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Biomedical subjects

S Fields

Publications and source records attributed to S Fields.

At least 37 records · Page 2Linked to original sources
PubMed1996

Image-guided core-needle biopsy in malignant lymphoma: experience with 100 patients that suggests the technique is reliable.

PURPOSE: In an initial evaluation of 1,500 computed tomography (CT)-guided core-needle biopsies performed at our institute during the period from 1989 to 1994, we encountered 100 patients with the diagnosis of lymphoma. Here, we review the clinical impact of 109 image-guided needle biopsies in these 100 patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). PATIENTS AND METHODS: NHL was diagnosed in 71 patients, and 29 had HD. Among the NHL patients, 17 (24%) had proven lymphoma diagnosed before the biopsy was performed; in 54 (76%) core-needle biopsy was performed as the first diagnostic procedure. Of 29 HD patients, nine (31%) were already established cases of HD, and in 20 (69%) core-needle biopsy was the first diagnostic procedure attempted. Most of the biopsies were performed under CT control using a 20- or 18-gauge Turner biopsy needle. RESULTS: Eighty-six patients received therapy based on the results of the needle biopsy alone. Fourteen patients received therapy after undergoing surgical biopsy for a suspected diagnosis of lymphoma, which could not be established with certainty on the basis of an earlier core-needle biopsy alone. In 78% of the patients, the needle biopsy saved a further surgical procedure that may have been difficult to perform because of the primary location of the tumor. CONCLUSION: From our experience in this study, image-guided core-needle biopsies provide sufficient information for the diagnosis of and subsequent therapeutic decision to treat most cases of lymphoma.

Adolescent↗
PubMed1995

Dissociation of transcriptional activation and oncogenic transformation by v-Myb.

The nuclear oncoprotein v-Myb is a transcriptional activator in both animal cells and the budding yeast Saccharomyces cerevisiae. Previous studies have suggested that an acidic domain of approximately 50 amino acids (amino acids 204-254 of v-Myb) is necessary and sufficient for transcriptional activation by v-Myb, c-Myb and GAL4-Myb fusion proteins. However, we find that first, none of the acidic residues within this region is essential for transcriptional activation in either animal cells or yeast. Second, transcriptional activation requires cooperation among multiple domains of v-Myb. In animal cells, transcriptional activation by v-Myb requires a central domain (amino acids 234-295), a C-terminal domain (amino acids 295-356), plus either of two more N-terminal domains (amino acids 163-197 or 198-232); in yeast, it requires the central domain plus either the C-terminal domain or a more N-terminal domain (amino acids 163-233). Third, although various subsets of these domains are sufficient for transcriptional activation by v-Myb, all of the domains must be present for transformation of primary hematopoietic cells. These results demonstrate that transcriptional activation by v-Myb is not sufficient for oncogenic transformation.

Amino Acid Sequence↗
PubMed1995

Protein-peptide interactions analyzed with the yeast two-hybrid system.

The yeast two-hybrid system was used to screen a library of random peptides fused to a transcriptional activation domain in order to identify peptides capable of binding to the retinoblastoma protein (Rb). Seven peptides were identified, all of which contain the Leu-X-Cys-X-Glu motif found in Rb-binding proteins, although their activity in the yeast assay varied over a 40-fold range. Mutagenesis of the DNA encoding two of these peptides followed by screening in the two-hybrid system allowed the delineation of residues apart from the invariant Leu, Cys and Glu that affect binding to Rb. Binding affinities of a peptide and one of its variants to Rb, determined by surface plasmon resonance, correlated with results from the two-hybrid assay. This method offers several advantageous features compared to existing technology for screening peptide libraries: in vivo detection of protein-peptide interactions, high sensitivity, the capacity for rapid genetic screening to identify stronger and weaker binding peptide variants, and the use of a simple assay (transcriptional activity) as a means to assess binding affinity.

Amino Acid Sequence↗
PubMed1995

Interrater agreement in the interpretation of microscopic urinalysis.

To determine the reliability of specimen interpretation by outpatient laboratories, 150 consecutive specimens from three family practice centers were analyzed by either two laboratory technicians (n = 99) or two family physicians (n = 51). The results showed good to excellent agreement for contamination (defined as five or more epithelial cells per high-power field) or significant pyuria (five or more white blood cells per high-power field) or hematuria (five or more red blood cells per high-power field). Agreement between laboratory technicians did not differ significantly from agreement between physicians for the interpretation of contamination or pyuria, but for hematuria, agreement was higher between technicians (P = .02). These results suggest that outpatient interpretation of microscopic urine specimens shows levels of interrater agreement similar to or better than other tests that have been evaluated.

Humans↗
PubMed1995

A phase I and pharmacokinetics study of 2-chlorodeoxyadenosine in patients with solid tumors.

Preclinical studies of 2-chlorodeoxyadenosine (2-CdA) against solid tumors in the human tumor cloning assay and evidence that 2-CdA is active against slow-growing or resting tumor cells have stimulated interest in the clinical activity of this agent against solid tumors. This study sought to estimate the maximum tolerated dose, dose-limiting toxicity, and plasma and urine pharmacokinetics accompanying the intravenous administration of 2-CdA by 120-h continuous infusion in patients with solid tumors. Treated patients were also assessed for other toxicities of therapy and for antitumor response. A total of 23 patients received 35 courses of treatment given at doses of 3.5, 5.3, 6.5 and 8.1 mg/m2 per day by continuous intravenous infusion for 5 days and repeated every 28 days. Blood and urine specimens were collected before, during, and after drug infusion. The dose-limiting toxicity at 8.1 mg/m2 per day manifested as granulocytopenia in 2 of 5 patients (3 of 7 courses of treatment) and as thrombocytopenia in 3 of 5 patients (3 of 7 courses of treatment). At the dose levels of 6.5 and 8.1 mg/m2 per day, recovery from thrombocytopenia was often delayed. Severe lymphocytopenia (< 1,000/microliters) was observed at all dose levels of 2-CdA. Dose-related anemia and leukopenia were observed and were infrequently severe. Non-hematological toxicities were confined to mild-to-moderate nausea, vomiting, fatigue, and anorexia. Fever of 37 degrees-40 degrees C was induced during drug infusion in 19 patients. No antitumor response was observed. Average plasma concentrations at steady-state (Cpss) ranged from 3 ng/ml at the initial dose level to 13 ng/ml at the dose level of 8.1 mg/m2 per day. Both the Cpss and the area under the plasma concentration-time curve (AUC) were proportional to the dose. A relationship was observed between the percentage of change in absolute neutrophil count and the AUC. Renal excretion accounted for only 18% of the elimination of 2-CdA over the 5-day infusion period. The maximum tolerated dose for 2-CdA given by 5-day continuous infusion was 8.1 mg/m2 per day in this study. The recommended dose on this schedule for phase II studies is 6.5 mg/m2 per day. Granulocytopenia and thrombocytopenia were dose-limiting. No antitumor activity was observed during this study. On the basis of the plasma concentrations of 2-CdA observed, it is unlikely that this schedule of drug administration will permit achievement of the concentrations consistent with antitumor activity observed in preclinical studies.

Adult↗
PubMed1995

A centralized communication system.

Patient care redesign involves people, processes and technology coming together to meet or exceed patient expectations. A centralized communication system promotes professional nursing practice and optimizes all the team members' roles through more efficient use of staff.

Hospital Communication Systems↗
PubMed1995

Protein-protein interactions: methods for detection and analysis.

The function and activity of a protein are often modulated by other proteins with which it interacts. This review is intended as a practical guide to the analysis of such protein-protein interactions. We discuss biochemical methods such as protein affinity chromatography, affinity blotting, coimmunoprecipitation, and cross-linking; molecular biological methods such as protein probing, the two-hybrid system, and phage display: and genetic methods such as the isolation of extragenic suppressors, synthetic mutants, and unlinked noncomplementing mutants. We next describe how binding affinities can be evaluated by techniques including protein affinity chromatography, sedimentation, gel filtration, fluorescence methods, solid-phase sampling of equilibrium solutions, and surface plasmon resonance. Finally, three examples of well-characterized domains involved in multiple protein-protein interactions are examined. The emphasis of the discussion is on variations in the approaches, concerns in evaluating the results, and advantages and disadvantages of the techniques.

Carrier Proteins↗
PubMed1995

Alprazolam for tinnitus.

There is insufficient evidence to support the use of alprazolam in the treatment of tinnitus. The Johnson trial is the only study to date assessing the role of alprazolam, and at best it is an open-label trial demonstrating activity. There is a need for definitive double-blind, controlled, crossover studies of sufficient statistical power to resolve the issue. Furthermore, once efficacy is demonstrated, further studies are needed to determine the appropriate length of therapy, the necessity for maintenance therapy, the role of "drug holidays," appropriate dose tapering schedules, and a more careful delineation of which populations of patients are more likely to respond to alprazolam.

Alprazolam↗
PubMed1995

Radiologic spectrum of localized Castleman's disease.

We report seven patients with the localized form of Castleman's disease, diagnosed by surgical biopsy; four had the plasma cell type and three the hyaline vascular type. A variety of nonspecific clinical and radiologic findings were identified in these patients. Precise clinical staging is important to separate the widespread from the localized form of Castleman's disease, as the localized form may be successfully treated surgically. Percutaneous core needle biopsy is not helpful in the diagnosis of Castleman's disease. Significant computerized tomography enhancement with intravenous contrast in the hyaline vascular type is indicative of increased vascularity which may cause surgical complications when resection is attempted.

Adolescent↗
PubMed1995

Docetaxel (Taxotere) in combination: a step forward.

Docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) is a hemisynthetic derivative from European yew that inhibits tubulin depolymerization and enhances the formation of microtubule bundle aggregates, causing cell death. Activity against a variety of tumor types has been reported. Single-agent chemotherapy is rarely curative; hence, combination regimens are the logical next step in the attempt to improve tumor reduction and prolong survival. In preclinical studies, docetaxel has shown synergism with vinorelbine (Navelbine; Burroughs Wellcome Company, Research Triangle Park, NC), etoposide, cyclophosphamide, 5-fluorouracil, and methotrexate against a variety of murine tumors; in each case, at least 60% of the maximum tolerated dose could be administered without additional toxicity. Similar studies indicated an overlap in dose-limiting toxicity for docetaxel with cisplatin or doxorubicin, whereas with vincristine at least 80% of the maximum tolerated dose could be administered without additional toxicity. A number of docetaxel combinations are currently undergoing clinical evaluation and preliminary results appear to be encouraging. In a phase I trial, the docetaxel/5-fluorouracil combination exhibited activity against refractory solid tumors; grade IV neutropenia was observed, but there was no increase in gastrointestinal toxicity. The docetaxel/doxorubicin combination demonstrated impressive antitumor activity as front-line therapy for metastatic breast cancer (response rate, 70%), with little evidence of mucositis and dose-limiting toxicity experienced by only a minority of patients. Among 12 heavily pretreated phase I patients, the docetaxel/cyclophosphamide combination produced two partial responses in patients with breast cancer; three patients had febrile neutropenia and two had grade II mucositis. The docetaxel/vinorelbine combination produced responses at all dose levels as front-line therapy for metastatic breast cancer; dose-limiting toxicity was experienced by two patients, but only when the vinorelbine dose was raised to 22.5 mg/m2. In phase II studies in non-small cell lung cancer, preliminary results have shown the docetaxel/cisplatin combination to have a promising level of activity and an acceptable toxicity profile. Future trials will continue to evaluate the role of docetaxel in combination and in sequential regimens, most particularly in metastatic breast cancer and non-small cell lung cancer.

Adult↗
PubMed1994

Activated Ras interacts with the Ral guanine nucleotide dissociation stimulator.

The yeast two-hybrid system was used to identify proteins that interact with Ras. The H-Ras protein was found to interact with a guanine nucleotide dissociation stimulator (GDS) that has been previously shown to regulate guanine nucleotide exchange on another member of the Ras protein family, Ral. The interaction is mediated by the C-terminal, noncatalytic segment of the RalGDS and can be detected both in vivo, using the two-hybrid system, and in vitro, with purified recombinant proteins. The interaction of the RalGDS C-terminal segment with Ras is specific, dependent on activation of Ras by GTP, and blocked by a mutation that affects Ras effector function. These characteristics are similar to those previously demonstrated for the interaction between Ras and its putative effector, Raf, suggesting that the RalGDS may also be a Ras effector. Consistent with this idea, the RalGDS was found to inhibit the binding of Raf to Ras.

Amino Acid Sequence↗
PubMed1994

Two cellular proteins that bind to wild-type but not mutant p53.

p53 is a tumor-suppressor protein that can activate and repress transcription. Using the yeast two-hybrid system, we identified two previously uncharacterized human proteins, designated 53BP1 and 53BP2, that bind to p53. 53BP1 shows no significant homology to proteins in available databases, whereas 53BP2 contains two adjacent ankyrin repeats and a Src homology 3 domain. In vitro binding analyses indicate that both of these proteins bind to the central domain of p53 (residues 80-320) required for site-specific DNA binding. Consistent with this finding, p53 cannot bind simultaneously to 53BP1 or 53BP2 and to a DNA fragment containing a consensus p53 binding site. Unlike other cellular proteins whose binding to p53 has been characterized, both 53BP1 and 53BP2 bind to the wild-type but not to two mutant p53 proteins identified in human tumors, suggesting that binding is dependent on p53 conformation. The characteristics of these interactions argue that 53BP1 and 53BP2 are involved in some aspect of p53-mediated tumor suppression.

Amino Acid Sequence↗
PubMed1994

[Percutaneous, CT-guided excision of femoral osteoid osteoma].

An osteoid osteoma in the distal femur of a 10-year-old girl was excised, percutaneously, under CT guidance. Location of the nidus was by insertion of a Kirshner wire under CT control. Hollow Mill was used to excise the nidus by drilling over the Kirshner wire, with CT guidance during each stage. There were no complications and pain ceased overnight. Follow-up after 4 months showed complete recovery and no pain.

Child↗
PubMed1994

Magnetic resonance imaging and spectroscopy of MCF7 human breast cancer: pathophysiology and monitoring of treatment.

Magnetic resonance imaging at high spatial resolution, dynamic-contrast enhanced imaging, and localized 31P magnetic resonance spectroscopy were applied to monitor in vivo growth and tamoxifen treatment of MCF7 human breast tumors implanted in athymic mice. Correlation of the imaging data with histological findings demonstrated significant differences between viable carcinoma, fibrous, and necrotic regions on T2 weighted images. At an early stage after tamoxifen treatment rapid necrosis preceded tumor regression suggesting tamoxifen inhibition of angiogenesis. The necrosis was followed by growth of reperative fibrous tissue at the boundary of the viable cancer cells and the necrotic regions. The dynamic of contrast enhancement after tamoxifen treatment revealed high permeability of microvessels at this boundary cord. In parallel to the induction of the repair process the tumor energy profile changed, showing a significant increase in the ratio of ATP to inorganic phosphate. Initial attempts to use MRI for evaluating the response of breast cancer patients to treatment are also described.

Adenosine Triphosphate↗
PubMed1994

The two-hybrid system: an assay for protein-protein interactions.

The two-hybrid system is a yeast-based genetic assay for detecting protein-protein interactions. It can be used to identify proteins that bind to a protein of interest, or to delineate domains or residues critical for an interaction. Variations on this methodology have been developed to clone genes that encode DNA-binding proteins, to identify peptides that bind to a protein and, potentially, to screen for drugs.

DNA-Binding Proteins↗