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Biomedical subjects

B Feinberg

Publications and source records attributed to B Feinberg.

At least 19 recordsLinked to original sources

Measurement of vacuum-assisted photoionization at 1 GeV for Au and Ag targets.

We report a measurement of photon impact ionization of K and L shell of Au and K shell of Ag targets in the 1-GeV energy range. We show that the cross section is dominated by a contribution from a new channel called vacuum-assisted photoionization. In this process the energy-momentum balance associated with the removal of the innershell electron is obtained by conversion of a high-energy photon into an electron-positron pair. This measurement is consistent with the theoretical prediction that vacuum-assisted photoionization is the most probable ionization mechanism at very high energies.

Journal Article↗

Overall survival of the medical oncologist: a new outcome measurement in cancer medicine.

BACKGROUND: Changing patterns of patient referral, decreasing payments for service provision, confusing network participation and reimbursement, as well as challenges to autonomous clinical decision-making jeopardize the traditional role of the oncologist in delivering cancer care. The cancer patient also may be at risk with unproven cancer delivery systems that displace the oncologist as decision-maker and care provider. The authors have constructed a model that preserves the oncologist's clinical and financial autonomy while meeting marketplace demands for improved access, decreasing costs and preserved quality of care. METHODS: During a 4-year period, a group of private practice medical oncologists initiated a formal business plan to evaluate marketplace needs, then designed and implemented a novel cancer care delivery model. The model required reconfiguring the practice into an integrated Joint Commission on Accreditation of Healthcare Organizations-certified cancer service corporation, providing medical, radiation, and gynecologic oncology. Palliative care, pain management, psychologic, and nutritional services were instituted as well as the vertical integration of home health and hospice care. Clinical pathways and treatment protocols were designed to enhance patient care and facilitate cost-of-care projections in designated populations using a cancer incidence forecasting model. Outcomes analysis are performed as part of ongoing continuous quality improvement, which continues to change this health care delivery system. RESULTS: In the 3 years since implementation of the model, the practice has increased from 16 to 24 physicians, and the number of offices has increased from 12 to 17. Patient encounters, both new and established, have doubled. Cost of services, specifically hospitalization, have been reduced by 50%. Clinical research referrals have increased 300%. Physician compensation has improved >20%. CONCLUSIONS: The model created a low cost, high value provider not burdened by allocated overhead. Decentralized care enhanced community access, which improved patient compliance, enhanced patient satisfaction, decreased hospitalization, and thereby decreased cost. The horizontal structure permited the flexibility for varied purchaser products and politically sensitive physician and hospital provider panels. Consensus-based protocol and pathway determination achieved maximum physician participation, which preserved clinical and financial autonomy, decreased variance, and facilitated clinical research.

Age Distribution↗

Phase I study of a combination of recombinant tumor necrosis factor-alpha and recombinant interferon-gamma in cancer patients.

Combinations of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) demonstrate synergistic antiproliferative activity in vitro. Therefore, we initiated a clinical study of recombinant TNF-alpha (rTNF-alpha) and rIFN-gamma combination therapy in humans. Twenty-five patients with metastatic cancer received both rTNF-alpha and rIFN-gamma by intramuscular injection for 5 consecutive days every 2 weeks for a total of 4 weeks. The dose levels were 5/5, 10/5, 10/10, 25/10, 25/25, 50/25, 50/50, 75/50, and 75/75 micrograms/m2 per day of rTNF-alpha/rIFN-gamma. A minimum of 2 patients were entered sequentially at each dose level. If the first 2-week cycle of therapy was well tolerated, the dose was increased to the next highest dose level during the second 2-week cycle. Fever, chills, and fatigue were observed at all doses. Severity of symptoms corresponded to increasing dose levels. Although TNF is identical to a molecule known as "cachectin," the vast majority of our patients did not lose weight while on study. However, alterations in lipid metabolism occurred and were manifested by a median change in triglyceride values of +40 mg/dl (range, -130 to +318 mg/dl), and in cholesterol values of -30 mg/dl (range, -103 to +2 mg/dl). The maximum tolerated dose was 75 micrograms/m2 of rTNF-alpha combined with 50 micrograms/m2 of rIFN-gamma, with dose-limiting side effects being mainly constitutional symptoms. A dose-related suppression in granulocyte and platelet counts was observed. Hematologic parameters returned to baseline within 72 h after therapy was discontinued, and neither infection nor bleeding occurred. Ten of 22 evaluable patients had stable disease for a median of 8 weeks (range, 4-21 weeks); 12 patients showed progressive disease. This study will form the framework for phase II trials of rTNF-alpha and rIFN-gamma combination therapy.

Adolescent↗

A phase I trial of intravenously-administered recombinant tumor necrosis factor-alpha in cancer patients.

We report a phase I clinical investigation of 30-minute and four-hour intravenous (IV) infusions of recombinant tumor necrosis factor (rTNF)-alpha. Thirty-nine patients with disseminated cancer received escalating doses of rTNF-alpha for five consecutive days every 2 weeks for a total duration of 8 weeks. Dose escalations followed a modified Fibonacci scale with a minimum of four patients entered at each dose level: 5, 10, 25, 50, 75, 100, 150, 200, and 250 micrograms/m2/d. Toxicities consisted mainly of constitutional symptoms including fever, chills, headache, and fatigue, increasing in severity with dose escalation. No significant differences in dose-limiting toxicities were seen between the two rates of IV infusion. The maximum tolerated dose (MTD) was 200 micrograms/m2 with dose limiting toxicity being constitutional symptoms and hypotension. Hematologic changes included median decrease in both granulocyte and platelet counts of 38% and 41%, respectively (range, 16% to 85%), although clinically significant granulocytopenia and thrombocytopenia were not observed. Hematological parameters returned to baseline within 72 hours after rTNF-alpha was stopped. rTNF-alpha induced changes in lipid metabolism were manifested by median fasting triglyceride elevations above baseline (median, 103 micrograms/dL) of 157% (range, 16% to 389%) after five days of therapy with doses greater than 75 micrograms/m2, associated with a median increase in very-low-density lipoprotein (VLDL) of 80%. Serum rTNF peak levels exceeding 10 ng/mL were observed 30 minutes following rTNF-alpha infusions at MTD dose. Twelve of 34 patients had no change in their evaluable disease for a median duration of 18 weeks (range, 8 to 30 weeks), and 22 patients showed progressive disease. This study forms the framework for phase II trials of IV administered rTNF-alpha.

Adult↗

Identification of an altered elongation factor in temperature-sensitive mutant ts 7'-14 of Saccharomyces cerevisiae.

Postpolysomal extracts from wild-type (wt A364A) and temperature-sensitive (ts 7'-14) yeast cells were preincubated for short periods of time at the nonpermissive temperature (37-41 degrees C) prior to incubations for protein synthesis at 20 degrees C. Whereas wt A364A extracts were relatively unaffected by preincubation at the elevated temperature, mutant extracts lost their ability to translate exogenous natural mRNA and poly(U). Phe-tRNA synthetase and ribosomes from ts 7'-14 cells were not inactivated by preincubation at 37-41 degrees C, but a cytosolic component required for chain elongation, as measured by poly(U) translation, was extensively inactivated. The three elongation factors (EF-1, EF-2, and EF-3) required for chain elongation in yeast were resolved chromatographically. Only one factor, EF-3, was able to restore the poly(U)-translational activity of mutant extracts inactivated at the elevated temperature. Heat-inactivated yeast cytosols, which did not support protein synthesis with yeast ribosomes, were perfectly able to translate poly(U) with rat liver ribosomes, which require only EF-1 and EF-2. These and other experiments indicated that the genetically altered component in 7'-14 mutant cells is EF-3.

Kinetics↗

A competitive solid-phase radioimmunoassay for translational factors employing monoclonal antibodies.

Monoclonal antibodies produced by the hybridoma techniques were purified by chromatography on DEAE Affi-Gel blue, and covalently coupled to Affi-Gel 10 to purify their antigens. The purified components were used to develop a sensitive competitive radioimmune assay for the quantitative determination of translational factors, as described here with a monoclonal antibody directed against yeast elongation factor 3. Antigen was adsorbed to polyvinyl chloride plastic surfaces and a limiting concentration of monoclonal antibody necessary to bind to the adsorbed antigen was determined. Varying concentrations of purified antigen and of samples containing unknown amounts of antigen were then mixed with the limiting concentration of monoclonal antibody, prior to or at the same time as the reaction of the antibody with the surface-adsorbed antigen. The amount of monoclonal antibody that bound to the surface-adsorbed antigen was determined with a second antibody, radioactive goat anti-mouse antibody. The addition of the free antigen preparations to the monoclonal antibody served to compete for the antibody with the antigen adsorbed to the plastic surfaces. The concentration of antigen in the unknown samples was estimated from the titration curves obtained with varying concentrations of pure antigen. This technique did not require isotopic labeling, modification or derivatization of the monoclonal antibody or its antigen.

Antibodies, Monoclonal↗

Monoclonal antibody specific for yeast elongation factor 3.

Hybridomas have been prepared by fusing mouse myeloma (P3 X 63 Ag8) cells with spleen cells of mice immunized with a yeast fraction enriched with respect to non-ribosomal translational components. Cloned hybridoma lines were grown in the form of ascites tumors, and the monoclonal antibodies produced were purified from the ascites fluid by chromatography on DEAE-Affi-Gel Blue. One of the antibodies, from a hybridoma cell line designated as PSH-1, inhibited the translation of natural mRNA and poly(U) and polysomal chain elongation in a cell-free protein-synthesizing system from yeast. Resolution and partial purification of the elongation factors indicated that the monoclonal antibody from PSH-1 did not interact with EF-1 or EF-2 but reacted with and inactivated EF-3, the 125 000 molecular weight additional elongation factor specifically required with yeast ribosomes. The EF-3 purified from the cytosol by immunoaffinity chromatography was comparable to that prepared by ion-exchange chromatography. Evidence was obtained which indicated that EF-3 was essential for the translation of natural mRNA as well as poly(U), was associated with polysomes but not ribosomal subunits, and was required for every cycle in the elongation phase of protein synthesis.

Animals↗