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Biomedical subjects

H Schreiber

Publications and source records attributed to H Schreiber.

At least 145 records · Page 8Linked to original sources

Intestinal polyposis and periampullary carcinoma--changing concepts.

Adenomatous polyps lead directly to carcinoma of the colon in patients with one of the familial syndromes of intestinal polyposis. Elective colectomy is prophylactic and life-saving. A subgroup of patients will develop periampullary carcinoma, again arising from the presence of adenomatous polyps. Such a case is presented. These polyps should be surgically excised to ensure adequate pathologic examination. Yearly upper endoscopic examination is an essential element of management. Either the presence of carcinoma in situ or the recurrence of these polyps following excision is confirmation of behavior with a high propensity for the development of invasive cancer and requires aggressive treatment.

Adenocarcinoma↗

Tumor growth and evasion of immune destruction: UV-induced tumors as a model.

A number of complex interrelating mechanisms contributing to progressive growth of an immunogenic tumor and its evasion of immune destruction are exemplified in the model of the UV-induced tumor 1591 (fig. 3). The effects of (i) carcinogen-induced immune suppression, (ii) age-related changes in immune competence, (iii) generation and immunoselection of tumor cell variants which do not express target tumor antigen and (iv) tumor-induced immune suppression have been documented. The findings may help to assess the problems and the possibilities of immunotherapy of cancer. The problems reside in the many avenues of escape available to the tumor. The possibilities for immunotherapy derive from the fact that progressively growing tumors may still retain immunogenic antigens and therefore be susceptible to immune attack.

Aging↗

Identification of a unique tumor-specific antigen as a novel class I major histocompatibility molecule.

Cancers induced by physical or chemical carcinogens express tumor-specific antigens that are uniquely specific for any given tumor; therefore, there is a seemingly endless variety of these unique antigens. We have studied a UV-induced fibrosarcoma, designated 1591, to elucidate the obscure molecular nature and genetic origins of unique tumor-specific antigens. A monoclonal antibody raised against syngeneic 1591 tumor cells has unique tumor specificity. This tumor-specific monoclonal antibody precipitated from the tumor a 45-kDa molecule associated with a 12-kDa molecule having the pI of beta2-microglobulin. This and other evidence indicated that the 1591 tumor expresses a novel class I molecule. A 1591 variant selected for the absence of binding to the monoclonal antibody lacked the novel class I MHC molecule as well as reactivity with cytotoxic T lymphocytes specific for the 1591 tumor. Furthermore, tumor cells bearing the antigen are rejected while variants that have lost the antigen grow progressively. Fourteen of 14 host-selected progressor tumor variants lost reactivity with the monoclonal antibody and provided further evidence that this novel class I molecule is a transplantation antigen on the parental 1591 tumor required for immune rejection. The identification of a unique tumor-specific antigen as a novel class I major histocompatibility complex gene product allows us to search for the possible genetic mechanisms involved and to explore further the role such molecules play in tumor immunity and malignancy.

Animals↗

Discharge planning as a teaching mechanism.

A framework that organizes content into performance objectives is presented for planning field instruction and in-service education. Intended to overcome the polarization between concrete services and therapeutic intervention frequently seen within the profession, the objectives highlight the social work knowledge and skills inherent in discharge planning to encourage learners to appreciate this sometimes deprecated but increasingly important function.

Curriculum↗

Dissection of tumour-specific antigenicity.

Unique tumour-specific antigens have been detected on many tumours induced by physical or chemical carcinogens. Although a seemingly endless diversity of such antigens has been identified, very little is currently known about the nature and complexity of the antigenicity of any single tumour. We describe the characterization of the complex unique antigenicity expressed on an ultraviolet-light-induced tumour. Such tumours are highly immunogenic and are clearly subject to immunosurveillance in the normal host. The antigenicity of an ultraviolet-light-induced regressor tumour was dissected with the aid of monoclonal T-cell probes and with antigen-loss tumour variants that were selected in vitro or in vivo. It was demonstrated that the total antigenicity of this tumour consisted of multiple antigens, all of which were independent, tumour-specific and expressed simultaneously on the same tumour cell. Additional experiments determined which antigens were critical for tumour rejection by studying the in vivo growth behaviour of antigen-loss variants selected in vitro. Evaluation of the complexity of the host anti-tumour response revealed that a hierarchy existed in the host recognition of these antigens, a finding that should have important implications on the effectiveness of tumour rejection and immune escape. Finally, using tumour-specific monoclonal antibodies against the syngeneic tumour, investigation into the molecular nature of these tumour antigens indicated that some of these antigens represent novel class I major-histocompatibility-complex molecules. Thus we describe the complexity of a unique tumour-specific antigen and discuss the implications of this complexity on tumour immunity and tumour escape.

Animals↗

[Biocompatibility of implants with and without fluorohydrocarbon glow polymer coating. 4. Recommendations for the histocompatibility (repair) index for the evaluation of various implant materials].

The measurement of the thickness of the fibrous capsula around implant materials to different titmes and the material dependent speed of the subsidence process of the tissue reaction were formed to an index. The derivation of the index is described by a course study with 4 materials about 5 periods. The determination of the index is represented simply mathematically and also delineating-geometrically. The index should be determined between 50 and 200 days, better between 90 and 150 days. Individual wound reactions superimpose the material effect before and the final state of the tissue reaction hinders the speed interpretation of the quickness of subsidence prgcess after this period.

Animals↗

Stercoral perforation of the colon. Concepts of operative management.

Stercoral perforation of the colon is a direct result of ischemic pressure necrosis by a stercoraceous mass. In over 90 per cent of cases, the perforation will involve either the sigmoid or rectosigmoid colon and is consistently centrally located within a region of mucosal ulceration of varying diameter and magnitude. A review of 33 surgically treated cases from the literature along with four cases presented here, support resection, end colostomy, and either mucous fistula or Hartmann's procedure as the operation of choice with the lowest operative mortality (23%) when compared to those patients treated by either loop colostomy or exteriorization (71%) or proximal colostomy with plication of the perforation (44%). Irrigation of the distal rectal segment as that for penetrating rectal injury is also recommended.

Aged↗

Timing function of the frontal cortex in sequential motor and learning tasks.

The timing aspects of human frontal lobe function are discussed in the light of the results of three experiments on movement-related cerebral potentials. Experiment I is based on use of a sequential tracking task and experiment II a motor learning task; experiment III deals with frontal hemispheric specialisation by comparing self-initiated writing and drawing. The Bereitschaftspotential (BP) preceding voluntary movement is maximum over the supplementary motor area (SMA) for all movements, including finger, toe, speech, and eye movements, regardless of each movement's different localisation in the brain, e.g., motor cortex, temporal lobe, or midbrain. The assumption that all motor events are governed by the primary (rolandic) motor cortex is erroneous. The motor system is widely decentralised. It is only when this decentralization is recognized that the close temporal association between the onset of all movements and the preceding Bereitschaftspotential in the SMA can be understood. A plausible explanation would be that the SMA decides on the starting time of all the various movements. The frontal function of motivation is not a single entity but has several subfunctions. It has to decide what to do, how to do and when to do. The latter is probably the task of the SMA. A comparison of different motivational situations makes this clear. In the usual BP paradigm, such as self-initiated simple finger or eye movements, only the SMA becomes active among all the frontal areas. If, however, motivation is required to modify motor programs in motor learning, as it is in experiment II, the entire convexity of the frontal lobe shows a large surface-negative potential, the amplitude of which reveals a significant positive correlation with the success in learning. On the other hand, in experiment I, which uses a manual pursuit-movement task requiring attention to unpredictable changes in stimulus direction but providing a fixed time for these changes (so that their timing is foreseeable), the SMA shows anticipatory behaviour; it takes the form of a large negative potential which ceases 0.5 s prior to the end of the directed-attention potential over parietooccipital areas. In other words, in this special situation, where the SMA can anticipate the onset of movement, it seems to delegate the final execution of the movement to the cortical area most specialised for it, in this case the parietooccipital cortex. The supervision of the tasks concerning what to do and how to do may be provided mainly by the orbital cortex and the frontolateral cortex, respectively (Kleist 1934).(ABSTRACT TRUNCATED AT 400 WORDS)

Cerebral Cortex↗

Pecking order among tumor-specific antigens.

The ultraviolet light-induced fibrosarcoma 1591 is regularly rejected upon transplantation into young syngeneic mice; in rare instances, however, this tumor grows progressively and the tumors that develop are then heritably stable variant progressor tumors (1591-PRO tumors). In this study, we have induced transplantation resistance to 1591-PRO tumors and determined which antigens were recognized by mice that rejected these progressor tumors. We found that cytolytic T cells of such mice recognized a 1591-specific antigen that was present not only on all the independently derived 1591-PRO tumors but also on the parental regressor tumor (1591-RE). However, the cytolytic immune response of mice that rejected 1591-RE lysed 1591-RE tumor cells but not 1591-PRO tumor cells. Thus, the 1591-RE tumor seemed to express two antigens that were specific for tumors of the 1591 lineage, one that was lost and a second that was retained by 1591-PRO tumor cells. Mice challenged with 1591-R# tumor cells mounted a response to only one of the tumor-specific antigens which was therefore "immunodominant" over the other "immunorecessive" antigen. This immunorecessive antigen became the target of the immune response once the immunodominant antigen was lost. This "pecking order" interfered with the simultaneous recognition of two tumor-specific antigens and this mechanism may favor immune escape.

Animals↗

Malignant growth in the normal host after variant selection in vitro with cytolytic T-cell lines.

Using variant selection in vitro, we have explored the changes necessary to convert potentially malignant cells into progressively growing cancer cells. As a model, we studied the murine ultraviolet light (UV)-induced tumor 1591-RE, which routinely regresses in the normal syngeneic host. The antigenicity of this tumor is specified by multiple independent tumor-specific antigens, named A, B, C, and D. Cells of this tumor were exposed in vitro to cytolytic T-cell lines specific for these separate antigens. Tumor variants were isolated that displayed selective antigenic losses. By challenging normal syngeneic mice with the variants, we could determine the significance of each antigen in tumor rejection--i.e., a switch from a regressor to a progressor phenotype upon selective loss of certain antigens. We found that variants which lost the A and C antigens grew progressively in normal mice, whereas variants which had lost the B antigen were still rejected like the parental tumor cells. Furthermore, the B and D antigens could be expressed on progressively growing variants. Thus, loss of the A and C antigens, but not the B and D antigens, was required for allowing malignant growth. Selection for loss of one T-cell-recognized antigen never selected simultaneously for loss of any of the other T-cell-recognized antigens, nor did such selections affect sensitivity to activated macrophages or natural killer cells. Therefore, our results strongly suggest that loss of defined components of a complex T-cell-recognized antigen are sufficient to allow escape from immunosurveillance.

Animals↗

[Biocompatibility of implants with and without fluorohydrocarbon glow-discharge polymer coating. 1. Histologic and semiquantitative estimation of subcutaneous reactions in guinea pigs].

The reaction of the subcutaneous tissue in guinea-pigs at implants of titanium, titanium/glow discharge polymer, Gisadent KCM (chromium cobalt molybdenum alloy), and Gisadent/glow discharge polymer was investigated by a semiquantitative method of informing character. The 4 tested materials were well-tolerated at which titanium caused the smallest reaction.

Animals↗

[Biocompatibility of implants with and without fluorohydrocarbon glow-discharge polymer coating. 2. Automated equidensitometric recording of tissue reactions].

A conclusion on the biocompatibility, the solubility, and the chronic toxicity of different implant materials showed the equidensitometric measurement of the capsular thickness in the environs of the implants by means of the electronic image interpretation equipment Densitron. The method, the results, and the advantages of the technique are described.

Animals↗

[Biocompatibility of implants with and without fluorohydrocarbon glow-discharge polymer coating. 3. Mathematical models of the subsiding processes of the tissue reaction].

The subsidence process of the tissue reaction was estimated by the thickness of the fibrous capsule as well as different histologic characteristics in dependence on the period after the implantation of 4 several implant materials. This subsidence process was fitted mathematically by an exponential function respectively a power function by means of the regression analysis. The power function described best the experimentally found curve. The correspondence, on principle, of the subsidence process of the fibrous capsula thickness on the one hand and the 9 histologic characteristics on the other hand could be proved. A standard valuation for subcutaneous tests is demanded which include the designation of the thickness of the fibrous capsula as well as characteristic cell type frequencies as histologic characteristics.

Animals↗

Rescue of the tumor-specific immune response of aged mice in vitro.

In contrast to young mice, old mice fail to reject a transplanted challenge of the highly immunogenic, ultraviolet light-induced tumor 1591-RE. Old mice also fail to mount a cytolytic tumor-specific immune response in vivo, and spleen cells of old mice are defective in their ability to generate tumor-specific T cells in vitro. In the present study we report the results of cell culture mixing experiments that show that this deficiency is due to a decreased responsiveness of the Lyt-2+ tumor-specific cytolytic T cell precursors of the old animals. We also demonstrate with limiting dilution analysis that the defective responsiveness is not due to a clonal exhaustion of the precursors. In fact, the responsiveness could be restored in vitro by culturing the spleen cells of old animals at high density or by the addition of excess Lyt-1-/Lyt-2-/2000-rad-resistant spleen cells from young or old mice. Our results suggest that the rescue of tumor immunity in old individuals may be possible, perhaps by educating effector cells in vitro for adoptive immunotherapy.

Aging↗