Victor F. German

From growth factor dependence to growth factor responsiveness: The genesis of an alveolar macrophage cell line

SummaryA rat pulmonary alveolar macrophage (PAM) cell line (NR8383) was initiated in culture in the presence of a gerbil lung cell conditioned medium (GLCM), and has been propagated continuously for over 36 mo. When examined at different times throughout this in vitro period, NR8383 exhibited characteristics typical of macrophages: (a) Zymosan ingestion was seen in 90 to 98% of the cells examined; (b)Pseudomonas aeruginosa phagocytosis in 50 to 80%; (c) Nonspecific esterase activity in >95%. During the first 6 mo., the PAM replicated with doubling times approximating 15 to 20 d. Throughout this period, GLCM dependence was evident. After 27 wk in vitro, NR8383 replication increased markeldy, and within 2 wk, the doubling time was less than 48h. NR8383 was readily monitored by [3H]thymidine (TdR) blastogenesis assay. In the presence of GLCM uptake of [3H]TdR was fivefold greater than in control cultures. Adherence and growth kinetics were effectively controlled by modulation of GLCM or serum content in culture medium. It was demonstrated that PAM growth factor(s) is ubiquitous, not species-specific, and under certain conditions, may be derived from “endogenous” sources of persisting non-PAM populations within the parent, uncloned line NR8383. Cloned progeny remain devoid of non-PAM “feeder” cells, but retain macrophage properties, including interleukin-1 secretion, Fc receptors, and H2O2 production.

A continuous alveolar macrophage cell line: Comparisons with freshly derived alveolar macrophages

SummaryResponses of a recently developed rat alveolar macrophage cell (NR8383.1) line were compared to those of freshly derived alveolar macrophages in vitro. Marked inter- and intraspecies heterogeneity in levels of phagocytosis of unopsonizedPseudomonas aeruginosa or zymosan was noted among freshly derived alveolar macrophages from rats, rabbits, and baboons. In contrast, phagocytic responses of alveolar macrophage cell line were predictable and highly reproducible. Similar results were obtained in measuring oxidative burst, as indicated by the production of H2O2 and luminol-enhanced chemiluminescence. Responses were again highly variable in freshly derived alveolar macrophages stimulated with zymosan or phorbol myristic acetate; moreover, freshly derived alveolar macrophages exhibited a wide range of chemiluminescence activity in unstimulated cultures. Results strongly suggest that data derived from the continuous alveolar macrophage culture NR8383.1 can be extrapolated to freshly derived alveolar macrophages of various species, and in many experiments will be useful in avoiding the significant animal-to-animal variance observed among freshly derived cell preparations.

Avian influenza virus infection of children in Vietnam and Thailand.

Influenza viruses from chickens (H5N1) have caused outbreaks in children from both Vietnam and Thailand in 2004. All infected patients presented with fever and cough. Striking laboratory findings included leukopenia and thrombocytopenia. All children who developed progressive pneumonia with acute respiratory distress syndrome died. However, very few children received antiviral therapy.

Risk behaviors and the prevalence of Chlamydia in a juvenile detention facility

The prevalence of Chlamydia trachomatis, a sexually transmitted disease, and the association of selected behavioral risk factors were assessed in a population of adolescents in two juvenile detention facilities. Urine was collected for Chlamydia testing and a brief interview conducted for risk and demographic information. Almost all of the 200 participants were sexually active, many before the age of 13 years. The prevalence of Chlamydia infection was 22.2% among female and 8.7% among male participants. Injection drug use was the only statistically significant variable associated with infection. Education and community services are necessary to break the cycle of infection for this high-risk population.

The structure of lamertianic acid. A new diterpenic acid

Abstract A new diterpene acid, lambertianic acid, has been isolated from the oleoresin of the sugar pine tree, Pinus lambertiana Dougl. The acid has been shown to have structure III making it the optical antipode of dianiellic acid. Spectra features of these two furanoditerpene acids are discussed.

Unmet Needs in Groups of Traditionally Underserved Individuals with HIV/AIDS: Empirical Models

SUMMARY Over the course of the HIV epidemic, the demographics of the populations of affected individuals have changed. Groups that traditionally have been underserved in systems of care have a number of unmet service needs. This article presents results based on data from 478 patients in five national demonstration projects which were funded to enroll individuals from traditionally underserved groups and to help them access services using different strategies. The participants in these programs had a high level of unmet need prior to enrolling in care. Data on client service needs were related to 17 indicators of traditionally underserved status including demographic characteristics and risk behaviors, using the data modeling method of Exhaustive CHAID (Chi-squared Automatic Interaction Detector). Crack cocaine users with HIV/AIDS were more likely than other patient groups to have unmet service needs. Patients who were homeless or in precarious housing also were vulnerable. Results are discussed in terms of designing and evaluating innovative service models to close these service gaps.

Perceived barriers to receiving HIV services in groups of traditionally underserved individuals: empirical models.

SUMMARY Persons living with HIV/AIDS face many issues that make them highly vulnerable to a number of health and social problems. As the demographics of the epidemic have shifted in recent years, many members of traditionally underserved groups have encountered barriers to entering the services system. This article uses data from seven national demonstration projects funded to enroll persons with HIV/AIDS who tend to “fall through the cracks” and help them access needed services. Data on the initial perceptions of the participants about barriers to accessing services were related to 17 indicators of traditionally underserved status including demographic characteristics and behavioral variables using the data modeling method of Exhaustive CHAID (Chi-squared Automatic Interaction Detector). Through the modeling methods, the groups most likely to experience a large number of barriers to service participation are identified. Having children needing care is particularly predictive of the level of barriers to care.

Systolic pressure amplification in pedal arteries in children

Sphygmomanometric indirect blood pressure readings on the arm were compared to direct blood pressure readings from the radial and pedal arteries in pediatric patients. The direct systolic pressure in the pedal arteries was significantly (p < 0.001) greater (25.1 ± 12.3 mm Hg) than the indirect arm systolic pressure. The direct systolic pressure from the radial artery was identical to the indirect systolic arm pressure. Although there were no statistical differences between direct and indirect diastolic pressures, correlations for diastolic pressures were relatively poor. These data indicate that (1) there is a significant and unpredictable amplification of systolic pressure in the pedal arteries which may result in erroneous diagnosis of hypertension or jeopardize early detection of circulatory shock, (2) indirect blood pressure measurement with the recommended cuff width (125% of arm diameter or 40% of arm circumference) accurately reflects direct systolic pressure in the radial artery, and (3) indirect blood pressure measurement gives a relatively poor prediction of direct diastolic pressures.

Impact of HIV/AIDS Education on Health Care Provider Practice: Results from Nine Grantees of the Special Projects of National Significance Program

The study assessed the impact of health care provider HIV/AIDS education and training on patient care from nine Special Projects of National Significance. Telephone interviews were conducted with 218 health care providers within 8 months, on average, following completion of training. Respondents provided examples of how the SPNS trainings affected their provision of patient/client care. Transcribed comments reflecting change in patient/client care were classified by independent coders under 1 of 10 broad practice change categories. Eighty-two percent of the trainees identified at least one instance of change in patient/client care as a function of their training experience. Self-reported findings included changes in the number/types of patients seen, interpersonal interactions with patients/clients, HIV testing and counseling practices, patient/family education, infection control, advocacy, referrals and collaboration, documentation, and other service changes.

The effects of cyclosporine and dexamethasone on an alveolar macrophage cell line (NR8383).

Lung infections are a major source of morbidity and mortality in recipients of lung transplants. Prominent among the pathogens that cause pneumonias in these subjects are gram-negative bacilli, particularly Pseudomonas strains. One important reason that bacteria infect the lungs of these patients is that pulmonary defenses are impaired by the drugs used to prevent transplant rejection. Using a rat alveolar macrophage cell line (NR8383), we measured the effects of exposure (24 hr) to cyclosporine and dexamethasone (DEX) on the ability of these cells to (1) kill Pseudomonas aeruginosa (Pa); (2) produce H2O2; and (3) release tumor necrosis factor. We found that the bactericidal activity against unopsonized or opsonized Pa of NR8383 cells was unaltered by CsA (0.1, 0.5, or 1 micrograms/ml), DEX (10(-6) M), or CsA + DEX (0.5 micrograms/ml + 10(-6) M, respectively). Likewise, LPS-induced TNF release, and zymosan A and Pa-induced H2O2 production were unaltered by CsA (0.1 or 1 microgram/ml). In contrast, H2O2 production and TNF release were decreased by about 50% and 90%, respectively, by DEX exposure (10(-6) M). Thus, while DEX but not CsA decreased TNF release and H2O2 production in NR8383 cells, bactericidal activity against Pa was unaffected. One explanation for these results is that decreases in TNF or H2O2 of the magnitude we observed do not impair bactericidal activity against Pa; however, an alternative explanation is that Pa are killed by NR8383 cells through other mechanisms. Interpretation of these results must take into consideration the fact that macrophages from different species and tissues may respond differently to various stimuli.