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Biomedical subjects

C Rosen

Publications and source records attributed to C Rosen.

At least 73 records · Page 4Linked to original sources
PubMed1996

Endoscopic laser medial arytenoidectomy versus total arytenoidectomy in the management of bilateral vocal fold paralysis.

Bilateral laryngeal paralysis can result in severe airway compromise. A widely accepted treatment is endoscopic laser total arytenoidectomy (TA); however, vocal results are usually poor. An alternative approach, resection of only the medial portion of the arytenoid (medial arytenoidectomy [MA]), has the potential for less vocal impairment, but may not provide a sufficient airway. Laryngeal resistance (LR) was measured in vivo and ex vivo in 12 adult mongrel dogs with bilateral laryngeal paralysis after TA, MA, or no surgery (controls). The LR was significantly lower than in controls in both TA and MA, but there was no significant difference between TA and MA. Glottic area was also significantly higher in both MA and TA compared to controls, but again, there was no significant difference between TA and MA. Phonation could be elicited in all controls and 2 of 4 dogs with MA, but no dogs with TA. Our results show that MA offers airway improvement similar to that with TA and also has the potential for better vocal function.

Animals↗
PubMed1995

Differentiating between orchiectomized rats and controls using measurements of trabecular bone density: a comparison among DXA, histomorphometry, and peripheral quantitative computerized tomography.

In studies of rat bone metabolism, trabecular bone density should be measured. Three established methods of measuring trabecular bone include trabecular bone volume by histomorphometry (BV/TV%), trabecular bone density by peripheral quantitative computerized tomography (pQCT), and areal bone density of trabecular-rich regions by dual x-ray absorptiometry (DXA). We compared the ability of these three methods to discriminate between orchiectomized (orchidectomized) rats and controls. Sixteen male Sprague-Dawley rats (400-425 g) were orchiectomized, and 16 others were controls. In vivo spine bone mineral density (BMD) was measured at the beginning of the study and again after 11 weeks. Rats were sacrificed, and ex vivo BMDs of the right femur and tibia were measured by DXA, followed by trabecular bone density of the right proximal tibia by pQCT. BT/TV% of the left proximal tibia was measured by histomorphometry. Differences between groups were detected by all three methods, but both the magnitude of the difference between groups and the variance of the measurements was much greater for histomorphometry and pQCT than for DXA. Consequently, the statistical significance for the difference between groups was comparable for all three methods. Of the sites measured with DXA, the proximal tibia had the greatest statistical significance for the difference between groups. In summary, all three methods can demonstrate the effect of orchiectomy on trabecular bone. The large differences between groups seen by histomorphometry are also seen by pQCT but not by DXA. We conclude that trabecular bone density by pQCT may be a reasonable surrogate for measurements by histomorphometry.

Absorptiometry, Photon↗
PubMed1995

Infant apnea detection after herniorrhaphy.

STUDY OBJECTIVE: To elucidate risk factors for apnea in preterm infants discharged from the hospital and in full-term healthy infants. To determine the efficacy of real-time cardiopulmonary monitoring versus computerized storage and retrieval for infants at risk. STUDY DESIGN: Prospective study. SETTING: Operating rooms and pediatric patient care units of university medical center. PATIENTS: 27 preterm infants and 20 full-term infants no more than 60 weeks' post-conceptional age, who were admitted for elective herniorrhaphy. INTERVENTIONS: Infants were monitored before and after herniorrhaphy with general anesthesia using an infant apnea impedance monitor, pulse oximetry, and nursing observation. MEASUREMENTS AND MAIN RESULTS: Demographic information and medical history were correlated with postoperative apnea. The sensitivity and specificity of nursing observation and oximetry were compared with computerized apnea monitors. Five patients (11%, four preterm, one full-term) were apneic postoperatively as recorded by computerized pneumocardiography. Previous apnea history, gestational age at birth, and postconceptional age at operation positively correlated with postoperative apnea. Nursing observation failed to detect 4 of 5 patients with documented apnea (sensitivity 20%, positive predictive value 50%). Pulse oximetry failed to detect 3 of 5 patients with apnea (sensitivity 40%, positive predictive value 66%). CONCLUSIONS: Although it is easier to predict postoperative respiratory dysfunction in previously sick or very young infants, absolute predictability for all neonates remains elusive. Clinical monitors with both storage and retrieval capabilities and real-time monitoring increase our ability to detect significant events in children at risk for apnea after herniorrhaphy.

Apnea↗
PubMed1994

Structural characterization of broadly neutralizing human monoclonal antibodies against the CD4 binding site of HIV-1 gp120.

The human monoclonal antibodies (mAbs) 15e and 21h are derived from HIV-1-infected individuals. They block CD4 binding, recognize conformation-dependent discontinuous epitopes on gp120 and neutralize a broad range of laboratory strains and primary isolates of HIV-1. To determine if a structural basis for neutralization could be identified, analysis of these CD4-binding site anti-gp120 human mAbs was performed, common features and differences were identified and a comparison was made with F105, a previously reported CD4-binding site anti-gp120 human mAb. The 15e and 21h mAb heavy chains are derived from different V region genes, i.e. V2-1 and VDP-35, which are members of the VHIV and VHIII families, respectively. Analysis of the genes encoding the heavy chain complementarity determining region (CDR) 3 revealed that both mAbs show a long DH segment of similar size that could arise from D-D fusions of the dxp1/dlr1 and daudi/d22-12 germline DH genes along with use of the JH6 and JH5 germline segments. Similarly, the 15e and 21h light chains are derived from different V region genes, i.e. Hum01/012 and Hum1v318, that are members of the V kappa I and V lambda IIIa gene families, respectively. These V genes are rearranged with J kappa 1 and J lambda 2 germline genes. For both mAbs, the pattern of replacement mutations in the V region genes of the heavy and light chains is consistent with a process of somatic mutation and antigen-driven clonal selection. By comparing the CDRs of 15e, 21h and F105, eight positions in the rearranged heavy chains and two positions in the rearranged light chains were found to have identical amino acids. These studies suggest that there is no absolute restriction in the use of V region germline genes and form the foundation for understanding the humoral immune response to the CD4-binding site of gp120.

Amino Acid Sequence↗
PubMed1993

Defective mitosis due to a mutation in the gene for a fission yeast 26S protease subunit.

We have isolated a mutant, mts2, in the fission yeast Schizosaccharomyces pombe which is defective in chromosome segregation. The predicted amino-acid sequence of the cloned mts2+ gene product is 75% identical to the S4 subunit of the human 26S ATP/ubiquitin-dependent protease. The human S4 subunit complementary DNA expressed from an S. pombe expression plasmid can rescue an S. pombe mts2 gene disruption. Both observations demonstrate that the mts2+ gene is the S. pombe homologue of the human S4 subunit. In addition, we provide genetic evidence for a physical interaction between the S4 and the related S7 subunit in the 26S multiprotein protease. We show that polyubiquitin-conjugated proteins accumulate in the mts2 mutant at the restrictive temperature, demonstrating that the mutant has an in vivo defect in the ubiquitin-dependent proteolysis pathway. Finally, the phenotype for the mts2 mutant indicates that protein degradation by the 26S protease is essential not for entry into but for the completion of mitosis.

Amino Acid Sequence↗
PubMed1993

1,25-Dihydroxyvitamin D3 increases secretion of insulin-like growth factor binding protein-4 (IGFBP-4) by human osteoblast-like cells in vitro and elevates IGFBP-4 serum levels in vivo.

Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) are thought to play an important role in the regulation of bone metabolism. In the present study, we investigated the effect of 1,25-dihydroxyvitamin D(3) [1,25-(OH)2D3] on the expression and secretion of IGFBPs in human osteoblast-like osteosarcoma cells (MG63) and untransformed human bone-derived cells in vitro. Northern blot analysis revealed that 1,25-(OH)2D3 (10(-8) mol/L) increased IGFBP-4 messenger RNA maximally 11-fold over control level in MG63 cells (after 24 h treatment) and 2.8-fold in human bone-derived cells (at 10(-10) mol/L). 1,25-(OH)2D3 increased secretion of IGFBP-4 2- and 3-fold, respectively, in MG63 cells and in human bone-derived cells. In normal human bone-derived cells, 1,25-(OH)2D3 also stimulated messenger RNA expression (3.9-fold) and the secretion of IGFBP-3 (2.2-fold). 1,25-(OH)2D3 also increased IGFBP-4 expression in skin fibroblasts but not in hepatocellular carcinoma cells. Consistent with these in vitro findings, treatment of human subjects with high doses of oral 1,25-(OH)2D3 (2-3 micrograms/day) for psoriasis resulted in a significant increase in serum IGFBP-4 concentration compared with pretreatment levels. Our observations present direct evidence that 1,25-(OH)2D3 plays an important role in the regulation of IGFBP secretion in vitro and in vivo.

Adult↗
PubMed1992

Osteoporosis after spinal cord injury.

Dual-photon absorptiometry characterized bone loss in males aged less than 40 years after complete traumatic paraplegic and quadriplegic spinal cord injury. Total bone mass of various regions and bone mineral density (BMD) of the knee were measured in 55 subjects. Three different populations were partitioned into four groups: 10 controls (healthy, age matched); 25 acutely injured (114 days after injury), with 12 reexamined 16 months after injury; and 20 chronic (greater than 5 years after injury). Significant differences (p less than 0.0001) in bone mass mineral between groups at the arms, pelvis, legs, distal femur, and proximal tibia were found, with no differences for the head or trunk. Post hoc analyses indicated no differences between the acutely injured at 16 months and the chronically injured. Paraplegic and quadriplegic subjects were significantly different only at the arms and trunk, but were highly similar at the pelvis and below. In the acutely injured, a slight but statistically insignificant rebound was noted above the pelvis. Regression techniques demonstrated early, rapid, linear (p less than 0.0001) decline of bone below the pelvis. Bone mineral loss occurs throughout the entire skeleton, except the skull. Most bone loss occurs rapidly and below the pelvis. Homeostasis is reached by 16 months at two thirds of original bone mass, near fracture threshold.

Absorptiometry, Photon↗
PubMed1992

Interaction of cellular factors with intragenic cis-acting repressive sequences within the HIV genome.

Expression of the human immunodeficiency virus (HIV) structural gene products is suppressed in the absence of the Rev protein. The block to expression reflects, in part, nuclear retention of those mRNAs which encode the structural proteins. The presence of intragenic cis-acting repressive sequences (CRS) and inefficient splicing of the primary viral transcript are thought to contribute to nuclear entrapment of viral RNA. To elucidate the mechanism for repression of HIV gene expression, the ability of a 270-bp segment of the pol gene shown previously to repress gene expression to interact with cellular factors was investigated. Incubation of RNA corresponding to the 270-bp CRS element with nuclear extract prepared from human T-cells revealed a strong and specific interaction with several cellular factors. Covalent cross-linking of the RNA-protein complex demonstrated the presence of at least three proteins, the predominant one having a molecular weight of approximately 42 kDa. A monoclonal antibody raised against hnRNP C, a component of the splicing machinery, recognized the CRS-protein complex, suggesting that hnRNP C or a closely related gene product interacts with CRS-containing RNA. Consistent with this conclusion, addition of RNA corresponding to a beta-globin intron sequence in the binding reaction completely blocked formation of the CRS-protein complex. These findings raise the possibility that the CRS elements elicit nuclear entrapment of viral RNA through formation of RNA-protein complexes that are not accessible to nuclear export pathways.

Gene Expression Regulation, Viral↗
PubMed1992

The 24/25-kDa serum insulin-like growth factor-binding protein is increased in elderly women with hip and spine fractures.

Fractures of the hip in elderly women represent a clinical syndrome (age-related osteoporosis) often marked by decreased calcium absorption and secondary hyperparathyroidism. We studied 13 elderly women with fractures of the hip and spine and 18 healthy similarly aged control women to determine whether serum insulin-like growth factor-I (IGF-I) or its carrier binding proteins (IGFBPs) were altered in this syndrome. Serum IGF-I concentrations were not different in the two groups (P = 0.50), but immunoreactive PTH was significantly higher in the fracture group (58.50 +/- 8.20 vs. 13.50 +/- 2.70 ng/L; P less than 0.003). Binding of [125I]IGF-I to IGFBP-3, IGFBP-2, and IGFBP-1, measured by ligand blotting, was not statistically different in the 2 groups, but binding intensities for the serum 24/25-kDa IGFBP were approximately 2.5 times greater in fracture women than control women (P less than 0.0005). In data pooled from both groups, PTH correlated strongly (r = 0.70; P less than 0.0001) with the relative binding intensities for the 24/25-kDa IGFBP. Based on previous work, we speculate that production of the 24/25-kDa IGFBP, which in vitro is known to inhibit IGF-I- and IGF-II-mediated osteoblast function, may be stimulated by PTH in patients with the syndrome of age-related osteoporosis.

Aged↗
PubMed1991

Lumbar facet fracture as a possible source of pain after lumbar laminectomy.

This study compared 50 patients with lumbar facet fractures and continued pain after lumbar laminectomy with a postlaminectomy control group without facet fractures. Computed tomographic analysis compared variables including direct measurements of bone resection. Average follow-up between surgery and postsurgical computed tomographic examination was 3.2 years. In the fracture group, more than one half of the bone immediately above the flare of the inferior articular process at the level of the laminectomy, measured in a medial to lateral direction, had been resected. No one in the control group had more than one quarter of this bone removed (P = .0001). Lumbar facet fractures may be one cause of late postlaminectomy pain. Caution in resection of a particular area of bone may avoid this problem.

Follow-Up Studies↗