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Biomedical subjects

F Chu

Publications and source records attributed to F Chu.

At least 37 records · Page 2Linked to original sources
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↗
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↗
PubMed1980

Treatment of regionally advanced epidermoid carcinoma of the extremity and trunk.

A retrospective study was made of 106 locally and regionally advanced epidermoid carcinomas of the trunk and extremity treated from 1949 to 1970. Forty-six of the tumors had a known cause, of which radiation exposure was the most common. In addition to axillary and inguinal nodal metastases, these cancers also manifested intransit, epitrochlear and popliteal lymphatic metastatic disease. Surgical treatment consisted of wide monobloc resection for the majority of the primary neoplasms, amputation being necessary for tumors fixed to skeletal or neurovascular structures. Clinically enlarged regional lymph nodes were subjected to biopsy, but elective regional node dissection did not offer therapeutic benefit. Patients with biopsy proved nodal metastases were treated by either radical nodal dissection or high exarticulation, with similar results. Actuarial five year survival rates after definitive surgical treatment were 71 per cent for patients with regional node-negative and 57 per cent for those with regional node-positive tumors. Local and regional recurrences of tumors were frequent in patients who had deep seated tumors of the trunk and postsacral region, or bulky nodal disease, despite pathologically negative resection margins. Uncontrolled recurrent tumor with sepsis and compromise of vital organ function was the most common cause of death. Radiation therapy achieved partial regression of the tumor in eight patients and complete regression in one of 15 patients. A critical analysis is made of the various clinicopathologic factors which affect prognosis, and the possible means of improving the results of treatment are discussed.

Adult↗
PubMed1979

Effect of deglycosylation of yeast invertase on its uptake and digestion in rat yolk sacs.

The uptake by rat yolk sacs of native invertase and invertase which was deglycosylated by treatment with endo-beta-N-acetylglucosaminidase was compared. The initial rate of uptake of the deglycosylated enzyme was severalfold greater and its accumulation leveled off much earlier than that of the native enzyme. Uptake rates of the deglycosylated and native forms of the enzyme were proportional to their concentration in the medium in the range employed and were inhibited about 85% by 10(-6) M glucagon in both cases. After preloading of yolk sacs with native invertase, the tissue level of activity remained relatively constant over a subsequent 6-h time period, while with the deglycosylated form, activity declined substantially. Since this difference appears not to be attributable to differences in thermal stability, it is suggested that the deglycosylated form of the protein is more susceptible to intracellular proteolytic digestion. In vitro studies on the digestion of these two forms of invertase by trypsin are consistent with this suggestion.

Animals↗