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Biomedical subjects

H Friedman

Publications and source records attributed to H Friedman.

At least 127 records · Page 7Linked to original sources
PubMed1994

Inhibition of Legionella pneumophila growth by gamma interferon in permissive A/J mouse macrophages: role of reactive oxygen species, nitric oxide, tryptophan, and iron(III).

A/J mouse macrophages infected with Legionella pneumophila and treated with gamma interferon (IFN-gamma) in vitro developed potent antimicrobial activity. This antilegionella activity was independent of the macrophage capacity to generate reactive oxygen intermediates, since the oxygen radical scavengers catalase, superoxide dismutase, mannitol, and thiourea had no effect on the antilegionella activity of IFN-gamma-activated macrophages. Likewise, whereas the ability of IFN-gamma-activated macrophages to synthesize reactive nitrogen intermediates was markedly inhibited by the L-arginine (Arg) analogs, NG-monomethyl-L-arginine and L-aminoguanidine, as well as by incubation in L-Arg-free medium, their ability to inhibit the intracellular growth of L. pneumophila remained intact. The intracellular growth of L. pneumophila in A/J macrophages was inhibited by the iron(III) chelator desferrioxamine and reversed by Fe-transferrin as well as by ferric salts. Additionally, IFN-gamma-activated macrophages incorporated 28% less 59Fe(III) compared with nonactivated cells. Nonetheless, only partial blocking of growth restriction was observed when IFN-gamma-stimulated macrophages were saturated with iron(III). Indole-propionic acid, which appears to inhibit the biosynthesis of L-tryptophan (L-Trp), was an L-Trp-reversible growth inhibitor of L. pneumophila in macrophages, implying that the intracellular replication of this pathogen is also L-Trp dependent. However, an excess of exogenous L-Trp did not reverse the growth inhibition due to IFN-gamma, though a small synergistic effect was observed when the culture medium was supplemented with both iron(III) and L-Trp. We conclude that IFN-gamma-activated macrophages inhibit the intracellular proliferation of L. pneumophila by reactive oxygen intermediate- and reactive nitrogen intermediate-independent mechanisms and just partially by nutritionally dependent mechanisms. We also suggest that additional mechanisms, still unclear, may be involved, since complete reversion was never obtained and since at higher concentrations of IFN-gamma, iron(III) did not induce any significant reversion in the L. pneumophila growth inhibition.

Animals↗
PubMed1994

Binding of Legionella pneumophila to macrophages increases cellular cytokine mRNA.

Infection of macrophages with Legionella pneumophila induces formation of interleukin 1 beta (IL-1 beta), but the molecular basis of this is not understood. Binding of bacteria to macrophage surfaces is the first step in an infection process. Therefore, we examined whether this step was sufficient to increase the cellular level of mRNAs for IL-1 beta and other cytokines. To assess the effect of binding of L. pneumophila on the steady-state levels of cytokine mRNAs, cultures of thioglycolate-elicited macrophages from L. pneumophila-susceptible A/J mice were treated with cytochalasin D and infected with L. pneumophila and the total RNA was extracted for analysis by reverse transcription-PCR with primers for IL-1 alpha, IL-1 beta, IL-6, tumor necrosis factor alpha, granulocyte macrophage colony-stimulating factor, and beta interferon (IFN-beta). L. pneumophila treatment increased the cellular steady-state mRNA levels of all cytokines except IFN-beta. To determine the specificity of this effect, macrophage cultures were treated with cytochalasin D and either bacterial lipopolysaccharide, bovine serum albumin-sensitized latex, Salmonella typhimurium, or Escherichia coli. Lipopolysaccharide treatment increased all mRNAs, bovine serum albumin-sensitized latex had no significant effect, and treatment with S. typhimurium or E. coli increased all mRNAs except that of IFN-beta. These results suggested that the binding of gram-negative bacteria to the macrophage surface was sufficient to induce a unique pattern of cytokine mRNAs. Additional studies that examined the characteristics of the bacterial ligands involved indicated involvement of both heat-labile and heat-stable surface ligands.

Animals↗
PubMed1994

Secondary immunity to Legionella pneumophila and Th1 activity are suppressed by delta-9-tetrahydrocannabinol injection.

Resistance to infection with Legionella pneumophila is primarily dependent upon cell-mediated immunity rather than humoral immunity. Recent evidence suggests that activation of cell-mediated immunity depends on Th1 cells and activation of humoral immunity depends on Th2 cells. In this report, delta 9-tetrahydrocannabinol (THC), the major psychoactive cannabinoid of marijuana and an immunomodulator, suppressed development of secondary immunity to L. pneumophila, which correlated with a reduction in Th1 activity. BALB/c mice, infected with a primary sublethal dose of L. pneumophila, developed resistance to a larger challenge infection 3 to 4 weeks later. However, intravenous injection of THC (4 mg/kg of body weight) 1 day prior to primary infection resulted in increased mortality after the challenge infection. The level of anti-L. pneumophila antibodies in serum increased in both THC-treated and control mice; however, in the THC group IgG1 antibodies which are stimulated by Th2 cells were elevated while Th1-regulated, IgG2a antibodies were depressed. Furthermore, cultured splenocytes from THC-treated mice had less L. pneumophila-specific lymphoproliferation, indicating a deficiency in cell-mediated immunity. Normal mouse splenocytes treated in vitro with THC and pokeweed mitogen showed suppressed production of gamma interferon, a cytokine associated with Th1 cells, but increased production of interleukin 4, a cytokine produced by Th2 cells. Splenocytes from THC-treated mice, stimulated in vitro with either pokeweed mitogen or anti-CD3 antibodies, also produced less gamma interferon, indicating less Th1 activity in these mice. These results suggest that THC decreases the development of anti-L. pneumophila immunity by causing a change in the balance of Th1 and Th2 activities.

Animals↗
PubMed1994

A rapid colorimetric assay for evaluating Legionella pneumophila growth in macrophages in vitro.

A rapid colorimetric technique for in vitro quantitation of Legionella pneumophila intracellular proliferation in macrophages is described. The assay is based on the electron transport activity of metabolically active L. pneumophila. The yellow tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) is cleaved by the mitochondrial activity of viable L. pneumophila, forming a dark formazan derivative with an absorption spectrum different from that of the native compound. The MTT method for measuring intracellular growth of L. pneumophila closely correlated with the CFU assay. The ability of macrophages from the A/J mouse strain to support intracellular growth of L. pneumophila and the ability of desferrioxamine to restrict L. pneumophila intracellular proliferation were confirmed by both methods. The MTT assay offers the advantages of rapidity, simplicity, and cost efficiency over the CFU assay, since it can be performed in the same flat-bottom microtiter plate with measurement in an enzyme-linked immunosorbent assay reader, allowing efficient processing of large numbers of samples.

Animals↗
PubMed1994

Posterior cruciate ligament injury: MR imaging diagnosis and patterns of injury.

PURPOSE: To illustrate the variety of posterior cruciate ligament (PCL) injuries and assess the type and frequency of associated knee injuries. MATERIALS AND METHODS: In a retrospective review of 1,950 magnetic resonance (MR) examinations of the knee, 47 patients with MR imaging findings of PCL injury were identified. In 24 patients, the findings on MR images were correlated with athroscopic findings (n = 14) or findings at physical examination (n = 10). Patterns of associated injuries were described and tabulated. RESULTS: Twenty-one patients (45%) had complete PCL tears; 22 patients (47%), partial tears; and four patients (9%), bone avulsion. Associated injuries were seen in 34 patients (72%). Patterns of injuries differed from those seen in anterior cruciate ligament injury and correlated with the mechanism of trauma. CONCLUSION: MR imaging proved accurate in assessment of the PCL in patients with clinical correlation and demonstrated patterns of associated injury that may affect management strategy.

Humans↗
PubMed1994

Distal biceps tendon injury: MR imaging diagnosis.

PURPOSE: To review the authors' experience with magnetic resonance (MR) imaging of patients with suspected injury of the distal biceps tendon. MATERIALS AND METHODS: Twenty-one patients with clinically suspected injury of the distal biceps tendon were evaluated with MR imaging. Surgical correlation was performed in 15 patients, and long-term clinical follow-up was performed in the remaining six cases. RESULTS: Twelve complete biceps tears, four partial tears, one brachialis rupture, and one ganglion were identified. Axial MR images were more valuable than sagittal images in accurately grading distal biceps tendon injury preoperatively. There was 100% agreement between MR imaging and surgical findings. MR imaging findings led to changes in clinical treatment plans in eight patients (38%). CONCLUSION: MR imaging is useful in the evaluation of patients with suspected distal biceps tendon injury. In particular, axial MR images of the distal biceps insertion are important for accurate grading of the injury.

Adult↗
PubMed1994

MR imaging of high-grade cerebral gliomas: value of diffusion-weighted echoplanar pulse sequences.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of diffusion-weighted echoplanar MR imaging in the examination of high-grade brain gliomas compared with that of conventional spin-echo (SE) or fast spin-echo (FSE) MR imaging. We hypothesize that diffusion-weighted MR imaging may enable us to differentiate various tumor components on the basis of differences in the diffusion of water. SUBJECTS AND METHODS: Conventional SE and FSE MR images were obtained in 10 patients with high-grade brain glioma. Diffusion-weighted echoplanar MR images were obtained with a head gradient coil capable of providing diffusion-weighted imaging along the cephalocaudal axis. Using SE and FSE MR images as a baseline, we evaluated the diffusion-weighted MR images for usefulness in distinguishing tumor components on the basis of differences in diffusion. RESULTS: Areas of tumor that showed significant enhancement on T1-weighted SE MR images obtained after injection of contrast material were markedly hyperintense on diffusion-weighted images and had a lower apparent diffusion coefficient (ADC) than the ADCs for nonenhancing tumor and peritumoral edema. Cystic or necrotic portions of tumor showed the most signal suppression on diffusion-weighted images and were associated with the highest ADCs. On T2-weighted FSE MR images, areas of hyperintensity observed in white matter oriented parallel to the direction of the diffusion gradient could be differentiated into two patterns on the basis of findings on diffusion-weighted images: areas that showed marked signal suppression with a higher ADC, most likely representing areas of predominantly peritumoral edema, and areas that showed a lesser degree of signal suppression with similar but slightly lower ADCs than those of edema, most likely representing areas of predominantly nonenhancing tumor. CONCLUSION: Diffusion-weighted echoplanar MR imaging is a useful technique for examining high-grade cerebral gliomas. It enabled us to differentiate various components of the tumor (e.g., enhancing, nonenhancing, cystic, or necrotic) and to distinguish areas of predominantly nonenhancing tumor from areas of predominantly peritumoral edema when the abnormality was located in the white matter aligned in the direction of the diffusion-weighted gradient. Diffusion-weighted echoplanar MR imaging appears to be a powerful tool in the characterization of brain neoplasms.

Adolescent↗
PubMed1994

Multiple low-dose streptozocin-induced diabetes in NOD-scid/scid mice in the absence of functional lymphocytes.

The murine severe combined immunodeficiency (scid) mutation was used to assess whether the diabetogenic effects of multiple low-dose streptozocin (MD-STZ) administration required the presence of functional T-cells. An STZ dose as low as 30 mg/kg body wt for 5 days induced hyperglycemia in young NOD/Lt-+/+ male mice, whereas a dose of 50 mg/kg for 5 days was required to elicit comparable hyperglycemia in C.B.-17-+/+ male mice. The greater NOD strain sensitivity was not a function of preexisting insulitis, because insulitis- and diabetes-free NOD male mice congenic for a diabetes-resistant major histocompatibility complex haplotype were equally susceptible to MD-STZ. This was confirmed in NOD-scid/scid and C.B.-17-scid/scid males. Both were completely insulitis-free, and despite the absence of functional T- cells and B-cells, both congenic stocks were as sensitive to MD-STZ as congenic +/+ controls. Indeed, MD-STZ-induced hyperglycemia in NOD-scid/scid male mice was significantly higher than in NOD/Lt-+/+ male mice. The NOD-scid/scid mouse as a recipient of adoptively transferred splenocytes clearly delineated a distinct pathogenesis of spontaneous insulin-dependent diabetes mellitus (IDDM) versus MD-STZ-induced hyperglycemia. Splenocytes from spontaneously diabetic NOD/Lt males, but not those from donors given MD-STZ, readily transferred IDDM, even when host beta-cells were sensitized by a single injection of STZ before adoptive transfer. We conclude that IDDM induced by MD-STZ is not mediated by T-cell- or B-cell-dependent autoimmune mechanisms in a fashion analogous to the spontaneous IDDM characteristic of NOD mice.

Animals↗
PubMed1994

Adherence of Treponema pallidum subsp. pallidum in the rabbit placenta.

Congenital syphilis is the consequence of transplacental passage of Treponema pallidum. A system was developed to deliver virulent T. pallidum, Nichols strain, through an isolated uterine horn of a pregnant rabbit in order to investigate the mechanism by which T. pallidum is able to cross the placenta. While the pregnant rabbit was anesthetized, the ovarian artery and the uterine vein were cannulated and attached to a peristaltic pump. Treponema pallidum (2-5 x 10(8) in 10-15 ml RPMI-1640) were circulated via the peristaltic pump throughout the horn for 2 hr, after which the placentas were removed, fixed in formalin, and embedded in paraffin. This system was used to investigate treponemal binding to rabbit placenta at Day 20 and 26 during the gestation period of the rabbit (29-32 days). Examination of 5-microns Dieterle silver stained tissue sections revealed (i) a greater number of spirochetes in the later gestational stage placentas (Day 26) than in the earlier placentas (Day 20), (ii) organisms adhering to the trophoblastic tissue surrounding the maternal blood channels, and (iii) organisms appearing to be in the process of penetrating the trophoblastic tissue or that had completely penetrated from the channels into the trophoblastic elements. We suggest that T. pallidum may be adhering to placental components that are differentially expressed during gestation of the rabbit.

Animals↗
PubMed1994

delta 9-Tetrahydrocannabinol enhances the secretion of interleukin 1 from endotoxin-stimulated macrophages.

Interleukin (IL) 1 is a pleiotropic cytokine and an important mediator of various physiological responses including the acute phase response, inflammation, lymphocyte function and certain central nervous system responses. Because delta 9-tetrahydrocannabinol (THC) treatment also has been reported to affect these physiological responses, we tested the drug effect on IL1 production and secretion. Addition of THC to endotoxin (ETX)-treated murine, resident peritoneal macrophage cultures increased, in a dose-dependent manner, supernatant IL1 activity over ETX only treatment. Treatment with THC alone had no effect. Enzyme-linked immunosorbent assay studies and specific antibody neutralization studies demonstrated both IL1 alpha and IL1 beta were increased by drug treatment. The steady-state levels of cellular IL1 alpha and IL1 beta mRNAs, determined by Northern blotting and reverse transcription-polymerase chain reaction, were unchanged, suggesting the possibility THC was not increasing IL1 production. To examine this possibility further, ETX-activated macrophages, pulsed-labeled with 35S-methionine, were chased for 2, 4 and 6 hr in the presence of THC and the levels of the various IL1 bioforms determined by immunoprecipitation. These results showed THC treatment had no effect on the level of ETX-induced intracellular promature IL1 alpha and IL1 beta proteins; however, a THC-induced increase and prolongation of release of promature IL1 alpha and mature IL1 beta were observed. The immunoprecipitation results were confirmed by studies examining supernatant bioactivity. These results suggest THC augments the ETX-induced processing of IL1 beta and release of IL1 alpha rather than increasing the cellular production of IL1 protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

SIN1 interacts with a protein that binds the URS1 region of the yeast HO gene.

Evidence has recently been mounting suggesting that a number of chromatin components previously thought to primarily or exclusively have structural function, also have a regulatory role in eukaryotic transcription. Notably, in yeast, histone H4 N-terminal sequence has been shown to be required for promoter activation of certain genes in vivo, and mutations in histone H3 (SIN2) or in SIN1 (which has some sequence similarity to HMG1) are able to suppress swi1, swi2, and swi3 mutations, restoring transcription to HO as well as a number of other genes. In this paper we report the identification of a novel protein or protein complex that specifically binds a short sequence in the HO regulatory region on the one hand, and on the other somehow appears to contact the SIN1 protein. We have shown that the DNA binding activity itself does not contain SIN1, since extracts from sin1 delta strains retain the activity. Interestingly, extracts made from cells carrying the dominant sin1-2 point mutation lack the binding activity. Furthermore, bacterially produced sin1-2 protein can dissociate a DNA/protein complex while a similarly produced SIN1 protein has no effect on the complex at similar concentrations. When the DNA sequence to which the protein complex binds is placed in a CYC1 promoter lacking a UAS (upstream activating sequence), it can serve as a weak UAS in a SIN1 dependent way. Our data imply that a sequence specific DNA binding protein(s) may mediate between the SIN1 protein and the basal transcription apparatus transcribing HO.

Base Sequence↗
PubMed1993

Syphilis and drugs of abuse.

In summary, treponemal infections in hamsters treated with THC were slightly enhanced in comparison with vehicle controls. A greater degree of enhancement was exhibited in rabbits; treponemes proliferated more readily during treatment with THC than in control animals. Contrary to expectations, this occurred even in lesions which were not developed fully, i.e., were not ulcerated. Thus, treponemes were present in aspirates earlier during infection and from sites which had received smaller inocula of treponemes in these rabbits than in controls. Lesions in control groups developed ulcerations earlier than did the THC-groups, but treponemes were too scarce to be seen in pre-ulcerative lesions in these animals. It appears that THC-treatment enhanced infection with T. pallidum. It may be that in the local skin lesion, macrophages which are vitally important in early host responses to treponemal infection may not have been functioning optimally and mediators of tissue damage may not have been produced and, therefore, ulceration was delayed in spite of enhanced infectivity of the treponemes.

Animals↗