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Biomedical subjects

T Randall

Publications and source records attributed to T Randall.

At least 19 recordsLinked to original sources
PubMed1998

Constructive dialogue.

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Attitude of Health Personnel↗
PubMed1996

Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine.

We tested the hypothesis that the level of the DNA repair protein O6-alkylguanine-DNA alkyltransferase in brain tumors was correlated with resistance to carmustine (BCNU) chemotherapy. Alkyltransferase levels in individual cells in sections from 167 primary brain tumors treated with BCNU were quantitated with an immunofluorescence assay using monoclonal antibodies against human alkyltransferase. Patients with high levels of alkyltransferase had shorter time to treatment failure (P = 0.05) and death (P = 0.004) and a death rate 1.7 times greater than patients with low alkyltransferase levels. Furthermore, the size of the subpopulation of cells with high levels of alkyltransferase was correlated directly with drug resistance. For all tumors the variables most closely correlated with survival, in order of importance, were age, tumor grade, and alkyltransferase levels. For glioblastoma multiforme, survival was more strongly correlated with alkyltransferase levels than with age. These results should encourage prospective studies to evaluate alkyltransferase levels as a method, for identifying brain tumor patients with the best likelihood of response to BCNU chemotherapy.

Antibodies, Monoclonal↗
PubMed1996

Intracellular Localization and intercellular heterogeneity of the human DNA repair protein O(6)-methylguanine-DNA methyltransferase.

O(6)-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that removes alkyl adducts from DNA and may be important in tumor resistance to alkylation chemotherapy. MGMT was visualized in human cells and tumor tissues with monoclonal antibodies against MGMT and immunofluorescence microscopy, and fluorescent signals were quantified by digital image analysis. MGMT was found both in the cytoplasm and the nucleus, and in either locale the protein reacts with alkylated DNA bases and becomes inactivated and lost from the cell. Cell lines in culture and xenografts showed a broad normal distribution of nuclear MGMT levels, but human brain tumors often showed a skewed distribution, with a significant fraction of cells with high levels of MGMT. O(6)-Benzylguanine, a suicide substrate inactivator for MGMT activity, reduced MGMT in human cells and in a mouse xenograft to levels undetectable by antibody assay 1 h post-treatment. In melanoma specimens taken from a patient 3 h post-treatment with temozolomide, MGMT levels were reduced by 70%. This quantitative immunofluorescence assay can be used to monitor MGMT and it depletion in human tumors to improve the use of alkylating agents in cancer chemotherapy.

Animals↗
PubMed1996

Rehabilitation of ten soldiers with exertional rhabdomyolysis.

This case study describes the rehabilitation of 10 active duty U.S. soldiers with exertional rhabdomyolysis. The pathophysiology of rhabdomyolysis is discussed. The initial management is concerned with accurate diagnosis and monitoring of laboratory values to prevent complications. Active and passive range of motion, strength, and induration were used as indicators of recovery. The goal of rehabilitation was to safely return patients to their basic training units without activity restrictions as quickly as possible. All 10 soldiers were able to pass the Army Physical Fitness Test at the end of their training cycle. For those patients with rhabdomyolysis who desire to return to a high level of function, close monitoring of exercise intensity appears to allow for a safe, expedient return to previous levels of function. This description of a rare disorder will increase awareness and stimulate discussion so that more specific guidelines for rehabilitation can be developed.

Adolescent↗
PubMed1995

O6-methylguanine-DNA methyltransferase in human brain tumors detected by activity assay and monoclonal antibodies.

O6-methylguanine-DNA methyltransferase (MGMT) activity was measured in 68 tissue samples taken from brain. A wide range in activity among samples was observed, with all nonmalignant samples showing transferase activity (Mer+) but approximately 15% of WHO grade II low-grade astrocytomas and WHO grade IV glioblastoma multiformes lacking activity (Mer-). On average, astrocytomas and glioblastomas showed less transferase activity than either nonmalignant tissue or meningiomas. Monoclonal antibodies specific for MGMT showed both cytoplasmic and nuclear staining of Mer+ brain tumor cells in culture but no staining of Mer- cells in culture. In pathology specimens from anaplastic astrocytomas, glioblastoma multiformes, and meningiomas, antibody staining revealed both cytoplasmic and nuclear MGMT, while one sample showed little or no MGMT-specific staining. These results help explain why nitrosoureas have been among the most successful agents in treatment of brain tumors and indicate the subcellular localization for the repair activity, which may be relevant to nitrosourea resistance.

Antibodies, Monoclonal↗
PubMed1994

Persistence of cell-mediated and humoral immune responses in healthy children immunized with live attenuated varicella vaccine.

Two hundred fourteen healthy seronegative children immunized with various doses of Oka/Merck varicella vaccine were studied for persistence of varicella-zoster virus (VZV)-specific lymphocyte proliferation and antibodies to VZV as determined by a glycoprotein (gp) ELISA. Of the 140 vaccinees tested for VZV-specific lymphocyte proliferation, 94% had positive responses, with a mean stimulation index of 8.9 (range, 3.0-44.6). Of 214 tested by gpELISA, 95% were positive for up to 6 years after immunization; the geometric mean titer was 30.2 (range, 1.3-3510.0). Of 122 individuals tested both by ELISA and for VZV-specific lymphocyte proliferation, 91% had persistence of both responses. Persistence of cellular and humoral immune responses in a large percentage of vaccinees for up to 6 years after immunization with Oka/Merck varicella vaccine suggests that protection against severe varicella is likely to be similarly long-lasting.

Adolescent↗
PubMed1994

Analysis of O6-methylguanine-DNA methyltransferase in individual human cells by quantitative immunofluorescence microscopy.

A quantitative assay of immunofluorescence is described that can be performed on individual cells from standard pathologic specimens using fluorescence microscopy. The technique has been applied to measurement of O6-methylguanine-DNA methyltransferase, a DNA repair protein that is a molecular marker for resistance to chloroethylnitrosources used in cancer chemotherapy. The immunofluorescence assay makes use of monoclonal antibodies with specificity for human transferase, fluorescence microscopy with digital imaging, fluorescent bead internal standards, and computerized image analysis. This method is specific for the transferase, produces results correlated with activity measurements, and yields new data about tissue heterogeneity and subcellular localization previously unavailable with standard assay methods.

Antibodies, Monoclonal↗