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S Moser

Publications and source records attributed to S Moser.

At least 19 recordsLinked to original sources
PubMed2001

Streptogramin- and tetracycline-responsive dual regulated expression of p27(Kip1) sense and antisense enables positive and negative growth control of Chinese hamster ovary cells.

We constructed a dual regulated expression vector cassette (pDuoRex) whereby two heterologous genes can be independently regulated via streptogramin- and tetracycline-responsive promoters. Two different constructs containing growth-promoting and growth-inhibiting genes were stably transfected in recombinant Chinese hamster ovary (CHO) cells that express the streptogramin- and tetracycline-dependent transactivators in a dicistronic configuration. An optimally balanced heterologous growth control scenario was achieved by reciprocal expression of the growth-inhibiting human cyclin-dependent kinase inhibitor p27(Kip1) in sense (p27(Kip1)S) and antisense (p27(Kip1)AS) orientation. Exclusive expression of p27(Kip1)S resulted in complete G(1)-phase-specific growth arrest, while expression of only p27(Kip1)AS showed significantly increased proliferation compared to control cultures (both antibiotics present), presumably by decreasing host cell p27(Kip1) expression. In a second system, a derivative of pDuoRex encoding streptogramin-responsive expression of the growth-promoting SV40 small T antigen (sT) and tetracycline-regulated expression of p27(Kip1) was stably transfected into CHO cells. Expression of sT alone resulted in an increase in cell proliferation, but the expression of p27(Kip1) failed to provide the expected G(1)-specific growth arrest despite having demonstrated expression of the protein. This illustrates the difficulty in balancing the complex pathways underlying cell proliferation control through the expression of two functionally distinct genes involved in those pathways, and how a single-gene sense/antisense approach using pDuoRex can overcome this barrier to complete metabolic engineering control.

Animals↗
PubMed2001

Surface characterization of poly(methyl methacrylate) microgrooved for contact guidance of mammalian cells.

High-resolution patterns of grooves have been made in poly(methyl methacrylate) films, PMMA, by an electron-beam microlithographic process. The surface of films processed over a large width was characterized in terms of chemical composition (X-ray photoelectron spectroscopy (XPS). time of flight secondary ion mass spectroscopy), wettability (sessile drop) and topography (atomic force microscopy). Collagen adsorption was also studied (radiocounting, XPS) as such or in competition with Pluronic F68. The chemical alteration of the surface induced by the electron-beam irradiation disappeared after the dissolution involved in the development process. W138 human fibroblasts cultivated on microgrooved substrata (grooves 1 microm deep and 0.5-10 microm wide) showed a strong orientation parallel to the grooves. The contact guidance is induced by the topography of the surface and not by the alternation of zones with different physico-chemical properties. It may be explained in terms of probability of successful substratum contact by cell protrusions.

Adsorption↗
PubMed2000

Observation of predicted resonance structure in the H+D2 --> HD(v(') = 0, j(') = 7) + D reaction at a collision energy of 0.94 eV

We present experimental verification of predicted resonance structure in the energy dependence of the H+D2 reaction. Specifically we predict and observe a broad resonance in the H+D2-->HD(v(') = 0,j(') = 7)+D reaction at a collision energy of 0. 94 eV. This resonance structure is roughly Gaussian with a full width at half maximum of 0.1 eV. These results represent the first experimentally observed resonance structure in the fundamental H+H2 reaction system.

Journal Article↗
PubMed1996

Ligation based HLA-B*27 typing.

We have established a ligation based typing method to detect HLA-B*27 alleles at the DNA level. The method requires amplification of exon 2 of the HLA-B locus from genomic DNA by the polymerase catalyzed chain reaction (PCR) using group specific primers. An aliquot of the PCR amplification product, heat stable ligase and a pair of oligonucleotide probes, designed to hybridize adjacently to HLA-B*27 specific sequences of the amplified DNA are subsequently thermocycled. If the probes are perfectly complementary they become ligated otherwise they stay separated. The ligation of probes can be detected through their different labels by an enzyme linked immunosorbent assay (ELISA). Ligation based detection of beta-actin sequences which have been co-amplified serves as positive control for each PCR reaction. We observed complete concordance when typing 76 HLA-B*27 positive and 107 HLA-B*27 negative individuals either by serology or by the ligation based approach. We conclude that ligation based typing is a reliable tool for the DNA based detection of HLA-B*27 alleles. The procedure allows automation to a large extent and should be easily applicable to the typing of other HLA-class I alleles.

Base Sequence↗
PubMed1996

Clinical utility of routine transthoracic echocardiographic studies after uncomplicated radiofrequency catheter ablation: a prospective multicenter study. The Atakr Investigators Group.

Unsuspected cardiac complications have been occasionally identified on postablation echocardiographic studies; however, the clinical utility of route echocardiographic studies following uncomplicated radiofrequency catheter ablation procedures has not been established. Two-dimensional/Doppler echocardiographic studies obtained preablation (within 3 months of the procedure) in 355 consecutive patients (180 males and 175 females, mean age 37 +/- 21 years) were compared to postablation (within 24 hours of the procedure) studies obtained after a total of 387 uncomplicated RF catheter ablation procedures for AV node slow pathway (n = 120), accessory AV pathways (n = 214), and complete AV junction (n = 39). Postablation studies identified 6 new cases (1.5%) of new wall motion abnormalities, and 3 additional patients had septal wall motion abnormalities during ventricular pacing. LVEF remained unchanged from baseline (62 +/- 10 vs 62 +/- 11). A small pericardial effusion was detected after 11 procedures (2.8%), and there were 9 (2.3%), 21 (5.4%), and 20 (5.2%) new findings of mild (1+) aortic, mitral, and tricuspid regurgitation, respectively; and no cases of significant valvular dysfunction in any patient. There were no new cases of cavity thrombus. There was no clear relationship between postablation echocardiographic findings and the type and approach to ablation, and no patient had any clinical sequelae possibly related to any of the new echocardiographic findings during a mean follow-up of 15 +/- 6.0 months (range 1-26 months). Routine transthoracic echocardiographic studies after uncomplicated RF catheter ablation procedures identify occasional minor abnormalities that (1) may or may not be procedure related, (2) are of no apparent clinical consequence, and (3) thus appear to be of limited value.

Adult↗
PubMed1995

Intracranial temperature across 24-hour sleep-wake cycles in humans.

The 24 h time course of intracranial temperature, recorded subdurally at the parahippocampal gyrus in six patients (19 24 h periods), exhibited a prominent 24 h rhythm with its crest located at 20-21 h. The declining trend of intracranial temperature between lights off and sleep onset persisted in the first nonREM sleep episode (studied in two patients, seven sleep episodes). The correlation between EEG slow-wave activity (SWA) in nonREM sleep and the change in temperature explained < 25% of the variance. Although the change in temperature tended to be more positive in REM sleep episodes than in nonREM sleep episodes, no significant increase was observed in REM sleep. The data indicate that intracranial temperature exhibits a marked 24 h rhythm, the time course of which is only slightly affected by nonREM/REM sleep and EEG synchronization.

Adult↗
PubMed1995

On the sensitivity of the human brain to magnetic fields: evocation of epileptiform activity.

Evocation of epileptiform activity by DC magnetic fields of between 0.9 and 1.8 millitesla (mT) has been demonstrated in 6 epileptic patients undergoing presurgical evaluation. The activity was monitored by electroencephalography (EEG) recording from both electrodes attached to the scalp as well as from intracranial electrodes inserted via the foramen ovale. Epileptiform activity evoked by the magnetic field application was distinguished from background levels by comparing the number of epileptiform discharges in the 10-s intervals before and after field applications. In nearly all cases, a delay of up to several seconds was observed between the application of the magnetic field and the onset of epileptiform firing. Removal of the field also appeared to cause firing in some instances, but this has not yet been investigated systematically. In all 6 patients, subsequent seizures confirmed that the epileptiform activity monitored during the experiments was originating from the primary epileptogenic zones of the patients.

Adult↗
PubMed1995

A combination of two distinct in vitro amplification procedures for DNA typing of HLA-DRB and -DQB 1 alleles.

The differential hybridisation of oligonucleotide probes to polymerase chain reaction (PCR)-amplified DNA has become a standard procedure for tissue typing. We describe a typing method in which differential ligation replaces differential hybridisation, which is a significant simplification of this strategy. After amplification by the PCR two labelled, sequence-specific oligonucleotides hybridise, in the fluid phase, to one strand of heat-denatured amplification product in juxtaposition. In the case of perfectly complementary sequences surrounding the gap, a thermostable ligase catalyses the ligation of the two oligonucleotides, otherwise they stay separated. The use of heat-resistant ligase enables easy repetition of the denaturation-annealing-ligation cycle in a thermocycler. The ligation products are detected by an enzyme linked immunosorbent assay. We tested this typing approach in a model system, the characterisation of three functional alleles of HLA-DRB3 using three probe pairs. No discrepancies were observed in typing 100 individuals of known genotypes. A total of 33 probe pairs combined with generic and group-specific amplification allowed the typing of alleles of HLA-DRB and -DQB1 loci at low resolution. We confirmed ligation-based typing results of 259 individuals with sequence-based HLA-DRB1 typing and HLA-DQB1 typing using PCR with sequence-specific primers (SSPs). In addition, more than 1,500 ligation-based HLA-DRB1 typings were concordant with SSP typing. Excellent signal-to-noise ratios in the enzyme-linked immunosorbent assay make ligation-based typing remarkably robust. The time requirement of 2.5 h post-PCR enables practicable typing of putative organ donors. The whole procedure is more easily amenable to automation than methods based on differential hybridisation requiring additional incubators and extra handling for hybridisation and washing.

Alleles↗
PubMed1994

Cytokines in the host response to mycotic agents.

In summary, different approaches have been taken to understand cytokine responses to different fungal infections. Singer-Vermes and co-investigators indirectly examined cytokine responses to paracoccidioidomycosis by studying the types of cellular and humoral immune responses that were induced in resistant and susceptible mouse strains. Their results implicated Th1 cell responses in the resistant mouse strain and Th2 cell responses in the mouse strain susceptible to paracoccidioidomycosis. By measuring cytokine production and through cytokine depletion experiments, Wu-Hsieh showed that besides IFN gamma, TNF alpha was important in host defences against the intracellular pathogen, H. capsulatum. Both cytokines play important roles in the regulation of other cytokines. In histoplasmosis, the dynamics of the complex interactions amongst cytokines govern the efficiency of host clearance of the fungus from tissues. Ferrante and collaborators, examining TNF alpha and TNF alpha receptors on neutrophils presented data showing that TNF alpha plays an important role in the activation of neutrophils for anti-Candida activity. Through the detection of cytokine mRNAs with RT-PCR, Moser and co-workers found that cytokine mRNAs of macrophage origin were produced preferentially in the lungs of mice infected with Histoplasma or Blastomyces. A great challenge still lies ahead of us. It is well understood that the interactions of cytokines are extremely complex at the levels of the induction and expression of the immune responses as well as on effects on natural cellular defences. Work accomplished thus far has laid the ground work for future studies in the effort to dissect host cytokine responses and to understand the roles of cytokines in protection against fungal infections.

Animals↗
PubMed1993

Left ventricular outflow tract obstruction following repair of pneumococcal mitral annular abscess.

An unusual case of a mitral annular abscess caused by Streptococcus pneumoniae was diagnosed by transesophageal echocardiography. The patient underwent surgical resection of the abscess and developed outflow tract obstruction. This is an unusual complication of the surgical procedure. The outflow tract obstruction may have been due to anterior displacement of the mitral valve by the abscess.

Abscess↗
PubMed1992

DDD pacing mode survival in patients with a dual-chamber pacemaker.

Dual-chamber (DDD) pacing mode survival was assessed by reviewing 486 consecutive initial transvenous DDD pacemaker implantations between December 1981 and December 1988 inclusive, with a mean follow-up time of 33 months. The patients' mean age was 71.4 years and 55% were male; 38% had dominant sinoatrial and 62% had dominant atrioventricular (AV) node disease. Nineteen patients (4%) underwent secondary operative intervention for lead dislodgement (n = 11), lead or pulse generator malfunction (n = 6) or infection (n = 2). During follow-up, 87 patients (18%) had their device permanently reprogrammed out of the DDD mode and 10 others (2%) required temporary reprogramming out of this mode; 12 patients who required device reprogramming were managed in other dual-chamber or atrial pacing modes. Reasons for reprogramming included atrial fibrillation (n = 48; 10%); loss of atrial sensing (n = 26; 5%); recurrent "endless loop" tachycardia (n = 5; 1%); lead dislodgement without repositioning (n = 4; 1%); pulse generator malfunction (n = 1; 1%) and other (n = 5; 1%). The occurrence of atrial fibrillation was associated with dominant sinoatrial disease and a prior history of atrial fibrillation; 19% of atrial sensing loss was attributable to early or faulty pacemaker technology. The DDD mode survival rate at 1, 2, 3, 4 and 5 years was, respectively, 90%, 88%, 84%, 79% and 78%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Toxic substances in the environment affecting respiratory function of people in Hawaii.

In this trilogy we have collected data from authors who are concerned with patients with respiratory complaints. Surprisingly there are unique problems in the residents of our State. The full impact of problems known to cause respiratory illnesses, such as asbestosis, will not be known for years to come. Other problems such as the effect of sugarcane burning are just now being identified and may show a parallel to the inhalation of asbestos dust. VOG may be simply an irritant or it may explain in part the high incidence of asthma in our State. Clearly more work needs to be done to explain the pathophysiology, the risk and possible treatment for the consequences on people of these putative toxic substances.

Air Pollutants↗
PubMed1990

Clinical predictors and natural history of atrial fibrillation in patients with DDD pacemakers.

Effective DDD pacing requires that patients remain free of atrial fibrillation (AF). Four hundred eighty-nine consecutive patients undergoing initial transvenous DDD implants were reviewed to determine the incidence of postimplant AF in this population and to assess what factors, known at implant, predicted the later development of AF. The variables analyzed included age, sex, indication for implant (dominant SA or AV node disease), history of AF, atrial electrogram characteristics and pacing threshold, and the status of retrograde conduction. Forty-eight patients (9.8%) developed AF a mean of 23 months postimplant, and 11 of these patients returned to sinus rhythm and were managed once again in DDD for significant periods. A prior history of AF and the presence of dominant sinoatrial disease were far more prevalent in the patients who developed AF (P less than 0.001) though the vast majority of patients with these two independent risk factors remained in sinus rhythm through much or all of their follow-up period. We conclude that the incidence of AF is not of a magnitude to preclude DDD pacing in the vast majority of patients in sinus rhythm at implant.

Aged↗