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Biomedical subjects

A M Zimmer

Publications and source records attributed to A M Zimmer.

At least 37 records · Page 2Linked to original sources
PubMed1995

Clinical significance of anti-At(a).

Ata is a high-frequency red blood cell (RBC) antigen. Anti-At(a) has been reported in rare At(a-) black subjects. We report two cases of anti-At(a). A clinically significant anti-At(a) was found in a 26-year-old black woman with systemic lupus erythematosus. The patient had a transfusion reaction with chills and nausea during a RBC survival study, and 95% of the radiolabeled At(a+) RBCs were destroyed within 3 h. A concurrently performed monocyte monolayer assay was strongly reactive. Anti-At(a) thus can cause rapid hemolysis of transfused RBCs, but At(a-) donor units are extremely scarce in rare donor registries. A second patient at our hospital had anti-At(a) which did not affect her newborn. She also had autoimmune disease, insulin-dependent diabetes mellitus.

Adult↗
PubMed1994

Reinfusion of postoperative wound drainage in total joint arthroplasty. Red blood cell survival and coagulopathy risk.

Fifty patients with total joint arthroplasties (28 total hip arthroplasties, 11 total knee arthroplasties, and 11 bilateral total knee arthroplasties) received autotransfusions from their postoperative wound drainage. The blood was collected in a closed sterile drainage system without any additional anticoagulant. Pre- and postoperative measurements were made of the patient's hemoglobin, platelets, fibrinogen, haptoglobin, fibrin degradation products, and D-dimer (a specific type of fibrin degradation product). Red blood cell survival was assessed in 16 of the patients by labeling the shed blood with 51Cr sodium chromate prior to reinfusion. To control for fluid shifts, continued bleeding, and dilution effects of further transfusions in the immediate postoperative period, 10 patients also had their native blood labeled with 111In oxime. In this study, the mean estimated blood loss was 1,062 mL (+/- 1,247) with a mean wound drainage of 836 mL (+/- 338). Of this, a mean of 450 mL (+/- 261) of blood was was given back to the patient in addition to routine, preoperative autologous donated blood. Six (12%) patients experienced transient fevers at the time of retransfusion. Detailed hematologic studies were performed on the shed blood in 19 patients. The collected blood was completely defibrinated, but did contain fibrin degradation products, as indicated by the D-dimer level, and hemolyzed blood as the haptoglobin was reduced. Even though the blood containing the above breakdown products was reinfused to the patients, there were no clinical manifestations of disseminated intravascular coagulation. Both the hemolyzed and defibrinated products were subsequently cleared by the body.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Factors↗
PubMed1994

Tissue specific expression of the retinoic acid receptor-beta 2: regulation by short open reading frames in the 5'-noncoding region.

The 40-S subunit of eukaryotic ribosomes binds to the capped 5'-end of mRNA and scans for the first AUG in a favorable sequence context to initiate translation. Most eukaryotic mRNAs therefore have a short 5'-untranslated region (5'-UTR) and no AUGs upstream of the translational start site; features that seem to assure efficient translation. However, approximately 5-10% of all eukaryotic mRNAs, particularly those encoding for regulatory proteins, have complex leader sequences that seem to compromise translational initiation. The retinoic-acid-receptor-beta 2 (RAR beta 2) mRNA is such a transcript with a long (461 nucleotides) 5'-UTR that contains five, partially overlapping, upstream open reading frames (uORFs) that precede the major ORF. We have begun to investigate the function of this complex 5'-UTR in transgenic mice, by introducing mutations in the start/stop codons of the uORFs in RAR beta 2-lacZ reporter constructs. When we compared the expression patterns of mutant and wild-type constructs we found that these mutations affected expression of the downstream RAR beta 2-ORF, resulting in an altered regulation of RAR beta 2-lacZ expression in heart and brain. Other tissues were unaffected. RNA analysis of adult tissues demonstrated that the uORFs act at the level of translation; adult brains and hearts of transgenic mice carrying a construct with either the wild-type or a mutant UTR, had the same levels of mRNA, but only the mutant produced protein. Our study outlines an unexpected role for uORFs: control of tissue-specific and developmentally regulated gene expression.

Amino Acid Sequence↗
PubMed1993

A phase I escalating-dose safety, dosimetry and efficacy study of radiolabeled monoclonal antibody LYM-1.

Thirteen patients with relapsed or refractory Non-Hodgkin's Lymphoma were treated with 131I-Lym-1 during the course of a dose escalation trial. Principal aims were to establish the maximum tolerated single dose (MTD), as well as to assess clinical and dosimetric effects of the MTD. Patients were eligible if > 25% of tumor cells bound Lym-1 on immunohistochemistry, stain intensity was +2/4 or greater and human anti-mouse antibody (HAMA) assay was negative. Radioimmunotherapy was performed with escalating doses at levels of 50 mCi, 65 mCi/m2 and 80 mCi/m2 (50-139 mCi total). Patients were eligible for retreatment after 6-10 weeks if there was no severe toxicity, their disease was at least stable and HAMA remained negative. Three were retreated. Four have achieved partial responses which lasted 11, 11, 18 and 22 weeks. Acute toxicities included rigors (69%), fever (62%), nausea (46%), vomiting (46%), pruritus (23%), urticaria (23%), chest pain (23%) and bronchospasm (15%). HAMA developed in 3 patients. Myelosuppression, manifested as thrombocytopenia and neutropenia, was dose-limiting and defined the single dose MTD at 65 mCi/m2. Plasma radioactivity clearance was biphasic, with a 0.9 hr alpha-T1/2 and a 19.8 hr beta-T1/2. At completion of Lym-1 infusion, a mean of 45% of the injected dose was recoverable in the circulation. Images obtained within the first 2 hours indicated mean hepatic and splenic uptake was 29% and 11%, respectively. Radiation absorbed doses to tumor ranged from 18-61 rads; mean doses to whole body ranged from 17 to 71 rads.

Adult↗
PubMed1992

Effects of hyperthermia and iodine-131-labeled anticarcinoembryonic antigen monoclonal antibody on human tumor xenografts in nude mice.

BACKGROUND: Many studies have demonstrated synergistic interaction between hyperthermia and radiation. This study was undertaken to determine whether hyperthermia could enhance the effect of radioimmunotherapy (RIT) in the treatment of human colon adenocarcinoma xenografts in nude mice. METHODS: The experiments were conducted in two parts. During the first part of the study, preliminary information was obtained regarding the effect of various temperatures (41 degrees C, 42 degrees C, and 43 degrees C for 45 minutes) and iodine-131-labeled anticarcinoembryonic antigen (CEA) monoclonal antibodies (RMoAb) with administered activity ranging from 130 +/- 19 microCi to 546 +/- 19 microCi on tumor regrowth delay (TRD) and volume doubling time. This information was used in Part 2 of the study, which included four groups of mice: (1) a control group, (2) a group treated with hyperthermia, (3) a group treated with RMoAb, and (4) a group treated with a combination of RMoAb and hyperthermia. RESULTS: Maximum and significantly increased TRD was observed in the group treated with RMoAb and hyperthermia (slope, 0.057) compared with the control group (slope, 0.322), the hyperthermia-treated group (slope, 0.302), and the group treated with RMoAb alone (slope, 0.098). The ratio of the slopes between the groups treated with RMoAb and those treated with RMoAb and hyperthermia was 1.72. No correlation was detected between the percent of antibody uptake in the tumor and tumor regression in the groups treated with heat and RMoAb and those treated with RMoAb alone. CONCLUSIONS: The results of these experiments show that hyperthermia increased the effectiveness of iodine-131-labeled anti-CEA monoclonal antibodies against human colon carcinoma xenografts in nude mice. This study offers a rationale for combining hyperthermia and low-dose radiation produced from RIT in clinical practice.

Adenocarcinoma↗
PubMed1990

Radioimmune localization of occult carcinoma.

Patients with a rising serum carcinoembryonic antigen level and no clinical or roentgenographic evidence of recurrent or metastatic cancer present a treatment dilemma. Eleven such patients, 10 with a previously treated colorectal carcinoma and 1 with a previously treated breast carcinoma, received an injection of the anticarcinoembryonic antigen monoclonal antibody ZCE-025 labeled with the radioisotope indium 111. Nuclear scintigraphy was performed on days 3 and 5 through 7 to detect potential sites of tumor recurrence. The monoclonal antibody scan accurately predicted the presence or absence of occult malignancy in 7 (64%) patients. Second-look laparotomy confirmed the monoclonal antibody scan results in the patients with colorectal cancer, and magnetic resonance imaging confirmed metastatic breast cancer. This study demonstrates that In-ZCE-025 can localize occult carcinoma and may assist the surgeon in facilitating the operative exploration. In-ZCE-025 assisted in the initiation of adjuvant therapy for the patient with breast cancer.

Antibodies, Monoclonal↗
PubMed1990

Nuclear medicine imaging workstations based on personal computer technology.

The development of personal computer technology has resulted in extremely powerful, inexpensive computers available as consumer items. With the addition of suitable hardware for gamma camera interfacing and image display, such systems can be transformed into fully functional nuclear medicine computers capable of performing all of the acquisition and processing tasks required in a modern radioisotope imaging department. Such an approach to nuclear medicine computerization offers many advantages in terms of flexibility, speed, cost, and expandability.

Hospital Departments↗
PubMed1990

Human IgE, IgG and IgA antibody responses to T101, a murine monoclonal antibody against human lymphocytes: implications for pathogenesis, risk and avoidance of adverse immunologic reactions.

To study immune responses that may play a role in immediate-type allergic reactions (ITAR) and serum-sickness-like reactions that have been reported with administration of monoclonal antibodies (MAb), we measured by enzyme-linked immunosorbent assay serum levels of IgE, IgG, and IgA human antimurine antibody (HAMA) to T101, a murine IgG2a antibody that has been used in the treatment of cutaneous T cell lymphoma (CTCL) and chronic lymphocytic leukemia (CLL). None of 8 patients (4 with CLL, 4 CTCL) pretreated with T101 had elevated titers of any HAMA class tested as compared to normal control sera. All CTCL patients who had elevated total serum IgE levels, but normal total serum levels of other antibody classes, had significant rises in IgE, IgG, and IgA HAMA to T101 after intravenous MAb infusion. However, the CLL patients who were hypogammaglobulinemic failed to develop significant rises in HAMA. Three patients (2 CLL, 1 CTCL) had ITAR (e.g., urticaria, angioedema, bronchospasm) associated with infusion of T101; prophylactic medication regimens based upon the control of radiographic contrast media reactions were used with apparent benefit in subsequent infusions in these patients. All 8 patients had negative immediate intradermal skin tests (1 microgram/ml) to T101 prior to its infusion. Our data confirm that (1) non-IgE-mediated mechanisms cause ITAR from this MAb, possibly by a mechanism inherent in the action of this MAb against lymphocytes, and (2) that isotypic antibody responses to MAb vary with the type of malignancy being treated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Monoclonal antibody therapy of lymphoproliferative disorders.

Monoclonal antibodies, either alone or as immunoconjugates, are now being utilized to treat patients with a wide range of hematologic malignancies. The aim of early studies was to delineate the feasibility of this form of therapy, assess toxicities, and identify potential obstacles. These trials demonstrated that MoABs can be safely administered, and that clinically significant and durable responses occur. Areas of future research include the development of more potent immunoconjugates, the study of MoABs in conjunction with other treatment modalities, and the evaluation of approaches that may eliminate the human anti-mouse antibody response. Methods using MoABs to block growth factor receptors or as vaccines are being considered. At present, MoAB therapy remains investigational and should be restricted to patients with diseases refractory to standard therapies. We are encouraged, however, by the therapeutic results witnessed in early Phase I/II trials.

Antibodies, Monoclonal↗
PubMed1989

Internalization and shedding of Lym-1 monoclonal antibody following interaction with surface antigens of a cultured human B cell lymphoma.

Modulation of surface antigens of Raji Burkitt's lymphoma cells by monoclonal antibody Lym-1 was investigated by flow cytometry and radioimmunoassay (RIA). Raji cells, treated with antibody conjugated with FITC, became bright green as determined by FACS and the FITC-labeled Lym-1 remained associated with target cells for up to 48 hr after incubation at either 4 or 37 degrees C. Lym-1 antibody linked with biotin also bound to Raji cells and rendered these cells highly reactive with avidin-phycoerythrin (APE). However, the APE fluorescence intensity measured by FACS decreased substantially when Raji cells were cultured at 37 degrees C for 1 hr prior to APE exposure but not when incubation was carried out at 4 degrees C, indicating a disappearance of antibody from the surface of the metabolically active cells. This process was time dependent with a total loss of surface-bound biotinylated antibody occurring over a period of approximately 2 hr. Raji cells exposed to both fluoresceinated and biotinylated Lym-1 in a double labeling experiment became positive to both reagents. The flow cytometric profile was not altered when these cells were incubated for 1 hr at 4 degrees C followed by reaction with APE. However, they failed to react with APE when the 1-hr incubation took place at 37 degrees C despite the fact that they remained FITC positive, suggesting that the antibody with its fluorescent label had entered the cells. Utilizing 131I-labeled Lym-1 it was determined that approximately 50% of initially bound antibody had dissociated from the cells within the first 2 hr of incubation at 37 degrees C, although the remainder persisted with targets for up to 48 hr. The HPLC protein profile indicated that the radioactivity found in the culture supernatants and cytoplasm was associated with whole antibody, degradation products, and Ig complexes with antigen. Therefore, the present findings suggest that Lym-1 Ig molecules react with cell surface antigens and are rapidly internalized and shed, resulting in the disappearance of antibody from the surface membrane of Raji cells.

Antibodies, Monoclonal↗
PubMed1989

Stability of radioiodinated monoclonal antibodies: in vitro storage and plasma analysis.

The in vitro stability and immunointegrity of four radioiodinated monoclonal antibodies was evaluated in various storage conditions and also in plasma samples. The monoclonal antibodies studied included T101, B72.3, Lym1, and 16.88. Stabilities of typical monoclonal antibody therapy solutions, with radioactivities ranging from 2220 to 3700 MBq (60-100 mCi) were assessed using conventional instant thin layer chromatography and size exclusion high performance liquid chromatography. Radioimmunoreactivity was assessed using a live cell attenuated cell, or mucin-linked bead assay. Results of the study demonstrated that therapy solutions were stable to degradation, if properly stored in 5 or 10% human serum albumin at 4 degrees C for the duration of the study (5 days). Minor losses in immunoreactivity were also measured in stabilized therapy solutions. When incubated in plasma samples, radioiodinated monoclonal antibodies generally remained stable for the duration of the study (3 days). However, significant decreases in immunoreactivity were measured for specific radioiodinated monoclonal antibody preparations.

Antibodies, Monoclonal↗
PubMed1989

Value of post-therapy whole-body I-131 imaging in the evaluation of patients with thyroid carcinoma having undergone high-dose I-131 therapy.

Post-therapy whole-body I-131 images were compared to 5 mCi pretherapy diagnostic studies in 39 cases of well-differentiated thyroid carcinoma treated with I-131 to evaluate the utility of this procedure for the detection of residual thyroid tissue and functioning metastases. The post-therapy studies were performed immediately before hospital discharge, when the patient's whole-body retained dose had just fallen below 30 mCi. The mean therapeutic dose given was 121 mCi, and the mean interval between administration of the therapy dose and imaging was 2.4 days. In 18 cases (46.2%), the post-therapy images demonstrated either additional findings, such as unsuspected cervical node or pulmonary uptake, or more accurate localization of abnormalities seen on the diagnostic study. In 6 additional cases (15.4%), questionable new findings were noted. Although the precise implications of these additional findings are uncertain at present, they may have a significant effect on future patient management and follow-up. Therefore, the authors recommend that post-therapy imaging be included in the post-therapy evaluation of these patients. In addition, these findings would also suggest reevaluation of the advisability of using 1-2 mCi doses of I-131 for diagnostic whole-body imaging.

Adenocarcinoma↗
PubMed1988

Rapid miniaturized chromatography for 111In labeled monoclonal antibodies: comparison to size exclusion high performance liquid chromatography.

Our laboratory investigated the use of a rapid miniaturized chromatography system, ITLC-SG with 0.9% NaCl, to assess the radiochemical purity of 111In labeled monoclonal antibodies (MoAbs). Radiochemical analysis was performed on numerous 111In labeled antibody preparations with labeling efficiencies ranging from 40 to greater than 95% and the results compared to those obtained with size exclusion high performance liquid chromatography (HPLC). The chromatographic procedure involved challenging radiolabeled antibodies with 0.05 M DTPA to chelate unbound and/or non-specific bound 111In, spotting on miniaturized instant thin layer-silica gel chromatography strips, developing in 0.9% NaCl, and counting appropriate segments for radioactivity. Results of the study demonstrated that the miniaturized chromatography procedure was rapid, taking less than 4 min to complete, and accurate in assessing the amount of unbound or non-specific bound 111In in 111In labeled monoclonal antibodies, when compared to size exclusion HPLC.

Antibodies, Monoclonal↗
PubMed1988

Radioimmunotherapy of patients with cutaneous T-cell lymphoma using an iodine-131-labeled monoclonal antibody: analysis of retreatment following plasmapheresis.

Radioimmunotherapy retreatment of patients receiving radiolabeled murine monoclonal antibodies is difficult because of human antimurine antibody (HAMA) formation. Retreatment therapy was initiated in three patients at the time of disease progression using a radioiodinated monoclonal antibody (T101). The clinical protocol consisted of a two day plasma exchange (4-6 L) to reduce HAMA titers. Immunoimaging was performed with 5 mCi 131I-T101 (10 mg). Gamma scintillation images were obtained 18 hr postinfusion, and radiation dosimetry estimates were performed. At 24 hr postinfusion, each patient received a 100-mCi 131I-T101 (10 mg) therapy dose. Results obtained after plasmapheresis showed a significant reduction, ranging from 28%-61%, in HAMA titers. Blood clearances were markedly different between initial therapy and retreatment therapy for patient with high HAMA titers, reflecting immune complex formation. Two patients responded to retreatment therapy with responses lasting 1 to 2 mo. Minimal acute and no chronic toxicities were observed during the retreatment protocol.

Antibodies, Monoclonal↗
PubMed1988

Long-term persistence of human anti-murine antibody responses following radioimmunodetection and radioimmunotherapy of cutaneous T-cell lymphoma patients using 131I-T101.

Five cutaneous T-cell lymphoma (CTCL) patients have been imaged and treated with radiolabeled murine monoclonal antibody 131I-T101 in our laboratory. All patients developed human anti-murine antibody responses (HAMA) 14 days after the primary antibody infusion. HAMA responses could still be detected more than 22 months after T101 treatment. A substantial proportion of HAMA was crossreactive with any IgG2a antibody tested, although there did exist a specific anti-idiotypic component to HAMA. HAMA were of both IgM and IgG isotype. We also analyzed the effects of plasmapheresis on the specific HAMA isotypes in three patients who were retreated at the time of disease progression.

Aged↗