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Biomedical subjects

A Weinberg

Publications and source records attributed to A Weinberg.

At least 19 recordsLinked to original sources
PubMed2006

Role of human beta-defensins in HIV infection.

Mechanisms of resistance to HIV-1 infection in the human oral cavity are incompletely understood. While salivary components have been implicated in protection, there is growing evidence that human beta-defensins (hBDs), originating in oral epithelial cells, may be playing an important role in the prevention of HIV infection. New antiviral, chemotactic, and immunosurveillance properties are being attributed to hBDs, which are small cationic antimicrobial innate response molecules expressed in mucosal epithelium. Inducible hBDs are always expressed in normal oral epithelium, a property not shared by other mucosal barriers. Data reviewed in this paper demonstrate that: (1) HIV-1 X4 and R5 phenotypes induce hBD-2 and -3 mRNA in normal human oral epithelial cells; (2) hBD-2 and -3 inhibit HIV-1 infection by both viral strains, with greater activity against X4 viruses; and (3) this inhibition is due to a direct interaction with virions and through modulation of the CXCR4 co-receptor. These properties may be exploited as strategies for mucosal protection against HIV-1 transmission.

Animals↗
PubMed2006

(C3) The oral epithelial cell and first encounters with HIV-1.

The oral epithelium is the site of first exposure of HIV-1 to host tissues during oral sex with an infected partner or through breast-feeding by an infected mother. Although the oral epithelium is distinguishable by its apparent resistance, the mucosal surfaces represent a primary target of HIV-1. After oral exposure and swallowing, infection is detected prominently in the gastrointestinal tract, which becomes depleted of CD4+ T-cells. The oral cavity and palatine tonsils appear to resist infection and transfer to susceptible lymphoid cells in the lamina propria by local anti-HIV-1 mechanisms. In some cases, expression of these antiviral mechanisms increases after exposure to HIV-1. During primary exposure and before seroconversion, based on limited in vitro and primate data, a window of opportunity for capture of HIV-1 by the oral epithelium may exist. After seroconversion, the risk of infectious HIV-1 appearing in saliva is negligible. This report considers evidence that oral epithelium has the potential both to enable and to resist infection by HIV-1.

Animals↗
PubMed2006

Stress fractures in the juvenile skeletal system.

Stress fractures affecting the juvenile skeletal system are rare and are described as having a good prognosis. Precisely because these fractures are so rare, studies allowing clear and generally applicable conclusions are lacking. The object of the present study was a systematic analysis of patients with stress fractures in an immature skeletal system, with special reference to the frequently difficult and delayed diagnosis and to the forms of therapy considered appropriate. Twenty-five patients with a total of 27 stress fractures affecting bones with the growth plates still open were examined according to a standardized procedure. The average duration of follow-up was 4.8 years (SD +/- 2.3) and the average age at occurrence 12.9 years (SD +/- 4.31). The risk factors were largely the same as those in adults. The most frequent site was the tibia (48% of cases; n = 13), followed by the metatarsal bones. Most (26/27) fractures were treated conservatively, with an average duration of therapy of 8.9 weeks (SD 8.2 weeks). Ultimately, 17 (63%) of the fractures healed in such a way as to allow the patients to return to full athletic activity with no restrictions within 3 months after diagnosis. In 9 cases (33%) it was not possible to achieve complete absence of symptoms within 12 months after diagnosis was made. No pseudarthroses were observed. There was a significant correlation between clinical outcome recorded as "free of symptoms" and an early diagnosis (less than 2 weeks after first symptoms (p = 0.033) and a fracture line seen on MR tomography in contrast to a stress reaction with merely increased signal intensity (p = 0.037). Overall, a strikingly high proportion of these patients had a prolonged course. This is attributable partly to the delay in diagnosis and to inappropriate initial treatment. When stress fractures were recognizable by a demonstrable fracture line--in contrast to just an edema--on MR tomography and their diagnosis was followed by an adequate form of therapy the chances of complete healing seemed to be better. It is essential to carry out targeted imaging investigations, e.g., by means of MR tomography, when there is a reason to consider a stress reaction. Furthermore, stress fractures should be adequately treated until all symptoms have disappeared.

Adolescent↗
PubMed2006

Treatment of multidrug-resistant cytomegalovirus retinitis with systemically administered leflunomide.

Multiresistant cytomegalovirus (CMV) infection is increasingly recognized in solid organ transplant recipients. Leflunomide is a novel drug with both immunosuppressive and anti-CMV properties. Herein we report a case of a renal transplant recipient treated with leflunomide for multiresistant CMV retinitis, and provide correlation between serum and vitreous levels of leflunomide. She had stabilization of her retinitis and measurable levels of drug in her vitreous fluid and serum. These initial findings suggest that leflunomide may be useful in the treatment of CMV disease, including retinitis in patients after solid organ transplantation.

Adult↗
PubMed2006

Safety and immunogenicity of varicella-zoster virus vaccine in pediatric liver and intestine transplant recipients.

Primary varicella-zoster virus (VZV) infections following organ transplantation may cause significant morbidity. We examined the safety and immunogenicity of Varivax after transplantation as a potential prophylactic tool. Pediatric liver and intestine transplant recipients without history of chickenpox received one dose of Varivax. VZV humoral and cellular immunity were assessed before and > or =12 weeks after vaccination. Adverse events (AE) and management of exposure to wild type VZV were monitored. Sixteen VZV-naïve subjects, 13-76 months of age, at 257-2045 days after transplantation were immunized. Five children developed mild local AE of short duration. Four subjects developed fever and four developed non-injection site rashes, three of whom received acyclovir. Liver enzymes did not increase during the month after vaccination. Eighty-seven percent and 86% of children developed humoral and cellular immunity, respectively. There were five reported exposures to varicella in four children, none of which resulted in chickenpox. One subject received VZV-immunoglobulin and another subject with liver enzyme elevations after exposure received acyclovir; all remained asymptomatic. Varivax was safe and immunogenic in pediatric liver and intestine transplant recipients. Larger studies are needed to establish the efficacy and role of varicella vaccination after transplantation.

Chickenpox↗
PubMed2005

Surface tension: floater clustering in a standing wave.

How do waves affect the distribution of small particles that float on water? Here we show that drifting small particles concentrate in either the nodes or antinodes of a standing wave, depending on whether they are hydrophilic or hydrophobic, as a result of a surface-tension effect that violates Archimedes' law of buoyancy. This clustering on waves may find practical application in particle separation and provides insight into the patchy distribution on water of, for example, plastic litter or oil slicks.

Journal Article↗
PubMed2005

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Aged↗
PubMed2005

Cancer-related disparities: weathering the perfect storm through comprehensive cancer control approaches.

During the last two decades extraordinary progress in developing and using effective cancer prevention strategies, early detection interventions, and cancer treatments has been made. This progress has resulted in an overall decline in mortality rates for all cancers combined. Nonetheless, cancer is the second most common cause of death in the United States. Although cancer is a diagnosis that many survive, cancer experiences across populations may vary considerably. These differences in cancer experiences have created an unequal disease burden that presents distinct professional and moral challenges to our nation. Many cancer control plans suggest specific strategies that prioritize eliminating cancer-related disparities. This article describes certain cancer-related disparities in the United States and gives several examples of how communities and disenfranchised populations are using comprehensive cancer control (CCC) approaches to eliminate these disparities. One or two interventions are highlighted in each example.

Delivery of Health Care↗
PubMed2005

Human beta-defensins: differential activity against candidal species and regulation by Candida albicans.

Oral epithelial cell-derived human beta-defensins-1, -2, and -3 participate in innate immune responses against Candida. We hypothesized that these peptides utilize several mechanisms for protection. Recombinant hBD-1 and -2 were produced with the use of an insect cell/baculovirus expression system, while rhBD-3 was expressed as a fusion protein in E. coli. RhBD-2 and -3 were more effective at killing the candidal species at low micromolar concentrations than was rhBD-1, except for C. glabrata. While this species was relatively resistant to rhBD fungicidal activity, its adherence to oral epithelial cells was strain-specifically inhibited by the rhBDs. C. albicans hyphae were important in regulating hBD2 and -3 mRNA expression in primary human oral epithelial cells. Confocal microscopy of rhBD-2-challenged C. albicans suggests disruption of the fungal membrane. Results support the hypothesis that hBDs control fungal colonization through hyphal induction, direct fungicidal activity, and inhibition of candidal adherence.

Anti-Infective Agents↗
PubMed2003

Cytomegalovirus (CMV) and human immunodeficiency virus (HIV) burden, CMV end-organ disease, and survival in subjects with advanced HIV infection (AIDS Clinical Trials Group Protocol 360).

We undertook a prospective study to analyze cytomegalovirus (CMV) end-organ disease (EOD) in subjects with advanced human immunodeficiency virus (HIV) infection. Of 403 individuals without prior CMV EOD who were followed up for a median of 151 weeks, 56 died and 21 developed CMV EOD. Twenty of the subjects with CMV EOD had CD4 cell counts of < or =50 cells/mm3 and HIV RNA level of >10,000 copies/mL of plasma at baseline; in these 20 subjects, an increase of CMV DNA level to greater than the quantification limits was associated with CMV EOD. A CD4 cell count of < or =100 cells/mm3 and an HIV RNA level of >10,000 copies/mL of plasma at baseline, a CMV DNA level of >200 copies/mL of blood during follow-up, or development of CMV EOD were all associated with decreased survival. HIV-infected subjects with CD4 cell counts of < or =50 cells/mm3 and HIV RNA levels of >10,000 copies/mL of plasma should have blood fractions screened for CMV DNA; if CMV DNA is detected, CMV prophylaxis might be considered.

AIDS-Related Opportunistic Infections↗
PubMed2003

Selective induction of human beta-defensin mRNAs by Actinobacillus actinomycetemcomitans in primary and immortalized oral epithelial cells.

Human beta-defensin-2, and -3 (hBD-2, -3) are small inducible antimicrobial peptides involved in host defense. Actinobacillus actinomycetemcomitans, a gram-negative facultative anaerobe, is frequently associated with oral disease in humans. A. actinomycetemcomitans, strain JP2, was examined for its ability to modulate hBD-2 and -3 gene expression in normal human oral epithelial cells (NHOECs) and in OKF6/Tert cells, an immortalized cell line derived from human oral epithelial cells. Stimulation of both cell types by live bacteria, at a minimal bacteria/cell ratio of 500 : 1, resulted in increased hBD-3 gene expression. This was not evinced for hBD-2 in either cell type with live bacteria, even at bacteria/cell ratios exceeding 500 : 1. The increased hBD-3 gene expression was dependent upon viable bacteria, and not their lipopolysaccharides (LPS), since heat-killed A. actinomycetemcomitans did not induce hBD-3 transcript expression. The overall similarity between results obtained in OKF6/Tert cells and NHOECs suggest that the OKF6/Tert cell line may be a useful tool in the study of beta-defensin expression in oral epithelium.

Aggregatibacter actinomycetemcomitans↗
PubMed2002

Screening positive urine pregnancy tests for sexually transmitted diseases expedites the treatment of infected adolescent gravidas.

OBJECTIVE: To test the utility of screening the urine samples used to diagnose pregnancies at urban teen clinics for Chlamydia trachomatis and Neisseria gonorrhoeae by polymerase chain reaction (PCR). We hypothesized that urine screening would increase the proportion of teenagers treated for these two sexually transmitted diseases (STDs) before they initiated pregnancy-related care. DESIGN: A randomly selected subset of the urine samples used to diagnose 212 teen pregnancies were tested for C. trachomatis and N. gonorrhoeae by PCR. Endocervical testing was at the providers' discretion. Bivariate analyses were used to compare the teenagers randomized to the urine screening group (n = 102) and the non-screening group (n = 110). RESULTS: Of the 102 urine PCR tests, 14 (13.7%) were positive. Endocervical swabs were obtained in 31 (14.6%) of the 212 teenagers and five (16.1%) were positive. Since pelvic examinations were performed so infrequently, the net endocervical swab detection rate was significantly lower than the urine-based detection rate (1.8% compared to 13.7%; p = 0.001). Only one infected teenager was untreated when she initiated pregnancy-related care. Thus, the treatment rate was more than six times higher when urine samples were screened (12.7% compared to 1.8%; p = 0.003). CONCLUSIONS: Screening the urine samples used to diagnose teen pregnancies for two common STDs is a simple, non-invasive procedure that is acceptable to providers and patients, and significantly increases the number of teenagers who are treated for genital infection before they initiate pregnancy-related care.

Adolescent↗
PubMed2001

Inconsistent reconstitution of cytomegalovirus-specific cell-mediated immunity in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy.

Cytomegalovirus (CMV)-immune recovery was characterized in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy. CMV lymphocyte proliferation (LP), responder-cell frequency (RCF), and interferon (IFN)-gamma and interleukin (IL)-2 secretion were studied in CMV-seropositive HIV-infected patients and in CMV-seropositive HIV-uninfected control subjects. HIV-infected patients and control subjects had similar proportions of IL-2 and IFN-gamma, but levels were lower in HIV-infected patients. LP and RCF were significantly less frequent and of lower magnitude in HIV-infected patients. The measures of CMV cell-mediated immunity were correlated in HIV-uninfected but not in HIV-infected subjects. To investigate this, IL-2, IL-12, anti-CD28 plus anti-CD49d, or anti-IL-10 was added in vitro, with no effect on LP. However, CD8 cell depletion of mononuclear cells from HIV-infected patients increased LP responses to levels similar to those of uninfected control subjects; before depletion, only RCF correlated with CD4 cell counts, but after depletion, LP also correlated with CD4 cell counts.

AIDS-Related Opportunistic Infections↗
PubMed2001

Prevalence of antibodies to four herpesviruses among adults with glioma and controls.

The authors previously reported statistically significant inverse associations between adult onset glioma and histories of chickenpox and shingles among 462 cases and 443 controls in the San Francisco Bay Area Adult Glioma Study (1991--1995) and a suggestive but nonsignificant inverse association with immunoglobulin G antibodies to varicella-zoster virus in a small subset of these cases. This report considers antibodies to four common herpesviruses (varicella zoster, herpes simplex, cytomegalovirus, and Epstein Barr) among 134 cases and 165 controls that represent all subjects for whom usable blood specimens were available. The prevalences of immunoglobulin G antibodies to varicella-zoster virus, herpes simplex virus, cytomegalovirus, and Epstein-Barr virus were 90%, 71%, 57%, and 90%, respectively. After adjustment for age, White versus non-White ethnicity, and gender, glioblastoma cases were less likely than controls to have immunoglobulin G antibodies to varicella-zoster virus (odds ratio = 0.4; 95% confidence interval: 0.1, 0.9). They were also somewhat less likely to have antibodies to Epstein-Barr virus but somewhat more likely to have antibodies to herpes simplex virus and cytomegalovirus. Antibody prevalences to all four herpesviruses were similar between cases with other glioma histologies and controls. These results corroborate our previously suggestive findings of an inverse association of varicella-zoster virus antibodies with adult onset glioma.

Adult↗
PubMed2001

Recurrences of cytomegalovirus retinitis in a human immunodeficiency virus-infected patient, despite potent antiretroviral therapy and apparent immune reconstitution.

We describe a 42-year-old man with human immunodeficiency virus infection who developed multiple recurrences of cytomegalovirus (CMV) retinitis despite receiving highly active antiretroviral therapy and having apparent immune reconstitution as evidenced by CD4(+) T lymphocyte counts of > 200 cells/mm(3). Laboratory investigation during one recurrence of retinitis confirmed that there was active CMV replication in the plasma and vitreous fluid. In addition, lymphoproliferative responses to CMV antigens were absent despite evidence of reactivity to Candida antigen and pokeweed mitogen. The clinical significance of this case and of other recently reported cases is discussed.

AIDS-Related Opportunistic Infections↗
PubMed2001

Genetic resistance factor for HIV-1 and immune response to varicella zoster virus.

A 32 bp deletion in the chemokine receptor CCR5 gene modulates HIV-1 infection. However, whether this CCR5 gene variation modifies immunity to common herpesvirus infections is unknown. We investigated whole blood IgG concentrations of 157 normal adult blood donors. Also we assessed whether the 32 bp deletion of CCR5 (delta32CCR5) was associated with circulating IgG to four herpesviruses: varicella zoster virus, Epstein-Barr virus, cytomegalovirus, and herpes simplex virus type 1 and type 2. Individuals who carried delta32CCR5 were 9.2 times more likely to be seronegative for varicella zoster virus than non-carriers (95% CI 2.9-29.1), but no differences were seen for the other herpesviruses studied. Variation in CCR5 may modulate humoral immunity to varicella zoster virus.

Chickenpox↗
PubMed2001

Localized antimicrobial peptide expression in human gingiva.

The stratified epithelia of the oral cavity are continually exposed to bacterial challenge that is initially resisted by innate epithelial factors and by the recruitment of neutrophils. Antimicrobial peptides from phagocytes and epithelia contribute to this antimicrobial barrier. Using antibodies and in situ hybridization, we explored antimicrobial peptide expression in the varied epithelia of the periodontium and in cultured gingival epithelial cells. In gingival tissue, mRNA for the beta-defensins, human beta-defensin 1 (hBD-1) and human beta-defensin 2 (hBD-2) was predominately localized in suprabasal stratified epithelium and the peptides were detected in upper epithelial layers consistent with the formation of the stratified epithelial barrier. In cultured epithelial cells, both hBD-1 and -2 peptides were detected only in differentiating, involucrin-positive epithelial cells, although hBD-2 required stimulation by proinflammatory mediators or bacterial products for expression. Beta-defensins were not detected in junctional epithelium (JE) that serves as the attachment to the tooth surface. In contrast, alpha-defensins and cathelicidin family member LL-37 were detected in polymorphonuclear neutrophils (PMNs) that migrate through the JE, a localization that persists during inflammation, when the JE and surrounding tissue are highly infiltrated with PMNs. Thus, the undifferentiated JE contains exogenously expressed alpha-defensins and LL-37, and the stratified epithelium contains endogenously expressed beta-defensins. These findings show that defensins and other antimicrobial peptides are localized in specific sites in the gingiva, are synthesized in different cell types, and are likely to serve different roles in various regions of the periodontium.

Adult↗