Biomedical subjects

L Lyndon Key

Publications and source records attributed to L Lyndon Key.

5 recordsLinked to original sources

PubMed2005

Functional characterization of human osteoclast inhibitory peptide-1 (OIP-1/hSca) gene promoter.

We have recently identified and characterized the human osteoclast (OCL) inhibitory peptide-1 (OIP-1/hSca), a member of Ly-6 gene family. OIP-1 is an important physiologic regulator of OCL development and bone resorption activity. To determine the molecular mechanisms that regulate OIP-1 gene expression in OCL precursor cells, we isolated and characterized the OIP-1/hSca gene (2 Kb) promoter sequence. IFN-gamma (50 ng/ml) treatment of RAW 264.7 macrophage cells transfected with OIP-1 gene (-1 to -1988 bp relative to transcription start site) promoter-luciferase reporter plasmid demonstrated a significant (4 fold) increase in OIP-1 gene promoter activity. Sequence analysis of OIP-1 gene promoter region further identified a potential Stat-1 binding motif at -1629 to -1639 bp position. Stat-1 specific inhibitor, fludarabine (50 muM) abolished IFN-gamma stimulated OIP-1 gene promoter activity. Electrophoretic mobility shift assay (EMSA) further confirmed activated Stat-1 binding to the OIP-1 gene promoter sequence suggesting that IFN-gamma regulates OIP-1 gene expression in OCL precursor cells through a Stat-1 dependent signaling pathway. We further show that knock-down of TRADD enhances IFN-gamma signaling to increase OIP-1 gene expression in OCL precursor cells. These results should provide insights into the molecular control of OIP-1 gene expression and inhibition of OCL activity in the bone microenvironment.

ATPases Associated with Diverse Cellular Activitie↗

PubMed2005

Otologic manifestations of malignant osteopetrosis.

OBJECTIVE: To determine the incidence of hearing loss and describe the neurotologic manifestations over time in a large series of patients with malignant osteopetrosis. STUDY DESIGN: Longitudinal study. SETTING: Tertiary care referral center. PATIENTS: Thirty-two patients, including 19 infants (< 1 yr of age at initial visit) and 13 children (aged 1-7.6 yr at initial visit), with autosomal recessive osteopetrosis were followed-up during a 10-year period from 1991 to 2001. The average length of follow-up was 2.5 years (range, 0-9.1 yr). INTERVENTIONS: Patients underwent annual otologic evaluations including clinical examination, audiologic evaluation (auditory brainstem response, pure-tone thresholds, speech discrimination scores, and tympanograms), and high-resolution computed tomography of the temporal bone. MAIN OUTCOME MEASURES: Incidence of hearing loss, otitis media, and facial paralysis. Serial changes in temporal bone anatomy by computed tomographic scan. RESULTS: Twenty-six percent of infants' ears demonstrated hearing loss during the first year of life, and 78% of children's ears demonstrated hearing loss during the study period. Of the children's ears with hearing loss, 100% had a conductive component and 26% had an additional sensorineural component (mixed hearing loss); VIIIth nerve conduction was normal in 100% of infants and 78% of children. Five patients (16%) had unilateral facial nerve palsy. Common temporal bone findings included thickening and sclerosis of the calvarium; poor pneumatization of the mastoid bone; and narrowing of the external auditory canal, eustachian tube, and internal auditory canal. CONCLUSION: Otologic manifestations are common in malignant osteopetrosis secondary to the formation of dense, brittle bone. Frequent findings include external auditory canal stenosis, otitis media, conductive and sensorineural hearing loss, and facial nerve paralysis.

Child↗

PubMed2003

Transplanted human cord blood cells give rise to hepatocytes in engrafted mice.

Recent studies suggest that rodent hepatocytes may be derived from hematopoietic stem cells. In the current study, the potential hematopoietic origin of hepatocytes was addressed using xenogeneic transplantation of human cord blood cells. CD34(+) or CD45(+) human cord blood cells were transplanted into "conditioned" newborn NOD/SCID/beta2-microglobulin(null) mice. At 4 to 5 months post-transplantation, livers of the recipient mice were cryosectioned and examined for evidence of human hepatocyte engraftment using RT-PCR to detect human albumin mRNA, immunohistochemistry to detect human hepatocytic proteins, and fluorescence in situ hybridization (FISH) to detect the presence of human centromeric DNA. Analysis of the bone marrow of transplanted mice revealed that 21.0-45.9% of the cells were human CD45(+) cells. FISH analysis of frozen sections of transplanted mouse liver revealed the presence of engrafted cells positive for human centromeric DNA. That engrafted human cells functioned as hepatocytes was indicated by the expression of human albumin mRNA, as judged by RT-PCR. FISH analysis with human and mouse centromeric DNA probes excluded spontaneous cell fusion as the cause for the generation of human hepatocytes. Human cord blood cells can give rise to hepatocytes in a xenogeneic transplantation model. This model will be useful to further characterize the cord blood progenitors of hepatocytes.

Animals↗

PubMed2003

Juvenile osteoporosis: recognizing the risk.

Osteoporosis in children is often an undiagnosed condition. Diagnosis is usually made after several fractures occur with minimal trauma or radiographs demonstrate hypodense bones. The relationship of bone mineral density (BMD) to fracture risk in children is controversial. In our study, we were referred 16 patients between the ages of 5 and 15 years who had had two or more fractures without serious trauma. Dual-energy X-ray absorptiometry (DEXA) scans were performed to determine each patient's BMD. The mean bone density of the hip for these 16 patients assessed by z-score was -2.78 +/- 1.4 (SD); the mean BMD of the spine assessed by z-score was -3.08 +/- 1.2 (SD). Fifteen of 16 patients were osteoporotic or osteopenic in either the hip or the spine; 12 patients were osteoporotic in both the hip and the spine; one patient was osteoporotic only in the spine. These data strongly suggest that children with multiple fractures should be screened for osteoporosis.

Absorptiometry, Photon↗

PubMed2002

Three-dimensional diffuse optical tomography of bones and joints.

We present for the first time full three-dimensional (3D) volumetric reconstruction of absorption images of in vitro and in vivo bones and joints from near-infrared tomographic measurements. Imaging experiments were conducted on human finger and chicken bones embedded in cylindrical scattering media using a Clemson multichannel diffuse optical imager. The volumetric optical images were recovered with our 3D finite element based reconstruction algorithm. Our results show that 3D imaging methods can provide details of the joint structure/composition that would be impossible from two-dimensional imaging methods.

Absorption↗