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Biomedical subjects

J Dilley

Publications and source records attributed to J Dilley.

At least 19 recordsLinked to original sources
PubMed2006

Increases in sexually transmitted infections and sexual risk behaviour without a concurrent increase in HIV incidence among men who have sex with men in San Francisco: a suggestion of HIV serosorting?

BACKGROUND: Sexually transmitted infections (STI) and unprotected anal intercourse (UAI) have been increasing among men who have sex with men (MSM) in San Francisco. However, HIV incidence has stabilised. OBJECTIVES: To describe recent trends in sexual risk behaviour, STI, and HIV incidence among MSM in San Francisco and to assess whether increases in HIV serosorting (that is, selective unprotected sex with partners of the same HIV status) may contribute to preventing further expansion of the epidemic. METHODS: The study applies an ecological approach and follows the principles of second generation HIV surveillance. Temporal trends in biological and behavioural measures among MSM were assessed using multiple pre-existing DATA SOURCES: STI case reporting, prevention outreach programmatic data, and voluntary HIV counselling and testing data. RESULTS: Reported STI cases among MSM rose from 1998 through 2004, although the rate of increase slowed between 2002 and 2004. Rectal gonorrhoea cases increased from 157 to 389 while early syphilis increased from nine to 492. UAI increased overall from 1998 to 2004 (p<0.001) in community based surveys; however, UAI with partners of unknown HIV serostatus decreased overall (p<0.001) among HIV negative MSM, and among HIV positive MSM it declined from 30.7% in 2001 to a low of 21.0% in 2004 (p<0.001). Any UAI, receptive UAI, and insertive UAI with a known HIV positive partner decreased overall from 1998 to 2004 (p<0.001) among MSM seeking anonymous HIV testing and at the STI clinic testing programme. HIV incidence using the serological testing algorithm for recent HIV seroconversion (STARHS) peaked in 1999 at 4.1% at the anonymous testing sites and 4.8% at the STI clinic voluntary testing programme, with rates levelling off through 2004. CONCLUSIONS: HIV incidence among MSM appears to have stabilised at a plateau following several years of resurgence. Increases in the selection of sexual partners of concordant HIV serostatus may be contributing to the stabilisation of the epidemic. However, current incidence rates of STI and HIV remain high. Moreover, a strategy of risk reduction by HIV serosorting can be severely limited by imperfect knowledge of one's own and one's partners' serostatus.

Adult↗
PubMed2001

Incidence of human immunodeficiency virus among male-to-female transgendered persons in San Francisco.

OBJECTIVE: To estimate HIV incidence among male-to-female transgendered persons (MtF transgendered persons) who repeatedly tested for HIV antibodies at public San Francisco counseling and testing sites between July 1997 and June 2000. METHODS: HIV seroconversions were identified and person-time of observation were estimated using the date and result of the current test and the self-reported date and result of the previous test. Factors independently associated with HIV seroconversion were determined using multivariable proportional hazard analysis. RESULTS: HIV incidence was 7.8 per 100 person-years (95% confidence intervals [CI], 4.6-12.3) based on 13 seroconversions among 155 repeat testers with 167.7 person-years of observation. African-American race/ethnicity (adjusted relative hazard ratio [HR], 5.0; 95% CI, 1.5-16.2) and unprotected receptive anal intercourse (HR, 3.9; 95% CI, 1.2-13.1) were independent predictors of HIV seroconversion. CONCLUSIONS: HIV is currently spreading at an extremely high rate among MtF transgendered persons in San Francisco, especially those who are African Americans.

Adult↗
PubMed2001

CV706, a prostate cancer-specific adenovirus variant, in combination with radiotherapy produces synergistic antitumor efficacy without increasing toxicity.

Radiation is an effective means of treating localized prostate cancer. However, up to 40% of men with certain risk factors will develop biochemical failure 5 years after radiotherapy. CV706, a prostate cell-specific adenovirus variant, is currently in clinical trials for the treatment of recurrent organ-confined prostate cancer. We demonstrated previously that a single administration of CV706 at 5 x 10(8) particles/mm3 of tumor eliminated established tumors within 6 weeks in nude mouse xenografts (Rodriguez et al., Cancer Res. 57: 2559-2563, 1997). We now demonstrate that CV706-mediated cytotoxicity is synergistic with radiation. In vitro, addition of radiation to CV706 resulted in a synergistic increase of cytotoxicity toward the human prostate cancer cell line LNCaP and a significant increase of virus burst size, with no reduction in specificity of CV706-based cytopathogenicity for prostate cancer cells. In vivo, prostate-specific antigen (+) LNCaP xenografts of human prostate cancer were treated with CV706 (1 x 10(7) particles/mm3 of tumor), 10 Gy of single fraction local tumor radiation, or both. Tumor volumes of the group treated with CV706 or radiation was 97% or 120% of baseline 6 weeks after treatment. However, when the same dose of CV706 was followed 24 h later with the same dose of radiation, the tumor volume dropped to 4% of baseline at this time point and produced antitumor activity that was 6.7-fold greater than a predicted additive effect of CV706 and radiation. Histological analyses of tumors revealed that, compared with CV706 or radiation alone, combination treatment with two agents increased necrosis by 180% and 690%, apoptosis by 330% and 880%, and decreased blood vessel number by 1290% and 600%, respectively. Importantly, no increase in toxicity was observed after combined treatment when compared with CV706 or radiation alone. These data demonstrate that CV706 enhances the in vivo radioresponse of prostate tumors and support the clinical development of CV706 as a neoadjuvant agent with radiation for localized prostate cancer.

Adenoviridae↗
PubMed2001

Antitumor synergy of CV787, a prostate cancer-specific adenovirus, and paclitaxel and docetaxel.

CV787, a PSA+ prostate cell-specific adenovirus variant, is currently in Phase I/II clinical trials for the treatment of prostate cancer. We have previously demonstrated that a single administration of CV787 at 1 x 10(11) particle/animal could eliminate established tumors within 6 weeks in nude mouse xenografts (Yu et al., Cancer Res., 59: 4200-4203, 1999). We now demonstrate that CV787-mediated replication-dependent cytotoxicity is synergistic with the chemotherapeutic agents paclitaxel (Taxol) or docetaxel (Taxotere) both in vitro and in vivo. In vitro, cells were pretreated with CV787 24 h before taxane, pretreated with taxane 24 h before CV787, or treated with both agents simultaneously. Cell viability was determined at various time points by 3-[4,5-dimethylthiazole-2-4]-2,5-diphenyl-2H-tetrazolium bromide assay, and virus yield was examined by plaque assay. Addition of taxane to CV787 resulted in a synergistic increase of cytotoxicity toward the human prostate cancer cell line LNCaP, regardless of the timing of administration. There was no reduction in virus replication or specificity of CV787-based cytopathogenicity for prostate cancer cells (approximately 10,000 to 1) with the taxanes. p53 expression was significantly elevated in the cells treated with CV787 and taxane. In vivo, using the PSA+ LNCaP xenograft model of prostate cancer, a single i.v. dose of 1 x 10(8) particles CV787 and docetaxel in combination eliminates large preexistent distant tumors. Toxicity studies do not show a synergistic increase of toxicity of CV787 and taxane. These experiments demonstrate a synergistic antitumor efficacy for CV787 when combined with taxane and demonstrate an in vivo single-dose curative therapeutic index for CV787 of over 1000:1.

Adenoviridae↗
PubMed2000

Mitochondrial ND1 sequence analysis and association of the T4216C mutation with Parkinson's disease.

Mitochondrial dysfunction originating from mutations in Complex I genes may play a role in the pathogenesis of Parkinson's disease (PD). In this study, the entire ND1 coding sequence was sequenced in 84 newly diagnosed PD cases and 127 age/gender-matched controls. Numerous missense mutations were found at low frequency (<5%), whereas a thymidine to cytosine missense mutation at position 4216 that results in the replacement of tyrosine with histidine was found in 25% of the PD case samples and in 18% of the controls. When calculated according to gender, the 4216 mutation was observed in 26% of the male cases versus 16% of male controls (Odds Ratio [OR] = 1.85; 95% CI = 0.79-4.34). In contrast, females exhibited approximately equal frequencies among cases (22.5%) and controls (21%), yielding an OR of 1.08 (95% C.I. = 0.36-3.22). The findings indicate only a weak association of this genetic variant with PD.

Humans↗
PubMed1999

Detection of early HIV infection and estimation of incidence using a sensitive/less-sensitive enzyme immunoassay testing strategy at anonymous counseling and testing sites in San Francisco.

Timely estimates of HIV incidence are needed to monitor the epidemic and target primary prevention but have been difficult to obtain. We applied a sensitive/ less-sensitive (S/LS) enzyme immunoassay (EIA) testing strategy to stored HIV-positive sera (N = 452) to identify early infections, estimate incidence, and characterize correlates of recent seroconversion among persons seeking anonymous HIV testing in San Francisco from 1996 to 1998 (N = 21,292). Sera positive on a sensitive EIA but negative on a less-sensitive EIA were classified as early HIV infections; sera positive on both EIA were classified as long standing. Seventy-nine sera were from people with early HIV infection. Estimated HIV incidence was 1.1% per year (95% confidence interval [CI], 0.68%-1.6%) overall and 1.9% per year (95% CI, 1.2%-3.0%) among men who have sex with men (MSM). Early HIV infection among MSM was associated with injection drug use, unprotected receptive anal sex, and multiple sex partners in the previous year. No temporal trend in HIV incidence was noted over the study period. The S/LS strategy provides a practical public health tool to identify early HIV infection and estimate HIV incidence in a variety of study designs and settings.

Adult↗
PubMed1999

The addition of adenovirus type 5 region E3 enables calydon virus 787 to eliminate distant prostate tumor xenografts.

CV787, a novel highly prostate-specific replication-competent adenovirus with improved efficacy, was constructed. CV787 contains the prostate-specific rat probasin promoter, driving the adenovirus type 5 (Ad5) E1A gene, and the human prostate-specific enhancer/promoter, driving the E1B gene. To improve efficacy, we constructed CV787 such that it also contains the entire Ad5 E3 region. CV787 replicates in prostate-specific antigen (PSA)+ cells as well as wild-type adenovirus, but in PSA- cells, CV787 replicates 10(4)-10(5) times less efficiently. CV787 destroys PSA+ prostate cancer cells 10,000 times more efficiently than PSA- cells. Incorporation of the Ad5 E3 region significantly improves the target cell killing ability or efficacy of CV787. In nu/nu mice carrying s.c. LNCaP xenografts, a single i.v. tail vein injection of CV787 eliminates 300-mm3 tumors within 4 weeks. CV787 could be a powerful therapeutic for human metastatic prostate cancer.

Adenoviridae↗
PubMed1998

A genetic polymorphism of MAO-B modifies the association of cigarette smoking and Parkinson's disease.

In a population-based case-control study, we found a reversal of the association of cigarette smoking with Parkinson's disease (PD) in relation to the monoamine oxidase B intron 13 genetic polymorphism. A reduced PD risk related to pack-years of smoking was detected for persons with the G allele, whereas an opposite effect was found among persons with the A allele. These results indicate an unexplained interaction between cigarette smoking and this genetic polymorphism.

Adult↗
PubMed1997

Estimation of human immunodeficiency virus (HIV) seroincidence among repeat anonymous testers in San Francisco.

The authors approximated human immunodeficiency virus (HIV) seroincidence in a population of men who have sex with men and who sought repeated anonymous HIV testing in San Francisco in 1995. The number of seroconversions and person-years of observation were estimated using the date and result of the current test and the self-reported date and result of the previous test. Estimates for HIV seroincidence (2.8 per 100 person-years, 95% confidence interval 2.3-3.4) and predictors of seroconversion were similar to those estimated from a prospective study of men who have sex with men conducted in San Francisco at the same time. While the limitations of self-reported data in a self-selected population are recognized, data from repeat testers may provide a practical surveillance tool.

Adult↗
PubMed1995

Noninvasive localization of experimental atherosclerotic lesions with mouse/human chimeric Z2D3 F(ab')2 specific for the proliferating smooth muscle cells of human atheroma. Imaging with conventional and negative charge-modified antibody fragments.

BACKGROUND: A murine monoclonal antibody designated Z2D3 (IgM) generated against homogenized human atherosclerotic plaques was demonstrated to be highly specific for proliferating smooth muscle cells. The primary clone subsequently was genetically engineered to provide a mouse/human chimeric antibody with human IgG1 constant region expressed in a rat myeloma cell line. The resulting Z2D3-73.30 chimeric retained the immunoreactivity relative to the parent Z2D3-IgM and was pepsin-digested to yield F(ab')2. 111In-labeled chimeric Z2D3 F(ab')2 was then used for noninvasive imaging of experimental atherosclerotic lesions. To improve the imaging characteristics, we modified chimeric Z2D3 F(ab')2 fragments to carry a high negative charge. Improved visualization of targets with 111In-labeled, negatively charged, polymer-modified antibodies most probably is the result of faster blood clearance and a decrease in nontarget background activity. METHODS AND RESULTS: Experimental atherosclerotic lesions were induced in rabbits by deendothelialization of the infradiaphragmatic aorta followed by a 6% peanut oil-2% cholesterol diet. After 12 weeks, localization of the conventionally labeled 111In-Z2D3 F(ab')2 (24 Mbq [650 microCi]/500 to 750 micrograms) (n = 4) was compared with 111In-labeled, negatively charged, polymer-modified Z2D3 F(ab')2 (24 Mbq [650 microCi]/25 to 50 micrograms) in eight atherosclerotic rabbits. Three control rabbits also received radiolabeled polymer-modified Z2D3. Ten rabbits with atherosclerotic lesions received 111In-labeled nonspecific human IgG1 F(ab')2 with (n = 6) or without (n = 4) negative charge modification. Atherosclerotic lesions were visualized in all rabbits with the conventional Z2D3 F(ab')2 at 48 hours. However, unequivocal lesion visualization was possible at 24 hours only with negatively charged, polymer-modified Z2D3 F(ab')2. Quantitative uptake of F(ab')2 fragments was essentially determined by the presence of atherosclerotic lesions (F1.37 = 69.8; P < .0001) and the specificity of the antibody (F1.37 = 36.6; P < .0001). Uptake of the conventional Z2D3 in atherosclerotic lesions (mean +/- SEM percent injected dose per gram, 0.112 +/- 0.024%) was six times higher than background activity in the normal aortic segments (nondenuded thoracic aorta; mean percent injected dose per gram, 0.019 +/- 0.003%). Uptake of the conventional Z2D3 was also significantly higher than that of nonspecific human IgG1 F(ab')2 (0.027 +/- 0.004%). Specific uptake of the conventional Z2D3 in the lesions was comparable to the charge-modified Z2D3 uptake (0.084 +/- 0.017; P = .20). Uptake of negative charge-modified Z2D3 in the lesions was significantly higher than in the corresponding background activity in normal thoracic aorta (0.021 +/- 0.002). Uptake of negative charge-modified Z2D3 F(ab')2 in the lesions was higher than the uptake of negative charge-modified nonspecific IgG1 F(ab')2 (0.020 +/- 0.002) in the lesions. Uptake of charge-modified Z2D3 in the atherosclerotic lesions was also significantly higher than the corresponding regions of the aorta of the control rabbits (0.017 +/- 0.002; F1.18 = 27.9; P = .0001). There was, however, no difference in the specific lesion uptake of negative charge-modified Z2D3 at 24 hours (0.079 +/- 0.014) and 48 hours (0.084 +/- 0.0017; P = .99) after intravenous administration. Nontarget organ activities were lower with negative charge-modified 111In-labeled Z2D3 F(ab')2 than with the conventional Z2D3 F(ab')2. Mean kidney activity was fourfold less with the modified (0.45 +/- 0.06) than with the conventionally radiolabeled (1.67 +/- 0.264; P = .001) Z2D3 F(ab')2.

Animals↗
PubMed1994

Case management of substance abusers with HIV disease.

Case management is a promising intervention that has been used widely in many settings but is not well evaluated with substance abusers. This article describes a case management approach for substance abusers with human immunodeficiency virus (HIV) disease. Clients are enrolled from emergency and outpatient clinics of a general hospital. Case management focuses on encouraging a substance-free lifestyle, linking clients with needed services, and reducing their risk of transmitting HIV. A research project is currently underway to determine the effect of case management on client outcomes, assess its cost-effectiveness, and identify predictors of treatment participation and retention. Innovative models, such as case management approaches, can link drug abuse treatment with health care. These approaches may reduce the costs of care and improve the health care delivery system.

Adult↗
PubMed1991

Psychotropic drug prescribing for hospitalized patients with acquired immunodeficiency syndrome.

PURPOSE: The purpose of this study was to investigate the prescribing practices for the use of psychoactive medication in treating hospitalized patients with the acquired immunodeficiency syndrome (AIDS). PATIENTS AND METHODS: The medical charts were studied for all patients admitted to a 20-bed AIDS inpatient ward from July through December 1986. One hundred and fifty-one patient-admissions comprised the sample. The average age of the patients was 37 years, and the average length of the hospital stay was 13 days. Retrospective chart review collected demographic data, length of stay, medical diagnosis, psychiatric history, and mental status on admission. Data on psychoactive drugs included the reasons for use, maximum daily dose and duration, and side effects ascribed to the drugs. RESULTS: Psychoactive drugs were used in 89% of the cases. Anxiolytics accounted for 49% of the psychoactive prescriptions, and hypnotics made up 43% of these prescriptions. The five most frequently used psychoactive drugs were benzodiazepines. The most frequent reasons for psychotropic prescriptions were insomnia (39%), psychologic distress (20%), and nausea (16%). The most frequently used anxiolytic and anti-psychotic medications were used in moderate dosage, while the most frequently used antidepressant was prescribed in low dosage. CONCLUSIONS: Hospitalized AIDS patients are highly likely to be prescribed a psychotropic medication, especially an anxiolytic or hypnotic. Anxiolytics are used for several purposes, including reduction of nausea associated with the use of antibiotics. Antidepressants and antipsychotics are rarely used. Practitioners must be sensitive to the presence of psychiatric conditions presenting as insomnia or disturbed mood so that the most specific and appropriate treatments can be used.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Evaluation of a hospital based substance abuse intervention and referral service for HIV affected patients.

This paper reports an outcome evaluation and needs assessment conducted by the AIDS and Substance Abuse Program (ASAP) of the San Francisco AIDS Health Project. The study was designed to: 1) evaluate effectiveness of a hospital based intervention and referral service for HIV affected substance abusers, and 2) gather information from this population regarding accessibility and barriers to drug treatment. Participants were 86 individuals consecutively referred to ASAP over an 8-month period. All received a brief needs assessment interview in addition to the standard ASAP evaluation protocol. Agency follow-up contacts were made for those individuals referred by ASAP to extended substance abuse treatment, with information limited to whether or not the client contacted the designated referral resource. Source of referral to ASAP, interest in treatment, and prior sexual risk behavior change were significant predictors of intervention outcome. Personal unreadiness and treatment program waiting lists were the most frequently reported obstacles to treatment. While most participants reported changing risk behavior in response to the AIDS epidemic, patterns of change differed according to intravenous drug use history.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Mouse x human heterohybridomas as fusion partners with human B cell tumors.

Surface idiotype (Id) of B cell malignancies is an excellent tumor-specific marker. We have, however, recently described heterogeneity of tumor Id in some cases. We therefore sought a way to isolate, reliably and efficiently, different species of idiotype from a potentially heterogeneous population. In this report we demonstrate our success using a series of mouse X human heterohybridomas as fusion partners with human B cell tumors. Three lines (K6H6/B5, K6H9/G12, SBC/H20) demonstrated excellent fusion efficiency with 75%-85% of wells plated containing hybrids. Two cell lines, K6H9/G12 and SBC/H20 had a tendency to secrete a single Ig chain (heavy or light chain), whereas the K6H6/B5 cell line secreted whole immunoglobulin (Ig) in greater than 80% of the hybrids. This line secreted significant amounts of Ig (2.73 micrograms/ml/10(6) cells) and was relatively stable in culture. Since this line has such a high fusion efficiency the products of normal B cells admixed with tumor may be recovered, allowing the opportunity of isolating host anti-tumor antibodies. In order to prove that hybrids were derived from the tumor, Southern blot analysis of rearranged DNA was performed in selected cases. Fusions with this line provide the potential for recovering many different species of idiotype in a mixed population. This will facilitate the production of mouse monoclonal anti-idiotype antibodies against many variants and against different idiotopes.

Antigens, Neoplasm↗
PubMed1984

Pan-leukocyte monoclonal antibody L3B12. Characterization and application to research and diagnostic problems.

In this report, the authors describe a murine anti-human monoclonal antibody, L3B12, which defines a pan-leukocyte cell surface antigen of approximately 180,000 m.w. Extensive screening against a variety of tissues indicates that L3B12 is sensitive and specific for leukocytes, related cells of bone marrow lineage, and their corresponding neoplasms. Unlike many lymphoid antigens that are not detectable following routine fixation and embedding, those recognized by L3B12 and related antibodies are variably preserved. L3B12 has proven useful in studying the antigen expression of normal leukocytic elements, lymphomas, and related disorders, and in enriching or depleting leukocytes from heterogeneous cell populations. From a diagnostic standpoint, L3B12 staining of tissue sections or cell suspensions is useful for distinguishing large cell lymphomas from undifferentiated carcinomas and in distinguishing lymphomas and leukemias from other small round cell tumors of childhood.

Adult↗
PubMed1983

A single monoclonal antibody identifies T-cell lineage of childhood lymphoid malignancies.

Immunophenotyping studies with monoclonal antibodies have revealed the heterogeneity of childhood acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). The lymphoid malignancies of T-cell lineage are particularly heterogeneous and, until now, no single monoclonal antibody has been found to identify all cases of T-ALL and T-NHL. A monoclonal antibody, 4H9, recognizes an antigen of 40,000 molecular weight on normal and malignant T cells. Thirty-six cases of childhood T-ALL and T-NHL were tested, and in all cases, the malignant blast cells were reactive with 4H9, whereas malignant cells from 61 cases of non-T ALL and NHL were not reactive with 4H9. Monoclonal antibody 4H9 is a sensitive and specific reagent for the identification of childhood T-cell ALL and NHL and should be extremely useful in immunophenotyping studies of lymphoid malignancies.

Antibodies, Monoclonal↗