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Facial palsy: unusual etiology.

This is a report of three patients who presented at the Mayo Clinic over a two-year period. All were initially diagnosed as having Bell's palsy but were later found to have a malignant neoplasm causing the paralysis. Two of the patients had breast carcinoma metastases involving the mastoid portion of the facial nerve. The third patient had an adenocarcinoma of the deep lobe of the parotid that involved the facial nerve distal to the stylomastoid foramen. The course of the facial paralysis in the two patients with the metastitic breast disease was almost identical. It consisted of episodes of pain in the mastoid area. generally in the late evening or during the night, often awakening the patient from sleep. This was then followed by peripheral facial-nerve paralysis, sometimes partial and at other times complete. These episodes lasted from 10 minutes to several hours and then resolved completely. They recurred over several months. The patients were completely asymptomatic and normal on examination in the intervals between episodes of paralysis until it became permanent. Metastatic lesions causing facial paralysis are extremely rare in the literature. In those cases that have been reported, the paralysis was progressive from the start and in the vast majority of cases was either painless or associated with other aural symptoms such as otorrhea, hearing loss, and periauricular swelling. There are two unusual features of these two cases: 1. the initial presentation of a breast metastasis as a facial paralysis; in the first case there were no other metastatic lesions present at diagnosis, whereas the second patient had other, asymptomatic, metastatic nodules; and 2. the multiple, brief, recurring episodes of facial paralysis, which have not previously been reported as a mode of presentation of metastitic disease. The third patient was diagnosed as having Bell's palsy. A facial nerve decompression was performed, and the nerve apparently looked normal. The paralysis failed to resolve. He was later found to have adenocarcinoma of the deep lobe of the parotid that involved the facial nerve distal to the stylomastoid foramen. A report of only one similar case could be found in the literature. The sequence of events in these three cases emphasizes the importance of submitting a patient suspected of having Bell's palsy to a thorough otoneurologic examination.

Adenocarcinoma↗

Ultrastructural aspects of freeze-fractured and etched elastin.

The ultrastructural organization of fresh and purified elastin from beef ligamentum nuchae was studied by means of the freeze-etching technique. Both fresh and purified elastin showed a regular three-dimensional network of filaments which seemed to be composed of a sequence of globular subunities. There were also areas, along the regular network, in which ridges of various lengths, packed with perpendicular side filaments, were visible. In replicas of deep-etched and rotary-shadowed specimens, a thicker and more defined three-dimensional network was observable. A great variability in appearance among the globular subunits of the filaments was noticed which was at least partially due to the etching treatment. By means of computerized simulation of replicas of various hypothetically collapsed globular structures, we obtained patterns which were superimposable on those obtained in the replicas of the specimens analyzed. It is thus assumed that each globular subunit of the filament, being subjected to collapsing, has a less dense central core.

Animals↗

[Differential diagnosis of thyrotoxic myopathy].

To differentiate between thyrotoxic myopathy and myodystrophy (of the limb-girdle type), severe myasthenia, polymyositis, Addison's disease, proximal spinal muscular atrophy, steroid myopathy and neurosis special diagnostic indices have been developed based on specific muscular weakness (and atrophy) pattern early in the disease, the sequence of separate muscles involvement as the pathological process progresses, disproportion between muscular weakness and atrophy, excessive folds of the skin above the affected muscles and the presence of deep reflexes, purposeful analysis of the anamnesis. The diagnosis is confirmed by thyroid function study and/or myopathy regression in response to antithyroid therapy.

Adolescent↗

[Magnetic resonance features in cerebral primary lymphomas in non-immunocompromised subjects].

In the past few years, non-Hodgkin's lymphomas have been paid increasing attention to because of their recently increasing frequency. We reviewed the MR images of 17 patients with histologically proved primary CNS lymphoma, all of them immunocompetent at diagnosis. We studied the site, number and shape of the lesions, the presence and grade of edema and possible periventricular spread. The exams were performed with 0.5 T and 1.5 T MR units, using SE sequences on the sagittal, axial and coronal planes, before and after Gd-DTPA administration. The most typical neuroradiologic signs which may suggest the diagnosis of CNS lymphoma are deep or periventricular lesion site, diffuse and marked contrast enhancement, poorly defined borders, moderate edema surrounding the mass and a tendency to periventricular spread. MRI demonstrated 35 lesions in 17 patients. The lymphoma was unifocal in 9 cases (53%) and 7 lesions were localized in subtentorial site. Lesion size did not exceed 2 cm in 49% of cases, ranged 2-4 cm in 40% and exceeded 4 cm in 11% of cases only. These lesions and hypo- to isointense on T1-weighted images (97%) and their signal intensity varies on T2-weighted images, with mainly iso-/hypointense patterns (79%). All lesions enhanced after Gd-DTPA administration, 74% of them markedly and 26% moderately; enhancement was mostly homogeneous (80% of cases). Perilesional edema was observed in 74% of cases. In conclusion, MRI yields some useful information for the diagnosis of primary CNS lymphoma, but the clinical and radiologic signs of this lesion may exhibit aspecific signal features, meaning that no correct diagnosis can be made even in immuno-competent patients.

Adult↗

Genomic and phylogenetic characterization of luminous bacteria symbiotic with the deep-sea fish Chlorophthalmus albatrossis (Aulopiformes: Chlorophthalmidae).

Bacteria forming light-organ symbiosis with deep-sea chlorophthalmid fishes (Aulopiformes: Chlorophthalmidae) are considered to belong to the species Photobacterium phosphoreum. The identification of these bacteria as P. phosphoreum, however, was based exclusively on phenotypic traits, which may not discriminate between phenetically similar but evolutionarily distinct luminous bacteria. Therefore, to test the species identification of chlorophthalmid symbionts, we carried out a genomotypic (repetitive element palindromic PCR genomic profiling) and phylogenetic analysis on strains isolated from the perirectal light organ of Chlorophthalmus albatrossis. Sequence analysis of the 16S rRNA gene of 10 strains from 5 fish specimens placed these bacteria in a cluster related to but phylogenetically distinct from the type strain of P. phosphoreum, ATCC 11040(T), and the type strain of Photobacterium iliopiscarium, ATCC 51760(T). Analysis of gyrB resolved the C. albatrossis strains as a strongly supported clade distinct from P. phosphoreum and P. iliopiscarium. Genomic profiling of 109 strains from the 5 C. albatrossis specimens revealed a high level of similarity among strains but allowed identification of genomotypically different types from each fish. Representatives of each type were then analyzed phylogenetically, using sequence of the luxABFE genes. As with gyrB, analysis of luxABFE resolved the C. albatrossis strains as a robustly supported clade distinct from P. phosphoreum. Furthermore, other strains of luminous bacteria reported as P. phosphoreum, i.e., NCIMB 844, from the skin of Merluccius capensis (Merlucciidae), NZ-11D, from the light organ of Nezumia aequalis (Macrouridae), and pjapo.1.1, from the light organ of Physiculus japonicus (Moridae), grouped phylogenetically by gyrB and luxABFE with the C. albatrossis strains, not with ATCC 11040(T). These results demonstrate that luminous bacteria symbiotic with C. albatrossis, together with certain other strains of luminous bacteria, form a clade, designated the kishitanii clade, that is related to but evolutionarily distinct from P. phosphoreum. Members of the kishitanii clade may constitute the major or sole bioluminescent symbiont of several families of deep-sea luminous fishes.

Animals↗

[Oligonucleotide probes for the detection of Thermoanaerobacter].

Based on the analysis of 16S rRNA nucleotide sequences, oligonucleotide probes were designed for the detection and identification of representatives of the genus Thermoanaerobacter. To increase the specificity level of detection, the genus Thermoanaerobacter was divided into three groups. The probe Tab 827 (5'-GCTTCCGCDYCCCACACCTA-3') detected all known representatives of the genus Thermoanaerobacter; the probe Tab_1 844 (5'-TTAACTACGGCACGRAATGCTTC-3') was specific for the first group of the species of the genus (T. wiegelii, T. siderophilus, T. sulfurophilus, T. brockii, T. kivui, T. ethanolicus, T. acetoethylicus, and T. thermohydrosulfuricus); the probe Tab_2 424 (5'-CACTAMYGGGGTTTACAACC-3') targeted the second group (T. thermocopriae, T. mathranii, and T. italicus); and the probe Tab_3 184 (5'-TC-CTCCATCAGGATGCCCTA-3') was specific for the third group (T. tengcongensis, T. yonseiensis, T. subterraneus, and Carboxydibrachium pacificum, an organism related to the genus Thermoanaerobacter according to its 16S rRNA sequence). The oligonucleotide probes were labeled with Dig-11-dUTP. Hybridization with the probes showed the affiliation with Thermoanaerobacter of several pure cultures that were morphologically similar to representatives of this genus but possessed metabolic features unusual for it (capacity for agarose hydrolysis, anaerobic oxidation of CO, growth at low pH values) or were isolated from habitats previously unknown for Thermoanaerobacter (deep-sea hydrothermal vents).

Bacteria, Anaerobic↗

Bacterial diversity in a deep-subsurface clay environment.

The presence of bacteria in a deep clay sediment was analyzed in a 20-m-long core horizontally drilled from a mine gallery at a depth of 224 m in the Boom clay formation (Mol, Belgium). This clay deposit is the result of a marine sedimentary process that occurred 35 million years ago. Bacterial activities were estimated by measuring respiration on [14C]glucose. Using the same samples, universal primers for the genes coding for eubacterial 16S rRNA were used to amplify extracted DNA. PCR products were then cloned, sequenced, and analyzed by molecular phylogeny. Our data showed a decrease in bacterial densities as a function of distance from the gallery, with few bacteria detectable by culture at more than 80 cm from the gallery wall. PCR experiments showed the presence of bacteria in all samples, and phylogenetic analyses were then used to tentatively identify these organisms. Because of low bacterial densities in deep clay samples, direct counts and enumeration of viable bacteria on diverse culture media remained negative. All experiments, both cultures and PCR, demonstrated the difficulty of analyzing samples that contain only a few poorly active bacteria as it is difficult to avoid a small contamination by active bacteria during sampling. Since the porosity of the Boom clay formation is less than the expected size of bacteria, it is possible that some of the bacteria present in this 35-million-year-old deep clay deposit derive from cells initially trapped during the sedimentation process.

Bacteria↗

Long-term inheritance of the 28S rDNA-specific retrotransposon R2.

R2 is a non-long-terminal-repeat (LTR) retrotransposon that inserts specifically into 28S rDNA. R2 has been identified in many species of arthropods and three species of chordates. R2 may be even more widely distributed in animals, and its origin may be traceable to early animal evolution. In this study, we identified R2 elements in medaka fish, White Cloud Mountain minnow, Reeves' turtle, hagfish, sea lilies, and some arthropod species, using degenerate polymerase chain reaction methods. We also identified two R2 elements from the public genomic sequence database of the bloodfluke Schistosoma mansoni. One of the two bloodfluke R2 elements has two zinc-finger motifs at the N-terminus; this differs from other known R2 elements, which have one or three zinc-finger motifs. Phylogenetic analysis revealed that the whole phylogeny of R2 can be divided into 11 parts (subclades), in which the local R2 phylogeny and the corresponding host phylogeny are consistent. Divergence-versus-age analysis revealed that there is no reliable evidence for the horizontal transfer of R2 but supports the proposition that R2 has been vertically transferred since before the divergence of the deuterostomes and protostomes. The seeming inconsistency between the R2 phylogeny and the phylogeny of their hosts is due to the existence of paralogous lineages. The number of N-terminal zinc-finger motifs is consistent with the deep phylogeny of R2 and indicates that the common ancestor of R2 had three zinc-finger motifs at the N-terminus. This study revealed the long-term vertical inheritance and the ancient origin of sequence specificity of R2, both of which seem applicable to some other non-LTR retrotransposons.

Amino Acid Sequence↗

mamp-ml: A deep learning approach to epitope immunogenicity in plants.

Eukaryotes detect biomolecules through surface-localized receptors, key signaling components. A subset of receptors survey for pathogens, induce immunity, and restrict pathogen growth. Comparative genomics of both hosts and pathogens has unveiled vast sequence variation in receptors and potential ligands, creating an experimental bottleneck. We have developed mamp-ml, a machine learning framework for predicting plant receptor-ligand interactions. We leveraged existing functional data from over two decades of foundational research, together with the large protein language model ESM-2, to build a pipeline and model that predicts immunogenic outcomes using a combination of receptor-ligand features. Our model achieves 73% prediction accuracy on a held-out test set, even when an experimental structure is lacking. Our approach enables high-throughput screening of LRR receptor-ligand combinations and provides a computational framework for engineering plant immune systems.

Journal Article↗

The role of the medial collateral ligament and posteromedial capsule in controlling knee laxity.

BACKGROUND: The medial aspect of the knee has a complex capsular structure; the biomechanical roles of specific structures are not well understood. HYPOTHESIS: The 3 strong stabilizing structures, the superficial and deep medial collateral ligaments and the posteromedial capsule, make distinct contributions to controlling tibiofemoral laxity. STUDY DESIGN: Controlled laboratory study. METHODS: Changes in knee laxity under anterior-posterior drawer, valgus, and internal-external rotation loads were found by sequential cutting in 18 cadaveric knees. Three cutting sequences allowed the roles of the 3 structures to be seen in isolation and in combination. Some force contributions were also calculated. RESULTS: The posteromedial capsule controlled valgus, internal rotation, and posterior drawer in extension, resisting 42% of a 150-N drawer force when the tibia was in internal rotation. The superficial collateral ligament controlled valgus at all angles and was dominant from 30 degrees to 90 degrees of flexion, plus internal rotation in flexion. The deep collateral ligament controlled tibial anterior drawer of the flexed and externally rotated knee and was a secondary restraint to valgus. CONCLUSION: Distinct roles in controlling tibiofemoral laxity have been found for these structures that vary according to knee flexion and tibial rotation. CLINICAL RELEVANCE: The restraining functions demonstrated provide new information about knee stabilization, which may allow better evaluation of structural damage at the medial aspect of the knee.

Aged↗

Novel uncultured Epsilonproteobacteria dominate a filamentous sulphur mat from the 13 degrees N hydrothermal vent field, East Pacific Rise.

Rapid growth of microbial sulphur mats have repeatedly been observed during oceanographic cruises to various deep-sea hydrothermal vent sites. The microorganisms involved in the mat formation have not been phylogenetically characterized, although the production of morphologically similar sulphur filaments by a Arcobacter strain coastal marine has been documented. An in situ collector deployed for 5 days at the 13 degrees N deep-sea hydrothermal vent site on the East Pacific Rise (EPR) was rapidly colonized by a filamentous microbial mat. Microscopic and chemical analyses revealed that the mat consisted of a network of microorganisms embedded in a mucous sulphur-rich matrix. Molecular surveys based on 16S rRNA gene and aclB genes placed all the environmental clone sequences within the Epsilonproteobacteria. Although few 16S rRNA gene sequences were affiliated with that of cultured organisms, the majority was related to uncultured representatives of the Arcobacter group (< or = 95% sequence similarity). A probe designed to target all of the identified lineages hybridized with more than 95% of the mat community. Simultaneous hybridizations with the latter probe and a probe specific to Arcobacter spp. confirmed the numerical dominance of Arcobacter-like bacteria. This study provides the first example of the prevalence and ecological significance of free-living Arcobacter at deep-sea hydrothermal vents.

Bacterial Adhesion↗

The role of galE in the biosynthesis and function of gonococcal lipopolysaccharide.

Lipopolysaccharide is an essential component of the outer membrane of Gram-negative bacteria and an important virulence factor of many pathogens, such as Neisseria gonorrhoeae. We have cloned the gonococcal galE gene which was found to be located in the gonococcal homologue of the meningococcal capsule gene complex region D. Sequence alignment indicated extensive homology with the Escherichia coli and Salmonella GalE proteins. Mutants with insertions in the galE gene were used as a tool to characterize the structure and function of gonococcal lipopolysaccharide. They displayed deep rough phenotypes, and chemical analysis confirmed the loss of galactose from the mutant lipopolysaccharide. Functional analysis indicated that the terminal oligosaccharides contain galactose and that these are lost in galE mutants. The importance of these oligosaccharides in gonococcal biology is clear from the fact that they contain the epitopes that are the targets for killing by normal human serum, and the acceptor site for sialic acid, which acts to protect the gonococcus from this killing. Furthermore, infection experiments in vitro indicate that the galE mutants exhibit unaltered intergonococcal adhesion as well as adhesion to, and invasion of, epithelial cells.

Amino Acid Sequence↗

Molecular phylogeny of the benthic shallow-water octopuses (Cephalopoda: Octopodinae).

Octopus has been regarded as a "catch all" genus, yet its monophyly is questionable and has been untested. We inferred a broad-scale phylogeny of the benthic shallow-water octopuses (subfamily Octopodinae) using amino acid sequences of two mitochondrial DNA genes: Cytochrome oxidase subunit III and Cytochrome b apoenzyme, and the nuclear DNA gene Elongation Factor-1alpha. Sequence data were obtained from 26 Octopus species and from four related genera. Maximum likelihood and Bayesian approaches were implemented to estimate the phylogeny, and non-parametric bootstrapping was used to verify confidence for Bayesian topologies. Phylogenetic relationships between closely related species were generally well resolved, and groups delineated, but the genes did not resolve deep divergences well. The phylogenies indicated strongly that Octopus is not monophyletic, but several monophyletic groups were identified within the genus. It is therefore clear that octopodid systematics requires major revision.

Amino Acid Sequence↗

[Contrast-enhanced three-dimensional angiography].

Rapid advances in the techniques of contrast-enhanced MR angiography (MRA) have made it possible to evaluate the entire aorta and main arteries as well as small arteries and veins of the whole body. In this article, the technical aspects and clinical applications of contrast-enhanced MRA are reviewed. Dynamic contrast-enhanced three-dimensional (3D) MRA is a first-pass vascular imaging technique that uses the 3D fast field echo sequence with rapid bolus injection of contrast material. By repeating imaging sequences, it is possible to trace the dynamics of the injected contrast material over time and apply various postprocessing techniques, such as double subtraction and addition, to demonstrate arteries and veins separately and to display the arteries in a single image, even when circulation time is prolonged. This technique is flexible enough to be applied in a variety of clinical settings by optimizing the examination. The abdominal aorta and main arteries of the lower extremities are examined by two methods, dynamic subtraction 3D MRA (MRDSA) and the moving-bed method. Three bolus injections of contrast material are used in MRDSA. In contrast, a slow continuous injection of a large dose (20 ml or more) of contrast material is used in the moving-bed method, which is a convenient, useful method of contrast-enhanced MR angiography when the study must focus on arterial imaging. Clinical indications include atherosclerotic occlusive disease, Takayasu arteritis, aortic dissection, anti-phospholipid antibody syndrome, aneurysm, patent and occluded bypass graft, and deep vein thrombosis, among others. The problem with contrast-enhanced MRA is its difficulty in depicting small vessels such as mesenteric arteries, distal renal arteries, and peripheral small arteries. The nature of gradient-echo sequences has certain inherent problems for the imaging of small vessels. The fat-tissue interface becomes dark because of chemical shift artifact (which occurs both when the echo time is set in-phase and when it is set out-of-phase), reducing the ability to detect small arteries with contrast-enhanced MR angiography. The fat suppression technique is very useful for satisfactorily demonstrating small vessels by reducing chemical shift artifact. MR angiography remains an exciting and challenging field, and the best methods of contrast-enhanced MR angiography will be developed and established on the foundation of all previous work.

Adult↗

Functional conservation of calreticulin in Euglena gracilis.

Calreticulin is the major high capacity, low affinity Ca2+ binding protein localized within the endoplasmic reticulum. It functions as a reservoir for triggered release of Ca2+ by the endoplasmic reticulum and is thus integral to eukaryotic signal transduction pathways involving Ca2+ as a second messenger. The early branching photosynthetic protist Euglena gracilis is shown to possess calreticulin as its major high capacity Ca2+ binding protein. The protein was purified, microsequenced and cloned. Like its homologues from higher eukaryotes, calreticulin from Euglena possesses a short signal peptide for endoplasmic reticulum import and the C-terminal retention signal KDEL, indicating that these components of the eukaryotic protein routing apparatus were functional in their present form prior to divergence of the euglenozoan lineage. A gene phylogeny for calreticulin and calnexin sequences in the context of eukaryotic homologues indicates i) that these Ca2+ binding endoplasmic reticulum proteins descend from a gene duplication that occurred in the earliest stages of eukaryotic evolution and furthermore ii) that Euglenozoa express the calreticulin protein of the kinetoplastid (trypanosomes and their relatives) lineage, rather than that of the eukaryotic chlorophyte which gave rise to Euglena's plastids. Evidence for conservation of endoplasmic reticulum routing and Ca2+ binding function of calreticulin from Euglena traces the functional history of Ca2+ second messenger signal transduction pathways deep into eukaryotic evolution.

Amino Acid Sequence↗

The 2 A resolution structure of the sulfate-binding protein involved in active transport in Salmonella typhimurium.

The crystal structure of the liganded form of the sulfate-binding protein, an initial receptor for active transport of sulfate in Salmonella typhimurium, has been solved and refined at 2.0 A resolution (1 A = 0.1 nm). The final model, which consists of 2422 non-hydrogen atoms, one sulfate substrate and 143 water molecules, yields a crystallographic R-factor of 14.0% for 16,959 reflections between 8 and 2 A. The structure deviates from ideal bond lengths and angle distances by 0.015 A and 0.037 A, respectively. The protein is ellipsoid with overall dimensions of 35 A x 35 A x 65 A and consists of two similar globular domains. The two domains are linked by three distinct peptide segments, which though widely separated in the amino acid sequence, are in close proximity in the tertiary structure. As these connecting segments are located near the periphery of the molecule, they further serve as the base or a "boundary" of the deep cleft formed between the two domains. Despite the unusual interdomain connectivity, both domains have similar supersecondary structure consisting of a central five-stranded beta-pleated sheet sandwiched by alpha-helices on either side. The arrangement of the two domains gives rise to the ellipsoidal shape and to the cleft between the two domains wherein the sulfate substrate is found and completely engulfed. A discovery of considerable importance is that the sulfate substrate is tightly held in place primarily by seven hydrogen bonds, five of which are donated by main-chain peptide NH groups, another by a serine hydroxyl and the last by the indole NH moiety of a tryptophan side-chain; there are no positively charged residues, nor cations, nor water molecules within van der Waals' distance to the sulfate dianion. All the main-chain peptide units associated with the sulfate are in turn linked (via the peptide CO group) to arrays of hydrogen bonds. Three of these arrays are composed of alternating peptide units and hydrogen bonds within the solvent-exposed part of three alpha-helices and two are linked to a histidine and an arginine residue. The sulfate-binding protein bears strong similarity to the structures of four other periplasmic binding proteins solved in our laboratory which are specific for L-arabinose, D-galactose/D-glucose, leucine/isoleucine/valine and leucine. The similarity includes the ellipsoidal shape and the two globular domain structures, each domain consisting of a central beta-pleated sheet flanked by alpha-helices.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Microanatomical compartments of clonal and reactive T cells in mycosis fungoides: molecular demonstration by single cell polymerase chain reaction of T cell receptor gene rearrangements.

Mycosis fungoides (MF) is a cutaneous T cell lymphoma, clinically characterized by patches, plaques and tumors occurring in successive stages of the disease. In early MF, an infiltrate consisting of mainly reactive T cells is seen in the papillary dermis while tumor cells are mostly confined to the epidermis. By contrast, later stages show nodular infiltrates formed mostly of tumor cells in the dermis while the epidermis is relatively devoid of tumor cells; however, knowledge of the localization of clonal T cells has been based on histomorphologic features and immunohistochemical stainings visualizing certain V-beta subfamilies of the T cell receptor (TCR). As these techniques do not allow for an unequivocal identification of clonal tumor cells, we used micromanipulation and single cell PCR amplifying the TCR chain gene rearrangement. A total number of 387 single T cells was isolated from six skin biopsies in five patients in patch, plaque, and tumor stages. Of these, 180 T cells were picked from the epidermis and 207 from the dermal infiltrate. The rearranged TCR-gamma DNA could be sequenced from 181 of 387 T cells. In three of six patients representing all three stages, epidermal T cells with a clonal rearrangement could be amplified. In early plaque stage a higher degree of epidermal T lymphocytes was found than in initial patch, later plaque, and tumor stages with an inverse distribution found for reactive T lymphocytes. In two patients a biallelic rearrangement was demonstrated that had not been detected in prior PCR analysis from blood and skin samples. These data show that clonal (neoplastic) and non-clonal (reactive) T lymphocytes in MF preferentially infiltrate different microanatomical compartments of the skin, depending on the stage of disease. The microanatomically distinct localization of reactive and clonal T cells suggests that the absence of direct contact between tumor and host-defense lymphocytes may contribute to tumor persistence and progression in epidermis, peripheral blood, and deep dermal tumor cell nests, respectively.

Aged↗

Molecular analysis of anti-N-propionyl Neisseria meningitidis group B polysaccharide monoclonal antibodies.

The capsular polysaccharide of Neisseria meningitidis group B (MBPS) is a polymer of alpha (2-->8) N-acetyl neuraminic acid, which is chemically identical to polysialic acid (PSA) expressed in human tissues. Antibodies from mice immunized with a MBPS-protein conjugate vaccine in which N-acetyl groups have been replaced by propionyl groups (N-Pr MBPS) can be bactericidal and show minimal or no cross-reactivity with human PSA. To investigate the molecular basis for antigen recognition, we cloned and sequenced the variable region (V) genes of five bactericidal anti-N-Pr MBPS murine mAbs and produced computer models of the combining sites. The results were compared to those reported in the literature for two autoreactive anti-MBPS. The V region genes of the anti-N-Pr MBPS mAbs and the anti-MBPS autoreactive mAbs are derived from a limited set of germline V, J, and D genes. However, the anti-N-Pr MBPS mAbs are more mutated than the anti-MBPS mAbs and the former use V-D-J editing that introduces arginine in H-CDR3. Models of the respective combining sites indicate that the anti-MBPS or anti-N-Pr MBPS mAbs that react with host PSA have relatively wide and shallow grooves with a high overall positive charge, consistent with recognition of extended helical polysaccharide structures recognized by the autoreactive mAbs. In contrast, anti-N-Pr MBPS mAbs that do not react with host PSA contain pockets and deep clefts that are consistent with recognition of discrete structural features of individual residues.

Amino Acid Sequence↗