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Biomedical subjects

J L Phillips

Publications and source records attributed to J L Phillips.

At least 19 recordsLinked to original sources
PubMed1995

Exposure of Drosophila melanogaster embryonic cell cultures to 60-Hz sinusoidal magnetic fields: assessment of potential teratogenic effects.

There is considerable concern about potential detrimental health effects associated with exposure to environmentally relevant magnetic fields. One specific concern relates to potential effects of magnetic field (MF) exposure on reproduction and development. Consequently, an in vitro teratogenesis (developmental toxicity) assay employing embryonic Drosophila cells has been used to determine whether exposure to a 60-Hz MF of 100 microT for 16-18 hr is itself teratogenic and whether such an exposure could potentiate the teratogenic response induced by a chemical teratogen (developmental toxicant). The results demonstrated that (1) MF exposure alone did not induce a teratogenic response, whether the MF was oriented parallel or perpendicular to the plane of the culture dishes; and (2) MF exposure did not alter the teratogenic response induced by optimal or suboptimal concentrations of three chemical teratogens (retinoic acid, hydroxyurea, and cadmium). Furthermore, in additional studies, Drosophila embryos were exposed to 60-Hz MFs of 10 and 100 microT for 24 hr or for their entire development time (i.e., until adult ecolsion, about 10 days). Results demonstrated that MF exposure did not produce an increase in developmental abnormalities over those observed in unexposed controls.

Animals↗
PubMed1992

Magnetic field-induced changes in specific gene transcription.

Magnetic fields are physical, environmental agents that have been shown to produce a variety of responses in cellular and animal studies, including general changes in gene transcription. In this study, the nuclear run-off assay has been employed to assess alterations in specific gene transcription in CEM-CM3 T-lymphoblastoid cells exposed for 15-120 min to a 1 gauss sinusoidal magnetic field at 60 Hz. Time-dependent and cell density-dependent changes in the transcription of c-fos, c-jun, c-myc and protein kinase C (beta-form) have been observed and quantitated. Additionally, changes in transcript levels, assessed by slot-blot analysis, have been found to parallel the changes in gene transcription. These data suggest an important role for magnetic field exposure in altering cellular processes.

Cell Line↗
PubMed1992

Coordinated development of myofibrils, sarcoplasmic reticulum and transverse tubules in normal and dysgenic mouse skeletal muscle, in vivo and in vitro.

We studied the development of transverse (T)-tubules and sarcoplasmic reticulum (SR) in relationship to myofibrillogenesis in normal and dysgenic (mdg/mdg) mouse skeletal muscle by immunofluorescent labeling of specific membrane and myofibrillar proteins. At E16 the development of the myofibrils and membranes in dysgenic and normal diaphragm was indistinguishable, including well developed myofibrils, a delicate network of T-tubules, and a prominent SR which was not yet cross-striated. In diaphragms of E18 dysgenic mice, both the number and size of muscle fibers and myofibrillar organization were deficient in comparison to normal diaphragms, as previously reported. T-tubule labeling was abnormal, showing only scattered tubules and fragments. However, many muscle fibers displayed cross striation of sarcomeric proteins and SR comparable to normal muscle. In cultured myotubes, cross-striated organization of sarcomeric proteins proceeded essentially in two stages: first around the Z-line and later in the A-band. Sarcomeric organization of the SR coincided with the first stage, while the appearance of T-tubules in the mature transverse orientation occurred infrequently, only after A-band maturation. In culture, myofibrillar and membrane organization was equivalent in normal and dysgenic muscle at the earlier stage of development, but half as many dysgenic myotubes reached the later stage as compared to normal. We conclude that the mdg mutation has little effect on the initial stage of membrane and myofibril development and that the deficiencies often seen at later stages result indirectly from the previously described absence of dihydropyridine receptor function in the mutant.

Animals↗
PubMed1992

The mental foramen: 2. Radiographic position in relation to the mandibular second premolar.

Seventy-five adult human mandibles were radiographed with a paralleling technique to determine the ability to visualize the mental foramen as well as its size and position. The foramen was seen on 75% of the horizontal periapical radiographs examined. When the foramen was not visualized, is was usually below the inferior edge of the film. The radiographic size of the foramen was smaller than the anatomical size previously reported. The position of the mental foramen was usually mesial and below the radiographic apex of the second premolar.

Adult↗
PubMed1992

The mental foramen: 3. Size and position on panoramic radiographs.

Panoramic radiographs were made of 75 dry, adult human mandibles. The size and position of the mental foramen in relation to the second premolar was determined. The mental foramen on panographic radiographs was slightly larger than reported on periapical radiographs. The average position of the foramen was mesial and below the radiographic apex of the tooth. Panoramic radiography may account for a distal shift of the foramen and a 23% increase in size of the mandibles examined.

Bicuspid↗
PubMed1992

Indoor 222Rn concentrations in a probability sample of 43,000 houses across 30 states.

The U.S. Environmental Protection Agency has assisted 30 of the 48 conterminous states in completing statistically designed surveys of indoor 222Rn over the past 4 y. In all states, the lowest livable level of 43,054 randomly selected houses was tested using charcoal canisters exposed for 48 h. The sampled population included owner-occupied ground-level houses having listed telephone numbers. Summary statistics along with the percentage of houses exceeding various concentration levels are given by state and over all states for houses with basements, for houses without basements, and for all houses. As expected, 222Rn concentration varies widely from one state to another and, in every state, basement houses exhibit higher concentrations than nonbasement houses. The lognormal distribution is shown to be a good approximation to the distribution of screening measurements over the 30-state area. There is, however, some evidence that the lognormal distribution underestimates, by a narrow margin, the upper tail of the observed distribution of basement measurements.

Air Pollutants, Radioactive↗
PubMed1991

Dihydropyridine receptor alpha subunits in normal and dysgenic muscle in vitro: expression of alpha 1 is required for proper targeting and distribution of alpha 2.

We have studied the subcellular distribution of the alpha 1 and alpha 2 subunits of the skeletal muscle dihydropyridine (DHP) receptor with immunofluorescence labeling of normal and dysgenic (mdg) muscle in culture. In normal myotubes both alpha subunits were localized in clusters associated with the T-tubule membranes of longitudinally as well as transversely oriented T-tubules. The DHP receptor-rich domains may represent the sites where triad junctions with the sarcoplasmic reticulum are being formed. In cultures from dysgenic muscle the alpha 1 subunit was undetectable and the distribution patterns of the alpha 2 subunit were abnormal. The alpha subunit did not form clusters nor was it discretely localized in the T-tubule system. Instead, alpha 2 was found diffusely distributed in parts of the T-system, in structures in the perinuclear region and in the plasma membrane. These results suggest that an interaction between the two alpha subunits is required for the normal distribution of the alpha 2 subunit in the T-tubule membranes. Spontaneous fusion of normal non-muscle cells with dysgenic myotubes resulted in a regional expression of the alpha 1 polypeptide near the foreign nuclei, thus defining the nuclear domain of a T-tubule membrane protein in multi-nucleated muscle cells. Furthermore, the normal intracellular distribution of the alpha 2 polypeptide was restored in domains containing a foreign "rescue" nucleus; this supports the idea that direct interactions between the DHP receptor alpha 1 and alpha 2 subunits are involved in the organization of the junctional T-tubule membranes.

Animals↗
PubMed1991

Effect of 72 Hz pulsed magnetic field exposure on macromolecular synthesis in CCRF-CEM cells.

Cells from the T-lymphoblastoid cell line, CCRF-CEM, have been exposed in vitro to a quasirectangular, asymmetric electromagnetic field pulsed at 72 Hz at 37 degrees for periods of 30 min to 24 h. RNA synthesis, assessed by incorporation of 3H-uridine, increased (relative to control cells) 2-fold after 30 min in exposed cells and achieved its greatest increase of 3.2-fold relative to controls after 2 h exposure. Increased precursor incorporation was observed at all subsequent exposure times up to 24 h. Synthesis of mRNA was similar, but not identical to that observed with total cellular RNA. Additionally, protein synthesis, determined by incorporation of radioactive precursor into acid-precipitable material, was increased 2.8-fold, compared to controls, after 2 h exposure. Longer exposure times resulted in an exponential decrease in precursor incorporation to 1.1-times control levels after 24 h. Using a dye reduction assay, mitochondrial activity was also found to be increased over a 24 h exposure period. No effect of electromagnetic field exposure was found on cellular synthesis of DNA. These data are generally consistent with other reports documenting effects of electromagnetic field exposure on macromolecular synthesis in vitro.

DNA, Neoplasm↗
PubMed1990

Using a population-based cancer registry for recruitment in a pilot cancer control study.

Cancer control investigations in the United States rarely use population-based registries as a resource for recruitment. A placebo-controlled, double-blind, randomized toxicity trial of tamoxifen was conducted among postmenopausal women with node negative breast cancer. To achieve the accrual goal of 140 subjects in this single institution study, the Wisconsin Cancer Reporting System (WCRS), a population-based cancer registry, was used. Registry information from the last 9 years was used to identify 3,585 women who met the study criteria with respect to age, stage, and previous therapy. The vital status of identified women was confirmed using Wisconsin state death records. For identified cases, rosters were prepared and sent to the physician with a cover letter and study description. The physicians were asked to update the list and, if appropriate, to sign letters to potentially eligible and interested women. Thirty-eight percent of women receiving a letter and study information from their physicians contacted the study office about participation. Eighteen months from its initiation, 140 women were entered on study. This successful use of a population-based cancer registry illustrates an efficient recruitment method which could be modified for other cancer control/chemoprevention trials.

Aged↗
PubMed1990

The mental foramen: 1. Size, orientation, and positional relationship to the mandibular second premolar.

Seventy-five adult human mandibles were examined to determine the size, orientation, and position of the mental foramen. The average size of the foramen was found to be larger on the left side of the mandible and its usual direction of exit was in a posterior-superior direction. The most common location of the mental foramen was inferior to the crown of the second premolar and approximately 60% of the distance from the buccal cusp tip of that tooth to the inferior border of the mandible.

Adult↗
PubMed1990

Phase I trial and biochemical evaluation of tiazofurin administered on a weekly schedule.

Tiazofurin (2-B-D-Ribofuranosylthiazole-4-Carboxamide: NSC 286193) is a nucleoside antimetabolite that acts as a potent inhibitor of IMP dehydrogenase resulting in a guanine nucleotide deprivation. Recent in vivo biochemical observations in rats bearing hepatoma suggested a correlation between depletion of guanine nucleotides and antitumor effect. The present phase I trial utilized a weekly x 3 bolus infusion schedule, repeated every 5 weeks. Biochemical measurements of GTP and dGTP were performed in patients at each dose level. Twelve patients received 16 courses of the drug in doses ranging from 1100 to 2050 mg/m2 weekly x 3. The dose limiting toxicities were pericarditis and clinical symptoms suggestive of a more generalized serositis (chest and abdominal pain). Other toxicities included reversible elevations in CPK (MM band only) and SGOT, nausea, vomiting, and arthralgias. Neurotoxic effects were generally mild, including headaches, anxiety, and malaise. Only 1 of 6 patients evaluated for tiazofurin's biochemical activity showed a sustained depletion of guanine nucleotide pools. No antitumor activity was observed. The maximally tolerated dose of tiazofurin on this intermittent weekly x 3 schedule was 1650 mg/m2. Toxicity and the overall lack of biochemical and biologic effect at clinically achievable doses may preclude further clinical evaluation of this drug on a weekly schedule. The toxicities observed in our study were similar to those reported for phase I investigations using a considerably higher dose intensity with daily x 5 schedules.

Aged↗
PubMed1990

Academic outreach: health careers enhancement program for minorities.

This article describes the 6-week Health Careers Enhancement Program for Minorities inaugurated in the summer of 1988 at Case Western Reserve University School of Medicine. The program was developed for minority and economically disadvantaged college undergraduates and postbaccalaureate premedical students. Its major objectives were to stimulate and maintain the interest of minority students in health careers and prepare these students for entry into health professions and for successful completion of these programs. A unique aspect of the program was academic outreach. Case Western Reserve University minority alumni and community minority physicians participated as clinical role models, mentors, and teachers; community and state minority leaders served as inspirational speakers and role models. The program was designed not only to incorporate cognitive and skill development activities, but to also include features distinctive to the Case Western Reserve University curriculum, specifically, organ system teaching, preceptor groups, medical apprenticeship program, and student tutors.

Career Choice↗
PubMed1989

Further characterization of skin tumor promotion and progression by mezerein in SENCAR mice.

This study evaluated the skin tumor-promoting activity of mezerein in SENCAR mice. The effect of initiation dose of 7,12-dimethylbenz(a)anthracene (DMBA) on tumor promotion by mezerein was examined. Excellent dose-response relationships were observed for initiation with DMBA at 0.2-20 micrograms per mouse with mezerein as a complete promoter. None of the mezerein-only promotion groups had papilloma responses similar to those of the corresponding groups receiving two-stage promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA) followed by mezerein, even when a 40-micrograms initiating dose of DMBA was used. The effect delaying promotion with mezerein for 10 weeks was also examined in mice initiated with either 0.2, 2, 20, or 40 micrograms of DMBA per mouse. The 10-week delay led to a slight increase in the number of papillomas per mouse in some but not all treatment groups. Again, none of the delayed-mezerein-treatment groups had papilloma responses similar to those of the corresponding two-stage promotion (TPA-mezerein) groups at any corresponding initiating dose of DMBA. Finally, the progression of papillomas to carcinomas during promotion with mezerein was examined in groups of mice initiated with either 2 or 20 micrograms of DMBA. Higher ratios of carcinomas to papillomas were observed in mice promoted with mezerein than in mice receiving TPA promotion or two-stage promotion (TPA-mezerein). However, the presence of two to four times more papillomas in some mezerein-treated groups did not lead to greater numbers of carcinomas than in the groups with fewer papillomas. The data do not support the idea that spontaneous stage I promotion can be induced by delaying mezerein treatment for 10 weeks. Furthermore, the data suggest that the higher ratio of carcinomas to papillomas observed with mezerein promotion may be a function of the lower tumor burdens obtained after promotion with this compound rather than a specific property of the chemical.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Transcriptional regulation of transferrin receptor expression by cultured lymphoblastoid T cells treated with phorbol diesters.

Expression of transferrin receptors (TFR) is required for lymphocyte proliferation. Treatment of lymphoblastic leukemia cell lines with phorbol diester tumor promoters decreases proliferation and induces differentiation. Among changes induced by phorbol diesters is decreased cell surface expression of TFR. To elucidate effects of phorbols on lymphocyte growth and differentiation, we examined TFR expression by measuring 125I-transferrin binding, levels of TFR mRNA by Northern analysis and dot-blot hybridization, and rates of TFR gene transcription by nuclear run-on experiments in CCRF-CEM lymphoblastoid T cells treated with PMA or phorbol dibutyrate. Cell surface expression of TFR was decreased 60 to 85% within 2 min of exposing cells to phorbols and remained decreased for 96 h. Steady state levels of TFR mRNA decreased to less than 30% of control after 48 h. After treating cells with actinomycin D, estimated TFR mRNA t 1/2 was 2.7 h and was unaltered in phorbol-treated cells. Levels of TFR mRNA were not affected by treatment of cells with cycloheximide in either control or phorbol-treated cells. Therefore, post transcriptional mRNA processing by protein factors did not account for decreased TFR mRNA in phorbol-treated cells. Compared to baseline levels, rates of TFR gene transcription in PMA-treated cells increased up to two-fold during the initial 6 h of culture, then decreased over the ensuing 12 h to less than 10% of baseline values. This pattern was not seen in control cultures. Therefore, regulation of TFR gene transcription is a consequence of treating CEM cells with phorbol diesters. Cell surface expression of TFR in phorbol-treated lymphoblastoid T cells may be mediated in part at the level of gene transcription.

Antigens, Surface↗