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Biomedical subjects

T M Anderson

Publications and source records attributed to T M Anderson.

At least 55 records · Page 3Linked to original sources
PubMed1988

Effects of systemic recombinant interleukin-2 on natural killer and lymphokine activated killer activity of human tumor infiltrating lymphocytes.

The purpose of these studies was to compare local and systemic human lymphokine activated killer (LAK) and natural killer (NK) cytotoxicity and to determine its modulation by the systemic administration of recombinant interleukin-2 (rIL-2). After preoperative systemic rIL-2, we extracted tumor infiltrating lymphocytes (TIL) and peripheral blood lymphocytes (PBL) from patients with pulmonary tumors and compared pre- and posttreatment spontaneous NK activity and their response to in vitro rIL-2. Spontaneous TIL NK activity was increased in patients receiving 15,000 units/kg rIL-2 preoperatively [6.6 lytic units (LU)] compared to those receiving 1,000-10,000 units/kg (0.8 LU) or no rIL-2 (1.4 LU). After 3 days incubation with 1,000 units/ml rIL-2, TIL NK cytotoxic activity was increased in patients receiving 15,000 units/kg rIL-2 (65.4 LU) compared to those receiving 1,000-10,000 units/kg (6.0 LU) or no treatment (24.9 LU). Spontaneous TIL LAK activity was low overall (1.1 LU) with the exception of two patients receiving 15,000 units/kg who had 3.1 and 3.7 LU spontaneously. TIL LAK precursor activity was only slightly increased in patients receiving 1,000-10,000 units/kg rIL-2, whereas those receiving 15,000 units/kg rIL-2 had an average of 22.8 LU. Systemic rIL-2 also increased spontaneous PBL NK activity. Reincubation of PBL obtained at time of surgery or 3 days after discontinuing systemic rIL-2 resulted in significant increases in cytotoxic response to in vitro rIL-2 compared to pre-IL-2 in vitro responses. Systemic rIL-2 had no effect on spontaneous PBL LAK activity. Thus, the immunosuppressive tumor environment can be partially reversed with 15,000 units/kg systemic rIL-2. Higher doses of systemic rIL-2 also increased spontaneous PBL NK activity at time of surgery and 3 days after discontinuing rIL-2. Both TIL and PBL inducible cytotoxicity were boosted in vitro following higher doses of systemic rIL-2.

Humans↗
PubMed1987

Natural killer activity of lymphocytes infiltrating human lung cancers following preoperative systemic recombinant interleukin 2.

Tumor-infiltrating lymphocytes (TILs) show depressed natural killer (NK) activity compared with peripheral blood lymphocytes (PBLs). To determine if TIL NK function can be reactivated in vivo, 11 patients with tumors metastatic to the lung were treated with systemic recombinant interleukin 2 (rIL-2). Spontaneous TIL NK activity and NK activity after three days' incubation with 100 U/mL of rIL-2 were increased in patients receiving 15,000 U/kg of rIL-2 preoperatively compared with those receiving between 1000 and 10,000 U/kg. Histologically, higher doses of rIL-2 increased the number of intratumoral lymphocytes, the level of peritumoral lymphocytic transferrin, and the expression of HLA-DR. Spontaneous PBL NK activity in patients receiving between 10,000 and 15,000 U/kg of rIL-2 was also increased and was further increased by in vitro culture with rIL-2. Thus, PBL NK activity and TIL NK function in vivo can be augmented with 15,000 U/kg of systemic rIL-2. Both TIL- and PBL-inducible cytotoxicities were further enhanced by in vitro culture with rIL-2.

Antibodies, Monoclonal↗
PubMed1987

Modification of natural killer activity of lymphocytes infiltrating human lung cancers.

The purpose of these studies was to compare local and systemic human lymphokine activated killer (LAK) and natural killer (NK) cytotoxic activity and to determine its modulation by biologic agents. Local immunity may be an important component in limiting local tumor growth. Therefore, as a model for studying immune function in the local compartment, we assessed NK activity of lymphocytes present at the site of human tumors and in peripheral blood (PBL). We extracted tumor infiltrating lymphocytes (TIL) and PBL from patients with pulmonary tumors and compared NK activity and response to the biological modifiers gamma interferon (IFN-gamma), indomethacin (INDO), and interleukin 2 (IL-2). We also studied TIL and PBL LAK activity using the NK-resistant M14 target cells and determined the TIL response to IL-2, plus IFN-gamma. Titration of K562 targets in a 51Cr release assay revealed that untreated TIL have low cytotoxicity (4.32%) compared to untreated PBL (34.3%, P = less than 0.001). This low level of TIL NK activity was not affected by IFN-gamma, INDO, or IL-2 at 1 h. However, at 3 days of culture, IL-2 with or without exogenous IFN-gamma significantly increased TIL NK cytotoxicity (20.5%, P = 0.02 without IFN-gamma and 32.52 lytic units (LU), P = less than 0.02 with IFN-gamma). Untreated TIL and PBL both had low cytotoxicity against M14 targets (1.08 LU and 1.26 LU), respectively. After 3 days culture with IL-2 plus IFN-gamma, both TIL and PBL LAK cytotoxicity were increased (14.34 LU and 40.63 LU). We conclude that local NK and LAK activity is intrinsically low. However, this activity can be modulated by biologic agents, thus giving hope for the development of local anti-tumor effectors capable of in vivo tumor control.

Cytotoxicity, Immunologic↗
PubMed1987

Monoclonal antibodies to human malignant mesothelioma.

Murine monoclonal antibodies were used to identify tumor-cell membrane antigens on a new human mesothelioma cell line. Hybridomas were constructed by fusing SP2/0 mouse myeloma cells with spleen cells from Balb/C mice immunized by the human mesothelioma cell line MT-1. Hybridoma antibody was detected in 55/672 microculture wells that reacted to these MT-1 tumor cells by an indirect 125I-protein A binding assay. Six cultures produced antibody binding selectively to the MT-1 tumor cells but not to a human lymphoblastoid cell line. These six hybridomas were cloned: three were IgG and three were IgM antibodies. One monoclonal, MAb 45, reacted with 4 of 7 human mesothelioma cell lines but with only 1 of 11 carcinomas, 1 of 3 sarcomas, 4 of 11 melanomas, and 0 of 5 lymphoid lines. The other five monoclonals had a much broader cross-reactivity. Using an immunoperoxidase technique, MAb 45 bound to mixed-type malignant mesotheliomas but not to normal lung and pleura. The specificity of MAb 45 for diffuse mesotheliomas and the low cross-reactivity with carcinomas and normal adjacent tissues suggest that this monoclonal may be clinically useful.

Antibodies, Monoclonal↗
PubMed1986

Mutation and enhanced virus transformation of cultured hamster cells by exposure to gaseous ethylene oxide.

Ethylene oxide is a classical mutagen and a carcinogen based on evidence from studies in experimental animals. It is widely distributed in industrial, research, hospital, and food environments. In an effort to explore the use of newly developed methods for exposing mammalian cells to gaseous or volatile mutagens/carcinogens, Chinese hamster V79 cells were treated for 2 hr with gaseous ethylene oxide, in sealed treatment chambers, and assayed for survival and mutagenic response by analysis of induced resistance to 6-thioguanine or ouabain. Significant numbers of mutants were produced at both genetic markers by 1,250-7,500 ppm ethylene oxide. Similarly, primary Syrian hamster embryo cells were treated for 2 or 20 hr with gaseous ethylene oxide in sealed treatment chambers and subsequently assayed for survival and increased sensitivity to SA7 virus transformation. Treatment concentrations extended from toxic to several nontoxic concentrations. After 2-hr ethylene oxide treatment at 625-2,500 ppm a significant enhancement of virus transformation was observed. At 20 hr after treatment no enhancement was observed. Treatment of hamster cells with ethylene oxide in both bioassay systems yielded concentration-related, quantitative results.

Adenoviruses, Simian↗
PubMed1986

Analysis of the interlaboratory and intralaboratory reproducibility of the enhancement of simian adenovirus SA7 transformation of Syrian hamster embryo cells by model carcinogenic and noncarcinogenic compounds.

The intralaboratory and interlaboratory reproducibility of a DNA virus (SA7) transformation enhancement assay was investigated using nine carcinogenic and noncarcinogenic compounds representing a variety of chemical classes. By the use of standardized procedures designed to limit assay variables, replicate assay data were collected in two independent laboratories and analyzed for concurrence. The carcinogens, 7,12-dimethylbenz(a)anthracene, benzo(a)pyrene, and N-methyl-N'-nitro-N-nitrosoguanidine yielded reproducible dose-dependent cytotoxicity and positive transformation effects (defined as statistically significant [p less than or equal to 0.05] enhancement of virus transformation at two or more consecutive dose levels) in all experiments in both laboratories. The carcinogens lead chromate, diethylnitrosamine, 4-nitroquinoline-N-oxide, and 2-acetylaminofluorene demonstrated enhancement of SA7 transformation at two or more dose levels in 40-50% of the assays. The noncarcinogenic structural analogs anthracene and pyrene consistently did not produce positive assay responses when tested at dose levels up to the limits of solubility. Good interlaboratory concurrence was demonstrated for these model compounds in the Syrian hamster embryo cell-SA7 assay.

2-Acetylaminofluorene↗
PubMed1986

Chemical enhancement of SA7 virus transformation of hamster embryo cells: evaluation by interlaboratory testing of diverse chemicals.

Twelve chemicals from diverse structural classes were tested under code for their capacity to enhance the transformation of Syrian hamster embryo cells by simian adenovirus SA7 in two independent laboratories. Pretreatment of hamster cells with eight of those chemicals (reserpine, dichlorvos, methapyrilene hydrochloride, benzidine dihydrochloride, diphenylhydantoin, cinnamyl anthranilate, 11-aminoundecanoic acid, and 4,4'-oxydianiline) produced repeatable enhancement of SA7 transformation at two or more consecutive dose levels, which constitutes clear evidence of enhancing activity in this assay. Both toxic and nontoxic doses of each of these chemicals caused enhancement of virus transformation. Two chemicals (2,6-dichloro-p-phenylenediamine and cinnamaldehyde) produced some evidence of enhancing activity (repeatable transformation enhancement at one dose). Dose ranges for cytotoxicity and enhancement of SA7 transformation were similar in both laboratories for all chemicals producing activity. The final two chemicals, chloramphenicol sodium succinate and ethylene thiourea, failed to reproducibly demonstrate either significant cytotoxicity or enhancement of SA7 transformation at concentrations up to 10-20 mM. The test results for these 12 chemicals were combined with the test results for 9 known carcinogens and noncarcinogens in order to evaluate relationships between activity, dose response, and lowest effective enhancing concentration for these compounds, as well as to correlate them with rodent carcinogenesis classifications. The Syrian hamster embryo cell-SA7 system demonstrated reproducible test responses in both intra- and interlaboratory studies and detected 13 out of 15 known rodent carcinogens.

Adenoviridae↗
PubMed1986

Factors affecting survival in superior sulcus tumors.

Fifty-five patients with superior sulcus syndrome were treated at the UCLA Medical Center and Wadsworth VA Hospital (Los Angeles) between 1956 and 1985. Twenty-eight underwent surgery, six of whom were found unresectable at the time of thoracotomy. Twenty-one of 22 in the resected group received preoperative irradiation. Twenty-seven patients received radiation only. Surgical morbidity was 21%, and there were two in-hospital deaths. Five-year survival for extended resection patients was 34%. The radiation only group had no 5-year survivors. Factors associated with a worse prognosis include positive margins, N2 disease, and vertebral body involvement. The best results for superior sulcus tumors are obtained by preoperative irradiation followed by en bloc resection of the tumor. In the event complete resection is impossible, radiation has a role in palliation of pain with occasional prolonged survival.

Adult↗
PubMed1986

Echocardiographic screening of the athletic adolescent.

Sports-related sudden death in adolescent athletes is usually the result of previously undetected heart disease. The most common causes are hypertrophic cardiomyopathy, left coronary artery anomaly, and Marfan's syndrome. Comprehensive cardiovascular history and physical examinations can select a group of adolescents suspected of having heart disease and increased risk of sudden death. Echocardiography plays an important role in the further diagnostic evaluation of these adolescents. Although echocardiography would make an ideal screening test, it is impractical at this time considering the millions of adolescents undergoing preparticipation sports evaluations each year. For now, continued education of the examining physician and appropriate use of diagnostic studies are needed.

Adolescent↗
PubMed1985

Successful percutaneous balloon valvuloplasty of the aortic valve in an infant.

Percutaneous balloon aortic valvuloplasty was attempted in an eight-month-old infant with severe aortic valve stenosis. The procedure resulted in a fall in the resting transvalvular systolic pressure gradient from 106 mmHg to 40 mmHg and no aortic regurgitation. Clinical and Doppler echocardiography findings suggest persistent improved status 3 1/2 months after the procedure.

Angioplasty, Balloon↗
PubMed1985

Long-term echocardiographic evaluation of cardiac size and function in patients with Kawasaki disease.

The long-term effects of Kawasaki disease on the cardiac function were evaluated in 67 patients. Serial M-mode echocardiograms were obtained at the time of the initial diagnosis, 1 to 3 months, at 3 to 12 months, and at greater than 12 months following the diagnosis. Left ventricular and left atrial dimensions, shortening fraction, left and right ventricular systolic time interval ratios, and computer analysis of digitized echoes of the left ventricular chamber and posterior wall were obtained. The left atrial and left ventricular dimensions were abnormal in half of the patients throughout the study periods. The shortening fraction was abnormal initially but became normal by the end of 3 months. The peak rates of emptying of the left ventricle and thickening of the posterior wall were significantly reduced in all evaluation periods. In addition, the peak rate of diastolic thinning of the posterior wall was reduced, although the peak rate of filling remained normal. Finally, more than 30% of patients studied beyond 12 months had a prolonged major filling and thinning period. There was no difference between patients with or without coronary artery aneurysms. All other systolic and diastolic phase intervals and rates of changes were normal. Contrary to previously published reports, we conclude that patients with Kawasaki disease who do not have demonstrable coronary artery disease, exhibit abnormalities of cardiac chamber size and function long after their acute illness.

Adolescent↗
PubMed1985

Experience with sphincteroplasty and sphincterotomy in pancreatobiliary surgery.

Review of a 26-year experience with transduodenal sphincteroplasty and sphincterotomy was undertaken (1) to analyze critically the indications for and results of these procedures and (2) to determine which preoperative factors correlate with a good or poor outcome. Of 109 patients, 78 underwent sphincteroplasty, whereas 31 had a transduodenal sphincterotomy. Surgical indications included: group 1, 53 patients with common duct stones; group 2, 28 patients with dyskinesia or stenosis of the sphincter of Oddi (without choledocholithiasis or recurrent pancreatitis); and group 3, 28 patients with recurrent pancreatitis. Three elderly group 1 patients who presented with cholangitis died after surgery (a hospital mortality of 2.7%). Seventy-nine of the 103 patients (77%) in whom follow-up was obtained achieved an excellent or good result. Results were almost identical with sphincteroplasty and sphincterotomy. Abnormal preoperative liver function tests were the only predictors of a good postoperative outcome (p less than 0.05). Group 3 patients (good results in 63%) had significantly poorer (p less than 0.05) outcome than group 1 and 2 patients. Results were worst in group 3 patients who had undergone previous abdominal or pelvic surgery (p less than 0.025) and in group 2 patients who were narcotic users (p less than 0.025). The authors conclude that transduodenal sphincteroplasty or sphincterotomy can be performed relatively safely, but caution that careful selection of patients is important when the indication for surgery is either ampullary stenosis or recurrent pancreatitis.

Adolescent↗
PubMed1985

Gastric ulcer localization by direct in vivo labeling of sucralfate. Work in progress.

We developed and evaluated a new procedure for imaging gastric ulcer disease with technetium 99m-labeled sucralfate. The new method employs direct in vivo labeling of sucralfate instead of in vitro labeling using human serum albumin, as previously reported in the literature. Tests using hydrochloric acid and a rabbit ulcer model showed the efficacy of the direct in vivo labeling technique and the ability of the tagged material to bind to ulcers, respectively. In 26 studies using humans with sucralfate labeled directly in vivo, 15 gave true-negative results and 11 gave true-positive results. Of 14 studies using humans with in vitro labeled sucralfate, three gave true-negative results, three gave true-positive results, and the results of eight were either false-negative or could not be interpreted because of high levels of activity remaining in the stomach. We suggest that the direct in vivo labeling method significantly improves the sucralfate gastric ulcer imaging technique.

Aluminum↗
PubMed1982

Tumoral calcinosis: serial images to monitor successful dietary therapy.

Tumoral calcinosis involves formation of periarticular calcified soft tissue masses. Experimental evidence suggests a metabolic etiology with dietary restriction of calcium and phosphorus as beneficial therapy. We prospectively monitored serum levels of calcium, phosphorous, alkaline phosphatase, and erythrocyte sedimentation rate (ESR) while successfully treating a patient with tumoral calcinosis. The values were compared with changes on serial radiographic and radionuclide bone and gallium images. Our work suggests using serial serum phosphate levels and the ESR as the most sensitive indications of progress in dietary treatment of tumoral calcinosis.

Alkaline Phosphatase↗
PubMed1981

Effect of crossover exposure on radiographic image quality of screen-film systems.

Modulation transfer functions (MTFs), Wiener spectra, and H & D curves of conventional and anticrossover screen-film systems were measured in an evaluation of the potential clinical use of anticrossover systems. The relative speed of anticrossover (3M) systems was reduced by 40%, compared with conventional (Kodak OG) systems. The anticrossover system improved both resolution and noise properties of screen-film systems (55% improvement of MTF at 2 cycles/mm and 40% reduction of radiographic mottle at low spatial frequencies) in a way that a combination of slow, sharp screens with conventional film may not accomplish, even when the speeds of different systems are matched. Detail visibility, in phantom images and radiographs of the hand, was considerably enhanced with anticrossover film compared with that of conventional film.

Humans↗