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Biomedical subjects

M S Mahaley

Publications and source records attributed to M S Mahaley.

At least 55 records · Page 3Linked to original sources
PubMed1984

Tumoricidal activity of an acute promyelocytic leukemia cell line (HL-60) is augmented by human interferon alpha.

Normal human peripheral blood polymorphonuclear leukocytes (PMNs) and cells from a human acute promyelocytic leukemia line (HL-60) were tested for cytotoxic potential against two human glioma and one normal fibroblast line. Both the PMNs and HL-60 exhibited significant cytotoxicity against the tumor targets while sparing the normal fibroblasts. However, the two glioma cell lines were not equally susceptible to the effector cells. Addition of low levels of purified human lymphoblastoid interferon alpha (IFN) during the assay period significantly enhanced the tumoricidal effect against one of the glioma targets. HL-60 cells, partially differentiated to myelocytes and metamyelocytes by incubation with dimethylsulfoxide (DMSO), expressed reduced levels of cytotoxicity; IFN added during the assay was able to restore the cytotoxic activity against both glioma cell lines. Undifferentiated HL-60 cells were also able to lyse K562 targets in a six hour 51Cr release assay; this activity was also significantly enhanced by IFN. Separate incubation of both effectors and targets proved that the enhancement of cytotoxic activity demonstrated was due to an effect on the HL-60 effector cells. In contrast, the lysis of HSB-2, another NK sensitive target cell, was not enhanced by the addition of IFN to a mixture of HSB-2 and HL-60 cells. Pretreatment of effector and target cells separately with IFN demonstrated a dual effect: IFN both protected HSB-2 targets from lysis by the HL-60 effectors and induced significantly greater cytotoxicity by HL-60 cells.

Cell Differentiation↗
PubMed1984

Immunobiology of primary intracranial tumors: IX. Phase I study of human lymphoblastoid interferon.

Interferon was administered intravenously on 3 consecutive days each week for 3 consecutive weeks in doses escalated each week from 10 to 20 to 30 megaunits (MU)/m2/day. Nine adult patients were treated, each of whom had undergone subtotal resection of a supratentorial anaplastic glioma within 3 weeks of beginning interferon treatment. Patients ranged in age from 34 to 71 years, and Karnofsky functional scores were 70 or greater. Evaluations included neurological examination, Karnofsky functional rating, computerized tomography brain scanning, and panels of hematologic, hepatic, renal, and coagulation testing. No dose-limiting or prohibitive toxicities were encountered, and each patient received nine interferon doses as scheduled. There were no symptoms of neurologic toxicity other than transient lethargy. Chills and fever occurred in all patients, while headache, lethargy, and back pain were experienced by half. These symptoms were most pronounced with the initial dose of each week and did not intensify with dose escalation. The most frequent side effect of interferon treatment was fever, usually peaking near the end of the initial 4-h infusion; it became less severe during the second and third weeks. Leukopenia and granulocytopenia were mild. Serum hepatic enzyme levels rose slightly during the course of interferon treatment and returned to normal after treatment was completed. Serum interferon levels reached a maximum concentration of 2,285 U/ml at the end of infusion and were proportional to the dosage. Interferon was not detectable in lumbar cerebrospinal fluid, but fluid from the tumor bed of one patient contained 120 U/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

The relative roles of neurological examination, functional abilities, and computed tomography in the definition of treatment failure in patients with anaplastic gliomas.

Forty-one patients with anaplastic gliomas undergoing postoperative treatment and evaluation underwent bimonthly evaluation of the following indices of treatment failure: neurological examination; Karnofsky functional rating; and computed tomography (CT) brain scanning. Treatment failure was declared when neurological examination or Karnofsky rating showed increased impairment or when CT scan revealed an increase in tumor sizes. Most often, all three indices simultaneously indicated treatment failure. In only 6 of 41 cases the CT scan alone was the first indication of treatment failure. During the first 6 months of follow-up, tumor enlargement on CT scan as a sole index of treatment failure occurred in only 3 of 26 cases that showed evidence of treatment failure during that time. For patients with glioblastoma, about 6% of treatment failures within 6 months are predicted to be missed by Karnofsky rating plus neurological examination, whereas CT scan alone is predicted to miss about 30%. It would seem reasonable to rely on the neurological examination and Karnofsky rating for follow-up during the first 6 months after surgery, without routine serial CT scanning during that time.

Brain Neoplasms↗
PubMed1983

Unilateral subdural hematoma without midline shift.

Two cases of radiographically isodense subdural hematoma are presented in which absence of displacement of midline cerebral structures was due not to bilateral lesions, but rather to "balancing" of the volumetric effect of a unilateral lesion by preexisting encephalomalacia. Attention to the past medical history and the computed tomography scan which showed evidence of unilateral loss of brain substance led to the proper diagnosis.

Adult↗
PubMed1983

Prevention of glioma induction in rats by simultaneous intracerebral inoculation of avian sarcoma virus plus bacillus Calmette-Guerin cell-wall preparation.

Bacillus Calmette-Guerin cell-wall preparation was injected along with avian sarcoma virus in the brains of newborn Fischer 344 rats, and subsequent glioma induction was compared with rats injected with avian sarcoma virus alone. The percentage of glioma induction and survival were found to be directly related to avian sarcoma virus concentration (10(0), 10(-1), 10(-2), and 10(-3)). A significant reduction in glioma induction occurred when BCG cell-wall preparation was injected with 10(-2) ASV concentration. Above that concentration of ASV, the tumor induction was not significantly affected by bacillus Calmette-Guerin cell-wall preparation; below that concentration, the tumor induction was too low with avian sarcoma virus alone to evaluate an effect.

Animals↗
PubMed1983

Metastatic renal cell carcinoma mimicking a meningioma.

We report a patient with renal cell carcinoma metastatic to the left trigone, which mimicked an intraventricular meningioma. The metastasis was recognized 1.3 years after removal of the primary tumor, a longer disease-free interval than any previously reported cases with brain metastases of renal cell carcinoma. The patient is now free of disease of years after resection and 17 years after the discovery of the primary tumor. Metastatic disease should be considered in all patients with prior resection of renal cell carcinoma who experience the onset of neurological disease, even after a prolonged disease-free interval. Long term survival is observed after the resection of solitary metastases, particularly if these appear after a prolonged disease-free interval.

Adenocarcinoma↗
PubMed1983

Immunobiology of primary intracranial tumors. Part 7: Active immunization of patients with anaplastic human glioma cells: a pilot study.

Twenty patients with malignant gliomas were selected for active immunization within 4 weeks following surgery. Each patient had a Karnofsky Functional Rating equal to or greater than 70, a peripheral blood lymphocyte count equal to or greater than 1000 cells/cu mm, skin test responses to one or more of four recall antigens, peripheral blood T-cells equal to or greater than half that of control, and was not receiving steroid therapy at the time of entry into the study. Each patient received subcutaneous inoculations with one of two human glioma tissue culture cell lines (D-54MG or U-251MG) monthly, with 500 micrograms of bacillus Calmette-Guérin cell wall (BCG-CW) being included with the first inoculation. Each patient also received levamisole, 2.5 mg/kg 3 days per week every other week. Radiotherapy and chemotherapy with BCNU were begun after the first month of immunization. Follow-up evaluations included computerized tomography brain scans, neurological examinations, Karnofsky Functional Ratings, and studies of general immune competence. No evidence of allergic encephalomyelitis was noted clinically, nor was any gross or microscopic evidence of such pathology obtained upon autopsy of three of these patients. Serial studies of general immune competence showed no alterations from those previously described with non-immunized patients. Patients who were inoculated with the U-251MG cell line have had a longer survival time compared to those inoculated with the D-54MG cell line (p less than 0.0590) or compared to 58 historical cases of glioma patients treated with levamisole, radiation therapy, and chemotherapy alone (p less than 0.02).

Adult↗
PubMed1983

Immunobiology of primary intracranial tumors. Part 8: Serological responses to active immunization of patients with anaplastic gliomas.

Serial serological studies were carried out on 19 of 20 patients with malignant gliomas who were actively immunized with one of two human glioma tissue culture cell lines (D-54MG or U-251MG). Most patients mounted a significant serum reaction to histocompatibility antigens (HLA's), as well as an antibody response to fetal bovine serum (FBS) which was added to the glioma-cell inoculum. These two sources of antibody accounted for greater than 90% of the antibody induced by these inoculations. Two patients continued to have significant amounts of binding antibody to the original immunizing cell line following exhaustive absorptions of FBS and these two had all remaining significant antibody removed by further absorption of the serum against the 2-T osteogenic sarcoma tissue culture cell line known to possess antigens cross-reactive with human gliomas. One single patient continued to show significant antibody binding to the original glioma cell line following absorption against FBS, human platelets, and the 2-T cell line, and therefore seems to have produced glioma-distinctive antibodies in response to immunization. The antibody preparation from this patient was also cytotoxic against the original glioma cell line, as well as another recently cultured human glioblastoma cell line. The significance of these serological studies is discussed as it relates to immunological responses patients with gliomas may make to active immunization.

Antibodies, Anti-Idiotypic↗
PubMed1981

Heterogeneity of Genotypic and phenotypic characteristics of fifteen permanent cell lines derived from human gliomas.

Six new permanent cell lines were established from human gliomas and compared to nine other cell lines from human gliomas. All fifteen lines had individually distinct HLA phenotypes and all but two, which were from a black patient, had type B glucose-6-phosphate-de;hydrogenase isoenzymes. Morphologically, the lines could be classified into four patterns descriptively designated as fibroblastic, fascicular, epithelial, or glial. Four of the lines grew progressively and could be serially transplanted when injected into athymic mice; two others grew initially and then regressed. From none to 100% of cells developed elongated tapering processes and showed reduction in nuclear-cytoplasmic ratio in the presence of 1 mM cyclic AMP and theophylline. Levels of 2'-3' cyclic nucleotide 3'-phosphohydrolase activity ranged from nondetectable to 12.78 +/- 1.49 micromoles 2' AMP formed per hr mgm total protein. None of the lines had detectable S-100 protein, but two had readily demonstrable glial fibrillary acidic protein in indirect immunofluorescence. Fibronectin levels in spent culture supernatants ranged from undetectable levels to 21.4 micrograms/ml/10(5) cells. All but one line shared surface antigens with normal human adult or fetal brain, as detected in absorption analyses with nonhuman primate antiserum raised against glioblastoma multiforme tissue or cell line U-251 MG. Although there were many common properties of the lines, each line had a unique profile of the parameters evaluated. This heterogeneity most likely reflects the individuality of the tumors of origin and individual genotypes and capacity for a range of phenotypic expression of cells.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1981

Immunobiology of primary intracranial tumors. Part 4: levamisole as an immune stimulant in patients and in the ASV glioma model.

Levamisole was evaluated as an immune stimulant in a randomized controlled study of patients with anaplastic gliomas, who had undergone surgical resection and who were also treated with radiotherapy and BCNU chemotherapy. Of 102 patients placed into the study, 85 were determined to comprise the adequately treated group (ATG): a full course of radiotherapy and two cycles of BCNU chemotherapy. Within the ATG, those patients who received levamisole did not demonstrate significantly different serial delayed hypersensitivity reactions, peripheral blood lymphocyte and T-cell counts, or serum IgM levels, compared to those patients not receiving levamisole. There was no significant difference in survival times of the two groups. Studies utilizing the avian sarcoma virus-induced glioma in rats also showed no improvement in survival with levamisole stimulation as the only immune agent, but the combination of active immunization and adjuvant stimulation with bacillus Calmette-Guerin plus levamisole was found to be therapeutically effective in this model and will be used in future pilot studies of active immunization in patients.

Adjuvants, Immunologic↗