Positional cloning of the gene for X-linked retinitis pigmentosa 3: homology with the guanine-nucleotide-exchange factor RCC1

The gene for retinitis pigmentosa 3 (RP3), the most frequent form of X- linked RP (XLRP), has been mapped previously to a chromosome interval of less than 1000 kbp between the DXS1110 marker and the OTC locus at Xp21.1-p11.4. Employing a novel technique, YAC Representation Hybridization (YRH)', we have recently identified a small XLRP associated microdeletion in this interval, as well as several putative exons including the 3' end of a gene that was truncated by the deletion. cDNA library screening and sequencing of a cosmid centromeric to the deletion has now enabled us to identify numerous additional exons and to detect several point mutations in patients with XLRP. The predicted gene product shows homology to RCC1, the guanine-nucleotide- exchange factor (GEF) of the Ras-like GTPase Ran. Our findings suggest that we have cloned the long-sought RP3 gene, and that it may encode the GEF of a retina-specific GTP-binding protein.      

Falloposcopy in conjunction with laparoscopy: possibilities and limitations

Falloposcopy is a transvaginal microendoscopic technique to explore the human Fallopian tube from the uterotubal ostium to the fimbrial end. Falloposcopy provides a unique possibility to visualize endotubal disease and may be used therapeutically for removal of debris and for cutting down filmy intraluminal adhesions. To assess the clinical performance of falloposcopy as part of an infertility investigation, a total of 43 women scheduled for laparoscopy as part of an investigation of infertility had a falloposcopy performed in conjunction with the laparoscopy. All women were investigated at Danderyd Hospital, Stockholm and Akademiska Hospital, Uppsala, during 1995 and 1996. Images from the endosalpinx were obtained in 26 of 43 women (60.5%). In 10 women (23.3%), it was possible to obtain images from both tubes. No images were of sufficient quality to describe the entire tubal mucosa in detail. Falloposcopy represents a unique tool for visualization of endotubal disease and may provide a valuable instrument for in-vivo exploration of tubal physiology. However, certain technical problems limit the usefulness of this method in routine clinical practice. These technical problems have to be solved before falloposcopy can achieve a central position in investigation and treatment of tubal disease.      

Modulation of acute visceral nociception and bladder inflammation by plant triterpene, α, β-amyrin in a mouse model of cystitis: role of tachykinin NK<Subscript>1</Subscript>-receptors,and K<Superscript>+</Superscript><Subscript>ATP</Subscript> channels

Objective and design: We previously described the visceral antinociceptive property of α, β-amyrin in a mouse model of cystitis induced by cyclophosphamide (CPM). This study examined the contribution of vanilloid-1 (TRPV1), peripheral NK1 receptors to CPM-evoked nociceptive behaviors and bladder edema, and its possible modulation by α, β-amyrin. Methods: The effect of α, β-amyrin (10, 30, and 100 mg/kg, p. o.) and N-acetylcysteine (NAC) on CPM (400 mg/kg, i. p.)-induced cystitis was studied in mice. Sensory deafferentation was done by a high dose capsaicin. The parameters analysed were: CPM-evoked noxious behaviors, bladder edema, vascular permeability, and NK₁ immunoreactivity. To assess the role of K⁺ _ATP channels in α, β-amyrin effect, animals were pretreated with glibenclamide. Results: α, β-amyrin (30 and 100 mg/kg) and NAC significantly (p < 0.01) suppressed the visceral pain-related behaviors and NK₁ immunoreactivity, but bladder edema was reduced weakly. Glibenclamide reversed the effects of α, β-amyrin. Sensory deafferentation by capsaicin significantly reduced the nociceptive responses and the NK₁ immunoreactivity to noxious stimulation by CPM. Conclusions: α, β-amyrin attenuates CPM-induced visceral pain and bladder edema by mechanisms that involve, at least in part, a block either of Substance P release or its receptor function, and partly by opening K⁺ _ATP channels. Received 13 February 2007; returned for revision 13 April 2007; accepted by G. Geisslinger 14 May 2007     

Translocation (11;11)(p13- p15;q23) in a child with therapy-related acute myeloid leukemia following chemotherapy with DNA-topoisomerase II inhibitors for Langerhans cell histiocytosis

We report a new case of therapy-related acute myeloid leukemia in a child with Langerhans cell histiocytosis. This patient was previously treated with a protocol of multidrug chemotherapy, containing a relatively low dose of etoposide (total dose of 900/m(2)). Twenty-six months after the end of the therapy, the patient returned to the hospital with fever and anemia. The white blood cell count was 53 x 10(9)/L. The bone marrow examination showed massive infiltration with French-American-British acute myeloid leukemia classification M4 blast cells. The patient did not respond to an intensive treatment with high dose ARA-C and idarubicin. He died 6 months later. The cytogenetic abnormality of the blast cells was a t(11;11)(p13 -15;q23), that has not been described before in a secondary leukemia case.     

A follow-up linkage study supports evidence for a bipolar affective disorder locus on chromosome 21q22

Evidence for linkage between bipolar affective disorder (BP) and 21q22 was first reported by our group in a single large pedigree with a lod score of 3.41 with the PFKL locus. In a subsequent study, with denser marker coverage in 40 multiplex BP pedigrees, we reported supporting evidence with a two-point lod score of 2.76 at the D21S1260 locus, about 6 cM proximal to PFKL. For cost-efficiency, the individuals genotyped in that study comprised a subset of our large pedigree sample. To augment our previous analysis, we now report a follow-up study including a larger sample set with an additional 331 typed individuals from the original 40 families, improved marker coverage, and an additional 16 pedigrees. The analysis of all 56 pedigrees (a total of 862 genotyped individuals vs. the 372 genotyped previously), the largest multigenerational BP pedigree sample reportedly analyzed to date, supports our previous results, with a two-point lod score of 3.56 with D21S1260. The 16 new pedigrees analyzed separately gave a maximum two-point lod score of 1.89 at D21S266, less than 1 cM proximal to D21S1260. Our results are consistent with a putative BP locus on 21q22.     

Viral etiopathogenesis of Sjögren's syndrome: role of the hepatitis C virus

Patients with hepatitis C virus (HCV) chronic infection present some extrahepatic manifestations that may mimic the clinical, immunologic and histological manifestations of primary Sj?gren's syndrome (SS). Thus, HCV patients with sicca symptomatology and positive autoantibodies could be misdiagnosed as a 'primary' SS. Nevertheless, there are several clinical and immunologic features that could help us differentiate both processes.     

Prenatal haloperidol treatment decreases nerve growth factor receptor and mRNA in neonate rat forebrain.

Pregnant rats were treated daily with haloperidol (2 mg/kg) for 11 days until 1 day before birth. The levels of nerve growth factor (NGF), its receptor (NGFR) and NGFR-mRNA were measured in forebrain of 2-day old postnatal rats. Using Northern blot analysis, we observed a decrease in NGFR-mRNA. Furthermore, in binding studies, Kd and Bmax of treated rats were lower than in controls, but only in the low affinity binding sites. However NGF and its mRNA did not change after haloperidol treatment. In conclusion, our results suggest that prenatal haloperidol treatment can modify the development of forebrain cells, by changing NGFR expression.     

Evaluation of Etest strips for rapid susceptibility testing of Mycobacterium tuberculosis

In this study, our objective was to evaluate Etest strips containing exponential gradients of isoniazid (INH), rifampin (RIF), and streptomycin (STR) for susceptibility testing of Mycobacterium tuberculosis. M. tuberculosis isolates were tested for antimicrobial susceptibilities by the standard proportion method using L?wenstein-Jensen (LJ) medium and by the Etest. The MICs determined by the Etest were obtained at 5, 7, or 10 days. In some strains with Etest-discrepant results, radiometric susceptibility testing (BACTEC) was performed to determine a consensus result. M. tuberculosis concordance between the two methods was 97% (86 of 89 isolates) for RIF, 96% for INH (84 of 87 isolates), and 80% (61 of 76 isolates) for STR. Most of the MICs determined by the Etest were easy to interpret and readable within 5 days. Results correlated well with those obtained by the LJ proportion and BACTEC methods for INH and RIF. However, a high proportion of false-sensitive and false-resistant results were observed, most often for STR. We also observed that variations in the inoculum size of M. tuberculosis isolates affected the MICs to a substantial degree. These discrepancies, along with the expense of the media, the Etest strips, and the specialized equipment required (CO2 incubator), make this method less useful in developing countries.