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Biomedical subjects

M Gross

Publications and source records attributed to M Gross.

At least 109 records · Page 6Linked to original sources
PubMed2001

Key role of teichoic acid net charge in Staphylococcus aureus colonization of artificial surfaces.

Staphylococcus aureus is responsible for a large percentage of infections associated with implanted biomedical devices. The molecular basis of primary adhesion to artificial surfaces is not yet understood. Here, we demonstrate that teichoic acids, highly charged cell wall polymers, play a key role in the first step of biofilm formation. An S. aureus mutant bearing a stronger negative surface charge due to the lack of D-alanine esters in its teichoic acids can no longer colonize polystyrene or glass. The mutation abrogates primary adhesion to plastic while production of the glucosamine-based polymer involved in later steps of biofilm formation is not affected. Our data suggest that repulsive electrostatic forces can lead to reduced staphylococcal biofilm formation, which could have considerable impact on the design of novel implanted materials.

Alanine↗
PubMed2001

Regulation of Escherichia coli RelA requires oligomerization of the C-terminal domain.

The E. coli RelA protein is a ribosome-dependent (p)ppGpp synthetase that is activated in response to amino acid starvation. RelA can be dissected both functionally and physically into two domains: The N-terminal domain (NTD) (amino acids [aa] 1 to 455) contains the catalytic domain of RelA, and the C-terminal domain (CTD) (aa 455 to 744) is involved in regulating RelA activity. We used mutational analysis to localize sites important for RelA activity and control in these two domains. We inserted two separate mutations into the NTD, which resulted in mutated RelA proteins that were impaired in their ability to synthesize (p)ppGpp. When we caused the CTD in relA(+) cells to be overexpressed, (p)ppGpp accumulation during amino acid starvation was negatively affected. Mutational analysis showed that Cys-612, Asp-637, and Cys-638, found in a conserved amino acid sequence (aa 612 to 638), are essential for this negative effect of the CTD. When mutations corresponding to these residues were inserted into the full-length relA gene, the mutated RelA proteins were impaired in their regulation. In attempting to clarify the mechanism through which the CTD regulates RelA activity, we found no evidence for competition for ribosomal binding between the normal RelA and the overexpressed CTD. Results from CyaA complementation experiments of the bacterial two-hybrid system fusion plasmids (G. Karimova, J. Pidoux, A. Ullmann, and D. Ladant, Proc. Natl. Acad. Sci. USA 95:5752-5756, 1998) indicated that the CTD (aa 564 to 744) is involved in RelA-RelA interactions. Our findings support a model in which RelA activation is regulated by its oligomerization state.

Adenylate Cyclase Toxin↗
PubMed2001

AlaArg motif in the carboxyl terminus of the gamma(1)34.5 protein of herpes simplex virus type 1 is required for the formation of a high-molecular-weight complex that dephosphorylates eIF-2alpha.

The gamma(1)34.5 protein of herpes simplex virus (HSV) type 1 functions to prevent the shutoff of protein synthesis mediated by the double-stranded-RNA-dependent protein kinase PKR. This is because gamma(1)34.5 associates with protein phosphatase 1 (PP1) through its carboxyl terminus, forming a high-molecular-weight complex that dephosphorylates the alpha subunit of translation initiation factor eIF-2 (eIF-2alpha). Here we show that Val193Glu and Phe195Leu substitutions in the PP1 signature motif of the gamma(1)34.5 protein abolished its ability to redirect PP1 to dephosphorylate eIF-2alpha and replication of mutant viruses was severely impaired. The gamma(1)34.5 protein, when expressed in Sf9 cells using a recombinant baculovirus, was capable of directing specific eIF-2alpha dephosphorylation. Deletions of amino acids 258 to 263 had no effect on activity of gamma(1)34.5. However, deletions of amino acids 238 to 258 abolished eIF-2alpha phosphatase activity but not PP1 binding activity. Interestingly, deletions in the AlaArg motif of the carboxyl terminus disrupted the high-molecular-weight complex that is required for dephosphorylation of eIF-2alpha. These results demonstrate that gamma(1)34.5 is functionally active in the absence of any other HSV proteins. In addition to a PP1 binding domain, the carboxyl terminus of gamma(1)34.5 contains an effector domain that is required to form a functional complex.

Alanine↗
PubMed2001

Infliximab.

Infliximab (Remicade, Centocor, Inc.) is an intravenously administered monoclonal antibody to TNF proven effective in the treatment of moderate to severe Crohn's disease (CD). Its introduction in October 1998 was heralded by some as the most important addition to therapy for this condition in 50 years. Since then, additional indications have been added as efficacy has been proven in fistulising CD and in rheumatoid arthritis. Even though the costs associated with a single dose are several thousand US dollars, more than 150,000 patients have received infusions since its approval.

Antibodies, Monoclonal↗
PubMed2001

The repeatability of serum carotenoid, retinoid, and tocopherol concentrations in specimens of blood collected 15 years apart.

Community-wide programs to collect blood for a research serum bank were carried out in Washington County, Maryland in 1974 and 1989. Of the 8395 persons who participated in both programs, 64 were controls in a nested case-control study of the association of antioxidant micronutrients with subsequent breast cancer, and 30 and 166 were controls in similar studies of lung and prostate cancer. Assay results for five carotenoids, two retinoids, and two tocopherols in samples of blood collected 15 years apart were thus available for comparisons of micronutrient concentrations. The mean Spearman rank order correlation coefficient for all comparisons was 0.44, with two coefficients greater than 0.60 and two less than 0.30. Blood pressure readings at the two blood collections had a mean rank order correlation coefficient of 0.46. Because blood pressure readings in 1974 were shown to be significantly predictive of atherosclerosis 15-18 years later, the present results suggest that ranked concentrations of antioxidant micronutrients from a single sample are sufficiently representative to be used as predictors of subsequent concentrations and are thus suitable for assessment as risk factors for subsequent illnesses.

Aged↗
PubMed2001

Patient demand matching in total knee arthroplasty: is it necessary?

Patient demand matching has been accepted as an appropriate method of implant management by hospitals for cost reduction. However, there have been no prospective studies to substantiate whether these patients change their demand levels postoperatively. Theoretically, functional activity levels should not increase significantly postoperatively in patients with preoperative low demand levels for patient demand matching to be effective in avoiding premature prosthetic failure. Preoperative and postoperative demand levels were prospectively reviewed in 279 patients undergoing total knee arthroplasty (TKA). Preoperatively, the medium/high-demand patients performed significantly more activities overall than low-demand patients. Postoperatively, both low- and medium/high-demand patients dramatically increased the number of activities performed. The hypothesis that prosthetic choice should be determined by preoperative activity level (demand matching) was not validated by this study because patient activity levels significantly increased in all categories subsequent to TKA.

Activities of Daily Living↗
PubMed2001

Predicting the success of retrograde stenting for managing ureteral obstruction.

PURPOSE: Retrograde ureteral stenting is often considered the first line option for relieving ureteral obstruction when temporary drainage is indicated. Several retrospective studies have implied that in cases of extrinsic obstruction retrograde ureteral stenting may fail and, therefore, percutaneous nephrostomy drainage is required. We examined the efficacy of retrograde ureteral stenting for resolving ureteral obstruction and identified clinical and radiological parameters predicting failure. MATERIALS AND METHODS: Enrolled in our prospective study were 92 consecutive patients with ureteral obstruction, which was bilateral in 8. Retrograde ureteral stenting was attempted in all cases by the urologist on call. When stent insertion failed, drainage was achieved by percutaneous nephrostomy. Patients were followed at 3-week intervals for 3 months. Each followup visit included a medical interview, blood evaluation, urine culture and ultrasound. Stent malfunction was defined as continuous flank pain manifesting as recurrent episodes of acute renal colic, 1 or more episodes of pyelonephritis, persistent hydronephrosis or elevated creatinine. Preoperative data and outcomes were compared in cases of intrinsic and extrinsic obstruction. Univariate and multivariate analysis was done to identify predictors of the failure of ureteral stent insertion and long-term function. RESULTS: The etiology of obstruction was intrinsic in 61% of patients and extrinsic in 39%. Extrinsic obstruction, which was associated with a greater degree of hydronephrosis, was located more distal. Retrograde ureteral stenting was successful in 94% and 73% of patients with intrinsic and extrinsic obstruction, respectively. At the 3-month followup stent function was maintained in all patients with intrinsic obstruction but in only 56.4% with extrinsic obstruction. On multivariate logistic regression the type of obstruction, level of obstruction and degree of hydronephrosis were the only predictors of stent function at 3 months. Stent diameter and preoperative creatinine had no predictive value. CONCLUSIONS: Retrograde ureteral stenting is a good solution for most acutely obstructed ureters. In patients with extrinsic ureteral obstruction a more distal level of obstruction and higher degree of hydronephrosis are associated with a greater likelihood of stent failure. These patients may be better served by percutaneous drainage.

Adult↗
PubMed2000

Synthesis and physical investigation of donor-donor and acceptor-acceptor end-functionalized monodisperse poly(triacetylene) oligomers.

Two series of monodisperse, terminally donor-donor [D-D, D=4-(dimethylamino)phenyl] and acceptor-acceptor [A-A, A=4-nitrophenyl] functionalized poly(triacetylene) (PTA) oligomers ranging from monomer to hexamer were synthesized by oxidative Hay oligomerization under end-capping conditions. The corresponding D-D and A-A end-substituted polymers with an average degree of polymerization (DP) of n approximately 18 and n approximately 12, respectively, were also prepared and served as reference points for the corresponding infinitely long polymers. These terminally functionalized PTA oligomers and polymers are yellow- to orange-colored compounds, displaying excellent solubility in aprotic solvents with melting points above 200 degrees C for the hexamers. For the 4-(dimethylamino)phenyl substituted compounds, a consistent first oxidation potential around +0.42 V versus Fc/Fc+ (ferrocene/ferricinium) was observed, whereas the 4-nitrophenyl functionalized systems underwent a reversible reductive two-electron transfer around -1.40V versus Fc/Fc+. The nature of the end-groups has a dramatic influence on the electronic absorption spectra. Saturation of the linear optical properties in the D-D series occurs at significantly shorter chain-length [effective conjugation length (ECL) of n approximately 4 monomer units] than in the A-A substituted or the previously reported Me3Si- and Et3Si-end-capped PTA oligomer series (ECL: n approximately 10 monomer units). Similar observations with respect to the ECL were made by measurement of the Raman-active v(C triple bound C) stretches. Third-harmonic generation (THG) and degenerate four-wave mixing (DFWM) experiments showed that shorter oligomers of terminally D-D or A-A functionalized PTAs display higher second hyperpolarizabilities gamma than the corresponding R3Si-end-capped series (R=alkyl). Moreover, they disclose a distinct peak of the nonlinearity per monomer unit at intermediate backbone lengths. In THG experiments, the second hyperpolarizabilities for long D/A-functionalized PTA oligomers attained the same saturation values as observed for the corresponding R3Si-end-capped rods. The nonlinearities measured by DFWM of the D-D and A-A substituted PTAs were found to be larger than for the silylated ones, which can be explained by the closeness of the two-photon resonance.

Journal Article↗
PubMed2000

German registry for hearing loss in children: results after 4 years.

Since April 1996 the German Registry for Hearing Loss in Children has been collecting and recording various data on permanent hearing loss in children. Up to now, the data of 3882 children have been gathered nation-wide. A particularly remarkable aspect of data so far collected is the alarmingly high age at the time of diagnosis (mild hearing loss is on average only diagnosed at 6; 2 years, moderate loss at 4; 4 years, severe at 2; 5 years and profound with 1; 9 years). The German Registry for Hearing Loss in Children provides the first reliable source of epidemiological data on permanent hearing loss in children in Germany. A constantly growing number of currently 112 co-operating partners takes part in the data acquisition. The periodical reports of results to the co-operating partners and the first publications have heightened the awareness of the importance of early diagnosis and therapy. A minimum standard for patient history was established by the primary examination report. Thus, an important contribution has been made to the prevention of avoidable secondary damage.

Child↗
PubMed2000

Improvement of myocardial perfusion reserve early after coronary intervention: assessment with cardiac magnetic resonance imaging.

OBJECTIVES: The purpose of this study was to determine the potential value of magnetic resonance myocardial perfusion in the follow-up of patients after coronary intervention. BACKGROUND: In some patients a residual impairment of myocardial perfusion reserve (MPR) early after successful coronary intervention has been observed. In this study we evaluated an MPR index before and after intervention with magnetic resonance. METHODS: Thirty-five patients with single- and multivessel coronary artery disease were studied before and 24 h after intervention. The signal intensity time curves of the first pass of a gadolinium-diethylene triamine pentacetic acid bolus injected via a central vein catheter were evaluated before and after dipyridamole infusion. The upslope was determined using a linear fit. Myocardial perfusion reserve index was estimated from the alterations of the upslope. RESULTS: The MPR index in segments perfused by the stenotic artery was significantly lower than in the control segments (1.07 +/- 0.24 vs. 2.18 +/- 0.35, p < 0.001) and improved significantly after intervention (1.89 +/- 0.39, p < 0.001) but did not normalize completely (p < 0.01). After intervention the MPR index remained significantly lower in the balloon percutaneous transluminal coronary angioplasty group (1.72 +/- 0.38; n = 13) in comparison with the stent group (1.99 +/- 0.36, n = 18, p < 0.05). In the stent group a complete normalization of the MPR index was found 24 h after stenting. CONCLUSIONS: Magnetic resonance perfusion measurements allow a reliable assessment of MPR index. An improvement of MPR index can be observed after coronary intervention, which is more pronounced after stenting. Magnetic resonance perfusion measurements allow the assessment and may be useful for the follow-up of patients with coronary artery disease after coronary intervention.

Angioplasty, Balloon, Coronary↗
PubMed2000

Spontaneous chirality in simple systems

Two simple examples of spontaneous chiral symmetry breaking are presented. The first is close-packed cylindrically confined spheres. As the cylinder diameter is varied, one obtains a variety of chiral phases. The second example involves unconfined dipolar particles with an isotropic attraction, which also exhibits chiral ground states. We speculate that a dilute magnetorheological fluid film, with the addition of smaller particles to provide an attractive entropic interaction, will exhibit a chiral columnar ground state.

Journal Article↗
PubMed2000

Monodisperse poly(triacetylene) oligomers extending from monomer to hexadecamer: joint experimental and theoretical investigation of physical properties

A series of monodisperse Et3-Si-end-capped poly(triacetylene) (PTA) oligomers ranging from monomer to hexadecamer was prepared by a fast and efficient statistical deprotection-oxidative Hay oligomerization protocol. The PTA oligomers exhibit an increasingly deep-yellow color with lengthening of the pi-conjugated backbone, feature excellent solubility in aprotic solvents, and exhibit melting points up to > 22 degrees C for the hexadecameric rod. This new dramatically extended oligo(enediyne) series now enables to investigate the evolution of the physico-chemical effects in PTAs beyond the linear 1/n versus property regime into the higher oligomer region where saturation becomes apparent. We report the results of joint experimental and theoretical studies, including analysis of the 13C NMR spectra, evaluation of the linear (UV/ Vis) and nonlinear [third-harmonic generation (THG) and degenerate four-wave mixing (DFWM)] optical properties, and characterization of the redox properties with cyclic and steady-state voltammetry. Up to the hexadecameric rod, an increasingly facile one-electron reduction step is observed, showing at the stage of the dodecamer, a leveling off tendency from the linear correlation between the inverse number of monomer units and the first reduction potential. The effective conjugation length (ECL) determined by means of UV/Vis spectroscopy revealed a pi-electron-delocalization length of about n = 10 monomeric units, which corroborates well with the oligomeric length for which in the 13C NMR spectrum C(sp2) and C(sp) resonances start to overlap. Third-harmonic generation (THG) and degenerate four-wave mixing (DFWM) measurements revealed for the second-order hyperpolarizability gamma a power law increase gammma-alpha-n(a) for oligomers up to the octamer with exponential factors a= 2.46+/-0.10 and a=2.64+/-0.20, respectively, followed by a smooth saturation around n = 10 repeating units. The power law coefficient a calculated with the help of the valence effective Hamiltonian (VEH) method combined to a sum-over-states (SOS) formalism corroborates well with the values found by both THG and DFWM experiments. Up to the PTA heptamer, INDO (intermediate neglect of differential overlap)-calculated gas-phase ionization potentials and electron affinities obey a linear relationship as a function of the inverse number of monomer units displaying a strong electron-hole symmetry. The onset of saturation for the electron affinity is calculated to occur around the octamer, in accordance with experimentally obtained results from electrochemical measurements.

Journal Article↗