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Biomedical subjects

T Griffin

Publications and source records attributed to T Griffin.

At least 73 records · Page 4Linked to original sources
PubMed1986

The effects of bisantrene on human platelets.

Bisantrene, (9,10-anthracenedicarboxaldehyde bis [(4,5-dihydro-1H-imidazol-2yl)hydrazone] dihydrochloride) is one of a series of anthracene dicarboxaldehyde compounds in Phase II trials. Preliminary studies suggested that bisantrene has anti-platelet activity. Therefore, in vitro studies of its effects on platelets were undertaken. Bisantrene in clinically attainable concentrations of 0.625 - 10 microM, caused a 95 +/- 1% decrease in maximal platelet aggregation to collagen (1 microgram/ml), and epinephrine (5-40 microM) and 90 +/- 10% inhibition of arachidonic acid (50 micrograms/ml) induced aggregation. Collagen induced platelet shape change was not affected. Aggregation to calcium ionophore A23187 was inhibited by 10-30%. No effect on ADP induced aggregation was seen at clinically relevant bisantrene concentrations. This inhibition was time dependent, reaching a maximum when platelets were preincubated with bisantrene for 10 minutes before exposure to agonist. Inhibition persisted after bisantrene was removed by washing. To determine the mechanism of platelet inhibition, platelet prostaglandin metabolism, oxygen consumption and release reaction were measured. In the presence of drug: normal cyclooxygenase activity was demonstrated by O2 consumption studies and normal secondary wave ADP (3.2 microM) aggregation; lipoxygenase activity, by O2 consumption was also normal. There was 30-50% inhibition of thromboxane A2 synthesis induced by arachidonic acid or collagen; ADP, collagen and AA induced release of serotonin was decreased by 30-60% but was never abolished. No effect on basal platelet cAMP levels nor additive effect on PGE1 induced elevation of platelet cAMP was detectable. These data demonstrate that bisantrene has potent antiplatelet activity probably mediated by several different mechanisms. The inhibition may have important clinical and theoretical consequences.

Anthracenes↗
PubMed1986

Analysis of neutron radiotherapy treatment complications.

A total of 6,345 patients have been entered in the RTOG particle registry since it was opened in 1980. Three hundred thirty of those patients were treated with neutrons alone for head and neck cancers, and 128 were treated with neutrons alone for pelvic cancers. The late normal Tissue Severe Toxicity (life-threatening and fatal) rates in the head and neck were 9% for high energy accelerators and 20% for low energy accelerators. The late normal Tissue Severe Toxicity rates in the pelvis were 4% for high energy accelerators and 39% with low energy accelerators.

Fast Neutrons↗
PubMed1984

Treatment of patients with metastatic osteogenic sarcoma: a report from the Children's Cancer Study Group.

Fifty-three patients with metastatic osteogenic sarcoma were treated with vincristine, high-dose methotrexate with citrovorum factor rescue, and cisplatin. Metastases were surgically removed in most patients, either prior to chemotherapy or following initial response to therapy. Among 29 previously treated patients, responses to initial chemotherapy included two complete remissions, six partial remissions, and eight patients with stable disease. Twenty-three patients were disease-free, six for greater than 12 months. Toxicity was moderate, but usually reversible. There were two toxic deaths and one unexplained death 48 hours following a dose of cisplatin.

Adolescent↗
PubMed1983

Prolonged second remissions in childhood acute lymphocytic leukemia: a report from the Childrens Cancer Study Group.

To date, median duration of second and subsequent remissions in childhood acute lymphocytic leukemia (ALL) has been short, with most studies reporting median remission duration less than 6 months. In May 1979, the Childrens Cancer Study Group (CCSG) undertook a pilot study to assess the efficacy of a vincristine, methotrexate, and L-asparaginase regimen (modified Capizzi) for maintenance in children with ALL in second or subsequent remission. Thirty patients were treated with this maintenance regimen. By life table analysis, predicted median duration of hematologic remission was 57 weeks. Ten patients (33%) were in continuous hematologic remission at 1 year and three (10%) continue in remission greater than 2 years from maintenance onset. Major toxicity included leukoencephalopathy in four patients, three of whom had experienced at least one central nervous system relapse prior to study entry. Allergic reactions to Escherichia coli L-asparaginase were common. Nine of 30 patients experienced at least one CNS relapse during therapy. We conclude that a modified Capizzi regimen is the most effective regimen reported to date for maintaining second and subsequent remission in childhood ALL. CCSG is currently utilizing this regimen in an ongoing open study.

Asparaginase↗
PubMed1983

Affinity precipitation of dehydrogenases.

Affinity precipitation, a novel technique closely related to immunoprecipitation and affinity chromatography, has been evaluated in systems comprised of dehydrogenases and a bifunctional NAD derivative, Bis-NAD. Lactate dehydrogenase and glutamate dehydrogenase were easily precipitated whereas yeast alcohol dehydrogenase required the presence of salt to enhance the affinity precipitation. Liver alcohol dehydrogenase did not precipitate, probably because most of the affinity complexes formed were composed of only two enzyme molecules. Affinity precipitation was carried out on a preparative scale for the isolation of ox heart lactate dehydrogenase from a crude extract. The yield and purity of the enzyme and the general properties of the procedure are considered very satisfactory.

Affinity Labels↗
PubMed1981

Hybrid antibodies with dual specificity for the delivery of ricin to immunoglobulin-bearing target cells.

Hybrid antibodies possessing one binding site for the toxic lectin ricin and a companion site directed against human immunoglobulin were constructed in vitro. This bifunctional reagent specifically attached to human lymphocyte surface immunoglobulin determinants and, thus situated, could simultaneously capture ricin molecules or its toxic A chain. Attachment of these components to the cell was revealed by specific fluorescein-labeled antibodies. Once concentrated at the target cell membrane, hybrid-bound toxin was subsequently released to function via its normal mechanism of biological action. It gained access to ribosomes, its intracellular target, and curtailed protein synthesis. Toxicity was not augmented for immunoglobulin-negative cells to which hybrid could not bind and free human immunoglobulin G could competitively block the enhanced effects observed for immunoglobulin-bearing cell lines. These results indicate that hybrid antibodies may be utilized to carry active agents within close proximity to the membrane of a specified cell type and thereby selectively enhance their effect.

Antibodies↗
PubMed1980

Specific cytotoxicity of a human immunoglobulin-directed Fab'-ricin A chain conjugate.

The toxic A chain of ricin and the Fab' fragment of antibody directed against human immunoglobulin (Ig) have been disulfide linked via their intrinsic sulfhydryl groups. This Fab'-A chain conjugate retained the activities of its component parts. It produced effective inhibition of protein synthesis in a cellfree rabbit reticulocyte lysate system and bound tightly ti Ig determinants on human cells. Attachment of the intact molecule to the cell surface was revealed by using fluorescein-labeled antibodies directed against both its Fab' and A chain halves. The Fab'-A chain conjugate was evaluated for cytotoxicity by using human, surface Ig positive target cells and surface Ig negative control cells. In vitro toxicity was entirely selective since the conjugate produced inhibition of de novo protein synthesis, impedence of growth, as well as death and lysis, only for cells possessing surface Ig determinants. Moreover, the effects on Ig positive cells were abrogated by the addition of free human IgG that competitively blocked the Fab' combining site of this conjugate and prevented cell surface binding. Addition of lactose, which inhibits binding of whole ricin, did not influence the action of the Fab'-A chain conjugate. These results verified that the specific binding site on the antibody half of the molecule could function as a directional carrier that facilitates A chain entry into the cytoplasm. Expression of cytotoxic effects was thereby restricted exclusively to cells bearing the appropriate target site. This new conjugate molecule thus possessed both the absolute specificity of the antibody and the potent lethality of its parent toxin.

Animals↗
PubMed1977

Optic nerve glioma: the role of radiation therapy.

Sixteen patients with optic nerve gliomas were treated with radiation therapy between 1962 and 1975. Surgical extirpaton was not attempted. Fifteen patients had biopsies with histologic confirmation: one had a craniotomy without biopsy. With a follow-up of 1 to 14 years, mean 6.3 years, 12 of the 16 patients are alive without evidence of disease. Vision was preserved or improved in all surviving patients. No patients who received 5000 rad or greater had a recurrence of his tumor, whereas four of seven patients receiving doses less than 5000 rad had recurrences and eventually died. We currently recommend 5000-rad megavoltage photon irradiation, delivered with standard fractionation, for all patients with optic nerve gliomas.

Adolescent↗