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Biomedical subjects

C S Johnson

Publications and source records attributed to C S Johnson.

At least 19 recordsLinked to original sources
PubMed2002

Nutritional considerations for bereavement and coping with grief.

PURPOSE: The purposes were 1) to examine the level of nutritional risk among recently bereaved individuals, with or without intervention for grief resolution, and those in coupled relationships and 2) to examine the dietary issues faced by the three groups. METHODS: Twenty-two individuals from the above-mentioned categories were selected. Background information was elicited using a questionnaire. Focus group interviews and the Determine Checklist were used to assess dietary issues and nutritional risk, respectively. RESULTS: Bereaved individuals, irrespective of whether they had counseling for grief resolution or not, had a moderate risk for poor nutrition (score >3). Although the level of risk was similar between the two bereaved groups, it was significantly different from those in coupled relationships, who had the lowest risk (1.43). Based on the interviews, the dietary issues included: 1) food acquisition, preparation and consumption; 2) difficult meals place and time; 3) influence of social network/spouse; and 4) food and nutrition information. The food-related issues faced by bereaved individuals were similar, but substantially different from those in coupled relationships. CONCLUSIONS: The results show that bereavement counseling does not serve as a gateway to reduced nutritional risk and highlights the need to address food issues in grief resolution interventions.

Aged↗
PubMed2001

Programmed cell death in extraocular muscle tendon/sclera precursors.

PURPOSE: This study was designed to examine the occurrence of natural cell death in the periocular mesenchyme of mouse embryos. METHODS: Vital staining with LysoTracker Red and Nile blue sulfate as well as terminal nick end labeling (TUNEL) were utilized to identify apoptotic cell death in whole and histologicaly sectioned gestational day 10.5 to 14 mouse embryos. Laser scanning confocal microscopy was used to provide a three dimensional representation of the cell death pattern. Immunohistochemical staining for neural crest and myoblast populations was utilized to indicate the cell population undergoing apoptosis. RESULTS: Programmed cell death was evident in the developing rectus muscle tendons/sclera on gestational days 11 through 12.5 (corresponding to the weeks 5-6 of human development). Although each of these peripheral periocular condensations has readily apparent amounts of apoptosis, the pattern of cell death varied among them. Cell death was most apparent in the superior rectus tendon primordium, while that for the lateral rectus had the least evidence of apoptosis. CONCLUSIONS: Although apoptosis was readily evident in the periocular mesenchyme in distinct regions located medial and distal to the developing rectus muscles, programmed cell death in these sites has not previously been reported. New imaging techniques coupled with stains that evidence apoptotic cell death have made it possible to define this tissue as a prominent region of programmed cell death. Although neuronal tissues, including particular regions of the developing eye, are well recognized as sites of programmed cell death, description of this phenomenon in the extraocular tendon/sclera precursors is novel.

Animals↗
PubMed2001

Vitamin D(3)-induced apoptosis of murine squamous cell carcinoma cells. Selective induction of caspase-dependent MEK cleavage and up-regulation of MEKK-1.

Vitamin D(3) inhibits cell growth and induces apoptosis in several human cancer lines in vitro and in vivo. However, little is known about the molecular events involved in vitamin D(3)-induced apoptosis. Here, we demonstrate that the growth-promoting/pro-survival signaling molecule mitogen-activated protein kinase kinase (MEK) is cleaved in a caspase-dependent manner in murine squamous cell carcinoma (SCC) cells induced to undergo apoptosis by treatment with vitamin D(3). Cleavage resulted in nearly complete loss of full-length MEK and ERK1/2 phosphorylation. ERK1/2 expression was affected only slightly. The phosphorylation and expression of Akt, a kinase regulating a second cell survival pathway, was also inhibited after treatment with vitamin D(3). However, the pro-apoptotic signaling molecule MEKK-1 was up-regulated in both apoptotic and non-apoptotic cells with greater induction and partial N-terminal proteolysis of MEKK-1 observed in apoptotic cells. In contrast to vitamin D(3), cisplatin and etoposide down-regulated Akt levels only modestly, did not promote significant loss of MEK expression, and did not up-regulate MEKK-1. We propose that vitamin D(3) induces apoptosis in SCC cells by a unique mechanism involving selective caspase-dependent MEK cleavage and up-regulation of MEKK-1. Additional evidence is provided that vitamin D(3)-induced apoptosis may be mediated via p38 MAPK.

Animals↗
PubMed2001

Accuracy of CO(2) angiography in vessel diameter assessment: a comparative study of CO(2) versus iodinated contrast material in a porcine model.

PURPOSE: To compare, with use of intravascular ultrasound (IVUS) as an internal reference standard in a porcine model, arterial diameters measured from arteriograms obtained with use of CO(2) to those obtained with use of iodinated contrast material (ICM). MATERIALS AND METHODS: In nine pigs, digital subtraction angiograms (DSAs) were obtained in the aorta and iliac arteries to compare vessel diameters measured with use of CO(2) to those measured with use of ICM. These measurements were divided by measurements made with use of intravascular ultrasound (IVUS) to yield a DSA/IVUS ratio. Differences between ICM and CO(2) were compared with analysis of variance to assess the effect of location (aorta vs iliac), contrast material used (ICM vs CO(2)), and position (posteroanterior, right anterior oblique, or left anterior oblique). Secondary analysis compared measurements of dependent and nondependent iliac arteries and compared the use of hand-injected CO(2) to that of CO(2) injected by an injector. RESULTS: The DSA/IVUS ratio was 70.7% +/- 4.4% with ICM use and 69.6% +/- 6.3% with CO(2) use, which did not represent a significant difference (P =.311). Animal position had no effect (P =.477). Underestimation was worse in the iliac arteries than in the aorta (67.4% +/- 1.5% vs 71.4% +/- 1.7%; P =.038). There was no difference in nondependent (P =.163) arteries, but CO(2) underestimated dependent iliac artery size more than ICM did (66.3% +/- 4.8% vs 70.3% +/- 5.4%; P =.051). Vessel diameter was underestimated more with the CO(2) injector than with hand-injected CO(2) (64.3% +/- 2.3% vs 71.7% +/- 1.7%; P <.0001). CONCLUSION: There is no difference in diameter underestimation between CO(2) and ICM in this animal model. Hand-injection of CO(2) causes less underestimation of vessel diameter than does the CO(2) injector.

Angiography↗
PubMed2001

Effects of vitamin D (calcitriol) on transitional cell carcinoma of the bladder in vitro and in vivo.

PURPOSE: Vitamin D (calcitriol) has significant antiproliferative effects on various tumor cells in vitro and in vivo. In the clinical situation a major impediment to systemic administration of calcitriol is the side effect of hypercalcemia. To test the potential usefulness of calcitriol for bladder cancer treatment, we studied the antiproliferative effect of vitamin D on 2 human bladder cancer cell lines, 253j and T-24, in vitro. We also examined the in vivo effects of calcitriol in an animal model of bladder cancer using intravesical administration to avoid the toxicity of systemic calcitriol therapy. MATERIALS AND METHODS: The presence of vitamin D receptors in normal and neoplastic human bladder tissue, and tumor cells T-24 and 253j was determined by immunoblot analysis. Tumor cell proliferation in the presence or absence of calcitriol was determined using a crystal violet assay. Calcitriol induced apoptosis was determined by morphology, polyadenosine diphosphate ribose polymerase cleavage and annexin V binding. In vivo studies were performed by weekly intravesical instillation of calcitriol in female Fischer 344 rats after induction of tumors by N-methyl nitrosourea. Calcitriol administration was started 3 weeks after tumor induction for 7 doses at weekly intervals. RESULTS: Normal and neoplastic human bladder tissue, and the cell lines expressed vitamin D receptors. In the 253j and T-24 cell lines proliferation was significantly inhibited by calcitriol. Progressive cleavage of full length polyadenosine diphosphate ribose polymerase was observed in calcitriol treated cells starting as early as 4 hours after exposure. Similar changes were not observed in the control cells treated with vehicle (ethanol) alone. After 24 hours of treatment with calcitriol 45.8% of 253j cells bound annexin compared to 16.5% of control cells (chi-square p <0.001). Of the control animals 66% developed bladder tumors and 55% of the animals treated with calcitriol early (3 weeks) after tumor induction developed bladder tumors. Almost all of the tumors that developed in the calcitriol group were unifocal, and only 20% were invasive compared to 50% of those in the control animals. CONCLUSIONS: These results demonstrate that calcitriol inhibits proliferation and induces apoptosis in human bladder tumor cells in vitro, and may have therapeutic potential in bladder cancer. In vivo studies using an N-methylnitrosourea induced model of bladder cancer demonstrate that early institution of intravesical calcitriol therapy after carcinogen exposure results in fewer tumors, which are also less likely to be multifocal, high grade or invasive. With our protocol a short course of intravesical calcitriol administration did not result in any significant toxicity.

Administration, Intravesical↗
PubMed2001

Calcitriol (1,25-dihydroxycholecalciferol) enhances paclitaxel antitumor activity in vitro and in vivo and accelerates paclitaxel-induced apoptosis.

We demonstrated that calcitriol has antiproliferative activity in squamous cell carcinoma and prostatic adenocarcinoma and enhances the antitumor activity of platinum-based agents. In this study, we examined whether calcitriol also increases paclitaxel cytotoxicity. The effect of treatment on growth of the murine squamous cell carcinoma (SCCVII/SF) and human prostatic adenocarcinoma (PC-3) was determined by clonogenic assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and monitoring tumor growth. Treatment of SCC or PC-3 cells in vitro with calcitriol prior to paclitaxel significantly reduced clonogenic survival compared with either agent alone. Median-dose effect analysis revealed that calcitriol and paclitaxel interact synergistically. Treatment of SCC or PC-3 tumor-bearing mice with calcitriol prior to paclitaxel resulted in substantially greater growth inhibition than was achieved with either agent alone, supporting the combined use of calcitriol and paclitaxel in the treatment of solid tumors. To explore the molecular basis for the enhanced antitumor activity of this combination, the effect of treatment on p21(Waf-1) (p21), Bcl-2, and poly(ADP-ribose) polymerase expression was evaluated in PC-3. A 72-h pretreatment with calcitriol reduced p21 expression and increased paclitaxel cytotoxicity (measured after 24 h) without evidence of apoptosis [poly(ADP-ribose) polymerase cleavage]. After 48 h, paclitaxel induced apoptosis, the extent of which was increased similarly by pretreatment or concurrent treatment with calcitriol. We therefore propose a model for calcitriol enhancement of paclitaxel cytotoxicity in which the "early" (24 h) effects are schedule dependent and not attributed to enhancement of paclitaxel-induced apoptosis. In contrast, the "delayed" (48-h) enhancement of paclitaxel activity by calcitriol is schedule independent and associated with acceleration of apoptosis.

Animals↗
PubMed2001

Combination of 1alpha,25-dihydroxyvitamin D(3) with dexamethasone enhances cell cycle arrest and apoptosis: role of nuclear receptor cross-talk and Erk/Akt signaling.

Previously we have shown that dexamethasone (DEX) enhances the antitumor activity and ligand binding of the active form of vitamin D, 1alpha,25-dihydroxyvitamin D(3) (1,25-D(3)), in the murine squamous cell carcinoma model SCC VII/SF. DEX also reduces the hypercalcemia toxicity of 1,25-D(3) treatment. However, the mechanism of the enhanced antitumor activity has not been defined. Here, we demonstrate that both cell cycle arrest and apoptosis were enhanced by DEX, effects that were inhibited by RU486. We also demonstrate that vitamin D receptor (VDR) protein levels were increased by the combination of 1,25-D(3) and DEX above the level observed with 1,25-D(3) treatment alone, whereas protein levels of the heterodimeric partner of VDR, retinoid X receptor, were lower for the combination than for 1,25-D(3) alone. Glucocorticoid receptor protein levels and ligand binding were increased by 1,25-D(3) but not by the combination. Treatment with the combination of 1,25-D(3) and DEX did not result in greater activation of a vitamin D response element-reporter than 1,25-D(3) alone or of a glucocorticoid response element-reporter than DEX alone. Nevertheless, the levels of phospho-Erk1/2 and phospho-Akt, signaling molecules that are modulated in 1,25-D(3)-treated squamous cell carcinoma cells, were reduced by the combination of 1,25-D(3) and DEX more than by either agent alone. These trends were also observed in vivo. Our results suggest the involvement of the Erk and Akt signaling pathways in the antiproliferative effects of the combination of 1,25-D(3) and DEX and that phospho-Erk1/2 and phospho-Akt may be useful markers of response to this combination.

Animals↗
PubMed2000

Toroid cavity detectors for high-resolution NMR spectroscopy and rotating frame imaging: capabilities and limitations.

The capabilities of toroid cavity detectors for simultaneous rotating frame imaging and NMR spectroscopy have been investigated by means of experiments and computer simulations. The following problems are described: (a) magnetic field inhomogeneity and subsequent loss of chemical shift resolution resulting from bulk magnetic susceptibility effects, (b) image distortions resulting from off-resonance excitation and saturation effects, and (c) distortion of lineshapes and images resulting from radiation damping. Also, special features of signal analysis including truncation effects and the propagation of noise are discussed. B(0) inhomogeneity resulting from susceptibility mismatch is a serious problem for applications requiring high spectral resolution. Image distortions resulting from off-resonance excitation are not serious within the rather narrow spectral range permitted by the RF pulse lengths required to read out the image. Incomplete relaxation effects are easily recognized and can be avoided. Also, radiation damping produces unexpectedly small effects because of self-cancellation of magnetization and short free induction decay times. The results are encouraging, but with present designs only modest spectral resolution can be achieved.

Magnetic Resonance Spectroscopy↗
PubMed2000

A novel approach for the identification of unique tumor vasculature binding peptides using an E. coli peptide display library.

BACKGROUND: Tumor neovascularization is necessary for continued tumor growth and metastasis. During the process of endothelial cell (EC) recruitment and tumor infiltration, specific molecular markers unique for this interaction are expressed on the EC surface. Targeting these molecular markers would, in effect, allow for specific tumor targeting. Tripeptide sequence motifs have previously been reported that will bind to angiogenic tumor ECs. These sequences were identified from in vivo phage peptide display libraries. The purpose of this study was to use a more simplified bacterial peptide display library in an in vitro system to seek out peptide motifs with unique binding to tumor microvasculature. METHODS: FliTrx is a bacterial peptide display library containing the entire repertoire of possible random dodecapeptides expressed on the flagella tip of E. coli. Two EC populations were used for the screening process, Matrigel invading cells (MAGIC) and tumor-derived endothelial cells (TDEC). MAGIC are obtained from ECs that infiltrate a subcutaneous fibroblast growth factor-containing Matrigel deposit, and TDEC are ECs selectively obtained from tumor vasculature. FliTrx cells were incubated with MAGIC at 4 degrees C to remove any potential clones displaying peptides that will bind to nonspecific EC surface targets. The non-binding cells were then incubated with TDEC, allowing for clones displaying potential binding peptides to bind tumor specific targets on TDECs. The bacterial population was then expanded and this "panning" process was carried out a total of five times. Peptide insert sequences from 100 bacterial colonies were analyzed for potential repetitive peptide motifs. RESULTS: Recurring peptide sequences were detected that were 3-mers (13 sequences) and 4-mers (4 sequences). Of the 3-mers, four repeated 3 times, whereas none of the 4-mers repeated more than twice. All of the repeated sequences were basic in charge, and arginine was the most commonly seen amino acid. A tripeptide basic-basic-nonpolar amino acid arrangement was the most prevalent charge sequence in all repetitive motifs (17 repeat sequences). Two test peptides showed TDEC binding specificity, and both conformed to the basic-basic-nonpolar motif. CONCLUSIONS: We report peptide sequences derived from panning an in vitro system designed to detect tumor-EC specific markers. These putative motifs may serve as molecular determinants for a novel therapeutic modality aimed at specifically targeting tumors through tumor angiogenic vessels.

3T3 Cells↗
PubMed2000

Unbiased determination of cytokine localization in bone: colocalization of interleukin-6 with osteoblasts in serial sections from monkey vertebrae.

Few data are available describing the in vivo localization of cytokines in bone. The objective of this study was to describe the histological localization of interleukin-6 (IL-6) relative to osteoblasts (alkaline phosphate [ALP]-positive cells) and osteoclasts (tartrate-resistant acid phosphate [TRAP]-positive cells) in midsagittal, paraffin-embedded serial sections of thoracic 13 (T-13) vertebrae from 49 female cynomolgus monkeys. Serial sections 1 and 4 were immunostained for IL-6, section 2 was histochemically stained for TRAP, and section 3 was immunostained for ALP. Sixteen centrally located fields were measured in the cancellous compartment and grid alignment among sections was verified using image analysis. Using a Merz grid, IL-6 localized to 6% of the bone surface on sections 1 and 4, whereas TRAP localized to 8.5% and ALP to 12% of the bone surface. Colocalization was defined as positive staining within an 80 x 80 microm block in the first serial section that "overlapped" staining in either the corresponding block or its eight surrounding blocks within the second serial section. For each section, 1600 blocks were analyzed. Using Monte Carlo simulations, random colocalization was calculated to determine the statistical significance of experimental colocalizations. Colocalization of approximately 90% between the two IL-6 sections verified staining reproducibility and proper grid alignment among sections. Colocalization of TRAP and ALP was not statistically different from random (p 0.3). As identified using ALP- or TRAP-positive surfaces, there was significant IL-6 colocalization with osteoblasts (p < 0.003), but not with osteoclasts (p 0.3). These in vivo colocalization data support the hypothesis that osteoblasts produce and respond to IL-6.

Animals↗
PubMed2000

Lecithin inverse microemulsions for the pulmonary delivery of polar compounds utilizing dimethylether and propane as propellants.

Lecithin inverse microemulsions were investigated as a means of pulmonary drug delivery, utilizing dimethylethyleneglycol (DMEG) and hexane as models for dimethyl ether (DME) and propane, respectively. Addition of lecithin to the model propellant mixtures increased the solubility of water in a nonlinear, solvent-dependent manner. The concentration of water necessary to fully hydrate cobalt(II) decreased as the solvent composition was varied from DMEG to hexane. Water proton chemical shift increased in the presence of lecithin, with the largest increases in high hexane content samples. Equilibrium dialysis and component diffusion rate determination (by pulsed-field gradient [PFG]-NMR) indicated the quantity of water associated with the dispersed phase. Collectively, these methods demonstrated that a greater fraction of water was associated with the microemulsion-dispersed phase as the solvent was varied from DMEG to hexane. Iodine solubilization indicated microemulsion formation (operational critical micelle concentration [cmc], 10 moles water per mole lecithin) at approximately 10(-4)-10(-5) molal lecithin. NMR data (trimethylammonium proton chemical shift, water, and lecithin T1) were consistent with microemulsion formation. Water-soluble compounds dissolved in lecithin inverse microemulsions in a lecithin- and water-dependent manner. Experiments with DME/lecithin demonstrated microemulsion characteristics similar to those in the model propellant. DME/lecithin metered-dose inhalers (MDIs) produced a particle size and a fine particle fraction (36% by twin impinger method) suitable for pulmonary drug delivery.

Aerosol Propellants↗
PubMed2000

In vivo antitumor activity and induction of insulin-like growth factor-1-resistant apoptosis by SC-alphaalphadelta9.

We previously showed that SC-alphaalphadelta9 (4-(benzyl-(2-[(2, 5-diphenyl-oxazole-4-carbonyl)-amino]-ethyl)-carbamoyl)-2-decanoylami no butyric acid) is a novel antiphosphatase agent that selectively inhibits the growth of transformed cells in culture and affects elements of insulin-like growth factor-1 (IGF-1) signaling. We now show that SC-alphaalphadelta9 induces IGF-1-resistant apoptosis and kills tumor cells in vivo. In cultured murine 32D cells, SC-alphaalphadelta9 induced concentration-dependent apoptosis that was blocked by ectopic Bcl-2 expression. No apoptosis was detected in 32D cells treated with the congener SC-alpha109, which lacks the ability to disrupt IGF-1 signaling. After interleukin-3 withdrawal or etoposide treatment, exogenous IGF-1 prevented apoptosis and elevated levels of Cdc2, a biochemical indicator of a functional IGF-1 receptor pathway. In contrast, exogenous IGF-1 did not prevent apoptosis or loss of Cdc2 expression caused by SC-alphaalphadelta9. Furthermore, IGF-1 receptor overexpression failed to protect cells against SC-alphaalphadelta9-induced apoptosis. Kinetic analyses demonstrated that Cdc2 down-regulation after SC-alphaalphadelta9 treatment preceded both apoptosis and loss of the IGF-1 receptor, indicating that loss of Cdc2 was a direct effect of SC-alphaalphadelta9 treatment and not secondary to cell death. IGF-1 receptor autophosphorylation studies indicated that SC-alphaalphadelta9 did not interact directly with the IGF-1 receptor nor bind to the growth factor itself, suggesting a site of action distal to the IGF-1 receptor. In the SCCVII murine tumor model, a single i.p. injection of SC-alphaalphadelta9 caused a dose-dependent decrease in clonogenic cell survival. The IC(50) of SC-alphaalphadelta9 was 35 mg/kg, comparable to 25 mg/kg carboplatin. The ability to induce IGF-1-resistant apoptosis distinguishes SC-alphaalphadelta9 from other apoptosis-inducing agents and suggests compounds of this class deserve further study as potential anticancer agents.

Aminobutyrates↗
PubMed2000

Loss of B7.2 (CD86) and intracellular adhesion molecule 1 (CD54) expression is associated with decreased tumor-infiltrating T lymphocytes in diffuse B-cell large-cell lymphoma.

Tumor-infiltrating CD8+ T-lymphocytes (T-TILs) are thought to be relevant to immunosurveillance of several tumor types including B-cell non-Hodgkin's lymphoma. B- and T-lymphocyte interactions via cellular adhesion molecules (CAMs), recognition molecules (HLAs), and costimulatory molecules (CSMs) are necessary for optimal antigen-specific T-cell activation to occur and may be important in generating effective host T-TIL responses. We previously found that low T-TIL response (CD8+ T cells < 6%) correlates with statistically shorter relapse-free survival in patients with diffuse large-cell lymphoma (DLCL). We now extend our observations in 71 DLCL patients by analyzing malignant B-cell expression of the following molecules important in T-cell activation: (a) recognition molecules [MHC I (MAS and MCA) and MHC II (HLA-DR, -DP, -DQ)]; (b) CAMs [leukocyte function antigen 1 (CD11a and CD18) and intracellular adhesion molecule 1 (CD54)]; and (c) CSMs [B7.1 (CD80) and B7.2 (CD86)]. Eighteen patients (25%) had low a T-TIL response, and 53 patients (75%) had a high T-TIL response. Overall, expression of the MHC class H molecules HLA-DR and HLA-DQ was most conserved. The loss of B7.2 (P = 0.04), intracellular adhesion molecule 1 (P = 0.0004), MAS (P = 0.02), and HLA-DR (P = 0.0004) expression was significantly associated with decreased T-TIL response. In 100% of patients with low T-TIL responses, at least one HLA, CAM, or CSM was undetectable on the malignant B cells by immunohistochemical staining (mean number of molecules lost = 2.67). In contrast, 49% of patients with high T-TIL responses had no losses in HLA, CAM, or CSM expression (mean number of molecules lost = 0.89). The mean number of absent molecules (HLA, CAM, or CSM) was significantly associated with T-TIL response (P = 0.0001). We conclude that loss of HLA, CAM, or CSM expression on malignant B cells is associated with a poor host T-cell immune response. In addition, because patients with low T-TIL response had lost expression of multiple cellular adhesion, recognition, and costimulatory molecules, our results suggest that a combination of immunorestorative therapies may be required to generate effective antitumor T-cell responses in B-cell DLCL.

Antigens, CD↗
PubMed1999

1,25-Dihydroxycholecalciferol (1,25-D3) inhibits the growth of squamous cell carcinoma and down-modulates p21(Waf1/Cip1) in vitro and in vivo.

1,25-Dihydroxycholecalciferol (1,25-D3) has significant antitumor effects in the murine squamous cell carcinoma (SCC) tumor model in vitro and in vivo. We investigated the basis for this antiproliferative activity and found that, in vitro, 1,25-D3 administration is associated with altered expression of cell cycle regulatory proteins, treatment results in retinoblastoma dephosphorylation, decreased expression of p21(Waf1/Cip1) (p21) mRNA and protein, and increased expression of p27Kip1 (p27) mRNA and protein. Dexamethasone, which acts synergistically with 1,25-D3 to inhibit SCC proliferation, enhanced 1,25-D3-induced down-modulation of p21 without affecting the ability of 1,25-D3 to increase p27 expression. 1,25-D3 did not induce cleavage of poly(ADP-ribose) polymerase. These in vitro data suggest that 1,25-D3 exerts antitumor activity in SCC by perturbing cell cycle progression rather than by inducing apoptosis. In vivo, a 1,25-D3 treatment regimen that results in a decrease in SCC tumor volume is associated with a statistically significant decrease in intratumoral p21 expression. p21 expression is not changed in tumors isolated from control animals or animals treated with a nontherapeutic dose of 1,25-D3. Intratumoral p27 levels were not modulated by 1,25-D3 treatment. Thus, both in vitro and in vivo, 1,25-D3-mediated growth inhibition is associated with p21 down-modulation.

Animals↗
PubMed1999

Perceived social support among depressed elderly, middle-aged, and young-adult samples: cross-sectional and longitudinal analyses.

BACKGROUND: A number of studies have concluded that the perceived quality of support is more strongly associated with mental health than with the actual structure of personal networks. This study examined clinical, historical, and phenomenological variables associated cross-sectionally and longitudinally with perceived social support. METHODS: Participants included elderly, middle-aged, and young-adult depressed samples derived from the Duke Clinical Research Center for the Study of Depression in Late Life. RESULTS: Cross-sectional multivariate analyses revealed that perceived social support was: (1) for the elderly associated with pessimistic thinking, being divorced, having strange ideas, the degree of social interaction, and instrumental support; (2) for middle-age associated with dysthymia, divorce, pessimistic thoughts, social interaction, and instrumental support; and (3) among young adults with instrumental support only. Longitudinal multivariate analyses indicated that only perceived social support at Time 1 predicted perceived social support 1 year later among elderly and middle-aged subjects, whereas only instrumental support predicted perceived social support 1 year later among the young-adult sample. LIMITATIONS: The small number of subjects among the young-adult sample limit conclusions regarding this group. In addition, only patients provided data. Future studies should consider using multiple informants to enhance the accuracy of reported social support. CONCLUSIONS: Our findings indicate that in addition to whatever else they do for depressed patients, clinicians must endeavor to address relationship or social support difficulties, especially in the elderly.

Adult↗
PubMed1999

Correlates of suicidal ideation among an elderly depressed sample.

BACKGROUND: Suicidal ideation has been shown to be strongly associated with suicide completion and elders take their own lives more than any other age group. METHODS: The present study examined clinical and phenomenological correlates of suicidal ideation among an elderly sample (n = 167) derived from subjects enrolled in the Duke Clinical Research Center for the Study of Depression in Late Life. RESULTS: Bivariate results indicated that clinical variables associated with psychomotor retardation, a history of dysthymia, a previous psychiatric in-patient stay, and being a 'younger' elder were related to greater suicidal ideation. Multivariate analyses indicated that feeling guilty, sinful, or worthless was associated with over six times greater odds of having suicidal thoughts. LIMITATIONS: Findings are based on correlational analyses, and thus, the direction of causality cannot be inferred. CONCLUSIONS: This study provides evidence for clinicians of some of the 'red flags' associated with the presence of suicidal ideation among depressed older adults.

Aged↗
PubMed1999

New onset and remission of suicidal ideation among a depressed adult sample.

BACKGROUND: Previous research has demonstrated that suicidal ideation often predicts suicide completion. METHODS: The present study examined clinical and phenomenological variables associated with the presence, development and remission of suicidal ideation among depressed adults. The sample (n = 81) was derived from subjects enrolled in the Duke Clinical Research Center for the Study of Depression in Late Life. RESULTS: Greater pessimistic thinking at baseline predicted the development of suicidal ideation one year later and the older a person was when he or she first experienced depression, the more likely he or she was to report remission from suicidal ideation one year following onset. LIMITATIONS: Longitudinal analyses were based on relatively small samples. Variables that were not significant in these analyses might be in a larger sample. CONCLUSIONS: The longitudinal design of this study mitigates limitations associated with cross-sectional or retrospective designs and advances our understanding of a clinical profile associated with the development and remission of suicidal thoughts.

Adolescent↗