Biomedical subjects

H Friedman

Publications and source records attributed to H Friedman.

At least 37 records · Page 2Linked to original sources

PubMed2001

Nicotine inhibition of apoptosis in murine immune cells.

Nicotine, the addictive component of tobacco, is thought to be at least partially responsible for the deleterious effects of smoking such as heart disease and cancer. Evidence shows that nicotine is an immunomodulator and that one of its possible mechanisms is regulation of apoptosis, or programmed cell death, in immune cells. This study examined the effects and the mechanisms of action of nicotine on dexamethasone (DEX)-induced apoptosis in murine immune cells by examining the expression of levels of the 17-kDa active caspase-3, a marker of apoptosis. Thymocytes and splenocytes from adult BALB/c female mice were incubated with concentrations of nicotine correlating to those found in the blood and tissue of smokers (0.01 microg/ml [0.022 microM] and 1 microg/ml [2.2 microM]), concurrently with 100 nM DEX, to induce apoptosis. Cytosolic protein fractions were analyzed by Western blotting with polyclonal antibodies that recognize the active form of caspase-3. The data showed that nicotine significantly blocked the formation of the DEX-induced 17-kDa caspase-3 subunit expression. This downregulation ranged from 65% to 100% of the active caspase-3 expressed in cultures treated with DEX alone. Addition of d-tubocurarine chloride (dTC), a general nicotinic receptor antagonist, inhibited nicotine downregulation of the DEX-induced active caspase-3 expression, providing evidence that this action of nicotine was receptor-mediated. These data support that nicotine is an important immunomodulator at the level of immune cell apoptosis, a process thought to be a contributory mechanism of autoimmunity, cardiovascular disease, and carcinogenesis.

Animals↗

PubMed2000

A methylthioadenosine phosphorylase (MTAP) fusion transcript identifies a new gene on chromosome 9p21 that is frequently deleted in cancer.

Homozygous deletions of human chromosome 9p21 occur frequently in malignant cell lines, and are also common in primary gliomas, lung cancers, and leukemias. Moving from the centromere to the telomere, this complex region encodes the tumor suppressor genes p15INK4B (CDKN2B), p14ARF, p16INK4A (CDKN2A), and the housekeeping gene methylthioadenosine phosphorylase (MTAP). However, not all chromosome 9p21 deletions in tumors include these tumor suppressor genes. Here we describe the partial sequence and the exact localization of a new gene on chromosome 9p21 centromeric of p15INK4B, that formed an in frame fusion transcript with MTAP in a glioma xenograft, and that is homozygously deleted in various malignant cell lines. Northern blot revealed corresponding 1.5 kb transcript in non-deleted cell lines as well as in normal lymphocytes. Using a RNA master blot membrane including 50 different tissues, we could show that this new transcript is expressed in all tissues of the adult but not or only at very low levels in most of the fetal tissues tested. The expression pattern is similar to that of p16INK4A. The localization as well as the deletion pattern makes this transcript a candidate for a new tumor suppressor gene.

Adult↗

PubMed2000

Anti-CD40, anti-CD3, and IL-2 stimulation induce contrasting changes in CB1 mRNA expression in mouse splenocytes.

The expression and function of cannabinoid receptor 1 (CB1) in mouse immune cells is unclear. Here we show that splenic B cells express more CB1 mRNA than T cells. Furthermore, splenocytes stimulated with the T cell mitogens, PMA/Io and anti-CD3, showed a decrease in CB1 message while cultures stimulated with the B cell mitogen, anti-CD40 antibody, showed an increase in message. In addition, co-treatment with mitogens and IL-2 uniformly caused an increase in CB1 mRNA. It is suggested that signaling pathways activated by T cell mitogens lead to decreased CB1 gene activation while pathways activated by B cell mitogens and IL-2 lead to increased CB1.

Animals↗

PubMed2000

Delta 9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma, IL-12, and IL-12 receptor beta 2 responses to Legionella pneumophila infection.

The marijuana cannabinoid, delta 9-tetrahydrocannabinol (THC), suppresses immunity to Legionella pneumophila and development of Th1 activity and cell-mediated immunity. In the current study, THC effects on cytokines regulating the development of Th1 cells were examined. BALB/c mice showed significant increases in serum IL-12 and IFN-gamma within hours of infection; however, the levels of these Th1-promoting cytokines as well as resistance to a challenge infection were suppressed by THC (8 mg/kg) injected 18 h before priming. The Th2-promoting cytokine, IL-4, was increased within hours of a Legionella infection and was further increased by THC treatment. These results suggested that THC injection suppressed the cytokine environment promoting Th1 immunity. In additional experiments, THC pretreatment and infection of IL-4 knockout mice showed that serum IL-12 and IFN-gamma were suppressed equally in both knockout and normal mice. This suggested that the drug-induced increase in IL-4 was not responsible for the decreases in serum IL-12 and IFN-gamma. However, THC treatment was shown to suppress the expression of IL-12 receptor beta 2 mRNA, indicating that, in addition to suppression of IL-12, THC injection suppressed the expression of IL-12 receptors. Finally, the role of cannabinoid receptors in Th1-promoting cytokine suppression was examined, and results with receptor antagonists showed that both cannabinoid receptors 1 and 2 were involved. It is suggested that suppression of Th1 immunity to Legionella is not due to an increase in IL-4 production but to a decrease in IFN-gamma and IL-12. Furthermore, both types of cannabinoid receptors are involved.

Animals↗

PubMed2000

A detrimental effect of a combined chemotherapy-radiotherapy approach in children with diffuse intrinsic brain stem gliomas?

PURPOSE: To compare the proportion of patients that survive at least 1 year following treatment with hyper-fractionated radiotherapy (HRT) to a dose of 70.2 Gy on Pediatric Oncology Group (POG) study #8495 with that of patients treated with similar radiotherapy plus cisplatinum given by continuous infusion on weeks 1, 3, and 5 of radiotherapy on POG #9239. METHODS AND MATERIALS: The eligibility criteria for the two studies were identical and included age 3 to 21 years, previously untreated tumor involving the brain stem of which two-thirds was in the pons, history less than 6 months, and clinical findings typical for diffuse intrinsic brain stem glioma, including cranial nerve deficits, long tract signs, and ataxia. The outcome of 57 patients who were treated at the 70.2 Gy dose level of POG #8495 between May 1986 and February 1988 was compared with that of 64 patients treated with identical radiotherapy plus cisplatinum on POG #9239 between June 1992 and March 1996. RESULTS: The number of patients accrued to POG #9239 was determined to guarantee that the probability was at least 0.80 of correctly detecting that the 1-year survival rate exceeded that of patients on POG #8495 by 0.2. However, the z value for this test was -1.564, giving a p value of 0.9411. That is, there is almost sufficient evidence to conclude that survival for patients receiving HRT plus cisplatinum on POG #9239 was worse than that for patients receiving the same radiotherapy alone on POG #8495. CONCLUSION: The finding that patients who received cisplatinum given as a radiosensitizing agent concurrent with HRT fared less well than those receiving the same dose of HRT alone was unexpected and is clearly a cause for concern as many current protocols for patients with diffuse intrinsic brain stem gliomas call for use of chemotherapeutic and/or biological agents given concurrent with radiotherapy.

Adolescent↗

PubMed2000

Neurodevelopment and predictors of outcomes of children with birth weights of less than 1000 g: 1992-1995.

OBJECTIVE: To examine the neurosensory and cognitive status of extremely low-birth-weight (ELBW; < 1,000 g) children born from January 1, 1992, through December 31, 1995, and to identify the significant predictors of outcome. DESIGN: An inception cohort of ELBW infants admitted to the neonatal intensive care unit (NICU) and observed to 20 months' corrected age. SETTING: A tertiary level urban NICU and follow-up clinic at a university hospital. POPULATION: Of 333 ELBW infants without major congenital malformations admitted to the NICU, 241 (72%) survived to 20 months' corrected age. We studied 221 children (92%) at a mean of 20 months' corrected age. The mean birth weight was 813 g; mean gestational age, 26.4 weeks. MAIN OUTCOME MEASURES: Assessments of cognitive and neurosensory development. RESULTS: Major neurosensory abnormality was present in 54 children (24%), including 33 (15%) with cerebral palsy, 20 (9%) with deafness, and 2 (1%) with blindness. The mean (+/- SD) Bayley-Mental Developmental Index (MDI) score was 74.7 +/- 17. Ninety-two children (42%) had a subnormal MDI score (<70). Neurodevelopmental impairment (neurosensory abnormality and/or MDI score <70) was present in 105 children (48%). Multiple stepwise logistic regression analysis that considered sex, social risk, birth weight, and neonatal risk factors revealed significant predictors of a subnormal MDI score to be male sex (odds ratio [OR], 2.73; 95% confidence interval [CI], 1.52-4.92), social risk (OR, 1.48; 95% CI, 1.09-2.00), and chronic lung disease (OR, 2.18; 95% CI, 1.20-3.94). Predictors of neurologic abnormality were a severely abnormal finding on cerebral ultrasound (OR, 8.09; 95% CI, 3.69-17.71) and chronic lung disease (OR, 2.46; 95% CI, 1.12-5.40); predictors of deafness were male sex (OR, 2.79; 95% CI, 1.02-7.62), sepsis (OR, 3.15; 95% CI, 1.05-9.48), and jaundice (maximal bilirubin level, >171 micromol/L [>10 mg/dL]) (OR, 4.80; 95% CI, 1.46-15.73). CONCLUSION: There is an urgent need for research into the etiology and prevention of neonatal morbidity.

Brain Damage, Chronic↗

PubMed2000

Murine macrophages differentially produce proinflammatory cytokines after infection with virulent vs. avirulent Legionella pneumophila.

Virulent Legionella pneumophila replicate readily in thioglycollate-elicited peritoneal macrophages from genetically permissive A/J mice, but avirulent L. pneumophila do not. The production of cytokines by macrophages infected with L. pneumophila has been studied, but the correlation of bacterial virulence with immune responses of macrophages, such as proinflammatory cytokine production, is not well understood. In this regard, production of the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1alpha, IL-1beta, and IL-6 were examined in macrophage cultures infected in vitro with virulent vs. avirulent L. pneumophila. Infection of macrophages from A/J mice with the virulent L. pneumophila up-regulated mRNA expression for these cytokines, whereas avirulent bacteria resulted in only a slight or no detectable increase in cytokine mRNA. Similarly, virulent L. pneumophila induced the macrophages to produce relatively high levels of TNF-alpha, IL-1alpha, IL-1beta, and IL-6 proteins as measured by enzyme-linked immunosorbent assays, whereas avirulent bacteria induced only low or often undetectable amounts of these cytokines. Thus, these results show the murine macrophages from susceptible A/J mice are readily infected with virulent L. pneumophila in vitro and stimulated to produce the proinflammatory acute-phase cytokines TNF-alpha, IL-1alpha, IL-1beta, and IL-6, but avirulent L. pneumophila did not. Such differences in induction of these proinflammatory cytokines by macrophages in response to virulent vs. avirulent L. pneumophila infections may be an important factor in the pathogenesis induced by these intracellular bacteria.

Animals↗

PubMed2000

Differential impact of nicotine on cellular proliferation and cytokine production by LPS-stimulated murine splenocytes.

The immunoregulatory effects of nicotine have not been fully clarified and the reported data are often conflicting. The present study investigated the role of nicotine as an immunomodulator of murine splenocytes stimulated by lipopolysaccharide (LPS), the endotoxin component of gram-negative bacteria. BALB/c female mice of two different ages, young (2-3 months) and old (18-22 months), were used. The cells were incubated with nicotine at two different time points, 3 h pre-incubation and concurrent incubation relevant to LPS stimulation, before further incubation for 48 or 72 h. Treatment of murine splenocytes with nicotine showed an impact on cellular proliferation as well as on the production of the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). The results indicated that nicotine significantly inhibited cellular proliferation of murine splenocytes in a concentration-related manner (32, 64 and 128 microg/ml). Timing of nicotine exposure prior to LPS stimulation was critical in terms of immunological impact on cytokine production. TNF-alpha and IL-6 production were significantly enhanced by 1 microg/ml of nicotine when cells were pre-incubated with nicotine for 3 h compared to concurrent incubation relative to LPS stimulation. The alteration in cytokine production varied with the age of the mouse. TNF-alpha production was significantly inhibited by nicotine in young mice, while IL-6 production was significantly inhibited by nicotine in old mice. Since any immunomodulation that alters the profile of these cytokines may cause an imbalance in the immune system impinging on health status, these findings may be important when dealing with the concept of nicotine as a therapeutic agent.

Animals↗

PubMed2000

Differential effects of nicotine and aging on splenocyte proliferation and the production of Th1- versus Th2-type cytokines.

Nicotine has a multitude of biological actions in the central and peripheral nervous systems where nicotinic acetylcholine receptors are found. Nicotinic acetylcholine receptors have also been identified on immune cells, but the effects of nicotine on immune responses are not well characterized. These studies tested the hypotheses that nicotine has an effect on both T-lymphocyte proliferation and the production of cytokines by activated T cells, processes that are necessary for effective T-cell-mediated immune responses. In addition, the effects of nicotine on these immune responses in aging animals and the effects of nicotine exposure prior to immunostimulation were investigated. Murine splenocytes were exposed to nicotine and stimulated with concanavalin A (ConA). The highest concentration of nicotine (128 microg/ml) significantly depressed proliferation of T cells both when nicotine and ConA were added concurrently and when nicotine was added 3 hr prior to ConA. Nicotine, added concurrently with ConA at concentrations between 0. 25 and 64 microg/ml, significantly inhibited the production of IL-10 by splenocytes from young adult mice, whereas the inhibition of production of IL-10 by splenocytes from old mice was significantly inhibited, but the response was more variable, depending on the nicotine concentration. In contrast, the production of IFN-gamma by splenocytes from either young adult or old mice was not affected when nicotine (0.016-64 microg/ml) was added concurrently with ConA. Pre-exposure to 1 microg/ml of nicotine for 3 hr significantly enhanced the production of IFN-gamma by splenocytes from young adult mice, whereas pre-exposure to 0.016 microg/ml of nicotine tended to but did not significantly enhance IFN-gamma production. Nicotine is now being used as an over-the-counter drug by people who differ in age and general immunocompetence. Therefore, the effects of nicotine on immune responses, independent from the effects of the other chemicals found in tobacco, need to be investigated.

Aging↗

PubMed2000

Tumor necrosis factor induces resistance of macrophages to Legionella pneumophila infection.

Legionella pneumophila is an ubiquitous opportunistic intracellular pathogen that replicates readily in thioglycollate-elicited peritoneal macrophages from genetically susceptible A/J mice. Treatment of macrophage cultures in vitro with tumor necrosis factor-alpha (TNF-alpha) induced resistance of the macrophages to infection by Legionella as compared with control macrophages treated with medium alone. Addition of small amounts of monoclonal antibody to TNF-alpha restored susceptibility of the macrophages. Furthermore, antibody to the proinflammatory cytokine interleukin-1 (IL-1) alpha/beta increased resistance, but recombinant IL-1 had little effect. Such decreased susceptibility to Legionella growth in anti-IL-1 antibody-treated cultures corresponded with enhanced levels of TNF-alpha in the supernatants of the treated cells. An antibody to another proinflammatory cytokine with known immunoregulatory properties (i.e., IL-6) had little or no effect on the ability of the macrophages to be infected by Legionella and, furthermore, treatment with recombinant IL-6, similar to recombinant IL-1, did not modify the ability of the cells to be infected in vitro. These results indicate that TNF-alpha is important in controlling L. pneumophila replication, and IL-1 can regulate TNF-alpha levels, affecting susceptibility of macrophages to infection with an intracellular opportunistic pathogen like Legionella.

Animals↗

PubMed2000

A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse.

A randomized, multicentre, open-label, phase II study compared temozolomide (TMZ), an oral second-generation alkylating agent, and procarbazine (PCB) in 225 patients with glioblastoma multiforme at first relapse. Primary objectives were to determine progression-free survival (PFS) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment. Secondary objectives were to assess overall survival and health-related quality of life (HRQL). TMZ was given orally at 200 mg/m(2)/day or 150 mg/m(2)/day (prior chemotherapy) for 5 days, repeated every 28 days. PCB was given orally at 150 mg/m(2)/day or 125 mg/m(2)/day (prior chemotherapy) for 28 days, repeated every 56 days. HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 [+3]) and the Brain Cancer Module 20 (BCM20). The 6-month PFS rate for patients who received TMZ was 21%, which met the protocol objective. The 6-month PFS rate for those who received PCB was 8% (P = 0.008, for the comparison). Overall PFS significantly improved with TMZ, with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group (P = 0.0063). The 6-month overall survival rate for TMZ patients was 60% vs. 44% for PCB patients (P = 0.019). Freedom from disease progression was associated with maintenance of HRQL, regardless of treatment received. TMZ had an acceptable safety profile; most adverse events were mild or moderate in severity.

Adult↗

PubMed2000

Practical considerations regarding the influence of the menstrual cycle on leukocyte parameters in clinical trials.

Variations in hormone levels during different phases of the menstrual cycle have been shown to alter the pharmacokinetics of some medications and are known to exert significant effects on seemingly unrelated physiologic parameters. Numerous studies have been undertaken to examine the effects of different phases of the menstrual cycle on leukocyte and differential counts, but results have often been inconclusive and contradictory. This study endeavored to reexamine these parameters, measured by standard laboratory assays, in healthy ovulating females to determine whether the menstrual cycle may have clinically relevant effects on leukocyte counts. Twenty-one women, aged 18 to 35 years and not taking hormonal contraception, were enrolled in an outpatient study within 12 hours after the onset of normal menses. The women reported to the clinical pharmacology unit for a complete blood count with differential on days 1, 2, 7, 10 through 17, 22, and 25 through 32. Blinded duplicate samples were obtained on day 2 to assess variability at the analytic site, and levels of luteinizing hormone and estradiol were measured on days 11 through 16 to determine the day of ovulation. Eighteen women completed the study, with cycle lengths ranging from 24 to 31 days (28.2 +/- 1.9 days, mean +/- SD). Evaluations of the data revealed a trend toward higher leukocyte counts and absolute neutrophil counts at the onset of menses but no significant or clinically relevant effects of different phases of the menstrual cycle on these parameters. Some split samples showed considerable variation in the assays (eg, a 42% increase in absolute neutrophil counts), suggesting that errors at the analytic facility may be a more important consideration than hormonal effects.

Adolescent↗

PubMed2000

Helicobacter pylori infection of human gastric epithelial cells induces IL-8 and TNFalpha, but not TGFbeta1 mRNA.

Helicobacter pylori (Hp) infection causes gastric ulcers and gastric carcinomas. The mechanisms of these diseases are not known but Hp induction of cytokines is believed to be involved. However, the profile as well as the involvement of cytokines induced by Hp infection is less clear. In the present study, steady state levels of interleukin-8 (IL-8), tumor necrosis factor-alpha (TNFalpha) and TGFbeta1 mRNA of human gastric epithelial cell lines Kato III, AGS and NCI-87N in response to Hp infection were investigated. The cell cultures were infected with Hp for up to 18 h. Total RNA was extracted and analyzed by reverse transcription-PCR. The three cell lines tested expressed low constitutive levels of mRNA for IL-8 and TNFalpha. The mRNA levels of IL-8 quickly increased within 2 h in all three cells tested and reached a peak at 4 h following infection with Hp. In contrast, the levels of TNFalpha after Hp infection increased in only Kato III cells. The other cells, AGS and NCI-87N, responded with minimum increases after Hp infection. The TGFbeta1 mRNA was constitutively expressed in both AGS and NCI-87N cells, but Kato III cells expressed only low levels prior to infection. The Hp infection did not increase the levels of TGFbeta1 mRNA as well as TGFbeta1 secretion in all cells tested. These results indicate that the cytokine response to Hp infection differs according to the cells studied and the response may be linked somewhat to TGF levels of gastric cells.

Cell Line↗

PubMed2000

Differential effects of virulent versus avirulent Legionella pneumophila on chemokine gene expression in murine alveolar macrophages determined by cDNA expression array technique.

The cDNA expression array technique is a powerful tool to determine, at one time from many genes, specific gene messages modulated by infection. In the present study, we identified genes modulated in response to virulent versus avirulent Legionella pneumophila infection of the alveolar macrophage cell line MH-S by the cDNA expression array technique. Many macrophage genes were found to be modulated after 5 h of in vitro infection with L. pneumophila. In particular, it was found that the monocyte chemotactic protein 3 (MCP-3) gene expression was significantly induced by infection with virulent L. pneumophila but not with avirulent L. pneumophila. In contrast, other chemokine genes, such as macrophage inflammatory protein (MIP) 1alpha, were induced by both virulent and avirulent L. pneumophila. Reverse transcription (RT)-PCR assay of total RNA isolated from macrophages infected with the bacteria for 5 or 24 h confirmed the differential induction of the chemokine genes by virulent versus avirulent L. pneumophila. Thus, the cDNA expression array technique readily revealed differential induction by L. pneumophila infection of select chemokine genes of macrophages from more than 1,100 genes. These results also indicate that certain chemokine genes may be selectively induced by virulent bacteria.

Animals↗

PubMed2000

Induction of interleukin-4 (IL-4) by legionella pneumophila infection in BALB/c mice and regulation of tumor necrosis factor alpha, IL-6, and IL-1beta.

Infection of BALB/c mice with a sublethal concentration of Legionella pneumophila causes an acute disease that is resolved by innate immune responses. The infection also initiates the development of adaptive Th1 responses that protect the mice from challenge infections. To study the early responses, cytokines induced during the first 24 h after infection were examined. In the serum, interleukin-12 (IL-12) was detectable by 3 h and peaked at 10 h, while gamma interferon was discernible by 5 h and peaked at 8 h. Similar patterns were observed in ex vivo cultures of splenocytes. A transient IL-4 response was also detected by 3 h postinfection in ex vivo cultures. BALB/c IL-4-deficient mice were more susceptible to L. pneumophila infection than were wild-type mice. The infection induced higher serum levels of acute-phase cytokines (tumor necrosis factor alpha [TNF-alpha], IL-1beta, and IL-6), and reducing TNF-alpha levels with antibodies protected the mice from death. Moreover, the addition of IL-4 to L. pneumophila-infected macrophage cultures suppressed the production of these cytokines. Thus, the lack of IL-4 in the deficient mice resulted in unchecked TNF-alpha production, which appeared to cause the mortality. Monocyte chemoattractant protein-1 (MCP-1), a chemokine that is induced by IL-4 during Listeria monocytogenes infection, was detected at between 2 and 30 h after infection. However, MCP-1 did not appear to be induced by IL-4 or to be required for the TNF-alpha regulation by IL-4. The data suggest that the early increase in IL-4 serves to regulate the mobilization of acute phase cytokines and thus controls the potential harmful effects of these cytokines.

Animals↗

PubMed2000

The cannabinoid system and cytokine network.

Many advances have been made in the last few years concerning our understanding of the receptors and ligands composing the cannabinoid system. Likewise, the science surrounding cytokine biology has advanced enabling us to measure these proteins more precisely as well as understand and interpret the meaning of changes in their levels. Scientists wishing to study the health consequences of smoking marijuana as well as understand the possible role of endogenous cannabimimetic ligands in immune regulation have continued to study the influence of these substances on the regulation and development of the cytokine network. Research has shown that two major cannabinoid receptor subtypes exist and that subtype 1 (CB1) is expressed primarily in the brain whereas subtype 2 (CB2) is expressed primarily in the periphery. A variety of ligands for these receptors based on the cannabinoid structure have been synthesized and studied as well as low affinity compounds, noncannabinoid ligands, and endogenous ligands derived from fatty acid eicosanoids. Highly selective receptor antagonists have also been introduced and studied. Synthetic, low affinity ligands such as (+)-HU-211 and DMH-11C have been shown to cause anti-inflammatory effects possibly through inhibiting the production and action of TNF-alpha and other acute phase cytokines. In addition, suppression of TNF and other cytokines such as GM-CSF, IL-6, IFNgamma, and IL-12 has also been seen following exposure to high affinity and psychoactive ligands such as marijuana and THC. However, some of these ligands have also been shown to increase rather than decrease interleukins such as IL-1, IL-4, IL-10, and IL-6, cytokines such as TNF-alpha, and chemokines such as IL-8, MIP-1, and RANTES. The endogenous ligand, anandamide, has been shown in culture to either suppress the proliferation response to prolactin or enhance the response to cytokines such as IL-3 and IL-6. This eicosanoid has also been shown to increase the production of interleukins and other cytokines. Cannabinoid receptors have been shown to be involved in some but not all of these effects. It is clear that psychoactive and nonpsychoactive compounds have demonstrated effects in vivo and in vitro on the production and function of a variety of cytokines. Depending upon the model system, these effects are often conflicting, and the involvement of cannabinoid receptors is unclear. However, enough evidence exists to suggest that the cannabinoid system significantly impacts the functioning of the cytokine network, and this association may provide clues to the mechanisms of certain immune diseases and form the basis for new immunotherapies.

Animals↗

PubMed2000

Photometric observations of a polychromatic laser guide star.

We report the photometric observation of a polychromatic laser guide star (PLGS) using the AVLIS laser at the Lawrence Livermore National Laboratory (LLNL). The process aims at providing a measurement of the tilt of the incoming wave front at a telescope induced by atmospheric turbulence. It relies on the two-photon coherent excitation of the 4D5/2 energy level of sodium atoms in the mesosphere. We used two laser beams at 589 and 569 nm, with a maximum total average output power of approximately 350 W. For the purpose of photometric calibration, a natural star was observed simultaneously through the same instrument as the PLGS at the focus of the LLNL 50-cm telescope. Photometric measurements of the 330-nm return flux confirm our previous theoretical studies that the PLGS process should allow us at a later stage to correct for the tilt at wavelengths as short as approximately 1 microm at good astronomical sites. They show also that, at saturation of two-photon coherent absorption in the mesosphere, the backscattered flux increases by a factor of approximately 2 when the pulse repetition rate decreases by a factor of 3 at constant average power. This unexpected behavior is briefly discussed.

Journal Article↗

PubMed2000

Differential expression of IL-1 and TNF receptors in murine macrophages infected with virulent vs. avirulent Legionella pneumophila.

Infection of macrophages from genetically susceptible A/J mice with Legionella pneumophila induces high levels of various cytokines in serum as well as in cultures of spleen or peritoneal cells from the mice. However, modulation of receptor expression for these cytokines during infection has not been studied in detail, even though these receptors on macrophages have a critical role in inflammatory responses during the infection. In the present study, the differential expression of mRNA for TNF and IL-1 receptors as well as receptor antigens during infection of macrophages with virulent vs. avirulent L. pneumophila was investigated. Mouse thioglycollate-elicited peritoneal macrophages showed by RT-PCR constitutive steady-state levels of mRNA for TNF-type I and -type II receptors as well as IL-1 type I receptor. However, IL-1 type II receptor mRNA was not expressed in thioglycollate-elicited macrophages. Infection of macrophages with virulent bacteria caused an upregulation of IL-1 type I and TNF type I receptor mRNA, but had no effect on TNF type II receptor message. Avirulent L. pneumophila infection caused much less induction of these receptor mRNAs. The amount of receptor antigen of IL-1 type I on the surface of macrophages was also increased by infection with virulent L. pneumophila determined by flow cytometric analysis. These results indicate that L. pneumophila infection not only causes induction of various cytokines, but also modulation of certain cytokine receptors, which may regulate the susceptibility to infection.

Animals↗