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Biomedical subjects

J Reeder

Publications and source records attributed to J Reeder.

15 recordsLinked to original sources
PubMed1997

Increasing the use of advance directives in medical outpatients.

OBJECTIVE: We studied whether a simple educational intervention would increase patient completion of advance directives and discussions on end-of-life issues. DESIGN: Randomized, controlled trial. SETTING: Outpatient clinic of a teaching hospital. SUBJECTS: One hundred eighty-seven outpatients of a primary care internal medicine clinic. INTERVENTION: Study subjects attended a 1-hour interactive seminar and received an informational pamphlet and advance directive forms. Control subjects received by mail the pamphlet and forms only. MEASUREMENTS AND MAIN RESULTS: Completion of the advance directive was the main measurement. There were no significant differences in baseline characteristics of either group. Follow-up at 1 month revealed advance directive completion in 38% of study versus 24% of control subjects (p = .04), and discussions on advance planning in 73% of study versus 57% of control subjects (p = .02). Patients most likely to complete the documents were white, married, or attendees at the educational seminar. CONCLUSIONS: Interactive group seminars for medical outpatients increased discussions and use of written advance directives.

Adult↗
PubMed1996

Interlaboratory variability in fluorescence in situ hybridization analysis. The NCI Bladder Tumor Marker Network.

Reliable interpretation of fluorescence in situ hybridization (FISH) data, especially data that have been generated in more than one laboratory, requires knowledge of the sources of variability inherent in FISH analysis. Possible sources of variation may derive from differences in sample preparation, probes used, intrasample heterogeneity, hybridization protocols, counting criteria within and between scorers, fluorescence microscopes, and filters. This study characterized the relative weight of some of these factors in order to determine the degree to which FISH results are comparable between laboratories. We used a hierarchical partitioned chi 2 analysis to measure sources of variation. We found that replicate counts varied no more than expected based on counting statistics (i.e., multinomial variation). However, with replicate hybridizations done in two separate laboratories, the variability increased significantly. Thus, care must be taken when interpreting FISH data that are derived from more than one institution. Previously agreed upon counting criteria as well as standardized FISH hybridization protocols may decrease this variability.

Chi-Square Distribution↗
PubMed1996

Murine bispecific antibody 1A10 directed to human transferrin receptor and a 42-kDa tumor-associated glycoprotein.

Previously, we observed that bispecific antibodies ("antigen forks") that bound to certain pairs of different tumor surface antigens could inhibit cell growth. The chemically linked heteroconjugate of MAb 454A12 (murine IgG1 recognizing human transferrin receptor) and 317G5 (murine IgG1 recognizing a 42-kDa tumor-associated glycoprotein) was particularly inhibitory toward human colorectal cancer cell lines, and the iron-chelating agent deferoxamine was found to augment inhibition of tumor cell growth by this antigen fork. Further experiments revealed that an antigen fork constructed by linking Fab' fragments instead of whole antibodies retained activity, which led us to construct a fork-secreting hybrid hybridoma. Hybridoma 454A12 was fused with hybridoma 34F2 (murine IgG1 with the same specificity as 317G5). Hybrid hybridomas whose supernatants blocked binding of both 454A12 and 34F2 probes were further tested for the ability to block growth of SW948 human colorectal cancer cells in an MTT growth assay, and were chosen for subcloning. Ascites produced by clone 1A10 was purified by affinity and cation exchange chromatography. Purified 1A10 bispecific antibody showed growth inhibitory activity comparable to that of a chemically linked heteroconjugate of its parental antibodies 34F2 and 454A12. Adding deferoxamine greatly enhanced the inhibitory activity of 1A10 and effectively prevented regrowth of tumor cells in vitro. By heterologously crosslinking two antigens that are coexpressed on many tumor cells, this bispecific antibody is able to inhibit tumor growth with enhanced selectivity.

Animals↗
PubMed1996

In vitro tumor growth inhibition by bispecific antibodies to human transferrin receptor and tumor-associated antigens is augmented by the iron chelator deferoxamine.

Previously, a panel of mouse monoclonal antibodies (mAbs) to several tumor-associated antigens was chemically crosslinked to an IgG1 anti-human transferrin receptor antibody, 454A12. We called this new class of bispecific antibodies (BmAbs) "antigen forks" and showed that these antigen forks inhibited but did not completely prevent tumor cell growth. We speculated that the conjugates acted by heterologously crosslinking two antigens in a manner that interfered with the functions of one or both. The most effective BmAbs all shared one specificity for the human transferrin receptor. A monoclonal antibody to this receptor has been shown by others to reduce tumor cell growth when used with the iron chelator deferoxamine. When we combined our antigen forks with deferoxamine, two of five BmAbs synergized with deferoxamine to arrest tumor cell count at or below input levels. The most effective BmAbs were 317G5/454A12 (3/4) and 520C9/454A12 (5/4). mAb 317G5 recognizes a 42-kDa tumor-associated glycoprotein, and mAb 520C9 recognizes the c-erbB-2 protooncogene product. BmAb 3/4 was most effective against colorectal cancer cell line HT-29, and BmAb 5/4 was most effective against breast cancer cell line SK-BR-3. When deferoxamine and BmAb were replaced by fresh medium after a 6- or 7-day treatment period, no regrowth of tumor cells was observed during the next 4 days, although regrowth was seen if either deferoxamine or BmAb was used alone. Our results show that BmAbs with specificities for transferrin receptor and certain tumor-associated antigens effectively inhibit tumor growth in vitro. When used in combination with deferoxamine, such BmAbs may have therapeutic potential for the treatment of cancer.

Adjuvants, Immunologic↗
PubMed1996

Lung volume reduction surgery. Case selection, operative technique, and clinical results.

OBJECTIVE: A clinical study was undertaken to define optimal preoperative strategies and intraoperative techniques that would result in the least morbidity and maximum physiologic improvements in patients with end-stage emphysema selected for lung volume reduction surgery. BACKGROUND: Lung volume reduction surgery recently has been advocated as an alternative or a bridge to lung transplantation for patients with end-stage chronic obstructive pulmonary disease. The risks, benefits, and long-term results have not been clarified. METHODS: Twenty-six patients underwent lung volume reduction surgery with a 3-month follow-up on 17 patients. Preoperative and postoperative changes in pulmonary function parameters, quality of life, and oxygen requirement were analyzed. The value of preoperative localization of diseased lung segments and how this affects intraoperative resection is addressed. RESULTS: Forty-nine percent improvement in FEV1 (forced expiratory volume in 1 second) and 23% improvement in FVC (forced vital capacity) were seen after lung volume reduction surgery. Supplemental oxygen requirement was decreased and 79% of patients reported a much better quality of life. Mortality was 3.8% and air leak morbidity was 18%. CONCLUSIONS: Lung volume reduction surgery can predictably improve objective and subjective pulmonary function in selected patients with end-stage emphysema with low morbidity and mortality. Careful patient selection, accurate preoperative localization of diseased target areas, skilled anesthetic technique, meticulous operative approach, and intense postoperative support are essential to achieve favorable results.

Adult↗
PubMed1995

High-affinity monoclonal antibodies against P-glycoprotein.

Cancer patients treated with one anticancer agent often develop resistance to a broad spectrum of chemotherapeutic agents. This type of multiple drug resistance (MDR) is often accompanied by a decrease in drug accumulation and an increase in expression of a 170,000-Da plasma membrane glycoprotein (P-170) that can effectively pump various anticancer agents out of cytoplasm. A panel of 12 IgG1, IgG2a, or IgG2b monoclonal antibodies was generated against the extracellular portion of P-glycoprotein by immunizing mice with a human MDR1 gene-transfected BA3T3 fibroblast line. We have characterized two of the anti-P-glycoprotein monoclonal antibodies, 15D3 and 17F9, in some detail. Both antibodies immunoprecipitate a 170- to 180-kDa protein from MDR cells, but do not block binding of the known anti-P-glycoprotein antibody MRK16, suggesting that 15D3 and 17F9 bind to a different epitope on the extracellular domain of P-glycoprotein than MRK16. Scatchard analysis revealed that 15D3 and 17F9 had association constants of 1.3 and 1.1 x 10(8) M-1, respectively. 15D3 and 17F9 had little effect on MDR cell growth except for a minor inhibition of KB-V1 cells when the cells were incubated in the presence of vinblastine. Neither antibody inhibited the efflux of P-glycoprotein substrates from MDR cells. Because of their strong binding activity, these antibodies may be useful for diagnostic detection of MDR in patients undergoing chemotherapy or as targeting components of immunotherapeutic agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Antigen forks: bispecific reagents that inhibit cell growth by binding selected pairs of tumor antigens.

Bispecific antibodies of a new category, termed "antigen forks", were constructed by crosslinking antibodies that recognized pairs of distinct tumor cell surface antigens. At concentrations of 1-100 nM, several such forks inhibited the growth of human tumor cell lines bearing both relevant antigens. The same cells were not inhibited by unconjugated component antibodies, and the active conjugates did not inhibit the growth of human cell lines that expressed lower levels of relevant antigens. The three most active antigen forks all contained monoclonal antibody 454A12, which recognizes human transferrin receptor. This antibody was conjugated respectively to antibodies 113F1 (against a tumor-associated glycoprotein complex), 317G5 (against a 42-kDa tumor-associated glycoprotein), or 520C9 (against the c-erbB-2 protooncogene product). The 317G5-454A12 fork strongly inhibited the HT-29 and SW948 human colorectal cancer cell lines, while the 113F1-454A12 and 520C9-454A12 forks strongly inhibited the SK-BR-3 human breast cancer cell line and the 113F1-454A12 fork was also effective against SW948. By designing forks against antigens of incompatible function that are co-expressed at high levels on tumor cells but not on normal tissues, it may be possible to generate reagents that inhibit tumor growth with enhanced selectivity.

Animals↗
PubMed1992

Functional characterization of a novel anti-B7 monoclonal antibody.

For optimal activation of T cells, binding of their T cell receptor to antigenic peptides in the context of major histocompatibility complex molecules on antigen-presenting cells (APC) is not sufficient. Accessory signals, provided by accessory cells, are needed to induce proliferation and clonal expansion of normal T cells. It has been shown previously that the B7 molecule, present on the cell surface of activated APC, can provide the second signal by binding to the CD28 molecule on T cells. Here we describe a novel anti-B7 (mAb), B7-24. This mAb binds to a functionally important epitope of the B7 molecule. Fab fragments of B7-24 can almost completely block anti-CD3-induced, B7-dependent T cell proliferation when tested in a model system where purified T cells are co-cultured with 3T6 cells expressing the human Fc gamma RII and human B7, in the presence of anti-CD3 mAb. In contrast, mAb B7-24 is not able to inhibit T cell proliferation in primary mixed lymphocyte reactions where purified T cells are co-cultured with Epstein-Barr virus-transformed B cells. These findings suggest that other cell surface molecules allow for maximal proliferation of T cells in mixed lymphocyte reactions, even when the interaction between B7 and CD28 is blocked by B7-24.

Animals↗
PubMed1989

The evolution of an operative registry--a commentary.

The Operative Registry, also known as DA Form 4108, constitutes the basic, geographically focused, sequential log of operative activities for any given Army Medical Treatment Facility. The information provided for the Registry, with specific refinements, constitutes an essential data base for quality assurance and utilization review. The experience at Madigan Army Medical Center in developing the structure and function of this computerized data base is summarized.

Hospitals, Military↗
PubMedDate not supplied

Human cerebral malaria: lack of significant association between erythrocyte rosetting and disease severity.

The ability of Plasmodium falciparum isolates from 103 Papua New Guinea children with cerebral malaria and 158 children with uncomplicated malaria to form rosettes in vitro was studied. Of these, 81 isolates from cerebral malaria and 151 isolates from uncomplicated malaria grew to schizogony and were included in the rosetting analysis. Wide variation occurred in the level of rosette formation, with all isolates from both cerebral and uncomplicated malaria patients being able to form rosettes. No statistically significant difference existed between the geometric mean rosetting rate of isolates obtained from cerebral malaria and those from uncomplicated malaria (9% versus 8.6%, P = 0.27). The ability of acute sera to inhibit rosette formation was not significantly different between 18 cerebral malaria cases and 20 controls tested [mean reduction in rosetting rate 6.1% (SD 11.5) versus 8.4% (SD 12.3), P = 0.57]. The rosetting rate of cerebral malaria cases was not associated with the clinical outcome. Among the clinical and laboratory variables tested, only blood group and parasite density were significantly associated with rosetting. These data do not support the hypothesis that rosette formation is associated with cerebral malaria in Papua New Guinea, but indicate that rosetting is an intrinsic property of parasites occurring in all manifestations of the disease.

Adolescent↗