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Background: We tested the in vitro activity of pleconaril and AG7088 against five numbered human rhinovirus (HRV) serotypes and 46 clinical HRV isolates of undefined serotype recovered from patients with common colds. Antiviral effect of pleconaril and AG7088 were assessed by cytophathic effect (CPE) inhibition assays in Ohio HeLaI cells using microscopic and spectrophotometric methods. Both compounds were tested at concentrations of 1.0, 0.1 and 0.01 microg/ml. For the numbered HRV serotypes, the median EC(50) value determined by the microscopic CPE inhibition was slightly better for AG7088 compared to pleconaril (P=0.02) but was similar by spectrophotometric assay (P=0.15). For clinical HRV isolates the median EC(50) value determined microscopically was 0.01 microg/ml range, <0.01-0.04 microg/ml) for AG7088 compared to 0.07 microg/ml (range, <0.01->1 microg/ml) for pleconaril (P<0.001). The median EC(50) value determined by spectrophotometric assay was 0.01 microg/ml (range, <0.01-0.04 microg/ml) for AG7088 compared to 0.04 microg/ml (range, <0.01->1 microg/ml) for pleconaril (P<0.001). By either the microscopic or spectrophotometric methods the median EC(50) value of AG7088 was <1.0 microg/ml for all isolates and was >10.0 microg/ml of pleconaril for approximately 9% of isolates. In vitro AG7088 appeared to be more potent and to have a broader antirhinoviral spectrum than pleconaril among clinical HRV isolates. The clinical relevance of these in vitro results needs to be determined in controlled clinical trials.

Perchlorate is known to suppress thyroid function by inhibiting uptake of iodide by the human thyroid at doses of 200 mg/day or greater. A study was conducted to investigate the potential effects of perchlorate in drinking water on thyroid function in newborns and school-age children. A total of 162 school-age children and 9784 newborns were studied in three proximate cities in northern Chile that have different concentrations of perchlorate in drinking water: Taltal (100 to 120 micrograms/L), Chañaral (5 to 7 micrograms/L), and Antofagasta (non-detectable: < 4 micrograms/L). Among schoolchildren, no difference was found in thyroid-stimulating hormone levels or goiter prevalence among lifelong residents of Taltal or Chañaral compared with those of Antofagasta, after adjusting for age, sex, and urinary iodine. No presumptive cases of congenital hypothyroidism were detected in Taltal or Chañaral; seven cases were detected in Antofagasta. Neonatal thyroid-stimulating hormone levels were significantly lower in Taltal compared with Antofagasta; this is opposite to the known pharmacological effect of perchlorate, and the magnitude of difference did not seem to be clinically significant. These findings do not support the hypothesis that perchlorate in drinking water at concentrations as high as 100 to 120 micrograms/L suppresses thyroid function in newborns or school-age children.

Individuals with a homozygous deletion of the glutathione S-transferase theta 1 (GSTT1) gene lack GSTT1 enzymatic detoxification of environmental carcinogens by conjugation with glutathione. The GSTT1 gene deletion has been associated with carcinogen-induced chromosomal changes in lymphocytes, and some but not all epidemiological evidence has suggested that the GSTT1 gene deletion may increase susceptibility to myelodysplasia. We conducted a case-control study to test whether individuals with an inherited homozygous deletion of the GSTT1 gene are at increased risk of acute myeloid leukemia (AML). The GSTT1 and GST mu 1 (GSTM1) genotypes were determined by PCR using lymphocyte or bone marrow DNA from 297 AML patients and 152 controls. AML patients were selected from Southwest Oncology Group clinical studies, and controls were identified by random digit dialing in Washington state. No association was observed between the GSTT1 gene deletion and AML [race-adjusted odds ratio (OR), 0.94; 95% confidence interval (CI), 0.55-1.60] or between the GSTM1 gene deletion and AML (race-adjusted OR, 1.26; 95% CI, 0.85-1.88). Patients with secondary AML had a slightly higher prevalence of the GSTT1 and GSTM1 gene deletions compared with de novo AML patients or controls, but this was consistent with chance. Exploratory analyses of AML cytogenetics suggested a few associations, i.e., between the GSTT1 gene deletion and trisomy 8, and between the GSTM1 gene deletion and non-8 trisomies or inv(16). These results do not support the hypothesis that the GSTT1 gene deletion is related to the incidence of AML.

Purpose: This study documents the prevalence of workplace health promotion activities at small worksites with 15 to 99 employees., Design: A random sample of U.S. worksites stratified by size and industry (n = 3628) was drawn using American Business Lists., Measures: Each worksite was surveyed using a computer-assisted telephone interview system to document activities related to health promotion and related programs, worksite policies regarding health and safety, health insurance, and philanthropic activities., Subjects: Participation varied by industry and size, with an overall response rate for eligible worksites of 78% for a total sample of 2680 worksites., Data Analysis: Data were analyzed using SUDAAN statistical software., Results: Approximately 25% of worksites with 15 to 99 employees offered health promotion programs to their employees, compared with 44% of worksites with 100+ employees. As with the larger worksites, the most common programs for worksites with 15 to 99 employees were those related to occupational safety and health, back injury prevention, and CPR. The majority of worksites in both size categories had alcohol, illegal drug, smoking, and occupant protection policies. The majority of both small and large worksites also offered group health insurance to their employees (92% and 98%, respectively), with many of the worksites also extending benefits to family members and dependents (approximately 80% for both business sizes)., Conclusions: The results indicated that small worksites are providing programs to their employees, with a primary focus on job-related hazards. Small worksites also have formal policies regarding alcohol, drug use, smoking, and seatbelt use and offer health insurance to their employees at a rate only slightly lower than that of large worksites.

Tyrosine based motifs conforming to the consensus YXXphi (where phi represents a bulky hydrophobic residue) have been shown to interact with the medium chain subunit of clathrin adaptor complexes. These medium chains are targets for phosphorylation by a kinase activity associated with clathrin coated vesicles. We have used the clathrin coated vesicle associated kinase activity to specifically phosphorylate a soluble recombinant fusion protein of mu2, the medium chain subunit of the plasma membrane associated adaptor protein complex AP-2. We have tested whether this phosphorylation has any effect on the interaction of mu2 with the tyrosine based motif containing protein, TGN38, that has previously been shown to interact with mu2. Phosphorylation of mu2 was shown to have no significant effect on the in vitro interaction of mu2 with the cytosolic domain of TGN38, indicating that reversible phosphorylation of mu2 does not play a role in regulating its direct interaction with tyrosine based internalisation motifs. In addition, although a casein kinase II-like activity has been shown to be associated with clathrin coated vesicles, we show that mu2 is not phosphorylated by casein kinase II implying that another kinase activity is present in clathrin coated vesicles. Furthermore the kinase activity associated with clathrin coated vesicles was shown to be capable of phosphorylating dynamin 1. Phosphorylation of dynamin 1 has previously been shown to regulate its interaction with other proteins involved in clathrin mediated endocytosis.

Objective: We examined adverse birth outcomes among Mexican-Americans to determine the effect of country of maternal birth, a measure of acculturation., Design: We conducted a retrospective cohort analysis of birth outcomes among 4800 Mexico-born and 4800 US-born Mexican-American women using Washington State birth certificate data from 1989 to 1994. Length of residence at current address was used to help refine our measure of acculturation., Results: US-born women had a slightly increased risk of preterm birth relative to Mexico-born women [relative risk (RR) 1.18, 95% confidence interval (CI) 1.04-1.33]. Among Mexico-born women, the risk of preterm birth increased with greater duration of current residence., Conclusions: US-born Mexican-American women had a slightly increased risk of preterm birth despite having more adequate prenatal care, more education, and higher socioeconomic indicators. This may be due to acculturation factors, such as earlier pregnancy, loss of social support systems, and increased smoking or alcohol use. Reducing this risk depends on recognition among health care workers and policy-makers of the potential influence of acculturation on health in this population.

Several intracellular membrane trafficking events are mediated by tyrosine-containing motifs found within the cytosolic domains of certain integral membrane proteins. Many of these tyrosine motifs conform to the consensus YXXPhi (where Phi represents a bulky hydrophobic residue). This YXXPhi motif has been shown to interact with the medium chain subunits of adaptor complexes that generally link relevant integral membrane protein cytosolic domains to the clathrin coat involved in vesicle formation. The motif YXXPhi is also very similar to motifs that are targets for phosphorylation by tyrosine kinases. Tyrosine kinase inhibitors known as tyrphostins are structural analogues of tyrosine, and so it is possible that tyrphostins could also inhibit interactions between medium chains and YXXPhi motifs. TGN38 is a type I integral membrane protein containing a tyrosine motif, YQRL, within the cytosolic domain. We have previously shown that this motif interacts directly with the medium chain subunit of the plasma membrane localized AP-2 adaptor complex (mu2). We have investigated a range of tyrphostins and demonstrated a specific inhibition of the interaction between mu2 and the TGN38 cytosolic domain by tyrphostin A23 through in vitro analysis and the yeast two-hybrid system. These data raise the exciting possibility that different membrane traffic events could be inhibited by specific tyrphostins.

TGN38 is a type I integral membrane protein that cycles between the trans-Golgi network and the plasma membrane. Internalization at the cell surface and targeting back to the trans-Golgi network is dependent on a hexapeptide motif, SDYQRL, in the cytosolic tail of the protein. It was recently demonstrated that this motif specifically interacts with the mu2 subunit of the AP2 adaptor complex. We have studied the interaction between the entire cytosolic domain of TGN38 and mu2 using the yeast two hybrid system, in vitro binding of recombinant fusion proteins and IAsys optical biosensor technology. A specific interaction has been demonstrated in each of the systems we have employed. We have shown an absolute requirement for Tyr-333 of TGN38 in binding to mu2. In addition we found that mutation of Ser-331 to alanine reduces the affinity of the interaction. By measuring tryptophan fluorescence at equilibrium, we have also determined the dissociation constant for the interaction between the entire cytosolic tail of TGN38 and mu2 as 58 nM. In contrast to previously published work, our data suggest that not only Tyr-333 but also its context is important in determining the specificity of binding of TGN38 to mu2.

Objective: To describe a coccidioidomycosis outbreak in Ventura County following the January 1994 earthquake, centered in Northridge, Calif, and to identify factors that increased the risk for acquiring acute coccidioidomycosis infection., Design: Epidemic investigation, population-based skin test survey, and case-control study., Setting: Ventura County, California., Results: In Ventura County, between January 24 and March 15, 1994, 203 outbreak-associated coccidioidomycosis cases, including 3 fatalities, were identified (attack rate [AR], 30 cases per 100,000 population). The majority of cases (56%) and the highest AR (114 per 100,000 population) occurred in the town of Simi Valley, a community located at the base of a mountain range that experienced numerous landslides associated with the earthquake. Disease onset for cases peaked 2 weeks after the earthquake. The AR was 2.8 times greater for persons 40 years of age and older than for younger persons (relative risk, 2.8; 95% confidence interval [CI], 2.1-3.7; P<.001). Environmental data indicated that large dust clouds, generated by landslides following the earthquake and strong aftershocks in the Santa Susana Mountains north of Simi Valley, were dispersed into nearby valleys by northeast winds. Simi Valley case-control study data indicated that physically being in a dust cloud (odds ratio, 3.0; 95% CI, 1.6-5.4; P<.001) and time spent in a dust cloud (P<.001) significantly increased the risk for being diagnosed with acute coccidioidomycosis., Conclusions: Both the location and timing of cases strongly suggest that the coccidioidomycosis outbreak in Ventura County was caused when arthrospores were spread in dust clouds generated by the earthquake. This is the first report of a coccidioidomycosis outbreak following an earthquake. Public and physician awareness, especially in endemic areas following similar dust cloud-generating events, may result in prevention and early recognition of acute coccidioidomycosis.

Two years after implantation of an ICD with epicardial patch leads, a patient presented with hemoptysis. The posterior left ventricular patch was found to have eroded into lingular segmental bronchus. During thoracotomy, the hardware was removed and the bronchus successfully repaired.

To assess whether high school chemistry teachers had higher urinary mercury concentrations than other high school teachers, 24 high school teachers from nine schools in northeastern Ohio were studied. First morning voided urine samples and air samples from the teachers' classrooms were analyzed for total mercury content by cold vapor atomic absorption. The median adjusted urinary mercury concentration in the 12 chemistry teachers was 4.6 microg/g creatinine (range 2.2-8.2 microg/g creatinine) and it was 6.3 microg/g creatinine in the 12 non-chemistry teachers. All classroom air samples contained mercury levels below detection limits. No evidence was provided that high school chemistry teachers are at increased risk of chronic mercury exposure from their teaching activities compared to other high school teachers.

Guided by a conceptual model, the authors used both qualitative data (e.g., individual interviews, focus groups) and quantitative data from an employee survey (N = 3,388) in 10 federal agencies to investigate whether organization context and implementation process affected participation in worksite health promotion and disease prevention (HPDP) activities among demographic subgroups. Overall, employees on average participated in fewer than two agency-supported health-related activities per year (17% in fitness, 40% in health risk assessment activities). Employees participated more where coworkers endorsed such programs. Minority employees and employees in lower level positions were more likely to participate in fitness activities when organizations had a more comprehensive program structure, engaged in more marketing strategies, gave time off to employees to participate, or had on-site facilities. Management support for the program was related to participation by employees who were male, white, and had upper level positions. The data supported the proposed model; also confirmed was two predicted relationships between model constructs, which provided a better understanding of differential participation by employee groups.

The recovery of human rhinovirus (HRV) from nasal washings and nasal and pharyngeal swabs from volunteers with naturally acquired colds was compared in different cell types. Human embryonic lung fibroblast (HELF) strain WI-38 (sensitivity, 61 to 84%) and HeLa-I, an HRV-susceptible HeLa clone (sensitivity, 86 to 94%), were the most sensitive cell types used. HELF-WI-38 cells showed a cytopathic effect earlier than the other cells used, and the different strains of HRV-susceptible HeLa cells varied in their sensitivities for HRV isolation. HRV was detected in a single cell type in 20 to 35% of the positive samples, suggesting that use of a combination of different HRV-susceptible cell lines is the best approach for the recovery of HRV. Although nasal washings tended to yield more HRV isolates than nasal and pharyngeal swabs, the two sampling methods were not found to be significantly different.

We monitored the responses of solid organ transplant recipients (SOTs) to influenza vaccine during consecutive influenza seasons. Standard 1993-1994 trivalent influenza vaccine was given to 68 SOTs and 29 healthy young adults, and hemagglutination-inhibition (HI) antibody titers were determined pre- and post-immunization. Significant rises in geometric mean antibody titers occurred post-immunization for all three antigens in both groups. However, the magnitude of the rise was lower in SOTs (1.5-2.3-fold vs. 8.7-10.4-fold, depending on the antigen) (P < .05), and significantly fewer SOTs had protective HI titers (> or = 1:40) for B/Panama/45/90 antigens (50% of SOTs vs. 76% of healthy subjects) and for A/Texas/36/91 (H1N1) antigens (60% vs. 90%). After exclusion of persons with high preimmunization titers, SOTs had significantly reduced frequencies of > or = 4-fold antibody responses compared with those of healthy subjects (23%-38% vs. 86%-100%) (P < .05 for each antigen). When a series of two injections of standard 1994-1995 vaccine was given to 23 SOTs, there was no significant improvement in vaccine response with the second dose. Some SOTs have deficient responses to inactivated influenza vaccines.

Purpose: To describe how well-established health promotion programs at selected federal worksites were designed, organized, and implemented and to identify factors related to employee participation., Design: This descriptive study related characteristics of the health promotion program, worksites, and workforce to employee participation and perceptions of program impacts., Setting: The study was conducted at 10 established federal worksite health promotion programs in various regions of the country., Subjects: A total of 3403 of 5757 federal employees (59%) sampled completed employee surveys., Measures: Study data were collected from on-site observations, interviews, focus groups, and employee surveys., Results: Overall, program participation rates were high, and employees reported positive impacts on their health and attitudes toward the agency. Participation in health screening, perceived program convenience, and perceived support by management and others were important determinants of participation and of perceived work-related outcomes., Conclusions: Although site selection and response rate limit generalizability, the sites evaluated represent a broad cross-section of different types and sizes of agencies. The findings should be relevant in many other settings. Study programs compare favorably with private sector programs. Employees viewed the programs very positively. The most cogent challenge in justifying these, and perhaps other, worksite programs is that most participants already or simultaneously engage in health promotion activities elsewhere "on their own."

We conducted a comparative study of the antirhinovirus activities of soluble intercellular adhesion molecule-1 (sICAM-1) and a chimeric ICAM-1/immunoglobulin A (IgA) molecule (ICI-5D/IgA) for nine major receptor group human rhinovirus (HRV) serotypes and for a variant of HRV-39 relatively resistant to inhibition by sICAM-1. ICI-5D/IgA inhibited the infectivity of eight of the nine wild-type HRVs and the resistant HRV-39 variant and was 60 to 170 times more potent than sICAM-1 on a molar basis. In contrast to sICAM-1, ICI-5D/IgA directly neutralized the infectivity of the representative HRVs by approximately 1 log10. These results expand on the antirhinovirus spectrum of ICI-5D/IgA, confirm that dimeric forms of sICAM-1 have a higher antirhinoviral potency than monomeric sICAM-1, and indicate that cross-linking of two adjacent receptor binding sites on the virus capsid by a divalent receptor enhances the direct inactivation of viral infectivity.

Variants of human rhinovirus serotype 39 (HRV-39) relatively resistant to inhibition by soluble intercellular adhesion molecule-1 (sICAM-1) were selected by serial passages in HeLa or WI-38 cells in the presence of sICAM-1. Moderate resistance (four- to fivefold increases in 50% effective inhibitory concentrations [EC50s]) was observed after the second passage in HeLa cells and remained constant during six further passages in the presence of 10 micrograms of sICAM-1 per ml. A 7- to 17-fold increase in EC50s was observed in WI-38 cells during passage with 10 micrograms/ml, and reversion to a nonresistant phenotype was not observed after four passages in the absence of sICAM-1. Resistance of a higher degree was obtained by passing HRV-39 in the presence of 100 micrograms of sICAM-1 per ml in HeLa cells (30-fold EC50 increase). The sICAM-1-resistant phenotype was estimated to constitute 1 in 10(4) to 1 in 10(5) PFU of a nonexposed HRV-39 population. Low to moderate levels of resistance to sICAM-1 inhibition emerge readily during in vitro passage in the presence of sICAM-1 and appear to be phenotypically stable.

We studied the in vitro antirhinovirus activity of a soluble form of intercellular adhesion molecule-1 (sICAM-1). sICAM-1 inhibited the cytopathic effect of 10 representative human rhinovirus (HRV) serotypes of the major receptor group with, 50% effective concentrations (EC50s) of 0.1 to 7.9 micrograms/ml. Cell type-dependent variation in the inhibitory activity of sICAM-1 was observed for two major receptor group serotypes in HeLa cells (EC50, greater than 32 micrograms/ml), and no inhibitory effect was observed for two serotypes which use different cell receptors. Yield reduction assays showed that sICAM-1 inhibited the replication of HRV serotype 39 (HRV-39) in human adenoid explants in a concentration-dependent manner. No direct inactivation of infectivity of HRV-39 (EC50, 0.5 microgram/ml) was observed after incubation with sICAM-1 (32 micrograms/ml) for up to 24 h. Single-cycle-of-replication experiments with the addition of sICAM-1 at 10 micrograms/ml at different times showed that the inhibitory effect occurs only when sICAM-1 is added within 30 min after infection. In experiments in which absorption was carried out at 4 degrees C and then a single cycle of replication incubation was carried out at 33 degrees C, it was found that sICAM-1 at 10 micrograms/ml was inhibitory only when it was present during the absorption period. Our data show that sICAM-1 is inhibitory for representative major receptor group serotypes of HRV in two cell lines and human respiratory epithelium, that the interaction of sICAM-1 with HRV is readily reversible by dilution, and that the inhibitory effect of sICAM-1 on virus replication is present early in the infection cycle.

Worksite fitness and health promotion programs have grown exponentially in the past 15 years. To examine the impact of these programs, the literature through 1988 was reviewed. In general, fitness and wellness programs result in increased levels of fitness and a reduction in the risk factors for coronary heart disease. Recent research using control groups has found relations between reduction in health care costs, absenteeism, and turnover and implementation of comprehensive health promotion programs. Issues related to participation rates, program implementation, and evaluation are also addressed.

A review of animals receiving a TAH with 4 mechanical valves suggests that the least damage to the blood cell components is associated with the BS valve when compared with the MH valve at similar heart rates. Clinical anemia in varying stages was observed in most animals in this study. However, most calves compensated for the increased rate of hemolysis and none required blood transfusions. The BS valve would appear to combine minimal turbulence and mechanical crushing in a physiological setting.

The male offspring of mice stressed by crowding during the final third of pregnancy showed reductions in sexual behavior and fertility. When paired with receptive females, their latencies to mount and to achieve intromission and ejaculation were greater than controls, and 30% of them failed to ejaculate in the 100-min test. When housed continuously for 4 days with females, 31% of them failed to impregnate their partners, compared with 4% of controls. The sexual receptivity of the untreated females paired with prenatally stressed males was not affected. Resting testosterone levels of prenatally stressed males did not differ from those of controls, and the pattern of rise and fall of testosterone during a 60-min interaction with a female showed only minor differences. The results suggest a central, rather than peripheral, mediation of the behavioral effects of prenatal stress.

Vegetative endocarditis and thromboembolism are the two leading pathologic findings and causes of death in calves receiving total artificial hearts (TAH). Percutaneous access devices (PAD) for the pneumatic drive lines often become infected and may serve as the nidus of infection of the vegetative lesions. Observations of 80 calves living with TAHs revealed that most infections began at the dorsal surface of the PAD. Chronic skin ulceration or acute, traumatic avulsion can result in PAD separation from the skin and bacterial implantation. Evaluation of 58 necropsy specimens from calves with TAHs demonstrated improper flange positioning in 76% of the PAD and gross infection in 57%. A new implantation technique and design of PAD have resulted in better flange position and less irritation at the skin/device interface. Necropsies of 11 animals with the new PAD have shown a reduction in superficial infections.

Bone marrow transplantation (BMT) is often followed by significant morbidity and mortality due to protracted immunodeficiency. We have hypothesized that the bone marrow-ablative regimen may delay the recovery of normal immune function following transplantation by impairing the interaction of host endothelial cells with circulating graft-derived lymphocytes. This report compares the relative effects of busulfan (an alkylating drug) and gamma-irradiation on the tissue-specific localization potential of lymphocytes and the eventual recovery of immune function within syngeneic murine transplant recipients. Localization of normal lymphocytes into peripheral lymph nodes of irradiated BMT recipients was markedly less (less than 50%) than in busulfan-treated or normal mice over the first 2 months post-BMT. This finding correlated with irradiation-induced endothelial cell edema and microvascular occlusions within lymphocyte-receptive areas of the nodal microvasculature. The effect of both preparative regimens on the recovery of contact hypersensitivity (CHS) was also analyzed. This response recovered more quickly (between 1 and 2 months) in busulfan-pretreated animals. Further experiments demonstrated that the decrease in CHS responsiveness appeared, in part, related to a depression in the capacity of lymphocytes to localize into skin sites of antigen deposition within irradiated mice. The impairment of tissue-specific lymphocyte localization may represent a novel mechanism by which whole body irradiation can contribute to delayed immunologic reconstitution following bone marrow transplantation.