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Biomedical subjects

W S Ferguson

Publications and source records attributed to W S Ferguson.

13 recordsLinked to original sources
PubMed1995

Treatment of osteosarcoma with ifosfamide: comparison of response in pediatric patients with recurrent disease versus patients previously untreated: a Pediatric Oncology Group study.

This study was designed to test if the activity of a phase II agent, ifosfamide, would have been underestimated if it was tested exclusively in a population of children and young adults with recurrent osteosarcoma. The response rate to ifosfamide was compared in patients younger than 30 years of age with previously untreated osteosarcoma with metastases at diagnosis and/or unresectable primary tumors (stratum 1) with that of patients with recurrent osteosarcoma following adjuvant chemotherapy who were not previously exposed to ifosfamide (stratum 2). Evaluation of response was conducted 3 weeks after two courses of ifosfamide (2400 mg/m2 x 5 days) were administered 3 weeks apart. Nine of 33 (27%) evaluable patients in stratum 1 responded (1 complete and 8 partial responses) to ifosfamide. Among 30 evaluable patients in stratum 2, only 3 (10%) responded (1 complete and 2 partial responses; P = .04) Both groups of patients received equal doses of ifosfamide and experienced comparable toxicities. Results from this study suggest that the activity of new agents will be underestimated if tested in a population of heavily pretreated patients with recurrent disease. When possible, new chemotherapeutic agents should be tested in patients with a poor prognosis who have not been exposed to chemotherapy.

Adolescent↗
PubMed1992

Skull base dumbbell tumor: surgical experience with two adolescents.

Pediatric skull base tumors are rare and until recently were considered unresectable. We present two patients with tumors of similar anatomic position with an extracranial component in the infratemporal fossa and parapharyngeal space, an isthmus at the foramen ovale, and a superior component in the middle cranial fossa in the region of the cavernous sinus. A 15-year-old girl experienced contiguous spread of a spindle cell sarcoma; an 18-year-old boy developed a chondrosarcoma. A middle fossa approach provided the advantage of surgical avoidance of structures such as the middle ear and mastoid, facial nerve, and mandible. Postoperative recovery was rapid. Our impression is that preoperative carotid artery occlusion and a middle fossa approach for tumor resection can be performed in a young patient with acceptable morbidity and at least short-term benefit. Surgery can, therefore, provide an additional therapeutic approach to complement irradiation and chemotherapy.

Adolescent↗
PubMed1988

Serine esterase and hemolytic activity in human cloned cytotoxic T lymphocytes.

Target cell lysis by most murine cytotoxic T lymphocytes appears to be mediated by a complement (C9)-like protein called perforin, contained in high-density cytoplasmic granules. These granules also contain high levels of serine esterase activity, which may also play a role in cytolysis. Analysis of 17 cloned human cytotoxic T lymphocytes revealed the presence of serine esterase that is very similar to its murine counterpart in substrate and inhibitor specificities, pH optimum, and molecular mass; dot blot hybridization with synthetic oligonucleotides corresponding to the active sites of two known murine CTL esterases suggests homology to the murine enzyme HF. However, serine esterase was present at only approximately 10% of the level found in murine CTLs, and was not secreted during CTL-target cell interaction; moreover, hemolytic activity could not be detected in any of the seven cell lines tested. The results suggest that the human CTLs examined here kill their target cells by a mechanism different from that used by most cloned murine CTLs.

Cell Line↗
PubMed1983

Localization of the disulfide bond in human antithrombin III required for heparin-accelerated thrombin inactivation.

Heparin accelerates the rate of inhibition of thrombin by antithrombin III. Reduction of one of the three antithrombin disulfide bonds with dithiothreitol under mild conditions abolishes this rate-enhancing effect without affecting the rate of reaction in the absence of heparin. Alkylation of mildly reduced antithrombin III with [3H]iodacetic acid followed by digestion with cyanogen bromide yielded two major labeled peptides. The smaller peptide, containing Cys-422, was identified as extending from Gly-414 to the C-terminus, Lys-424. Our data are consistent with the larger labeled peptide being the one extending from Glu-104 to Met-243 and containing Cys-239. Cys-422 has been shown by others to be linked to Cys-239. These data indicate that the sensitive disulfide bond in antithrombin III extends between Cys-239 and Cys-422; the site at which thrombin cleaves the antithrombin III is between these two half-cystines.

Antithrombin III↗
PubMed1983

Formation and stability of the complex formed between human antithrombin-III and thrombin.

The inhibition of thrombin by antithrombin-III involves formation of a 1:1 covalent complex between protease and inhibitor and concomitant cleavage of the antithrombin-III peptide chain after Arg-385. The resultant fragment remains connected to the complex via a disulfide bond. This complex spontaneously breaks down into a fragment of approximately 55,000 daltons and smaller peptides. Breakdown is prevented by the presence of hydroxylamine or diisopropylflurophosphate, or by denaturation with urea. It occurs even if the purified complex is treated with diisopropylflurophosphate prior to purification, and can be greatly accelerated by the presence of small amounts of active thrombin. The initial sites of proteolytic attack on the complex are after Arg-13 of the thrombin A chain and Arg-68 of the thrombin B chain. These data indicate that active thrombin can be released from the antithrombin-thrombin complex, and that thrombin becomes more susceptible to proteolytic attack when complexed with antithrombin.

Antithrombin III↗
PubMed1981

Lead chromate.

Explore the source record for details and available documents.

Chromates↗
PubMed1980

A disulfide bond in antithrombin is required for heparin-accelerated thrombin inactivation.

Heparin accelerates the rate of reaction of antithrombin with thrombin, an effect which is abolished by mild reduction of the antithrombin with dithiothreitol. Reduced antithrombin incorporates 1.7 mol of [14C]acetamide/mol of protein, with cysteine as the only amino acid modified. Tryptic digestion of the reduced and alkylated antithrombin results in the formation of only two labeled peptides. In the absence of heparin, the second order rate constant for the reaction of thrombin with both reduced and native antithrombin is 5.9 to 9.6 x 10(5) M-1 min-1. In the presence of heparin, the rate constant for the reaction between reduced antithrombin and thrombin is 8.3 to 12.2 x 10(5) M-1 min-1, while the rate of reaction between native antithrombin and thrombin is too fast to follow under the conditions used. Reduced antithrombin elutes from a heparin-Sepharose column at 0.5 M NaCl, contrast to 10 M NaCl required for elution of the native protein. The intrinsic tryptophan fluorescence enhancement caused by heparin binding to native antithrombin is not observed with reduced antithrombin. These data indicate that cleavage of one of the three antithrombin disulfide bonds results in reduced affinity for heparin and the loss of heparin-accelerated antithrombin activity and imply that heparin and thrombin bind at different sites on the antithrombin molecule.

Antithrombins↗
PubMed1979

Statistical analysis of epidemiological data from a chromium chemical manufacturing plant.

A statistical analysis was performed on reported bronchogenic carcinoma incidence in a group of chromium chemical manufacturing workers over the period 1929 to 1977. The purpose was to determine if post-1950 process improvements corresponded to favorable trends in morbidity. Because the paucity of data on the population at risk prevented meaningful calculations of SMR's, a recently developed method called "probability window analysis" was used to evaluate for statistically valid changes in the "numerators" or number of reported cases. A significant downward trend in reported bronchogenic carcinoma was found which coincided with major process improvements made in 1951 and 1961. Although adjustment for all competing risk factors was not possible because of insufficient data on the population at risk, the improved working environment has to be considered a major contributing factor to the favorable trend.

Carcinoma, Bronchogenic↗
PubMed1977

Human physiological response and adaption to ammonia.

Other than anecdoted observations, there are no published reports on the physiological effects of ammonia at concentrations normally encountered industrially or information on whether inurement develops after repeated exposure. Six unacclimated male and female volunteers were exposed six hours per day over a six week period to concentrations of 25, 50, and 100 ppm ammonia in an industrial environment, under strict medical surveillance. Inurement to eye, nose, and throat irritation was demonstrated after two to three weeks in addition to short-term subjective adaption. There were no significant differences between subjects or controls on common biological indicators, in physical examinations, or in performance of normal job duties. After acclimation, continuous exposure to 100 ppm, with occasional excursions to 200 ppm, is easily tolerated and has no observed effect on general health.

Adaptation, Physiological↗