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Biomedical subjects

E Richardson

Publications and source records attributed to E Richardson.

At least 19 recordsLinked to original sources
PubMed2003

Development of an Ad7 cosmid system and generation of an Ad7deltaE1deltaE3HIV(MN) env/rev recombinant virus.

A strategy to circumvent immune responses to adenovirus (Ad) resulting from natural infection or repeated vector administrations involves sequential use of vectors from different Ad serotypes. To further develop an Ad-HIV recombinant AIDS vaccine approach, a replication-defective recombinant Ad from a non-subgroup C virus was required. Using a cosmid system, we generated an Ad7deltaE1deltaE3HIV(MN) env/rev recombinant virus and compared expression of the inserted HIV genes with a similarly constructed replication-competent Ad7deltaE3HIV(MN)env/rev recombinant. Ad7deltaE1deltaE3HIV(MN)env/rev expressed both HIV env and rev gene products. The envelope protein was correctly processed and functional, mediating syncytia formation of Ad7deltaE1deltaE3HIV(MN) env/rev-infected cells and CD4(+) T lymphocytes. Ad7deltaE1deltaE3HIV(MN)env/rev could be amplified on 293-ORF6 cells, containing the E4 ORF6 gene, shown earlier to support production of an Ad7 vector lacking the E1a gene. The utility of this cell line is now extended to the production of replication-defective Ad7 recombinants lacking E1a, E1b, and protein IX genes. Sequential immunizations with Ad-HIV recombinants based in different Ad serotypes have been shown to effectively elicit both humoral and cellular HIV-specific immune responses. The recombinant Ad7deltaE1deltaE3HIV(MN)env/rev will be useful in such AIDS vaccine strategies. Further, these studies have created new cosmid vectors that can be applied to generation of single- or double-deleted Ad7 recombinants with foreign genes inserted into the E1 and/or E3 regions.

AIDS Vaccines↗
PubMed2001

A conformational C4 peptide polymer vaccine coupled with live recombinant vector priming is immunogenic but does not protect against rectal SIV challenge.

The conserved, immunogenic CD4 binding site on the viral envelope is an attractive HIV or SIV vaccine candidate. Polymerization of an 18 amino acid segment derived from the C4 domain of SIV gp120 produced a peptide polymer or "peptomer," having an alpha-helical conformation possibly mimicking a proposed structure of the C4 domain in the unbound native protein. The SIV peptomer and native gp120 were compared as subunit boosts following two adenovirus type 5 host range (Ad5hr)-SIVenv recombinant priming immunizations. Both vaccine regimens successfully elicited SIV-specific CTL responses in five of six immunized macaques. Peptomer-boosted macaques exhibited significantly higher envelope-specific T cell proliferative responses than either the gp120-boosted macaques or controls. Peptomer immunization also elicited peptomer and SIV gp120-specific binding antibodies, but only native gp120 boosting elicited SIV neutralizing antibodies. Upon intrarectal challenge with SIVmac32H, all nine macaques became infected. The solely envelope-based vaccine conferred no protection. However, changing the boosting immunogen to the C4 peptomer did not improve protective efficacy in spite of its elicitation of humoral and cellular immune responses, including robust T-helper activity. In spite of the peptomer's strong immunogenicity and potential for induction of broadly protective immune responses, it was not effective as a subunit vaccine.

Adenoviridae↗
PubMed2001

Preparation of monoclonal antibodies against human telomerase.

Telomerase, a ribonucleoprotein enzyme that extends telomeres of eukaryotic chromosomes, consists of the catalytic protein submit telomerase reverse transcriptase (TERT) and a telomerase RNA subunit. Nearly 85% of human tumors have tested positive for high telomerase activity. Telomerase activity is very low or not present in normal cells, whereas it is up-regulated in immortalized cells. Telomerase, partially purified from the breast tumor cell line MCF-7, was used to immunize Balb/C mice. Monoclonal antibodies (MAbs) were prepared by conventional hybridoma technology and screened by enzyme-linked immunoadsorbent assay (ELISA), followed by a polymerase chain reaction (PCR) based telomeric amplification repeat protocol (TRAP) assay to detect binding to or inhibition of telomerase activity. Reactive MAbs were found to be of IgM type by mu specific ELISA. Two MAbs were characterized, one that neutralizes telomerase activity in TRAP assay and the other non-neutralizing. In Western blotting, crude telomerase extract and HIV-1 virus lysate (control) were blotted on nitrocellulose membranes and the strips were treated with both MAbs and a nonrelated HIV polymerase-specific MAb, also IgM type. A band of approx. 65-kDa was detected in extracts of 293 cells with both the MAbs, but no reaction occurred with the HIV polymerase-specific MAb used as control. Similarly, when HIV-1 virus lysate strips were treated with HIV polymerase-specific MAb, a 65-kDa band was detected and no band was observed with either of the hybridoma supernatants. These antibodies may be useful for studying regulatory mechanism of telomerase and inhibition of its activity in vitro and in vivo.

Antibodies, Monoclonal↗
PubMed2000

Childhood vaccination against pneumococcal otitis media and pneumonia: an analysis of benefits and costs.

OBJECTIVE: To examine the economic benefits and costs of routine vaccination of children younger than 5 years of age against pneumococcal otitis media and pneumonia with the pneumococcal conjugate vaccine. STUDY DESIGN: A decision-analytic model of the cumulative numbers of cases and costs to age 10 years of acute otitis media (AOM), tympanostomy and related procedures (TRP), and community-acquired pneumonia (CAP) in children who either did or did not receive the pneumococcal conjugate vaccine. PATIENTS AND METHODS: Seven hypothetical cohorts of 1000 children, stratified by age at initial vaccination, were followed. Outcome measures include costs of vaccination, cumulative numbers of cases of AOM, TRP, and CAP to age 10 years, and related disease costs, including medical treatment and parental work loss. RESULTS: Routine vaccination of 1000 children against pneumococcal infection would cost between $57,000 and $226,000, depending on age (the recommended number of doses varies by age at initial vaccination). Acute otitis media, TRP, and CAP to age 10 years would decline by 139 to 330, 8 to 22, and 15 to 30 cases, respectively; costs of medical treatment and work loss would correspondingly decline by $56,000 to $138,000. Expected net economic benefits (benefits minus costs) of vaccination against pneumococcal otitis media and pneumonia range from -$88,000 to $15,000 for children less than 2 years of age, and from -$1,000 to $31,000 for those aged 2 to 5 years at vaccination. CONCLUSION: Routine vaccination against pneumococcal otitis media and pneumonia appears to be cost-increasing for children less than 2 years of age who require multiple doses, but cost-saving for children aged 2 to 5 years who would require only a single dose of the vaccine.

Bacterial Vaccines↗
PubMed1999

Current issues in the economics of depression management.

In this paper, we present a systematic review of the literature on current issues in the economics of depression management, focusing on studies within three distinct areas of interest: 1) the clinical and economic outcomes of alternative patterns of antidepressant use; 2) the impact of depression and antidepressant therapy on the costs of general medical-care services; and 3) the effects of depression and associated benefits of antidepressant therapy on worker productivity. Our review suggests that 1) patterns of antidepressant use are important predictors of symptom improvement, relapse/recurrence, and costs of care, and that use patterns vary according to the antidepressant received as initial therapy; 2) patients with depression have higher costs of general medical-care services compared with their nondepressed peers, and that treatment of depression may reduce these costs; and 3) depression can result in productivity losses via increased rates of absenteeism and short-term disability as well as via impaired on-the-job performance.

Absenteeism↗
PubMed1999

Two nursing home outbreaks of respiratory infection with Legionella sainthelensi.

OBJECTIVE: To describe outbreaks of infection caused by Legionella sainthelensi occurring in older residents of two nursing homes and to determine risk factors for the development of infection. DESIGN: Descriptive epidemiology and a case-control study. SETTING: Two nursing homes (140 beds and 254 beds in nursing homes A and B, respectively) located in southern Ontario, Canada, experiencing outbreaks of respiratory tract infection in July and August 1994. SUBJECTS: Case-residents of the two nursing homes who met clinical and laboratory criteria for Legionella infection. Control-residents were defined as those who were in the homes during the outbreaks and were asymptomatic. MEASUREMENTS: Active surveillance was conducted in both nursing homes to identify symptomatic residents. Residents with fever or respiratory tract symptoms had nasopharyngeal swabs taken for viral antigen detection and culture, urine for Legionella antigen detection, and acute and convalescent serology for viruses, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella. Chest X-rays were performed, and an attempt was made to obtain blood and sputum cultures. Water samples from shower heads, faucets, and air conditioning units were collected for Legionella culture and polymerase chain reaction (PCR) assay. A case-control study was done to assess possible risk factors for legionellosis. RESULTS: Twenty-nine cases -- 17 in nursing home A; 12 in nursing home B - were identified. Four (14%) case-residents had documented pneumonia and four case-residents died. Univariate analysis revealed that a history of stroke (odds ratio (OR) 2.3 (95% CI, 1.0-5.3)), eating pureed food (OR 4.6 (95% CI, 1.6-12.7)), and having fluids administered with medication (OR 2.5 (95% CI, 1.0-5.9)) were significant risk factors. Cases were less likely to wear dentures (OR .4 (95% CI, .2-.9)) or to eat solid food (OR .3, (95% CI, .1-.6)). Only eating pureed food remained significant in a multivariable analysis (OR 4.6 (95% CI, 1.6-13.0, P = .01)). CONCLUSION: This report describes outbreaks of legionellosis in two nursing homes, representing the first reported outbreaks of infection caused by Legionella sainthelensi. The association with illness of dietary characteristics indicative of swallowing disorders suggests that aspiration was the most likely mode of infection. The diagnosis of legionellosis should be considered during outbreaks of respiratory infection in nursing homes.

Aged↗
PubMed1998

Memory processes in depressed geriatric patients with and without subcortical hyperintensities on MRI.

In this study, 12 patients over age 60 with depression with moderate to severe subcortical hyperintensities (SH) localized to the periventricular white matter were identified by quantitative MRI. Using the California Verbal Learning Test, they were compared with 12 age-, education-, and severity-matched patients with depression with minimal white matter changes on specific aspects of memory performance. Patients with cortical lesions, neurologic or systemic illness affecting cognition, and history of substance abuse were excluded. Patients in the group with high SH showed reduced use of semantic encoding strategies (p < 0.05), reduced learning efficiency (p < 0.05), and a greater discrepancy between free recall and recognition discriminability (p < 0.05) than their low SH counterparts. This pattern of performance on memory tasks is similar to that found in previous studies to be associated with subcortical degenerative disorders such as Huntington's and Parkinson's diseases. Geriatric patients with depression with SH may represent a subgroup with greater subcortical involvement, with associated cognitive and functional decline.

Aged↗
PubMed1998

Vaccine protection against a heterologous, non-syncytium-inducing, primary human immunodeficiency virus.

Vaccine-induced protection of chimpanzees against laboratory-adapted and syncytium-inducing, multiply passaged primary human immunodeficiency virus type 1 (HIV-1) isolates, but not against non-syncytium-inducing, minimally passaged ones, has been demonstrated. Following challenge with such an isolate, HIV-15016, we obtained complete protection in one of three chimpanzees previously protected against low- and high-dose HIV-1SF2 exposures after immunization with an adenovirus-HIV-1MN gp160 priming-HIV-1SF2 gp120 boosting regimen. At challenge, the protected chimpanzee exhibited broad humoral immunity, including neutralizing antibody activity. These results demonstrate the potential of this combination vaccine strategy and suggest that vaccine protection against an HIV isolate relevant to infection of people is feasible.

AIDS Vaccines↗
PubMed1997

An adenovirus-simian immunodeficiency virus env vaccine elicits humoral, cellular, and mucosal immune responses in rhesus macaques and decreases viral burden following vaginal challenge.

Six female rhesus macaques were immunized orally and intranasally at 0 weeks and intratracheally at 12 weeks with an adenovirus type 5 host range mutant (Ad5hr)-simian immunodeficiency virus SIVsm env recombinant and at 24 and 36 weeks with native SIVmac251 gp120 in Syntex adjuvant. Four macaques received the Ad5hr vector and adjuvant alone; two additional controls were naive. In vivo replication of the Ad5hr wild-type and recombinant vectors occurred with detection of Ad5 DNA in stool samples and/or nasal secretions in all macaques and increases in Ad5 neutralizing antibody in 9 of 10 macaques following Ad administrations. SIV-specific neutralizing antibodies appeared after the second recombinant immunization and rose to titers > 10,000 following the second subunit boost. Immunoglobulin G (IgG) and IgA antibodies able to bind gp120 developed in nasal and rectal secretions, and SIV-specific IgGs were also observed in vaginal secretions and saliva. T-cell proliferative responses to SIV gp140 and T-helper epitopes were sporadically detected in all immunized macaques. Following vaginal challenge with SIVmac251, transient or persistent infection resulted in both immunized and control monkeys. The mean viral burden in persistently infected immunized macaques was significantly decreased in the primary infection period compared to that of control macaques. These results establish in vivo use of the Ad5hr vector, which overcomes the host range restriction of human Ads for rhesus macaques, thereby providing a new model for evaluation of Ad-based vaccines. In addition, they show that a vaccine regimen using the Ad5hr-SIV env recombinant and gp120 subunit induces strong humoral, cellular, and mucosal immunity in rhesus macaques. The reduced viral burden achieved solely with an env-based vaccine supports further development of Ad-based vaccines comprising additional viral components for immune therapy and AIDS vaccine development.

Adenoviruses, Human↗
PubMed1997

Characteristics of automatic or semiautomatic firearm ownership in the United States.

OBJECTIVES: This study examined ownership patterns of automatic/ semiautomatic firearms in the United States. METHODS: Data were derived from a national random-digit-dialing telephone survey of 800 gun owners. RESULTS: Sixty percent of gun owners reported owning an automatic or semiautomatic firearm. In comparison with other gun owners, owners of automatics or semiautomatics were more likely to be male, live in the South, own a gun for protection, and have a gun for work. They were also more likely to report binge drinking. CONCLUSIONS: Owners of automatic or semiautomatic firearms differ from other gun owners in several respects, including frequency of binge drinking.

Adult↗
PubMed1996

MRI and neuropsychological differences in early- and late-life-onset geriatric depression.

We sought to determine whether geriatric patients with late-life-onset major depression have more subcortical hyperintensities on MRI and greater cognitive impairment than age-matched geriatric patients with early-life-onset major depression, suggesting that subcortical disease may be etiologic in late-life depression. Most negative studies of the clinical significance of subcortical hyperintensities on MRI in geriatric patients have sampled from a restricted range of subjects, have employed limited batteries of neuropsychological tests, or have not quantified MRI changes; the present study attempted to address these limitations. Thirty subjects from a geriatric psychiatry inpatient service who were over 60 years of age and presented with major depression were divided into groups with onset of first depression after age 60 (mean = 72.4 years, 15 women, 0 men), and onset of first depression before age 60 (mean = 35.8 years, 12 women, 3 men). Quantitative analysis of MRI yielded the volume of: periventricular hyperintensities (PVH) and deep white-matter hyperintensities (DWMH). Subjects were administered a neuropsychological battery and measures of depression by raters blind to age of onset. The late-onset group had significantly more PVH and DWMH. They were also more impaired on executive and verbal and nonverbal memory tasks. Discriminant analysis using the severity or subcortical signal hyperintensities on MRI, cognitive index, and depression scores correctly predicted late versus early onset of depression in 87% of the early-onset group and 80% of the late-onset group. These findings suggest that late-life-onset depression may be associated with an increased severity of subcortical vascular disease and greater impairment of cognitive performance.

Adult↗
PubMed1996

Colobomatous microphthalmia with midfacial clefting: part of the spectrum of branchio-oculo-facial syndrome?

A young male infant was noted at birth to have bilateral cleft lip and palate, bilateral microphthalmos and ocular colobomata, and a dysplastic left kidney. His mother had similar ophthalmological findings and milder facial anomalies which included abnormality of the philtrum and bilateral congenital nasolacrimal duct obstruction. His maternal grandmother had mild facial anomalies including a short philtrum and bilateral congenital nasolacrimal duct obstruction but had no evidence of any ocular abnormalities. The spectrum of abnormalities seen in this family are similar to those described in the branchio-oculo-facial syndrome, a rare dominantly inherited syndrome in which there are a number of developmental abnormalities of the eye, face, and kidney. Although the precise cause of this syndrome is unknown, it is likely to be caused by mutations in a gene responsible for the ordered closure of the foetal fissure and fusion of facial structures.

Adult↗
PubMed1996

Family support services for stroke patients.

Provision of long-term support and rehabilitation after stroke varies in the UK. Patients and their carers are not always aware of services available. Family support service organisers can help increase awareness of risk factors and minimise recurrence of stroke.

Cerebrovascular Disorders↗
PubMed1995

Evaluation of a tuberculosis screening program for high-risk students in Toronto schools.

OBJECTIVE: To evaluate the effectiveness of a tuberculosis (TB) screening program for high-risk students in elementary and secondary schools. DESIGN: Cross-sectional study of the 1992-93 school screening program conducted by the Department of Public Health of the City of Toronto. Program costs were calculated with the use of 1993 wages, and costs for medical care were based on the 1993 fee schedule of the Ontario Medical Association. SETTING: Elementary and secondary schools in the City of Toronto. PARTICIPANTS: Students enrolled for the first time in any grade who were born in a country where TB is endemic or who were aboriginal Canadians were eligible. Of 44,179 students in Toronto schools 1775 met the eligibility criteria. INTERVENTION: Students were administered a Mantoux skin test, and those with a significant reaction (an induration of 10 mm or more in diameter) were advised to consult a physician for follow-up. OUTCOME MEASURES: Participation rate, number of participants with a significant reaction, percentage of these who were prescribed isoniazid and who completed chemoprophylaxis, potential number of preventable cases and costs associated with preventing each case. RESULTS: Of 1775 eligible students 42.9% (761) agreed to participate, and 40.6% (720) were screened. Significant skin-test reactions were detected in 22.5% (162/720) of the participants screened. Of these, 87.7% (142/162) saw a physician; subsequently, 2 cases of TB (1 active and 1 inactive) were detected. Of the remaining 140 students 44.3% (62) were prescribed isoniazid, of whom 9.7% (6/62) refused chemoprophylaxis. Of the remaining 56 students 82.1% (46) completed at least 6 months of chemoprophylaxis and 10.7% (6) were completing treatment at the end of the study. An estimated 3.2 cases were prevented, at a cost of $13,493.15 per case, whereas the undiscounted cost of treatment for an uncomplicated active case of TB in a patient under 19 years of age was $4503.82. CONCLUSIONS: The effectiveness of this screening program was significantly reduced by poor participation and poor rates of prescription of isoniazid by physicians. Appropriate strategies are needed to reduce barriers to the implementation of these programs.

Adolescent↗
PubMed1995

UV-light induces delayed mutations in Chinese hamster cells.

The possibility was examined that mutational events at the glucose 6-phosphate dehydrogenase locus can be delayed for significantly more than one or two cell divisions following treatment of Chinese hamster cells with UV light. To detect these later mutant events, the proportion of G6PD-mutant cells in a colony was obtained by replating cells from a single colony 5-7 days after UV irradiation and staining the resulting colonies for G6PD activity. Eight colonies out of a total of 1657 colonies from the treated population yielded G6PD-negative colonies upon replating, while no mutant clones were obtained from 947 colonies grown from untreated cells. One clone contained only mutant cells suggesting that the mutation occurred before the first cell division after irradiation. A second clone contained a 1:1 ratio of mutant to wild-type cells suggesting that the mutation occurred at the first cell division. The remaining six clones contained low numbers of mutant cells and the ratio of mutant to wild-type cells in these clones was in agreement with the theoretical ratios expected for mutations occurring at the fourth (1:13), sixth (1:63), seventh (1:127), eighth (1:255), ninth (1:511), and eleventh (1:2047) cell division after UV light exposure. G6PD-mutant cells deficient in staining activity were isolated from five clones and all have significant reductions in G6PD activity confirming the genetically stable character of these mutants. These results support the conclusion that UV light induces mutants for up to 11 cell generations after treatment of mammalian cells and suggest that mutagens can induce in mammalian DNA long-term alterations which act to increase the apparently spontaneous mutation frequency.

Animals↗
PubMed1994

Depression, suicidal ideation, and substance use among adolescents. Are athletes at less risk?

OBJECTIVES: To determine the relationship between participation in high school athletic programs and depression, suicidal ideation, and substance use, and to study the high-risk behaviors of suicidal ideation and substance use. DESIGN: Survey. SETTING: A suburban public high school in Kentucky. PARTICIPANTS: We received 823 (80%) responses from 1030 potential respondents. Athletes (ie, participation on a high school athletic team) were compared with non-athletes. MEASURES: Depression was measured by the Children's Depression Inventory by an index of suicidal ideation by an indicator of a past suicide attempt, and by current use of tobacco, alcohol, marijuana, and cocaine. RESULTS: Thirty percent of the sample participate in school athletic teams. Athletes are less depressed, have less suicidal ideation and attempts, and are less likely to currently smoke cigarettes or marijuana. The use of smokeless tobacco and cocaine was not related to athletic participation. After controlling for demographic characteristics, no difference in alcohol use was found between athletes and nonathletes. CONCLUSIONS: Athletic participation is a marker for a decreased likelihood of depression and some high-risk behaviors in adolescents. Future research could help in creating alternative interventions beyond participation in varsity and junior varsity athletic teams.

Adolescent↗
PubMed1994

Large corneal transplants in corneal destructive disease.

PATIENTS AND METHODS: Forty nine keratoplasties were performed in 18 eyes of 17 patients with severe corneal destructive disease. RESULTS: One eye became phthisical and 5 others lost useful visual acuity but retained a satisfactory cosmetic result. No eyes were enucleated. Recurrence of the host disease in the graft was the largest cause of visual failure. Primary allograft rejection was rare in spite of the large size of the grafts and their proximity to the limbus and new vessels. CONCLUSION: For these grafts to succeed it is essential to bring the underlying systemic disease under control by intensive systemic immunosuppressive therapy before, during and for many months after surgery. It was found that those with Mooren's ulcer had the worst prognosis for the retention of vision.

Corneal Diseases↗