Detection of trisomy 12 by fluorescence in situ hybridization on archival cytopathologic material in chronic lymphocytic leukemia/small lymphocytic lymphoma.

OBJECTIVE: To evaluate fluorescence in situ hybridization (FISH) for the detection of trisomy 12 in archival cytologic specimens of chronic lymphocytic leukemia/small lymphocytic lymphoma. STUDY DESIGN: The cytopathology database was searched for all cases of chronic lymphocytic leukemia/small lymphocytic lymphoma. Six cases of chronic lymphocytic leukemia/small lymphocytic lymphoma obtained by fine needle aspiration and one case of small lymphocytic lymphoma with plasmacytoid features were analyzed for trisomy 12 by FISH. These cases had been archived between 1 week to 16 months prior to analysis. RESULTS: We detected trisomy 12 in four of the six cases of small lymphocytic lymphoma/chronic lymphocytic leukemia. The case of small lymphocytic lymphoma with plasmacytoid features was negative for trisomy 12. CONCLUSION: Detection of trisomy 12 by FISH can be effectively performed on routinely prepared, stained and coverslipped archival cytologic material.

Molecular cloning of a human homologue of Drosophila heterochromatin protein HP1 using anti-centromere autoantibodies with anti-chromo specificity.

We have identified a novel autoantibody specificity in scleroderma that we term anti-chromo. These antibodies recognize several chromosomal antigens with apparent molecular mass of between 23 and 25 kDa, as determined by immunoblots. Anti-chromo autoantibodies occur in 10-15% of sera from patients with anti-centromere antibodies (ACA). We used anti-chromo antibodies to screen a human expression library and obtained cDNA clones encoding a 25 kDa chromosomal autoantigen. DNA sequence analysis reveals this protein to be a human homologue of HP1, a heterochromatin protein of Drosophila melanogaster. We designate our cloned protein HP1Hs alpha. Epitope mapping experiments using both human and Drosophila HP1 reveal that anti-chromo antibodies target a region at the amino terminus of the protein. This region contains a conserved motif, the chromo domain (or HP1/Pc box), first recognized by comparison of Drosophila HP1 with the Polycomb gene product. Both proteins are thought to play a role in creating chromatin structures in which gene expression is suppressed. Anti-chromo thus defines a novel type of autoantibody that recognizes a conserved structural motif found on a number of chromosomal proteins.

Overlapping domains of the heterochromatin-associated protein HP1 mediate nuclear localization and heterochromatin binding.

The Drosophila protein HP1 is a 206 amino acid heterochromatin-associated nonhistone chromosomal protein. Based on the characterization of HP1 to date, there are three properties intrinsic to HP1: nuclear localization, heterochromatin binding, and gene silencing. In this work, we have concentrated on the identification of domains responsible for the nuclear localization and heterochromatin binding properties of HP1. We have expressed a series of beta-galactosidase/HP1 fusion proteins in Drosophila embryos and polytene tissue and have used beta-galactosidase enzymatic activity to identify the subcellular localization of each fusion protein. We have identified two functional domains in HP1: a nuclear localization domain of amino acids 152-206 and a heterochromatin binding domain of amino acids 95-206. Both of these functional domains overlap an evolutionarily conserved COOH-terminal region.

Genetic linkage map of 46 DNA markers on human chromosome 16.

We have constructed a genetic linkage map of human chromosome 16 based on 46 DNA markers that detect restriction fragment length polymorphisms. Segregation data were collected on a set of multigenerational families provided by the Centre d'Etude du Polymorphisme Humain, and maps were constructed using recently developed multipoint analysis techniques. The map spans 115 centimorgans (cM) in males and 193 cM in females. Over much of the chromosome there is a significantly higher frequency of recombination in females than males. Near the alpha-globin locus on the distal part of the short arm, however, there is a significant excess of male recombination. Twenty-seven (59%) of the markers on the map have heterozygosities greater than or equal to 0.50. The largest interval between loci on the sex-average map is 14 cM and the average marker spacing is 3 cM. Using loci on this map, one could detect linkage to a dominant disease on chromosome 16 with as few as 10-15 phase-known meioses.

Linkage studies with chromosome 17 DNA markers in 45 neurofibromatosis 1 families.

A locus for von Recklinghausen neurofibromatosis (NF1) has recently been mapped near the chromosome 17 centromere. We have extended these linkage studies by genotyping 45 NF1 families with three DNA probes known to be linked to the chromosome 17 centromeric region. Of 34 families informative for NF1 and at least one of the three probes, 28 families show no recombinants with the disease gene. These data provide additional support for genetic homogeneity of NF1 and for a primary NF1 locus linked to the chromosome 17 centromere. Among the informative families were 7 families with apparent new NF1 mutations. Our data suggest that these mutations are probably at the chromosome 17 NF1 locus.

Magnetic resonance imaging in marrow diseases.

Magnetic resonance imaging is an exciting and promising diagnostic tool. It employs a powerful magnet and radio frequency waves to produce details of the human body with no known risk to patients or staff. It produces superior soft-tissue contrast between muscle, fat, ligaments and tendons, nerves, and blood vessels. Magnetic resonance imaging has potential diagnostic value in avascular necroses of bone caused by trauma, Legg-Perthes diseases, sickle cell syndrome, and other conditions. It is useful in determining the extent of marrow lesions, including tumors and metabolic disturbances, muscle trauma and diseases, spinal cord and peripheral nerve lesions including compression neuropathies, and perhaps in preoperative evaluation of the patient with intervertebral disc disease.

Pubourethral supports in perspective: modified pereyra procedure for urinary incontinence.

The present study supports the thesis that failures in urethral suspensory-type operations in women with anatomic stress urinary incontinence often are caused by pull-out of suspensory sutures attached to attenuated endopelvic fascia around the urethrovesical junction. Thickening of this fascia helps impede suture pull-out. Such thickening is facilitated by detaching the fascia from the pubis to enfold it. Freeing the fascia from the inferior pubis exposes the posterior pubourethral ligaments to direct view. Binding the much stronger posterior pubourethral ligaments and enfolded fascia together with the suspensory sutures provides maximum resistance to suture pull-out. Of 54 women treated with this modified Pereyra procedure as a primary operation for anatomic stress urinary incontinence, 94.5% showed complete cure or marked improvement 4 to 6 years postoperatively.

Characteristic features of injuries in the knee in women.

There are anatomic and physiologic differences in the knee joints and supporting structures of males and females. These variations are most noticeable in the reduced muscle mass and increased mobility in women. Injuries to the knee in women differ from men because of these variations. Meniscal lesions are uncommon in women but sprains and strains occur more frequently. Internal derangements of the knee in women are often the result of their increased hypermobility. These include recurrent patellar subluxation and popliteal cysts. Meniscal tears in females are over-diagnosed and may result in unnecessary meniscectomies even in the hands of experienced orthopaedic surgeons. Arthrography and arthroscopy should increase diagnostic accuracy. Injuries in the knee in women may be reduced by better education as to the type of injury sustained, by better protection to the knee in supporting activities and by screening those women who might be more susceptible to injury.

Coxa magna.

Coxa magna is probably due to a period of relative hyperemia of the capial femur epiphysis between 2 and 8 years of age. The peripheral cartilage of the metaphysis and epiphysis proliferate as a response to reactive hyperemia secondary to synovitis. We have observed 11 patients with coxa magna and have followed five in detail. Good function is expected in childhood and adolescence, but traumatic arthritis will probably occur as these patients get older.