Malignant melanoma of the nasal cavity and maxillary sinus.
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Biomedical subjects
Publications and source records attributed to J L Clark.
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The records of 66 patients with osteosarcoma of the jaw were reviewed. The ages of the 42 males and 24 females ranged from 12 to 79 years (mean, 34.2 years). Swelling and pain, the most frequent presenting complaints, were noted an average of three months before the patient was seen by a physician. Fifty-one percent of the lesions involved the maxilla and 49% involved the mandible. The most common sites of involvement were the body of the mandible and the alveolar ridge of the maxilla. Radiologically, most of the lesions in the maxilla were osteoblastic (50%), whereas most of those in the mandible were osteolytic (43%). Chondroblastic osteosarcoma was the most frequent histologic type (48%) and was associated with the best survival rate (47%). Treatment included radical and local surgery with radiotherapy, chemotherapy, or various combinations. The recurrence rate for all treatment modalities was 70%. Patients treated by initial radical surgery had the best survival (80%). Survival decreased to 27% with local surgery. Of the 43 (65%) patients who died, most died with uncontrolled local disease; only four patients had documented distant metastasis, which involved lung, cervical lymph nodes, spinal column, and brain.
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The stability of both rapidly and slowly degraded proteins in wild type CHO cells is similar to that in three ts aminoacyl-tRNA synthetase mutants at both permissive and non-permissive temperatures, although the degree of tRNA charging in the synthetase mutants differs considerably with temperature. These results indicate that the altered rate of protein breakdown seen under a variety of physiological conditions in eukaryotic systems is not mediated by uncharged tRNA.
A mutant of BHK cells (ts422E) temperature-sensitive for processing 32S rRNA to 28S rRNA (Toniolo et al., '73) also loses the ability to synthesize polyamines and 5.8S rRNA when shifted to the non-permissive temperature (39 degrees). The activity of several enzymes not involved with polyamine synthesis, methylation of 32S rRNA, and small nuclear RNA production are apparently unaffected after at least 24 hours at 39 degrees. When cultures are returned to the permissive temperature (33 degrees), polyamine synthesizing capacity returns to normal as mature rRNA production resumes.
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Two patients with congenital deafness had spontaneous CSF otorrhea and recurrent bacterial meningitis. A careful workup, including tomograms, is especially important in the treatment of the closed type of CSF otorrhea. At operation of our patients, the leak was found to be at or near the oval window. The stapes was removed, and muscle was packed into the defect. The profuse flow of CSF was believed to be secondary to a wide-open cochlear aqueduct in the first case, and to an abnormal communication between the internal auditory meatus and the vestibule in the second case. These findings were the bases for the recurrent bacterial meningitis.
Sera from chickens naturally infected with Marek's disease herpesvirus (MDHV) form preciptin lines with at least two immunologically distinct soluble antigens designated MDHV-A and MDHV-B. Partial purification and characterization of the glycoprotein MDHV-A antigen was previously reported. MDHV-B was found predominantly in the sonically treated extracts of infected cells, in contrast to the predominantly extracellular MDHV-A. Analysis of these extracts from [14C]glucosamine-labeled cells by immunodiffusion with chicken anti MDHV-B serum negative for MDHV-A followed by autoradiography confirmed that MDHV-B was a common antigen between MDHV and herpesvirus of turkeys and revealed that it was also a glycoprotein. Because of their glycoprotein nature, both MDHV-A and MDHV-B bound to concanavalin A affinity chromatography columns and could then be eluted by alpha-methyl-D-mannoside and recovered for further analysis. Concanavalin A affinity chromatography was an excellent technique for initial purification of MDHV-A and MDHV-B, since approximately 5- and 15- fold purification, respectively, was achieved in a single simple step. MDHV-B was resistant to trypsin under conditions where MDHV-A was sensitive, but was similar to MDHV-A in resistance to pH 2.0 and to 1.0 or 2.0 M urea and 0.05% Brij 35. Partially purified MDHV-B was analyzed by sucrose gradient sedimentation, isoelectric focusing, and gel filtration on Sephadex G-200 in the presence of 1.0 or 2.0 M urea and 0.05% Brij 35 to purify the antigen and to determine its physical and chemical properties in comparison with those already reported for MDHV-A. MDHV-B had a much lower isoelectric point in pH 4,54, a higher sedimentation coefficient of 4.4S, and a greater molecular weight of 58,250. These data indicate that MDHV-B is physically distinct from MDHV-A antigen, although the size difference is not sufficient to allow for effective separation. In contrast, the isoelectric point difference of greater than 2 pH units makes isoelectric focusing an effective means of purifying the antigens free of one another. The four-step purification procedure achieved greater than 200-fold purification of MDHV-B. Immunization of rabbits with this highly purified antigen results in the preparation of antisera that appeared monospecific for MDHV-B in immunodiffusion.
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Seroma formation was most apparent in the A-treated groups and was probably related to the continued leakage of methyl alcohol from the graft. Warping in the pinna, fibrosis around grafts, graft resorption, and cellular infiltration were least evident in the FZ and R groups. Both produced better results than storage in BSS or A, but because radiation is far more expensive and less convenient than FZ, the latter is the better preparation and preservation technique.
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There are two forms of ornithine decarboxylase with respect to pyridoxal 5'-phosphate (pyridoxal-P) affinity in exponentially-growing Swiss 3T3 mouse fibroblasts: form I (Km approximately 10 muM) accounts for 30% of the total activity, and form II (Km approximately 0.4 muM) the remainder. Each form of the enzyme is in rapid equilibrium with ornithine and pyridoxal-P; neither form recognizes the Schiff base between ornithine and pyridoxal-P as a substrate. Total pyridoxal-P concentrations indicate that both forms may normally be at least partially active in vivo. Upon stimulation of 3T3 cells by pituitary growth factors, form I becomes undetectable within 4 h. As total activity increases over 10-fold during this time and continues to increase thereafter, a possible conversion of form I to form II could account for this increase only if the Km change reflects other changes in preexisting enzyme. The rates of cofactor dissociation are apparently the same for each form and neither rate changes with the growth state. Since rapid equilibrium kinetics apply, the forms apparently differ in their rate of cofactor association. The half-lives of the two forms in vivo are the same in unstimulated cells when measured concurrently. Also, the half-life of total activity decreases markedly upon stimulation as form II becomes dominant. These and other observations are not consistent with pyridoxal-P serving a major protective function for the enzyme in vivo.
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Addition of putrescine of spermidine prevents the increase in ornithine decarboxylase activity in cultures of 3T3 cells brought about by pituitary growth factors and results in a rapid, specific, and reversible reduction of enzyme activity in cultures previously stimulated by the growth factors. These effects are not due to polyamine toxicity and do not require other organic medium components. The amines apparently share a single carrier-mediated transport system in 3T3 cells. Methylglyoxal bis(guanylhydrazone), an inhibitor of spermidine synthesis from putrescine was found to also inhibit uptake of each amine. Studies with this drug indicate that each amine is effective without further metabolism. Since ornithine decarboxylase activity decays more rapidly in the presence of each polyamine after addition of camptothecin, the major locus of amine action appears to be in the cytoplasm. However, direct inhibition of the enzyme in vivo by assimilated amines appears to account for at most a small part of the reduction in activity, a conclusion supported by the inability to recover activity in vitro. Also, neither amine seems to act by accelerating enzyme inactivation. When amines are removed from the medium, the subsequent recovery of enzyme activity is totally prevented by trichodermin, an inhibitor of protein synthesis, but is only slightly reduced by camptothecin. It is suggested that both putrescine and spermidine reduce ornithine decarboxylase activity by selectively inhibiting translation.
Marek's disease herpesvirus A antigen was purified greater than 200-fold with a 24% recovery by ion exchange column chromatography, isoelectric focusing, and preparative polyacrylamide gel electrophoresis. The antigen had an isoelectric point of 6.68 +/- 0.03 in the presence of 1 M urea and 0.05% Brij 35, a nonionic detergent, and approximately 6.5 in the absence of dissociating agents. When analyzed by electrophoresis on analytical polyacrylamide gels, the purified antigen migrated as a single broad band which stained for both protein and carbohydrate, suggesting that it was a highly purified heterogeneous glycoprotein. However, the antigen was not purified to homogeneity as determined by electrophoresis on polyacrylamide gels in the presence of sodium dodecyl sulfate and by immunodiffusion analysis. Antibody to Marek's disease herpesvirus A antigen was prepared in a rabbit, and antibody to two contaminating antigens was removed by adsorption to yield monospecific antisera.