injection. ALD50S ranged from 50 to 4.4 x 10(5) cells with approximately 1-log 95% confidence intervals. Of five strains tested by suspension in milk or by growth in milk, none gave i.g. ALD50S that were lower than those of washed cells. Results with 10- to 21-g mice supported the use of 15-g mice for i.g. testing; 21-g mice were more resistant to i.g. infection. These results indicate that i.g. feeding permits an evaluation of the role of the carrier (such as milk) in the determination of listerial virulence, permits strain characterization by i.p. and i.g. ALD50S, and emphasizes a potentially more rapid infection when the bacterium is introduced i.g.     

A duplication/paracentric inversion associated with familial X-linked deafness (DFN3) suggests the presence of a regulatory element more than 400 kb upstream of the POU3F4 gene

X-linked deafness with stapes fixation (DFN3) is caused by mutationsin the POU3F4 gene at Xq21.1. By employing pulsed field gelelectrophoresis (PFGE) we identified a chromosomal aberrationin the DNA of a DFN3 patient who did not show alterations inthe open reading frame (ORF) of POU3F4. Southern blot analysisindicated that a DNA segment of 150 kb, located 170 kb proximalto the POU3F4 gene, was duplicated. Fluorescence in situ hybridization(FISH) analysis, PFGE, and detailed Southern analysis revealedthat this duplication is part of a more complex rearrangementincluding a paracentric inversion involving the Xq21.1 region,and presumably the Xq21.3 region. Since at least two DFN3-associatedminideletions are situated proximal to the duplicated segment,the inversion most likely disconnects the POU3F4 gene from aregulatory element which is located at a distance of at least400 kb upstream of the POU3F4 gene.