Ligands with an NPNPN-framework and their application in chromium catalysed ethene tri-/tetramerization.

Novel Cr(iii) catalysts supported by linear phosph(iii)azanes of the type R(1)R(2)N-P(Ph)-NR(3)-P(Ph)-NR(4)R(5) have been prepared, all of which, upon activation with MMAO-3A, are highly active for ethene tri-/tetramerization with considerable selectivity. The effect of ligand substitution as well as solvent on the catalytic performance has been examined.

Peripheral blood-derived, γ9δ2 t cell-enriched cell lines from glioblastoma multiforme patients exert anti-tumoral effects in vitro.

The goal of this work was to assess the potential of T cells expressing Vγ9Vδ2+ T cell receptors (TCR, γ9δ2T cells) present in peripheral blood (PB) m ononuclear cells (MC, PBMC) of glioblastoma multiforme (GBM) patients to act as anti-tumoral agents. We found that γ9δ2T cell levels were decreased in patients' PB relative to a cohort of healthy donors (HD) (respectively 0.52±0.55%, n=16, vs 1.12±0.6%, n=14, p=0.008) but did not significantly correlate with postoperative survival (R=0.6, p=0.063). Importantly, however, the γ9δ2T cells could be expanded in vitro to consist 51±23% of the cultured lymphocytes (98% CD3+). This was achieved after 14 days of culture in medium containing the amino-bisphosphonate (ABP) Zoledronate (Zol) and interleukin (IL)-2, resulting in γ9δ2T cell-enriched lines (gdTCEL) similar to those of HD derived gdTCEL (54±19%). Moreover, gdTCEL from patients and HD mediated cytotoxicity to GBM-derived cell lines (GBMDCL), which was abrogated by immune-magnetic removal of the γ9δ2T cells. Furthermore, low level interferon (IFN) γ secretion was induced by gdTCEL briefly co-cultured with GBMDCL or autologous - tumor-derived cells, which was greatly amplified in the presence of Zol. Importantly, IFNγ secretion was inhibited by mevastatin but enhanced by cross-linking of butyrophilin 3A1 (CD277) on a CD277+ GBMDCL (U251MG) or by pretreatment of GBMDCL with temozolomide (TMZ). Taken together, these data suggest that γ9δ2T cells in PB of GBM patients can give rise to gdTCEL that mediate anti-tumoral activities.

Gremlin-1 associates with fibrillin microfibrils in vivo and regulates mesothelioma cell survival through transcription factor slug.

Malignant mesothelioma is a form of cancer that is highly resistant to conventional cancer therapy for which no major therapeutic advances have been introduced. Here, we identify gremlin-1, a known bone morphogenetic protein inhibitor crucial for embryonic development, as a potential therapeutic target for mesothelioma. We found high expression levels of gremlin-1 in the mesothelioma tumor tissue, as well as in primary mesothelioma cells cultured from pleural effusion samples. Downregulation of gremlin-1 expression by siRNA-mediated silencing in a mesothelioma cell line inhibited cell proliferation. This was associated with downregulation of the transcription factor slug as well as mesenchymal proteins linked to cancer epithelial-to-mesenchymal transition. Further, resistance to paclitaxel-induced cell death was associated with high gremlin-1 and slug expression. Treatment of gremlin-1-silenced mesothelioma cells with paclitaxel or pemetrexed resulted in efficient loss of cell survival. Finally, our data suggest that concomitant upregulation of fibrillin-2 in mesothelioma provides a mechanism for extracellular localization of gremlin-1 to the tumor microenvironment. This was supported by the demonstration of interactions between gremlin-1, and fibrillin-1 and -2 peptides as well as by colocalization of gremlin-1 to fibrillin microfibrils in cells and tumor tissue samples. Our data suggest that gremlin-1 is also a potential target for overcoming drug resistance in mesothelioma.

The acceptability of a directly-administered antiretroviral therapy (DAART) intervention among patients in public HIV clinics in Los Angeles, California.

Directly administered antiretroviral therapy (DAART) is an intensive adherence support strategy for highly active antiretroviral therapy (HAART) that requires patient acceptance to be effective. In one arm of a randomized adherence study, community workers (CW) delivered and observed ingestion of one HAART dose to participants five days a week for six months. We evaluated acceptability by study participation, retention, attendance and a satisfaction survey. Chi-square and nonparametric tests were used to examine differences between participants who did and did not complete DAART. Between November 2001 and March 2004, 416 eligible participants were identified; 250 were enrolled and 166 refused to participate (22 of these (13%) because of DAART specifically). Of the 82 randomized to DAART (70% Latino, 20% African American, 27% female and 69% foreign-born), 65 (79%) completed six months of DAART. Participants attended 6,953/7,390 (94%) appointments. Latinos were more likely to complete DAART compared to African Americans (OR=4.76, 95%CI=1.38, 16.44, p=0.01). In addition, foreign-born participants were more likely to complete DAART than US-born participants (OR=3.38, 95%CI=1.11-10.22, p=0.03). Participants completing DAART reported high rates of satisfaction. Retention, attendance and participant satisfaction suggest that DAART is an acceptable adherence support strategy in this public clinic population, particularly among Latino and foreign-born participants.

Comparison of AIDS progression and survival in persons with pulmonary versus extrapulmonary tuberculosis in Los Angeles.

The objective of this research was to compare the demographics, acquired immune deficiency syndrome (AIDS) progression, and survival in persons with AIDS with pulmonary tuberculosis (PTB) versus extrapulmonary tuberculosis (EPTB), because there are limited population-based data on this topic. A population-based longitudinal study with 3 years of follow-up was performed. Data were collected every 6 months from medical records of persons with AIDS and TB treated at private and public medical facilities throughout Los Angeles County (LAC). Participants included a population-based sample of 216 persons with AIDS and PTB and 166 persons with AIDS and EPTB (including 113 persons with both PTB and EPTB), with an AIDS diagnosis reported in 1993. Compared to persons with AIDS with PTB, persons with AIDS and EPTB were 2.2 times more likely to be Latino than white (95% confidence intervals [CIs]: 1.2, 4.0) and 1.7 times more likely to be foreign-born (95% CIs: 1.1, 2.5). Compared to persons with AIDS with PTB, persons with AIDS and EPTB had similar antiretroviral and PCP prophylaxis use; lower CD4 counts at time of AIDS diagnosis (p = 0.0004); no differences in CD4 counts over the total follow-up period (p = 0.4); higher rates of total opportunistic infections (OIs) (incidence density ratio [IDR] = 2.0; 95% CIs: 1.6, 2.4); and comparable survival curves (p = 0.07). Persons with AIDS and EPTB had a more complicated medical course with lower CD4 counts at time of AIDS diagnosis and more OIs over the follow-up period than persons with AIDS and PTB, however the survival profiles for the two groups were comparable.

Evolving characteristics of AIDS-related lymphoma.

Over time, the epidemiologic and demographic characteristics of AIDS have changed in the United States, while the use of highly active antiretroviral therapy has changed the natural history of the disease. The goal of the study was to ascertain any changes in the epidemiologic, immunologic, pathologic, or clinical characteristics of AIDS-related lymphoma (ARL) over the course of the AIDS epidemic. Records of 369 patients with ARL diagnosed or treated at a single institution from 1982 through 1998 were reviewed. Single institutional data were compared to population-based data from the County of Los Angeles. Significant changes in the demographic profile of patients with newly diagnosed ARL have occurred, with the later time intervals associated with a higher prevalence in women (P =.25), in Latino/Hispanic individuals (P <.0001), and in those who acquired human immunodeficiency virus (HIV) heterosexually (P =.01). These changes were similar in both countywide, population-based analyses and in those from the single institution. The median CD4(+) lymphocyte count at lymphoma diagnosis has decreased significantly over the years, from 177/dL in the earliest time period (1982-1986), to 53/dL in the last time period from 1995 to 1998 (P =.0006). The pathologic spectrum of disease has also changed, with a decrease in the prevalence of small noncleaved lymphoma (P =.0005) and an increase in diffuse large cell lymphoma (P <.0001). Despite changes in the use of antiretroviral or chemotherapy regimens, the median survival has not significantly changed.

High-risk behaviors during incarceration in African-American men treated for HIV at three Los Angeles public medical centers.

OBJECTIVES: This paper describes research that examined the association between high-risk sexual and drug-using behaviors during incarceration and HIV infection for African-American men receiving HIV care at three public medical centers in Los Angeles County (LAC), California. METHODS: A case-control study was conducted in which 305 HIV-infected African-American men and 305 neighborhood controls, ages 20 to 49, were frequency-matched by age. RESULTS: After controlling for anal sex while not incarcerated, we found no association between anal sex during incarceration and HIV (odds ratio [OR], 1.1; 95% confidence interval [CI], 0.6-2.2). Among men with a history of incarceration (n = 332), the percentage reporting anal sex with men outside of incarceration (45%) was greater than those reporting anal sex while incarcerated (16%). Injection drug use (IDU) during incarceration was also not associated with HIV when controlling for IDU outside of incarceration (OR, 1.6; 95% CI, 0.5- 4.9). Increased time in jail or prison was associated with less HIV infection (p =.001). CONCLUSIONS: Although high-risk behaviors are more common in the community than in the incarcerated setting for this study group, incarcerated populations represent a high-risk group for whom access to prevention messages is limited. Periods of incarceration represent a unique opportunity to convey prevention messages that focus on high-risk behaviors outside the incarcerated setting.

Sociodemographic and behavioral characteristics of African-American women with HIV and AIDS in Los Angeles County, 1990-1997.

African-American women have the highest AIDS rate of any racial/ethnic group of women in both Los Angeles County (LAC), California and in the United States. Limited population-based epidemiologic studies of African-American women with HIV and AIDS describe this group and examine the factors associated with the excessive rates. Interview data collected from 1990 to 1997 on a population-based sample of AIDS cases and a group of HIV-infected women in LAC were analyzed to highlight the sociodemographic and behavioral characteristics of African-American women. This group of African-American women with HIV or AIDS in LAC were unemployed (88%), single mothers (64%), living on public assistance (86%) with annual household incomes <$10,000 U.S. (76%). A history of crack use predominated (50%). Compared with women of other races with HIV and AIDS, African-American women reported more sexual partners; reported more infections with sexually transmitted diseases; sought treatment for their HIV infection later; were more likely to trade sex; and were almost five times more likely to have ever used crack cocaine. HIV prevention for African-American women in LAC should focus on improving self-esteem and negotiation skills within the context of the crack cocaine culture and the disadvantaged social and economic situation described.

Evaluation of lead levels in children living near a Los Angeles county battery recycling facility.

This cross-sectional study examined the association between environmental lead measurements surrounding a Los Angeles County battery recycling facility and the blood lead levels of the children living nearby. Environmental lead measurements and blood lead levels of young children living in a community adjacent to a stationary lead source were compared to those living in a community without a stationary lead source. Predictors of blood lead level were identified. The blood lead levels of the children living near the secondary lead smelter were within the normal range (< 5 micrograms/dl). The absence of ground cover was associated with slightly increased blood lead levels; however, this increase was not of biological significance. Lead levels in surface soil near the stationary lead source were elevated compared to the control community; however, the soil affected community, which may be due in part to controls recently installed at the stationary lead source.

Occupational injury in female aerospace workers.

We conducted a population-based case-control study in women in high-risk manufacturing occupations to examine occupational injury and its association with possible risk factors inside and outside the work place. The primary hypothesis was that women with young children are at greater risk of occupational injury than are women without young children, owing to the responsibility and fatigue associated with raising young children. The odds of reported injury was 2.9 times greater in women with a child less than 6 years of age than in women without children less than age 6 [odds ratio (OR) = 2.9; 95% confidence interval (CI) = 1.5-5.6]. The same effect was not observed for women with older children. Other predictors of injury were a history of previous injury (OR = 2.7; 95% CI = 1.8-3.9) and a body mass index greater than or equal to 25 (OR = 1.6; 95% CI = 1.08-2.4). We found small or zero effects for age, years of work experience, total number of children at home, ethnicity, marital status, and shift worked. These findings indicate that factors outside the work place, such as the presence of young children at home, may increase the risk of occupational injury for women employed in manufacturing jobs.

Thallium-201 myocardial perfusion studies in patients with the mitral valve prolapse syndrome.

To determine whether regional myocardial ischemia plays a role in patients with the mitral valve prolapse syndrome, we examined myocardial perfusion with exercise stress testing and thallium-201 myocardial scintigraphy. Twelve patients were studied, 11 women and one man aged 18 to 56 years, mean age 30 years. In all patients, mitral valve prolapse was documented by echocardiography or phonocardiography. Patients over 35 years of age underwent cardiac catheterization. Electrocardograms disclosed abnormalities during maximal exercise in eight of the 12 patients. In two patients, angina developed during exercise. Thallium-201 (201Tl) scintigrams were normal in the 11 patients with presumed or documented normal coronary arteries. One patient, in whom an apical defect was demonstrated on scintigraphy, had significant disease of the left main and left anterior descending coronary artery. Repeat testing after successful aortocoronary bypass grafting revealed improved exercise capacity and a normal 201Tl myocardial scintigram. The data indicate that patients with mitral valve prolapse alone do not have regional myocardial ischemia and that the presence of a defect on 201Tl myocardial scintigraphy following maximal stress testing would suggest the existence of concomitant coronary artery disease.

Cardiovascular function during early recovery from acute myocardial infarction.

Fifty patients with acute myocardial infarction were studied serially to evaluate the extent and nature of functional cardiovascular impairment and the time course of recovery. Reinfarction or death occurred in six patients. Peak workload during bicycle exercise in a subgroup of 25 patients with maximal initial test and complete follow-up increased from 334 to 409 kpm/min (P less than 0.01) bwtween three and six weeks. There was further significant (P less than 0.01) improvement between three and six months from 438 to 488 kpm/min. The incidence of ischemia at a constant workload decreased between three and six weeks without any significant changes in heart rate or blood pressure. Mean cardiac output during exercise at three months was 6.5 and at six months 7.8 L/min (P less than 0.05). Corresponding values for stroke volume were 61 and 72 ml (P less than 0.05). The data suggest that in clinically stable patients there is an early improvement of the relation between myocardial oxygen supply and demand and a late improvement of functional capacity associated with increased stroke volume and cardiac output.

Pharmacology of Sch 11973, N-(2-phenylisopropyl)-N-p-toluene sulfonyl urea, a potential new antianginal agent.

Antianginal drugs were evaluated on the basis of their ability to protect against subepicardial electrogram changes induced by local ventricular ischemia in anesthetized dogs. Sch 11973 [N-(2-phenylisopropyl)-N-p-toluene sulfonyl urea], a potential new antianginal agent, was also effective against local ventricular ischemia with its maximum effect appearing at 1mg/kg, i.v. or i.d. and with a duration of at least 2 hours. Nitroglycerin, at a dose of 0.04 mg/kg given bucally, exerted less protection, lasting on the average less than 15 minutes. Protection by propranolol at 1 mg/kg, i.v., was not better than nitroglycerin, but lasted up to one hour, while dipyridamole was ineffective when given in a dose range of 0.1-10 mg/kg, i.v. Sch 11973 differed from standard antianginal agents which may act via beta-adrenergic blocking activity or alteration of cardiac or circulatory dynamics since no acute pharmacological changes were observed after Sch 11973 was administered.

Prognosis of patients permanently paced for sick sinus syndrome.

In 39 patients (mean age, 66 years) treated for sick sinus syndrome (SSS) with pacemaker insertion, the long-term prognosis was studied. Fifteen patients (42%) died during the follow-up period of 6 to 59 months (mean, 25 months). Three patients were unavailable for follow-up. Eleven of the 15 deaths (73%) were cardiac-related, yet none could be associated with either an arrhythmia or pacemaker failure. Symptoms recurred or persisted after pacemaker insertion in 14 patients (mean age, 71 years), nine of whom died (31 deaths per 100 patient follow-up years). Twenty-two patients (mean age, 63 years) were asymptomatic after pacer insertion, six of whom died (11 deaths per 100 patient follow-up years). These follow-up results demonstrate a poor long-term prognosis in patients with SSS and persistent symptoms following permanent pacing.