No abstract

Polyhomeotic-like 3 (PHC3) is a ubiquitously expressed member of the polycomb gene family and part of the human polycomb complex hPRC-H. We found that in normal cells PHC3 associated with both hPRC-H complex components and with the transcription factor E2F6. In differentiating and confluent cells, PHC3 and E2F6 showed nuclear colocalization in a punctate pattern that resembled the binding of polycomb bodies to heterochromatin. This punctate pattern was not seen in proliferating cells suggesting that PHC3 may be part of an E2F6-polycomb complex that has been shown to occupy and silence target promoters in G 0 . Previous loss of heterozygosity (LoH) analyses had shown that the region containing PHC3 underwent frequent LoH in primary human osteosarcoma tumors. When we examined normal bone and human osteosarcoma tumors, we found loss of PHC3 expression in 36 of 56 osteosarcoma tumors. Sequence analysis revealed that PHC3 was mutated in nine of 15 primary osteosarcoma tumors. These findings suggest that loss of PHC3 may favor tumorigenesis by potentially disrupting the ability of cells to remain in G 0 .

We report on a 12-year-old boy who presented with delayed development and CNS dysmyelination. Genetic studies showed a normal 46,XY karyotype by routine cytogenetic analysis, and 46,XY.ish del(18)(q23)(D18Z1+, MBP-) by FISH using a locus-specific probe for the MBP gene (18q23). Though the patient appeared to have normal chromosome 18s by repeated high resolution banding analysis, his clinical features were suggestive of a deletion of 18q. These included hearing loss secondary to stenosis of the external auditory canals, abnormal facial features, and foot deformities. FISH studies with genomic probes from 18q22.3 to 18qter confirmed a cryptic deletion which encompassed the MBP gene. In an attempt to further characterize the deletion, whole genome screening was conducted using array based comparative genomic hybridization (array CGH) analysis. The array CGH data not only confirmed a cryptic deletion in the 18q22.3 to 18qter region of approximately 7 Mb, it also showed a previously undetected 3.7 Mb gain of 4q material. FISH studies demonstrated that the gained 4q material was translocated distal to the 18qter deletion breakpoint. The 18q deletion contains, in addition to MBP, other known genes including CYB5, ZNF236, GALR1, and NFATC1, while the gained 4q material includes the genes FACL1 and 2, KLKB1, F11 and MTNR1A. The use of these combined methodologies has resulted in the first reported case in which array CGH has been used to characterize a congenital chromosomal abnormality, highlighting the need for innovative molecular cytogenetic techniques in the diagnosis of patients with idiopathic neurological abnormalities.

This is the first reported case of human disease caused by Tricosporon dermatis, an organism recently transferred to the genus Trichosporon from Cryptococcus and now confirmed to be a human pathogen. CASE REPORTA 13-month-old male with a history of autoimmune enteropathy developed a fever of unknown origin (FUO) and malaise. The patient was the product of a full-term uncomplicated pregnancy and delivery. At 9 days of life he had a rotavirus infection and subsequently developed a malabsorption-dysmotility syndrome. The etiology of his enteropathy was unknown, but it was suspected to be autoimmune. He had been on immunosuppressant therapy, including prednisolone and tacrolimus; and his caloric needs had been maintained with total parenteral nutrition through a central venous catheter (CVC) since his first month of life. Numerous bacterial line infections had required catheter replacement, and at the time of this presentation he had a Broviac catheter in place in his right internal jugular vein. His physical examination was notable for rhinitis with a temperature of 101.0°F, and the differential diagnosis for his FUO included viral illness versus bacterial line infection. The patient had a normal total white blood cell count of 5.01 ϫ 10 6 per liter, with relative lymphopenia (5%) and neutrophilia (73%). Following the collection of blood samples for microbiologic analysis, the patient was started on intravenous vancomycin therapy.The blood specimens were taken from both the central line and a peripheral vein and were inoculated into BACTEC Plus Aerobic/F culture vials and processed in a blood culture system (BACTEC 9240 fluorescent series instruments; BD Diagnostic Systems, Sparks, MD). Growth was detected in the blood cultures after 48 h, with gram-positive organisms and yeast observed by microscopic examination. Subcultures were performed onto Trypticase soy sheep blood agar, which grew a coagulase-negative Staphylococcus, and CHROMagar, which produced mucoid mauve-colored colonies at 30°C after 24 h of incubation. Microscopic examination of subcultures grown on cornmeal agar revealed hyphae with the formation of arthroconidia and lateral and terminal blastoconidia (Fig. 1). The organism was found to be urease positive on Christensen's urea and displayed robust growth on Mycosel agar containing 0.01% cycloheximide. Urease positivity and cycloheximide resistance combined with the macroscopic and microscopic morphologies of the organism were consistent with the characteristics of Trichosporon spp. Further biochemical analysis with the VITEK 1 and 2 systems (bioMerieux, Inc., Durham, NC) identified Trichosporon mucoides with excellent confidence levels and t indices of 1.0 and 96.55, respectively. A second blood sample obtained 3 days after the initial sample was obtained, as well as a third sample obtained 8 days later, were again positive for T. mucoides. Based upon the initial colony morphology, which resembled a Candida sp. (especially Candida glabrata), a fluconazole susceptibility test was performed by the Cli...

Prostate cancer is the second leading cause of cancer deaths among American men.