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L Young

Publications and source records attributed to L Young.

At least 235 records · Page 13Linked to original sources
PubMed1987

Species-specific and common epitopes on the secreted and surface antigens of Toxocara cati and Toxocara canis infective larvae.

It is widely accepted that the major cause of visceral larva migrans (VLM) in man is Toxocara canis infection. This has been largely based on the detection of antibodies to this species. We have compared the antigens of T. canis and Toxocara cati in order to establish whether assay for the former might be compromised by infection with the latter. Comparisons were made by radioiodination of the surface and excretory/secretory (ES) glycoproteins of the infective larvae of both species, immunoprecipitation with poly- and monoclonal reagents, and SDS-PAGE. The SDS-PAGE profiles of surface antigens of the two species showed few similarities, whereas that of the ES material indicated considerable homology. Serum from infected animals and a human VLM patient exhibited complete cross reactivity, although there was evidence in the mouse of a specific response to one of the components of T. cati ES. Testing of ES against a panel of monoclonal antibodies (MoAbs) confirmed the similarity; all but one of the MoAbs recognized several of the components of both sources of ES. The only exception was MoAb Tcn-2, which did not react with T. cati surface, somatic or ES antigens. This antibody is known to recognize a carbohydrate determinant which is widespread on T. canis glycoproteins. This species-specific determinant, therefore, represents a reversal of the consensus that peptide determinants tend to be the more specific. Finally, the MoAbs were used to examine the exposure of shared epitopes on the surface of intact larvae of T. cati. Again, fine differences in binding by anti-carbohydrate monoclonals were observed when the two species of Toxocara were compared, reflecting a distinction in exposure or orientation of surface molecules on these nematodes. Moreover, these epitopes were absent or variably present on the surface of freshly hatched larvae, and full exposure did not occur until about 24 h post-hatching. This delay in the presentation of epitopes might have implications for the process of infection in sensitized hosts. In conclusion, it is probable that the serological response in man to T. canis is, by current serological methods, indistinguishable in specificity from that induced by T. cati infection, and that the MoAb which we describe could be used to permit discrimination.

Animals↗
PubMed1987

Antineoplastic effects of tumor necrosis factor alone and in combination with gamma-interferon on tumor biopsies in clonogenic assay.

Tumor colony-forming cells were grown from fresh biopsy specimens from 102 patients with a variety of nonhematologic malignant neoplasms and exposed in vitro to pharmacologically achievable doses of recombinant human tumor necrosis factor (rTNF). In 68 instances, the tumor specimens were also tested against recombinant human gamma-interferon (rIFN-gamma), as well as the combination of rTNF and rIFN-gamma. rTNF exhibited dose-dependent and tumor-type-dependent antitumor effects. Sensitivity to rTNF at doses of less than 100 U was observed in 28% of the tumors tested. A higher than average frequency of sensitivity was observed in colorectal and lung cancer. Resistance to rTNF was observed in 42% of the tumors, including 52% of the ovarian cancer specimens tested. In paired experiments, exposure of tumor specimens to rTNF and rIFN-gamma in combination often resulted in a greater antitumor effect than was observed with either agent alone, with at least subadditive effects seen in 62% of the specimens tested against the combination. Antagonism between rTNF and rIFN-gamma was observed in 18% of the studies. Overall, exposure to the combination of rTNF and rIFN-gamma reduced the dose of rTNF required for significant antitumor activity by about threefold. Normal bone marrow granulocyte-macrophage colony-forming cells were also tested against both rTNF and rIFN-gamma and the combination. The bone marrow progenitors were more sensitive to rTNF and the combination with rIFN-gamma than were the tumor cells; however, the significance of this comparison between two different in vitro assay systems is indeterminate. Based on our observations, rTNF warrants phase II clinical trials in selected solid tumors with definite emphasis on colorectal and lung cancer. Additionally, studies of the combination of rTNF and rIFN-gamma are indicated and will be of particular interest in endometrial and breast cancer.

Antineoplastic Agents↗
PubMed1987

Tumor metastasis after hyperoxic injury and repair of the pulmonary endothelium.

Pulmonary metastasis is a common event. The studies described here were done to test the hypothesis that there is a relationship between endothelial injury and the localization and metastasis of circulating tumor cells. Mice were exposed for periods of up to 4 days to an atmosphere of 90% oxygen; some were allowed to recover in room air for 3 or 14 days. Air-exposed animals served as controls. Endothelial injury, demonstrated morphologically and quantitated by measuring protein levels in bronchoalveolar lavage fluid, increased from 2 to 4 days exposure when injury was maximal. Metastatic events increased in frequency concurrently. When radiolabeled syngeneic fibrosarcoma cells were injected, a 5-fold increase in localization at 24 hours was seen in the 3-day exposed group and a 36-fold increase was found in the 4-day group. Tumor cells were found by electron microscopy at sites of denuded endothelial basement membrane, often associated with small platelet-fibrin thrombi and sometimes, after 4-day exposure, with sequestered neutrophils. The subsequent development of metastatic nodules in the lung and the percentage of lung occupied by tumor were also maximal in the 4-day group. Increased metastasis and endothelial injury were also seen in mice returned to air for 3 days, but by 14 days the endothelium was normal and metastases were at control levels. The results demonstrate a relationship between the degree of pulmonary endothelial damage produced by hyperoxia and the extent of metastatic tumor growth.

Animals↗
PubMed1986

Effects of injury and repair of the pulmonary endothelium on lung metastasis after bleomycin.

Acute endothelial injury induced by bleomycin has been shown to enhance the localization and metastasis of circulating tumour cells. In the present study we wished to determine whether increased metastases to the lung is related to the degree of endothelial damage as indicated by morphology and protein leakage to alveoli and whether the progression to repair with pulmonary fibrosis also effects metastatic tumour growth. C57b1/6 mice were injected with a single intravenous dose of bleomycin (120 mg/kg). After 5 days, severe enothelial injury was demonstrated by morphology and by increased levels of protein in lung lavage fluid. When [131I]-iododeoxyuridine labeled syngeneic fibrosarcoma cells were injected intravenously at this time, a 9-fold increase in their localization was detected 24 h later in bleomycin-treated lungs compared with saline controls. By electron microscopy tumour cells were observed at sites of denuded vascular basement membrane. There was also a significant increase in the number of gross metastases which developed subsequently and in the percentage of lung occupied by tumour in the bleomycin group. Animals examined 10 days after bleomycin showed less endothelial damage and a smaller increase in tumour cell localization and metastases. At 21 days, when endothelial structure and alveolar protein levels had returned to normal, and at 6 weeks, when there was focal fibrosis, no increase in tumour cell localization or metastases was found. It is concluded that damage to the pulmonary endothelium is a key factor in enhancing the trapping of circulating tumour cells and increasing metastatic tumour growth after bleomycin.

Animals↗
PubMed1986

Promotion of pulmonary metastasis in mice by bleomycin-induced endothelial injury.

The passage of circulating tumor cells across the vascular wall is an important step in the evolution of cancer metastases. Since tumor cells attach preferentially to subendothelial matrix at sites of endothelial injury and retraction in vitro, we have used an established in vivo model of pulmonary endothelial damage to examine the effects of endothelial injury on the localization and metastasis of circulating tumor cells in vivo. C57BL/6 mice were given a single i.v. dose of bleomycin (120 mg/kg) or multiple i.p. injections (10 mg/kg, twice weekly for 6 wk). Five days after the single injection or 4 days after the last i.p. injection, 2 X 10(5) [131I] iododeoxyuridine-labeled fibrosarcoma cells or unlabeled cells were injected i.v. Two to 8 times as many labeled cells were found in the lungs of bleomycin-treated animals after 24 h. Two and 3 wk after injecting unlabeled fibrosarcoma cells, 1.4 to 5 times more metastatic lung colonies were counted in bleomycin-treated animals than in controls. Morphometric analysis of histological sections demonstrated that the percentage of lung area occupied by tumor in bleomycin-treated animals was between 4 and 16 times that of controls. Analysis of bronchoalveolar lavage fluids demonstrated 5-fold increases of total protein content and leakage of previously injected 125l-labeled albumin, indicating increased endothelial permeability. Electron microscopic examination of lungs of bleomycin-treated mice demonstrated endothelial retraction with exposure of the underlying basement membrane. Electron microscopy of [3H]thymidine-labeled tumor cells, located by autoradiography, demonstrated their attachment to exposed basal lamina. Data from these experiments in vivo support the hypothesis that endothelial damage can facilitate the metastasis of circulating tumor cells.

Animals↗
PubMed1985

Benign mediastinal teratoma with immature elements exhibited clonal growth and motility in the human tumor clonogenic assay.

The human tumor clonogenic assay has been used to study the growth and drug sensitivity of a wide variety of malignant and a limited number of benign tumors. We conducted detailed studies on a multipotential benign teratoma from a young child that gave rise to colonies in soft agar culture. The colonies separated themselves from the surrounding agar and exhibited rapid rotary movement (15 r/min). Morphologic, ultrastructural, and immunologic studies showed the colonies to be comprised exclusively of ciliated respiratory epithelium. The uniform beating of the cilia resulted in a constant rolling motion of the colonies in a single direction.

Cell Differentiation↗
PubMed1985

Surgical templates for immediate denture insertion.

Criteria for an ideal surgical template for immediate dentures were presented. Laboratory and clinical studies were made of five types of templates. The Biostarformed template with improvements, followed by the sprinkled acrylic resin template, best fit the established criteria (Table I).

Alveoloplasty↗
PubMed1985

Delayed phase of hematoporphyrin-induced phototoxicity: modulation by complement, leukocytes, and antihistamines.

We have investigated the role of complement, leukocytes, and histamine in the delayed phase of hematoporphyrin-induced phototoxicity in guinea pigs. The phototoxic response was quantified by the accumulation of intravenously injected [125I]bovine serum albumin in the skin. There was a greater than 6-fold increase in the vascular response at the completion of irradiation, which subsided partially to reach a plateau of twice the preirradiation level between 0.5 h and 12 h. At 18 h, the vascular responsiveness returned to the baseline value. The 7 h timepoint was selected in this study to evaluate the modulation of the delayed phase. In complement-depleted guinea pigs, as well as in leukopenic animals, the enhancement in the vascular response was significantly suppressed (p vs control, less than 0.0001 and 0.0022, respectively). Cimetidine, when administered prior to irradiation, significantly suppressed the phototoxic response (p vs control, 0.0365). The combination of diphenhydramine and cimetidine, administered 6 h after the induction of phototoxicity, also suppressed the vascular response (p vs control, less than 0.0001). These data indicate that the expression of the delayed phase of hematoporphyrin-induced phototoxicity, similar to the early phase, requires the presence of an intact complement system, leukocytes, and histamine.

Animals↗
PubMed1985

Cognitive methods of preparing women for hysterectomy: does a booklet help?

Thirty women about to undergo hysterectomy were sequentially assigned to three equal groups. The first two groups were taught methods of cognitive control over anxiety, either through a detailed booklet (group 1) or orally (group 2). The third group served as attention-placebo controls. The two experimental groups reported less pain and distress than the control group, who spent longer in hospital and were more prone to post-operative vomiting. The booklet proved neither more nor less beneficial than oral teaching on the criteria adopted, and is therefore seen as more cost effective.

Adaptation, Psychological↗
PubMed1985

Pulmonary inflammation generates chemotactic activity for tumor cells and promotes lung metastasis.

Previous studies have demonstrated a chemotactic factor for tumor cells in inflammatory peritoneal exudates. Because the lung is a frequent site of inflammation and of secondary tumors, we looked for tumor cell chemotactic factors in alveolar inflammatory exudates and examined the effect of inflammation on the localization and metastasis of circulating syngenic fibrosarcoma cells. Intratracheal injections of a 1-mg carbon suspension (0.03-mu particles in 0.1 ml sterile water) were given to C57 b1/6 mice that were killed between 6 h and 28 days later. The total number of cells recovered in bronchoalveolar lavage (BAL) fluids rose from 8 X 10(4) to 240 X 10(4), and was maximal at 3 days. Neutrophils accounted for more than 75% of the inflammatory cells in the first week when there was a greater than twentyfold rise in the levels of glucosaminidase in lavage fluids. Injection of water alone caused a mild inflammatory response that subsided rapidly. In Boyden chambers, the tumor cells demonstrated chemotactic responses to lavage supernatants from animals with inflamed lungs, and the magnitude of response correlated directly with the number of neutrophils (r = 0.60) or total exudate cells (r = 0.47) but not with macrophages (r = 0.05). Intravenous injection of 2 X 10(5) 131I-iododeoxyuridine labeled tumor cells on the third to fifth day after intratracheal injection was followed after 24 h by pulmonary localization of 3 to 5 times more tumor cells in inflamed lungs than in control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Mechanism of priming of human neutrophils by a soluble lymphoblastoid cell factor.

Treatment of human neutrophils (PMN) with a cytokine-like factor in the supernatants of human lymphoblastoid cells (Raji) increased the random mobility and enhanced the migration of treated cells in response to other chemoattractants nearly 21/2-fold, although the supernatant itself was not a chemoattractant. Supernatant treatment also increased the adherence of bacteria threefold and the bacterial killing fourfold compared with PMN treated with control media. In examining the metabolic basis for the enhanced bactericidal ability, we observed a significant increase in spontaneous hexose monophosphate shunt activity of Raji cell supernatant (RS)-treated neutrophils even in the absence of additional stimuli. RS-treated PMN also had significantly enhanced production of superoxide anion and chemiluminescence response upon subsequent stimulation with a variety of soluble and particulate stimuli. Unlike other agents that prime neutrophil activation, however, the factor(s) in RS did not cause degranulation. It also differed in its ability to progressively enhance PMN functions with a longer period of preincubation (up to 3 hr). These data suggest that the RS factor(s) primes neutrophils by a unique mechanism. The neutrophil-enhancing activities of RS, which are the opposite of those activities described for leukocyte inhibitory factor, eluted off a Sephacryl S-200 column at approximately 30,000 m.w. This factor expands the relationship between neutrophils and lymphocytes, and may be a useful agent to provide valuable insights into the mechanism of respiratory burst activation and regulation.

B-Lymphocytes↗
PubMed1985

In vitro evaluation of anticancer drugs against ovarian cancer at concentrations achievable by intraperitoneal administration.

High-dose intraperitoneal chemotherapy is a current developmental approach in the treatment of advanced ovarian cancer. Considerable pharmacologic data have been obtained on the intraperitoneal X time product for a number of agents administered by this route. We used the human tumor cloning assay (HTCA) to compare the activities of both standard and experimental agents used for intraperitoneal treatment. In vitro dose-survival curves were constructed for each drug over a two-log range of concentrations using fresh ovarian cancers from more than 50 patients. The mean concentration X time product (CXT) achievable in the intraperitoneal space after high-dose intraperitoneal drug administration was divided by the corresponding ID50 value (concentration of drug in vitro associated with 50% survival of tumor colonies) for each agent to calculate in vivo CXT: in vitro ID50 ratios. Using this approach, the standard agents, melphalan, cisplatin, and 5-FU were predicted to have similar efficacies by intraperitoneal administration, but doxorubicin and mitomycin were significantly inferior. Of the drugs tested, the new agent mitoxantrone was associated with the most favorable CXT to ID50 ratio and is, therefore, predicted to be particularly promising for intraperitoneal administration.

Anthraquinones↗
PubMed1984

Evaluation of an automated image analysis system for counting human tumor colonies.

The Omnicon FAS II image analysis system was applied to counting tumor colonies grown in a soft agar human tumor clonogenic assay with a detailed protocol designed to assess the instrument's sensitivity, specificity, precision, and accuracy. Comparisons of technician and instrument counts were done on a blinded basis. Sensitivity studies (which used metal microspheres) yielded a correlation coefficient (r) of 0.999 between technicians and the counter. A field-by-field analysis of the instrument's specificity for identifying individual objects correctly as tumor colonies rather than artifacts (as identified by the technician) was excellent (r = 0.95). In the precision studies (determined with repeated automated counting of the same samples for five days), the median coefficient of variation was less than 7%. Accuracy was evaluated on cultures of fresh biopsies from 30 human cancers obtained for drug sensitivity testing as well as on a series of tumor cell lines. The correlation between the mean number of colonies counted by the technicians and by the colony counter was greater than 0.91. Similar comparisons of mean percent survival of tumor colony-forming cells after drug exposure between technician and machine were also quite acceptable (r = 0.85). We conclude that the colony counter provided sufficient reliability to be applied to counting human tumor colonies grown in vitro. In addition, the colony counter performed the Petri dish counts ten times faster than experienced technicians and without associated operator fatigue.

Animals↗