PubMed Health⌕ Search

Biomedical subjects

A Stone

Publications and source records attributed to A Stone.

At least 37 records · Page 2Linked to original sources
PubMed1999

Loss of differentiation of 4NQO-induced rat malignant oral keratinocytes correlates with metastatic dissemination and is associated with a reduced cellular response to TGF-beta1 and an altered receptor profile.

This study examined the metastatic capacity of clonal populations of 4NQO-induced rat malignant oral keratinocytes following orthotopic transplantation to athymic mice. Polygonal and spindle cells formed well-differentiated squamous cell carcinomas (keratin positive and vimentin negative) and undifferentiated spindle cell tumours (keratin negative and vimentin positive), respectively, in almost 100% of animals at the site of inoculation (floor of mouth). Transplantation of 5x 10(6) cells of either cell type at high cell density resulted in approximately 50% of animals forming pulmonary metastases. By contrast, inoculation of 2x 10(6) differentiated polygonal cells resulted in the formation of significantly fewer pulmonary metastases than the undifferentiated spindle cells. A single well-differentiated clone of polygonal cells and 3 of 4 of the undifferentiated spindle cell lines produced comparable levels of TGF-beta1. One undifferentiated spindle cell line expressed significantly more TGF-beta1 and, following transplantation orthotopically, fewer animals formed pulmonary metastases despite the formation of primary tumours in almost all grafted animals, suggesting that TGF-beta1 can act as a tumour suppressor in this cell type. All cell lines produced comparable amounts of TGF-beta2. The clones of polygonal cells were markedly inhibited and the spindle cells were only partially inhibited by exogenous TGF-beta1. Both cell types expressed high-affinity TGF-beta cell surface receptors; the ratio of type I to type II TGF-beta receptors was 1.0:<3.0 in the spindle cells and 1.0:17.9 in the polygonal clone. The results suggest that differentiated rat malignant oral keratinocytes are less aggressive and have a decreased potential to metastasise than their undifferentiated spindle cell counterparts. This may be attributable, in part, to a change in TGF-beta receptor profile leading to the partial loss of response to exogenous TGF-beta1.

4-Nitroquinoline-1-oxide↗
PubMed1999

Cellulite.

Explore the source record for details and available documents.

Adipose Tissue↗
PubMed1999

Long-term followup of the North American multicenter UroLume trial for the treatment of external detrusor-sphincter dyssynergia.

PURPOSE: We determine the long-term efficacy and safety of the UroLume stent as minimally invasive treatment for external detrusor-sphincter dyssynergia in spinal cord injured men. MATERIALS AND METHODS: A total of 160 spinal cord injured men with a mean age plus or minus standard deviation of 36.3 +/- 12.1 years (range 16 to 74) were prospectively treated with an endoprosthesis at 15 centers as part of the North American UroLume trial for external detrusor-sphincter dyssynergia. Urodynamic parameters, including voiding pressure, residual urine volume and bladder capacity, were compared before treatment and at 1, 2, 3, 4 and 5 years after treatment. RESULTS: Mean voiding pressure was 75.1 +/- 28.2 cm. water before treatment in the 160 patients, and 37.4 +/- 23.9 at year 1 in 97, 39.5 +/- 22.2 at year 2 in 84, 42.6 +/- 27.3 at year 3 in 61, 46.3 +/- 33.2 at year 4 in 57 and 44.2 +/- 28.9 cm. at year 5 in 41 after stent insertion (p <0.001). Residual urine volume decreased after stent placement and was maintained throughout the 5-year followup (p <0.001). Mean cystometric capacity remained constant from 269 +/- 155 before insertion to 337 +/- 182 ml. 5 years later (p = 0.17). Hydronephrosis and autonomic dysreflexia improved or stabilized in most patients with functioning stents. Stent explant was necessary in 24 patients (15%), of whom 4 (16.7%) had another stent implanted. CONCLUSIONS: The UroLume stent demonstrates long-term safety and efficacy for the treatment of external detrusor-sphincter dyssynergia. The outcome was similar in men with and without previous sphincterotomy.

Adolescent↗
PubMed1998

Genetic polymorphisms in catechol-O-methyltransferase, menopausal status, and breast cancer risk.

Polymorphic catechol-O-methyltransferase (COMT) catalyzes the O-methylation of estrogen catechols. In a case-control study, we evaluated the association of the low-activity allele (COMT(Met)) with breast cancer risk. Compared to women with COMT(Val/Val), COMT(Met/Met) was associated with an increased risk among premenopausal women [odds ratio (OR), 2.1; confidence interval (CI), 1.4-4.3] but was inversely associated with postmenopausal risk (OR, 0.4; CI, 0.2-0.7). The association of risk with at least one low-activity COMT(Met) allele was strongest among the heaviest premenopausal women (OR, 5.7; CI, 1.1-30.1) and among the leanest postmenopausal women (OR, 0.3; CI, 0.1-0.7), suggesting that COMT, mediated by body mass index, may be playing differential roles in human breast carcinogenesis, dependent upon menopausal status.

Body Mass Index↗
PubMed1998

Destructible toys as enrichment for captive chimpanzees.

The use of destructible objects or toys as enrichment for nonhuman primates has had promising results in terms of increased use and positive behavioral effect. The purpose of this project was to determine the use and durability of a number of inexpensive, destructible toys provided one at a time or several at once. Nine singly caged chimpanzees were provided with 8 different toys made of plastic, vinyl, or cloth, and the frequency of use of the toys was determined during 15 min trials 2 times per day. A toy was removed when it was destroyed or when it was not contacted during 4 trials. The chimpanzees contacted the toys an average of 11 times per trial, and the use of the individual toys was significantly higher when provided 1 at a time rather than all at once. Use of the toys was fairly stable over time, and the toys remained in the cages an average of 3.2 days. The durability of the toys was related to the type of toy (e.g., more flexible cloth and vinyl toys lasted longer than rigid plastic toys). The destructible toys were used significantly more often than other permanent cage toys or televisions. Toy use was not related to age, level of abnormal behavior, or use of existing permanent toys or television. The implications of the results were related to the management of an environmental enrichment program and indicated that the provision of flexible, inexpensive toys 1 at a time can be an effective method of enrichment for captive chimpanzees.

Journal Article↗
PubMed1997

Symptomatic improvement of premenstrual dysphoric disorder with sertraline treatment. A randomized controlled trial. Sertraline Premenstrual Dysphoric Collaborative Study Group.

CONTEXT: Premenstrual dysphoric disorder is an important cause of symptoms and functional impairment in menstruating women. OBJECTIVE: To evaluate the efficacy of sertraline hydrochloride for treatment of premenstrual dysphoria by measuring changes in symptom expression and functional impairment. DESIGN: Two screening cycles followed by 1 single-blind placebo cycle and 3 cycles of randomized, double-blind, placebo treatment. SETTING: Twelve university-affiliated outpatient psychiatry and gynecology clinics. PATIENTS: Of the 447 women who requested participation, 243 met criteria for premenstrual dysphoric disorder and were randomized; 200 women completed the study. INTERVENTION: A flexible (50-150 mg) daily dose of sertraline hydrochloride. MAIN OUTCOME MEASURES: The Daily Record of Severity of Problems, Hamilton Rating Scale for Depression, Clinical Global Impression Scale, and Social Adjustment Scale. RESULTS: Mean (+/-SD) total daily symptom scores decreased significantly (P<.001) in the sertraline-treated (64+/-22 to 44+/-19) compared with the placebo-treated (62+/-22 to 54+/-24) groups. Significant improvement (P<.05) was found for all clinically derived symptom clusters (depressive, physical, and anger/irritability symptoms). Hamilton Rating Scale for Depression scores decreased by 44% and 29% in the sertraline and placebo groups, respectively (P<.002). End-point global ratings showed much or very much improvement in 62% of the active treatment group and 34% of the placebo treatment group (P<.001). Reported functional impairment was substantial at baseline. Improvement in psychosocial functioning with treatment was similar to what is found in studies of major depression. CONCLUSIONS: Sertraline was significantly better than placebo for treatment of premenstrual dysphoria as reflected by symptomatic improvement and change in reported functional impairment. Serotonin reuptake inhibitors such as sertraline are useful therapeutic options for women with premenstrual dysphoria.

1-Naphthylamine↗
PubMed1997

Neandertal DNA sequences and the origin of modern humans.

DNA was extracted from the Neandertal-type specimen found in 1856 in western Germany. By sequencing clones from short overlapping PCR products, a hitherto unknown mitochondrial (mt) DNA sequence was determined. Multiple controls indicate that this sequence is endogenous to the fossil. Sequence comparisons with human mtDNA sequences, as well as phylogenetic analyses, show that the Neandertal sequence falls outside the variation of modern humans. Furthermore, the age of the common ancestor of the Neandertal and modern human mtDNAs is estimated to be four times greater than that of the common ancestor of human mtDNAs. This suggests that Neandertals went extinct without contributing mtDNA to modern humans.

Animals↗
PubMed1997

Oxidative stress in diabetic macrovascular disease: does homocysteine play a role?

BACKGROUND: Non-insulin-dependent diabetes mellitus (NIDDM) and hyperhomocysteinemia are both associated with increased lipid peroxidation (oxidative stress). This may contribute to the accelerated vascular disease associated with these conditions. It is not known whether the coexistence of elevated homocysteine levels will stimulate oxidative stress further than that caused by diabetes alone. METHODS: Plasma concentrations of thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, were measured in patients with NIDDM who had previously had a methionine load test; some of the patients had hyperhomocysteinemia. RESULTS: Plasma TBARS concentrations were elevated in diabetics with vascular disease. The additional presence of hyperhomocysteinemia was not associated with a further increase in plasma TBARS concentrations. CONCLUSIONS: Lipid peroxidation is increased in patients with diabetes mellitus and macrovascular disease and is not further elevated by the coexistence of elevated homocysteine levels. It is possible that diabetes maximally stimulates oxidative stress and any further acceleration of vascular disease in patients who have coexistent hyperhomocysteinemia is mediated through mechanisms other than lipid peroxidation.

Adult↗
PubMed1997

The mitogenic effect of KGF and the expression of its cell surface receptor on cultured normal and malignant human oral keratinocytes and on contiguous fibroblasts.

This study examined the mitogenic response to keratinocyte growth factor (KGF) of normal and tumour-derived human oral keratinocytes in which the degree of cellular differentiation was known and in contiguous fibroblast cultures derived from the malignant epithelial cultures. Keratinocytes, but not fibroblasts, were stimulated by KGF, thereby demonstrating epithelial target cell specificity of the ligand. KGF-induced stimulation of the tumour-derived keratinocytes cultured in the absence of the 3T3 fibroblast support broadly correlated with the degree of cellular differentiation; well-differentiated keratinocytes were stimulated more by KGF than their less differentiated counterparts. Malignant oral keratinocytes expressed KGF cell surface receptors (KD 451-709 pM; receptors/cell 2306-13645), but KGF receptor mRNA did not correlate with either KGF-induced mitogenesis or the degree of epithelial cell differentiation. When the tumour-derived keratinocytes were cultured in the presence of 3T3 fibroblasts, the mitogenic response to KGF was comparable to normal epithelial cells. The results suggest that KGF-mediated growth stimulation may not be significant in providing a selective advantage for the growth of malignant keratinocytes.

3T3 Cells↗
PubMed1997

Differential nitric oxide production by microvascular and macrovascular endothelial cells.

Phenotypic heterogeneity among endothelial cell populations may account for important organ-specific behaviors. Experimental evidence suggests that endothelium-derived nitric oxide mediates certain of these unique responses. The purpose of these investigations was to compare rat pulmonary microvascular endothelial cells with pulmonary artery and aortic macrovascular endothelial cells in their ability to generate nitric oxide (NO). Cultures of these microvascular and macrovascular endothelial cells were incubated with interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and Salmonella typhimurium lipopolysaccharide (LPS) alone or in combination, and nitrite production was measured. Single-agent exposure with IFN-gamma (up to 1,000 U/ml), TNF-alpha (up to 60,000 U/ml), or LPS (up to 500 ng/ml) had little effect on nitrite generation. Nitrite production by rat aortic macrovascular endothelial cells (RAEC) was significantly greater than that by the rat lung microvascular endothelial cells (RLMVEC) when stimulated with TNF-alpha + IFN-gamma, LPS + IFN-gamma, or TNF-alpha + LPS. The maximal response by all endothelial cell types (approximately 15-fold increase in RAEC and 8-fold increase in RLMVEC) was observed with LPS + IFN-gamma. The nitrite generation from rat pulmonary artery endothelial cells was intermediate between RAEC and RLMVEC responses when stimulated with IFN-gamma + LPS or TNF-alpha. Similar patterns of heterogeneous inducible nitric oxide synthase mRNA induction occurred when Northern analysis of specimens from the cultured endothelial cell types was done. These data suggest that phenotypic heterogeneity between these endothelial cell populations is substantial and, by inference, that site-specific NO. generation may occur.

Animals↗
PubMed1997

A preliminary study on the efficacy of sertraline and imipramine on anger attacks in atypical depression and dysthymia.

There is clinical and biological evidence suggesting that patients with anger attacks, sudden spells of anger accompanied by intense autonomic activation, may represent a distinct psychopathological subgroup of patients with depressive disorders. We compared the prevalence of anger attacks in 168 outpatients with atypical depression or primary dysthymia with 38 normal subjects and tested the effect of treatment on anger attacks in a double-blind, placebo-controlled trial of sertraline versus imipramine. Patients were randomly assigned to sertraline (n = 56), imipramine (n = 52), or placebo (n = 60) and were administered the Anger Attacks Questionnaire before and after treatment. Depressed outpatients were significantly more likely to report anger attacks than controls. Anger attacks ceased in 53 percent of the patients receiving sertraline, 57 percent of those receiving imipramine, and 37 percent of those in the placebo group. Our findings support previous studies indicating that anger attacks are more prevalent among depressed outpatients than normals. Our results also suggest that sertraline and imipramine may be more effective than placebo in reducing the number of anger attacks following treatment although the differences were not statistically significant. Larger studies are needed to confirm our findings.

1-Naphthylamine↗