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Biomedical subjects

J C Stewart

Publications and source records attributed to J C Stewart.

At least 19 recordsLinked to original sources
PubMed2001

EphA2 overexpression causes tumorigenesis of mammary epithelial cells.

Elevated levels of protein tyrosine phosphorylation contribute to a malignant phenotype, although the tyrosine kinases that are responsible for this signaling remain largely unknown. Here we report increased levels of the EphA2 (ECK) protein tyrosine kinase in clinical specimens and cell models of breast cancer. We also show that EphA2 overexpression is sufficient to confer malignant transformation and tumorigenic potential on nontransformed (MCF-10A) mammary epithelial cells. The transforming capacity of EphA2 is related to the failure of EphA2 to interact with its cell-attached ligands. Interestingly, stimulation of EphA2 reverses the malignant growth and invasiveness of EphA2-transformed cells. Taken together, these results identify EphA2 as a powerful oncoprotein in breast cancer.

Animals↗
PubMed2001

Cardiovascular recovery from stress predicts longitudinal changes in blood pressure.

Cardiovascular reactivity and recovery were examined as predictors of blood pressure changes over 3 years. Blood pressure and heart rate readings were obtained from 73 men and women aged 18-20 years during cold pressor, mental arithmetic, tourniquet ischemia, cycle exercise and step exercise tasks. Regression analyses indicated that after adjustment for initial blood pressure, initial age, initial body-mass index, sex, parental history of hypertension, and length of follow-up, heightened heart rate reactivity to mental arithmetic was associated with increased follow-up systolic blood pressure (DeltaR(2)=0.04, P<0.05). Systolic blood pressure recovery from cold pressor and tourniquet ischemia were also positively related to follow-up systolic blood pressure (DeltaR(2)=0.04 and 0.04, respectively, P<0.05) and remained so even after adjustment for the corresponding cardiovascular reactivity measures. These findings suggest that cardiovascular reactivity and recovery measures are modest predictors of longitudinal changes in blood pressure.

Adolescent↗
PubMed2001

Assessing a computerized routine health information system in Mali using LQAS.

BACKGROUND: Between 1987 and 1998 Save the Children conducted a child survival programme in Mali with the goal of reducing maternal and child morbidity and mortality. An integral part of this programme was a computerized demographic surveillance and health information system (HIS) that gathered data on individuals on an on-going basis. OBJECTIVE: To assess the overall coverage and quality of the data in the HIS, to identify specific health districts that needed improvements in data collection methods, and to determine particular areas of weakness in data collection. METHODS: Random samples of 20 mothers with children <5 years were selected in each of 14 health districts. Mothers were interviewed about pregnancies, live births, deaths of children <5, and children's growth monitoring and immunization status. The Lot Quality Assurance Method (LQAS) was used to identify districts in which records and interview results did not meet predetermined levels of acceptability. Data collected in the interviews were combined to estimate overall coverage and quality. RESULTS: When all variables were analyzed, all 14 lots were rejected, and it was estimated that 52% of all events occurring in the community were registered in ProMIS. Much of this poor performance was due to immunization and growth monitoring data, which were not updated due to printer problems. Coverage of events increased (92%) when immunizations and growth monitoring were excluded, and no lots were rejected. When all variables were analyzed for quality of data recorded, six lots were rejected and the overall estimation was 83%. With immunizations and growth monitoring excluded, overall quality was 86% and no lots were rejected. CONCLUSIONS: The comprehensive computerized HIS did not meet expectations. This may be due, in part, to the ambitious objective of complete and intensive monitoring of a large population without adequate staff and equipment. Future efforts should consider employing a more targeted and streamlined HIS so that data can be more complete and useful.

Adolescent↗
PubMed2001

Perpetrators as victims: understanding violence by female street-walking prostitutes.

Little is known about the perpetration of violence by women who engage in street prostitution. While some researchers have examined the incidence of abuse among this population, the association between receipt of abuse and violence and later perpetration of violence is unclear. This study presents data from a recent evaluation of a case management program for street-walking prostitutes. A description of the program clients is provided, and factors that are associated with assaultive behavior against clients are examined. Bivariate analyses revealed statistically significant differences between assaultive and nonassaultive women with regard to history of psychiatric hospitalization, history of sexual abuse, history of physical abuse, history of emotional abuse, and whether they had been assaulted on the streets. However, logistic regression on variables related to abuse and violence indicates that controlling for other variables, the only statistically significant predictor of assaultive behavior was history of physical abuse. These results indicate the need for further research on this population as well as access to treatment for these women to address their own abuse and victimization.

Adult↗
PubMed2000

Analysis of in situ protease activity in chronic adult periodontitis patients: expression of activated MMP-2 and a 40 kDa serine protease.

BACKGROUND: Periodontitis is characterized by extensive destruction of the gingival tissues and associated supporting structures of the teeth. Although the pathogenesis of the various forms of this disease is not completely understood, host-derived proteases are believed to have an important role. In this study, we analyzed human tissue samples from chronic adult periodontitis patients to assess the levels of specific proteases and determine the effect of pH and tetracyclines on their activity. METHODS: Gingival tissue samples were obtained from patients with chronic adult periodontitis (probing depths ranged from 5 to 9 mm) and periodontally healthy controls. Tissue extracts were prepared and analyzed for protease activity by zymography and Western blotting. RESULTS: Maximal protease activity from clinically normal and diseased tissues was observed at pH 8. Latent matrix metalloproteinase (MMP)-9 and MMP-2 were expressed in all samples examined, while active MMP-2 was detected only in tissues obtained from patients with clinical disease. The MMP activities were differentially inhibited by derivatives of tetracycline. At pH 6, a protease with a mass of approximately 40 kDa was observed in diseased samples. The enzymatic activity was inhibited by phenylmethylsulfonyl fluoride, suggesting it is a serine protease. CONCLUSIONS: The results of the current study substantiate the proposed role of host-derived proteases in the pathogenesis of chronic adult periodontitis. Specifically, they indicate that activated MMP-2 and a 40 kDa serine protease are involved in tissue destruction associated with this form of periodontal disease and also suggest that tissue pH influences protease activity in situ.

Adult↗
PubMed1999

Photodynamic therapy with mTHPC and polyethylene glycol-derived mTHPC: a comparative study on human tumour xenografts.

The photosensitizing properties of m-tetrahydroxyphenylchlorin (mTHPC) and polyethylene glycol-derivatized mTHPC (pegylated mTHPC) were compared in nude mice bearing human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts. Laser light (20 J/cm2) at 652 nm was delivered to the tumour (surface irradiance) and to an equal-sized area of the hind leg of the animals after i.p. administration of 0.1 mg/kg body weight mTHPC and an equimolar dose of pegylated mTHPC, respectively. The extent of tumour necrosis and normal tissue injury was assessed by histology. Both mTHPC and pegylated mTHPC catalyse photosensitized necrosis in mesothelioma xenografts at drug-light intervals of 1-4 days. The onset of action of pegylated mTHPC seemed slower but significantly exceeds that of mTHPC by days 3 and 4 with the greatest difference being noted at day 4. Pegylated mTHPC also induced significantly larger photonecrosis than mTHPC in squamous cell xenografts but not in adenocarcinoma at day 4, where mTHPC showed greatest activity. The degree of necrosis induced by pegylated mTHPC was the same for all three xenografts. mTHPC led to necrosis of skin and underlying muscle at a drug-light interval of 1 day but minor histological changes only at drug-light intervals from 2-4 days. In contrast, pegylated mTHPC did not result in histologically detectable changes in normal tissues under the same treatment conditions at any drug-light interval assessed. In this study, pegylated mTHPC had advantages as a photosensitizer compared to mTHPC. Tissue concentrations of mTHPC and pegylated mTHPC were measured by high-performance liquid chromatography in non-irradiated animals 4 days after administration. There was no significant difference in tumour uptake between the two sensitizers in mesothelioma, adenocarcinoma and squamous cell carcinoma xenografts. Tissue concentration measurements were of limited use for predicting photosensitization in this model.

Adenocarcinoma↗
PubMed1997

Experimental assessment of photodynamic therapy with chlorins for malignant mesothelioma.

OBJECTIVE: Photodynamic therapy (PDT) with two chlorin sensitisers was assessed on nude mice bearing human mesothelioma xenografts, and on intrathoracic tissues of minipigs with the same drug-light conditions to optimise the antitumour activity of PDT while preventing photosensitising injury to normal tissues. METHODS: Laser light (20 J/cm2) at 652 nm was delivered to the xenografts 1-4 days after i.p. administration of 0.1 mg/kg m-tetrahydroxyphenyl-chlorin (mTHPC) or an equimolar dose of polyethylene glycol-derived mTHPC (pegylated mTHPC), respectively. The extent of tumour necrosis was assessed by histomorphometry. Intraoperative PDT was then performed to the thoracic cavity of minipigs through a sternotomy with the same drug-light conditions at drug-light intervals ranging from 12 h to 6 days after i.v. administration of mTHPC and pegylated mTHPC, respectively. RESULTS: Both, mTHPC and pegylated mTHPC, resulted in photosensitised necrosis of mesothelioma xenografts at drug-light intervals from 1 to 4 days but the extent of necrosis was significantly larger by use of pegylated mTHPC instead of mTHPC at a drug-light interval of 3 and 4 days. The optimal tumourcidal effect was achieved with pegylated mTHPC at a drug-light interval of 4 days. The photosensitising effect of mTHPC on intrathoracic tissues of minipigs revealed severe damage of virtually all tissues except nerves at short drug-light intervals. Tissue damage gradually became less at longer drug-light intervals and was absent at intervals of 3 days and longer. In contrast, pegylated mTHPC resulted in no obvious change to any structure at any drug-light interval assessed. CONCLUSIONS: PDT with pegylated mTHPC reveals the potential of selective tumour destruction in this experimental setting and deserves further evaluation for intraoperative application in patients with malignant mesothelioma.

Animals↗
PubMed1997

Does the in-vitro efficiency of meso-tetrahydroxy-phenyl-chlorin depend on pre-treatment of sensitizer?

The efficiency of a new photosensitizer of the second generation, meso-tetra-hydroxyphenyl-chlorin (mTHPC), which has a strong absorption at 652 nm, was investigated by oxygen consumption measurements and membrane integrity testing. The experiments proved a great increase in the efficiency of mTHPC after preincubation at 37 degrees C for 24 hours. From these findings it can be assumed that tumor cells can be treated in an optimal way with PDT after a longer delay following drug administration.

Cell Line↗
PubMed1997

Relationship of cytomegalovirus to salivary gland dysfunction in HIV-infected patients.

In a previous retrospective study of HIV-infected patients we detected a relationship between xerostomia and the presence of cytomegalovirus in saliva. This prospective study compares 13 patients with HIV and a complaint of xerostomia and low salivary flow rates with a control group of 7 patients with HIV without xerostomia and normal salivary flow rates. Both groups were evaluated for the presence of cytomegalovirus in saliva, peripheral blood mononuclear cells, and labial minor salivary glands. Viral cultures, polymerase chain reaction, and histopathologic examination were used to detect cytomegalovirus. Xerostomia and low salivary flow rates were associated with the presence of CMV in saliva. The virus was detected in 10 of 13 xerostomia patients and 2 of 7 controls (p = 0.05, Fisher's exact test). Cytomegalovirus was detected in the saliva of patients who did not also have it in their blood suggesting a local source of virus replication such as the salivary glands. The minor salivary glands were not a major site of cytomegalovirus. Culture was more sensitive then polymerase chain reaction in detecting salivary cytomegalovirus as a result of the presence of inhibitors to the reaction in saliva. These results suggest a link between cytomegalovirus in saliva and salivary gland dysfunction in HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1997

Oral mucosal melanomas: the WESTOP Banff workshop proceedings. Western Society of Teachers of Oral Pathology.

A workshop to discuss primary oral melanomas was convened at the annual Western Society of Teachers of Oral Pathology meeting in Bannf, Alberta, Canada. Fifty oral melanomas, identified from the files of the participants, were reviewed in order to better understand the clinical features, histologic spectrum, and natural history of these perplexing lesions. Results confirmed that oral melanomas occur in adults almost three times more frequently in men than women and have a decided predilection for the palate and gingiva. Some lesions exhibit a clinically detectable and prolonged in situ growth phase, whereas others seem to lack this property and exhibit only or predominantly invasive characteristics. Recurrences, metastases, and death from tumor were characteristic of the follow-up of a limited number of patients. Until definitive prospective data are collected that elucidate natural history, oral mucosal melanomas should be tracked separately from cutaneous lesions. All oral pigmented lesions that are not clinically diagnostic should be biopsied. Lesions with equivocal histopathologic features might be referred to as "atypical melanocytic proliferation" and should be excised. Recognition of lesions in an early in situ phase and aggressive treatment should have a favorable effect on prognosis. To enhance future or prospective study of these rare neoplasms, guidelines for reporting oral melanomas are suggested.

Adult↗
PubMed1997

Elephantiasis nostras of the lips: a case report.

Elephantiasis nostras (EN) is a clinical entity that usually presents as a persistent swelling of the lower extremities. It has been related to recurrent lymphangitis of bacterial origin that causes a fibrosis and thickening of both epidermal and connective tissue. Although very rare, EN has been previously reported in the lips. This is the first case reported in the oral medicine literature that describes EN involving the lips. We describe the clinical features and a differential diagnosis of the lip lesions and a treatment protocol to which this patient has responded. A diagnosis of EN should be entertained in patients with chronically edematous, scaling lip lesions.

Adult↗
PubMed1997

Photodynamic therapy of a transplanted pancreatic cancer model using meta-tetrahydroxyphenylchlorin (mTHPC).

Pancreatic cancer is difficult to treat, even for tumours localized to the pancreas. Photodynamic therapy (PDT) is a non-thermal technique for producing localized tissue necrosis with light after prior administration of a photosensitizing drug and it could have a role in the local treatment of these cancers. We studied PDT in a transplanted cancer in the hamster pancreas using the photosensitizer mTHPC (meta-tetrahydroxyphenylchlorin). Fluorescence microscopy showed maximum levels of mTHPC in normal pancreas 2-4 days after sensitization and in tumour at 4-5 days. For PDT, animals were given 0.1 or 0.3 mg kg(-1) mTHPC and the tumour was treated at laparotomy 2 or 4 days later with red light (50 J at 650 nm, continuous or fractionated) delivered via a single fibre touching the tumour surface. The maximum zone of tumour necrosis (seen 3 days after PDT) was 8.7 mm in diameter with continuous irradiation, increasing to 12.4 mm with light fractionation (four equal fractions with 3 min between fractions). The main complication was sealed duodenal perforation, seen in 3 of 16 animals, probably due to inadequate shielding of the duodenum from the light. The duodenal problems seen in hamsters are unlikely to cause trouble in the much thicker human duodenum. PDT tumour necrosis in this animal model has now been shown with a range of photosensitizers, but mTHPC is attractive as it is likely to produce the largest volumes of necrosis around each treatment point with short light exposure times. This technique could have a role in the treatment of localized cancers of the pancreas in patients unsuitable for surgery and can now be considered for preliminary clinical trials.

Animals↗
PubMed1997

Central giant cell granulomas of the jaws: phenotype and proliferation-associated markers.

Central giant cell granulomas (CGCGs) are jaw tumors of unknown origin that often exhibit an aggressive, though unpredictable, clinical course. The purpose of this study was to determine the immunoprofile of the mononuclear cells that seem to be responsible for the biologic behavior of these tumors. Numbers of cells in cell cycle were also determined and compared in clinically aggressive and non-aggressive CGCGs. Sixteen aggressive and 12 non-aggressive CGCGs were immunohistochemically stained with antibodies to CD34, CD68, factor XIIIa, alpha-smooth muscle actin, prolyl 4-hydroxylase, Ki-67, and p53 protein. Cell populations and numbers of cells in cell cycle were determined through microscopic quantitative assessment. CD34-positive cells were limited to support vessels. CD68-positive mononuclear cells constituted a small population of cells in all tumors. With two exceptions, factor XIIIa-positive cells were rarely seen. Alpha-smooth muscle actin staining was present in approximately half the tumors, and occasionally large numbers of positive cells were seen. Most mononuclear cells were positive for fibroblast-associated antigen. No phenotypic differences were detected between aggressive and non-aggressive tumors. P53 protein did not appear to be overexpressed in CGCGs. Ki-67 staining showed that only mononuclear cells were in cell cycle, and that there were no differences between aggressive and non-aggressive tumors. We conclude that CGCGs are primarily fibroblastic (and myofibroblastic) tumors in which macrophages appear to play a secondary role. Tumor cells show no differentiation toward endothelial cells or macrophage-related dendrocytes (factor XIIIa). Cellular phenotypes and numbers of cells in cell cycle are similar in both aggressive and non-aggressive tumors.

Actins↗
PubMed1997

Topical lithium succinate ointment (Efalith) in the treatment of AIDS-related seborrhoeic dermatitis.

A randomised, double-blind, placebo-controlled trial with lithium succinate ointment was conducted in patients with AIDS-associated facial seborrhoeic dermatitis. Twice daily applications of the ointment brought about a rapid (2.5 days) and highly significant (P = 0.007) improvement in the severity of the condition. Lithium succinate ointment is well tolerated and can be a useful treatment for seborrhoeic dermatitis in this group of patients.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Substance use and abuse in adolescence: an overview.

Substances are widely used by youth as a means of excitement, consolation, belonging to a referent group, rebellion, a symbol of social and sexual maturity and independence. The destabilization of the family, permissiveness, indifference of the adult world, ethical confusion, peer pressure and the decline of self-discipline among the young are the essential causes of adolescent substance use and abuse. Preventive and treatment efforts are flawed by disagreements in the area of diagnosis and strategy, lack of cohesiveness, insufficient funds and deficiencies in follow-up procedures.

Adolescent↗
PubMed1996

Distribution and photodynamic effects of meso-tetrahydroxyphenylchlorin (mTHPC) in the pancreas and adjacent tissues in the Syrian golden hamster.

Photodynamic therapy (PDT) has the potential to destroy small tumours with safe healing of adjacent normal tissue. This study looks at the effects of PDT on the normal pancreas and adjacent tissues in hamsters using the photosensitiser meso-tetrahydroxyphenylchlorin (mTHPC). Pharmacokinetic studies used fluorescence microscopy on sections of pancreas, stomach and duodenum 1 h to 6 days after mTHPC. Highest levels of sensitiser were seen in the gastric and duodenal mucosa and in the acinar pancreas after 2-4 days. For PDT, light at 652 nm was delivered by placing a 0.2 mm diameter bare-ended fibre against the tissue. An energy of 50 J was used 2 or 4 days after 0.1 or 0.3 mg kg-1 mTHPC and animals killed 1 to 7 days later. Maximum necrosis was seen 3 days after PDT with lesions up to 4 mm in pancreas, 4.5 mm in duodenum and 2.5 mm in stomach. By fractionating the light dose, the lesion size could be increased by 30%. The main complication was free or sealed duodenal perforation (avoided by shielding the duodenum). Partial, reversible bile duct obstruction was seen occasionally. There was no macroscopic damage to the bile ducts or major blood vessels. Apart from the duodenum, all lesions healed safely. In this animal model, only the duodenum was at risk of serious, irreversible damage. Treatment is likely to be safer in the much thicker human duodenum. mTHPC is a powerful photosensitiser and suitable for further study for tumours in the region of the pancreas although care is required near the duodenum.

Animals↗
PubMed1996

Wounding effects of the Winchester Black Talon bullet.

Winchester Ammunition has developed a bullet that was specifically designed to perform better than other hollow-point missiles. The resulting cartridge, the Black Talon bullet offers a low-velocity missile that retains its weight, penetrates even when interrupted by intervening objects, and remains capable of expansion in soft tissue. The bullet causes extensive tissue damage and presents a hazard to those responsible for handling it after expansion.

Fatal Outcome↗