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Biomedical subjects

J L Phillips

Publications and source records attributed to J L Phillips.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1989

In vitro distribution of diacetyl didemnin B in human blood cells and plasma.

We have utilized [3H]diacetyl-didemnin B ([3H]DB) in a series of in vitro experiments to determine the time course of equilibration of [3H]DB between plasma and blood cells, the distribution of [3H]DB among blood cells, and the distribution of [3H]DB in plasma. Within 45-60 min at 37 degrees C, approximately 55% of [3H]DB added to whole blood remained in the plasma. Of the drug associated with blood cells, 77% was found with the red blood cells, 18% with the lymphocytes, and 5% with the granulocytes. However, on the basis of amount of drug uptake per cell, lymphocytes incorporated nearly 400 times more and granulocytes nearly 30 times more [3H]DB than red blood cells. No specific association of [3H]DB with a particular lymphocyte subset was detected. Additionally, it appears that [3H]DB in plasma was associated to a large extent with albumin.

Antineoplastic Agents↗
PubMed1988

Enhancement of mezerein-promoted papilloma formation by treatment with 12-O-tetradecanoylphorbol-13-acetate or mezerein prior to initiation.

The effects of promoter treatments prior to initiation on subsequent promotion by mezerein were examined in SENCAR mice. Groups of mice received two applications of various complete as well as first and second stage promoters given at various time intervals prior to initiation ranging from 3 days to 10 weeks. The mice were then initiated with 2 micrograms of 7,12-dimethylbenz[a]anthracene (DMBA) followed 2 weeks later by twice-weekly treatments with 2 micrograms of mezerein. The papilloma response in mice, receiving pretreatments with 2 micrograms of 12-O-tetradecanoylphorbol-13-acetate (TPA) either 3 days, 1, 2, 3 or 5 weeks before initiation, was similar to that seen when TPA was given after initiation during stage I of promotion followed by stage II of promotion with mezerein (4-5 papillomas per mouse in all groups). Surprisingly, pretreatment with the stage II promoter, mezerein (2 micrograms), either 2 or 5 weeks prior to initiation, also gave papilloma responses similar to that induced with the standard two-stage promotion protocol (4.7 and 6.4 papillomas per mouse, respectively). The papilloma response was less than that in the standard two-stage promotion protocol when pretreatments with the stage I promoter A23187 (80 micrograms/mouse) were given either 2 or 5 weeks before initiation (2.6 and 2.3 papillomas per mouse, respectively). However, a repeat experiment (currently in progress) with a higher dose of A23187 (160 micrograms/mouse) given 2 weeks prior to initiation indicates that it is more effective than the 80 micrograms dose. When the time interval between pretreatment and initiation was increased to 10 weeks, the papilloma response with TPA and A23187 pretreatment was reduced to below two papillomas per mouse and with mezerein pretreatment to below three papillomas per mouse, indicating the effect was reversible. Histological changes in epidermis of mice which received two applications of these compounds correlated with the tumor response. In this regard, treatment with two applications of TPA and mezerein resulted in an epidermal hyperplasia of similar magnitude (epidermal thickness of 53.5 +/- 1.5 and 50.0 +/- 1.1 microns, respectively). The hyperplasia produced by treatment with two applications of 80 micrograms A23187 (39.4 +/- 1.8 microns) was significantly less. The ability of pretreatments with benzoyl peroxide (20 mg) and chrysarobin (50 micrograms) to affect the subsequent promoting activity of mezerein was also examined.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Insulin resistance after oral glucose tolerance testing in patients with major depression.

An association between affective disorders and alterations in glucose utilization has been recognized. The authors administered a 5-hour oral glucose tolerance test (GTT) to 28 depressed patients and 21 healthy volunteer control subjects and measured serum glucose as well as plasma insulin and glucagon responses. Depressed patients demonstrated significantly higher basal glucose levels, greater cumulative glucose responses after the GTT, and larger cumulative insulin responses after the GTT than control subjects. Values for cumulative glucagon did not significantly differ between groups. These findings indicate the presence of a functional state of insulin resistance during major depressive illness and suggest the presence of a more generalized biological disturbance in some depressed patients.

Administration, Oral↗
PubMed1987

Disparity between expression of transferrin receptor ligand binding and non-ligand binding domains on human lymphocytes.

We compared transferrin receptor (TfR) expression on human peripheral blood lymphocytes (PBL) activated by phorbol myristate acetate (PMA) or L-phytohemagglutinin (LPHA) using two techniques: (1) 125I-iron-saturated transferrin (FeTf) binding, (2) reactivity with monoclonal anti-TfR antibodies--OKT9 and B3/25. These monoclonal antibodies do not block FeTf binding, and therefore bind to TfR domains separate from the ligand binding site. Unstimulated PBL bound fewer than 1,000 molecules of 125I-FeTf per cell, and less than 5% of cells expressed TfR antigens detected by OKT9 or B3/25. 125I-FeTf binding and antibody binding increased in parallel on LPHA-activated PBL. After exposure to LPHA for 72 hr, 125I-FeTf binding increased 100-fold to 10(5) molecules per cell and greater than 50% of cells expressed TfR antigens. By contrast, PMA activation of PBL markedly increased binding of OKT9 and B3/25 but not the binding of 125I-FeTf. Cell surface expression of TfR antigens seen by OKT9 and B3/25 did not differ between LPHA- and PMA-activated PBL. However, after 72 hr with PMA, 125I-FeTf binding increased only 6-fold and consistently remained at less than 10(4) molecules per cell. Therefore, PMA induced a disparity between expression of TfR ligand binding domains and immunological domains at the cell surface. Cell proliferation assessed by fluorescent DNA analysis was similar in cultures stimulated by LPHA or PMA. These data indicate that lymphoid cells may possess a mechanism for modulating TfR expression in which down-regulation of FeTf binding occurs without receptor internalization. Alternatively, it is possible that this observation may reflect a membrane perturbation effect of PMA.

Antibodies, Monoclonal↗