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Biomedical subjects

J S Harrison

Publications and source records attributed to J S Harrison.

At least 19 recordsLinked to original sources

Stability of a single-chain Fv antibody fragment when exposed to a high shear environment combined with air-liquid interfaces.

The effect of shear on the antigen binding activity of a recombinant scFv antibody fragment was investigated in the presence of air-liquid interfaces using a stirred vessel that was incompletely filled. Changes in binding activity of the scFv to its antigen were monitored using an optical biosensor which had been sensitized with hen egg lysozyme (the antigen). The biosensor response was used as a measure of scFv binding activity. In buffer solution (mean velocity gradient approximately 20,000 s-1), loss of binding activity followed a first-order model with a mean rate constant of 0.83 h-1. In unstirred buffer solution, no such loss was observed. Similarly, in sheared fermentation broth there was no loss of binding activity and protective effects were attributed to the antifoam PPG.

Biosensing Techniques

Factors associated with Hispanic women's HIV-related communication and condom use with male partners.

To determine factors influencing Hispanic women's HIV-related communication and condom use with their primary male partner, 189 Dominican, Puerto Rican, and Mexican women were interviewed regarding sexual behaviour and condom use, relationship characteristics, perceived risk for HIV, and HIV-related communication with the primary male partner. Level of HIV-related communication with the primary male partner was associated with the woman's perceived risk for HIV and her rating of the openness with which she could communicate with her primary partner. Mexican women were less likely than Puerto Rican or Dominican women and women with multiple partners were less likely than those with one partner to communicate about HIV-related issues with their primary partner. Women reporting more condom use with their primary partner were younger, had discussed HIV-related issues more with the primary partner, and were less likely to expect negative reactions to requests for condom use than those reporting less condom use. These results suggest that prevention programmes that increase both general and HIV-specific communication between members of a couple may facilitate safer sex practices by the couple. Prevention programmes that encourage women to insist on condom use should consider the woman's expectations about her partner's reaction as a potential barrier to the initiation of safer sex practices.

Acculturation

HIV risk behavior among Peace Corps Volunteers.

OBJECTIVE: To describe HIV risk behaviors among Peace Corps Volunteers (PCV) and to examine correlates of sexual risk behaviors. METHOD: Cross-sectional data were collected from 1242 randomly selected PCV serving in 28 countries in 1991. PCV reported the frequency of specific risk behaviors in self-administered questionnaires, which were completed anonymously and returned to the Centers for Disease Control and Prevention. RESULTS: Non-sexual HIV risk behaviors were rarely reported by PCV. Sixty-one per cent of the 1080 PCV who answered questions about sexual behavior during their Peace Corps service reported having at least one sex partner. Sixty per cent of PCV had another PCV partner, 39% had a host-country national partner, and 29% had a non-PCV expatriate partner. Overall, less than one-third (32%) of unmarried PCV used condoms during every episode of sexual intercourse; more frequent use was reported in relationships with non-steady and (for male PCV) host-country national partners. Among male PCV, condom use was positively related to lower alcohol use and the belief that HIV was a problem in the host country. Female PCV reporting more condom use with male partners were younger and had fewer partners than those reporting less use. CONCLUSION: These data indicate that PCV are at risk for acquiring HIV through unprotected vaginal intercourse. All persons who become sexually active with new partners while travelling or living abroad should be encouraged to use condoms consistently.

Adult

Emotional, behavioral, and HIV risks associated with sexual abuse among adult homosexual and bisexual men.

From May 1989 through April 1990, 1,001 adult homosexual and bisexual men attending urban sexually transmitted disease clinics were interviewed regarding abusive sexual contacts during childhood and adolescence. Sexual abuse was found to be significantly associated with mental health counseling and hospitalization, psychoactive substance use, depression, suicidal thought or actions, social support, sexual identity development, HIV risk behavior including unprotected and intercourse and injecting drug use, and risk of sexually transmitted diseases including HIV infection. Data suggest that sexual abuse may have a wide-ranging influence on the quality of life and health risk behavior of homosexual men. Increased awareness as to the potential outcomes of male sexual abuse is critically important to the design and implementation of medical and psychological services for sexually abused men.

Adolescent

Pharmacokinetics and toxicity of continuous infusion (6S)-folinic acid and bolus 5-fluorouracil in patients with advanced cancer.

Twenty-seven patients with advanced cancer were entered in a phase I study of bolus i.v. 5-fluorouracil at a dose of 370 mg/m2/day for 5 days combined with a continuous i.v. infusion of (6S)-folinic acid for 5.5 days, starting 24 h in advance of the first 5-fluorouracil dose. The dose of (6S)-folinic acid was escalated in cohorts of patients from 250 mg/m2/day to a maximum of 1000 mg/m2/day. The pharmacokinetics of (6S)-folinic acid were studied in the 3 patients given 250 mg/m2/day and in 6 patients given 1000 mg/m2/day. The mean steady-state plasma concentrations of (6S)-folinic acid and its principal metabolite (6S)-5-methyltetrahydrofolate at the 250 mg/m2/day dose were 2.7 and 5.1 microM, respectively. Both concentrations were comparable to the concentrations produced when (6S)-folinic acid was administered as half of a (6R,S)-folinic acid mixture (E. M. Newman et al., Cancer Res., 49:5755-5760, 1989). At the 1000 mg/m2/day dose of (6S)-folinic acid, the concentration of (6S)-folinic acid was 15.3 microM, more than the 4-fold increase predicted by linear pharmacokinetics, while the concentration of (6S)-5-methyltetrahydrofolate was only 16.5 microM. The change in the ratio of the parent compound to its metabolite was accounted for by a decrease in the nonrenal clearance of (6S)-folinic acid, probably indicating saturation of its metabolism. The toxicities observed in this phase I trial, including stomatitis, diarrhea, neutropenia, and anemia, did not differ in nature or severity from those produced by 5-fluorouracil and (6R,S)-folinic acid when administered on the same schedule. Finally, the degree of toxicity did not appear to depend on the dose of (6S)-folinic acid over the range of doses tested.

Adult

Severe von Willebrand disease due to a defect at the level of von Willebrand factor mRNA expression: detection by exonic PCR-restriction fragment length polymorphism analysis.

von Willebrand disease (vWD), the most common inherited bleeding disorder in humans, results from abnormalities in the plasma clotting protein von Willebrand factor (vWF). Severe (type III) vWD is autosomal recessive in inheritance and is associated with extremely low or undetectable vWF levels. We report a method designed to distinguish mRNA expression from the two vWF alleles by PCR analysis of peripheral blood platelet RNA using DNA sequence polymorphisms located within exons of the vWF gene. This approach was applied to a severe-vWD pedigree in which three of eight siblings are affected and the parents and additional siblings are clinically normal. Each parent was shown to carry a vWF allele that is silent at the mRNA level. Family members inheriting both abnormal alleles are affected with severe vWD, whereas individuals with only one abnormal allele are asymptomatic. The maternal and paternal silent alleles are identical at two coding sequence polymorphisms as well as an intron 40 variable number tandem repeat, suggesting a possible common origin. Given the frequencies of the two exon polymorphisms reported here, this analysis should be applicable to approximately 70% of type I and type III vWD patients. This comparative DNA and RNA PCR-restriction fragment length polymorphism approach may also prove useful in identifying defects at the level of gene expression associated with other genetic disorders.

Alleles

Relationship between AIDS latency period and AIDS survival time in homosexual and bisexual men.

We identified 277 homosexual and bisexual men diagnosed with acquired immune deficiency syndrome (AIDS) whose estimated human immunodeficiency virus (HIV) seroconversion dates, ranging from 1977-85, could be well approximated. These men were from a cohort of 6,705 homosexual and bisexual men originally recruited for studies of sexually transmitted hepatitis B in San Francisco in 1978-80. We compared the time from HIV seroconversion to the initial disease diagnostic of AIDS (AIDS latency period) with the time from first AIDS diagnosis to death (AIDS survival time) and found no significant overall correlation between latency period and survival time. Both Kaplan-Meier and Cox proportional hazard stepwise analyses found the initial AIDS diagnosis to be significantly associated with latency period, with individuals first diagnosed with Kaposi's sarcoma (KS) having a shorter latency but longer survival than those first diagnosed with Pneumocystis carinii pneumonia (PCP) or other AIDS diagnoses. Individuals with KS tended to be diagnosed earlier in the epidemic compared to those with PCP and other non-KS diagnoses. The AIDS survival time was significantly associated with the initial AIDS diagnosis but not with the estimated year of seroconversion, the year of first AIDS diagnosis, age at seroconversion, or racial/ethnic group. The information presented here on the relationship between the AIDS latency period and survival times suggests a model for the pathogenesis of HIV infection in which there is continual deterioration of the immune system. The wider use of antiviral and prophylactic therapies both preceding and following a diagnosis of AIDS may change this model as both latency and survival times are improved.

Acquired Immunodeficiency Syndrome

Association of a mature B cell leukemia with a 4p+ chromosomal abnormality: derivation and characterization of a cell line.

We have found a single 4p+ chromosomal abnormality, 46,XX, -4, +der(4)t(3;4)(q13.3;p16), in a patient with an unusual B cell leukemia of mature phenotype characterized by a high white cell count, tartrate-resistant acid phosphatase-positive malignant cells, splenic white pulp proliferation, and a serum IgM monoclonal gammopathy. The malignant cells were characterized by surface expression of CD19 (B4), CD20 (B1), IgM, IgD, kappa, and HLA-DR. They were weakly positive for CD21 (B2) and negative for CD25 (interleukin-2 receptor). The malignant cells also showed clonal rearrangement of the immunoglobulin heavy chain and kappa light chain genes. A cell line, designated HCLW-3B, was derived from unstimulated peripheral blood obtained during the leukemic phase and was found to contain the same 4p+ chromosomal abnormality as well as genomic sequences of the Epstein-Barr virus nuclear antigen. A somatic cell hybrid constructed from HCLW-3B containing the derivative chromosome 4 was used to confirm that chromosome 3q was the source of the translocated material. The availability of a cell line which is clonally derived from the patient's circulating leukemia cells should permit further characterization of this translocation at the molecular level.

Blotting, Southern

Yeast production.

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Aerobiosis

Self-reported childhood and adolescent sexual abuse among adult homosexual bisexual men.

From May 1989 through April 1990, 1,001 adult homosexual and bisexual men attending sexually transmitted disease clinics were interviewed regarding potentially abusive sexual contacts during childhood and adolescence. Thirty-seven percent of participants reported they had been encouraged or forced to have sexual contact before age 19 with an older or more powerful partner; 94% occurred with men. Median age of the participant at first contact was 10; median age difference between partners was 11 years. Fifty-one percent involved use of force; 33% involved anal sex. Black and Hispanic men were more likely than white men to report such sexual contact. Using developmentally-based criteria to define sexual abuse, 93% of participants reporting sexual contact with an older or more powerful partner were classified as sexually abused. Our data suggest the risk of sexual abuse may be high among some male youth and increased attention should be devoted to prevention as well as early identification and treatment.

Adolescent

Homosexual men who engage in high-risk sexual behavior. A multicenter comparison.

To describe homosexual men who continue to engage in unprotected oral and anal sex, 601 men who attended three urban STD clinics and who had engaged in these behaviors with a male partner in the previous 4 months were interviewed regarding their sexual and drug-use behaviors. Although approximately one fourth of participants had engaged in 1 to 2 episodes of unprotected anal sex, more than 20% reported engaging in greater than 23 episodes. Higher frequency of anal sex was associated with lower condom use rates. Although 50% had primary relationships, less than 22% had sex with just one partner, and less than 10% were in relationships concordant for HIV-antibody status. Multiple regression analyses showed that number of drugs used each month, sex in a steady relationship, and Hispanic ethnicity were the most consistent predictors of risk behavior across sites. Careful evaluation of the diverse nature and characteristics of these men is essential to target risk-reduction programs for this population.

Adult