The cellular and molecular mechanisms for neutropenia in Barth syndrome

Barth syndrome (BTHS), a rare, X-linked, recessive disease, is characterized by neutropenia and cardiomyopathy. BTHS is caused by loss-of-function mutations of the tafazzin (TAZ) gene. We developed a model of BTHS by transfecting human HL60 myeloid progenitor cells with TAZ-specific shRNAs. Results demonstrate a significant downregulation in TAZ expression, mimicking the effects of naturally occurring truncation mutations in TAZ. Flow cytometry analyses of cells with TAZ-specific, but not scrambled, shRNAs demonstrate nearly twofold increase in the proportion of annexin V-positive cells and significantly increased dissipation of mitochondrial membrane potential as determined by DIOC6 staining. Transfection of TAZ-specific shRNA had similar effects in U937 myeloid cells but not in lymphoid cell lines. Further studies in HL60 myeloid progenitor cells revealed aberrant release of cytochrome c from mitochondria and significantly elevated levels of activated caspase-3 in response to TAZ knockdown. Treatment with caspase-specific inhibitor zVAD-fmk resulted in substantially reduced apoptosis to near-normal levels. These data suggest that neutropenia in BTHS is attributable to increased dissipation of mitochondrial membrane potential, aberrant release of cytochrome c, activation of caspase-3, and accelerated apoptosis of myeloid progenitor cells, and that this defect can be partially restored in vitro by treatment with caspase-specific inhibitors.     

Infection with a proposed new subspecies of Babesia canis, Babesia canis subsp. presentii, in domestic cats

Parasitemia with a large Babesia species was identified in two domestic cats from Israel. One cat, also coinfected with feline immunodeficiency virus and "Candidatus Mycoplasma haemominutum," had profound icterus and anemia which resolved after therapy, whereas a second cat was an asymptomatic carrier. Amplification and sequencing of the 18S rRNA gene, followed by phylogenetic analyses, indicated that infection was caused by Babesia canis. However, the sequences of the internal transcribed and 5.8S rRNA regions of the ribosomal operon used for subspeciation of B. canis were markedly different from the recognized subspecies of B. canis, which include B. canis vogeli, B. canis canis, and B. canis rossi. Based on phylogenetic comparisons of the 18S rRNA gene, 5.8S, and internal transcribed spacer sequences of the isolates from the cats and on the smaller sizes of the merozoite and trophozoite stages of this parasite, which distinguish it from the subspecies of B. canis present in dogs, we propose to identify the novel feline genotype of B. canis described in the present study as a new subspecies, B. canis subsp. presentii.     

Mid- to long-term outcome of disc excision in adolescent disc herniation.

BACKGROUND CONTEXT: Adolescent disc herniation and its surgical treatment have been the subjects of many published clinical series. The majority of these series were heterogeneous; the number of adolescent patients (12-17 years) as opposed to young adults (18-20 years) was generally small and the length of follow-up varied greatly. Although the short-term outcome of disc excision in adolescents was mostly favorable, their long-term outcome is unknown. OBJECTIVES: To evaluate the mid- and long-term results of discectomy in patients younger than 17 years of age. STUDY DESIGN: Retrospective examination of a series of adolescent patients under the age of 17 years who underwent surgery for lumbar intervertebral disc herniation. PATIENT SAMPLE: The medical records of 26 patients (15 males, 11 females, 12-17 years old [average 14.6]) who were operated for lumbar intervertebral disc herniation in three spine centers between 1984 and 2002 were reviewed. These subjects represented the total number of patients meeting the criteria of adolescents undergoing discectomy for lumbar disc herniation in these institutions during the study period. All patients were located and contacted by an independent observer not involved in the care of these patients. Low back pain associated with leg pain was the main clinical symptom in 20 patients (77%), leg pain in 4 (15%), and back pain in 2 (8%). They all underwent posterior disc excision: 23 (88%) patients had one level discectomy, and 3 (12%) had simultaneous discectomy at two levels. The L4-L5 interspace was involved 19 times, and the L5-S1 interspace 10 times. Slipped vertebral apophysis was diagnosed in 4 patients (15%). Twelve of the 26 patients (46%) had a first-degree relative with a history of lumbar disc herniation. OUTCOME MEASURES: Telephone interviews provided follow-up data for 26 patients. Results were classified as excellent, good, moderate, or poor according to current symptom status, the need for additional surgery, the Oswestry Disability Index, and back and leg pain scores. RESULTS: The average time from surgery to follow-up was 8.9 years (range 3-21 years). At follow-up, the clinical results were excellent in 13 patients (50%), good in 4 (15%), moderate in 8 (31%), and poor in 1 (4%). Four subjects (15%) underwent a subsequent disc excision in the lumbar region, and one of them later underwent fusion. CONCLUSIONS: Discectomy provides satisfactory clinical results in young patients with disc herniation. The rate of reintervention (15%) is comparable to that in adults, indicating that discectomy for young patients should be approached similarly to that in adults.