Crystalline monoclonal antibody Fabs complexed to hen egg white lysozyme

The Fab of a monoclonal anti-lysozyme antibody (HyHEL-10) has been crystallized as the free Fab and as the Fab-antigen complex. Crystals have also been grown of the antigen complex of the Fab of another monoclonal anti-lysozyme antibody (HyHEL-9), which recognizes a different binding surface of lysozyme. All three crystals diffract to at least 3 A resolution and are suitable for X-ray diffraction studies.     

Crystallographic studies and primary structure of the antitumor monoclonal CC49 Fab′

The Fab′ of CC49, a murine monoclonal antibody directed against the human tumor-associated antigen TAG-72 has been crystallized. The crystals are monoclinic, space group P2₁ with cell parameters a = 115.6 Å, b = 116.4 Å, and c = 70.3 Å; β = 97.8°. The size of the unit cell is compatible with four Fab′ molecules in the asymmetric unit. The Fab molecules are related by two approximately perpendicular pseudo-2-fold axes. One pseudo-2-fold axis is parallel to the crystallographic 2-fold axis and was found by inspection of the Harker section of the native Patterson map; the other was found by a self rotation function. The primary structures of the variable regions of the CC49 antibody light and heavy chains have been determined and are compared with those of the related antitumor antibody B72.3. © 1993 Wiley-Liss, Inc.     

A crystallographic study of deoxy cobalt (II) mesoporphyrin IX myoglobin.

The crystal structures of acid metmyoglobin and deoxy cobalt(II)mesoporphyrin IX myoglobin were compared by a difference Fourier analysis at 2.5 A resolution. No large differences in protein conformation were observed. The greatest density of structural differences was found in the heme region. There was a loss of the histidine-bound sulfate ion and of the metal-bound water molecule, as well as a shift in the position of the prosthetic group with associated changes in the adjacent globin. The structural changes resulting from the substitution of ethyl for the vinyl side chains of the porphyrin were clearly observed. There was also a suggestion of a conformational change of the porphyrin ring. It was not clear whether there was any change of the metal position relative to the porphyrin plane or proximal histidine.     

A comparison of menotropin, highly-purified menotropin and follitropin alfa in cycles of intracytoplasmic sperm injection

Background  

Over the last several decades, as a result of an evolution in manufacturing processes, a marked development has been made in the field of gonadotropins for ovarian stimulation. Initially, therapeutic gonadotropins were produced from a simple process of urine extraction and purification; now they are produced via a complex system involving recombinant technology, which yields gonadotropins with high levels of purity, quality, and consistency.     

Glucocorticoid receptor gene polymorphisms and disease activity during pregnancy and the postpartum period in rheumatoid arthritis

Introduction

The mechanism underlying the spontaneous improvement of rheumatoid arthritis (RA) during pregnancy and the subsequent postpartum flare is incompletely understood, and the disease course varies widely between pregnant RA patients. In pregnancy, total and free levels of cortisol increase gradually, followed by a postpartum decrease to prepregnancy values. The glucocorticoid receptor (GR) polymorphisms BclI and N363S are associated with relatively increased glucocorticoid (GC) sensitivity, whereas the 9β and ER22/23EK polymorphisms of the GR gene are associated with a relatively decreased GC sensitivity. We examined the relation between the presence of these GR polymorphisms and level of disease activity and disease course of RA during pregnancy and postpartum.

Methods

We studied 147 participants of the PARA study (Pregnancy-Induced Amelioration of Rheumatoid Arthritis study), a prospective study investigating the natural improvement during pregnancy and the postpartum flare in women with RA. Patients were visited, preferably before pregnancy, at each trimester and at three postpartum time points. On all occasions, disease activity was scored by using DAS28. All patients were genotyped for the GR polymorphisms BclI, N363S, 9β, and ER22/23EK and divided in groups harboring either polymorphisms conferring increased GC sensitivity (BclI and N363S; GC-S patients) or polymorphisms conferring decreased GC sensitivity (9β or 9β + ER22/23EK; GC-I patients). Data were analyzed by using a mixed linear model, comparing GC-S patients with GC-I patients with respect to improvement during pregnancy and the postpartum flare. The cumulative disease activity was calculated by using time-integrated values (area under the curve, AUC) of DAS28 in GC-I patients versus GC-S patients. Separate analyses were performed according to the state of GC use.

Results

GC-S patients treated with GC had a significantly lower AUC of DAS28 in the postpartum period than did GC-I patients. This difference was not observed in patients who were not treated with GCs. During pregnancy, GC-S and GC-I patients had comparable levels of disease activity and course of disease.

Conclusions

Differences in relative GC sensitivity, as determined by GR polymorphisms, are associated with the level of disease activity in the postpartum period in GC-treated patients, but they do not seem to influence the course of the disease per se.     

Quantitative genomics of locomotor behavior in <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

Background  

Locomotion is an integral component of most animal behaviors, and many human health problems are associated with locomotor deficits. Locomotor behavior is a complex trait, with population variation attributable to many interacting loci with small effects that are sensitive to environmental conditions. However, the genetic basis of this complex behavior is largely uncharacterized.     

Two Ig framework I epitopic specificities recognized by a rabbit antiserum and a monoclonal antibody to mouse VH chains.

The reactivity of 23 mouse monoclonal Ig with a rabbit polyclonal antiserum to VH of anti-alpha(1----6)dextran 19.22.1 and with a monoclonal anti-VH of anti-DNP MOPC315, when correlated with amino acid sequence, identified several residues in the first and third framework regions as being of potential importance in forming the epitope. Inhibition studies using synthetic peptides corresponding to residues 1-15 of the monoclonal Ig used to produce the poly- and monoclonal reagents provide evidence that the epitopes are predominantly, if not exclusively, specific for the N-terminal strand of the domain. Examination of known x-ray structures of mouse VH suggests that the primary difference between the two epitopes in the N-terminal strands is determined by the peptide chain structure due to Pro at position 9. Pro 9 appears essential for the epitope reactive with anti-VH MOPC315.