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Biomedical subjects

S Abrams

Publications and source records attributed to S Abrams.

At least 19 recordsLinked to original sources

Apoptosis, growth arrest and suppression of invasiveness by CRE-decoy oligonucleotide in ovarian cancer cells: protein kinase A downregulation and cytoplasmic export of CRE-binding proteins.

The CRE (cyclic AMP response element)-transcription factor complex plays a critical role in response to hormonal signals for cell proliferation, differentiation, and apoptosis. We have reported previously that the CRE-transcription factor decoy oligonucleotide specifically slows tumor cell proliferation and inhibits CRE- and Ap-1-directed transcription in vivo (Park et al., 1999). We have investigated the effect of inhibiting CRE-directed transcription on ovarian cancer cell growth. Here, we report that CRE-decoy oligonucleotide treatment results in the inhibition of cell growth and a marked reduction in the expression of the regulatory and catalytic subunits of protein kinase A and the type I and type II protein kinase A holoenzymes. Growth inhibition was accompanied by changes in cell morphology, appearance of apoptotic nuclei, and DNA fragmentation. In addition, MMP-9 (matrix methalloproteinase-9) activity was markedly reduced in CRE-decoy treated cells. Indirect immunofluorescence revealed that CRE-decoy oligonucleotide treatment promoted export of the CRE-binding protein, CREB, from the nucleus to the cytoplasm, while importing the catalytic subunit of protein kinase A from the cytoplasm to the nucleus. The results indicate that the decoy oligonucleotide, by binding specifically to CRE-transcription factors, interferes with CRE-directed transcription in vivo. These results show a critical role for CRE-directed transcription in ovarian cancer cell growth. Thus, the CRE-decoy oligonucleotide may provide a powerful means to combat ovarian cancer.

Apoptosis↗

Peak bone mass.

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Adolescent↗

Compartmental analysis of magnesium kinetics in Mg-sufficient and Mg-deficient rats.

In this study, we determined magnesium kinetic values in normal rats using stable-isotope techniques. Additionally, we calculated the mass of the exchangeable pools of Mg in Mg-deficient rats to determine whether it can be used as a marker of Mg status. Rats were fed either a control diet (1,000 mg Mg/kg) or a Mg-deficient diet (60 mg Mg/kg). After 2 weeks on the experimental diets, each rat received an intravenous injection of 26Mg. The plasma Mg disappearance curve over the next 7 days was used to measure the mass and fractional transport rate of 3 rapidly exchanging Mg metabolic pools. In control rats, the mass of pool 1 (1.37 mg) was half that of pool 2 (2.46 mg), and pool 3 (47.7 mg) accounted for greater than 90% of exchangeable Mg. In Mg-deficient rats, we observed a significant decrease in the size of the 3 exchangeable pools of Mg (0.36, 0.72, and 20.2 mg, respectively) relative to the control rats. Furthermore, the fractional transport rate of Mg from pool 1 to pool 3 in Mg-deficient rats was 3 times the rate in the control rats, and the rate of irreversible loss from pool 1 was lower in Mg-deficient rats. In summary, this study allows us to establish Mg kinetic data in Mg-sufficient and Mg-deficient rats. The present experiment supports the conclusion that the isotopic test identifies animals with severe Mg deficiency.

Animals↗

Complete denture covering mandibular tori using three base materials: a case report.

The torus mandibularis presents many challenges when fabricating a complete denture. The mucosa tends to be thin and will not tolerate normal occlusal loads on a denture. Large mandibular tori can prevent complete seating of impression trays and denture. To address this problem, we fabricated a new mandibular complete denture incorporating a combination of soft acrylic flanges and liners.

Acrylic Resins↗

Coordinating developmental and psychoanalytic processes: conceptualizing technique.

Throughout childhood and adolescence, psychological growth proceeds in a sequence of progressive hierarchical organizations. Consequently, children are continuously consolidating existing positions or are in transition from one to another. When analytic treatment is proposed, analysts often find themselves in the position of being required to technically coordinate the requirements of the analytic process with those of the ongoing developmental process. While it is the patient who will ultimately bring the needs of both processes together, the approach the analyst assumes to recognizing and addressing these needs can have a facilitating influence on the treatment. Play, for example, is a window on old conflicts and impaired object relationships from the past, but it is also a way in which children consolidate existing organizational hierarchies. Similarly, the analytic interaction provides a pathway to the past, but it is also used by children to provide the building blocks for newly emerging structures. To facilitate further clinical research, a conceptual outline of the relationship between the two processes is provided.

Adolescent↗

Vitamin K status and bone health: an analysis of methods for determination of undercarboxylated osteocalcin.

Recent studies suggest that fracture risk is associated with increased undercarboxylated osteocalcin. Methods use differences in binding of undercarboxylated and fully carboxylated osteocalcin to hydroxyapatite or barium sulfate. We evaluated these methods and found that results varied with the amount and preparation of the salts. Furthermore, patient samples with differing amounts of total osteocalcin could not be directly compared. Errors in the determination of undercarboxylated osteocalcin were minimized by expressing data as the percent of the total osteocalcin in the sample, and correcting for the basal level of osteocalcin using a polynomial equation derived from multiple binding curves. Errors from 5-15% in estimation of undercarboxylated osteocalcin were observed without both of these corrections. When differing types of assays were employed (RIA, intact, N-terminal), results also were affected. In normal adults and children and in patients on long-term warfarin therapy, the percent osteocalcin not bound to hydroxyapatite was lower when measured with an intact assay than by a polyclonal RIA. Differences were related to the amount of N-terminal osteocalcin fragments, which had low affinity for hydroxyapatite and resulted in variable overestimation of undercarboxylated osteocalcin. In a kit specific for uncarboxylated osteocalcin, we found good discrimination between carboxylated and uncarboxylated intact osteocalcin. However, the assay detected large osteocalcin fragments and overestimated their concentration by up to 350%. Values for uncarboxylated osteocalcin were not different in patients on coumadin compared with normal adults with this kit, but when normalized to the total intact osteocalcin, percent uncarboxylated osteocalcin was greater in patients on coumadin than in controls, as would be expected. Kit values for uncarboxylated osteocalcin in normal children were higher than intact values in the same subject, because of the increased reactivity of the kit toward circulating fragments that were elevated in children. Thus, for estimation of undercarboxylated osteocalcin, care must be taken to standardize the hydroxyapatite or barium sulfite used for binding, to correct for the basal level of osteocalcin in the sample, to use immunoassays that do not detect small fragments, and to express the results as the percent of the total osteocalcin in the sample. Without these precautions, the assessment of undercarboxylated osteocalcin is not reliable.

Adult↗

HIV in Southeast Asia.

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Acquired Immunodeficiency Syndrome↗

Child psychiatric patients' interactions with their mothers.

This study investigated whether child psychiatric patients' and their mothers interacted differently as a function of whether the children were diagnosed as having internalizing or externalizing disorders. Twenty children and their mothers were rated on eight behavior dimensions as they engaged in a ten-minute play session. Maternal depression was found to interact with their children's diagnoses and behavioral ratings.

Adult↗

Immunization with a syngeneic tumor infected with recombinant vaccinia virus expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) induces tumor regression and long-lasting systemic immunity.

A recombinant vaccinia virus encoding the gene for granulocyte-macrophage colony-stimulating factor (rV-GM-CSF) was used to infect the poorly immunogenic murine colon adenocarcinoma cell line, MC-38. Infection of MC-38 tumor cells with rV-GM-CSF completely suppressed the growth of the MC-38 primary tumors, whereas progressively growing tumors were formed in mice injected with MC-38 cells infected with wild type V-Wyeth. Irradiation of the recipient B6 mice before implantation of rV-GM-CSF-infected tumor cells resulted in the development of progressively growing tumors. Moreover, in vivo T-cell depletion studies revealed that growth suppression of the rV-GM-CSF-infected tumor cells was dependent on the presence of both CD4+ and CD8+ T-cell subsets. Subsequent studies established that this immunity was long-lasting and antigen specific, as demonstrated by the protection of rV-GM-CSF-immunized mice from MC-38 tumor challenge but not from challenge with another syngeneic tumor cell type. No such effects were observed when MC-38 tumor cells were infected with recombinant vaccinia viruses expressing interleukin (IL)-2 or IL-6. The results demonstrate that paracrine release of biologically active murine GM-CSF by tumor cells infected with rV-GM-CSF enhances the intrinsic immunogenicity of a poorly immunogenic murine tumor. Presumably the augmentation of tumor immunogenicity induces an antigen-specific T-cell-dependent antitumor response that prevents the formation of primary tumors and protects mice from tumor challenge. Thus in this experimental model, GM-CSF functions as a highly effective vaccine adjuvant.

Adenocarcinoma↗

Randomised controlled trial of a synthetic triglyceride milk formula for preterm infants.

AIMS: To test whether use of infant formula containing synthetic structured triglycerides results in: (i) increased palmitate absorption; (ii) increased total fat absorption; (iii) reduction in calcium soap formation in the gut; and hence (iv) increased calcium absorption. METHODS: A randomised study was made of 24 infants comparing three formulas, one containing the synthetic fat Betapol with 74% of palmitate in the 2-position, which was substantially higher than in the two comparison diets (8.4% and 28%). The hypothesised outcomes were tested using balance studies, detailed chemical analysis of stool specimens and dual calcium isotope tracers (44calcium orally and 46calcium intravenously). RESULTS: Three of the four hypotheses were confirmed: use of a formula rich in 2-position palmitate (i) improved palmitate (16:0) and also (18:0) absorption; (ii) reduced the formation of insoluble calcium soaps in the stool; and (iii) improved calcium absorption, determined by the dual tracer technique from 42 (SE 3)% to 57 (7)%. CONCLUSION: Synthetic triglycerides that mimic the stereoisometric structure of those in breast milk may have a valuable role in the design of formulas used for preterm infants in neonatal intensive care units.

Animals↗

Magnesium kinetics in adolescent girls determined using stable isotopes: effects of high and low calcium intake.

Magnesium kinetics were measured in five adolescent girls who were participating in a calcium balance study. Two calcium levels were fed in a randomized crossover design. After an acclimation period, 26Mg was consumed orally and 25Mg was given intravenously, and then blood, urine, and feces were collected for 14 days. Total magnesium and percent enrichment were determined, and data were fitted to a eight-compartment model. There was no significant difference between high and low calcium intakes for any of the parameters examined. Mean values for control (800 mg/day) and high (1,800 mg/day) calcium intake were as follows: Mg intake, 305 +/- 30 and 286 +/- 9 mg/day; absorption (percent), 44 +/- 7 and 39 +/- 9; absorption (mg/day), 134 +/- 35 and 110 +/- 28; urinary excretion, 96 +/- 22 and 101 +/- 31 mg/day; fecal excretion, 175 +/- 32 and 200 +/- 11 mg/day; and magnesium balance, 13 +/- 35 and -34 +/- 48 mg/day, respectively. In conclusion, high calcium intake did not alter magnesium kinetics or balance in adolescent girls.

Absorption↗

RVU Task Force report: does it really reflect the current methods of practice?

The ODA in a publication in December 1996 gave two reasons for commissioning this study. 13 First, over the years a number of anomalies had crept into the Fee Guide and needed to be addressed. For instance, code 14301 (motivation of a patient with a bad habit) had a higher responsibility than a root canal treatment code. The second reason was to keep the guide reflective of the current methods of practice of dentistry. These are very noble ideals and unfortunately they were not achieved with the publication of this report. I have provided a few examples of times and responsibility which are not in keeping with the current methods of practice of dentistry. Common sense along with the scientific literature bears this out. The report is filled with inaccuracies and anomalies. In numerous instances there are procedures with times that would not allow for the provision of quality care. One over riding concern is that only 100 procedures had their times directly measured and the remaining 1,100 procedures had their times extrapolated from these measured times. If any of these 100 measured times are inaccurate or do not reflect the current methods of practice, then the extrapolated times will also not be correct. The RVU Task Force has asked for input from the membership. Copies of the report were initially only distributed in limited numbers to the Dental Societies and not to the membership at large. The membership could request additional copies and was given three months to prepare and submit a response on prepared feedback forms. The Task Force received feedback from over 300 members. They now claim that this feedback has generated extensive changes in the diagnostic and restorative sections, recall packages, the endodontic section and fixed and removable prosthodontics. 14 There appears to have been major changes throughout the entire report. How can one then claim that the report was scientifically done or that it produced valid results? How are we sure that these 300 members actually reviewed each and every one of the times and "R" factors for all 1,200 procedures in the Fee Guide? Does this input from the membership now create a valid study? Do these subsequent changes alter the supposed "scientific" underpinning of the RVU Report? Are we sure that these changes will now create a document that meets the objectives of this study? Why should the membership have to review, critique and fix a report that had numerous glaring flaws from its outset? Why must the membership of the Ontario Dental Association and every practicing dentist in Ontario be subjected to the ramifications of this flawed and inaccurate report? The final report will be available prior to the General Council Meeting of the Ontario Dental Association in May 1997. I urge every member to read and review the entire report to see if it meets the objectives of the Task Force. From reviewing the Draft Final Report of the RVU Task Force, and the proposed changes, I would strongly urge all members of the General Council of the Ontario Dental Association to reject any implementation of this report.

Fee Schedules↗

Total body calcium and bone mineral content: comparison of dual-energy X-ray absorptiometry with neutron activation analysis.

The aim of this study was to compare the dual-energy X-ray absorptiometry (DXA) measurement of bone mass with an independent measure of body calcium obtained by neutron activation analysis (NAA). Total body bone mineral content (BMC) was measured using DXA in 46 subjects in the age range 5-47 years (17 children, 28 young women, and 1 adult male). Total body calcium (TBCa) was measured in the same subjects by in vivo NAA. The correlation between the two measures of bone mass was highly significant (BMC[g] = 3.22 x TBCa[g] - 51.4, r > 0.98, p < 0.0001, SEEBMC = 122.7 g). When BMC was the independent parameter, the SEETBCa was 37.5 g. Bland-Altman analysis indicated a mean difference of 2.8 g with a standard error +/- 4.7 g for TBCaNAA versus TBCaDXA when the BMC values were converted to TBCa. The relative change in bone mass (delta TBCa/delta BMC) for DXA was higher than that reported for dual-photon absorptiometry versus NAA. The findings presented in this study provide translational equations among the DXA and NAA measurements and for the conversion of total body BMC to TBCa in children and young adults.

Absorptiometry, Photon↗

Strategies for the development of recombinant vaccines for the immunotherapy of breast cancer.

The development of recombinant vaccines for specific immunotherapy of carcinoma represents a novel approach for the treatment of breast cancer and other tumor types. This article reviews the various parameters that should be considered in the development of recombinant vaccines. Several breast cancer associated antigens are also discussed which may provide potential target molecules. The human carcinoembryonic antigen (CEA), which is expressed on approximately 50% of breast cancers, represents one such target for immunotherapy. To enhance the immunogenicity of this antigen, a recombinant CEA-vaccinia vaccine, designated rV-CEA, was produced. To study the effects of this vaccine in an animal model, a murine colon carcinoma cell line was transduced with CEA and transplanted into immunocompetent mice for protection and therapy studies. Pre-clinical toxicity studies were also conducted in non-human primates. The results of these studies showed the rV-CEA vaccine to be immunogenic and safe in both rodents and primates, and to elicit good anti-tumor responses in the rodent model. In a Phase I clinical trial in metastatic breast, lung, and colorectal cancer patients involving three immunizations of rV-CEA, at three dose levels, enhancement of T-cell and antibody responses to vaccinia virus proteins were observed with no toxicity. Specific T-cell responses were studied via stimulation of peripheral blood lymphocytes with specific peptide epitopes from the CEA molecule. These studies demonstrated clear cut differences in establishment of T-cell lines pre- versus post-immunization. The T-cell lines were shown to be CD8+ and/or CD4+/CD8+, to lyse EBV transformed B-cells transduced with the CEA gene, and to lyse CEA positive carcinoma cells in a HLA restricted manner. Thus, in a Phase I clinical trial the rV-CEA vaccine has been shown to stimulate a CTL response specific for CEA defined epitopes in cancer patients.

Animals↗

Differentiation and integration.

The purpose of this paper is to propose a clinical approach to coordinating the psychoanalytic process with the developmental process in treating children. The paper is constructed as a dialogue between the spirit of Anna Freud and myself; a vignette brings together the principal traditional features Ms. Freud understood as "psychoanalytic" with her innovative propositions about the "developmental."

Adolescent↗