Search PubMed⌕ Search

Biomedical subjects

T J Dougherty

Publications and source records attributed to T J Dougherty.

At least 145 records · Page 8Linked to original sources
PubMed1981

Photoradiation therapy for cutaneous and subcutaneous malignancies.

Photoradiation therapy (PRT) using hematoporphyrin derivative (Hpd) as the photosensitizing agent is being developed for local treatment of a wide variety of malignant lesions including those involving the skin. The largest group of patients in this category are those with metastatic breast carcinoma in which 34/35 showed response to PRT. Other patients showing response to PRT are those with basal cell carcinoma, malignant melanoma, and squamous cell carcinoma.

Aged↗
PubMed1981

Competition of beta-lactam antibiotics for the penicillin-binding proteins of Neisseria gonorrhoeae.

The affinities of nine structurally different beta-lactam antibiotics for the three major gonococcal penicillin-binding proteins (PBPs) were determined by using a competition assay with tritium-labeled penicillin and live, growing bacteria. Each determination was carried out in parallel in isogenic pairs of penicillin-susceptible (minimal inhibitory concentration of penicillin, 0.0075 microgram/ml) and intrinsically penicillin-resistant (minimal inhibitory concentration of penicillin, 0.5 microgram/ml) cells. Evidence is presented indicating that (i) PBP 3 may be a dispensable function; (ii) acquisition of resistance is accompanied by change in the beta-lactam antibiotic affinities of PBP 2 but not of PBP 1; (iii) PBP 2 appears to be the most important physiological target in the penicillin-susceptible strain; in the penicillin-resistant strain, PBP 1 seems to assume this role. The relative affinities of various beta-lactam antibiotics for the individual PBPs showed substantial variation with the antibiotic structure.

Bacterial Proteins↗
PubMed1981

Autoradiographic distribution of hematoporphyrin derivative in normal and tumor tissue of the mouse.

The distribution of isotopically labeled hematoporphyrin derivative (HPD) has been studied in mice bearing the spontaneous mammary tumor (fast growing). In stomach, liver, spleen, and pancreas, 3 hr after i.p. injection of [3H]HPD, grains were uniformly distributed over the tissue sections. After 24 hr, the grain density overlying parenchymous areas of these tissues was lower than that over the stromal or reticuloendothelial areas. In the spontaneous mammary tumor (fast growing), higher grain densities were seen over pseudocapsule, stromal septa, and necrotic areas at 3, 6, 12, 24, and 48 hr after injection. At 168 hr postinjection, only isolated stomal cells, presumably macrophages, showed high grain densities. From the temporal changes observed in the distributions of HPD in normal tissues and the relative stability of the distribution seen in the spontaneous mammary tumor (fast growing), we speculate that tissue factors such as vascular permeability, lack of an adequate lymphatic drainage, and nonspecific binding of serum proteins to stromal elements may be responsible for or contribute to the preferential uptake and/or retention of HPD observed in both human and animal tumors.

Animals↗
PubMed1981

Interstitial photoradiation therapy for primary solid tumors in pet cats and dogs.

Photoradiation therapy, a new method for treatment of solid malignant tumors, depends upon the tumor localization and retention of hematoporphyrin derivative, which is activated in vivo by light in the red region of the spectrum. As currently applied to cutaneous and s.c. lesions, the light dose is limited by both normal tissue reactions and the effective penetration of the light through the tissues. In this report, primary solid malignant lesions in pet cats and dogs have been treated by interstitial photoradiation therapy by applying the activating light from a laser [635 +/- 5 (S. D.) nm] directly into the tumor masses thrugh a 200-micrometer quartz fiber optic. Twelve of 14 lesions (four osteosarcomas, two squamous cell carcinomas, two malignant melanomas, one mast cell sarcoma, one fibrosarcoma, one sebaceous gland sarcoma, and a metastatic prostatic carcinoma) responded to treatment, and three are currently considered permanently controlled at 1 year or more following treatment. This method has not only allowed photoradiation therapy to be applied to some remote lesions but has also nearly eliminated normal tissue effects, thus greatly extending the applicability of this treatment to a wide range of human tumors.

Adenocarcinoma↗
PubMed1980

Penicillin-binding proteins of penicillin-susceptible and intrinsically resistant Neisseria gonorrhoeae.

The penicillin-binding proteins (PBPs) of Neisseria gonorrhoeae were investigated by using [3H]benzylpenicillin of high specific activity. This made it possible to label the PBPs both in cytoplasmic membranes and in the membranes of actively growing cells (in vivo labeling). A total of 20 strains isolated from different geographic locales showed the same pattern of three major PBPs, which had molecular weights of approximately 90,000, 63,000, and 48,000. Five clinical isolates of intrinsically penicillin-resistant gonococci each exhibited reduced penicillin binding of PBPs 1 and 2. The construction of an isogenic set of transformants with increasing levels of penicillin resistance indicated that the penA gene was associated with a decrease in penicillin binding fo PBP 2. Decreased binding to PBP 1 is likely to accompany the newly reported pem and tem genes, which govern to highest level of penicillin resistance.

Bacterial Proteins↗
PubMed1979

Fluorescence bronchoscopy for detection of lung cancer.

A system using the fluorescence bronchoscope has been designed for localization of small, early bronchogenic carcinoma by the fluorescence of previously injected hematoporphyrin derivative. The system included a 200W mercury vapor lamp and primary filter, flexible fiberoptic bronchoscope with special violet-transmitting light conductor, secondary filter, and image intensifier tube. Tests indicated the system could detect a tumor only 100 micron thick at the expected concentration of hematoporphyrin derivative: 1 microgram/gm at 48 to 96 hours following intravenous injection at a dosage of 2.5 mg/kg. Examination of resected specimens (six of lung, one of esophagus) showed positive fluorescence in all cases, with fluorescence visible beyond the region visible under conventional white light examination. Fluorescence bronchoscopy has been performed on four patients thus far. Positive fluorescence was observed in all three cases where the tumor had been known to occur. Positive fluorescence was also observed in the patient with sputum positive for lung cancer, but negative x-ray film findings. However, additional examinations are required to demonstrate the smallest lesion that can be detected in vivo.

Bronchoscopes↗
PubMed1979

Photoradiation in the treatment of recurrent breast carcinoma.

Photoradiation, with the use of hematoporphyrin derivative (Hpd) activated by visible light in the red region of the spectrum, was an effective treatment for controlling local and regional chest wall recurrences of breast carcinoma. With sufficient time between iv injection of the drug and local activation with red light, cutaneous and subcutaneous masses were treated effectively without undue damage to overlying and adjacent skin. This high therapeutic ratio resulted from the ability to Hpd to accumulate and/or to be retained to a higher degree in malignant tissue than in many normal tissues. This technique can be used as a primary treatment or upon tumor recurrence following conventional modalities such as surgery, chemotherapy, and radiation therapy.

Breast Neoplasms↗
PubMed1979

Determination of [3H]- and [14C]hematoporphyrin derivative distribution in malignant and normal tissue.

The synthesis and tissue-localizing ability of [14C]- and [3H]hematoporphyrin derivative (HPD) in mice have been described. Tissue levels and distributions were the same for both radioactive compounds, indicating that in vivo tritium exchange did not occur with [3H]HPD. The amount of [14C]HPD or [3H]HPD which localized in the transplanted tumor tissue of mice at various times following i.p. injection (10 mg/kg) was higher than in skin or muscle tissue but was less than in liver, kidney, or spleen tissue. These results tend to disprove the generalization that HPD accumulates in malignant tissue to a higher degree than in all normal tissue. It is also reported that gross visualization of porphyrin fluorescence cannot be correlated with actual tissue concentrations of the dye.

Animals↗
PubMed1978

Photoradiation therapy for the treatment of malignant tumors.

Administration of hematoporphyrin derivative i.v. followed by local exposure to red light has resulted in complete or partial response in 111 of 113 cutaneous or s.c. malignant lesions. Tumors treated have included carcinomas of the breast, colon, prostate, squamous cell, basal cell, and endometrium; malignant melanoma; mycosis fungoides; chondrosarcoma; and angiosarcoma. No type has been found to be unresponsive. In several cases complete clearing of chest wall metastatis has been achieved in treated areas. Deep-seated and pigmented tumors required a higher dose of drug for effective treatment than did the more superficial and nonpigmented lesions. A high therapeutic ratio between tumor and skin response has been obtained by allowing at least 3 days between drug injection and exposure to the therapeutic light for 2,5-mg/kg doses and at least a 4-day interval for 5.0-mg/kg doses.

Adult↗
PubMed1976

A study of Salmonella contamination in broiler flocks.

The study was designed to follow the Salmonella infection rate in a poultry flock during the growth period until processing at 8-9 weeks. The infection rate was as high as 37.5% initially and dropped significantly by the 3rd to the 5th weeks. There was no difference between various types of litter and the species of Salmonella isolated. Little correlation was found between Salmonella species in feed ingredients and those identified from the flocks.

Animals↗
PubMed1976

Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumor.

Singlet oxygen, a metastable state of normal triplet oxygen, has been identified as the cytotoxic agent that is probably responsible for in vitro inactivation of TA-3 mouse mammary carcinoma cells following incorporation of hematoporphyrin and exposure to red light. This photodynamic inactivation can be completely inhibited by intracellular 1,3-diphenylisobenzofuran. This very efficient singlet oxygen trap is not toxic to the cells nor does it absorb the light responsible for hematoporphyrin activation. We have found that the singlet oxygen-trapping product, o-dibenzoylbenzene, is formed nearly quantitatively intracellularly when both the furan and hematoporphyrin are present during illumination but not when only the furan is present during illumination. The protective effect against photodynamic inactivation of the TA-3 cells afforded by 1,3-diphenylisobenzofuran coupled with the nearly quantitative formation of the singlet oxygen-trapping product indicates that singlet oxygen is the probable agent responsible for toxicity in this system.

Animals↗
PubMed1976

Energetics and efficiency of photoinactivation of murine tumor cells containing hematoporphyrin.

Hematoporphryrin derivative at an intracellular concentration in TA-3 mouse mammary carcinoma cells of 0.6 or 0.9 mM required input of 3.0 X 3.6 X 10(9) quanta/cell of red light (620 nm) to achieve a 90% kill. At an intracellular concentration of 1.2 mM, this light requirement drops to 1.5 X 10(9)quanta/cell. The energy for this photodynamic process is about 100 times higher than that required for ionizing radiation to achieve the same level of kill for these cells. The quantum yield for singlet oxygen formation (the cytotoxic agent in most photodynamic processes) from hematoporphyrin derivative is 0.75 +/- 0.07 in ethanol but only 0.16 +/- 0.07 within TA-3 cells, indicating possible intracellular complexing and quenching.

Animals↗
PubMed1975

Photoradiation therapy. II. Cure of animal tumors with hematoporphyrin and light.

Exposure of mouse and rat tumors of various types to more than 600 nm light 24 or 48 hours after an injection of hematoporphyrin resulted in a substantial number of long-term cures. Since hematoporphyrin is preferentially retained in tumor tissue, selective tumor destruction could be obtained. Light penetration studies and the high efficiency of this technique indicated its applicability even to certain deep-seated human tumors.

Animals↗