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Biomedical subjects

R Chandler

Publications and source records attributed to R Chandler.

12 recordsLinked to original sources

Randomized study of preoperative versus postoperative radiation therapy in advanced head and neck carcinoma: long-term follow-up of RTOG study 73-03.

This is a report of a 10-year median follow-up of a randomized, prospective study investigating the optimal sequencing of radiation therapy (RT) in relation to surgery for operable advanced head and neck cancer. In May 1973, the Radiation Therapy Oncology Group (RTOG) began a Phase III study of preoperative radiation therapy (50.0 Gy) versus postoperative radiation therapy (60.0 Gy) for supraglottic larynx and hypopharynx primaries. Of 277 evaluable patients, duration of follow-up is 9-15 years, with 7.6% patients lost to follow-up before 7 years. Loco-regional control was significantly better for 141 postoperative radiation therapy patients than for 136 preoperative radiation therapy patients (p = 0.04), but absolute survival was not affected (p = 0.15). When the analysis was restricted to supraglottic larynx primaries (60 postoperative radiation therapy patients versus 58 preoperative radiation therapy patients), the difference for loco-regional control was highly significant (p = .007), but not for survival (p = 0.18). In considering only supraglottic larynx, 78% of loco-regional failures occurred in the first 2 years. Thirty-one percent (18/58) of preoperative patients failed locally within 2 years versus 18% (11/60) of postoperative patients. After 2 years, distant metastases and second primaries became the predominant failure pattern, especially in postoperative radiation therapy patients. This shift in the late failure pattern along with the increased number of unrelated deaths negated any advantage in absolute survival for postoperative radiation therapy patients. The rates of severe surgical and radiation therapy complications were similar between the two arms. Because of an increased incidence of late distant metastases and secondary primaries, additional therapeutic intervention is required beyond surgery and postoperative irradiation to impact significantly upon survival.

Adult

Isolation of transferrin from porcine gastric mucosa: comparison with porcine serum transferrin.

1. An iron-binding glycoprotein has been purified to homogeneity from porcine gastric mucosa. 2. The molecular weight (80,000), amino acid composition, carbohydrate content, N-terminal amino acid sequence, tryptic map, stoichiometry of iron binding (2 mol/mol), visible absorption spectrum of the ferric complex and chromatographic behaviour of the gastric protein are all strikingly similar to the corresponding properties of porcine serum transferrin. 3. The quantity of the gastric protein (1.3 mg/g wet weight) present in the gastric mucosa suggests that it is not serum transferrin (plasma concentration 1.8 mg/ml) contaminating the tissue. 4. A role for transferrin in the uptake of dietary iron by the gastrointestinal tract is proposed.

Amino Acid Sequence

DNA analysis by flow cytometry.

Accurate quantification of DNA from cells of several species is possible with flow cytometry. When one species is used as a reference, cytometric readings from two or more different species can be compared to obtain relative percent DNA or DNA indices. Differences in DNA from the male and female of the same species also can be measured. The method allows rapid screening of chromosomal abnormalities among large clinical populations, and evaluation of errors of sex determination such as XY sex reversal.

Animals

Structural studies on a 75-kDa glycoprotein isolated from porcine gastric mucosal membranes: close homology with the 78-kDa glucose-regulated family of proteins.

A 75-kDa glycoprotein (P75) has been purified to homogeneity from washed membranes isolated from the corpus of porcine gastric mucosa. The purification procedure employed chromatography on concanavalin A-Sepharose and DEAE-Sepharose, and preparative polyacrylamide gel electrophoresis. Reversed-phase microbore high-performance liquid chromatography was employed to fractionate and purify a number of tryptic peptides generated from approximately 1100 pmol purified P75. The use of reversed-phase microbore (2.1 mm internal diameter) columns facilitated the purification of subnanomole amounts of polypeptides in small volumes (40-60 microliter) suitable for loading onto the gas-phase sequencer without further concentration. N-Terminal amino acid sequence analyses were performed on the intact polypeptide and on 13 tryptic peptides and one Staphylococcus protease V8 peptide, yielding 170 unique assignments; this corresponds to approximately 26% of the molecule. A comparison of this amino acid sequence information with the cDNA-deduced primary structure of a 70-kDa heat-shock-related protein (P72), which is expressed in normal rat liver reveals that these protein sequences are almost identical, differing in only 1 of the 170 positions positively assigned thus far. The probable correspondence of P72 with the 78-kDa glucose-regulated protein (GRP78) isolated from hamster fibroblasts has been reported.

Amino Acid Sequence

Identification of a gastrin binding protein in porcine gastric mucosal membranes by covalent cross-linking with iodinated gastrin.

A gastrin binding protein (GBP) has been identified in detergent extracts of porcine gastric mucosal membranes by covalent cross-linking to 125I-[Nle15]gastrin with disuccinimidyl suberate. The apparent molecular weight of the cross-linked complex (80,000) is uneffected by reduction suggesting that the GBP is not composed of disulfide-bonded subunits. Subtraction of the molecular weight of 125I-gastrin indicates that the molecular weight of the GBP is 78,000. A similar molecular weight has been observed previously for the gastrin receptor (74,000) on intact canine parietal cells and plasma membranes therefrom, and for the receptor for the related hormone cholecystokinin (76,000-85,000) on pancreatic acinar membranes under reducing conditions. The similarity in molecular weight between the gastrin receptor and the solubilized GBP suggests that the latter protein is probably the gastrin receptor. However, the concentration (2 microM) of [Nle15]gastrin required for 50% inhibition of cross-linking of gastrin to the GBP solubilized in 0.1% Triton X-100 is 200-fold greater than the value (10 nM) observed for the gastrin receptor on isolated canine gastric parietal cells. A lower concentration (0.3 microM) of [Nle15]gastrin was required to inhibit cross-linking in a milder detergent (0.4% digitonin, 0.08% cholate). Thus, the reduced affinity for gastrin of the putative solubilized form of the gastrin receptor appears to be a result of detergent extraction.

Animals

Binding of gastrin to gastric transferrin.

Binding of 125I-gastrin to porcine gastric transferrin has been demonstrated by covalent cross-linking with disuccinimidyl suberate. The concentration of gastrin required to reduce cross-linking by 50% was approx. 100 microM. The occurrence of both gastrin and gastric transferrin in porcine gastric mucosa and lumen suggests a novel synergistic role for the observed interaction in the uptake of dietary iron.

Animals

Treatment of femoral neck fractures with total hip replacement versus cemented and noncemented hemiarthroplasty.

A prospective study of displaced femoral neck fractures was conducted with patients randomized into three groups: cemented total hip replacement (THR), cemented hemiarthroplasty (UHR-C), and noncemented hemiarthroplasty (UHR-NC). Eighty-nine patients were treated for displaced (Garden type 3 or 4) fracture with a prosthesis; 39 patients had THR, 37 had UHR-C, and 13 had UHR-NC. No difference was found in the level of pain, ambulation, or aids required between the THR group and the UHR-C group, except for active community ambulators, who demonstrated decreased endurance capability when treated with UHR-C. The patients treated with UHR-NC had increased pain and decreased ambulation and required assistive devices. The most significant complication was dislocation, which occurred in 7 patients with THR and 2 with UHR-C. The mortality rate at 2 years was 18%; all but two of the deaths were in patients with one of five different medical diseases: clinically significant cardiac or pulmonary disease, cancer, alcoholism, or psychosis. The mortality rate was insignificant in patients younger than 70 years of age. Roentgenographic review showed only 2 of 76 cemented stems with progressive cement-bone demarcation, with one patient requiring revision for a loose prosthesis. No evidence of protrusio was seen with the use of the bipolar cap. The uncemented hemiarthroplasties demonstrated lucency between the metal and bone in the proximal femur in 9 of 13 stems. The authors make recommendations regarding hip replacement.

Adult

Comparison of the distribution and binding of monoclonal antibodies labeled with 131-iodine or 111-indium.

The distribution of two monoclonal antibodies with reactivity against human leukemia/lymphoma associated antigens (BA-1 antibody) and carcinoembryonic antigen (202 antibody) when labeled with 131I or 111In was studied in normal Balb/c mice. The BA-1 antibody of the IgM subclass was labeled with 131I by the micro iodine monochloride method at a 12:1 molar ratio and with 111In by the cyclic DTPA anhydride method at a 10:1 molar ratio. In vitro, the 131I-labeled BA-1 antibody bound 35.5% to 10(7) KM-3 leukemic cells while the 111In-labeled BA-1 antibody bound 29.9% to the same number of KM-3 cells. In vivo, the 111In-labeled BA-1 antibody showed a higher accumulation in liver, spleen, and kidney than the 131I-labeled BA-1 antibody. The 202 antibody of the IgG1 subclass was labeled with 131I at a 5:1 molar ratio and with 111In at a 7:1 molar ratio. In vitro, the 131I-labeled 202 antibody bound 30.9%, 27.4%, and 30.0% to 10(7) CO-112, WIDR, and LS-174T colon cancer cells, respectively. The 111In-labeled 202 antibody bound 20.5%, 30.2%, and 33.6%, respectively to the same number of colon cancer cells. In vivo, the 131I-labeled 202 antibody showed a higher tissue to blood ratio in liver, spleen, and kidney than the 111In-labeled 202 antibody. The data indicate that the relative distribution of 131I-labeled versus 111In-labeled monoclonal antibody may depend on the immunoglobulin subclass of the antibody and the molar ratio used in labeling.

Animals

In-111-labeled leukocytes in the diagnosis of rejection and cytomegalovirus infection in renal transplant patients.

Indium-111-labeled (In-111) leukocytes have been shown to be useful in the localization of inflammatory processes, including renal transplant rejection. Using previously reported labeling methods, 63 studies with this agent have been performed in 53 renal transplant patients. Indications for study included suspected rejection or cytomegalovirus (CMV) infection. Studies were performed in 33 men and 20 women, with ages ranging from 6 to 68 years. Autologous cells were normally used for labeling, although leukocytes obtained from ABO-compatible donors were used in three subjects. Rectilinear scanner and/or scintillation camera images were obtained at 24 hours after intravenous administration of 0.1 to 0.6 mCi of In-111-leukocytes. There was abnormal uptake of In-111-leukocytes in the transplanted kidney in 11 of 15 cases of rejection. In three additional cases of increased transplant uptake, CMV infection was present in two. Abnormal lung uptake was present in 13 of 14 patients with CMV infection. In four additional cases, increased lung uptake was associated with other pulmonary inflammatory disease. Increased lung activity was not seen in patients with uncomplicated transplant rejection. These results suggest that In-111-leukocyte imaging may be useful in the differential diagnosis of rejection versus CMV infection in renal transplant patients.

Adolescent

Anti-"i" antibody and hemolytic anemia associated with spontaneous cytomegalovirus mononucleosis.

Hemolytic anemia occurred in a 23-year-old woman with spontaneous cytomegalovirus mononucleosis who had not received a blood transfusion. The patient's serum gave positive reactions in Coombs' antiglobulin test with human cord erythrocytes but did not react with adult "O" cells. Complement-fixation antibody titers against cytomegalovirus and levels of activity against cord erythrocytes increased as the anemia worsened and remained at high levels when recovery from the anemia occurred.

Adult

Combined radiation therapy and surgery in the management of advanced head and neck cancer: final report of study 73-03 of the Radiation Therapy Oncology Group.

Between March 1973 and June 1979, patients with advanced operable squamous cell carcinoma of the supraglottic larynx or hypopharynx were randomly allocated to receive either preoperative radiation therapy (5,000 rad) or postoperative radiation therapy (6,000 rad). Patients with oral cavity or oropharynx lesions were randomly assigned either preoperative radiation, postoperative radiation, or definitive radiation therapy (6,500-7,000 rad), with surgery reserved for salvage if residual disease was present 6 weeks after completion of irradiation. Three hundred twenty patients were evaluable with a median follow-up of 60 months. Based on results in 277 patients across all four regions combined, locoregional control was significantly better for patients assigned to receive postoperative radiation therapy (65%) compared with those assigned to receive preoperative radiation therapy (48%, P = 0.04). This was due to a higher rate of both persistent and recurrent local and regional disease in the preoperative group. Survival also showed a trend to be better in the postoperative group (38%) compared with the preoperative group (33%, P = 0.10). Rates of severe surgical and radiation therapy complications were similar overall. Forty-three patients were evaluable for each of the three treatment regimens assigned to patients with oral cavity or oropharynx lesions. Due to the small number of patients available for this portion of the trial, the observed differences for overall survival (4-year percentage 33% overall; 30% preoperative, 36% postoperative, 33% definitive radiation therapy) and for locoregional control (45% overall; 43% preoperative, 52% postoperative, 38% definitive radiation therapy) were not statistically significant. The use of definitive radiation therapy with surgical rescue as an ethically justified alternative treatment for these tumors remains a question for further research.

Carcinoma, Squamous Cell