Biomedical subjects
J Foley
Publications and source records attributed to J Foley.
Strategies for selective cancer photochemotherapy: antibody-targeted and selective carcinoma cell photolysis.
A principle objective in chemotherapy is the development of modalities capable of selectively destroying malignant cells while sparing normal tissues. One new approach to selective photochemotherapy, antibody-targeted photolysis (ATPL) uses photosensitizers (PS) coupled to monoclonal antibodies (MAbs) which bind to cell surface antigens on malignant cells. Selective destruction of human T leukemia cells (HBP-ALL) was accomplished by coupling the efficient PS chlorin e(6) to an anti-T cell MAb using dextran carriers. Conjugates with chlorin: MAb ratios of 30:1 retained > 85% MA b binding activity, and had a quantum yield for singlet oxygen production of 0.7 +/- 0.1, the same as that of free chlorin e(6). Cell killing was dependent on the doses of both MAb-PS and 630-670 nm light and occurred only in target cell populations which bound the MAb. On the order of 10(10) singlet oxygen molecules were necessary to kill a cell. A second approach to specific photochemotherapy, selective carcinoma cell photolysis (SCCP), relies on preferential accumulation of certain cationic PS by carcinoma cell mitochondria. We have evaluated several classes of cationic dyes, and in the case of N,N'-bis-(2-ethyl-1,3-dioxolane)-kryptocyanine (EDKC) and some of its analogs, have demonstrated highly selective killing of human squamous cell, bladder and colon carcinoma cells in vitro. In isolated mitochondria, EDKC uptake and fluorescence depended on membrane potential, and the dye specifically photosensitized damage to Complex I in the electron transport chain. N,N'-bis-(2-ethyl-1,3-dioxolane)-kryptocyanine and some of its analogs accumulated within subcutaneous xenografts of human tumors in nude mice with tumor:skin ratios > 8. Photoirradiation caused significant inhibition of tumor growth, without cutaneous phototoxicity.
Photobleaching of a cyanine dye in solution and in membranes.
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Genetic and antigenic differences of serologically indistinguishable leptospires of serovar hardjo.
Pathogenic leptospires of serovar hardjo isolated from North American cattle were compared genetically and antigenically to reference strain hardjoprajitno of the Sejroe serogroup. Guanine-plus-cytosine (G+C) contents were determined for the genomes, and microscopic agglutination, Western blotting (immunoblotting), and immunoprecipitation were used to characterize antigenic relatedness. Major differences were demonstrated between the isolates and the reference strain. The G+C content of the reference strain was calculated to be approximately 34 +/- 1%, and those of the isolates were calculated at 39 +/- 1%. Antigenic differences between the isolates and the reference strain were identified by using rabbit immune serum raised against a hardjo isolate exhaustively adsorbed with hardjoprajitno whole and sonicated cells. Western blot analysis and immunoprecipitation using this adsorbed serum revealed antigens apparently unique for the hardjo isolates. Microscopic agglutination with the adsorbed rabbit serum did not agglutinate hardjoprajitno when diluted 1:2 but agglutinated bovine isolates to a 1:32 dilution. Bovine antiserum raised against the isolates was also used to identify antigens by immunoprecipitation.
Systemic lupus erythematosus presenting as polymyalgia rheumatica.
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An experimental microcomputer controlled system for synchronized pulsating anti-gravity suit.
An experimental system to deliver synchronized external pressure pulsations to the lower body is described in this technical note. The system is designed using a microcomputer with a real time interface and an electro-pneumatic subsystem capable of delivering pressure pulses to a modified anti-G suit at a fast rate. It is versatile, containing many options for synchronizing, phasing and sequencing of the pressure pulsations and controlling the pressure level in the suit bladders. Details of its software and hardware are described along with the results of initial testing in a Dynamic Flight Simulator on human volunteers.
Free fatty acid metabolism and obesity in man: in vivo in vitro comparisons.
We have examined the relationship of free fatty acid (FFA) turnover and lipid oxidation rates in vivo to the size of body triglyceride stores and compared these findings with the in vitro lipolytic rates of isolated abdominal fat cells. The studies were performed in 20 Pima Indian women 18 to 35 years of age, both lean and obese. FFA turnover rate was measured using a 1-14C-palmitate infusion, lipid oxidation rate by indirect calorimetry using a ventilated hood, body composition by underwater weighing with correction for residual lung volume, and fat cell lipolytic rates in vitro by published methods. Both FFA turnover and lipid oxidation rates, expressed per kg of body fat, decreased with increasing degree of obesity (as measured by percent body fat) (r = -0.90, and r = -0.75, P less than or equal to 0.0001, respectively). In contrast, the rate of lipolysis determined in vitro, expressed per kg of fat, increased with increasing degree of obesity (r = 0.58, P less than 0.01). A ratio of FFA turnover/lipolysis, which directly compares these in vivo and in vitro measurements, decreased significantly with increases in the degree of obesity (r = -0.81, P less than or equal to 0.0001). Furthermore, there were no positive correlations between the measures of in vivo FFA metabolism and in vitro lipolysis when both were expressed per fat mass, per fat cell number, or per fat cell surface area. The in vivo data also demonstrated that lipid oxidation could only account for 50% of the FFA disappearance rate. While lipid oxidation rate adjusted to the metabolic size increased with increasing plasma FFA concentration (r = 0.75, P less than 0.0003), the nonoxidative component of the FFA turnover failed to increase with increases in plasma FFA concentration (P = 0.5). We conclude that FFA is not available in vivo in proportion to the size of the triglyceride stores. The reason for this is not due to an inability of fat cells to release their stored triglyceride as assessed in vitro. Hence, in vitro measurements of fat cell lipolysis cannot be used to directly predict in vivo FFA metabolism. The large nonoxidative FFA disposal is likely to be important in the regulation of plasma FFA concentrations.
Effects of oral calcium carbonate on control of serum phosphorus and changes in plasma aluminum levels after discontinuation of aluminum-containing gels in children receiving dialysis.
Orally administered calcium carbonate was evaluated as a phosphate binding agent in 15 children, ages 0.6 to 17.2 years, receiving maintenance dialysis. Changes in plasma aluminum concentration were assessed after discontinuation of treatment with aluminum-containing gels. The mean daily dose of calcium carbonate was 5.1 +/- 2.5 gm (384 +/- 315 mg/kg/day), and correlated inversely with body weight (r = 0.72, P less than 0.01) and age (r = 0.71, P less than 0.01). Mean serum calcium, phosphorus, and bicarbonate values were unchanged throughout the study. Plasma aluminum concentration fell from 90 +/- 51 to 34 +/- 22 micrograms/L (P less than 0.005). Dietary phosphorus intakes were 44 +/- 21 and 42 +/- 19 mg/kg/day during the control period and at the end of the study, respectively. Transitory hypercalcemia was the only side effect in 92% of the patients. In none of the patients did uncontrolled hyperphosphatemia, metabolic alkalosis, diarrhea, or symptoms or signs of hypercalcemia develop. Our data indicate that calcium carbonate is an effective phosphate binding agent in children receiving dialysis, and should be used in lieu of aluminum-containing gels in young children with renal failure.
Intramitochondrial dyes allow selective in vitro photolysis of carcinoma cells.
Carcinoma cell mitochondria preferentially accumulate and retain certain cationic dyes to a much greater extent than most normal cells. Thus, they can potentially serve as targets for highly selective photochemotherapy. We evaluated 10 rhodamine and cyanine dyes as carcinoma-specific mitochondrial photosensitizers in vitro. The most effective, N,N'-bis(2-ethyl-1,3-dioxolane)kryptocyanine (EDKC), caused marked, light-dependent killing of human bladder, squamous, and colon carcinoma cell lines after 30-min incubations at 1-0.01 microM but was minimally toxic to human keratinocytes and to normal monkey kidney epithelial cells (CV-1). Carcinoma cell phototoxicity was proportional to the amount of dye incorporated by the different cell lines. Selective killing ratios were 70-1000 for 0.1 microM dye and light doses of 100-175 J/cm2 between 680 and 720 nm.
Immediate ascites conversion of mammary tumors induced in NYLR/Nya mice by 7,12-dimethylbenz-[a] anthracene and urethane feeding and by forced breeding.
Intragastric feeding of dimethylbenz-[a]anthracene in corn oil together with urethane in the drinking water and forced breeding were successful in rapidly inducing (2-4 months) mammary tumors (adenoacanthomas) in inbred NYLR/Nya mice, which have a low incidence of spontaneous breast tumors and of other tumors. The tumors could be quickly and permanently transformed to an ascites form by intraperitoneal inoculation of enzyme-dissociated cells and subsequent serial passage of free cells. Only 10 (3 in some cases) serial passages were required, thus conveniently providing multiple isogeneic carcinoma cell lines in this strain of mice. Some tumor cell lines proliferated strongly in the abdominal cavity even on the first passage.
Primary health care. Learning how to feel well.
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Recovery from cortical blindness.
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Correlation of histopathologic evidence of disease activity with the presence of immunoglobulin-containing cells in the colons of patients with inflammatory bowel disease.
Immunofluorescence of formalin-fixed, paraffin-embedded tissues was performed to study the plasma cell population in 114 colonic specimens from 58 patients. Correlation of the histopathologic stage of disease activity with the isotypes and numbers of immunoglobulin-containing cells in the lamina propria demonstrated highly significant (P less than 0.001) increases in the mean numbers of IgG- (18-fold), IgA- (twofold) and IgM- (sixfold) containing cells in specimens from patients with active inflammatory bowel disease as compared with control specimens. Increased numbers of immunoglobulin-containing cells were uncommon in inactive inflammatory bowel disease and in reactive mucosa. No deposition of immunoglobulin-containing immune complexes was found at any stage of disease activity. These findings suggest that immune complex-mediated damage does not play a major role in the epithelial damage in inflammatory bowel disease. In future studies, it will be of importance to determine whether the antibody from immunoglobulin-containing cells seen in patients with inflammatory bowel disease can effect damage via an antibody-dependent cell-mediated cytotoxicity mechanism.
Insulin therapy in obese, non-insulin-dependent diabetes induces improvements in insulin action and secretion that are maintained for two weeks after insulin withdrawal.
The effects of rigorous insulin treatment on insulin action (insulin clamp) and secretion (plasma insulin response to glucose) were studied in 13 obese patients with non-insulin-dependent diabetes mellitus (NIDDM). Improvements were documented in fasting (P less than 0.0001) and postprandial (P less than 0.0001) plasma glucose concentrations, insulin secretion after oral glucose (P less than 0.001), and insulin action (P less than 0.005) after 30 days of therapy. Mean integrated plasma insulin response to glucose increased 2.5-fold after insulin therapy, but this improvement varied considerably from patient to patient. Insulin action also increased with insulin treatment and the resulting values were no longer significantly different from a weight- and age-matched group of subjects with normal glucose tolerance. However, there was considerable patient-to-patient variation in the degree to which insulin action was enhanced. The insulin-induced improvements in glucose tolerance persisted for at least 2 wk after insulin withdrawal, and were associated with continued increased insulin secretion and insulin action. In conclusion, control of hyperglycemia for 1 mo led to improvements in both insulin secretion and action in a series of obese patients with NIDDM that persisted for at least 2 wk after cessation of therapy.
St. Louis housekeepers helping the disabled also helped themselves.
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Peanut lectin agglutinin and alpha-lactalbumin. Binding and immunohistochemical localization in breast tissues.
We analyzed 31 breast lesions immunohistochemically for alpha-lactalbumin (ALA) production and T-antigen presence as defined by peanut lectin agglutinin (PNA). Most cases of well-differentiated infiltrating carcinomas (14 of 17) and of poorly differentiated carcinomas (two of four) showed positive immunoreactivity for ALA; ALA was also localized in three cases of normal breast tissues, in two fibroadenomas, and in five intraductal carcinomas. The PNA binding pattern was primarily along the luminal cytoplasmic cell membrane in normal breasts and in fibroadenomas. We saw both cell membrane and cytoplasmic binding in carcinomas. In seven cases of primary and metastatic carcinomas to axillary lymph nodes, both primary and metastatic tumors expressed T antigen and produced ALA. These studies indicate that ALA can be used as a diagnostic marker in breast carcinoma and that the PNA binding pattern in normal and benign breast tissues is primarily at the luminal cytoplasmic cell membrane, whereas both cytoplasmic and cell membrane binding are present in carcinomas. The production of ALA does not appear directly related to T-antigen expression or to metastatic disease.
The athetoid syndrome. A review of a personal series.
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High-performance liquid chromatography of the oral anti-asthmatic agent pirquinozol and its active metabolite.
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