Inhibition of HIV-1 replication by chimeric phosphorothioate oligodeoxynucleotides applied in free solution.

Oligodeoxynucleotides (ODNs) containing a variable number of 3' and 5' terminal phosphorothioate linkages were applied in free solution to cells infected by HIV-1. ODNs of 28 nt length were applied at up to 5 microM concentration. The ODNs were found to inhibit HIV-1 infection in a dose dependent manner, which correlated with the number of modified linkages (4, 8 and 12, respectively).

Myocardial structure as a determinant of pre- and postoperative ventricular function and long-term prognosis after valve replacement for aortic stenosis.

Background: Long-term results after aortic value replacement for aortic stenosis can be correlated to a cardiac-related pre-operative risk profile. This predictability indicates that there is a common basis in subtle or overt structural abnormalities of left ventricular myocardium.

Methods And Results: Forty-nine patients aged 24-82 (mean 61) years, with aortic stenosis had a full wall thickness transmural biopsy of the left ventricular antero-lateral free wall during aortic valve replacement.

[Mortality and worsening of prognosis for patients with aortic stenosis while on the waiting list].

In a prospective study, 99 consecutive patients with an operative indication due to severe aortic stenosis (AS) were put on a surgical waiting list. The waiting time to aortic valve replacement (AVR) averaged 6.3 months (0.

NetOglyc: prediction of mucin type O-glycosylation sites based on sequence context and surface accessibility.

The specificities of the UDP-GalNAc:polypeptide Nacetylgalactosaminyltransferases which link the carbohydrate GalNAc to the side-chain of certain serine and threonine residues in mucin type glycoproteins, are presently unknown. The specificity seems to be modulated by sequence context, secondary structure and surface accessibility. The sequence context of glycosylated threonines was found to differ from that of serine, and the sites were found to cluster.

Protein distance constraints predicted by neural networks and probability density functions.

We predict interatomic Calpha distances by two independent data driven methods. The first method uses statistically derived probability distributions of the pairwise distance between two amino acids, whilst the latter method consists of a neural network prediction approach equipped with windows taking the context of the two residues into account. These two methods are used to predict whether distances in independent test sets were above or below given thresholds.

O-GLYCBASE Version 3.0: a revised database of O-glycosylated proteins.

O-GLYCBASE is a revised database of information on glycoproteins and their O-linked glycosylation sites. Entries are compiled and revised from the literature, and from the sequence databases. Entries include information about species, sequence, glycosylation sites and glycan type and is fully cross-referenced.

Left ventricular systolic and diastolic function in aortic stenosis. Prognostic value after valve replacement and underlying mechanisms.

Aims: The aims of the study were to examine the prognostic value of pre-operative left ventricular systolic and diastolic function on early, and late mortality after valve replacement for aortic stenosis, and to identify possible underlying mechanisms.

Methods And Results: Ninety-one prospectively recruited consecutive patients with a mean age of 61 years underwent valve replacement for aortic stenosis with concomitant coronary artery bypass grafting in 32 and a minimum postoperative observation period of 5.4 years.

IsK and KvLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome.

The Jervell and Lange-Nielsen syndrome (JLNS) comprises profound congenital sensorineural deafness associated with syncopal episodes. These are caused by ventricular arrhythmias secondary to abnormal repolarisation, manifested by a prolonged QT interval on the electrocardiogram. Recently, in families with JLNS, Neyroud et al.

Gene therapy of T helper cells in HIV infection: mathematical model of the criteria for clinical effect.

This paper presents a mathematical analysis of the criteria for gene therapy of T helper cells to have a clinical effect on HIV infection. The analysis indicates that for such a therapy to be successful, it must protect the transduced cells against HIV-induced death. The transduced cells will not survive as a population if the gene therapy only blocks the spread of virus from transduced cells that become infected.

Impact of size mismatch and left ventricular function on performance of the St. Jude disc valve after aortic valve replacement.

Background: The hemodynamic function of the St. Jude valve may change relative to changes in left ventricular function after aortic valve replacement for aortic stenosis. From theoretical reasons one may hypothesize that prosthetic valve hemodynamic function is related to left ventricular failure and mismatch between valve size and patient/ventricular chamber size.

Complement-mediated enhancement of HIV-1 infection in peripheral blood mononuclear cells.

We investigated if complement-mediated enhancement of HIV infection occurs in peripheral blood mononuclear cells (PBMC). In 7 experiments, we evaluated the effect of human complement on HIVIIIB infection in vitro. We measured HIV antigen production on day 4 and found that pre-incubation of HIV with complement led to enhanced production of antigen with a median enhancement of 2.

M-mode echocardiography in aortic stenosis. Clinical correlates and prognostic significance after valve replacement.

To relate preoperative findings at M-mode echocardiography to preoperative clinical and haemodynamic status and to identify possible echocardiographic risk factors for mortality after aortic valve replacement (AVR), 250 patients with AVR for aortic stenosis (AS) were studied. In follow-up averaging 3.2 years there were 22 early (< 30 days) and 23 late deaths.

O-GLYCBASE version 2.0: a revised database of O-glycosylated proteins.

O-GLYCBASE is an updated database of information on glycoproteins and their O-linked glycosylation sites. Entries are compiled and revised from the literature, and from the SWISS-PROT database. Entries include information about species, sequence, glycosylation sites and glycan type.

Mortality and worsening of prognostic profile during waiting time for valve replacement in aortic stenosis.

In a prospective study 99 consecutive patients with operative indication due to severe aortic stenosis (AS) were put on a surgical waiting list. The waiting-time to aortic valve replacement (AVR) averaged 6.3 months (0.

Relationship between protein structure and geometrical constraints.

We evaluate to what extent the structure of proteins can be deduced from incomplete knowledge of disulfide bridges, surface assignments, secondary structure assignments, and additional distance constraints. A cost function taking such constraints into account was used to obtain protein structures using a simple minimization algorithm. For small proteins, the approximate structure could be obtained using one additional distance constraint for each amino acid in the protein.

Distance distributions in proteins: a six-parameter representation.

We present a statistical analysis of protein structures based on interatomic C alpha distances. The overall distance distributions reflect in detail the contents of sequence-specific substructures maintained by local interactions (such as alpha-helixes) and longer range interactions (such as disulfide bridges and beta-sheets). We also show that a volume scaling of the distances makes distance distributions for protein chains of different length superimposable.

The potential for normal long term survival and morbidity rates after valve replacement for aortic stenosis.

Background And Aim Of The Study: The sequelae of early aortic valve replacement (AVR) for aortic stenosis (AS) are controversial, with an increasing body of opinion regarding the patient risk profile as having an influence on long term survival and prosthesis-related morbidity rates. We therefore undertook a comparison of the morbidity and mortality rates of the patients undergoing AVR at our institution over a 22 year period with those in the background population to establish whether early intervention leads to an increased incidence of either.

Methods: A multivariate risk analysis of 630 consecutive patients with AS who were alive 30 days after AVR performed between January 1965 and December 1986 was completed.

Prediction of the secondary structure of HIV-1 gp120.

The secondary structure of HIV-1 gp120 was predicted using multiple alignment and a combination of two independent methods based on neural network and nearest-neighbor algorithms. The methods agreed on the secondary structure for 80% of the residues in BH10 gp120. Six helices were predicted in HIV strain BH10 gp120, as well as in 27 other HIV-1 strains examined.

O-GLYCBASE: a revised database of O-glycosylated proteins.

O-GLYCBASE is a comprehensive database of information on glycoproteins and their O-linked glycosylation sites. Entries are compiled and revised from the SWISS-PROT and PIR databases as well as directly from recently published reports. Nineteen percent of the entries extracted from the databases needed revision with respect to O-linked glycosylation.

Inhibition of HIV-1 in vitro by C-5 propyne phosphorothioate antisense to rev.

A 15-mer C-5 propyne modified phosphorothioate oligodeoxynucleotide antisense to rev was approximately 5-fold more effective in providing viral inhibition compared to a 28-mer unmodified phosphorothioate oligodeoxynucleotide targeted to the same sequence and previously shown to inhibit HIV-1 in a sequence-dependent manner. The antiviral effect was obtained by lipofection or simple addition of 0.2-1 microM modified oligodeoxynucleotide to the culture medium of H9 cells chronically infected with the HIV-1LAI isolate of human immunodeficiency virus type 1.

Fourteen-year experience with homovital homografts for aortic valve replacement.

Two hundred seventy-five unprocessed, viable homograft ("homovital") aortic valves were used for aortic valve replacement in patients aged 1.5 to 79 years (mean 45.8 +/- 19 years) with maximum follow-up of a 14-year period (mean 4.

Prediction of O-glycosylation of mammalian proteins: specificity patterns of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase.

The specificity of the enzyme(s) catalysing the covalent link between the hydroxyl side chains of serine or threonine and the sugar moiety N-acetylgalactosamine (GalNAc) is unknown. Pattern recognition by artificial neural networks and weight matrix algorithms was performed to determine the exact position of in vivo O-linked GalNAc-glycosylated serine and threonine residues from the primary sequence exclusively. The acceptor sequence context for O-glycosylation of serine was found to differ from that of threonine and the two types were therefore treated separately.

Increased adhesion as a mechanism of antibody-dependent and antibody-independent complement-mediated enhancement of human immunodeficiency virus infection.

Enhancement of human immunodeficiency virus (HIV) infection by complement alone or in conjunction with antibodies was studied experimentally and theoretically. Experimental studies showed that while HIV-positive sera neutralize HIV infection, the addition of fresh complement abrogated neutralization and could even cause enhancement. Enhancement was blocked by anti-complement receptor 2 antibodies, and infection under enhancing conditions could be blocked by soluble CD4.