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Biomedical subjects

J D Beatty

Publications and source records attributed to J D Beatty.

88 records · Page 5Linked to original sources
PubMed1985

High-specific-activity 111In-labeled anticarcinoembryonic antigen monoclonal antibody: improved method for the synthesis of diethylenetriaminepentaacetic acid conjugates.

A new method has been developed for conjugating diethylenetriaminepentaacetic acid (DTPA) to proteins using the N-hydroxysuccinimide active ester of DTPA. The DTPA-active ester was prepared using diisopropylcarbodiimide in a simple single step synthesis. DTPA-conjugated proteins were prepared by adding the DTPA-active ester reaction mixture to protein solutions (5 mg/ml) buffered at pH 7.0 and purified by Sephadex G-50 chromatography. A monoclonal antibody directed against carcinoembryonic antigen was reacted with four different amounts of the DTPA-active ester. Solid-phase enzyme immunoassay showed that the immunological activity of the antibody conjugate was not altered when the active ester: antibody molar ratio was 36:1 or 72:1; however, it decreased when the ratio was 180:1 or 360:1. The antibody heavy and light chains had slightly decreased electrophoretic mobilities when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a result consistent with the covalent attachment of DTPA to the protein. Sephadex G-200 chromatography showed that the native and conjugated antibodies were the same size. When the DTPA-conjugated antibody was incubated with 10, 50, and 100 microCi of 111In/micrograms of protein, specific activities of 9.8, 43.1, and 56.3 microCi/micrograms were obtained. Enzyme immunoassay and radioimmunoassay of the 111In-labeled antibody showed that it retained its full immunological activity. The high specific activity of the 111In-labeled antibody makes it suitable for imaging carcinoembryonic antigen-bearing tumors using low doses of antibody.

Animals↗
PubMed1985

High-specific-activity 111In-labeled anticarcinoembryonic antigen monoclonal antibody: biodistribution and imaging in nude mice bearing human colon cancer xenografts.

Tumor imaging and biodistribution of an indium-labeled monoclonal antibody (MAB) to carcinoembryonic antigen (CEA) [anti-CEA MAB-diethylenetriaminepentaacetic acid (DTPA)-111In] have been investigated using LS174T human colon cancer xenografts in nude mice. Antibody specificity, dose, and specific activity were examined with respect to tumor uptake and quality of scintiscans at different times following injection. The CEA-bearing LS174T tumors were imaged specifically with anti-CEA MAB-DTPA-111In. Using 62.5 ng of indium-labeled MAB (50 microCi/micrograms) the ratio of activity in tissue expressed as a percentage of the total radioactive dose injected into the animal per gram tissue for tumor:blood increased from 0.66 +/- 0.02 (SE) at 1 h to 14.8 +/- 1.1 at 72 h. Scintiscan quality improved with the rise in tumor:blood ratio until 48 h. At longer intervals insufficient counts remained for imaging. The tumor:blood ratio and the scintiscan quality were not improved by increasing the MAB dose to 625 or 6250 ng but good images were obtained at longer times postinjection. By decreasing the 111In from 50 to 10 microCi/micrograms of MAB, the unbound 111In was decreased from 7 microCi/micrograms (14%) to 0.2 microCi/micrograms (2%). Even with the lower specific activity (9.8 microCi/micrograms) of the 10-microCi/micrograms preparation, scintiscan quality at the 62.5-ng dose was maintained. This anti-CEA MAB-DTPA-111In preparation was stable, retained immunological activity, did not require column chromatography to remove unbound 111In, was specific for a CEA-bearing tumor, and was effective for tumor imaging over a wide range of antibody doses (3 to 300 micrograms MAB/kg body weight). This anti-CEA MAB-DTPA-111In preparation is feasible and practical for imaging CEA-bearing tumors in humans.

Animals↗
PubMed1984

Cancer of the breast after prophylactic subcutaneous mastectomy.

We have reported a case of carcinoma of the breast in a patient that occurred after bilateral prophylactic subcutaneous mastectomy. We recommend that the patient and physician be aware of the limitations of prophylactic mastectomy in terms of cancer prevention and that patients who undergo prophylactic mastectomy continue to be carefully followed.

Adenocarcinoma↗
PubMed1984

Liposomes as immune adjuvants: T cell dependence.

The T cell dependence of the immune adjuvant action of liposomes containing the soluble antigens bovine serum albumin (BSA) and chicken immunoglobulin (CIgG) was studied with use of a quantitative enzyme-linked immunosorbent assay to measure serum antibody levels. Normal BALB/c mice, adult thymectomized mice, and congenitally athymic (nu+/nu+) mice were intravenously inoculated with liposomes containing BSA (Lip-BSA). The high levels of serum anti-BSA antibody that were seen in the normal group were decreased in the adult thymectomized group and were almost completely abrogated in the nu+/nu+ group. Reconstitution of nu+/nu+ mice with normal thymocytes and cortisone-resistant thymocytes led to a partial restoration of the anti-BSA antibody production after Lip-BSA immunization. Examination of the class of immunoglobulin produced in normal mice, immunized with Lip-BSA, showed an early low IgM response and a sustained higher IgG response that was primarily due to the IgG1 subclass. Trypsin removal of BSA exposed on the liposome surface decreased the resulting serum anti-BSA antibody level by 30% to 50%. Animals could be primed equally with a very low dose (0.2 micrograms) of Lip-BSA or with peritoneal macrophages that had phagocytosed the same dose of Lip-BSA. The adjuvant effect of liposomes containing CIgG on the number and type of specific anti-CIgG antibody-producing cells in the spleen was an early increase in IgM-producing cells followed by a substantially higher increase in IgG-producing cells. These observations suggest that liposome encapsulation of a soluble T-dependent antigen stimulates the helper T cell, not the suppressor T cell population, and that this stimulation involves uptake by macrophages.

Adjuvants, Immunologic↗
PubMed1983

A prospective analysis of nosocomial wound infection after mastectomy.

We evaluated the postoperative course of all patients who had mastectomies from 1978 through 1982 at City of Hope National Medical Center (Duarte, Calif). The overall clean mastectomy wound infection rate was 24/294 (8.2%). The incidence of mastectomy wound infection varied with the method of biopsy and was 3.2% after needle aspiration and 9.5% after open biopsy. Mastectomy immediately after open biopsy ("one step") had an infection rate of 5.3%, whereas mastectomy at a subsequent procedure ("two step") had a rate of 12.4%. The maximal infection rate (23.0%) occurred following the two-step procedure when the interval was four to seven days. The infection rates for patients hospitalized three or more days before mastectomy were elevated, but no significant correlation was observed between the infection rate and other demographic factors. We recommend that needle aspiration biopsy be used prior to open biopsy to minimize the need for a two-step approach to mastectomy.

Adult↗
PubMed1979

Clinical value of carcinoembryonic antigen: diagnosis, prognosis, and follow-up of patients with cancer.

Plasma carcinoembryonic antigen (CEA) in nanograms per milliliter was assayed in 149 patients with benign and 567 patients with malignant disease. Elevated CEA level (greater than 5.0) was a good indicator of malignant disease but a poor screening test for cancer because of the high false-negative rate. Degree of elevation of plasma CEA level correlated with incidence of metastatic disease in patients with colorectal, gastric, and breast carcinomas, but no correlation was seen between CEA levels and status of lymph nodes in patients with localized disease. Patients with localized colorectal cancer, but elevated CEA levels before resection, had a 2.1-fold increase in the incidence of recurrence; however, this added to the prognostic value of Dukes' staging only when the CEA level remained elevated postoperatively. In 87% of patients with colorectal cancer, the CEA level was elevated at the time of recurrence, but a therapeutic value of reexploration for unexplained CEA level elevation was not confirmed.

Carcinoembryonic Antigen↗
PubMed1979

Carcinoma of the esophagus: pretreatment assessment, correlation of radiation treatment parameters with survival, and identification and management of radiation treatment failure.

Between January 1969 and February 1975, 344 patients with carcinoma of the esophagus were managed primarily at the Princess Margaret Hospital, Toronto. One hundred sixty-eight (168) of the patients were treated palliatively and 176 of the patients were treated by radical doses of radiation, surgical resection or both. Survival of the radical treatment group was biphasic, the steeper component being identical to the survival of the palliative treatment group, thereby representing a group of patients that did not respond to radical treatment. Analysis of pretreatment assessment parameters indicated that all patients with T1 lesions (length less than or equal to 5 cm, circumference incomplete) and all patients with Stage I disease responded to treatment. Patients who were female, age greater than or equal to 70 years, N0 or had well differentiated squamous cell histology, responded to treatment in at least 80% of cases. No patient with extralymphatic distant metastases responded to treatment. The presence of other major disease did not affect response to treatment. Thirty patients had surgical resections and their survival was not significantly greater than the 146 patients who had radical radiation alone. Survival analysis revealed an optimum range of nominal standard dose (NSD) of 1602--1714 rets (median 1679 rets) for patients treated by radiation alone. An optimum port size (area) of 100--140 cm2 was observed for patients receiving 5000 rads and supervoltage irradiation gave a significantly improved survival in comparison with megavoltage irradiation. Sixty-seven percent (67%) of patients treated by radical doses or radiation developed esophageal strictures postradiation and on the basis of radiological, endoscopic or histological evidence 75% of these strictures were considered to be associated with the persistence of malignancy. On the basis of postmortem examinations (32) and death certificates there was overall an 80% failure to control the disease locally and 95% of strictures were associated with persistence of malignancy in the esophagus. Thirty-one of the 146 patients receiving radical radiation alone had palliation for esophageal obstruction following radiotherapy. The construction of a physiological bypass (e.g., colon) resulted in a mean survival of 215 days which was much longer than the survival observed with rigid esophageal tubes (35 days) or gastrostomy tubes (58 days).

Aged↗
PubMed1979

Chemotherapy and cancer of the gastrointestinal tract.

Less than 40 percent of all carcinomas of the gastrointestinal tract will be controlled by the current modalities of treatment. Early diagnosis and appropriate surgical resection are still the only rational and effective approach to the control of this cancer. The tremendous strides in cancer chemotherapy in the management of leukemia, children's solid tumors, and neoplasms of lymphoid origin have not been evident in the management of gastrointestinal carcinoma. Extensive clinical trials with single agents and various drug combinations have resulted so far in partial response rates. Adjuvant chemotherapy to surgical resection has also failed to alter the natural course of the disease and, therefore, to establish its benefits in a series of projective randomized studies. Only continued research in cancer cell biology and basic and clinical pharmacology with carefully controlled therapeutic trials with new agents will eventually lead to the more effective use of chemotherapy in management of gastrointesinal cancer.

Antineoplastic Agents↗
PubMed1978

Effects of conjugated and nonconjugated antithymocyte globulin and trenimon on T lymphocytes and skin graft rejection.

These studies were undertaken to investigate the use of a technique for "homing" of an alkylating agent to lymphocytes as an immunosuppressive approach to inhibit allograft rejection. Trenimon (Tr) was bound covalently to antithymocyte globulin (ATG) and the effects of the complex on peripheral blood cells, thymus cells, spleen cells, and on foreign skin graft rejection assessed. When rabbit ATG was bound covalently to Tr, an alkylating agent, the conjugate (ATG-Tr) retained both complement-dependent antithymus cell acitivity and alkylating activity in vitro, but these activities were reduced. In vivo ATG decreased lymphocytes and increased neutrophils in the blood. ATG-Tr reduced circulating lymphocytes to lower levels and partially attenuated the rise in neutrophils. The in vivo effects of ATG, Tr, ATG-Tr, and ATG mixed with Tr (ATG + Tr) on thymus cells, spleen cells, T lymphocytes in the spleen, and rejection of a foreign skin graft were compared. Tr decreased all cell types, especially thymocytes, but did not delay graft rejection. ATG and ATG-Tr decreased thymocytes, eradicated T cells from the spleen, and delayed graft rejection 3-fold. ATG + Tr decreased thymocytes as Tr had done, eradicated T cells from the spleen, and delayed graft rejection 5-fold. It was concluded that ATG-Tr possessed antithymocyte antibody activity and Tr alkylating activity, but did not confer an immunological advantage over ATG alone, and that ATG and Tr mixed together unbound acted synergistically to delay graft rejection.

Animals↗
PubMedDate not supplied

A technical analysis of an intraoperative radiation detection probe.

A technical evaluation was made of a commercial intraoperative radiation probe. This device utilizes a CsI (T1) scintillation detector and light pipe arrangement to count gamma radiation in vivo. After determining the optimal window and threshold setting, additional evaluations included linearity, distance response function, detector dead time, counter reproducibility, detector sensitivity, angular resolution, and energy resolution. Detector dead time (21.2 microseconds) was found to be characteristic of a nonparalysable system. Activity response for each radionuclide was linear (R = 0.99) both with and without collimation. Energy resolution, 25% at 210 keV, was not sufficient to separate the two photons (172 and 247 keV) emitted by 111In. Detector sensitivity was 1136 and 626 counts per s per microcurie of 111In and 99mTc, respectively. The mean effective distance from the face of the uncollimated probe to the crystal was determined to be 2.03 cm in air.

Antibodies↗
PubMedDate not supplied

Altered gentamicin pharmacokinetics during the perioperative period.

The effect of surgery on the pharmacokinetics of gentamicin sulfate in hospitalized patients was studied. Patients with cancer undergoing surgery of the head and neck were given gentamicin sulfate in doses calculated to achieve peak serum concentrations of 6-8 micrograms/mL and trough concentrations of 1-2 micrograms/mL. Each patient received a loading dose at the time of surgical incision, followed by five maintenance doses at eight-hour intervals. Steady-state peak and trough serum gentamicin concentrations were predicted using a one-compartment open pharmacokinetic model and literature values for volume of distribution (V) and first-order elimination rate constant (k). Serum gentamicin concentrations were measured 0.25 hours before and at 0.5, 3.5, and 6.5 hours after completion of infusion of the second maintenance dose. Peak and trough serum concentrations were obtained by extrapolation from these measured concentrations using weighted, nonlinear least squares regression. Predicted versus measured serum gentamicin concentrations and estimated versus observed values for V and k were compared. Eight men and seven women had evaluable serum gentamicin concentrations. Patients received a mean calculated maintenance dose of 4.4 +/- 0.7 mg/kg/day. Mean extrapolated peak and trough serum gentamicin concentrations were significantly lower than predicted, and observed values of V and k were significantly greater than estimated values. Gentamicin dosages calculated using standard pharmacokinetic variable values may not produce therapeutic concentrations in patients undergoing surgery. Monitoring of serum concentrations with dosage adjustment when indicated is necessary for optimal therapy in these patients.

Aged↗