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Biomedical subjects

G H Strauss

Publications and source records attributed to G H Strauss.

18 recordsLinked to original sources
PubMed1995

The single cell gel electrophoresis/comet assay: a potential tool for detecting radiation-induced DNA damage in humans.

This review evaluates the applicability of the single cell gel (SCG)/comet assay as a tool for the biomonitoring of individuals accidently, environmentally or occupationally exposed to ionizing radiation. This technique detects single-strand DNA breaks, alkali-labile damage, incomplete excision repair sites and DNA:DNA crosslinking at the level of the individual cell. The advantages of this technique include: (a) data are collected at the level of the individual cell, providing information on the intercellular distribution of damage and repair; (b) only small numbers of cells are required (i.e., only a few thousand); (c) virtually any eukaryotic cell population can be used; and (d) the assay is relatively sensitive (detection limit of 5 cGy gamma rays in human lymphocytes), simple and cost effective. What the assay lacks is specificity for radiation-induced DNA damage. However, the possibility of identifying types of DNA damage specific for ionizing radiation in selected subtypes of cells may be feasible. While additional research is required before the SCG assay can readily be applied as a standard biomonitoring tool for exposure to ionizing radiation, the data collected thus far support a conclusion that such research is clearly warranted.

Animals↗
PubMed1993

An analysis of gamma-ray-induced DNA damage in human blood leukocytes, lymphocytes and granulocytes.

Lymphocytes and granulocytes were separated from human peripheral blood and irradiated with low doses of gamma-rays (0.05-0.5 Gy) from a 137Cs source. The magnitude and intercellular distribution of DNA damage, i.e., single-strand breaks and alkali-labile lesions, were compared with those obtained in unfractionated leukocytes irradiated in whole blood, using the alkaline single-cell gel-electrophoresis technique. Based on the extent of DNA migration, irradiation resulted in a linear and dose-dependent increase in DNA damage in all 3 cell populations, with a significant increase being detected at 0.05 Gy. The dose-dependent increase for DNA migration was not significantly different between separated lymphocytes and granulocytes, but their responses were significantly elevated over that obtained for leukocytes irradiated in whole blood. Based on an analysis of the ratio of the range to the standard deviation for each cell population at each dose of radiation, the distribution of damage among cells was relatively homogeneous and independent of dose and cell population. These results are consistent with a hypothesis that irradiation of leukocytes in whole blood partially protects against radical-induced DNA damage.

Analysis of Variance↗
PubMed1992

Assessment of radiation-induced DNA damage in human blood lymphocytes using the single-cell gel electrophoresis technique.

The ability of the alkaline single-cell gel (SCG) electrophoresis technique to detect single-strand breaks and alkali-labile DNA damage in human cells induced by low doses of radiation was evaluated. Peripheral blood lymphocytes were irradiated with gamma-rays from a 137Cs source at doses from 0.01 to 1 Gy and exposed to alkali (pH greater than 13) for 20, 40 or 60 min and then electrophoresed at 25 V and 300 mA for either 20 or 40 min. The extent of DNA damage that was expressed and detected as DNA migration depended directly on the dose of radiation, the duration of exposure to alkali and the length of electrophoresis. At all experimental conditions tested, it was possible to detect a significant increase in DNA damage induced by a radiation dose as low as 0.05 Gy. Based on an analysis of the ratio of the range to the standard deviation for each radiation dose and experimental condition, the distribution of damage among cells for all doses was neither excessively homogeneous nor heterogeneous. Furthermore, the distribution was independent of radiation treatment. The SCG technique is rapid and sensitive, and useful for investigations concerned with effects of low doses of radiation.

Adult↗
PubMed1992

High-dose combination alkylating agents with autologous bone-marrow support in patients with breast cancer: preliminary assessment of DNA damage in individual peripheral blood lymphocytes using the single cell gel electrophoresis assay.

The single cell gel (SCG) assay is a sensitive electrophoretic technique for detecting the presence of DNA single strand breaks and alkali-labile damage in individual cells. This technique was used to evaluate the levels of DNA damage in cryopreserved peripheral blood lymphocytes (PBLs) from 11 breast cancer patients treated with high doses of cyclophosphamide and cisplatin and provided autologous bone marrow transplantation after treatment. PBL specimens for the SCG study were obtained just prior to treatment, following the administration of cyclophosphamide and cisplatin for 2 days, and upon lymphocytic recovery. Based on a concurrent analysis of DNA damage in cryopreserved and non-cryopreserved PBL samples from three patients, the mean level of DNA migration or the dispersion of damage among cells was not affected by the process of cryopreservation. The pre-treatment samples of several patients contained PBL with increased levels of DNA damage, presumably reflecting persistent DNA damage induced by previous treatment regimens. Chemotherapy resulted in a significant but variable increase in DNA damage in PBL samples from all patients. In this limited study, the level of damage did not correlate with serum levels of cyclophosphamide or with lymphocyte toxicity. Among the post-treatment samples, increased levels of DNA damage were absent in most but not all patients. The presence of damaged cells in the post-treatment samples may be indicative of an inadequate therapy regimen or of DNA damage resulting from non-therapy related processes. Because of its simplicity and short processing time, the SCG assay can be used to evaluate levels of DNA damage during the course of therapy, allowing the dose schedule to be altered to achieve a desired effect level.

Adult↗
PubMed1992

Acute hemorrhagic conjunctivitis.

Acute hemorrhagic conjunctivitis, an infection caused by enterovirus 70 and a variant of coxsackievirus A24, is characterized by the rapid onset of severely painful conjunctivitis and subconjunctival hemorrhage. The condition is usually benign and resolves in five to seven days; however, a polio-like paralysis (radiculomyelitis) develops in approximately one in 10,000 patients infected with enterovirus 70. No treatment is available. Information about acute hemorrhagic conjunctivitis should be provided to patients and the community in order to prevent undue alarm, discourage home remedies and control the spread of this highly contagious disease.

Conjunctivitis, Acute Hemorrhagic↗
PubMed1991

Non-random cell killing in cryopreservation: implications for performance of the battery of leukocyte tests (BLT), I. Toxic and immunotoxic effects.

To eliminate between-tests error in longitudinal human studies, for specimen sharing, convenient scheduling, etc., it is necessary for us to freeze leukocytes as well as non-transformed, continuous T lymphocyte (CTL) lines. Two commonly used cryopreservation methods were compared in terms of efficacy. Isolated peripheral blood mononuclear cells and CTLs were each aliquoted into three sets of vials. Two sets each were frozen in a 1:1 mixture of 15% DMSO in Mixed Medium (MM) and 20% FBS in MM using a commonly employed styrofoam freezer insert method for liquid nitrogen refrigerators and a programmed freezer (temperature falls at an optimal rate), respectively. The remaining set was held in MM with 20% FBS at 20 degrees C during the 2-h freezing process. The cells were thawed and/or washed and assayed for viability and T helper (Th)/T suppressor (Ts) ratio. It is clear that inadequate freezing (via the styrofoam method) non-randomly damages cells of T cell subpopulations, Th being more sensitive than Ts. Further, it is shown that inadequate cryopreservation can confound results from a number of assessment methods owing to morphological and functional damages. The battery of leukocyte tests (BLT) under development in this laboratory, is designed to detect toxic, immunotoxic and genotoxic effects of in vivo mutagen exposure on human blood. It is concluded that minimization of non-random cell losses (as quantitated on the basis of morphology) and preservation of related regulatory cell function is essential if one would assess the in vivo and in vitro states of heterogeneous cells. Further, it is suggested that freezing methods should be used only after verification that selective damage to subpopulations is not occurring among cells that otherwise might wrongly be assumed to be intact.

Blood Component Removal↗
PubMed1991

Subconjunctival high dose plasminogen activator in rabbit filtration surgery.

The primary cause of failure in glaucoma filtration surgery is fibroblastic proliferation and subconjunctival fibrosis at the bleb site resulting in decreased aqueous flow. We evaluated New Zealand white rabbits in a masked, placebo controlled pilot study to determine the potential reduction of episcleral fibrosis at the surgical bleb site utilizing 0.3 mls of: balanced salt solution (n = 11); an inert gel delivery vehicle (n = 13); the gel delivery vehicle with incorporated recombinant tissue plasminogen activator (tpa; n = 14), 1 mg/ml. Statistical analysis of computer assisted area measurements from multiple histologic sections demonstrated a significant decrease in episcleral fibrosis in the t-PA group as compared to the two other groups (p less than 0.05). Results from the t-PA group did not demonstrate an effect on intraocular pressure. There was no clinical evidence of toxicity or healing complications in the t-PA group.

Animals↗
PubMed1990

The development of the U.S. EPA health effects research laboratory frozen blood cell repository program.

We have suggested that proper blood-cell freezing and storage is necessary in longitudinal studies with reduced between tests error, for specimen sharing between laboratories and for convenient scheduling of assays. Our present purpose is to describe the design and use of a prototype computer program, Cryovial, for data-based management of frozen cell repositories. We are pleased to provide, free of charge upon request, a 5.25" (specify 0.36 or 1.2 MB) disk containing all files required to run Cryovial.

Blood Preservation↗
PubMed1990

Evidence that drug-resistant alloreactive T cells may contribute to human graft rejection.

The objective of our study was to determine whether resistance to immunosuppressive drugs by transplant recipient's T cells could contribute to continued graft rejection, in spite of immunosuppressive therapy. The T cell lines used in this series of experiments were originally established from T cells that had infiltrated kidney or liver grafts and initiated rejections in patients receiving immunosuppressive drugs, including the purine analogue azathioprine (AZ). We have used a proliferation assay and the Strauss-Albertini test to analyze the T cell lines. Both assays use 6-thioguanine (6-TG), an amino derivative of AZ, as the selective agent to measure the resistance to AZ. Although the frequency of 6-TG-resistant variants in the majority of T cell lines closely resembled the frequency found in peripheral blood lymphocytes of controls, we identified four cell lines that demonstrated virtually complete resistance to the purine analogue 6-TG in both assays. These observations indicate that a more effective immunosuppressive treatment may be achieved by using a combination of drugs.

Azathioprine↗
PubMed1989

The Computerized Laboratory Notebook concept for genetic toxicology experimentation and testing.

We describe a microcomputer system utilizing the Computerized Laboratory Notebook (CLN) concept developed in our laboratory for the purpose of automating the Battery of Leukocyte Tests (BLT). The BLT was designed to evaluate blood specimens for toxic, immunotoxic, and genotoxic effects after in vivo exposure to putative mutagens. A system was developed with the advantages of low cost, limited spatial requirements, ease of use for personnel inexperienced with computers, and applicability to specific testing yet flexibility for experimentation. This system eliminates cumbersome record keeping and repetitive analysis inherent in genetic toxicology bioassays. Statistical analysis of the vast quantity of data produced by the BLT would not be feasible without a central database. Our central database is maintained by an integrated package which we have adapted to develop the CLN. The clonal assay of lymphocyte mutagenesis (CALM) section of the CLN is demonstrated. PC-Slaves expand the microcomputer to multiple workstations so that our computerized notebook can be used next to a hood while other work is done in an office and instrument room simultaneously. Communication with peripheral instruments is an indispensable part of many laboratory operations, and we present a representative program, written to acquire and analyze CALM data, for communicating with both a liquid scintillation counter and an ELISA plate reader. In conclusion we discuss how our computer system could easily be adapted to the needs of other laboratories.

Cell Line↗
PubMed1986

Genotoxicity of gamma-irradiation in L5178Y mouse lymphoma cells.

The ability of gamma-irradiation to induce gene mutation at the thymidine kinase locus and gross chromosome aberrations in L5178Y TK+/- 3.7.2C mouse lymphoma cells was evaluated. Positive results were obtained for both end-points. The majority of mutants were found to be small-colony mutants which correlated with the induction of gross chromosome aberrations.

Animals↗
PubMed1980

Inhibition of delayed hypersensitivity reaction in skin (DNCB test) by 8-methoxypsoralen photochemotherapy. Possible basis for pseudo-promoting action in skin carcinogenesis?

Fifty-five of a hundred and two subjects undergoing photochemotherapy with 8-methoxypsoralen and near ultraviolet showed an abnormally low or undetectable delayed cellular hypersensitivity reaction in the skin as judged by the dinitrochlorobenzene test. It is suggested that photochemotherapy may act as a pseudo-promotor by blocking an immunologically based control process in the skin so allowing the relatively rapid appearance of squamous skin tumours, documented elsewhere, in individuals whose skin already contains a population of potentially tumorous cells. Immune surveillance of a kind may thus operate in human skin. Impairment of delayed cellular hypersensitivity to dinitrochlorobenzene was more likely to occur with more intensive treatments and in patients with less skin pigmentation.

Adolescent↗
PubMed1980

An enumerative assay of purine analogue resistant lymphocytes in women heterozygous for the Lesch-Nyhan Mutation.

In females heterozygous for the Lesch-Nyhan (LN) mutation, there is mosaicism of peripheral blood lymphocytes (PBLs) with regard to sensitivity to 6-thioguanine (TG) inhibition of tritiated thymidine ([3H]Tdr) incorporation following phytohemagglutinin (PHA) stimulation. That there are two populations of PBLs, normal and mutant (LN-like), has been demonstrated by an autoradiographic enumerative assay. A single three-generation family containing six potentially heterozygous females was studied. Five of the six were mosaics with frequencies of TG-resistant (TGr) PBLs rangling from 1.4 x 10(-3) to 4.2 x 10(-3) when tested at 2 x 10(-4) M TG. The median frequency of TGr PBLs in 63 healthy non-LN individuals between the ages of 11 and 75 years was found to be 1.1 x 10(-4) (mean 1.3 x 10(-4)) (10th and 90th percentiles--6.1 x 10(-5) and 2.1 x 10(-4)) and was not age related. The sixth potentially heterozygous female in the current family had a TGr PBL frequency of 1.9 x 10(-4). In the five females with elevated TGr PBL frequencies, TGr skin fibroblasts with frequencies ranging from 26% to 100% of the sample tested were found; in the female with the normal TGr PBL frequency, no TGr skin fibroblasts were found. The former group was considered to be LN heterozygous. Four of the five had been previously diagnosed as such. The latter individual is considered to be genotypically normal. Females who are heterozygotes for the LN mutation have two populations of PBLs.

Adolescent↗
PubMed1979

Enumeration of 6-thioguanine-resistant peripheral blood lymphocytes in man as a potential test for somatic cell mutations arising in vivo.

An autoradiographic method to enumerate variant 6-thiogunanine-resistant (TGr) peripheral blood lymphocytes (PBLs) that occur in vivo in man is described. Variant cells are detected in PBL cultures stimulated to tritiated thymidine (3HTdr) incorporation in vitro with phytohemagglutinin (PHA) in the presence of TG. Cells with the naturally-occurring Lesch--Nyhan (LN) mutation served as prototype-variant cells. PBLs from a LN hemizygous male were found to be resistant to TG inhibition of PHA-stimulated 3HTdr in corporation in vitro while a LN heterozygous female was found to be a mosaic with 2/1000 PBLs resistant to 2 X 10(-4) M TG. Experiments with artificial mixtures of LN and normal PBLs showed that the LN cells were virtually all detectable even when present in low frequency (10(-5)). TGr PBLs were found in healthy non-LN individuals at median frequencies of 1.0 X 10(-4) and 1.1 X 10(-4) when determined at 2 X 10(-3) M TG and 2 X 10(-4) M TG respectively. Their frequencies were not age-related. TGr PBL-variant frequencies (Vf's) were determined in 47 cancer patients who were being treated with cytotoxic agents that are known to be mutagens. The median TGr PBL Vf determined at 2 X 10(-3) M TG in cancer patients was 2.2 X 10(-4) while, when determined at 2 X 10(-4) M TG, it was 8.5 X 10(-4). The distribution of Vf's for the treated cancer-patient group differed from that for the normal control group in that more than half of the treated cancer patients had TGr PBL Vf's greater than the highest seen for controls. Unlike those of the normal controls, the TGr PBL Vf's of treated cancer patients differed if determined at 2 X 10(-3) M TG and 2 X 10(-4) M TG, a behavior that suggested partial resistance and mimicked that seen with LN TGr PBLs. PBLs resistant to 2,6-diaminopurine (DAPr) were not found in two individuals, although the TGr PBL Vf was elevated in one. TGr PBL Vf's were greatly elevated under conditions of in vivo selection in patients receiving purine-analogue immunosuppressive therapy. The TGr PBL enumerative assay system is presented as one of potential value to detect somatic cell mutations occurring in vivo in man.

Cytological Techniques↗
PubMed1979

6-Thioguanine resistant peripheral blood lymphocytes in humans following psoralen, long-wave ultraviolet light (PUVA) therapy.

A recently described method that enumerates variant 6-thioguanine resistant peripheral blood lymphocytes present in vivo in man as a potential marker of somatic cell mutations occurring in vivo was used to study 18 psoriatic patients receiving PUVA therapy, 16 conventinally treated psoriatic patients, 10 vitiligo patients receiving PUVA therapy and 7 untreated individuals with vitiligo. Variant lymphocyte frequencies determined for these individuals were compared with those determined for groups of 10 concurrent and 63 cumulative healthy control individuals. Variant frequencies were elevated in psoriatic and vitiligo patients receiving PUVA therapy and in conventionally-treated psoriatic patients. They were not elevated over control values in untreated vitiligo patients.

Adult↗