Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling

Achromatopsia is an autosomal recessive disease of the retina, characterized clinically by an inability to distinguish colors, impaired visual acuity, nystagmus and photophobia. A genome-wide search for linkage was performed using an inbred Jewish kindred from Iran. To facilitate the genome-wide search, we utilized a DNA pooling strategy which takes advantage of the likelihood that the disease in this inbred kindred is inherited by all affected individuals from a common founder. Equal molar amounts of DNA from all affected individuals were pooled and used as the PCR template for short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected members of the kindred was used as a control. A reduction in the number of alleles in the affected versus control pool was observed at several loci. Upon genotyping of individual family members, significant linkage was established between the disease phenotype and markers localized on chromosome 2. The highest LOD score observed was 5.4 (theta = 0). When four additional small unrelated families were genotyped, the combined peak LOD score was 8.2. Analysis of recombinant chromosomes revealed that the disease gene lies within a 30 cM interval which spans the centromere. Additional fine-mapping studies identified a region of homozygosity in all affected individuals, narrowing the region to 14 cM. A candidate gene for achromatopsia was excluded from this disease interval by radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an essential first step in the identification of the disease-causing gene.      

US-guided percutaneous biopsy: use of a screw biopsy stylet to aid needle detection

Insertion of a screw biopsy stylet into a thin-walled biopsy needle greatly enhances detection of the needle during ultrasound-guided percutaneous biopsy. This technique is helpful when precise needle-tip localization is needed for biopsies of small lesions.     

The chemotherapy of lymphoblastic lymphoma

Thirty-two patients treated on consecutive Southwest Oncology Group (SWOG) protocols for malignant lymphoma were subsequently diagnosed as having lymphoblastic lymphoma. Combination chemistry, usually adriamycin-based, produced complete responses (CR) in 17 patients (53%). Median survival was 15 mo. Patients achieving a CR survival significantly longer than patients with partial or no response (p < 0.01). Ten of 24 patients not receiving central nervous system (CNS) prophylaxis developed leptomeningeal lymphoma while none of the seven patients who received prophylactic intrathecal cytosine arabinoside or methotrexate developed CNS lymphoma (p = 0.04). Implications of these results for planning future treatment programs of lymphoblastic lymphoma are discussed.     

Rhabdomyosarcoma-associated locus and MYOD1 are syntenic but separate loci on the short arm of human chromosome 11.

The MYOD1 locus is preferentially expressed in skeletal muscle and at higher levels in its related neoplasm, rhabdomyosarcoma. We have combined physical mapping of the human locus with meiotic and physical mapping in the mouse, together with synteny homologies between the two species, to compare the physical relationship between MYOD1 and the genetically ascertained human rhabdomyosarcoma-associated locus. We have determined that the myogenic differentiation gene is tightly linked to the structural gene for the M (muscle) subunit of lactate dehydrogenase in band p15.4 on human chromosome 11 and close to the p and Ldh-1 loci in the homologous region of mouse chromosome 7. Because the rhabdomyosarcoma locus maps to 11p15.5, MYOD1 is very unlikely to be the primary site of alteration in these tumors. Further, these analyses identify two syntenic clusters of muscle-associated genes on the short arm of human chromosome 11, one in the region of rhabdomyosarcoma locus that includes IGF2 and TH and the second the tightly linked MYOD1 and LDHA loci, which have been evolutionarily conserved in homologous regions of both the mouse and the rat genomes.     

Effect of previous hormone replacement therapy on endometrial polyps during menopause

The aim of this study was to evaluate the effect of hormone replacement therapy (HRT) on the expression of Ki-67, bcl-2 and c-erb.B2 in endometrial polyps during menopause. Sixteen patients using HRT and 24 untreated controls with endometrial polyps were enrolled in this study. Polypectomy was carried out by hysteroscopy. The presence of c-erb.B2, bcl-2 and Ki-67 expression was determined by immunohistochemistry. HRT was found to decrease Ki-67 and bcl-2 expression in endometrial polyps without affecting the c-erb.B2 staining reaction. HRT may cause endometrial polyp involution by decreasing proliferation and stimulating apoptosis.