Biomedical subjects

J L Jones

Publications and source records attributed to J L Jones.

At least 37 records · Page 2Linked to original sources

PubMed2001

Synergism between the potato glycoalkaloids alpha-chaconine and alpha-solanine in inhibition of snail feeding.

Snails (Helix aspersa L.) were fed filter paper treated with the potato glycoalkaloids, alpha-solanine and alpha-chaconine, singly or together. In pure form, both glycoalkaloids deterred feeding, with chaconine being the more active compound. In combination, authentic solanine and chaconine interacted synergistically in their inhibition of feeding. The antifeedant activities of methanolic extracts of tuber peel of the potato varieties Majestic and Sharpe's Express presented via filter paper discs did not differ significantly from those of authentic glycoalkaloid solutions of comparable concentration and ratio. In contrast, feeding inhibition by diluted tuber peel extracts of the variety Homeguard was greater than that elicited by comparable authentic glycoalkaloid solutions suggesting additional inhibitory compound(s) in the peel of this variety. Comparison of data from peel extracts of all three potato varieties and authentic glycoalkaloids indicated that the level of feeding inhibition by the extracts was, at least in part, a consequence of a synergism between solanine and chaconine.

Animals↗

PubMed2001

Towards a biological staging model for operable non-small cell lung cancer.

Non-small cell lung cancer is the most common cause of cancer-related death in North America and Europe. Despite improvements in the diagnosis and treatment of the disease the prognosis remains poor, the overall 5-year survival being 4-14%. An increased understanding of the molecular biology of the disease may identify novel targets for drug development. We evaluated epidermal growth factor receptor (EGFR), HER-2/neu, matrix metalloproteinase (MMP)-2, MMP-9, p53 and bcl-2 expression and microvessel density (MVD) in patients who underwent surgery with curative intent in our department between 1991 and 1996. Co-expression of EGFR/MMP-9, MVD and bcl-2 were found to be independent prognostic variables, which allowed prediction of patient outcome independent of surgical stage. Other prognostic factors identified in our series were gender, surgical stage, platelet count, extent of necrosis, the hypoxia marker carbonic anhydrase-9 and beta-catenin. In collaboration with groups in Oxford and Greece, we were also able to establish the angiogenic growth factors vascular endothelial growth factor and platelet-derived endothelial growth factor as prognostic variables. The inter-relationships between these factors are currently being examined in an expanded patient series. Through this work we hope to be able to construct an integrated biological prognostic model which can be tested in prospective studies. This work has identified several potential targets for novel therapeutic agents currently in development.

Adult↗

PubMed2001

Congenital toxoplasmosis: a review.

Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii. In the United States, approximately 85% of women of childbearing age are susceptible to acute infection with T. gondii. Acute infections in pregnant women may cause serious health problems when the organism is transmitted to the fetus (congenital toxoplasmosis), including mental retardation, seizures, blindness, and death. An estimated 400 to 4000 cases of congenital toxoplasmosis occur in the U.S. each year. Manifestations of congenital toxoplasmosis may not become apparent until the second or third decade of life. Serologic tests are used to diagnose acute infection in pregnant women, but false-positive tests occur frequently, therefore, serologic diagnosis must be confirmed at a reference laboratory before treatment with potentially toxic drugs should be considered. Much of congenital toxoplasmosis can be prevented by educating women of childbearing age and pregnant women to avoid eating raw or undercooked meat, to avoid cross-contamination of other foods with raw or undercooked meat, and to use proper cat-litter and soil-related hygiene.

Animals↗

PubMed2001

Localization of matrix metalloproteinase 1 in cholesteatoma and deep meatal skin.

HYPOTHESIS: Matrix metalloproteinase 1 (MMP-1) is overexpressed in cholesteatoma. BACKGROUND: Cholesteatoma destroys bone, whereas deep meatal skin does not. MMP-1 is a type I collagenase that may be responsible for this destruction. This prospective study was designed to identify overexpression of MMP-1 by cholesteatoma in comparison with deep meatal skin. METHODS: Ten cholesteatoma specimens and nine deep meatal skin specimens were removed during otologic surgery and then fixed in formalin and embedded in paraffin. Immunocytochemistry studies were performed using a monoclonal antibody to MMP-1. A pathologist assessed the slides in a blinded fashion. Expression of MMP-1 protein in epidermis and in stroma was scored from 0 to 10. Five further cholesteatoma specimens and three deep meatal skin specimens underwent reverse transcriptase polymerase chain reactions to assess messenger ribonucleic acid production. Paired and unpaired Student's t tests were used to assess the difference in expression levels. RESULTS: Cholesteatoma stroma expressed significantly more MMP-1 protein than did deep meatal skin stroma (p = 0.04). MMP-1 was localized to stromal fibroblasts. There was no difference in the epidermal expression levels of the two tissue types (p = 0.42). The reverse transcriptase polymerase chain reaction showed expression at the messenger ribonucleic acid size of MMP-1 (262 base pair) in all cholesteatoma specimens examined. One deep meatal skin specimen showed a weak signal; no signal was seen in the other specimens. CONCLUSIONS: MMP-1 is overexpressed by the stromal fibroblasts present in cholesteatoma as compared with deep meatal skin. It is possible that these cells rather than the keratinocytes are responsible for bone destruction in this disease.

Cell Culture Techniques↗

PubMed2001

Efficacy of high-dose interferon in combination with ribavirin in patients with chronic hepatitis C resistant to interferon alone.

OBJECTIVE: Interferon combined with ribavirin has efficacy in the treatment of patients with chronic hepatitis C virus (HCV) infection. However, its utility in patients who have not responded to prior interferon therapy is not clear. Furthermore, the effect of using an increased dose of interferon in combination with ribavirin in patients with chronic hepatitis C resistant to conventional doses of interferon is not known. The aim of our study was to evaluate the effect of high-dose interferon in combination with ribavirin on the efficacy of treating patients with chronic hepatitis C resistant to interferon monotherapy in a large multicenter trial. METHODS: We randomized 154 patients with chronic hepatitis C who failed to achieve a sustained response with prior interferon therapy to receive either 3 or 5 MU of interferon alpha-2b and ribavirin (1000-1200 mg/day) for 12 months. There were 119 patients who had not responded and 35 who initially responded but relapsed after prior interferon monotherapy. Serum HCV RNA levels were measured at entry, 6, and 12 months of treatment and at the end of a 6-month follow-up period. RESULTS: The mean age of the subjects was 47 yr (range 28-68 yr), and 110 (71.4%) were men. One hundred thirty-two patients (86%) had HCV genotype 1, whereas 21 (14%) had cirrhosis. Eighty-one subjects (53%) were randomized to receive 3 MU of interferon alpha-2b. Fifteen of 35 relapse subjects (43%) and 12 of 119 prior nonresponder entrants (10%) achieved a sustained virological response to the 12-month course of treatment. Overall, 11 of 81 patients (14%) receiving 3 MU, and 16 of 73 patients (22%) receiving 5 MU of interferon maintained an undetectable HCV RNA level after cessation of therapy. The difference in sustained response rates between the two interferon dosage groups did not reach statistical significance (p = 0.09). However, among the nonresponder patients alone, there was an increased sustained response in the high-dose interferon group compared with the standard interferon dose group (15.5% vs 4.9%, p = 0.055). Twenty-six patients discontinued therapy before 6 months, including 10 patients (12.3%) in the 3-MU and 16 patients (21.9%) in the 5-MU groups (p = 0.17). CONCLUSIONS: Sustained virological response to combined interferon alpha-2b and ribavirin was significantly higher in relapse patients than those who did not respond to prior interferon monotherapy. Although, when all treated patients were analyzed, there was no significant difference in sustained response between subjects receiving 3 and 5 MU of interferon, among the prior nonresponder patients, treatment with 5 MU of interferon with ribavirin resulted in a slightly increased response compared with treatment with the standard interferon dosage. The tolerability of the treatment regimens was comparable.

Adult↗

PubMed2001

A biological staging model for operable non-small cell lung cancer.

BACKGROUND: Currently the best prognostic index for operable non-small cell lung cancer (NSCLC) is the TNM staging system. Molecular biology holds the promise of predicting outcome for the individual patient and identifying novel therapeutic targets. Angiogenesis, matrix metalloproteinases (MMP)-2 and -9, and the erb/HER type I tyrosine kinase receptors are all implicated in the pathogenesis of NSCLC. METHODS: A retrospective analysis of 167 patients with resected stage I-IIIa NSCLC and >60 days postoperative survival with a minimum follow up of 2 years was undertaken. Immunohistochemical analysis was performed on paraffin embedded sections for the microvessel marker CD34, MMP-2 and MMP-9, EGFR, and c-erbB-2 to evaluate the relationships between and impact on survival of these molecular markers. RESULTS: Tumour cell MMP-9 (HR 1.91 (1.23-2.97)), a high microvessel count (HR 1.97 (1.28-3.03)), and stage (stage II HR 1.44 (0.87-2.40), stage IIIa HR 2.21 (1.31-3.74)) were independent prognostic factors. Patients with a high microvessel count and tumour cell MMP-9 expression had a worse outcome than cases with only one (HR 1.68 (1.04-2.73)) or neither (HR 4.43 (2.29-8.57)) of these markers. EGFR expression correlated with tumour cell MMP-9 expression (p<0.001). Immunoreactivity for both of these factors within the same tumour was associated with a poor prognosis (HR 2.22 (1.45-3.41)). CONCLUSION: Angiogenesis, EGFR, and MMP-9 expression provide prognostic information independent of TNM stage, allowing a more accurate outcome prediction for the individual patient. The development of novel anti-angiogenic agents, EGFR targeted therapies, and MMP inhibitors suggests that target specific adjuvant treatments may become a therapeutic option in patients with resected NSCLC.

Adult↗

PubMed2001

Survey of obstetrician-gynecologists in the United States about toxoplasmosis.

BACKGROUND: Although the incidence of toxoplasmosis is low in the United States, up to 6000 congenital cases occur annually. In September 1998, the Centers for Disease Control and Prevention held a conference about toxoplasmosis; participants recommended a survey of the toxoplasmosis-related knowledge and practices of obstetrician-gynecologists and the development of professional educational materials for them. METHODS: In the fall of 1999, surveys were mailed to a 2% random sample of American College of Obstetricians and Gynecologists (ACOG) members and to a demographically representative group of ACOG members known as the Collaborative Ambulatory Research Network (CARN). Responses were not significantly different for the random and CARN groups for most questions (p value shown when different). RESULTS: Among 768 US practicing ACOG members surveyed, 364 (47%) responded. Seven per cent (CARN 10%, random 5%) had diagnosed one or more case(s) of acute toxoplasmosis in the past year. Respondents were well-informed about how to prevent toxoplasmosis. However, only 12% (CARN 11%, random 12%) indicated that a positive Toxoplasma IgM test might be a false-positive result, and only 11% (CARN 14%, random 9%) were aware that the Food and Drug Administration sent an advisory to all ACOG members in 1997 stating that some Toxoplasma IgM test kits have high false-positive rates. Most of those surveyed (CARN 70%, random 59%; chi2 p < 0.05) were opposed to universal screening of pregnant women. CONCLUSIONS: Many US obstetrician-gynecologists will encounter acute toxoplasmosis during their careers, but they are frequently uncertain about interpretation of the laboratory tests for the disease. Most would not recommend universal screening of pregnant women.

Acute Disease↗

PubMed2001

Trends in HIV testing among pregnant women: United States, 1994-1999.

OBJECTIVES: This study evaluated 1995 guidelines for HIV testing of pregnant women. METHODS: Analysis focused on Behavioral Risk Factor Surveillance System data for the years 1994 through 1999. Data were aggregated across states. RESULTS: Percentages of pregnant women tested for HIV increased from 1995 to 1996 (from 41% to 53%) and again from 1997 (52%) to 1998 (60%). CONCLUSIONS: After implementation of the guidelines, the percentage of pregnant women tested for HIV increased, although nearly half had not been tested. More efforts are needed to encourage women to undergo testing for HIV during pregnancy, thus maximizing opportunities for offering antiretroviral therapy.

AIDS Serodiagnosis↗

PubMed2000

Electrophysiological deterioration during long-duration ventricular fibrillation.

BACKGROUND: Probability of survival from sudden cardiac arrest caused by ventricular fibrillation (VF) decreases rapidly with fibrillation duration. We hypothesized that cellular ischemia/fibrillation-induced electrophysiological deterioration underlies decreased survival. METHODS AND RESULTS: We determined fibrillation monophasic action potential (MAP) morphology including action potential frequency content, duration, cycle length, developing diastolic intervals, and amplitude as a function of ischemic fibrillation duration in 10 isolated rabbit hearts. We also correlated ECG frequency (used clinically) and MAP amplitude and frequency. Fibrillation cycle length and diastole duration increased, whereas APD(100) shortened significantly with time (P:<0.001). Between 1 and 3 minutes, diastole appeared primarily as the result of APD(100) shortening, with only small changes in cycle length. Between 2 and 5 minutes, diastole increased primarily as the result of increased cycle length. Diastole developed progressively from 5% of VF cycles at 5 seconds to approximately 100% of VF cycles by 120 seconds (P:<0.001). Diastole increased from 1% of cycle length at 5 seconds to 62% at 5 minutes. Its duration increased from 4.7 ms at 5 seconds to 90 ms at 5 minutes (P:<0.001). Both MAP and ECG 1/frequency closely correlated with fibrillation cycle length. CONCLUSIONS: These results show a rapid and progressive electrophysiological deterioration during fibrillation, leading to electrical diastole between fibrillation action potentials. This rapid deterioration may explain the decreased probability of successful resuscitation after prolonged fibrillation. Therefore, a greater understanding of cellular deterioration during fibrillation may lead to improved resuscitation methods, including development of specific defibrillator waveforms for out-of-hospital cardiac arrest.

Action Potentials↗

PubMed2000

Effect of influenza vaccination on disease progression among HIV-infected persons.

OBJECTIVE: To describe the effect of influenza vaccination on long-term change in CD4 count and HIV RNA level, and on progression to AIDS or death. DESIGN AND SETTING: A longitudinal medical record review set in 113 medical clinics in 10 United States cities. PATIENTS: A total of 36,050 HIV-infected persons aged > or = 13 years in care for HIV infection. MAIN OUTCOME MEASURES: Change in CD4 count and HIV RNA level at follow-up (3-12 months after vaccination); hazard ratios (HR) for association of influenza vaccine with progression from baseline CD4 or HIV RNA level to AIDS and to death. RESULTS: The median CD4 count among all persons decreased 28 cells/year during follow-up, with no difference in change in CD4 count between the 8007 (40%) vaccinated (median = 6 months, vaccine to follow-up CD4 count) and the 11,794 unvaccinated persons. In a viral load subanalysis, median HIV RNA level decreased 90 copies/ml per year among all persons during follow-up; decreases were not different between vaccinated and unvaccinated persons (median = 7 months, vaccine to follow-up HIV RNA level determination). Influenza vaccination was weakly associated with decreased risk of progression to clinical AIDS [HR 0.93; 95% confidence interval (CI), 0.87-0.99], but not associated with time to death (HR, 0.97; CI, 0.93-1.01). CONCLUSIONS: No negative long-term effect of influenza vaccination on CD4 counts, HIV RNA levels, or progression to AIDS or death was found in this HIV-infected population. These data suggest that physicians should not withhold influenza vaccine because of concerns about long-term detrimental effects of increased viral replication.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Aspergillosis among people infected with human immunodeficiency virus: incidence and survival. Adult and Adolescent Spectrum of HIV Disease Project.

Aspergillosis is a life-threatening fungal infection in immunocompromised people, including people infected with human immunodeficiency virus (HIV). We determined the incidence of aspergillosis among HIV-infected people and survival after aspergillosis diagnosis by use of a national HIV surveillance database. Among 35,252 HIV-infected patients, the incidence of aspergillosis was 3.5 cases per 1000 person-years (p-y; 95% confidence interval [CI], 3.0-4.0 per 1000 p-y). Incidence was higher among people aged > or =35 years (4.1 per 1000 p-y, 95% CI, 3. 5-4.8), among people with CD4 counts of 50-99 cells/mm(3) (5.1 per 1000 p-y, 95% CI, 2.8-7.3), or CD4 counts of <50 cells/mm(3) (10.2 per 1000 p-y, 95% CI, 8.0-12.2), versus people with CD4 counts of >200 cells/mm(3), people with > or =1 acquired immune deficiency syndrome-defining opportunistic illness (8.6 per 1000 p-y, 95% CI, 7.4-9.9), and people who were prescribed at least one medication associated with neutropenia (27.7 per 1000 p-y, 95% CI, 21.0-34.3). Median survival time after diagnosis of aspergillosis was 3 months, and 26% survived for > or =1 year. These findings suggest that aspergillosis is uncommon, occurs especially among severely immunosuppressed or leukopenic HIV-infected people, and is associated with poor survival.

AIDS-Related Opportunistic Infections↗

PubMed2000

Association between crack cocaine use and high-risk sexual behaviors after HIV diagnosis.

OBJECTIVE: To describe the prevalence of crack cocaine use in an HIV-infected population and to examine the association between crack use after HIV diagnosis and high-risk sexual behaviors for heterosexual men, heterosexual women, and men who have sex with men (MSM). METHODS: Analysis of cross-sectional interviews conducted from January 1995 through December 1998 with HIV infected adults in 12 states. RESULTS: Of 10,415 persons with HIV or AIDS, 66.6% never used crack, 10.7% used crack before HIV diagnosis but not after, and 22.7% used crack after diagnosis. High-risk sexual behaviors were more prevalent among those who had ever used crack and were most prevalent among those who used crack after diagnosis. In multivariable analyses, crack use after diagnosis was associated with having multiple sex partners and trading sex for drugs/money in all three groups: heterosexual men, heterosexual women, and MSM. For heterosexual women and MSM, crack use after diagnosis was associated with unprotected sex with a main partner, and among heterosexual men and MSM, with unprotected sex with casual partners. CONCLUSIONS: Crack use after HIV diagnosis was associated with high-risk sexual behaviors. Treatment programs to assist people in quitting crack are needed to help reduce the risk of HIV transmission from this population.

Adolescent↗

PubMed2000

Risk for preventable opportunistic infections in persons with AIDS after antiretroviral therapy increases CD4+ T lymphocyte counts above prophylaxis thresholds.

To determine incidence and risk for preventable opportunistic infections (Pneumocystis carinii pneumonia [PCP] and disseminated Mycobacterium avium-complex [MAC] infection) in persons whose CD4(+) T lymphocyte counts had increased by >/=100 cells/microL to exceed the threshold of risk and in persons whose CD4(+) counts had never dropped below the threshold of risk, we analyzed data collected during the period 1990-1998 in the Adult/Adolescent Spectrum of HIV (Human Immunodeficiency Virus) Disease Project. Using a counting-process formulation of the Cox model, we analyzed observation time in these 2 groups for persons who were prescribed antiretroviral therapy but not prophylaxis. The incidences of the infections were low for patients whose CD4(+) count rose above the threshold of risk (PCP, 0.6 cases per 100 person-years [PY]; MAC, 1. 0 cases per 100 PY) and not higher than in persons whose CD4(+) counts had not decreased below these thresholds, which suggests that discontinuation of primary prophylaxis for opportunistic infections may be considered for some patients.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Incidence and trends in Kaposi's sarcoma in the era of effective antiretroviral therapy.

OBJECTIVE: To evaluate the impact of antiretroviral and antiherpesvirus therapies on the incidence of KS and assess trends in incidence of Kaposi's sarcoma (KS) in a large multicenter HIV/AIDS surveillance system between 1990 and 1998. METHODS: Incidence was calculated per 100 person-years (py); the effects of therapies on risk for KS were calculated by using multivariate Poisson regression controlling for gender, race/ethnicity, age, HIV exposure mode, CD4+ cell count, and calendar year. Antiretroviral therapy was defined as monotherapy, dual therapy, or triple therapy (95% of triple therapy regimens contained a protease inhibitor). Acyclovir, ganciclovir, and foscarnet were the antiherpesvirus therapies evaluated. RESULTS: There were 37,303 HIV-infected people in the study contributing 70,238 py. Those prescribed triple antiretroviral therapy had a 50% reduction in the incidence of KS (95% confidence interval, 20%-70%) compared with those who were not prescribed antiretroviral therapy and there was a reduction in risk for KS among persons prescribed foscarnet (p =.05). Overall, KS incidence declined an estimated 8.8% per year (observed incidence 4. 1 per 100 py in 1990 to 0.7 per 100 py in 1998; p <.001). CONCLUSION: Incidence of KS is declining in this large U.S. population and may continue to decline as new, more effective antiretroviral agents are developed and used widely.

AIDS-Related Opportunistic Infections↗

PubMed2000

Preventing congenital toxoplasmosis.

SCOPE OF THE PROBLEM: Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii. Acute infections in pregnant women can be transmitted to the fetus and cause severe illness (e.g., mental retardation, blindness, and epilepsy). An estimated 400-4,000 cases of congenital toxoplasmosis occur each year in the United States. Of the 750 deaths attributed to toxoplasmosis each year, 375 (50%) are believed to be caused by eating contaminated meat, making toxoplasmosis the third leading cause of foodborne deaths in this country. ETIOLOGIC FACTORS: Toxoplasma can be transmitted to humans by three principal routes: a) ingestion of raw or inadequately cooked infected meat; b) ingestion of oocysts, an environmentally resistant form of the organism that cats pass in their feces, with exposure of humans occurring through exposure to cat litter or soil (e.g., from gardening or unwashed fruits or vegetables); and c) a newly infected pregnant woman passing the infection to her unborn fetus. RECOMMENDATIONSFOR PREVENTION: Toxoplasma infection can be prevented in large part by a) cooking meat to a safe temperature (i.e., one sufficient to kill Toxoplasma); b) peeling or thoroughly washing fruits and vegetables before eating; c) cleaning cooking surfaces and utensils afterthey have contacted raw meat, poultry, seafood, or unwashed fruits or vegetables; d) pregnant women avoiding changing cat litter or, if no one else is available to change the cat litter, using gloves, then washing hands thoroughly; and e) not feeding raw or undercooked meat to cats and keeping cats inside to prevent acquisition of Toxoplasma by eating infected prey. RESEARCH AGENDA: Priorities for research were discussed at a national workshop sponsored by CDC in September 1998 and include a) improving estimates of the burden of toxoplasmosis, b) improving diagnostic tests to determine when a person becomes infected with Toxoplasma, and c) determining the applicability of national screening programs. CONCLUSION: Many cases of congenital toxoplasmosis can be prevented. Specific measures can be taken by women and their health-care providers to decrease the risk for infection during pregnancy and prevent severe illness in newborn infants.

Female↗

PubMed2000

Epidemiology of thrombosis in HIV-infected individuals. The Adult/Adolescent Spectrum of HIV Disease Project.

OBJECTIVE: To describe the incidence of clinically recognized thrombosis and associated factors among individuals infected with HIV. DESIGN: A longitudinal medical record review. SETTING: Over 100 medical clinics in nine US cities. PATIENTS: A total of 42 935 individuals aged 13 years or older with HIV infection, observed for an average of 2.4 years. MAIN OUTCOME MEASURES: The incidence of thrombosis among HIV-infected individuals; adjusted odds ratios for factors associated with thrombosis. RESULTS: The incidence of thrombosis among HIV-infected individuals was 2.6/1000 person-years (PY). Factors significantly associated with thrombosis included: age of 45 or more years (adjusted odds ratio [AOR], 1.9; 95% confidence interval [CI], 1.4-2.7); a diagnosis of cytomegalovirus disease or retinitis (AOR, 1.9; CI, 1.2-2.9), or other AIDS-defining opportunistic illness (AOR, 1.5; CI, 1.1-2.2); hospitalization (AOR, 3.3; CI, 2.5-4.4); and the prescription of megestrol acetate (AOR, 2.0; CI 1.3-2.9) or indinavir (AOR, 2.4; CI 1.4-4.3). The prescription of other protease inhibitors, sex, race, and mode of HIV exposure were not associated with thrombosis. CONCLUSION: Among HIV-infected individuals, clinically detected thrombosis is more common in those who have opportunistic illnesses, for whom megestrol acetate or indinavir have been prescribed, who have been hospitalized, and who are aged 45 years or older. Physicians should be aware of the risks of thrombosis in order to promote the early identification and appropriate treatment or prophylaxis. Further study is needed to characterize the association between indinavir and thrombosis.

Adolescent↗

PubMed2000

Angiogenesis and non-small cell lung cancer.

Lung cancer is the commonest cause of cancer death in the western world. Recent evidence suggests that angiogenesis is related to poor prognosis in many solid tumours including non-small cell lung cancer. Angiogenesis is controlled by a complex interaction between growth and apoptotic factors, proteases and adhesion molecules. The angiogenic process may prove a target for novel therapies such as matrix metalloproteinase inhibitors, growth factor antisense RNA, growth factor receptor antagonists and naturally occurring antiangiogenic peptides. These agents may be used alone or in combination with traditional chemotherapy, radiotherapy and surgery.

Angiogenesis Inhibitors↗

PubMed2000

Localization of matrix metalloproteinase 2 within the aneurysmal and normal aortic wall.

BACKGROUND: Current research has shed new light on the role of matrix metalloproteinase (MMP) 2 in the development of abdominal aortic aneurysms (AAAs). MMP-2 is a major protease in the wall of small aneurysms and is produced at increased levels by smooth muscle cells derived from AAAs compared with normal controls. In vivo, MMP-2 is produced as an inactive proenzyme that is activated predominantly by the cell membrane-bound enzyme, membrane type 1 matrix metalloproteinase (MT1-MMP). This study investigated the production of the MMP-2-MT1-MMP-tissue inhibitor of metalloproteinases (TIMP) 2 system within the wall of aortic aneurysms and in age-matched control arterial tissue. METHODS: Arterial tissue from four patients with aortic aneurysms and four age-matched aortic samples was examined for the production and expression of MMP-2, TIMP-2 and MT1-MMP protein using immunohistochemistry, in situ hybridization and in situ zymography. RESULTS: All components of the MMP-2-TIMP-2-MT1-MMP enzyme system were detected in the arterial wall of both aneurysm and control samples, specifically in the medial tissue. The enzymes co-localized with medial smooth muscle cells. Gelatinolytic activity was localized to elastin fibres in normal and aneurysmal aorta. CONCLUSION: The presence of MT1-MMP within the media of arterial tissue suggests a powerful pathway for the activation of MMP-2. The localization of the MMP-2-TIMP-2-MT1-MMP enzyme system to the medial layer of the arterial wall gives support to the concept that this system may play an aetiological role in the pathogenesis of AAAs.

Aged↗