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Biomedical subjects

R Rosenberg

Publications and source records attributed to R Rosenberg.

At least 73 records · Page 4Linked to original sources

Methylene blue inhibits hippocampal nitric oxide synthase activity in vivo.

The aim of the present study was to investigate the effect of methylene blue, a guanylate cyclase inhibitor, on the hippocampal nitric oxide synthase activity in vivo. We used a microdialysis-based technique of measuring conversion of [3H]l-arginine to [3H]l-citrulline in freely moving rats. The administration of methylene blue (0.1 and 1 mM) via the microdialysis probe caused a dose-dependent decrease in [3H]l-citrulline efflux comparable with the effect of unselective NOS inhibitor NG-nitro-L-arginine (2 mM). We conclude that methylene blue inhibits brain NOS activity in vivo and thus interferes with NO-cGMP cascade in different levels.

Animals↗

CT imaging of intrathoracic lymph nodes in dogs with bronchoscopically administered iodinated nanoparticles.

RATIONALE AND OBJECTIVES: The purpose of the study was to determine if airway instillation of iodinated nanoparticles results in contrast material enhancement of tracheobronchial lymph nodes in dogs. MATERIALS AND METHODS: Eight dogs underwent intrabronchial instillation of iodinated nanoparticles; six dogs received 900 mg each, and two dogs received 450 mg each. Spiral computed tomography (CT) was then performed 2-34 days later. RESULTS: CT scans obtained 2 days after instillation showed the presence of contrast material within the lung parenchyma but no nodal enhancement. Scans obtained 6-34 days after instillation showed enhancement of the right, left, and middle tracheobronchial lymph nodes (analogous to the mediastinal nodes in humans). Mean nodal attenuation on CT images was 117 HU +/- 43, and the mean nodal volume was 129 mm3 +/- 113. Histologic specimens of the nodes showed macrophage hyperplasia. CONCLUSION: Iodinated nanoparticles instilled into small airways are transported to the tracheobronchial lymph nodes, where they result in contrast enhancement.

Administration, Topical↗

Decreased expression of the p21ras stimulatory factor hSOS in PBMC from inactive SLE patients.

Expression of the p21 ras protooncogene is reported to be increased in animal models and in patients with SLE. However, the expression of p21ras regulatory elements has not been determined. We determined the expression of p21ras, and its regulatory elements p120-ras-GAP and hSOS, in PBMC of 10 patients with inactive SLE (mean SLEDAI score 1.8+/-0.53) and 10 age- and sex-matched healthy controls. No difference was found between the two groups in the levels of p21 ras (3760+/-513 and 3367+/-335, P=0.25) and ras-GAP (1048+/-261 and 1534+/-247, P=0.11) in patients and controls, respectively. In contrast, levels of hSOS were significantly decreased in patients as compared to controls: 955+/-218 and 2306+/-327, P = 0.002, respectively. The mitogen-induced proliferative response was comparable in the two groups: SI 20.8+/-4.2 and 15.03+/-4.9, P=0.135, in patients and controls, respectively. Taken together, our data demonstrate that nonactive SLE patients are characterized by reduced hSOS expression and underscore the need for a comprehensive evaluation of p21ras pathway in these patients.

Adult↗

CD87-positive tumor cells in bone marrow aspirates identified by confocal laser scanning fluorescence microscopy.

Dissemination of single tumor cells to the bone marrow is a common event in cancer. The clinical significance of cytokeratin-positive cells detected in the bone marrow of cancer patients is still a matter of debate. In gastric cancer, overexpression of the receptor (uPAR or CD87) for the serine protease urokinase-type plasminogen activator (uPA) in disseminated cancer cells indicates shorter survival of cancer patients. A new immunofluorescence approach, applying confocal laser scanning microscopy, is introduced to locate CD87 antigen in cytokeratin-positive tumor cells and to quantify the CD87 antigen by consecutive scanning. At first, cytokeratin 8/18/19-positive carcinoma cells are identified at excitation wavelength 488 nm using monoclonal antibody A45B/B3 to the cytokeratins and goat anti-mouse IgG labeled with the fluorochrome Alexa488. Next, CD87 in tumor cells is identified by chicken antibody HU277 to the uPA-receptor and goat anti-chicken IgY labeled with fluorochrome Alexa568 (excitation wavelength 568 nm) and the fluorescence signal quantified on a single cell basis using fluorescently labeled latex beads as the fluorescence reference. From 16 patients with gastric or esophageal carcinoma, bone marrow aspirates were obtained, stained for cytokeratins and CD87 and then subjected to laser scanning fluorescence microscopy. Three of six gastric cancer patients had tumor cells present in the bone marrow of which 2 stained for CD87. Three of ten esophageal carcinoma patients had tumor cells in the bone marrow, all three samples stained for CD87. CD87-positive tumor cells were also dissected from stained bone marrow aspirates by laser microdissection microscope to allow analysis of single cells at the gene level.

Adenocarcinoma↗

Zolpidem for persistent insomnia in SSRI-treated depressed patients.

BACKGROUND: Depressed individuals effectively treated with selective serotonin reuptake inhibitors (SSRIs) often report persistent insomnia and require adjunctive sleep-promoting therapy. METHOD: Men (N = 40) and women (N = 150) with a mean age of 41.6 years who had persistent insomnia in the presence of effective and stable treatment (at least 2 weeks) with fluoxetine (< or =40 mg/day), sertraline (< or =100 mg/day), or paroxetine (< or =40 mg/day) for DSM-IV major depressive disorder, dysthymic disorder, or minor depressive disorder of mild-to-moderate severity (and score of < or =2 on item 3 of the Hamilton Rating Scale for Depression [HAM-D]) participated in this randomized, double-blind, parallel-group study. At study entry, patients were required to score < or =12 on the HAM-D. During a 1-week single-blind placebo period, patients had to report on at least 3 nights a latency of > or =30 minutes or a sleep time of <6.5 hours and clinically significant daytime impairment. Patients received either placebo (N = 96) or zolpidem, 10 mg (N = 94) nightly, for 4 weeks and single-blind placebo for 1 week thereafter. Sleep was measured with daily questionnaires and during weekly physician visits. RESULTS: Compared with placebo, zolpidem was associated with improved sleep: longer sleep times (weeks 1 through 4, p<.05), greater sleep quality (weeks 1 through 4, p<.01), and reduced number of awakenings (weeks 1, 2, and 4; p<.05), together with feeling significantly more refreshed, less sleepy, and more able to concentrate. After placebo substitution, the zolpidem group showed significant worsening relative to pretreatment sleep on the first posttreatment night in total sleep time and sleep quality, reverted to pretreatment insomnia levels on the other hypnotic efficacy measures, or maintained improvement (fewer number of awakenings). There was no evidence of dependence or withdrawal from zolpidem (DSM-IV criteria). Incidence rates of adverse events were similar in both treatment groups (74% and 83% for placebo and zolpidem, respectively), but 7 zolpidem patients discontinued compared with 2 placebo patients. CONCLUSION: In this defined patient population, zolpidem, 10 mg, was effectively and safely co-administered with an SSRI, resulting in improved self-rated sleep, daytime functioning, and well-being.

Adult↗

An unusually high prevalence of asthma in Ethiopian immigrants to Israel.

BACKGROUND AND OBJECTIVES: The past 20 years have seen a large immigration of Ethiopian Jews to Israel, primarily in 2 airlifts, one in 1984-1985 and one in 1991. Infectious and parasitic diseases were the dominant health problems in the early years. Recently, we noticed changing health patterns in this population, particularly an increase in clinic visits for asthma, which contrasted with asthma rates of 2.5% reported among Ethiopian Jews at the time of immigration to Israel. This study evaluated the prevalence and characteristics of asthma in a population of Jews of Ethiopian origin who had been in Israel for 8-17 years. METHODS: We audited 302 files of adult patients of Ethiopian origin and 604 files of age- and gender-matched patients of non-Ethiopian origin. Each file was reviewed by 2 physicians. Asthma was defined by published clinical criteria as found in the patient file. Data on allergies and eosinophilia were collected as well. RESULTS: The average age of the 2 groups of asthmatics was 44.1 +/- 16.2 and 42.4 +/- 20.7 years, respectively. The prevalence of asthma in the patients of Ethiopian origin was 51/302 (17%), compared with 35/604 (5.8%) in the control group. Thirty-three percent of the Ethiopian asthmatics and 37% of the control group suffered from various allergic diseases. Among the patients of Ethiopian origin, the prevalence of eosinophilia was 44%, with no significant difference between asthmatics and non-asthmatic patients (49% versus 43%). Eosinophilia was found in 8.4% of the control group. Asthma was more prevalent among patients with eosinophilia (22%) than without eosinophilia (6.4%). CONCLUSIONS: Asthma is 3 times as prevalent in adults of Ethiopian origin, compared with the general population in our clinics, and markedly increased above the rate reported for newly immigrated Ethiopian Jews. We conclude that the move from the rural hills of Ethiopia to the more urban and industrialized setting of Israel has resulted in an increased prevalence of asthma in this population, but the specific cause is uncertain.

Adult↗

Xanthurenic acid induces gametogenesis in Plasmodium, the malaria parasite.

A small, heat stable chromophore extracted from mosquitoes has recently been implicated as the signal that induces mating of Plasmodium, the malaria parasite. We have used high resolution electrospray mass spectrometry to determine that this gamete activation factor (GAF) has a m/z = 205.0450, suggesting a molecular species composition of C10H7NO4. Xanthurenic acid (XA), a product of tryptophan catabolism, was determined to have an elemental composition, ultraviolet absorbance maxima, and mass spectrum consistent with those characteristics of GAF. XA activated gametogenesis of Plasmodium gallinaceum and P. falciparum in vitro at concentrations lower than 0.5 microM in saline buffered to pH 7.4. A structural analog of XA, kynurenic acid (C10H6NO3), also activated gametogenesis but only at higher concentrations and with less effect. We propose that XA is GAF. This is the first evidence that XA has induction activity.

Animals↗

The mosquito Anopheles stephensi limits malaria parasite development with inducible synthesis of nitric oxide.

We have discovered that the mosquito Anopheles stephensi, a natural vector of human malaria, limits parasite development with inducible synthesis of nitric oxide (NO). Elevated expression of A. stephensi NO synthase (NOS), which is highly homologous to characterized NOS genes, was detected in the midgut and carcass soon after invasion of the midgut by Plasmodium. Early induction is likely primed by bacterial growth in the blood meal. Later increases in A. stephensi NOS expression and enzyme activity occurred at the beginning of sporozoite release. Circulating levels of nitrite/nitrate, end-products of NO synthesis, were significantly higher in Plasmodium-infected mosquitoes. Dietary provision of the NOS substrate L-arginine reduced Plasmodium infections in A. stephensi. In contrast, dietary provision of a NOS inhibitor significantly increased parasite numbers in infected mosquitoes, confirming that A. stephensi limits Plasmodium development with NO.

Amino Acid Sequence↗

Increased saturation of the fatty acids in the sn-2 position of phospholipids reduces cholesterol crystallization in model biles.

Changes in the molecular structure of biliary phospholipids were shown to have major effects on cholesterol solubility, carriers and crystallization in human and model biles. This study investigated systematically the effects of varying saturation of the phosphatidylcholine (PC) sn-2 fatty acid on the cholesterol crystallization process in 3 different model biles. Twenty % of the egg PC (EPC) in these biles were replaced by synthetic PC's with 16:0-18:0, 16:0-18:1, or 16:0-18:2 fatty acyl chains. With 18:0 in the sn-2 position, the crystal observation time (COT) was prolonged from 2 days in the control EPC solution to 14 days (p<0.05). The crystal growth rate (CGR) was reduced from 0.1 OD/day to unmeasurable levels, and the total crystal mass on day 14 decreased by 86%. The introduction of one (18:1), and two (18:2) double bonds in the sn-2 fatty acid rapidly reversed these effects. Ultracentrifugal analysis showed precipitable cholesterol as monohydrate crystals. In the 16:0-18:0 test solution, most of the precipitable cholesterol remained in the supersaturated multilamellar vesicles. Saturation of the biliary PC sn-2 fatty acyl chain prolongs the COT, slows the CGR, reduces the crystal mass, and extends cholesterol solubility in multilamellar vesicles. Desaturation of the sn-2 fatty acid reverses these effects.

Bile↗

The effects of phospholipid molecular species on cholesterol crystallization in model biles: the influence of phospholipid head groups.

BACKGROUND/AIMS: Variations in the molecular species of biliary phospholipids have been shown to exert major effects on cholesterol solubility and carriers in model and human biles. The aim of this study was to explore systematically the effects of various phospholipid head groups on the cholesterol crystallization process in model biles. METHODS: Three different control model biles were prepared using varying proportions of egg lecithin, cholesterol and Na taurocholate. In the test biles, 20% of the egg lecithin was replaced with synthetic phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol or phosphatidylcholine, keeping the phospholipid acyl chains and other biliary lipids constant in each experiment. RESULTS: Phosphatidylserine and phosphatidylglycerol significantly prolonged the crystal observation time, from 2 days to 10 and 6 days, respectively (p<0.02), while phosphatidylethanolamine had little and phosphatidylcholine no effect. The crystal growth rate was significantly slowed down with 20% phospholipid replacement in the following order: phosphatidylglycerol >phosphatidylserine >phosphatidylethanolamine. The total crystal mass after 14 days, as measured by chemical analysis, was reduced by 59% with phosphatidylserine (p<0.05), and by 73% with phosphatidylglycerol (p<0.05); while phosphatidylethanolamine had little effect. The precipitable cholesterol crystal fractions after 14 days were significantly reduced with phosphatidylserine (54%) and phosphatidylglycerol (37%), but not with phosphatidylethanolamine or phosphatidylcholine. CONCLUSIONS: Variations in the head groups of biliary phospholipids may markedly slow down the cholesterol crystallization process in model biles.

Bile↗

Self-efficacy as a psychological moderator of chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is characterized by debilitating fatigue and a variety of somatic symptoms. Few studies have examined psychological aspects of CFS. In the present study, self-efficacy is shown to be a significant predictor of CFS symptoms beyond the variance accounted for by demographic variables and distress. Further psychological CFS research is encouraged by (1) identifying dimensions that are salient in the experience and study of CFS, (2) providing preliminary psychometric data for measures of those dimensions, and (3) identifying psychological variables that serve as moderators of the experience of CFS.

Adaptation, Psychological↗

Continuous in vitro propagation of the malaria parasite Plasmodium vivax.

The difficulty in controlling Plasmodium vivax, the most common cause of human malaria, has been complicated by growing drug resistance. We have established a method to cycle parasite generations in continuous culture using human blood cells. Chesson strain parasites were passaged from owl monkey erythrocytes to human reticulocytes in McCoy's 5A medium modified with L-glutamine with 25 mM Hepes buffer supplemented with 20% AB+ human serum. Reticulocytes were separated by differential centrifugation in homologous plasma from the peripheral blood of a hemochromatosis patient. Parasites were grown during each 48-hr cycle in a static candle jar environment until the beginning of schizogony, at about 36-40 hr, when reticulocytes were added and cultures transferred to a shaker for 10-12 hr. The addition of a concentration of 10% reticulocytes resulted in stabilizing parasite densities between 0.28 and 0.57 after cycle 3 and increasing the total number of parasites at least 2-fold with each generational cycle. Cultured parasites successfully infected an owl monkey. The morphology of cultured parasites was typical of P. vivax, with highly ameboid trophozoites evident; however, infected erythrocytes were enlarged and distorted on thin film preparations. The species identity of cultivated parasites was confirmed by analysis of the A and C 18S rRNA genes from genomic DNA and expression of only the A gene during erythrocytic asexual growth. The ability to culture P. vivax opens new opportunities to develop vaccines, test drugs, and clone parasites for genome sequencing.

Animals↗