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Biomedical subjects

R Gordon

Publications and source records attributed to R Gordon.

At least 73 records · Page 4Linked to original sources
PubMed1997

Resistance to cytotoxic drugs in DNA mismatch repair-deficient cells.

Loss of DNA mismatch repair is a common finding in many types of sporadic human cancers as well as in tumors arising in patients with hereditary nonpolyposis colon cancer. The effect of the loss of DNA mismatch repair activity on sensitivity to a panel of commonly used chemotherapeutic agents was tested using one pair of cell lines proficient or deficient in mismatch repair due to loss of hMSH2 function and another due to loss of hMLH1 function. 6-Thioguanine and N-methyl-N'-nitro-N-nitrosoguanidine, to which these cells are known to be resistant, were included in the panel as controls. The results were concordant in both pairs of cells. Loss of either hMSH2 or hMLH1 function was associated with low level resistance to cisplatin, carboplatin, and etoposide, but there was no resistance to melphalan, perfosfamide, 5-fluorouracil, doxorubicin, or paclitaxel. The results are consistent with the concept that the DNA mismatch repair proteins function as a detector for adducts produced by 6-thioguanine, N-methyl-N'-nitro-N-nitrosoguanidine, cisplatin, and carboplatin but not for melphalan and perfosfamide. They also suggest that these proteins play a role in detecting the DNA damage produced by the binding of etoposide to topoisomerase II and propagating signals that contribute to activation of apoptosis.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Loss of DNA mismatch repair in acquired resistance to cisplatin.

Selection of cells for resistance to cisplatin, a well-recognized mutagen, could result in mutations in genes involved in DNA mismatch repair and thereby to resistance to DNA-alkylating agents. Parental cells of the human ovarian adenocarcinoma cell line 2008 expressed hMLH1 when analyzed with immunoblot. One subline selected for resistance to cisplatin (2008/A) expressed no hMLH1, whereas another (2008/C13*5.25) expressed parental levels. Microsatellite instability was readily demonstrated in 2008/A cells but not in 2008 and in 2008/C13*5.25 cells. In addition, the 2008/A cells were 2-fold resistant to methyl-nitro-nitrosoguanidine and had a 65-fold elevated mutation rate at the HPRT locus as compared to 2008 cells, both of which are consistent with the loss of DNA mismatch repair in these cells. To determine whether the loss of DNA mismatch repair itself contributes to cisplatin resistance, studies were carried out in isogenic pairs of cell lines proficient or defective in this function. HCT116, a human colon cancer cell line deficient in hMLH1 function, was 2-fold resistant to cisplatin when compared to a subline complemented with chromosome 3 and expressing hMLH1. Similarly, the human endometrial cancer cell line HEC59, which expresses no hMSH2, was 2-fold resistant to cisplatin when compared to a subline complemented with chromosome 2 that expresses hMSH2. Therefore, the selection of cells for resistance to cisplatin can result in the loss of DNA mismatch repair, and loss of DNA mismatch repair in turn contributes to resistance to cisplatin.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Tracheal growth in congenital tracheal stenosis.

Two cases of congenital tracheal stenosis were managed conservatively despite mild to moderate initial respiratory symptomatology in infancy. Serial CT examinations were performed on each child, with tracheal dimensions and cross-sectional areas measured in the region of stenosis at each CT examination. The examinations document increases in tracheal cross-sectional area in the region of stenosis over time, confirming tracheal cartilage growth. We present these data to dispel the hypothesis that tracheal growth does not occur in complete-ring tracheal stenosis. The selection of cases for surgical repair must be considered with the knowledge that this anomaly does not carry an inevitably poor prognosis.

Follow-Up Studies↗
PubMed1996

Computed tomography using algebraic reconstruction techniques (ARTs) with different projection access schemes: a comparison study under practical situations.

In a previous report we presented a novel ART technique with the projections arranged and accessed in a multilevel scheme (MLS) for efficient algebraic image reconstruction, but whether the scheme is still superior in real situations where the data are noisy is unknown. In this paper, we make a detailed comparison between MLS and the other two conventional projection access orderings in ART: the random permutation scheme (RPS) and the sequential access scheme (SAS). By simulating reconstructions of a human head using different sizes of detector, taking different numbers of projections, each measurement under a different number of photons, a full mapping of the reconstruction accuracy measured by correlation coefficient for the three schemes has been made. Test results demonstrate that one-iteration MLS produces the best reconstruction in many situations. It outperforms one-iteration RPS when the noise level is low. SAS in many cases can never attain the image quality of one-iteration MLS, even with many more iterations. A convergence test using different initial guesses also demonstrates that MLS has less initial dependence. In the Fourier domain, it also represents an efficient and fast implementation of the Fourier slice theorem.

Adult↗
PubMed1996

Surface contraction and expansion waves correlated with differentiation in axolotl embryos. II. In contrast to urodeles, the anuran Xenopus laevis does not show furrowing surface contraction waves.

We have observed a number of contraction waves traversing the axolotl (Ambystoma mexicanum) embryo (a urodelan amphibian) from the midblastula transition up to at least neural tube closure, and wished to learn if similar "differentiation waves" appear on the popular laboratory anuran amphibian, the South African clawed toad, Xenopus laevis. Time lapse video microscopy showed that no contraction waves are visible on the surface of Xenopus from gastrulation through neurulation. It is possible that cell intercalations in the double-layered ectoderm of the Xenopus embryo are homologous to the surface waves in the single layered ectoderm of the axolotl embryo. In any case, a simple, universal correspondence between surface waves and induction phenomena and differentiation does not exist.

Ambystoma↗
PubMed1996

Binding ties: the roles of adult siblings of persons with mental retardation.

Current relationship patterns and future role expectations of 140 adult siblings of a brother or sister with mental retardation still living in the parental home were examined. Results showed that siblings maintained regular and personal contact, provided emotional support, and felt knowledgeable about the varied needs of their brother or sister with mental retardation. Of the siblings who had firm plans for the future, 36% intended to co-reside with their brother or sister with mental retardation, whereas 64% intended to live apart. Factors differentiating groups included gender (of both the sibling and the brother or sister with retardation), mother's health, level of mental retardation, and frequency of activities shared by the siblings during the past year.

Adult↗
PubMed1995

Cyclooxygenase-2 inhibitors. Synthesis and pharmacological activities of 5-methanesulfonamido-1-indanone derivatives.

The recent discovery of an alternative form cyclooxygenase (cyclooxygenase-2, COX-2), which has been proposed to play a significant role in inflammatory conditions, may provide an opportunity to develop anti-inflammatory drugs with fewer side effects than existing non-steroidal anti-inflammatory drugs (NSAIDs). We have now identified 6-[(2,4-difluorophenyl)-thio]-5-methanesulfonamido-1-indanone++ + (20) (L-745,337) as a potent, selective, and orally active COX-2 inhibitor. The structure-activity relationships in this series have been extensively studied. Ortho- and para-substituted 6-phenyl substitutents are optimal for in vitro potency. Replacement of this phenyl ring by a variety of heterocycles gave compounds that were less active. The methanesulfonamido group seems to be the optimal group at the 5-position of the indanone system. Compound 20 has an efficacy profile that is superior or comparable to that of the nonselective COX inhibitor indomethacin in animal models of inflammation, pain, and fever and appears to be nonulcerogenic within the dosage ranges required for functional efficacy. Although 20 and its oxygen linkage analog 2 (flosulide) are equipotent in the in vitro assays, compound 20 is more potent in the rat paw edema assay, has a longer t1/2 in squirrel monkeys, and seems less ulcergenic than 2 in rats.

Animals↗
PubMed1995

Allelic losses on chromosome band 11q13 in aldosterone-producing adrenal tumors.

We examined loss of heterozygosity (LOH) in 14 aldosterone-producing adrenal tumors, with six linearly ordered restriction fragment length polymorphism (RFLP) markers that map within a 12-cM region containing the MEN1 locus on 11q13. Among 11 tumors that were informative for at least one marker, five showed LOH at one or more loci, and two distinct regions of deletion were identified. The proximal region overlapped with the location of the MEN1 locus previously predicted by linkage analyses in MEN1 families and the commonly deleted region in hyperparathyroid tumors. This suggests that one of the genes associated with development of aldosterone-producing adrenal tumors may coincide with the MEN1 locus, and that a second gene, distal to the MEN1 locus, may also play a role in the development of this type of tumor.

Adrenal Gland Neoplasms↗
PubMed1995

Arthroscopic treatment for posterior impingement in degenerative arthritis of the elbow.

Twenty-one patients underwent arthroscopic treatment for posterior impingement associated with degenerative elbow arthritis. Anterior debridement and removal of loose bodies was performed first. The posterior procedure consisted of three parts: removal of posterior loose bodies, removal of the posterior olecranon osteophyte, and removal of the osteophytes in the olecranon fossa to the point of fenestration. Patients were assessed for pain, strength, motion, stability, and function. They were classified as excellent, good, fair, or poor. Twenty-one of 25 patients were followed an average of 35 months. There was a statistically significant improvement in all criteria. There were 10 good and 11 fair ratings preoperatively; this improved to 14 excellent and 7 good results postoperatively (P = .0001). Arthroscopic treatment for posterior impingement in the degenerative elbow offers substantial improvement with minimal risk, provided proper intraoperative precautions are followed.

Adolescent↗
PubMed1995

CT in patients with scirrhous carcinoma of the GI tract: imaging findings and value for tumor detection and staging.

OBJECTIVE: The purposes of this study were to analyze the CT features of scirrhous carcinoma of the gastrointestinal (GI) tract and to assess the usefulness of CT in detecting and staging these lesions. MATERIAL AND METHODS: This is a retrospective evaluation of 31 proven cases of scirrhous carcinoma (linitis plastica) of the GI tract imaged in our institution from 1986 to 1994. Twenty-two patients had primary gastric carcinoma, and nine had carcinoma of the colon (rectosigmoid in eight and right colon in one). CT examinations were reviewed and correlated with pathologic and/or surgical findings in all patients and with barium examinations in 19 cases. A modified Dukes classification was used to stage these lesions without knowledge of the pathologic and surgical results. RESULTS: Four gastric lesions were missed during the initial CT examination. Seventeen patients had extensive circumferential lesions, and five had focal plaquelike lesions. The wall thickness ranged from 1 to 3 cm (mean, 1.8 cm). Homogeneous enhancement was seen in 17 patients, slightly heterogeneous enhancement was seen in one, a target configuration was present in two patients, and intramural calcification was present in one patient. All colonic lesions were circumferential, homogeneously enhancing with a wall thickness ranging from 1 to 3 cm (mean, 2 cm). CT scans showed limitations in evaluating local parameters. Compared with surgical and pathologic staging, CT correctly staged 26 patients, understaged four patients, and overstaged one patient. Among the 19 patients with pathologically proven stage D lesions (61%), CT correctly staged 17 patients (89%) and had a 100% positive predictive value. One case of hepatic metastases, 13 cases of malignant ascites, and 11 cases of omental and peritoneal metastases were found. CONCLUSION: CT is an important complimentary imaging technique to detect scirrhous carcinoma. The sensitivity of detection depends on the size of the lesion and the quality of the examination. CT has limitations in staging early lesions but shows a high sensitivity (89%) in detecting Dukes stage D lesions. Accurate CT staging in these individuals (61% in this series) allows a more adequate treatment strategy and avoids unnecessary exploratory laparotomies.

Adenocarcinoma, Scirrhous↗
PubMed1995

Pharmacology of a selective cyclooxygenase-2 inhibitor, L-745,337: a novel nonsteroidal anti-inflammatory agent with an ulcerogenic sparing effect in rat and nonhuman primate stomach.

Recent studies have shown that there are two isoforms of cyclooxygenases. The constitutive form, cyclooxygenase 1 (COX-1), is believed to be involved in the maintenance of physiological functions. A second isoform, cyclooxygenase 2 (COX-2), has been shown to be induced in inflammation. In the present study, the pharmacology of a selective inhibitor of COX-2, L-745,337 (5-methanesulfonamido-6-(2,4-difluorothiophenyl)-1-indano ne), is described. L-745,337 has IC50 values of 23 +/- 8 nM and > 10 microM for the inhibition of prostaglandin E2 production in whole-cell assays for COX-2 and COX-1, respectively. This compound inhibited carrageenan-induced rat paw edema and rat paw hyperalgesia with ID50 values of 2.00 and 0.37 mg/kg, respectively. In an endotoxin-induced pyresis assay in the rat, L-745,337 significantly reversed the pyretic responses (ID50 = 3.75 mg/kg). L-745,337 did not cause visible gastric lesions in rats at up to 30 mg/kg (4 hr after dosing). In a fecal 51chromium (51Cr) excretion assay to detect gastrointestinal integrity in rats and primates, L-745,337 had no effect at doses up to 100 mg/kg (rat) or after chronic dosing at 20 mg/kg per day for 5 days (primates). In contrast, oral administration of indomethacin, diclofenac or flurbiprofen resulted in substantial increase in fecal 51Cr excretion and/or frank gastric ulceration (rats). L-745,337 significantly inhibited the prostaglandin E2 levels in the inflammatory exudates from the rat pleural cavity after injection with carrageenan but did not inhibit prostaglandin E2 levels in the stomach.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Patients achieve accurate home blood pressure measurement following instruction.

This study evaluates the effects of an instruction program conducted by registered nurses on subjects' ability to achieve three blood pressure measurements that were within 2 mmHg of simultaneous readings taken by an instructor listening through a dual headed stethoscope. The sample comprised 30 subjects aged between 22 and 76 years who were referred to a Hypertension Unit over a two month period for home blood pressure instruction. After approximately 45 minutes of individual instruction and practice in the use of an aneroid home blood pressure machine, subjects' ability to measure their blood pressure was assessed by the accuracy of their readings, their responses to a multiple choice knowledge questionnaire, their self-reported confidence in their ability to measure their blood pressure at home and an instructor's evaluation of their technique. Twenty seven percent of subjects achieved three measurements that were the same as those of their instructor, 57% and 17% obtained readings that were within 2 mmHg and 4 mmHg of an instructor respectively. Ninety percent of subjects obtained perfect scores in the knowledge questionnaire, 93% obtained perfect scores in the technique competency checklist and 100% of subjects either strongly agreed or agreed with the statement 'I feel confident enough to measure my blood pressure at home'. The study demonstrates that patients can be taught to accurately measure their blood pressure at home and, herefore, to provide reliable data to assist in the diagnosis and treatment of hypertension and hypotension.

Adult↗
PubMed1995

The healing event in Graeco-Roman folk-medicine.

The inexplicit character of Graeco-Roman folk-medicine, together with the distorted and haphazard nature of our evidence, has led to easy denigration of its aims and methods. Analysis of the structure of the healing event, especially its spoken component, the charm, provides some insight into tacit beliefs about illness, and into the skills through which folk-practitioners won reputations for competence. Just as in school medicine, the basic aim is acquisition of the authority to intervene: correct diagnosis, drawing upon folk-categories, is followed by the reassertion of order through setting the present contingency into the context of a natural law or regularity, drawing upon the stock of shared knowledge.

Greece, Ancient↗