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Biomedical subjects

R G Martin

Publications and source records attributed to R G Martin.

At least 55 records · Page 3Linked to original sources
PubMed1989

Characterization of the binding specificity of two anticruciform DNA monoclonal antibodies.

Two monoclonal antibodies (2D3 and 4B4) have been raised against a stable cruciform DNA structure containing the 27-base pair palindrome of the SV40 origin of replication on one strand and an unrelated 26-base pair palindrome on the complementary strand (pRGM 21 x pRGM 29) and have been shown to recognize conformational determinants specific to cruciform DNA structures (Frappier, L., Price, G.B., Martin, R. G., and Zannis-Hadjopoulos, M. (1987) J. Mol. Biol. 193, 751-758). To define the region(s) of the cruciform that is recognized by these antibodies, we examined the ability of 2D3 and 4B4 to protect the single-stranded tips of the loops or the four-way junctions at the base of the stem of stable cruciform molecules against cleavage by mung bean nuclease or T7 endonuclease 3, respectively. Both antibodies were found to protect two of the four elbow-like structures at the base of the cruciform from T7 endonuclease 3 cleavage, but not the tips of the cruciform arms from mung bean nuclease cleavage. Also, predigestion of the cruciform with mung bean nuclease did not affect the binding of either antibody. In addition, 2D3 bound to a cruciform and a T-shaped structure involving the palindromic sequence at the cloning site of pUC7, which is completely unrelated in sequence to the palindrome of pRGM 21 x pRGM 29, and protected the base of these stem-loop structures against cleavage by T4 endonuclease VII. These results indicate that 2D3 and 4B4 bind at or near the base of the cruciform molecules and that, at least for 2D3, binding is independent of DNA sequence.

Antibodies, Monoclonal↗
PubMed1989

Advanced basal cell carcinoma and successful treatment with chemotherapy.

The patient presented in this report has a large basal cell carcinoma on the wrist and thigh. The lesion on the wrist was nonresectable without amputation. The patient showed an impressive response to chemotherapy with systemic cyclophosphamide, adriamycin, and intra-arterial cisplatin. The tumor could be excised by a simple excision on both sites and showed no residual tumor on the hand and only a microscopic focus on the thigh. The patient continues to be free of disease 3 years after the initiation of the therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Radiotherapy for anal cancer: experience from 1979-1987.

Seventy patients with squamous cell carcinoma or cloacogenic carcinoma of the anus treated from 1979-1987 were reviewed. Five groups were analyzed: (a) local excision (LE) with postoperative radiotherapy (n = 9); (b) abdominoperineal resection (APR) with either pre- or postoperative radiotherapy (n = 22); (c) definitive radiotherapy alone (n = 8); (d) radiotherapy with continuous 5-Fluorouracil (5-FU) infusion (chemoradiation) (n = 25); and (e) patients treated for recurrent disease (n = 6). Abdomino-perineal resection and radiotherapy resulted in an actuarial local control (LC) rate of 90% and an overall 5-year survival rate of 77% (median follow-up, 48 months). All patients in Group 1 and 5/8 patients in Group 3 had locally controlled disease and were disease-free. The chemoradiation protocol resulted in a complete clinical response rate of 75% (18/24, one patient died during treatment) assessed 4-6 weeks after treatment. The colostomy-free local control rate with chemoradiation is 67% (16/24). Local control was 50% for all stages receiving 45-49 Gy and 90% for those patients receiving greater than or equal to 55 Gy but was not correlated with total 5-FU dose. Abdomino-perineal resection was performed to salvage six patients with persistent disease and two with recurrent disease, resulting in an overall local control rate of 92% (22/24). The actuarial survival was 96% (median follow-up, 14 months; range, 1-30). The acute complications of radiotherapy included diarrhea and perineal skin reactions that were increased by 5-FU infusion. However, diarrhea can be ameliorated by a modified treatment technique that reduces irradiation to the small intestine. For the entire patient group, minor late complications occurred in 23%, and major complications occurred in 9%.

Adult↗
PubMed1988

Adjuvant therapy of breast cancer with or without additional treatment with alternate drugs.

Three hundred ten patients with Stage II or Stage III breast cancer were entered on an adjuvant protocol consisting of a combination of 5-fluorouracil, doxorubicin, cyclophosphamide, vincristine, and prednisone (FACVP). In the second phase of the study, patients with estrogen receptor-negative tumors received sequential courses of methotrexate and vinblastine. Other patients, who were estrogen receptor-positive or unknown, were randomized to receive either tamoxifen alone or tamoxifen plus methotrexate and vinblastine. All therapy was completed within 1 year. The estimated disease-free rate at 5 years was 68% among patients with Stage II disease and 52% for patients who had Stage III disease. Among patients with estrogen receptor-positive tumors, disease-free survival was significantly prolonged in patients who received methotrexate and vinblastine in addition to tamoxifen (P = 0.04). However, this difference was less pronounced when all randomized patients (including those whose estrogen receptor status was unknown) were included in the comparison. Although most patients experienced moderate to severe granulocytopenia, infectious complications were infrequent. One patient died of septicemia. Congestive heart failure developed in two patients, one of whom had a history of myocardial infarction and congestive heart failure.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Pausing in simian virus 40 DNA replication by a sequence containing (dG-dA)27.(dT-dC)27.

A 200 bp sequence including a stretch of 54 base pairs of alternating guanosine and adenosine nucleotide residues [(dG-dA)27.(dT-dC)27] was cloned in the simian virus 40 (SV40) genome between the KpnI and HpaII sites. This sequence was discovered earlier as part of a region limiting the amplification of sequences adjacent to an integrated polyoma virus in a transformed rat cell line. The newly constructed DNA was transfected into African Green monkey kidney CV1 cells and the variant virus was isolated by plaque-purification. The insertion was stably maintained and the variant virus grew more slowly than the wild type, had lower titers and gave smaller plaques. In mixed infection experiments, the variant was found to be stable, though the wild type replicated more rapidly. Pulse labeling experiments indicated that the unusual inserted sequence acts as a pause site for fork progression during DNA replication, as evidenced by the rate of incorporation of radioactively labeled nucleotides into various regions of the SV40 genome. Statistical fit of the experimental curves with theoretically generated curves suggested the pause of fork progression to be about one minute.

Animals↗
PubMed1988

Abundance and degree of dispersion of genomic d(GA)n.d(TC)n sequences.

The abundance of d(GA)n.d(TC)n tracts was determined in genomes of rodents and primates. Dot blot hybridization assays revealed that such tracts constitute 0.40%, 0.30%, and 0.40%, respectively, of the rat, hamster, and mouse genomes, but only 0.07% and 0.05% of the human and monkey genomes. A plaque hybridization assay of rat and human genomic libraries showed that 37% and 16%, respectively, of the recombinant phages in these libraries contain d(GA)n.d(TC)n tracts. A survey of sequences stored in the GenBank data bank showed that a significant fraction of the stored rodent genes (about 2.0%) contain long d(GA)n.d(TC)n tracts (n greater than 30) with greater than 10% mismatching. The primate genes contain only shorter tracts (n less than 15) with less than 10% mismatching. In addition, the rodent and the primate genes contain tracts with larger degrees of mismatching. The chicken, which represents an entirely different branch of the evolutionary tree, was found to be as low in d(GA)n.d(TC)n tracts as the primates. It is suggested that a common ancestor of the rodents has acquired the ability to amplify d(GA)n.d(TC)n tracts.

Animals↗
PubMed1988

Treatment of soft tissue sarcomas by preoperative irradiation and conservative surgical resection.

From 1970-1984, 114 patients with soft-tissue sarcomas received preoperative irradiation at U.T.M.D. Anderson Hospital. Two patients refused surgery and two had progressing disease and therefore did not proceed to surgery; in the remaining 110 patients, conservative surgical resections were performed 3-6 weeks following irradiation. Analysis of survival by histologic type, age, primary size, and histologic grade revealed a significant negative correlation with grade 3 and to a lesser extent to primary size greater than 15 cm. Eleven patients failed within the radiation portal for the primary, four in conjunction with distant metastases. Of the remaining seven, four were salvaged by further surgery for an ultimate primary-only failure rate of three. Distant metastasis occurred in 35 patients and was the major mechanism of treatment failure in this experience. Adjunctive chemotherapy was not used for the majority of patients and it remains to be seen if its routine employment in large, high-grade, lesions will diminish the deaths caused by distant metastases.

Adult↗
PubMed1988

Structural state of newly replicated closed circular simian virus 40 DNA.

We have studied the early transition of newly replicated, segregated daughter molecules of simian virus 40 (SV40) into their mature, fully supercoiled state. The DNA of SV40 replicating in African green monkey kidney CV1 cells was chronically labeled with [14C]thymidine and pulse-labeled with [3H]thymidine. The cells were lysed and the viral DNA was isolated. Density gradient centrifugation of viral DNA in cesium chloride revealed that the pulse-labeled, newly synthesized, closed circular supercoiled DNA molecules banded at a slightly higher density (delta sigma = 0.0025) than the chronically labeled DNA, suggesting that the newly completed molecules were in a different structural state. Electrophoresis of DNA in agarose gels at appropriate chloroquine concentrations demonstrated that the mobility of the pulse-labeled closed, superhelical DNA was retarded relative to that of the chronically labeled DNA. These observations indicated that the newly completed SV40 DNA molecules existed in a structural state more relaxed than that of mature DNA by one or two linking numbers.

Animals↗
PubMed1988

Factors affecting the composition of mare uterine fluid.

The influx of protein and polymorphonuclear leucocytes (PMN) into the uterine lumen was examined at different intervals after intrauterine infusion of fluids. The intrauterine infusion of both phosphate buffered saline (PBS) and a solution of lipopolysaccharide (LPS) derived from Escherichia coli resulted in a biphasic influx of protein in the uterine flushings peaking three and six hours after infusion. LPS infusion caused an additional influx of protein at 24 hours. The initial influx of protein preceded a biphasic influx of PMN which peaked six and 24 hours after both infusions. Uterine flushings obtained following PBS and LPS infusion contained both serum-derived and uterine-specific proteins. To investigate whether the influxes were a general response to reproductive mucosal stimulation, several regions of the reproductive tract were subjected to physical manipulation. Results suggested that these influxes were initiated chiefly by stimulation of the cervical and, or, uterine region.

Animals↗
PubMed1987

Combined antiestrogen and cytotoxic therapy with pseudomonas vaccine immunotherapy for metastatic breast cancer. A prospective, randomized trial.

One hundred thirty-three consecutive, previously untreated patients who had metastatic breast cancer were treated with a combination of 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC). They were randomly assigned to receive nonspecific immunotherapy with a heptavalent pseudomonas vaccine. Sixty-five patients were treated with pseudomonas vaccine, whereas 68 did not receive immunotherapy. In addition, all patients with estrogen receptor-positive tumors or tumors with an estrogen receptor status were also treated with tamoxifen. To allow clinical assessment of hormone sensitivity in vivo, tamoxifen was started 6 weeks before chemotherapy except in patients who had life-threatening disease. After the initial 6 weeks of tamoxifen, 3% of patients had achieved a complete remission, 9% a partial remission, while 16% achieved a minor response. The maximum response after tamoxifen and chemotherapy included complete remissions in 20% of patients and partial remissions in 61% of patients for an overall remission rate of 81%. The median response duration was 15 months, and the median survival time, 27 months. There were no differences in remission rate, remission duration, or survival time between the groups treated with or without pseudomonas vaccine. Eleven patients with limited metastatic disease received radiotherapy consolidation to initially involved sites. In these patients the median time from radiotherapy to progression of disease was 33 months, and the median survival time was 46 months. We conclude that nonspecific immunotherapy with pseudomonas vaccine failed to increase remission rate or survival time. Furthermore, the addition of tamoxifen to FAC chemotherapy did not improve the remission rate or duration compared to a recent, historical control group of patients treated with only FAC chemotherapy.

Adult↗
PubMed1987

Monkey (CV-1) mitochondrial DNA contains a unique triplication of 108 bp in the origin region.

A fragment of monkey kidney cells (CV-1) mitochondrial DNA (mtDNA) containing the origin of replication has been cloned and sequenced. The nucleotide sequence, 640 bp, extends from the coding sequence of phenylalanyl tRNA to the flanking sequence upstream of the origin region. A unique triplication of 108 bp, including the evolutionary conserved sequence CSB-3, was found. Comparison between the origin regions of monkey, human and mouse mtDNA is presented.

Animals↗
PubMed1987

Monoclonal antibodies to cruciform DNA structures.

Two monoclonal antibodies, 2D3 and 4B4, have been raised against a cruciform structure in a heteroduplex DNA molecule. Antibody binding to DNA fragments was determined by a radioimmunoassay in which DNA--antibody complexes were separated from unbound DNA by acrylamide gel electrophoresis. These antibodies seem to recognize conformational determinants specific to cruciform structures. 2D3 and 4B4 antibodies do not bind to linear double-stranded homoduplex DNA fragments, linear single-stranded DNA or single-stranded simian virus 40 DNA containing a stem--loop structure, but do bind to the original cruciform and to a different cruciform with one shortened arm. 2D3 also bound to a T-shaped double-stranded DNA molecule, while 4B4 binding to this structure was weak. The monoclonal antibodies 2D3 and 4B4 were found to be immunoglobulin G1 and immunoglobulin M, respectively.

Animals↗
PubMed1987

Proton NMR of human breast tumors: correlation with clinical prognostic parameters.

Proton NMR spectroscopy and imaging of human breast tissue have provided new methods in studying breast carcinomas. Continuous wave proton NMR spectroscopy in this study is able to discriminate breast carcinomas from normal breast tissue on the basis of the integrated area under the water and lipid peaks, width at half height of the water peak, and chemical shift of the lipid peak. In addition, the NMR parameters were correlated with the following clinical and pathologic prognostic indices: TNM tumor stage, nuclear grade, and estrogen receptor status (ER). Width at half height of the lipid peak (1/2 delta lipid) correlated with tumor content and ER. Studies using higher resolution proton or phosphorus NMR spectra may separate signals that can correlate with biological information on breast neoplasms useful to the clinician. Chemical shift of the lipid peak may be used to sharpen contrast on MRI of breast tumors.

Adenofibroma↗
PubMed1987

Asteroid hyalosis affecting the choice of intraocular lens implant.

Asteroid hyalosis can create ultrasonic echoes capable of interfering with A-scan ultrasonic measurement of ocular length. Two cases are reported, one of which includes a measurement error necessitating a second implantation. Surgeons who entrust measurements to technicians should be aware of the measurement technique and should establish protocols that preclude such errors.

Aged↗
PubMed1986

The significance of synchronous carcinoma and polyps in the colon and rectum.

The relationship of colorectal carcinoma with polyps was studied retrospectively in 1202 patients. The incidence of synchronous carcinoma (SC) and metachronous carcinoma (MC), prognosis, and recurrence patterns were studied. Synchronous polyps (SP) were found in 36% of the patients. SC was found in 4.4% of the patients, and MC developed in 3.5% of patients. The incidence of SC and of MC increased with SP, and varied according to number, size, and histologic features of the polyps. The adjusted 5-year survival rate was improved in patients with SP compared with those without SP, both overall (79% versus 64%, respectively) and by Dukes' Stage B (87% versus 73%, respectively) and Dukes' Stage C (56% versus 39%, respectively). The pattern of relapse was the same for the SP and non-SP groups. Subtotal colectomy is recommended for colorectal carcinoma and SP in good-risk patients.

Adult↗
PubMed1986

Recurrence-free survival time for surgically treated soft tissue sarcoma patients. Multivariate analysis of five prognostic factors.

A staging system, based upon the experience of 1215 patients, was published by the American Joint Committee Task Force on Soft Tissue Sarcoma in 1977. A subset of these patients, 594, was selected to study recurrence-free survival time. The authors found 331 patients with a recurrence within 5 years (100 local only, 123 metastatic only, and 108 local + metastatic); median months to recurrence was 9.7. Within 5 years, recurrence was clearly associated with mortality: among the 331 patients who experienced a recurrence, 245 died, whereas only 31 died among the 263 who had no recurrence. To further evaluate the utility of the published staging system, a multivariate analysis of five factors was carried out for 297 of the 594 patients (patients with unknown information for any one of these factors were excluded). Factors in addition to grade that exerted a significant influence on recurrence were: direct extension, symptoms, and location of tumor when survival was measured to the first of any recurrence, and tumor size, measuring survival to the first metastatic recurrence. It is therefore recommended that these factors be taken into account in staging this disease. Estimates of probable recurrence-free survival time based upon the multivariate model (Weibull) are also presented.

Analysis of Variance↗