Search PubMed⌕ Search

Biomedical subjects

H Schreiber

Publications and source records attributed to H Schreiber.

At least 127 records · Page 7Linked to original sources
PubMed1987

Protective immunity to progressive tumors can be induced by antigen presented on regressor tumors.

Immunization of animals with 1591-RE tumor cells, a highly immunogenic UV-induced epithelia cell tumor from C3H/HeN mice, that were haptenated with trinitrophenol (TNP) leads to protective immunity against a challenge of TNP-haptenated 3152-PRO tumor cells, a progressive highly malignant. MCA-induced fibrosarcoma from syngeneic mice. Animals that rejected TNP-1591-RE and subsequently TNP-3152-PRO tumor cells showed increased tumor-specific resistance to another challenge of 3152-PRO tumor cells, even when these fibrosarcoma cells had not been haptenated with TNP. Induction of protection required the presence of TNP-hapten groups on both 1591-RE and 3152-PRO during the initial immunization, and could be induced by immunization with other haptenated syngeneic highly immunogenic regressor tumor lines. In addition, TNP-haptenated progressor variants of the 1591-RE were ineffective in generating protection, suggesting that the immunogenicity of the haptenated tumor used for the initial immunization was a determining factor in whether or not protective immunity against the highly malignant tumor was later generated. Protection required at least two T cell types: a Lyt-1-2+ T cells, and a Lyt-1+2- T cell that also expressed I-J determinants and was Vicia villosa lectin adherent, suggesting it was not a classical helper T cell. These results suggest that presentation of a hapten by highly immunogenic tumor cells can lead to enhanced protective immunity to poorly immunogenic noncross-reactive tumors that co-express the same hapten, and rejection of these haptenated poorly immunogenic tumors leads to enhanced protection against a subsequent challenge of the same, but not noncross-reactive progressor tumors.

Animals↗
PubMed1987

[Skin diving].

Explore the source record for details and available documents.

Diving↗
PubMed1987

Relationship of tumour necrosis factor and endotoxin to macrophage cytotoxicity, haemorrhagic necrosis and lethal shock.

In this communication we discuss preliminary evidence suggesting a very strong synergism between tumour necrosis factor (TNF) and lipopolysaccharide (LPS) or between TNF and other bacteria in causing haemorrhagic necrosis and lethal shock. We found that TNF by itself does not cause haemorrhagic necrosis when injected into normal skin. TNF also had a rather low systemic toxicity when injected into disease-free, germfree-derived, defined-flora animals. On the other hand the addition of small amounts of LPS markedly raised the lethality of intravenous TNF treatments, and LPS injected into normal skin 'prepared' the site of injection for subsequent induction of haemorrhagic necrosis by locally injected TNF. Similar synergism was observed between TNF and mycoplasma. We suggest that the synergism between TNF and bacterial endotoxin (or other bacteria or bacterial products) may be part of an important defence mechanism against infections which is independent of specific immunity mediated by B and T cells. This synergism may be useful in increasing the therapeutic effects of TNF on tumours if the development of systemic toxicity in this treatment can be prevented.

Animals↗
PubMed1987

Mesenteric artery embolization by an unsuspected aortic tumor: diagnostic evaluation and operative management.

Malignant tumor embolus recovered at the time of superior mesenteric artery embolectomy is an uncommon experience. A report of such a case is presented and the literature is reviewed. In this clinical setting, guidelines for further diagnostic evaluation are not well defined. We suggest an algorithm for the evaluation and management of these patients. In the near future, use of intraoperative angioscopy and the intravascular laser to eradicate the tumor may represent the optimal method of treatment.

Algorithms↗
PubMed1987

Effects of midbrain stimulation and iontophoretic application of serotonin, noradrenaline, morphine and GABA on electrical thresholds of afferent C- and A-fibre terminals in cat spinal cord.

We have used the single-fibre excitability testing method to investigate whether electrical stimulation in midbrain periaqueductal gray or lateral reticular formation, as well as intraspinal iontophoretic application of the suspected inhibitory neurotransmitters serotonin (5-hydroxytryptamine), noradrenaline, the opiate morphine, or gamma-aminobutyric acid (GABA), exert presynaptic actions at the central terminals of cutaneous afferent unmyelinated or myelinated fibres. Thresholds to antidromically excited 42 single unmyelinated and 18 myelinated fibres in the sural nerve by intraspinal microstimulation were determined before and during periaqueductal gray or lateral reticular formation stimulation (3 100 ms trains/s at 100 Hz; 100-900 microA) or intraspinal iontophoretic application (40-300 nA) of 5-hydroxytryptamine, noradrenaline, morphine or GABA from a multibarrel micropipette. Periaqueductal gray or lateral reticular formation stimulation had mixed effects on unmyelinated and myelinated fibre thresholds, with most threshold measurements within +/- 10% of control. There was a tendency for thresholds to increase more during periaqueductal gray than lateral reticular formation stimulation. Thresholds of unmyelinated fibres were predominantly raised during iontophoretic application of 5-hydroxytryptamine (20/29 fibres), noradrenaline (10/13) and morphine (15/21), while GABA had mixed effects; thresholds of nearly all myelinated fibres were raised by each drug. Both periaqueductal gray or lateral reticular formation stimulation and application of 5-hydroxytryptamine, noradrenaline or morphine tended to raise thresholds in the majority of the 53 unmyelinated and myelinated fibres tested. Methodological problems in interpreting the physiological significance of these results for presynaptic modulation are discussed.

Animals↗
PubMed1987

Endogenous plasminogen activator and venous flow: therapeutic implications.

This study is concerned with the changes in endogenous plasminogen activator (PA), in response to the augmentation of venous blood flow by external pneumatic compression (EPC). EPC was applied to the left leg in ten patients undergoing surgery under general anesthesia. Two-ml samples of venous blood were obtained from the left and right femoral veins and an arm vein at baseline (induction), and then at 30 and 60 min of compression. Ninety samples were analyzed in duplicate in a single blind technique, using an assay specific for PA activity. In the control right arm and leg, PA activity levels increased at 30 min (106% and 110% of baseline, respectively), and then declined to baseline levels by 60 min. These changes did not reach statistical significance. In the leg undergoing compression, however, PA activity decreased progressively, reaching 75% of baseline at 60 min (significant at both 30 [p less than .001] and 60 min [p less than .01] as compared to baseline). In vitro, PA activity varies directly with the concentration of fibrin. The progressive decline in activity in this study may, therefore, represent a decline in substrate (molecular fibrin), as a result of increased venous blood flow. Alterations in the activity of the endothelial cell, as observed, may lead to new approaches in the prophylaxis against thromboembolism.

Femoral Vein↗
PubMed1986

Identification of a unique tumor antigen as rejection antigen by molecular cloning and gene transfer.

Tumor-specific transplantation antigens are antigens that can lead to complete immunological destruction of a transplanted cancer by the syngeneic host. When such antigens are expressed on cancers induced by chemical or physical carcinogens, then they are usually unique, i.e., antigenically different for each independently induced tumor. In this study, we show that the product of a gene encoding a novel MHC class I molecule and isolated from the murine UV light-induced regressor tumor 1591 represents one such unique tumor-specific transplantation antigen that causes tumor rejection. The major evidence comes from our finding that 1591 progressor variants regularly lost the gene encoding this antigen that is expressed in the parental tumor that regresses in normal mice; furthermore, reintroduction of this gene into a 1591 progressor variant by DNA transfection caused the progressor variant to regress in normal immunocompetent mice. Thus, the progressor tumor reverted to the parental regressor phenotype following transfection. Consistent with the conclusion that the expression of the novel MHC class I gene following transfection was responsible for the regressor phenotype is also our finding that a variant of the transfected tumor that had lost expression of the transfected gene resumed its progressive growth behavior. Finally, we show that the molecule encoded by the novel class I gene is specifically recognized by a syngeneic tumor-specific cytolytic T cell clone that we have previously shown to select in vitro for progressor variants from the parental regressor tumor cell line. It remains to be determined to what extent unique tumor-specific rejection antigens of other highly immunogenic regressor tumors are encoded by novel MHC class I genes and whether these genes represent germline mutations or somatic mutations caused by the carcinogen treatment.

Animals↗
PubMed1986

Highly malignant tumor variants retain tumor-specific antigens recognized by T helper cells.

We have studied the components of a complex of tumor-specific antigens to determine if all of the components of the complex were lost during progression from a rather benign regressor tumor to a highly malignant (HM) cancer. We find that the HM tumor cells have lost antigens recognized by CTL but retained antigens recognized by Th cells. Immunization with variants expressing Th-defined antigens induced tumor-specific immunity to challenge with a parental variant that expressed a CTL-recognized target antigen, but did not induce immunity to challenge with the variant that expressed the Th-defined antigen alone. Together, these findings suggested that Th cells fail to exert direct selective pressure upon the tumor, resulting in retention of "lineage-specific," Th-recognized antigens by highly immunoselected variants. Possible advantage could be taken of this fact for the development of specific immunotherapy.

Animals↗
PubMed1986

Stepwise immunologic selection of antigenic variants during tumor growth.

Using tumor-specific effector cells as probes, we have studied the immunologic changes that occur in tumor cells during continuous growth in a host. As a model, we used a highly immunogenic ultraviolet light (UV)-induced tumor that is rejected regularly by normal mice but grows progressively when transplanted into UV-irradiated mice. The immunogenic tumor growing continuously in these partially immunocompromised mice gave rise to genetically stable progressor variants that were poorly immunogenic. A sequence of changes in susceptibility to activated macrophages and tumor-specific cytolytic T cells was observed when serial reisolates from the continuously growing tumors were analyzed. First, the tumor cells developed resistance to the cytocidal effects of activated macrophages. This was followed by the loss of one and then a second tumor-specific antigen defined by syngeneic cytolytic T cells. The phenotypes of the developing antigen loss variants and their sequence of appearance were the same in several independent experiments, and the process was apparently determined by a hierarchy of the host's immune response to multiple independent tumor-specific antigens expressed by a single malignant cell. Our ability to generate the predicted variants in vitro before they actually appear in vivo suggests a possible approach to preventing the outgrowth of such immunoselected variants from a tumor.

Animals↗
PubMed1986

Tumor necrosis factor: a potent effector molecule for tumor cell killing by activated macrophages.

Activated macrophages (aM phi) destroy more effectively cancer cells than normal cells. The mechanism by which macrophages destroy cancer cells is not known. We report here that tumor cells susceptible to aM phi were killed by recombinant (r) tumor necrosis factor type alpha (TNF-alpha), whereas variant tumor cells resistant to aM phi after selection in vitro or in vivo were resistant to killing by rTNF-alpha. The converse selection for rTNF-alpha-resistant variants resulted in cells that were also resistant to killing by aM phi. The sensitivity of macrophage-resistant variants was not changed to other tumoricidal cells or soluble mediators, except that the macrophage-resistant variants were also resistant to the effects of another cytotoxic protein, B-cell lymphotoxin, which is structurally related to rTNF-alpha. Similar results were obtained regardless of whether short-term or long-term cytotoxic effects of aM phi were measured. Finally, it was shown that killing of tumor cells by murine aM phi was completely inhibited with a polyclonal antibody that neutralizes the effects of murine TNF-alpha. These results suggest a major role for TNF-alpha in tumor cell destruction by aM phi in vitro and in vivo.

Animals↗
PubMed1986

[Procedure for the biological testing of substances in the guinea pig subcutaneous test. I. The results of an improved semiquantitative assessment of the histological criteria].

Different materials were implanted into the subcutaneous connective tissue of guinea pigs to evaluate biotolerance by means of the tissue response. The investigations were carried out with reference materials and newly developed implant materials in short-term studies and in case control studies. The semiquantitative valuation standards lead mostly only to informing statements in the sense of a compatibility degree. Alternative assertions are possible when comparing very different materials.

Animals↗
PubMed1986

[Procedure for the biological testing of substances in the guinea pig subcutaneous test. III. The results of the quantitative determination of the cell division pattern in the area of reaction].

The counting of the type of cells in the surroundings of implanted materials enables the estimation of specific material effects and improved the statement of the biologic testing methods. The explained method is described in the example of reference materials and is applied to different new materials for the estimation of their histocompatibility.

Animals↗
PubMed1985

Multiple cancers. Tumor burden permits the outgrowth of other cancers.

We demonstrate that tumor-bearing hosts permit the outgrowth of "potentially malignant" cells that are located at a different site. These second cancers continued to grow and kill their hosts even though they retain the "premalignant" phenotype, even after removal of the original malignancy. The potentially malignant cells used in these experiments were ultraviolet light- or methylcholanthrene-induced regressor tumor cells that are rejected regularly by normal mice at any testable dose, and only form progressive tumors in immunosuppressed individuals. The immunological rejection of these highly immunogenic, potentially malignant cells was suppressed by Thy-1+, Ly-2-, nonadherent, radio-sensitive suppressor cells in the tumor-bearing mice. These suppressor cells were absent in nude tumor-bearing mice. Unlike helper and cytolytic T cell-mediated responses, which are exquisitely tumor specific, the suppression caused by a progressively growing tumor was crossreactive among many syngeneic, independently derived tumors induced by different carcinogens. However, T cell-mediated immune responses to alloantigens, allogeneic tumors, certain syngeneic tumors, and humoral responses to xenogeneic red blood cells were normal in these mice. The immune suppression in the tumor-bearing animals closely simulated that induced by ultraviolet light irradiation, and both types of suppression might therefore share common mechanisms. Our findings may contribute to understanding the growth, development, and possible control of multicentric malignancies and add a precaution to the potential use of strongly immunogenic tumor variants for active immunotherapy in hosts bearing less immunogenic tumors.

Animals↗