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Biomedical subjects

K Hagen

Publications and source records attributed to K Hagen.

At least 73 records · Page 4Linked to original sources

Long-term prognosis after radical treatment for squamous-cell carcinoma of the anal canal and anal margin.

Sixty-seven of 100 (67 percent) and 24 of 58 (41 percent) apparently radically treated patients with squamous-cell carcinoma of the anal canal (AC) and the anal margin (AM) developed recurrent disease during a median observation time of ten years (range, 0 to 38 years). A significantly higher number of patients treated for AC tumors with local excision had recurrent disease compared with patients treated with abdominoperineal resection (P less than .05). Twenty patients with AC tumors had local recurrence, 21 regional recurrence, and 26 visceral metastases. Eighteen patients with AM tumors had local recurrence, five regional, and one brain metastases. The latest recurrences among AC and AM tumor patients were diagnosed 11 and nine years after primary treatment, respectively. The estimated cure rate by the actuarial method after 15 years was 26 percent and 53 percent for AC and AM tumors, respectively. Thus, if recurrent carcinomas of the anus are to be detected early, frequent life-long control examinations are necessary. It is obvious from this study that, in order to reduce recurrent disease of carcinoma of the anus, new treatment regimens must be tried under controlled circumstances. Surgical therapies alone are clearly insufficient in the treatment of carcinoma of the anus.

Actuarial Analysis↗

Does an erroneous diagnosis of squamous-cell carcinoma of the anal canal and anal margin at first physician visit influence prognosis?

Patients with squamous-cell carcinoma of the anal canal (n = 125) and its margin (n = 76) were divided into five groups: those with an erroneous diagnosis and a correct diagnosis made at first physician visit; those with a history of less than six months, between six and 18 months, and more than 18 months. Patients with canal tumors had an erroneous diagnosis made more frequently than patients with margin tumors. In both groups patients with an erroneous diagnosis had longer histories than patients with a correct diagnosis. Among patients with erroneously diagnosed canal tumor, pain, the feeling of a lump, anal discharge, and pruritus ani occurred less frequently than among correctly diagnosed patients. The prognosis was worse among patients with erroneously diagnosed canal tumors compared with correctly diagnosed patients. Such a difference could not be found among patients with margin tumors. There was a gradual worsening of the prognosis among patients with increasing length of history and canal tumors, in contrast to patients with margin tumors, in whom only a history of more than 18 months was associated with a worse prognosis.

Adult↗

Hepatoblastoma: an immunohistochemical and ultrastructural study.

The ultrastructural and immunohistochemical features of 19 hepatoblastomas were examined to evaluate the phenotypic expressivity of this solid embryonic neoplasm of childhood. Electron microscopy confirmed the embryonal and fetal characteristics of the neoplastic hepatocytes, but in addition, cells with features intermediate between these two cell types were identified. Dense bundles of collagen corresponding to the osteoid-like material by light microscopy surrounded nests of cells; the cells within this matrix stained for epithelial membrane antigen and vimentin and focally for cytokeratin, and they showed ultrastructural features of epithelial cells. The two cases of small cell hepatoblastoma reacted positively for vimentin and cytokeratin; the remaining 17 cases were immunoreactive for cytokeratin and alpha-fetoprotein, and some also for alpha 1-antitrypsin, ferritin, and vimentin. A histogenetic scheme based on our findings is proposed to explain the divergent morphologic features of this neoplasm.

Carcinoembryonic Antigen↗

Immunity to murine leukemia induced in susceptible mice by transfected mouse fibroblasts.

A cultured cell line of mouse fibroblasts was transfected with DNA from murine leukemia cells expressing a previously characterized tumor-associated antigen. Antigen-positive cells were used as immunogens in an immunotherapy protocol to determine if they stimulated resistance to the malignant proliferation of the leukemia in susceptible mice. For the experiments, LM(TK-) mouse fibroblasts, a thymidine kinase-deficient mouse cell line, were cotransfected with DNA from ASL-1 murine leukemia cells and the plasmid pSV2neo conferring resistance to Geneticin. Integration of the plasmid into cellular DNA was confirmed by restriction digest blot analysis. A/J mice, highly susceptible to the malignant proliferation of passively transferred ASL-1 leukemia cells, were immunized with the transfected cells. Animals receiving two prior injections of antigen-positive transfected cells and then challenged with an injection of viable ASL-1 cells survived longer than animals in the unprotected control group or in the group receiving immunizations with LM(TK-) cells transfected with plasmid only (p less than 0.01). Some of the mice appeared to have rejected the tumor and lived more than 80 days. One group of protected animals rechallenged with a second injection of ASL-1 cells, 40 days after the first, survived for more than 50 additional days, without evidence of recurrent disease.

Animals↗

Formation of macrophage (M) colony-stimulating factor by murine leukemia x fibroblast hybrid cells.

Clonogenic assays for M, GM, and G precursors of rat or mouse marrow cells were performed in the presence of medium conditioned by the growth of ASL-1 leukemia X LM fibroblast hybrid cells. Both GM- and M-colony-forming units (CFUs) were present in marrow cultures maintained in conditioned medium (CM) from hybrid cells (up to 162 +/- 10 total colonies per 10(5) cells) and from LM cells (65 +/- 5). Conditioned medium from ASL-1 cells did not lead to the formation of CFUs. The hybrid cell-derived CM supported the development of M and GM-CFUs from the marrows of DBA, CAF1, BDF1, C3D2F1, and C57B1/6 mice as well as Lewis, Brown Norway, and Wistar Furth rats. G-CFU were not detected in any of the preparations. Hybrid cell-CM supported the long-term growth and proliferation of macrophage-like cells from mouse spleen, consistent with the presence of M-colony-stimulating factor (CSF). Evidence that M-CSF formed by the hybrid cells and M-CSF formed by L cells shared structural features was provided by antibody neutralization studies. The CFU-promoting activity of hybrid cell-derived M-CSF was neutralized by an antiserum raised in goats against M-CSF purified from L cells. Independently prepared ASL-1 X LM hybrid cells, like the original, led to the formation of GM and M-CFUs. Attempts to detect each of several other previously defined growth factors in medium conditioned by the hybrid cells were unsuccessful. Interleukins 1, 2, and 3; B cell growth factors interferons alpha, beta, and gamma; erythropoietin; and burst promoting factor were not detected.

Animals↗

Neuromas of the appendix. A light-microscopic, immunohistochemical and electron-microscopic study of 20 cases.

The neural origin and even the existence of appendiceal neuromas have been questioned. We have studied 20 examples, 7 discovered during a prospective examination of 26 consecutive routine appendectomy specimens (for an incidence of 27%), 2 selected from random cases, and 11 discovered in a retrospective review of 11 randomly selected cases of appendices diagnosed as "fibrous obliteration." By light-microscopy, appendiceal neuromas appear as a loose proliferation of spindle cells usually in a myxoid background, frequently with entrapped fat and connective tissue and infiltrated by eosinophils. Seventeen were located centrally in the appendix without nodule formation. One was central with nodularity and two were confined to the mucosa. The spindle cells were positive for S-100 protein and neuron-specific enolase in all cases. In 12, serotonin positive cells entrapped in the proliferation were present. In 5 of 11 cases with apparent uninvolved appendix present in the specimen, the number of serotonin cells in the crypts was greater than in normal appendix controls. Two appendiceal neuromas contained somatostatin positive cells. Stains for vasoactive intestinal polypeptide, substance P, neurotensin, bombesin and gastrin were negative. Ultrastructural examination of one case confirmed the presence of a mixture of Schwann cells and cells containing neurosecretory granules. We conclude that appendiceal neuroma is a rather common entity, and that most cases of so-called fibrous obliteration actually represent appendiceal neuroma.

Adolescent↗

The role of intercellular contacts in the activation of B lymphocytes by anti-immunoglobulin antibodies.

It has been proposed that anti-Ig antibody activates B cells in a way analogous to the antigens, i.e., it delivers its signal by cross-linking and clustering the Ig receptors on the surface of one cell. However, the cross-linking of different B cells which may deliver to each other a signal has not been considered. Thus, we examined the effect of preventing cell contacts on the response of rabbit B cells to anti-Ig allotype antibody by using a solid agarose medium. First, we examined the 14C-uridine incorporation in liquid medium and in liquid or solid agarose in cultures stimulated with anti-Ig antibody (Ab). The response was high in liquid agarose or liquid medium but was absent when the agarose-containing medium was solidified at the start of the cultures. If the agarose was solidified 6 hr after the start, a good response was obtained. Moreover, if the cells were sedimented at the start before solidifying the agarose-containing medium, a good response was also obtained. Similar results were obtained when T cells were activated by Con A. To examine whether B cells require contacts with other B cells or with non-B cells, we examined their response to anti-Ig Ab in the absence of macrophages or T cells, and found that purified B cells from lymphoid organs or from thoracic duct responded well in the absence of T cells and/or macrophages. The response was also absent when the cells were cultured in agar at a "local" concentration close to 10(8) cell/ml. Also, concentrated supernatants of anti-Ig-stimulated cells did not increase the response to anti-Ig in solid agarose. These two last observations suggest that the lack of response in solid agarose is not due to a lack of diffusible factors or to a lack of feeder cells. Therefore, because the only difference between the cultures that responded to anti-Ig or Con A and those that did not was the distance between the cells, we concluded that the contact between B cells or between T cells is essential to their activation by their respective mitogens. We speculate that the anti-Ig Ab or the antigen cross-links B cells, which then provide each other with the activating signal or with one of the activating signals.

Animals↗

Leukaemia x fibroblast hybrid cells augment the antibody response to sheep red blood cells in inbred mice.

ASL-1 x LM(TK-) hybrid cells, an established murine leukaemia x fibroblast hybrid cell line, augment the antibody response to sheep red blood cells in inbred mice, as determined by the plaque assay method. The intraperitoneal injection of viable hybrid cells or of growth medium conditioned by the cells leads to an increase both in the total number as well as the proportion of cells forming antibodies to sheep red blood cells. CSF-1, (M-CSF), is detected by radioimmunoassay in the medium conditioned by the hybrid and LM(TK-) cells, but not ASL-1 parental cells. Prior treatment of the conditioned medium with CSF-1 antiserum reduces its capacity to augment the antibody response, and its proliferative stimulus on cells from the marrow indicating that CSF-1 may be at least partly responsible for the adjuvant effect observed. The intraperitoneal implantation of diffusion chambers containing viable CSF-1 producing hybrid cells, like the cells themselves, also leads to an increase in the number of spleen cells forming antibodies to sheep red blood cells.

Animals↗