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Biomedical subjects

M Rosenberg

Publications and source records attributed to M Rosenberg.

At least 19 recordsLinked to original sources

Rapid progressive eosinophilic cardiomyopathy in a patient with Churg-Strauss syndrome (CSS).

Churg-Strauss syndrome (CSS) is a rare necrotizing, systemic vasculitis that is almost invariably associated with bronchial asthma. Although overall prognosis is good and treatment with corticosteroids alone or in combination with other immunosuppressive agents is typically successful, there are reports of patients that do not show signs of clinical improvement under the usual pharmacotherapy. Small clinical studies suggested that cardiac or gastrointestinal involvement is associated with an adverse prognosis. We here report the case of a 38 year old male patient with a history of bronchial asthma who was admitted to our hospital for further evaluation of progressive dyspnea. Blood eosinophilia, infiltrates of both lungs, signs of necrosis and eosinophil deposits on myocardial biopsy combined with a history of bronchial asthma established the diagnosis of CSS with cardiac involvement. We initiated an immunosuppressive therapy with prednisone and methotrexate. Upon tapering of the dosage of prednisone, we noticed worsening of symptoms and further deterioration of cardiac function. Despite the addition of cyclophosphamide and adjustment of heart failure medication, we were not able to stabilize the cardiac situation. Due to rapid progressive eosinophilic cardiomyopathy associated with CSS refractory to medical therapy, our patient was placed on the urgent heart transplantation waiting list and, in the meantime, has undergone successful cardiac transplantation.

Adult↗

Streptococcus salivarius promotes mucin putrefaction and malodor production by Porphyromonas gingivalis.

Although the contribution of the oral microbiota to oral malodor is well-documented, the potential role of Gram-positive micro-organisms is unclear. In the current study, we tested the hypothesis that Gram-positive micro-organisms contribute to malodor production by deglycosylating oral glycoproteins, rendering them susceptible to subsequent proteolysis. To this end, we examined the effect of Streptococcus salivarius on Porphyromonas gingivalis-mediated putrefaction of a model glycoprotein (pig gastric mucin). Malodor was scored by two odor judges, and volatile sulfides were determined with the use of a sulfide monitor. Mucin degradation was followed by electrophoresis on SDS-PAGE. Results showed that the addition of S. salivarius or beta-galactosidase promoted mucin degradation and concomitant malodor production. Addition of glycosidic inhibitors (p-APTG and glucose) inhibited this process. These results suggest that Gram-positive micro-organisms such as S. salivarius contribute to oral malodor production by deglycosylating salivary glycoproteins, thus exposing their protein core to further degradation by Gram-negative micro-organisms.

Animals↗

Computational protein design: a novel path to future protein drugs.

Computational protein design emerges in recent years as a field that could make a substantial impact on the design of protein drugs. It still consists mainly of redesigning parts of a protein sequence for increasing the stability of a given 3-dimensional conformation of a protein, but has already been extended from redesigning core residues to redesigning in all other protein regions, as well as to the design of backbone conformations. More recently, proteins with new binding functions and new enzymes, protein libraries, designs of full folds and of a new protein fold, have been some of the main highlights. The search and the scoring problems are however not fully solved, and many of the design processes should be examined on much larger scales in order to assess their usefulness. We examine some of the basic assumptions in computational protein design, in particular, the separation between sequence and scaffold designs. Among others, we suggest to include more protein residues in computations, to include relevant parts of the backbone, to use appropriate reference states, to produce the proteins and to validate the designs by structural examination of the protein products.

Computational Biology↗

Efficacy of a novel whey protein gel complex to increase the unsaturated fatty acid composition of bovine milk fat.

A novel whey protein emulsion gel (WPEG) complex was developed to protect dietary unsaturated fatty acids from rumen biohydrogenation with the goal of modifying the fatty acid composition of milk fat. Three experiments were conducted with WPEG complexes made from either whey protein concentrate containing 80% crude protein, whey protein isolate, or whey protein concentrate high-gel capacity. Each experiment lasted 3 wk. All cows received a basal total mixed ration (TMR). During wk 1 and 3, all cows received only the TMR. During wk 2, 3 control cows received 330 g/d of soybean oil added to the TMR, and the other 3 cows received 330 g/d of soybean oil in one of the WPEG complexes. During wk 2, C18:2 increased from 3.29 to 5.88 g/100 g of fat in Experiment 1, 2.91 to 7.42 g/100 g of fat in Experiment 2, and 3.57 to 6.56 g/100 g of fat in Experiment 3 for WPEG cows. Fatty acid C18:3 increased from 0.51 to 0.84, 0.52 to 1.15, and 0.51 to 0.97 g/100 g of fat for Experiments 1, 2, and 3, respectively, for WPEG cows. Higher proportions of C18:1 trans-9 in milk fat of control cows compared with WPEG cows were seen in all experiments. The proportion of C18:1 trans-11 was also higher in control cows in Experiments 1 and 2, but not in Experiment 3. The WPEG complexes successfully protected unsaturated fatty acids from rumen biohydrogenation and resulted in an increase in the unsaturated fatty acid composition of milk fat produced by Holstein cows without increasing the trans 18-carbon monoenes.

Animals↗

[Guidelines of lipid therapy translation into clinical practice].

Alterations in lipid metabolism play a major role in the pathogenesis of atherosclerosis and are an important risk factor for cardiovascular events. Lowering of LDL cholesterol by statins reduces morbidity and mortality in patients with coronary artery disease (CAD), both in primary and secondary prevention. The results of large controlled trials that included more than 50,000 patients are the basis for target values promoted by current guidelines. According to the NCEP-ATP III guidelines LDL cholesterol should be lowered to less than 100 mg/dl in high risk patients (CAD or CAD equivalent) and in very high risk patients optional to less than 70 mg/dl. Up to now even in high risk patients the recommended goals are not sufficiently achieved: Up to 80% of high risk patients do not receive a statin and only a minority of those being treated with a statin have a LDL cholesterol below 100 mg/dl. Furthermore, after a major event (e.g. myocardial infarction) the quality of lipid reduction decreases over time. Further efforts are required to improve this situation as a guide-line oriented approach may help to prevent up to 100,000 myocardial infarctions and deaths alone in high risk patients in Germany.

Coronary Artery Disease↗

High efficiency ethanol fermentation by entrapment of Zymomonas mobilis into LentiKats.

AIMS: To examine the potential of Zymomonas mobilis entrapped into polyvinylalcohol (PVA) lens-shaped immobilizates in batch and continuous ethanol production. METHODS AND RESULTS: Cells, free or immobilized in PVA hydrogel-based lens-shaped immobilizates - LentiKats, were cultivated on glucose medium in a 1 l bioreactor. In comparison with free cell cultivation, volumetric productivity of immobilized batch culture was nine times higher (43.6 g l(-1) h(-1)). The continuously operated system did not improve the efficiency (volumetric productivity of the immobilized cells 30.7 g l(-1) h(-1)). CONCLUSIONS: We demonstrated Z. mobilis capability, entrapped into LentiKats, in the cost-efficient batch system of ethanol production. SIGNIFICANCE AND IMPACT OF THE STUDY: The results reported here emphasize the potential of bacteria in combination with suitable fermentation technology in industrial scale. The innovation compared with traditional systems is characterized by excellent long-term stability, high volumetric productivity and other technological advantages.

Biotechnology↗

Association between oral malodour and periodontal disease-related parameters in a population of 71 Israelis.

The aim of the present study was to determine whether oral malodour and periodontal disease parameters are associated with one another in 71 Israeli subjects (mean age 36.2 +/- 18.4; ages ranging from 15 to 65). Parameters measured included whole mouth odour judge scoring, Halimeter, OK to Kiss test, gingival index, plaque index and probing depth. Odour judge scores were significantly associated with Halimeter (r = 0.55; P < 0.001), as well as the OK to Kiss test (r = 0.52; P < 0.001). However, neither gingival index, plaque index nor probing depth was significantly associated with odour judge scores or Halimeter scores. Logistic regression analysis showed that both Halimeter and OK to Kiss scores factored significantly (P = 0.005 and 0.018, respectively, odds ratios 14.9 and 2.7, respectively) in predicting the severity of oral malodour. Results suggest that in the population studied, periodontal health and oral malodour are not associated with one another.

Adolescent↗

[Oral hygiene, caries status and bad breath among young Israeli recruits].

The purpose of the present study was to evaluate the extent of self-reported bad breath in an Israeli population of young army recruits and to assess its relationship with other self-reported parameters, as well as general dental status. Self-reported parameters included smoking status, bad taste, gingival bleeding and the presence of tonsilloliths. The study comprised 426 young adults recruits (ages 18-19), almost all males (95%), all of whom agreed to answer a questionnaire. All participants underwent a dental screening and were divided into three groups regarding to their dental status (do not need treatment, need moderate treatment, need extensive treatment). Statistical analysis included Pearson's chi square test of association using BMDP statistical software. Among the recruits, 142 (33%) were active smokers. Thirty-five participants (8.2%) reported bad breath as well as bad taste. Twenty-seven (6.3%) reported being told that they had bad breath. Tonsilloliths were reported by 31 participants (7.3%) and gingival bleeding by 80 (18.8%). Self-reported bad breath was positively associated with bad taste, gingival bleeding, the presence of tonsilloliths and general dental status (p<0.05). The study indicates that self reports of bad breath are associated by objective factors (e.g. dental status, tonsilloliths) as well as subjective parameters (bad taste).

Adolescent↗

Two-dimensional Yukawa liquids: correlation and dynamics.

A combined theoretical and molecular dynamics (MD) simulation study of the collective modes and their dispersion in a two-dimensional Yukawa system in the strongly coupled liquid state is presented. The theoretical analysis relies upon the quasilocalized charge approximation; the MD simulation generates static pair correlation functions and dynamical current-current correlation spectra.

Journal Article↗

Attractive potential around a thermionically emitting microparticle.

We present a simulation study of the charging of a dust grain immersed in a plasma, considering the effect of thermionic electron emission from the grain. It is shown that the orbit motion limited theory is no longer reliable when electron emission becomes large: screening can no longer be treated within the Debye-Huckel approach and an attractive potential well can form, leading to the possibility of attractive forces on other grains with the same polarity. We suggest to perform laboratory experiments where emitting dust grains could be used to create nonconventional dust crystals or macromolecules.

Journal Article↗

Real-time myocardial contrast echocardiography for the detection of stress-induced myocardial ischemia. Comparison with 99mTc-sestamibi single photon emission computed tomography.

BACKGROUND: Real-time contrast echocardiography (MCE) is a new promising technique for assessing myocardial perfusion. The purpose of this study was to test whether realtime MCE can be used to detect functionally significant coronary artery stenosis in patients with known or suspected coronary artery disease. Myocardial contrast echocardiographic studies were compared with nearly simultaneous 99mTc-sestamibi single photon emission computed tomography (SPECT) as a clinical standard reference to evaluate regional myocardial perfusion defects. METHODS: Real-time MCE based on continuous infusion of Optison (8-10 ml/h) was performed in 66 patients during standard 99mTc-SPECT dipyridamole (0.56 mg/kg x 4 min) stress testing. Images were obtained in apical 4- and 2-chamber views, each divided into 6 segments. Tracer uptake and myocardial opacification were visually analyzed for each segment by two pairs of blinded observers and graded as normal, mildly reduced, severely reduced, or absent. In 792 myocardial segments, myocardial opacification by MCE was uninterpretable in 143 (18%) segments and tracer uptake by SPECT was not clearly defined in 92 (12%) segments. Interobserver variability for MCE was good with concordance rates of 83% (kappa=0.72) for rest- and 86% (kappa=0.76) for stress images. Overall concordance between MCE and SPECT was good (83%, kappa=0.63) at a segmental level. In the diagnosis of fixed and reversible defects, and of normal perfusion, concordance rates were 73, 65 and 83%, respectively. When analysis was performed at the regional level, we found comparable levels of concordance rates for LAD (83%, kappa=0.59), LCX (86%, kappa=0.64) and RCA (80%, kappa=0.68) perfusion territories. CONCLUSIONS: These findings suggest that realtime MCE is a clinically acceptable method to evaluate myocardial perfusion defects during dipyridamole stress testing.

Albumins↗

Calcium-alginate coated, whey protein-based microspheres: preparation, some properties and opportunities.

An 'all aqueous' encapsulation process followed by a heat treatment was used to prepare calcium-alginate-coated, whey protein-based, water insoluble microspheres containing micronized calcium carbonate as a model core. Results obtained with this process were compared to those obtained with a similar process in which chemical cross-linking was utilized. At an initial core load of 25 or 50% (w/w), core retention ranged from 84.2-95.12% and was not significantly affected by the initial core load or by the cross-linking method. Regardless of the cross-linking method, protein retention during the process was high and ranged from 78.2-87.5%. Outer topography of the microspheres was not influenced by the cross-linking method, however, at a given composition, the inner structure of heat treated microspheres differed from that obtained with chemically-cross-linked microspheres. Swelling properties of denovo microspheres were affected by pH. Results indicated that the micronized calcium carbonate could be used as a porogenic core. Removal of the core, by an acid treatment, allowed preparing microporous delivery devices. In addition to offer opportunities for encapsulation and delivery of crystalline core, the investigated process can provide means to prepare 'ghost' microporous delivery systems that can, in potential, be loaded, following their preparation, with sensitive core materials at conditions that favour the stability and functionality of this core.

Alginates↗

Study on the organoleptic intensity scale for measuring oral malodor.

The 0-5 organoleptic scale is used widely in breath research and in trials to measure the efficacy of anti-odor agents. However, the precise relationship between odor scores and gas concentrations of target odorants is unknown. The purpose of this study was to relate mean organoleptic scores from odor judges (n = 7) for pure odorants (n = 8) representative of those found in oral malodor. Judges used a common 0-5 scale to report the odor intensity of sample sets in random order of concentration. Regression analysis of data showed that odor score was proportional to the log concentration of odorant, and comparison of slopes showed H(2)S to be the most significant in terms of odor power. Detection thresholds (mol.dm(-3)) were: Skatole (7.2 x 10(-13)) < methylmercaptan (1.0 x 10(-11)) < trimethylamine (1.8 x 10(-11)) < isovalerate (1.8 x 10(-11)) < butyrate (2.3 x 10(-10)) < hydrogen sulphide (6.4 x 10(-10)) < putrescine (9.1 x 10(-10)) < dimethyl disulphide (5.9 x 10(-8)). The study demonstrates the exponential nature of the olfactory response and shows that any single compound's contribution to malodor depends on odor power and threshold in addition to concentration.

Butyrates↗

Experience with the Jostra Rotaflow and QuadroxD oxygenator for ECMO.

Since April 1988, we have been able to offer extracorporeal membrane oxygenation (ECMO) to patients who are either failing ventilation or who need cardiopulmonary support following cardiac surgery. During this time, we have supported 211 patients, the majority of whom have been supported with the Avecor (Affinity, Avecor Cardiovascular Inc., Minneapolis, MN, USA) spiral wound silicone-membrane oxygenator. Microporous hollow-fibre oxygenators have been used (18%) at our center. However, due to their early failure, they have necessitated conversion to a device that potentially would last for the entire ECMO course, i.e., Avecor and, subsequently, have not been used routinely until the introduction of the QuadroxD (Jostra Medizintechnik AG, Hirrlingen, Germany). The recent development of the poly-4-methyl-1-pentene diffusion membrane allows us to utilize hollow-fibre technology with a true (nonmicroporous) membrane. This has enabled us to use this low-resistance device with all its inherent advantages, without plasma leakage necessitating circuit changeover. From July 2000, we have used the QuadroxD oxygenator for our patients requiring ECMO support. This has been in patients with weights ranging from 2.16-51.0 kg (n = 23), with the longest support being for 1119 hours. This new technology has enabled us to utilize a single device for all patient sizes, so we now have an ECMO circuit set up at all times, minimizing the time required for support to be available, potentially improving survivor morbidity.

Cardiac Surgical Procedures↗

Pump-induced haemolysis: a comparison of short-term ventricular assist devices.

Centrifugal pumps are superior to roller pumps for extended support durations in terms of pump-induced haemolysis. In this study, we evaluated the commonly used Biomedicus BP 50 and compared it with the Jostra Rotaflow and a standard roller pump in an in vitro test circuit. Each circuit was run for a six-day period and repeated five times. Plasma haemoglobin values showed the roller pump to become more haemolytic than the Biomedicus (p = 0.022) and the Rotaflow. A statistically significant difference between the Biomedicus and the Rotaflow was observed on day six of the trial (p = 0.016), with the Rotaflow showing lower levels of haemolysis than the Biomedicus. These results support the use of the new generation centrifugal pump, the Rotaflow, as a suitable device for short-term ventricular assist.

Assisted Circulation↗

Effects of GnRH administered to cows at the onset of estrus on timing of ovulation, endocrine responses, and conception.

Two experiments examined effects of GnRH administered within 3 h after onset of estrus (OE) on ovulation and conception in dairy cows. In experiment 1, 46 cows received either saline, 250 microg of GnRH, or 10 microg of the GnRH analogue, Buserelin. Cows were observed for estrus, blood samples were collected, and ovulations were monitored by ultrasound. In controls, 76% of cows had intervals from estrus to ovulation of < or = 30 h and 24% had intervals > 30 h. Treatment with either GnRH or GnRH analogue (data combined) increased magnitude of LH surges and decreased intervals from estrus to LH surge or to ovulation. Treated cows all ovulated < or = 30 h after OE. Among control cows, plasma estradiol concentrations before estrus correlated positively with amplitudes of LH surges. Higher plasma progesterone was observed in the subsequent estrous cycle in GnRH-treated cows compared to control cows with delayed ovulations. Experiment 2 included 152 primiparous and 211 multiparous cows in summer and winter. Injection of GnRH analogue at OE increased conception rates (CR) from 41.3 to 55.5% across seasons. In summer, GnRH treatment increased CR from 35.1 to 51.6%. Across seasons, GnRH increased CR from 36.0 to 61.5% in cows with lower body condition at insemination and GnRH increased CR (63.2 vs. 42.2%) in primiparous cows compared to controls. Use of GnRH eliminated differences in CR for cows inseminated early or late relative to OE and increased CR in cows having postpartum reproductive disorders. In conclusion, GnRH at onset of estrus increased LH surges, prevented delayed ovulation, and may increase subsequent progesterone concentrations. Treatments with GnRH increased conception in primiparous cows, during summer, and in cows with lower body condition.

Animals↗

Effect of nitrous oxide on intracellular events of GT1-7 GnRH-secreting neurons.

Exposure to nitrous oxide (N2O) may result in decreased fertility and other reproductive problems in women working in dental offices. This study explored direct effects of N2O on gonadotropin-releasing hormone (GnRH) neurons involved in pituitary-gonadal function. An immortalized GnRH-secreting GT1-7 cell line was used to evaluate the effects of 60% N2O exposure for 24 hours on pro-GnRH mRNA levels, KCl-stimulated GnRH levels, and certain signaling pathways. N2O exposure for 24 hours decreased pro-GnRH mRNA levels by approximately 80% without affecting cell viability or intracellular GnRH levels. The ability of KCl to release GnRH stores was also significantly reduced. Western blot analyses of ERK1/2, and p38 phosphorylation and IkappaB did not indicate any change in phosphorylation, although p63 tyrosine phosphorylation was increased after short-term N2O exposure. Levels of c-fos, a nuclear transcription factor, were not changed by N2O exposure. These results indicate that N2O significantly decreases evoked release of GnRH as well as GnRH mRNA levels either by decreased synthesis or by mRNA stability. These results may be important in understanding adverse effects of N2O on female workers in dental practice where the gas is not scavenged.

Analysis of Variance↗