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Biomedical subjects

J A Roth

Publications and source records attributed to J A Roth.

At least 559 records · Page 31Linked to original sources
PubMed1976

Detection of tumor-associated antigen in human melanoma cell line supernatants.

Spent tissue culture medium (CDM-S) removed from a single cell line of human malignant melanoma grown in serum-free CDM, contained tumor-associated antigenic activity. Antibodies to CDM-S measured by complement fixation were detected in 44% (31/70) melanoma, 55% (15/27) sarcoma, 63% (24/38) carcinoma and 15% (11/72) normal sera. Delayed cutaneous hypersensitivity reactions (DCHR) were demonstrated in 4/5 melanoma patients at a 500 mug dose, 3/5 at a 100 mug dose and in 1/7 carcinoma patients at the 500 mug dose. One ml of CDM-S was shown to contain antigen equivalent to that obtained from the membranes of 2.9 X 10(7) tissue-cultured melanoma cells. After purification, 84% (16/19) sera from melanoma patients, 66% (12/18) from sarcoma and carcinoma patients and 8% (2/26) from normal controls were positive to the antigen by complement fixation.

Antibodies, Neoplasm↗
PubMed1976

Isolation of a soluble tumor-associated antigen from human melanoma.

Human melanoma-associated antigen was solubilized from fresh surgical specimens by 3 M KC1 extraction. The antigenicity of this extract was demonstrated by delayed cutaneous hypersensitivity responses and inhibition of complement fixation. Twenty-one of 33 melanoma patients had delayed cutaneous hypersensitivity responses to melanoma antigen, while only four of 28 reacted to autologous muscle. Although KC1 extracts did not fix complement directly, they reacted with antibody, thus inhibiting complement fixation by the autologous melanoma antigen extracted from tissue culture supernatants. The soluble antigenic moiety was then purified by fractionation on a G-150 Sephedex column and polyacrylamide gels, and the antigenic activity was monitored by delayed cutaneous hypersensitivity responses in melanoma patients. A 20-fold purification was achieved. Solubilization of tumor antigens with 3 M KC1 provides tumor-associated antigen of high activity which is amenable to further biochemical purification.

Antigens, Neoplasm↗
PubMed1976

Evidence for a single catalytic binding site on human brain type B monoamine oxidase.

The tricyclic antidepressant drug, amitriptyline, inhibited the B form of human brain mitochondrial monoamine oxidase (MAO) under normal atmospheric conditions in a noncompetitive manner when phenylethylamine (PEA) was used as substrate and competitively when benzylamine (BzNH2) was employed as substrate. In addition, it was also found that PEA and BzNH2 inhibited each other's degradation noncompetitively. Similar results have previously been reported with human platelet MAO. These data suggest that the catalytic binding sites for PEA and BzNH2 on the B form of human brain MAO may be different. Attempts were made to further distinguish these catalytic binding sites on the brain oxidase using the irreversible MAO inhibitors, pargyline and clorgyline. Though these drugs have considerably different affinities for the B form of the oxidase, the degree to which either compound inhibited PEA or BzNH2 deamination was essentially identical. When incubations were performed at elevated oxygen concentrations PEA and BzNH2 became mutually competitive inhibitors of each other's metabolism. Also at the higher levels of oxygen, amitriptyline inhibition of PEA deamination approached a competitive fashion. These results suggest that PEA and BzNH2 share a common catalytic binding site on the B form of MAO and, in addition, bind to an inhibitory site on the reduced form of the oxidase. Accordingly, the data indicate that amitriptyline also binds to both the oxidized and reduced forms of this human brain oxidase.

Benzylamines↗
PubMed1976

Production of melanoma-associated antigen(s) by a defined malignant melanoma cell strain grown in chemically defined medium.

A human malignant melanoma cell strain, UCLA-SO-M14 (M14), was adapted to grow in serum-free, chemically defined medium (CDM). The 3 M KCl extract prepared from the CDM-grown cells (M-14-CDM) was assayed against leukocytes from melanoma patients, patients with other cancers, and normal donors by leukocyte migration inhibition (LMI). The leukocytes from 15 to 27 (56%) melanoma patients tested were LMI positive. In contrast, 4 of 18 (22%) other cancer patients and 5 of 30 (17%) normal donors leukocytes were LMI positive. One of 14 melanoma patients' leukocytes were LMI positive for a control 3 M KCI extract from autologous muscle. Comparative studies were performed with the M14-CDM extract and a 3 M KCI extract from a freshly biopsied tumor specimen from the donor of the M14 cell strain. Seven of 12 (58%) melanoma patients' leukocytes were LMI positive to the M14-CDM extract, but only 2 of 12 (17%) were LMI positive to the autologous melanoma tissue extract. Furthermore, only 100 to 300 mug protein of M14-CDM extract were required to educe delayed cutaneous hypersensitivity response in 6 of 8 (75%) melanoma patients and 0 of 5 lung cancer patients, but 500 mug protein from biopsied autologous melanoma tissue extract were needed to produce delayed cutaneous hypersensitivity response in 24 of 42 (57%) melanoma patients and 7 of 28 (25%) nonmelanoma cancer patients. These data suggest: (a) the M14-CDM cells synthesized melanoma-associated antigen(s) (MAA) in CDM; (B) the 3 M KCI extraction procedure effectively removed the MAA from the M14-CDM cells; (c) the M14-CDM cells were a more potent source of MAA than the surgical autologous melanoma specimen; and (d) the M14-CDM cells provided a continuous source of standard MAA.

Antigens, Neoplasm↗
PubMed1976

Effects of operation on immune response in cancer patients: sequential evaluation of in vitro lymphocyte function.

The effect of operation on in vitro lymphocyte function in 35 cancer patients was studied. Lymphocyte proliferative responses to phytohemagglutinin (PHA), poke-weed mitogen (PWM), and concanavalin A (Con A) were measured by 3H-thymidine incorporation. Sheep red blood cell (SRBC) rosette formation also was quantitated. These tests were performed preoperatively and at 24 hours, one week, and 4 weeks postoperatively. Intra-abdominal and intrathoracic procedures, transfusions, and longer operating times depressed the lymphocyte proliferative response. However, an increased lymphocyte proliferative response was noted in sarcoma patients 24 hours postoperatively, possibly as a result of lowered tumor burden. Several of these changes still were evident 4 weeks after operation. Rosette formation also decreased significantly 24 hours postoperatively in patients who had intrathoracic or intra-abdominal procedures, but returned to preoperative levels after one week. In general, operation appears to cause transient depression of lymphocyte function in some cancer patients. However, lymphocyte function returns to normal by the fourth postoperative week in most patients.

Concanavalin A↗
PubMed1976

Metastatic potential of metastases.

Nine cases of known metastases originating from other metastatic foci were documented at operation. The primary tumors included four melanomas, two osteosarcomas, a synovial sarcoma, an anaplastic lung carcinoma, and a rhadbomyosarcoma. Secondary metastatic sites to the regional lymph nodes were noted in the pulmonary hilum (one), mediastinum (one), pulmonary hilum and mediastinum (three), small bowel mesentary (two), retroperitoneum (one), and axilla (one). All patients were immunocompetent as evidenced by their ability to be sensitized to 2,4-dinitrochlorobenzene (DNCB) and/or their positive response to common skin test antigens. The metastatic potential of cells from metastases does not appear to differ from cells of the primary.

Adolescent↗
PubMed1976

Purification of soluble human melanoma-associated antigens.

Soluble extracts of melanoma specimens were prepared by 3 M KCl extraction. Delayed cutaneous hypersensitivity reactions to these antigens were noted in 25 of 39 melanoma patients and 7 of 30 patients with other neoplasms. Only 4 of 34 melanoma patients reacted to an extract of autologous muscle. Maximum reactivity to these antigens occurred at 24 hr and was demonstrated histologically by skin biopsy. Chromatography on Sephadex G-150 resulted in two fractions that elicited delayed cutaneous hypersensitivity reactions in melanoma patients. These fractions were subjected to polyacrylamide gel electrophoresis. The first region of the Sephadex 1 gel reacted in 8 of 13 melanoma patients and only 1 of 7 patients with other neoplasms. Some activity was found in other regions of the gel. Skin test activity was confined to the second polyacrylamide gel electrophoresis region of the Sephadex II gel, to which 7 of 9 melanoma patients reacted compared with 1 of 7 patients with other tumors. Recovery of antigenic activity in excess of the total present in the original extract after partial purification indicated that inhibitors of delayed cutaneous hypersensitivity reactions present in the crude KCl extract were removed. A 20-fold increase in antigenic activity per unit protein was achieved.

Adult↗
PubMed1976

A rapid assay for stimulation of human lymphocytes by tumor-associated antigens.

Lymphocyte-stimulated protein synthesis (SPS) in response to human tumor-associated antigens was assessed by measuring [3H]leucine incorporation. Correlation of SPS with other in vivo and in vitro response was demonstrated by immunizing normal subjects with keyhole limpet hemocyanin and testing sequentially frozen lymphocytes and serum samples. One week after immunization, lymphocytes from normal subjects demonstrated increased SPS to keyhole limpet hemocyanin. This correlated with the appearance of delayed cutaneous hypersensitivity responses and preceded detection of hemagglutinating antibodies and increases in lymphocyte [3H]thymidine incorporation. There was no difference in the reactivity of fresh and viable frozen lymphocytes, and as few as 5X 10(5) lymphocytes/microtiter plate well could be used. Tumor-associated antigens were prepared from four lung carcinomas, six sarcomas, and six melanomas, using 3 M KCI extraction. Lymphocyte responses to both autologous and allogeneic tumor extracts were observed. Five of 15 patients demonstrated significant SPS to autologous tumor antigens. Fourteen of 20 lung cancer patients responded to lung cancer antigen, whereas only 11 of 41 patients with other tumors and 3 of 19 normal subjects reacted. Significantly, more lung cancer patients reacted to the tumor extract than to an extract of uninvolved lung from the same patient. Twenty-one of 42 melanoma patients responded to melanoma antigen. Ten of 33 patients with other tumors and 3 of 24 normal subjects reacted to the melanoma extract. Eight of 30 melanoma patients reacted to an extract of muscle from the same donor as was the melanoma antigen. Tumor-associated antigenic activity of 3 M KCI extracts can therefore be detected by measuring lymphocyte [3h]leucine incorporation.

Antigens, Neoplasm↗
PubMed1975

Inhibition of human leukocyte migration in agarose by kcl extracts of carcinoma of the lung.

The leukocyte migration in agarose assay recently developed by Clausen (Clausen, 1971), was used to test 22 lung cancer patients against soluble extracts of allogeneic lung cancer and allogeneic normal lung. Seventeen were inhibited to a significantly greater degree by at least one tumor extract (average migration index (MI equals 0.58) than by the corresponding normal lung extract (average MI equals 0.83). DNCB-positive and DNCB-negative patients reacted with equal frequency to tumor extracts. Three patients tested against their autologous tumor and normal lung extracts were specifically inhibited by the tumor extract (average MI equals 0.53) but not by the normal lung extract (average MI equals 0.83). None of seven lung cancer patients tested against non-pulmonary tumor extracts was significantly inhibited (average MI equals 1.1). Only 6/53 controls including patients with other tumors, patients with emphysema and age-matched non-smokers showed significant inhibition against any of the lung cancer extracts. These findings strongly suggest the presence of tumor-associated antigens in KCl-solubilized extracts of human lung cancer.

Antibodies, Neoplasm↗
PubMed1975

Radionuclide photoscanning. Usefulness in preoperative evaluation of melanoma patients.

The results of radionuclide scans (liver, bone, and brain scans and whole-body scans using bleomycin tagged with radioactive indium [111In]) performed on 100 melanoma patients during their initial evaluation were reviewed to determined whether or not they effected a change in clinical staging or therapeutic decision. Patients were classified as stage I (primary disease) or stage II (regional disease) on the basis of regional lymph node dissections. Only one patient (stage II) of 73 stage I and II patients had an abnormal finding on the initial radionuclide scan. Fifteen of 26 patients thought to be stage III (disseminated disease) on clinical grounds had abnormal findings on at least one scan. A therapeutic change as a result of scanning occurred in the stage II patient after abnormal bone and whole-body scans. As an initial routine screening test for stage I and II melanoma patients, radionuclide scanning was unproductive and rarely influenced therapeutic decisions.

Adult↗
PubMed1975

Synovial sarcoma of the neck: a followup study of 24 cases.

This article reviews the clinicopathologic features and the biological behavior of 24 cases of synovial sarcoma that took origin from the cervical prevertebral connective tissue space and manifested as a retropharyngeal tumor or as a palpable mass in the anterior or posterior cervical triangle. The age of the 24 patients ranged from 10 to 51 years, with a median of 19 years. Ten patients were women and 14 men. Hoarseness or difficulty in breathing or swallowing were the first symptoms in eight patients. The tumors were solitary and ranged from 2 to 10 cm in greatest dimension. Microscopically, all of the cases showed the characteristic biphasic cellular pattern of a synovial sarcoma, with epithelioid and fibrosarcoma-like areas in varying proportions. Synovioblastic origin of the neoplasm was confirmed by the results of histochemical staining procedures and, in 1 case, by the examination with the electron microscope. Of the 21 cases followup information, 12 had died (10 with pulmonary metastasis) and 9 were alive and free of symptoms. Prompt and complete surgical removal is required to prevent complications from recurrent tumor growth or metastasis.

Adolescent↗