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Biomedical subjects

F Chu

Publications and source records attributed to F Chu.

At least 55 records · Page 3Linked to original sources
PubMed1990

Multispot, multianalyte, immunoassay.

Consideration of the basic principles of immunoassay design reveals that highly sensitive assays can, in principle, be developed using amounts of "sensor" antibody far smaller than are currently conventional in this field. Furthermore, when using such amounts, the fractional occupancy of antibody binding sites by analyte is independent of both sample volume and antibody concentration. Labelling of both the sensor-antibody and a developing antibody (designed to recognize either occupied or unoccupied sensor-antibody binding sites) permits the development of "ratiometric" immunoassays relying on measurement of the ratio of signals emitted by the two labelled antibodies. Furthermore, the sensor-antibody can be located within a "microspot" a few microns 2 in area. By labelling both sensor and developing antibodies with fluorescent labels, and scanning the microspot using a highly focussed laser beam, microspot immunoassays at least comparable in sensitivity with conventional "macroscopic" immunoassays are made possible. This in turn permits the development of immunoassay "arrays" capable in principle of measuring very large numbers of different substances within small samples (such as a drop of blood). The general principles and theory underlying these concepts are discussed, and preliminary experimental data using currently available instrumentation reported.

Fluorescent Antibody Technique↗
PubMed1989

High specific activity chemiluminescent and fluorescent markers: their potential application to high sensitivity and 'multi-analyte' immunoassays.

The sensitivities of immunoassays relying on conventional radioisotopic labels (i.e. radioimmunoassay (RIA) and immunoradiometric assay (IRMA) permit the measurement of analyte concentrations above ca 10(7) molecules/ml. This limitation primarily derives, in the case of 'competitive' or 'limited reagent' assays, from the 'manipulation errors arising in the system combined with the physicochemical characteristics of the particular antibody used; however, in the case of 'non-competitive' systems, the specific activity of the label may play a more important constraining role. It is theoretically demonstrable that the development of assay techniques yielding detection limits significantly lower than 10(7) molecules/ml depends on: (1) the adoption of 'non-competitive' assays designs; (2) the use of labels of higher specific activity than radioisotopes; (3) highly efficient discrimination between the products of the immunological reactions involved. Chemiluminescent and fluorescent substances are capable of yielding higher specific activities than commonly used radioisotopes when used as direct reagent labels in this context, and both thus provide a basis for the development of 'ultra-sensitive', non-competitive, immunoassay methodologies. Enzymes catalysing chemiluminescent reactions or yielding fluorescent reaction products can likewise be used as labels yielding high effective specific activities and hence enhanced assay sensitivities. A particular advantage of fluorescent labels (albeit one not necessarily confined to them) lies in the possibility they offer of revealing immunological reactions localized in 'microspots' distributed on an inert solid support. This opens the way to the development of an entirely new generation of 'ambient analyte' microspot immunoassays permitting the simultaneous measurement of tens or even hundreds of different analytes in the same small sample, using (for example) laser scanning techniques. Early experience suggests that microspot assays with sensitivities surpassing that of isotopically based methodologies can readily be developed.

Antibody Affinity↗
PubMed1988

Combination chemotherapy with mastectomy or radiotherapy for stage III breast carcinoma: a Cancer and Leukemia Group B study.

One hundred thirteen evaluable patients with previously untreated stage III breast carcinoma were treated with three monthly cycles of cyclophosphamide (CYC), doxorubicin (DOX), 5-fluorouracil (5-FU), vincristine (VCR), and prednisone (PRED) (CAFVP). Subsequently, 91 (81%) were deemed operable. Patients were then randomized to receive surgery or radiotherapy (RT) to determine which of these modalities afforded better local tumor control. All patients also received 2 additional years of CAFVP in a further attempt to eradicate local disease and systemic micrometastases. Forty-one of the randomized patients have relapsed. Approximately half of the initial relapses in each arm were local. The overall duration of disease control was similar following either modality, with a median of 29.2 months for surgery patients and 24.4 months for RT patients. Similarly, there was no major difference in survival related to randomized treatment with an overall median of 39 months (median follow-up 37 months). Pre- or perimenopausal status and inflammatory disease were associated with shorter disease control and survival. Treatment was generally well tolerated and toxicity was acceptable. This study demonstrates that prolonged control of stage III breast carcinoma can be achieved with combined modality therapy in which cytotoxic chemotherapy precedes and follows treatment directly primarily at the breast tumor, using either surgery or RT. Nevertheless, new regimens must be designed if significant advances that may lead to the cure of this disease are to be achieved.

Adult↗
PubMed1987

Two domains for splicing in the intron of the phage T4 thymidylate synthase (td) gene established by nondirected mutagenesis.

Of 97 nondirected T4 thymidylate synthase-defective (td) mutations, 27 were mapped to the intron of the split td gene. Clustering of these intron mutations defined two domains that are functional in splicing, each within approximately 220 residues of the respective splice sites. Two selected mutations, tdN57 and tdN47, fell within phylogenetically conserved pairings, with tdN57 disrupting the exon I-internal guide pairing (P1) in the 5' domain and tdN47 destabilizing the P9 helix in the 3' domain. A splicing assay with synthetic oligonucleotides complementary to RNA junction sequences revealed processing defects for T4tdN57 and T4tdN47, both of which are impaired in cleavage at the 5' and 3' splice sites. Thus prokaryotic genetics facilitates association of specific residue changes with their consequences to splicing.

Base Sequence↗
PubMed1986

Pulmonary edema and acute upper airway obstruction.

Pulmonary edema following the relief of acute upper airway obstruction is unusual and unpredictable. The cause is usually attributed to pulmonary and hemodynamic changes resulting from high negative intrathoracic pressures during obstructed respiration. The incidence of this problem is not known. Why pulmonary edema develops in only certain patients is also unclear. We reviewed the records of 27 consecutive adult patients admitted and treated for acute upper airway obstruction. Three of 27 (11%) developed pulmonary edema. Age, sex, diagnosis, duration of obstruction, history of cardiopulmonary disease, and perioperative fluid administration were evaluated. No differences were noted between those who did and those who did not develop pulmonary edema. Pulmonary edema following acute upper airway obstruction appears to be more common than is generally appreciated, however, no specific factors seem related to its occurrence.

Adult↗
PubMed1986

Reuse and reprocessing of disposable medical devices. Legal liability issues.

Reuse and reprocessing of disposable medical devices raises issues of legal liability, especially among physicians, hospitals, and device manufacturers. The practice of reuse has been, at least informally, reported to be fairly widespread. However, the medical risks associated with reuse are unresolved in most cases, which may lead to circumstances conducive to litigation. In this paper, the characteristics of reuse pertaining to legal liability, the parties potentially subject to civil liability suits as a result of reuse, the legal theories underlying claims of injury, and the legal implications of possible policy actions will be examined.

Disposable Equipment↗
PubMed1985

Processing of the intron-containing thymidylate synthase (td) gene of phage T4 is at the RNA level.

The interrupted T4 phage td gene, which encodes thymidylate synthase, is the first known example of an intron-containing prokaryotic structural gene. Analysis of td-encoded transcripts provides evidence in favor of maturation at the RNA level. Northern blotting with T4 RNA and with region-specific probes revealed three classes of RNA: diffuse premessage (ca. 2.5 kb), a low-abundance mature mRNA (ca. 1.3 kb), and an abundant free intron RNA (ca. 1.0 kb). The existence of covalently joined mature mRNA was suggested by hybridization and S1 protection experiments and was confirmed by primer extension analysis of the splice junction. In analogy to expression of interrupted eukaryotic genes, these results are consistent with an RNA processing model that would account for the direct gene transcript serving as precursor for both free intron RNA and a spliced mRNA that is colinear with the thymidylate synthase product.

Base Sequence↗
PubMed1985

A clinical study of benzydamine for the treatment of radiotherapy-induced mucositis of the oropharynx.

A double-blind, randomized clinical study was undertaken to determine the analgesic and antiinflammatory effectiveness of benzydamine in patients with radiation-induced mucositis of the oropharynx. Of the 67 patients in the study, 37 patients were on benzydamine and 30 patients on a placebo. The results of the study showed that benzydamine possessed a significant analgesic activity as evidenced by relief of mouth and throat pain induced by radiation therapy. It is also noted that the patients on benzydamine exhibited a cumulative relief of oral pharyngeal pain and discomfort over the time of treatment, as compared to those on the placebo. These effects of benzydamine in the present study might be a result of the antiinflammatory property of the drug. The cumulative and prolonged effectiveness of benzydamine makes it of distinct value compared with the commonly available local anaesthetics such as lidocaine. Benzydamine appears to provide a useful addition to the therapeutic armamentarium for alleviating the symptoms of oral pharyngeal mucositis.

Adult↗
PubMed1983

Perception of moving, sounding objects by four-month-old infants.

Infants and adults were presented with two moving objects accompanied by a single percussive sound. In different experiments, the sound occurred when one object moved through a particular spatial position, when it abruptly changed its direction of movement, or when it made contact with a rigid surface. Infants responded to the sound-object relationship whenever the sound occurred as the object changed direction, irrespective of its impacts with the surface. Adults, in contrast, responded to the sound-object relationship most clearly when sounds were synchronized with impacts. In infancy, perception of auditory-visual relationships thus depends in part on detection of discontinuities in the movement of a visible object.

Auditory Perception↗