Whither Griffiths?
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Biomedical subjects
Publications and source records attributed to L Young.
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The vibrational contribution to the free energy, entropy, and the temperature factors of the different atoms in the unit cell are calculated using the method of helix lattice dynamics for the DNA homopolymer poly(dG.poly(dC) in the B conformation. These results are compared to other theoretical calculations and the temperature (B) factors are compared to experiment as well. The problems encountered in using small molecule approximations to describe B factors in DNA like long chain molecules are discussed and a corrected estimate of the temperature factors are presented. Significant differences are found between the different theoretical approaches as reflected in the results of temperature factor calculations.
The effects of various extracellular matrices and collagenous components on the morphology, growth, and function of cultured alveolar type 2 cells is examined. Cells grown on an endothelial matrix (EC) showed the greatest adherence, some cell division, and spreading to reach confluence sooner than cells grown on an epithelial matrix or on various types of collagen. The attenuated cells from all cultures were not true type 1 cells because, on trypsinization, they detached as sheets, reverted immediately to a cuboidal shape held together by junctional complexes, and showed an apparently normal content of lamellar bodies. The greatest synthesis of disaturated phosphatidylcholine (DSPC) was seen in cells grown on EC soon after confluence, but all cultures showed reduced but equal levels of DSPC-DNA by Day 4. This occurred whether cells were attenuated or cuboidal in shape. The results suggest that some component(s) of the endothelial matrix at the alveolar basement membrane facilitates epithelial cell growth. However, over longer culture periods the matrix preparations had little effect on type 2 cell proliferation whereas function diminished. This suggests that maintenance of these cells as normal type 2 cells or their further differentiation to the type 1 form requires some additional cell derived factor(s).
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The authors compared tests of stereognosis using shape recognition and two-point discrimination with a paper-clip in evaluating sensation in the fingers of 51 patients with cerebral palsy between the ages of six and 20 years, and of 170 controls in the same age-range. The two-point discrimination test had significantly higher sensitivity in detecting tactile sensation than shape recognition, with slightly less specificity. Testing hand sensation should be part of the assessment of patients when considering reconstructive surgery, therapy, or the teaching of specific hand-skills. The two-point discrimination test with a paper-clip is a simple and reliable method of doing so.
Forty-four oxygen-dependent infants were discharged home in oxygen from an NICU during an 8-year period. Survivors were followed for 3 years. The infants' discharge diagnoses were bronchopulmonary dysplasia (BPD) (39), sleep apnea (2), and congenital cardiac defects (3). The five infants who had diagnoses other than BPD all died, but 34 of 39 infants with BPD survived. Supplemental oxygen was discontinued at a mean age of 13.4 months. The infants with BPD experienced health, growth, nutritional, neurodevelopmental and sensory problems that necessitated frequent rehospitalizations and utilization of a variety of medical and support services.
This experiment assessed the efficacy of proprioceptive and visual information for the performance of "vertical position" by synchronized swimmers. Three skill groups of 5 senior, 5 intermediate, and 5 novice synchronized swimmers performed 40 vertical positions under four conditions. The conditions were: self-initiated with and without vision, and following experimenter perturbation, with and without vision. The dependent measure was degrees of error from true vertical. Analysis indicated that either proprioception or proprioception and vision may be used in performing vertical positions. A significant main effect was found among skill groups.
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The vascular bed of the lung is susceptible to environmental and host-mediated injury from free radicals. The lung is also a frequent site for the formation of cancer metastases. Since the circulation is important for the spread of cancer and because the endothelium is a barrier between the circulation and extravascular tissue, we have postulated that free radical damage to the pulmonary microvasculature enhances the formation of metastases. Pulmonary endothelial injury was induced in mice by bleomycin (120 mg/kg i.v.) or by exposure to 90% oxygen for 2-4 days. In rats, damage was elicited by intravenous injection of cobra venom factor which activates the circulating leukocytes. Endothelial damage was demonstrated by morphology and by measurement, in lung lavage fluids, of increased protein and/or leakage of 125I-albumin, previously injected intravenously. When radiolabeled cancer cells were injected into the tail vein during periods of pulmonary endothelial damage, there was a 3-36 fold increase in the numbers of these cells located in the lung after 24 hours. Subsequently more metastatic tumors formed in the animals with injured lungs. In rats, the enhanced localization was prevented by pretreatment of the animals with catalase or with antineutrophil antibodies. We have also demonstrated that stimulation of rat cancer cells by the chemotactic peptide N-fMLP is followed by chemiluminescence, amplified in the presence of luminol. Evidence for the generation of oxygen radicals by these cells includes inhibition of the response in the absence of oxygen or in the presence of superoxide dismutase, catalase, and mannitol, and dose-dependent reduction of acetylated cytochrome C. We conclude that free radical-mediated damage to the pulmonary endothelium significantly increases the metastasis of circulating tumor cells and we postulate that some cancer cells may directly facilitate their spread by generating free radicals.
The ganglion is the most common soft tissue tumor of the hand and wrist, originating from the joint capsule or tendon sheath. Accurate diagnosis and proper treatment of these entities require a thorough knowledge of the anatomy of the wrist and hand as well as of the ganglion itself. Definitive therapy is based on total surgical removal of the cyst and its connections to the joint or tendon sheath.
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Explants of mouse lung were cultured at various stages of injury after exposure to hyperoxia for determination of whether endothelial or epithelial injury alone could stimulate fibrosis in a blood-free environment. Mice were exposed to 95% O2 for periods up to 6 days. Then one lobe of lung was prepared for organ culture, and others were used for assessment of lung damage by morphologic studies and by the protein and cellular content of bronchoalveolar lavage (BAL) fluid. Explants cultured when the lung showed endothelial injury only were not different from air-exposed controls. As alveolar damage, particularly to Type 1 epithelial cells, increased at 6 days, more protein was found by lavage; and after culture, overall DNA synthesis in explants was reduced. Autoradiography showed that epithelial cell proliferation was preferentially retarded while fibroblast growth became predominant. Collagen production was also significantly increased after 3 and 6 days of culture. In these explants there were few macrophages and no white blood cells or other blood components. Some mice, returned to air after hyperoxia, showed prompt epithelial repair, and cultures of these lungs were not different from controls. The results suggest that severe injury and retarded repair of the alveolar epithelium disturbs normal epithelial-fibroblast interactions and is sufficient to promote the fibrotic process. Less severe injury involving the endothelium only is not associated with fibrosis.
A human monoclonal antibody (IgG2, lambda), 1B8.env, was produced, reactive with the envelope glycoprotein of human immunodeficiency virus (HIV). The antibody specifically stains cells infected with HIV, as assessed by indirect immunofluorescence analysis and reacts with determinants displayed on the surface of infected cells. In Western blot analysis, the antibody reacts with bands of 160 and 41 kD, consistent with the precursor and transmembrane forms of the HIV envelope glycoprotein. The antibody also reacts specifically in immunofluorescence and Western blot analysis with cells infected with the recombinant vaccinia virus VSC-25, which contains the envelope gene of HIV. With the lambda gt11 expression vector, the epitope recognized by 1B8.env was mapped to a region of 11 amino acids in the coding region of gp41. This domain is highly conserved between several otherwise highly variable HIV isolates. In addition, this epitope appears to be recognized by the vast majority of HIV seropositive individuals. Although antibody IB8.env does not neutralize HIV virion infectivity or virally mediated cell fusion, the results presented here demonstrate the feasibility of generating and characterizing human monoclonal antibodies to HIV with these techniques. Additional antibodies produced in this manner will help to further characterize the humoral response to HIV infection, define biologically significant determinants on HIV proteins, and may be useful in clinical applications.
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