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Biomedical subjects

R B Roth

Publications and source records attributed to R B Roth.

At least 19 recordsLinked to original sources
PubMed1999

DNA repair methyltransferase (Mgmt) knockout mice are sensitive to the lethal effects of chemotherapeutic alkylating agents.

We have generated mice deficient in O6-methylguanine DNA methyltransferase activity encoded by the murine Mgmt gene using homologous recombination to delete the region encoding the Mgmt active site cysteine. Tissues from Mgmt null mice displayed very low O6-methylguanine DNA methyltransferase activity, suggesting that Mgmt constitutes the major, if not the only, O6-methylguanine DNA methyltransferase. Primary mouse embryo fibroblasts and bone marrow cells from Mgmt -/- mice were significantly more sensitive to the toxic effects of the chemotherapeutic alkylating agents 1,3-bis(2-chloroethyl)-1-nitrosourea, streptozotocin and temozolomide than those from Mgmt wild-type mice. As expected, Mgmt-deficient fibroblasts and bone marrow cells were not sensitive to UV light or to the crosslinking agent mitomycin C. In addition, the 50% lethal doses for Mgmt -/- mice were 2- to 10-fold lower than those for Mgmt +/+ mice for 1,3-bis(2chloroethyl)-1-nitrosourea, N-methyl-N-nitrosourea and streptozotocin; similar 50% lethal doses were observed for mitomycin C. Necropsies of both wild-type and Mgmt -/mice following drug treatment revealed histological evidence of significant ablation of hematopoietic tissues, but such ablation occurred at much lower doses for the Mgmt -/- mice. These results demonstrate the critical importance of O6-methylguanine DNA methyltransferase in protecting cells and animals against the toxic effects of alkylating agents used for cancer chemotherapy.

Alkylating Agents↗
PubMed1996

Incorrect base insertion and prematurely terminated transcripts during T7 RNA polymerase transcription elongation past benzo[a]pyrenediol epoxide-modified DNA.

DNA replication and transcription are affected adversely by the presence of bulky adducts that are generated by the covalent binding of a variety of metabolically activated environmental pollutants to cellular DNA. When these lesions are not cleared by cellular repair enzymes prior to replication, mutations and ultimately tumor initiation can occur. Transcription and DNA repair appear to be intimately connected, since certain adducts are more efficiently removed from the transcribed strands of active loci than from non-transcribed strands and other quiescent domains in the genome. The mechanism by which RNA polymerases deal with bulky adducts during DNA transcription is therefore of great interest. The availability of site-specifically modified and stereochemically defined oligodeoxyribonucleotides derived from the covalent reaction of 7r, 8t-dihydroxy-9, 10t-epoxy- 7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) with guanine residues prompted us to study the efficiencies of transcription past these lesions using bacteriophage T7 RNA polymerase. We show here that T7 RNA polymerase can bypass such lesions in a DNA template, providing that a cytosine residue is incorporated opposite anti-BPDE-modified guanine. However, when an incorrect base (most frequently a purine) is inserted opposite the modified site, the RNA polymerase stalls, and the complex dissociates, resulting in a truncated transcript. The ability of the T7 RNA polymerase to discriminate between a correct and an incorrect inserted base and, accordingly, to continue or terminate transcription, might constitute an important mechanism that ensures the fidelity of transcription past a modified base present on the transcribed strand of the DNA template.

Bacteriophage T7↗
PubMed1990

Predictors of increased mitral regurgitation after percutaneous mitral balloon valvotomy.

Left ventriculography (LVG) was performed to assess severity of mitral regurgitation (MR) on a scale of 0-4+ in 157 patients before and immediately after percutaneous mitral balloon valvotomy (PMV). There were 129 women and 28 men aged 51 +/- 1 (range 13-87) yr. With PMV, mitral valve area increased from 0.9 +/- 0.1 cm2 to 2.0 +/- 0.1 cm2 (P less than .0001). Increase in mitral regurgitation (MR) occurred in 69 patients (44%). Patients were divided into two groups based on increase in MR after PMV. Group A (n = 136) had 0-1+ increase in MR. Group B (n = 20) had greater than or equal to 2+ increase in MR after PMV. The only predictor of increase in MR greater than or equal to 2+ was the ratio of effective balloon dilating area to body surface area (EBDA/BSA). EBDA/BSA was 4.0 +/- 0.1 cm2/m2 in Group A vs. 4.37 +/- 0.2 cm2/m2 in Group B (P = .02). Follow-up of patients in Group B showed: Four patients remained NYHA Class III and required mitral valve replacement 4.3 +/- 1.1 (range 5-21) mo after PMV. One patient who had undergone combined aortic and mitral valvotomy died in the hospital of worsening heart failure. One patient died 1 mo later of sepsis related to a dental abscess. Follow-up of the remaining 14 patients at 9.5 +/- 1.1 (range 2-7) mo showed 10 in NYHA Class I and four in NYHA Class II. Eight of 15 patients (53%) who had repeat left ventriculogram at 9.0 +/- 0.8 mo after PMV had a decrease in MR of one grade when compared to LVG immediately after PMV.

Adolescent↗
PubMed1989

Percutaneous aortic balloon valvuloplasty: its role in the management of patients with aortic stenosis requiring major noncardiac surgery.

Seven patients with severe aortic stenosis underwent percutaneous aortic balloon valvuloplasty in preparation for major noncardiac surgery. There were four men and three women (mean age 82 +/- 1.3 years, range 78 to 88). A significant reduction in the transaortic pressure gradient from 77 +/- 7.8 to 31 +/- 6.2 mm Hg (p = 0.002) and increase in calculated aortic valve area from 0.5 +/- 0.1 to 1.0 +/- 0.3 cm2 (p = 0.05) was noted. Three of the seven procedures were performed anterograde with use of transseptal puncture: two of the three because of abdominal aortic aneurysm and one because of peripheral vascular disease. All seven patients underwent uncomplicated noncardiac surgery under general anesthesia 10 +/- 4.3 days (range 0 to 29) after aortic valvuloplasty. One patient had exploratory laparotomy, one underwent stabilization of a hip fracture and two underwent resection of an abdominal aortic aneurysm. Of the three other patients who underwent colectomy, one had repeat aortic valvuloplasty and repair of a hip fracture 7 months later and one required exploratory laparotomy without repeat valvuloplasty 7 weeks later. Percutaneous aortic balloon valvuloplasty is an effective and safe procedure that may reduce the risk of general anesthesia and major noncardiac surgery in elderly patients with aortic stenosis.

Aged↗
PubMed1988

Renal cholesteatoma.

Renal cholesteatoma is being reported more frequently in the literature. A case with a twenty-year documented history is presented, together with observations on differential diagnosis.

Cholesteatoma↗
PubMed1987

Medical decision making for the incompetent patient.

In America competent adult patients have a right to refuse unwanted medical treatments. For incompetent patients who have made no advance directive, the family ordinarily makes decisions about medical treatments. But in many healthcare facilities, problems arise in choosing a surrogate to make decisions for an incompetent patient and in working with that surrogate. Concrete, step-by-step procedures for resolving conflict are needed. Every effort should be made to have competent patients fill out advance directives or indicate their treatment preferences in the event of loss of competence. Family members may not override decisions made by competent patients, but anyone closely involved with the patients' care may question their competence. The physician generally assesses the patients' competence, but sometimes the courts are involved. The physician may be the appropriate person to choose a surrogate for a patient with limited competence or to make decisions for a totally incompetent patient. The surrogate may be a relative, close friend, physician who knows the patient well, or someone provided by the hospital or government. Treatment decisions are made within the surrogate-patient-physician triad. When different value judgments about the proper treatment conflict, the surrogate may have to mediate to restore physician-patient communication, or institutional proceedings through the ethics committee may be needed to resolve disputes quickly, amicably, and at low cost. As a last resort, the case may be referred to the courts.

Conflict, Psychological↗
PubMed1985

Institutional ethics committees: what, how, and why.

Because institutional ethics committees can reduce the risk of tragic mistakes by clinical decision makers and provide interdisciplinary input into decisions, they may be a requirement for all hospitals by the end of this decade. Ethics committees should not in themselves be decision-making entities, however. Their proper functions are to advise physicians, patients, and families; facilitate communication; provide in-house education; assist in policy formulation; mediate between ethical theory and concrete medical judgments as well as between the institution's values and those of the larger community; provide support for those involved in painful decisions; and minimize the institution's vulnerability to litigation. Although ethics committees have been endorsed by federal agencies, a presidential commission, and numerous health care organizations, several obstacles remain. Physicians are afraid that their decisional prerogatives will be wrested from them; a committee could become a rubber-stamp organ for one powerful member, one special-interest group, or one perspective, confidentiality policies would have to be extended to nonhospital committee members; and medical personnel feel threatened by the exposure of errors or bad judgment. Nonetheless, ethics committees are a promising structural adjustment to ethical pressures exerted by new technology and the growing number of health care disciplines.

Ethical Review↗
PubMed1976

Regression of prostatic cancer metastasis by high doses of diethylstilbestrol diphosphate.

Diethylstilbestrol diphosphate (DES-P) has shown effective symptomatic relief in patients with metastatic carcinoma of the prostate. Although there is little known about its role in soft tissue metastasis, our experience in 3 patients with advanced carcinoma of the prostate infiltrating the trigone and ureterovesical junction revealed significant improvement of hydronephrosis. All patients failed to respond to conventional doses of stilbestrol. Diethylstilbestrol diphosphate is recommended in the treatment of advanced carcinoma of the prostate with soft tissue metastasis. It is safe and effective, and the tumor responses outweigh the side effects of the drug. The mechanism of action of this compound is discussed.

Aged↗
PubMed1975

Complete duplication of urethra.

Complete duplication of the urethra with a single bladder is an exceptional finding. The anomalous urethral canal originates from the bladder separately, runs parallel and usually dorsal to the normally situated urethra, and opens on the dorsum of the penis. To our knowledge there are 41 reported cases of this anomaly. We present 2 cases of complete urethral duplication originating from a single bladder, one in a male patient and the other in a female. It is concluded that conservative therapy is the treatment of choice, and that surgery should be reserved for incontinent patients only. The complications of surgery have been emphasized.

Adult↗
PubMed1975

Medicine in China.

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Acupuncture Therapy↗