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Biomedical subjects

S M Fischer

Publications and source records attributed to S M Fischer.

At least 109 records · Page 6Linked to original sources
PubMed1985

The first stage and complete promoting activity of retinoic acid but not the analog RO-10-9359.

Retinoic acid has the ability to act as either a weak first stage promoter or a weak complete promoter in the initiation-promotion protocol for skin carcinogenesis in the SENCAR mouse. The retinoid analog RO-10-9359 lacks this tumor promoting activity. Both retinoids however inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion. Additional comparisons revealed that retinoic acid alone can induce dark keratinocytes, a characteristic of tumor promoters, while RO-10-9359 cannot. Retinoic acid but not RO-10-9359 can induce an immediate chemiluminescence response in human polymorphonuclear cells. Both retinoids, however, inhibit a TPA-induced response. Since the chemiluminescence response is believed to be due to oxygen free radical generation, the data suggest that the ability of retinoic acid but not RO-10-9359 to promote tumors and induce dark cells may be due to initial oxidative reactions at the cell membrane.

Animals↗
PubMed1985

Evidence that the centrally and peripherally located cells in the murine epidermal proliferative unit are two distinct cell populations.

The purpose of this investigation was to characterize the [3H]thymidine label-retaining and the "maturing" classes of basal cells from the dorsal epidermis of adult SENCAR mice and to compare their early cellular kinetic responses to topical application of the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Autoradiography of epidermal whole mounts and cross sections demonstrated that injection of [3H]thymidine every 6 h for 1 week labeled 95% of the basal nuclei, including those in the central region of the epidermal proliferative units. One month later, the labeling index was reduced to 2%; 90% of the label-retaining cells were within a nuclear diameter of the central suprabasal column of the proliferative units. When mice were treated with 2 micrograms of TPA 1 month after labeling, mitotic label-retaining cells were found within 22 h after treatment. Seventy-five percent of the label-retaining cells remained on the basal layer through the 28-h experimental period. In contrast, the basal labeling index following a 1-h pulse of [3H]thymidine was 5%. Eighty-five percent of the labeled cells were found in the periphery of the proliferative units. By 4 days after pulse labeling, most of the originally labeled cells had divided, although vertical cross sections indicated that 92% remained on the basal layer. When mice were treated with TPA on day 4, labeled cells were rarely found in mitosis. Instead, about 60% of the labeled cells were displaced to the suprabasal layers. These observations suggest that 2 classes of epidermal basal cells have different early responses to TPA treatment: the label-retaining cells proliferate, and most of the "maturing" cells continue to differentiate.

Animals↗
PubMed1985

Suppression of tumor promoter-induced chemiluminescence in mouse epidermal cells by several inhibitors of arachidonic acid metabolism.

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) is a stimulator of chemiluminescence (CL) in SENCAR mouse epidermal cells. The CL response is TPA dose dependent (8 to 800 nM) as well as proportional to the number of cells used. Treatment with 166 nM TPA results in a CL response that peaks by 15 min although a strong response persists for over 30 min. The CL response can be inhibited by superoxide dismutase and the superoxide dismutase mimetic copper(II) (3,4 diisopropylsalicylic acid)2, suggesting that the CL response may be due to or mediated by superoxide anions. Catalase, which is specific for H2O2, and mannitol, which is a scavenger for hydroxyl radicals, had negligible inhibitory effects. The CL response is also inhibited by retinoic acid and the analogue ethyl all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8- nonatetraenoate. A series of phorbol esters with different promoting abilities produced corresponding CL responses. The second stage tumor promoter mezerein is as effective as TPA in stimulating CL. Inhibitors of various parts of the arachidonic acid cascade were found to affect the TPA-induced CL response in a manner that corresponds to their effects in vivo tumor promotion experiments: agents which are predominantly lipoxygenase inhibitors, i.e., nordihydroguaiaretic acid, benoxaprofen, or agents which are effective against both lipoxygenase or cyclooxygenase, i.e., 5,8,11,14-eicosatetraynoic acid and phenidone, are effective in diminishing the CL response. Cyclooxygenase inhibitors, i.e., indomethacin and flurbiprofen, have no or a slight enhancing effect at low doses. These data suggest that at least a major part of the TPA-induced CL response is due to the metabolism of arachidonic acid, most probably by the lipoxygenase(s). This CL assay may provide a useful system for studying the involvement of oxidants in tumor promotion.

Animals↗
PubMed1984

Prolonged human kidney preservation by intracellular electrolyte flush followed by cold storage.

No kidney transplant center responding to a kidney preservation questionnaire would accept a kidney flushed with an intracellular electrolyte solution and cold-stored for over 40 hours. This study from one center is a comparison of 50 primary cadaver kidney grafts preserved with an intracellular electrolyte flush followed by cold storage for 40 to 61 hours to 82 primary cadaver kidney grafts preserved by the same method for 9 to 24 hours. Kidneys cold-stored for over 40 hours had a significantly increased requirement for dialysis in the 1st week following transplantation (82% versus 34%) and a significantly increased 1-month serum creatinine nadir (2.3 mg/dL versus 1.7 mg/dL). Actuarial graft survivals and serum creatinine levels at 1, 2, and 3 years after grafting were not significantly different. Cadaver donor methylprednisolone (30 to 60 mg/kg) two to nine hours prior to kidney removal significantly reduced the requirement for 1st-week hemodialysis in the kidneys cold-stored for over 40 hours (60% versus 91%). Kidneys preserved by flushing with cold intracellular electrolyte solution can be successfully transplanted after over 40 hours of simple cold storage when the warm ischemia time is very short.

Cadaver↗
PubMed1984

The growth of cultured human foreskin keratinocytes is not stimulated by a tumor promoter.

The tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA) does not stimulate the growth of human epidermal cells in foreskin explant cultures; a dose-dependent inhibition is seen at doses higher than 10(-5) micrograms/ml. TPA also inhibits epidermal growth factor-stimulated growth and does not induce ornithine decarboxylase activity or increase polyamine levels. This is not due to the rapid breakdown of TPA, since TPA is not metabolized to any appreciable extent.

Cell Division↗
PubMed1983

The lack of initiating and/or promoting activity of sodium malondialdehyde on SENCAR mouse skin.

Malondialdehyde (MDA), a lipid peroxidation product, has been implicated in carcinogenesis, in part for its reported mutagenic activity. It was of interest therefore, to determine its activity as either a complete carcinogen, a tumor initiator, or a tumor promoter. Using the SENCAR mouse skin model, pure sodium MDA (NaMDA) was found to lack activity in any of these categories. Furthermore, NaMDA was determined to be negative in the Chinese hamster V-79 metabolic cooperation assay for promoters.

Animals↗
PubMed1983

Diazepam inhibition of phorbol ester tumor promotion.

Diazepam (Valium) had previously been shown to enhance the growth rate of some transplantable tumors although studies in other systems have suggested an inhibitory effect. Skin tumor promotion studies were therefore carried out to determine the effect of diazepam on 12-O-tetradecanoyl phorbol-13-acetate (TPA) promotion in SENCAR mice. A sex-independent dose response inhibition occurred over a dose range of 100 g to 5 mg, both in number of papillomas and percent of mice bearing tumors. Furthermore, a dose-response reduction in tumor size was observed. By itself, diazepam had no tumor promoting activity.

Animals↗
PubMed1983

Beneficial effect of pre-transplant splenectomy for leukopenia in primary cadaver kidney transplants.

Pre-transplant splenectomy is controversial. We compared 21 nondiabetic, transfused recipients of first cadaver kidney grafts who underwent pre-transplant splenectomy for steroid-resistant leukopenia to 114 without steroid-resistant leukopenia. Kidney graft survivals at 2 years were 80.2 plus or minus 8.9 and 48.5 plus or minus 5.3 per cent, respectively (p less than 0.05). The 2-year actuarial patient survivals were not significantly different (89.6 plus or minus 7.0 versus 87.8 plus or minus 3.9 per cent). Azathioprine doses and serum creatinine levels at 1 year were not significantly different. Pre-transplant splenectomy for steroid-resistant leukopenia resulted in a significant decrease in kidney graft losses owing to rejection without an increased risk of death of sepsis or thromboembolism.

Azathioprine↗
PubMed1982

Effect of donor surgeon on first cadaver kidney transplant function.

Community urologists and general surgeons were recruited into a cadaver kidney program in 1976. This study from 1 center compares 41 primary cadaver kidney grafts retrieved by community hospital retrieval teams to 60 primary cadaver kidney grafts retrieved by a center-based transplant team. Of the kidneys 100 were preserved with Collins' C2 flushing followed by simple cold storage and 1 was preserved with pulsatile machine perfusion. Cold storage time ranged from 9 to 44.5 hours in the community hospital kidney group and from 11 to 44 hours in the university hospital group. There was no significant difference between the 2 kidney retrieval teams with respect to 1) incidence of acute tubular necrosis, 2) 1-month serum creatinine nadir of surviving grafts, 3) 1 and 2-year serum creatinine levels and 4) actuarial graft survivals up to 5 years. Community hospital retrieval teams can provide kidneys as satisfactory for transplantation as a center-based transplant team and are a valuable resource for cadaver kidney transplant programs.

Adult↗
PubMed1982

Inhibition of mouse skin tumor promotion by several inhibitors of arachidonic acid metabolism.

12-O-Tetradecanoylphorbol-13-acetate promotion of skin tumors in mice can be inhibited by topical application of either the phospholipase A2 inhibitor dibromoacetophenone or the cyclooxygenase-lipoxygenase inhibitors 5,8,11,14-eicosatetrayonic acid or 1-phenyl-3-pyrazolidinone. The phospholipase A2 inhibitors in particular appear to be among the most potent inhibitors of skin tumor promotion known. These results support the hypothesis that at least some of the products of arachidonic acid transformation are essential for tumor promotion.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1982

Separation of epidermal cells by density centrifugation: a new technique for studies on normal and pathological differentiation.

Murine keratinocytes, isolated by flotation trypsinization of skin, can be separated into five groups by centrifugation through Percoll, a colloidal silica gradient. Within each group a good correlation was found between density, plating efficiency, morphological appearance, DNA synthesis, and degree of keratinization/cornification. This method can be applied equally well to fetal, newborn, or adult keratinocytes and should be useful in a variety of studies including isolation of subpopulations of pathological cell types, work on chalones and hyperplastic diseases such as psoriasis, and in vitro transformation studies.

Animals↗
PubMed1982

A computerized data management system for behavioral teratology studies.

A computerized system was designed for behavioral teratology studies to (1) generate preprinted data recording/submission forms, (2) calculate testing dates, (3) generate a daily activity schedule for testing, and (4) update established data sets for access by data entry personnel. The computer-generated forms are used to record data from the following behavioral/developmental tests for rats: pup weights, pinna detachment, surface righting, cliff avoidance, incisor eruption, eye opening, negative geotaxis, olfactory discrimination, swimming development, open field, swimming maze and operant visual discrimination learning. Three behavioral teratology studies have been conducted in our laboratory using this computerized system. The human error rates in these studies were 0.26, 0.34 and 0.46 percent, respectively. The advantages of this system include: (1) computer-calculated test dates; (2) elimination of manual data transcription; (3) more consistent data recording and scoring conditions; (4) better scheduling control; and (5) faster data entry and statistical analysis.

Animals↗
PubMed1980

Improved conditions for murine epidermal cell culture.

An improved method for cultivating newborn mouse epidermal cells has been developed that increases the longevity, epithelial nature and efficiency of cell-line establishment. The use of Super Medium, an enriched Waymouth's formulation, increased proliferation for long periods of time, as did incubation at 31 degrees C rather than 37 degrees C. The fetal bovine serum requirement was found to be reduced at the lower temperature. An increase in labeling indices was seen when epidermal growth factor (EGF) or the cyclic nucleotides were added and the presence of EGF receptors was determined. Of the prostaglandins (PG) examined, PGE1 and PGE2 produced the greatest increase in DNA synthesis. The PG precursors, arachidonic and 8,11,14-eicosatrienoic acid, were also greatly stimulatory. The use of a lethally irradiated 3T3 feeder layer at 31 degrees C proved superior in maintenance of an epithelial morphology. Subculturable cell lines were established much more readily and reproducibly in carcinogen-treated cultures grown under the improved conditions.

Animals↗