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Biomedical subjects

H F Seigler

Publications and source records attributed to H F Seigler.

At least 163 records · Page 9Linked to original sources

DTIC, CCNU, bleomycin and vincristine (BOLD) in metastatic melanoma.

Treatment of 91 consecutive patients having metastatic, Stage IV melanoma who had not received any previous chemotherapy was begun between January 1977 and April 1978. The therapy included bleomycin (B) at 7.5 units subcutaneously in the first course and 15 units in subsequent courses on days 1 and 4; vincristine or Oncovin (O) at 1 mg/m2 intravenously on days 1 and 5; CCNU or lomustine (L) at 80 mg/m2 p.o. on day 1 and DTIC (D) 200 mg/m2 intravenously on days 1 through 5. Evaluable patients (72) were those who had measurable tumours in the viscera and on the skin. Seven patients (9%) responded with complete tumor regression (CR), 22 (31%) with partial regression (PR) (50% or more tumor regression), 12 (17%) with stabilization of disease, and 31 (43%) with progression of the disease. Patients who responded with CR, PR, and stable disease (41 patients) had a median survival of 67 weeks, while those who did not respond (31 patients) had a median survival of 20 weeks (P < .0001). Overall median survival was 31 weeks. The bleomycin-Oncovin-lomustine-DTIC (BOLD) regimen is an effective alternative treatment for metastatic melanoma; there is good tumor response and prolongation of survival in the responding patients. Its overall toxicity is mild to moderate.

Antineoplastic Agents↗

Sex steroid receptor analysis in human melanoma.

Melanomas from 20 patients were evaluated for estrogen and progesterone receptors. No restriction as to patient's age, sex, race, or menstrual status was made. Fifteen of the tumors were melanin producing. Of the 20 tumors examined, seven contained more than 3 fm/mg protein of specifically inhibitable estrogen binding. None of the tumors reported here demonstrated either a 4S or 8S binding protein as shown by sucrose density gradient analysis. All tumors in which estradiol binding was observed were melanin producing, whereas none of the amelanotic melanomas (five tumors) bound this steroid. Purified tyrosinase appeared to mimic the estrogen binding detected in melanoma cytosols, as demonstrated with the dextran-coated charcoal technique. Although the binding of estradiol to tyrosinase was inhibited by DOPA, the binding of estradiol to estrogen receptor preparations was not. These studies represent an extensive of previous studies of sex steroid binding in melanomas and suggest that gradient analysis and DOPA inhibition studies should be included in the evaluation of the estrogen binding phenomenon in human melanoma.

Adult↗

Characterization of melanoma cell membrane tumor-associated antigens using xenoserum, alloserum, and autoserum: I. immunofluorescence.

Xenoantiserum, alloantiserum, and autoantiserum prepared against human melanoma cells from cell lines maintained in tissue culture were evaluated by indirect immunofluorescence (ind IF) for their content of antibodies reactive with melanoma cell membrane tumor-associated antigens (TAA). Following absorptions which removed all detectable anti-human species, anti-RBC, and anti-HLA antigen activity, the antisera were tested against a panel of human cell lines. Three apparently distinct melanoma-associated cell membrane antigens were detected. The first of these was present on all human cells maintained in tissue culture including cells of both malignant and nonmalignant origin. The second antigen was expressed on all cells of malignant origin and also by fetal fibroblasts. The third antigen was detectable only on melanoma cells and was expressed by a majority of the melanomas tested. No evidence was obtained to suggest the presence of melanoma TAA unique to a single melanoma cell line. Marked differences were observed in the antigenic profile detected by the three antisera.

Animals↗

Transplantation of insulinoma into the diabetic Syrian hamster.

Syrian hamsters were rendered diabetic with intraperitoneal streptozotocin and were maintained in the diabetic state for a minimum of 14 days. A hamster islet cell tumor was transplanted subcutaneously with a prompt return of water intake (38 +/- 9.1 ml/day to 7.1 +/- 2.2 ml/day, mean +/- SD), urine glucose (4.8 +/- 0.84 g/day to less than 250 mg/day), urine output (37.4 +/- 10.9 ml/day to 7.6 +/- 2.1 ml/day), blood glucose (297 +/- 31.9 mg/dl to 87.6 +/- 28 mg/dl), and weight gain (1.0 to 0.8 g/day) to normal control levels. Histologic examination of the engrafted tumors revealed a well encapsulated tumor with no evidence of metastatic disease. The transplanted insulinomas maintained well differentiated histologic features without evidence of necrosis. Immunopathologic studies failed to reveal any evidence of either humoral or cell mediated immunity directed toward the allograft. Each animal was successfully transplanted with a 1 mm tumor explant. A single rodent tumor donor provided adequate material for engraftment for five recipients. The transplanted insulinomas maintained full functional and enzymatic capabilities. Similar studies utilizing the hamster insulinoma engrafted into the athymic nude mouse showed amelioration of the same diabetic symptomatology. Many of the technical difficulties encountered with whole organ and isolated islet transplantation encourages development of a more practical model. These experimental results suggest an alternative method for supplying the diabetic with an endogenous insulin source.

Adenoma, Islet Cell↗

Postoperative function of "free" jejunal transplants for replacement of the cervical esophagus.

The postoperative function of "free" jejunal autotransplants for replacement of the pharyngoesophagus after palliative resection was evaluated in nine patients using clinical assessment, cinefluoroscopy, manometry, and electrical studies. After an initial period of adjustment, all patients swallowed solids and liquids with minimal difficulty, gained weight appropriately and were satisfied with their operations. Cinefluoroscopy and esophageal manometry demonstrated normal function of the intact distal esophagus, which correlated with the absence of reflux symptoms. The grafts were capable of contraction in response to local distension and maintained an intrinsic myoelectrical activity. These results indicate that jejunal autotransplantation may provide excellent palliation with restoration of a near normal swallowing mechanism for patients with large resectable lesions of the pharyngoesophagus. An additional observation was that the instillation of food directly into the gastric antrum caused a change in the motor activity in the transplantd jejunum, indicating physiological hormonal control of intestinal motility.

Aged↗

Immunological consequences of transplanting rat insulinomas.

We investigated the genetics of transplanting a NEDH rat insulinoma in various donor-recipient combinations. The insulinoma survived indefinitely when it was transplanted in the NEDH strain. Mean survival times of 8.6 +/- 1.2 and 3.3 +/- 1.0 days were recorded in allogeneic and xenogeneic combinations, respectively. No prolongation of mean survival time was found when the rat insulinoma was first passed through the athymic nude mouse and then transplanted as either an allograft or xenograft. The findings of the major histocompatibility antigen (Ag-B7) on the original insulinoma and the tumor that had been passed through the nude mouse demonstrates no demonstrable loss of transplantation antigens during passage.

Adenoma, Islet Cell↗

Primary intracranial melanoma presenting as a suprasellar tumor.

A 37-year-old white woman presented with progressive visual loss in the right eye. The diagnostic evaluation suggested a tumor in the suprasellar area. At operation an isolated melanoma was found just superior to the sella turcica. No evidence of other intracranial lesions was present and complete diagnostic studies failed to reveal any other primary site. The patient subsequently underwent a second neurosurgical procedure in an effort to remove the tumor completely. This was followed by recurrent symptomatology and she was then treated with a combination of multiple drug chemotherapy and immunotherapy. Approximately 3 years after her initial operation the patient succumbed secondary to her disease. The autopsy findings were consistent with a primary melanoma of the leptomeninges in the area just above the sella turcica. This unusual presentation is discussed and plausible hypotheses are given.

Adult↗

Melanoma.

Explore the source record for details and available documents.

Humans↗

Selection of patients for heterotopic implantation of the areola and nipple.

In a prospective analysis of 291 specimens taken at mastectomy for carcinoma, 48 contained tumor in the nipple-areola complex. The characteristics of greater tumor size, higher frequency of lymph node involvement, midbreast tumor location and multifocality of tumor correlated well with the probability of involvement of the nipple. The findings emphasize the importance of close clinical and histopathologic examination of the nipple and areola when preservation of the nipple is being considered.

Adult↗

Non-specific and specific active immunotherapy in a B16 murine melanoma system.

Conflicts amongst reports concerning the efficacy of both nonspecific and specific attempts at immunotherapy may be ascribed to different animal models utilizing tumors of different immunogenicity. We have selected the B16 mouse melanoma model as the example of a spontaneously occurring neoplasm that is histocompatible with the host and does have tumor-associated antigens. Attempts to alter tumor growth or survival with nonspecific active immunotherapy as well as with specific active immunotherapy were not successful. Nonspecific active pre-immunization failed to alter tumor take or growth. Specific active immunotherapy both with and without adjuvant did decrease tumor take and prolong host survival. The effects were increasingly documented at lower tumor cell inoculums and became less apparent with increase in the tumor cell challenge.

Adjuvants, Immunologic↗

Monoamine oxidase and catechol-O-methyltransferase activity in hamster and rat insulinomas.

Hamster and rat insulinomas were assayed for norepinephrine, dopamine and serotonin concentration and for monoamine oxidase and catechol-o-ethyltransferase (COMT) activity. The concentration of norepinephrine (mean 0.55 mumol/kg, range less than 0.20 to 2.64 mumol/kg) and serotonin (mean 5.22 mucol/kg, rang less than 0.6 to 26.5 mumol/kg) in hamster insulinomas were comparable to previously reported concentrations. Dopamine conentration (mean 0.34 mumol/kg, range less than 0.20 to 0.95 mumol/kg) was only 2 to 2.5% of that reported previously. Monoamine oxidase activity of the hamster and rat insulinomas were comparable to those of normal hamster islets. In contrast, the COMT activity of both insulinomas was much greater than the COMT activity of normal pancreatic islets of both species and was greater than in several other tissues and tumours. The tumour COMT, which was predominantly in the cytosol, was Mg2+ dependent and had a comparable sensitivity to inhibition by tropolone as purified beef-liver COMT. Hamster insulinoma monoamine oxidase was more sensitive than rat insulinoma monoamine oxidase to inhibition by tranylcypromine and deprenyl, while rat insulinoma monoamine oxidase was more sensitive to inhibition by clorgyline and was more heat labile.

Adenoma, Islet Cell↗

Alimentary tract complications after renal transplantation.

A computer analysis of post renal transplantation gastrointestinal problems was performed to identify important associated clinical factors. Thirty-seven per cent of all transplant recipients developed one or more significant problems. Hemorrhage, nondiverticular intestinal perforation, and esophagitis occurred most frequently in hospitalized patients. Pancreatitis, diverticulitis, and gastroduodenal perforation occurred characteristically in long-term survivors with well functioning allografts. Eleven of 32 HLA identical recipients treated with maintenance corticosteroids during stable kidney function developed gastrointestinal disease while only one of 13 HLA identical recipients not given maintenance steroids developed a problem, which strongly suggests a causal role for steroids in the development of late complications. The association of preexisting peptic ulcer and diverticular disease with hemorrhage and perforation supports previous recommendations that documented peptic ulcer disease or diverticulitis should be corrected surgically prior to transplantation.

Adolescent↗

Cystosarcoma phylloides. A steroid receptor and ultrastructure analysis.

Six cases of cystosarcoma phylloides were evaluated by ultrastructure and steroid receptor analysis. Electron microscopy of the lesions supported previous reports of a heterogeneous tumor consisting of pleomorphic mesenchyme and normal or proliferative epithelium. In each case estrogen and progesterone receptor analysis indicated the presence of a nonsaturable estrogen and progesterone 4S binding protein rather than a specific steroid receptor as suggested by previous studies.

Adolescent↗

The spectrum of small bowel melanoma.

Twenty-one patients with documented secondary small bowel involvement by malignant melanoma are reviewed. Roentgen mainfestations are discussed and illustrated. A vigorous diagnostic approach emphasizing enteroclysis is described. Clinical awareness and aggressive radiologic investigation are providing these patients with earlier surgical and adjuvant therapy, which appears to be leading to increased length of survival.

Adolescent↗