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Biomedical subjects

P R Miller

Publications and source records attributed to P R Miller.

At least 19 recordsLinked to original sources

Radiation resistance in a doxorubicin-resistant human fibrosarcoma cell line.

In clinical practice, cancers refractory to chemotherapy can appear relatively radioresistant. Recent work in multidrug-resistant cell lines has yielded conflicting results concerning the relationship between drug resistance and radiation resistance. The current study examines the radiation response of a human fibrosarcoma (HT1080) and a doxorubicin-resistant subline (HT1080/DR4). Using soft-agar colony formation after graded doses of x-rays as an endpoint, HT1080/DR4 had an increased D0 (D0 = 2.1 Gy) and a broader initial shoulder (n = 2.7, Dq = 2.1 Gy) than the parental HT1080 line (D0 = 0.7, Gy, n = 1.2, Dq = 0.3 Gy), suggesting that HT1080/DR4 has an increased capacity to repair radiation-induced DNA damage. This possibility was tested by comparing the cell lines' ability to accumulate sublethal damage. In split-dose recovery experiments, HT1080/DR4 demonstrated increased ability to repair sublethal radiation damage following fractionated irradiation, compared with the HT1080 parental line. The mechanism for this radiation resistance is not clear, but a variety of cellular alterations seen in drug-resistant cell lines are discussed with reference to areas of further study.

Cell Cycle

Effects of v-src oncogene activation on radiation sensitivity in drug-sensitive and in multidrug-resistant rat fibroblasts.

Recent work has implicated the activated ras oncogene, whose gene product is a G-protein located in the plasma membrane, as well as the activated raf oncogene, whose gene product is a membrane-associated protein kinase, in contributing to radioresistance. Another transforming oncogene whose gene product is localized to the plasma membrane is v-src. We have examined a rat fibroblast line (RAT-1) infected with an avian sarcoma virus carrying a temperature-sensitive mutation in the v-src tyrosine kinase domain (LA-24). At 40 degrees C, LA-24 cells have a flat morphology and grow as a contact-inhibited monolayer, while at 35 degrees C, LA-24 cells have a transformed morphology, lose contact inhibition, grow in soft agar, and exhibit 3.5-fold higher tyrosine kinase activity. The parental RAT-1 line, not infected by the virus, grows at both temperatures as a contact-inhibited monolayer. This well-characterized system represents a good model for examining the effect of v-src transformation on radiosensitivity. RAT-1 and LA-24 cells grown at 35 and 40 degrees C were irradiated with graded doses of radiation, and clonogenic survival was assayed. For LA-24 cells grown at 35 and 40 degrees C, and for RAT-1 cells grown at 35 and 40 degrees C, calculated D0, n, alpha, and beta values did not differ significantly. To determine whether there might be differences in radiation damage repair capacity too subtle to detect by comparing radiation survival curves, sublethal damage repair capacity was assessed. There was no difference in sublethal damage repair capacity for LA-24 cells grown at 35 or 40 degrees C. Other studies have associated multidrug resistance with radioresistance. We have examined the radiation sensitivity of two colchicine-resistant LA-24 clones with four- to fivefold amplification of the P-glycoprotein gene, which are four-to fivefold more resistant to colchicine than the parental LA-24 line. In these multidrug-resistant clones, v-src activation does appear to increase radiation resistance. This did not appear to be due to alteration in cell cycle kinetics. We conclude that oncogene activation, or even protein kinase activity per se, does not necessarily lead to radiation resistance. Rather, radiation resistance following oncogene activation depends upon the oncogene and cell line studied, and perhaps upon specific protein phosphorylation.

Animals

Medial dislocation of the patella.

Medial dislocation of the patella is a previously unreported entity. This disorder can be disabling to the patient and may require a hospital visit for reduction. Three cases are presented in this article in which computed tomography demonstrated the dislocation. All three patients had undergone a lateral retinacular release to the involved knee for treatment of chronic knee pain or recurrent lateral patellar subluxation.

Adult

Acute ureteral obstruction as a complication of suprapubic catheterization.

Suprapubic cystostomy catheters are an important tool for the management of patients who require urinary drainage. Although complications occur after the procedure, they are usually minor. A case of acute obstruction at the ureterovesical junction caused by a suprapubic cystostomy catheter tip is presented.

Acute Disease

Detection and quantification of laryngotracheopulmonary aspiration with scintigraphy.

Aspiration is analyzed by a new scintigraphic technique and standard videofluoroscopy in 78 patients with head and neck pathology and neurologic disorders. When both methods are compared to clinical aspiration and a positive x-ray film of pneumonia, they appear to complement each other and provide a very accurate evaluation. Scintigraphy is a more sensitive method for detecting aspiration below the vocal cords and also provides for flow dynamics and a method of quantifying the amount of aspirated material. Videofluoroscopy shows more clearly the mechanism of the swallowing disorder and how the bolus enters the tracheobronchial tree. Studies in patients following head and neck surgery demonstrate a high incidence of dysphagia, aspiration, and pneumonia.

Deglutition

Celestin tube use: radiographic manifestations of associated complications.

Celestin intubation of the esophagus is occasionally employed in the palliation of unresectable esophageal carcinoma and in the obturation of malignant tracheoesophageal fistulas. Fourteen of 192 patients with carcinomas of the esophagus had Celestin tubes inserted at our institution between October 1977 and October 1982. Although tube insertion carries a low operative risk, there is significant subsequent morbidity associated with its use. Complications were identified radiographically in 11 of the 14 patients. Gastroesophageal reflux with aspiration pneumonia, tube obstruction, and tube migration were demonstrated most often. When Celestin tube use is deemed appropriate, the clinician and radiologist should be aware of the possible complications.

Adult

Simplification and spin-spin analysis of the side chain proton magnetic resonance spectrum of the decapeptide gramicidin S using difference scalar decoupling and biosynthesis of specifically deuterated analogs.

Biosynthesis of specifically deuterated molecules and difference scalar decoupling permitted an analysis of all C alpha-C beta spin systems of gramicidin S. Proof is presented that proton magnetic resonance spectra obtained by difference scalar decoupling yield not only spectral assignments and simplification but also accurate chemicals shifts and scalar coupling constants. The variations in (3J alpha beta) and in proton chemical shifts at temperatures over the range of -54 degrees -+66 degrees C are consistent with the internal rotation around the C alpha-C beta bonds of Val1, Orn2, Leu3, and Phe4 residues discovered using carbon 13 spectroscopy. The value (3J alpha beta) = 1.5 Hz for the proline residue is consistent with there being only one C alpha-C beta conformer. This is supported by the small temperature dependence of (3J alpha beta). However, it cannot be rigorously excluded that oscillation between a major and a minor C alpha-C beta conformation occurs for proline.

Amino Acids

Response of women with primary orgasmic dysfunction to audiovisual education.

Of 17 women ages 19 to 38 with primary orgasmic dysfunction, 7 achieved orgasm within a week after viewing an audiovisual sex education program, a statistically significant change (p less than .02). No other intervention (educational, behavioral, psychotherapeutic) occurred between the audiovisual session and later inquiry about subsequent sexual response. These results suggest that explicit sex education can help remedy sexual dysfunction in a significant number of women and that further investigation is needed.

Adult

The hazards of tibial pin replacement in 90--90 skeletal traction.

Tibial pin placement and 90--90 traction may lead to serious knee difficulties. Not only proximal tibial epiphyseal insult, but also serious displacement of the tibia on the femur may occur. In light of these potential complications, distal femoral pin placement should always be preferable for 90--90 traction in treatment of fractured femurs in children.

Adolescent

Substance abuse attitude changes in medical students.

The authors describe a course in substance abuse given to sophomore medical students with the intention of positively influencing their attitudes toward substance-abusing patients and their treatment. Clinical problem solving and small group discussion were emphasized in addition to field trips. By pretest and posttest measures, significant positive changes were obtained in student attitudes: they reported feeling less upset when they encountered alcoholics, "hard" drug abusers, "soft" drug abusers, compulsive smokers, and obese overeaters as well as having a more positive view of the physician's role in the treatment of substance dependence. Personal experience with alcohol and other drugs was shown to have an influence on attitude changes.

Alcoholism

Hair strangulation.

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Constriction, Pathologic

Primary subacute pyogenic osteomyelitis in long bones of children.

Ten cases of primary subacute osteomyelitis illustrate its clinical resemblance to various bone neoplasms. Diagnosis was established by open biopsy. Treatment with curettage, cast immobilization, and antibiotics, when indicated, resulted in radiographic healing and resolution of symptoms.

Adolescent