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PubMed2002

Conserved low-affinity nickel-binding amino acids are essential for the function of the nickel permease NixA of Helicobacter pylori.

Nickel acquisition is necessary for urease activity, a major virulence factor of the human gastric pathogen Helicobacter pylori. The nickel permease NixA of H. pylori is a member of the single-component nickel-cobalt transporter family. To identify functionally relevant amino acids of NixA, single-site exchanges were introduced into NixA via PCR-based mutagenesis. This study investigated one of the recognition motifs for this family in transmembrane segment III and other conserved amino acids, mostly with possible nickel-binding capacities. The mutant alleles were expressed in Escherichia coli, and activity of the altered permeases was analyzed by measuring nickel accumulation and urease activity. Expression was checked by immunoblotting after sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a NixA-specific antibody. Replacement of Phe-75 and His-79-both part of the characteristic sequence motif-and of Asn-127, Thr-195, and Ser-197 with alanine abolished nickel uptake in the E. coli system. The results were unchanged if these amino acids were replaced with residues more similar to the original amino acid. The phenotype of the null mutants was independent of the culture medium. Mutation of Val-82, Tyr-242, Thr-260, His-181, and His-15 strongly affected uptake activity under nickel limitation on complex Luria-Bertani medium but had little effect in minimal medium. Eight other conserved amino acids (Ser-80, Ser-81, Phe-119, Trp-180, Tyr-183, Trp-244, Pro-249, and Asn-256) were found to be dispensable for the function of NixA. These results show that atypical nickel-binding amino acids play an important function in nickel uptake and that most of the essential amino acids are clustered in conserved motifs.

Amino Acid Motifs↗
PubMed1994

Functional analysis of two tetanus toxin universal T cell epitopes in their interaction with DR1101 and DR1104 alleles.

In this study we have investigated the interaction between two DR11 alleles (DB*1101 and DB*1104) and two previously described tetanus toxin (tt) universal T cell epitopes P2(tt830-843) and P30(tt947-967) by means of a functional cytotoxic competition assay. Both truncation analysis and single alanine substitution analysis were performed. In addition, the capacity of truncated and single alanine substituted peptides to be recognized by human T cell clones from donors bearing the DR1101 or DR1104 alleles was assessed. In the case of truncated peptides the same binding and recognition pattern was observed with both alleles. Longer peptides were better competitors and more potent stimulators, a result that should be taken into account when these peptides are used as immunogens. None of the single alanine substitutions could abrogate or strongly diminish the inhibitory capacity of the analogues tested indicating the lack of strong "anchor residues" present in P2 and P30 and implicated in DR binding. In addition, although the original peptide sequences were presented to specific T cell clones with comparable efficiency, some of the alanine single substituted peptides were better recognized in association with one of the alleles by clones derived from individuals bearing the homologous allele. The only exception was the tt951-967 analogue ttW955A, which was preferentially recognized in association with the DR1104 allele regardless of the clone tested. This suggests that, although it binds to both alleles with comparable efficiency, the MHC-peptide complex so formed is conformationally distinguishable by specific T cell clones.

Alleles↗
PubMed2006

Evolution of arthropod visual systems: development of the eyes and central visual pathways in the horseshoe crab Limulus polyphemus Linnaeus, 1758 (Chelicerata, Xiphosura).

Despite ongoing interest into the architecture, biochemistry, and physiology of the visual systems of the xiphosuran Limulus polyphemus, their ontogenetic aspects have received little attention. Thus, we explored the development of the lateral eyes and associated neuropils in late embryos and larvae of these animals. The first external evidence of the lateral eyes was the appearance of white pigment spots-guanophores associated with the rudimentary photoreceptors-on the dorsolateral side of the late embryos, suggesting that these embryos can perceive light. The first brown pigment emerges in the eyes during the last (third) embryonic molt to the trilobite stage. However, ommatidia develop from this field of pigment toward the end of the larval trilobite stage so that the young larvae at hatching do not have object recognition. Double staining with the proliferation marker bromodeoxyuridine (BrdU) and an antibody against L. polyphemus myosin III, which is concentrated in photoreceptors of this species, confirmed previous reports that, in the trilobite larvae, new cellular material is added to the eye field from an anteriorly located proliferation zone. Pulse-chase experiments indicated that these new cells differentiate into new ommatidia. Examining larval eyes labeled for opsin showed that the new ommatidia become organized into irregular rows that give the eye field a triangular appearance. Within the eye field, the ommatidia are arranged in an imperfect hexagonal array. Myosin III immunoreactivity in trilobite larvae also revealed the architecture of the central visual pathways associated with the median eye complex and the lateral eyes. Double labeling with myosin III and BrdU showed that neurogenesis persists in the larval brain and suggested that new neurons of both the lamina and the medulla originate from a single common proliferation zone. These data are compared with eye development in Drosophila melanogaster and are discussed with regard to new ideas on eye evolution in the Euarthropoda.

Animals↗
PubMed1995

Determinants of RNA hairpin loop-loop complex stability.

Complexes formed by RNA hairpin loops with complementary loop sequences derived from Escherichia coli RNA I and RNA II, which are involved in the control of DNA replication of plasmid ColE1, have been analyzed to determine the sequence and structural elements required to achieve full affinity. Of particular interest is the origin of the enhanced stability of the complex formed by hairpin loops whose loop sequences have been inverted 5' to 3' with respect to wild-type sequences. Full complementarity of the two interacting loops is required to achieve full or enhanced affinity, while the stems of the two hairpins can differ. The major determinant of enhanced affinity lies in the base-pairs formed at positions 1 and 7 of the loops, together with the two base-pairs of each stem which are closest to the loop. Sequence variation in the middle of the loops, or further down the stem away from the loops, exerts only a modest influence on complex stability. We incorporate these results into a model for the loop-loop interaction which accounts for the importance of positions one and seven and the first two nucleotides of the stem, while providing potentially unique structures for recognition by the RNA one modulator protein.

Base Sequence↗
PubMed1978

Adaptive differentiation of murine lymphocytes. I. Both T and B lymphocytes differentiating in F1 transplanted to parental chimeras manifest preferential cooperative activity for partner lymphocytes derived from the same parental type corresponding to the chimeric host.

The concept of adaptive (selective) differentiation preducts that early differentiation of lymphocytes is conditioned by the environment in which such differentiation takes place. These processes appear to involve selection of lymphocytes according to their self-recognition between interacting lymphocytes is, at least in part, controlled by major histocompatibility complex-linked genes, then adaptive differentiation is also controlled by these genes. In these studies, we have tested the capacities of helper T lymphocytes and hapten-specific B lymphocytes primed in the environments of various combinations of bone marrow chimeras prepared between two parental strains (i.e. A/J and BALB/c) and their corresponding F1 hybrid (CAF1) to interact with primed B and T lymphocytes derived from conventional parent and F1 donors as well as all of the corresponding bone marrow chimera combinations. The results demonstrate clearly that (a) F1 transplanted to F1 chimeric lymphocytes display no restriction in terms of cooperative activity with all of the various partner cell combinations; (b) parent transplanted to F1 chimeric lymphocytes manifest effective cooperative activity only for partner cells from F) or parental donors corresponding to the haplotype of the original bone marrow donor, thereby behaving phenotypically just like conventional parental lymphocytes; and (c) F1 transplanted to parent chimeric lymphocytes display restricted haplotype preference in cooperating best with partner lymphocytes sharing the H-2 haplotype, either entirely or codomimantly, of the parental chimeric host. The implications of these findings for understanding certain controlling mechanisms for lymphocyte differentiation are discussed.

Animals↗
PubMed1996

A critical arginine residue mediates cooperativity in the contact interface between transcription factors NFAT and AP-1.

The heterologous transcription factors NFAT and AP-1 coordinately regulate cytokine gene expression through cooperative binding to precisely juxtaposed DNA recognition elements. The molecular origins of cooperativity in the binding of NFAT and AP-1 to DNA are poorly understood. Herein we have used yeast one-hybrid screening and alanine-scanning mutagenesis to identify residues in AP-1 that affect cooperative interactions with NFAT on DNA. Mutation of a single conserved Arg residue to Ala in the cJun spacer region (R285A) led to a virtually complete abolition of cooperative interactions with NFAT. The DNA-binding activity of AP-1 alone was unaffected by the cJun R285A mutation, thus indicating that this residue influences cooperative binding only. Ala-scanning mutations elsewhere in AP-1, including the cFos subunit, revealed no other strongly interacting single positions. We thus conclude that NFAT contacts AP-1 in the spacer region of the cJun subunit, making an especially important contact to R285, and that these interactions drive formation of the cooperative NFAT/AP-1/DNA complex. These results provide a general strategy for selectively ablating cooperativity between transcription factors without affecting their ability to act alone and yield insights into the structural basis for coordinate regulation of gene expression.

Alanine↗
PubMed1999

Recognition of the class Ib molecule Qa-1(b) by putative activating receptors CD94/NKG2C and CD94/NKG2E on mouse natural killer cells.

The heterodimeric CD94/NKG2A receptor, expressed by mouse natural killer (NK) cells, transduces inhibitory signals upon recognition of its ligand, Qa-1(b), a nonclassical major histocompatibility complex class Ib molecule. Here we clone and express two additional receptors, CD94/NKG2C and CD94/NKG2E, which we show also bind to Qa-1(b). Within their extracellular carbohydrate recognition domains, NKG2C and NKG2E share extensive homology with NKG2A (93-95% amino acid similarity); however, NKG2C/E receptors differ from NKG2A in their cytoplasmic domains (only 33% similarity) and contain features that suggest that CD94/NKG2C and CD94/NKG2E may be activating receptors. We employ a novel blocking anti-NKG2 monoclonal antibody to provide the first direct evidence that CD94/NKG2 molecules are the only Qa-1(b) receptors on NK cells. Molecular analysis reveals that NKG2C and NKG2E messages are extensively alternatively spliced and approximately 20-fold less abundant than NKG2A message in NK cells. The organization of the mouse Cd94/Nkg2 gene cluster, presented here, shows striking similarity with that of the human, arguing that the entire CD94/NKG2 receptor system is relatively primitive in origin. Analysis of synonymous substitution frequencies suggests that within a species, NKG2 genes may maintain similarities with each other by concerted evolution, possibly involving gene conversion-like events. These findings have implications for understanding NK cells and also raise new possibilities for the role of Qa-1 in immune responses.

Amino Acid Sequence↗
PubMed1999

Synthesis of aspartyl-tRNA(Asp) in Escherichia coli--a snapshot of the second step.

The 2.4 A crystal structure of the Escherichia coli aspartyl-tRNA synthetase (AspRS)-tRNA(Asp)-aspartyl-adenylate complex shows the two substrates poised for the transfer of the aspartic acid moiety from the adenylate to the 3'-hydroxyl of the terminal adenosine of the tRNA. A general molecular mechanism is proposed for the second step of the aspartylation reaction that accounts for the observed conformational changes, notably in the active site pocket. The stabilization of the transition state is mediated essentially by two amino acids: the class II invariant arginine of motif 2 and the eubacterial-specific Gln231, which in eukaryotes and archaea is replaced by a structurally non-homologous serine. Two archetypal RNA-protein modes of interactions are observed: the anticodon stem-loop, including the wobble base Q, binds to the N-terminal beta-barrel domain through direct protein-RNA interactions, while the binding of the acceptor stem involves both direct and water-mediated hydrogen bonds in an original recognition scheme.

Anticodon↗
PubMed2001

Structural and thermodynamic behavior of eukaryotic initiation factor 4E in supramolecular formation with 4E-binding protein 1 and mRNA cap analogue, studied by spectroscopic methods.

The structural and thermodynamic behavior of the complex formation of eIF4E with either or both mRNA cap analogue (m7GTP, m7GpppA, or m7GpppG) and 4EBP1 has been investigated by spectroscopic measurements. Although the circular dichroism (CD) spectrum of eIF4E was little affected by the association with any cap analogue, the association constant of eIF4E with m7GpppA/G, estimated from the fluorescence quenching, was about 10 times larger than that with m7GTP. The van't Hoff analyses showed that the m7GpppA/G binding is enthalpy-driven with a large negative deltaH(o), and this is in contrast with the entropy-driven binding of m7GTP, where the positive deltaS(o) is large enough to overcome an increase of deltaH(o). This different behavior obviously originates in the interaction of the second nucleotide in m7GpppA with eIF4E, suggesting the importance of the nucleotide sequence linked to the m7Gppp terminal moiety, in addition to the specific interaction with the m7G base, for the recognition of mRNA cap structure by eIF4E. On the other hand, the CD spectra indicated that the binding of 4EBP1, an endogenous eIF4E-regulatory protein without having any defined secondary structure, shifted the m7GTP- or m7GpppA/G-bound eIF4E to an irregular structure, although such a structural change was not observed for eIF4E alone. The association constant of 4EBP1 with m7GTP- or m7GpppA/G-bound eIF4E was by two orders of magnitude larger than that with eIF4E alone. These results suggest the close interrelation in the supramolecular formation of 4EBP-eIF4E-mRNA cap structure.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Tumor cell recognition by lymphocytes: is the MHC always essential?

Phenotypic and functional analyses of tumor-infiltrating lymphocytes (TILs) used in clinical trials revealed that cells other than CTLs can have antitumor efficacy. This observation led us to search for mechanisms for tumor recognition by lymphocytes that utilize alternatives to surface structures of tumor cells, for example, MHC antigen complexes; the latter are generally believed to be the immunogenic platforms for CTLs. Therefore, as a possible source of immunostimulatory activity, we compared the ability of plasma membrane components of tumor cell lines with first secreted tumor cell components and then intracellular tumor components to act as mitogenic sources for human TIL lines. Surprisingly, the latter was found to be most potent, particularly Oncoimmunin-L, which is a 45-kDa protein with sequence similarity to members of the serpin family of proteins. This protein, which has at least a 31% sequence identity to human leukocyte elastase inhibitor and stimulates [3H]-thymidine incorporation into the DNA of human TILs, may be found in the cytosol of many tumor cells. Taken together with our earlier work in which a 36-kDa protein, also of tumor cytosolic origin, was shown to induce differentiation of myeloid cells, we propose soluble factors derived from tumor cells as a pathophysiological source of tumor immunogenicity. Moreover, detailed biochemical and biophysical characterization of tumor cell-immunocyte interactions will define the tumor immunoenvironment.

Forecasting↗
PubMed1989

Self recognition by T cells. I. Bystander killing of target cells bearing syngeneic MHC antigens.

Activated CTL can kill any cell to which they bind or by which they are bound. This observation has been used to determine whether alloreactive CTL can recognize cells bearing self-MHC. When activated by their specific targets, 19 CTL clones of 4 different specificities and origins killed bystander targets bearing syngeneic but not third-party MHC antigens. Using target cells derived from MHC-recombinant animals, syngeneic bystander killing was shown to be restricted to a single self MHC-encoded molecule. These results provide the first clear demonstration that T cells, or more precisely CTL, are capable of self recognition in the absence of their specific antigen. Our findings support the model that T cell repertoire selection occurs as a result of positive selection during maturation in the thymus of precursor cells whose antigen receptors have low but real affinity for self-MHC.

Animals↗
PubMed2005

Organization of Kenyon cells in subdivisions of the mushroom bodies of a lepidopteran insect.

The mushroom bodies are paired structures in the insect brain involved in complex functions such as memory formation, sensory integration, and context recognition. In many insects these centers are elaborate, sometimes comprising several hundred thousand neurons. The present account describes the mushroom bodies of Spodoptera littoralis, a moth extensively used for studies of olfactory processing and conditioning. The mushroom bodies of Spodoptera consist of only about 4,000 large-diameter Kenyon cells. However, these neurons are recognizably similar to morphological classes of Kenyon cells identified in honey bees, Drosophila, and cockroaches. The spodopteran mushroom body is equipped with three major divisions of its vertical and medial lobe, one of which, the gamma lobe, is supplied by clawed class II Kenyon cells as in other described taxa. Of special interest is the presence of a discrete tract (the Y tract) of axons leading from the calyx, separate from the pedunculus, that innervates lobelets above and beneath the medial lobe, close to the latter's origin from the pedunculus. This tract is comparable to tracts and resultant lobelets identified in cockroaches and termites. The article discusses possible functional roles of the spodopteran mushroom body against the background of olfactory behaviors described from this taxon and discusses the possible functional relevance of mushroom body structure, emphasizing similarities and dissimilarities with mushroom bodies of other species, in particular the fruit fly, Drosophila melanogaster.

Animals↗
PubMed1979

Is there a carcinoma in situ of gastric mucosa?

Carcinoma in situ, a precancerous lesion in the strict sense, was first recognized in stratified squamous epithelia. It is characterized by markedly atypical cells replacing the autochthonous epithelial cells without stromal invasion, the basement membrane being well preserved. Notwithstanding gradual transitions between carcinoma in situ on the one hand and dysplasias and invasive cancer on the other hand, its histological separation from the latter is feasible in the uterine portio. Its recognition has decisive therapeutic and prognostic implications, particularly in view of the frequently observed latent period between purely superficial spread and early invasive growth. In contrast difficulties are encountered in applying the concept of Carcinoma in situ to mucosal lesions of the stomach, though an analogous replacement stage has to be postulated, because the gastric and cervical mucous membranes differ fundamentally in their structural characteristics. The epithelial cells of the surface, pits and tubular glands do exhibit progressive atypia during cancerization. However, the single-layered epithelium offers far less distinctive criteria than the stratified squamous epithelium. Newly formed glandular complexes cannot be accepted as evidence for in situ growth. The latent period between purely superficial replacement by atypical cells and invasion appears to be considerably shorter in the stomach than in the portio, probably because the mechanical resistance of the loosely textured gastric lamina propria is small. In addition, stromal invasion may originate from any one epithelial cell in the gastric mucosa, whilst it is just the basal layer from which invasively growing cells may emanate in the uterine portio. The occurrence of dysplasia in the mucosa of the stomach does not justify a gastrectomy, according to our current experience, there being no intervention in gastric surgery equivalent to that of conization.

Carcinoma in Situ↗
PubMed2000

Stakeholder analysis: a review.

The growing popularity of stakeholder analysis reflects an increasing recognition of how the characteristics of stakeholders--individuals, groups and organizations--influence decision-making processes. This paper reviews the origins and uses of stakeholder analysis, as described in the policy, health care management and development literature. Its roots are in the political and policy sciences, and in management theory where it has evolved into a systematic tool with clearly defined steps and applications for scanning the current and future organizational environment. Stakeholder analysis can be used to generate knowledge about the relevant actors so as to understand their behaviour, intentions, interrelations, agendas, interests, and the influence or resources they have brought--or could bring--to bear on decision-making processes. This information can then be used to develop strategies for managing these stakeholders, to facilitate the implementation of specific decisions or organizational objectives, or to understand the policy context and assess the feasibility of future policy directions. Policy development is a complex process which frequently takes place in an unstable and rapidly changing context, subject to unpredictable internal and external factors. As a cross-sectional view of an evolving picture, the utility of stakeholder analysis for predicting and managing the future is time-limited and it should be complemented by other policy analysis approaches.

Decision Making, Organizational↗
PubMed1996

The characterological basis of multiple personality.

This review has focused on the characterological features of dissociative identity disorder (DID), extending the "state versus trait" debate to the realm of the dissociative disorders. A number of different theories are presented describing DID as a variant of, on a continuum with, or being comorbid with the narcissistic and the borderline personality disorders. It is then hypothesized that DID is best considered a distinct characterological entity. Two theories are put forth, which describe a personality disorder whose predominant defense is dissociation. The more developed model which possibly has more explanatory value is the "dissociative character." In this schema, DID would be considered a lower-level dissociative character, utilizing primitive forms of dissociation in which splitting is enhanced by an autohypnotic defensive altered state of consciousness. These altered states originate in response to the overstimulation of external trauma, but get reactivated in the service of here-and-now intrapsychic conflicts. Recognition of this dual quality of dissociation seems helpful in psychodynamic treatment, which allows for analysis of the defense and analysis of the content of these states. The nature of the content of what is "in dissociation" appears to have a dreamlike quality to it that may correspond to previous trauma but also be subject to some secondary revision. There is clinical evidence to suggest that "dream work" of the ego is operative in both the representation of a separate self in dreams and in alter personalities. Another organizing influence which contributes to seemingly separate identities is that of perverse sexuality. It appears that a number of dissociated sexual pathways may be followed in the same individual, which encapsulate aggression, childhood trauma, anxiety, and a sense of self. When this exceedingly complex psychic structure is successful, it may then free up some ego to proceed with aspects of healthy development.

Borderline Personality Disorder↗
PubMed1997

A crystallographic comparison between mutated glyceraldehyde-3-phosphate dehydrogenases from Bacillus stearothermophilus complexed with either NAD+ or NADP+.

Mutations have been introduced in the cytosolic glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Bacillus stearothermophilus in order to convert its cofactor selectivity from a specificity towards NAD into a preference for NADP. In the B-S mutant, five mutations (L33T, T34G, D35G, L187A, P188S) were selected on the basis of a sequence alignment with NADP-dependent chloroplastic GAPDHs. In the D32G-S mutant, two of the five mutations mentioned above (L187A, P188S) have been used in combination with another one designed from electrostatic considerations (D32G). Both mutants exhibit a dual-cofactor selectivity at the advantage of either NAD (B-S) or NADP (D32G-S). In order to analyse the cofactor-binding site plasticity at the molecular level, crystal structures of these mutants have been solved, when complexed with either NAD+ (D32G-Sn, resolution 2.5 A, R = 13.9%; B-Sn, 2.45 A, 19.3%) or NADP+ (D32G-Sp, 2.2 A, 19.2%; B-Sp, 2.5 A, 14.4%). The four refined models are very similar to that of the wild-type GAPDH and as expected resemble more closely the holo form than the apo form. In the B-S mutant, the wild-type low affinity for NADP+ seems to be essentially retained because of repulsive electrostatic contacts between the extra 2'-phosphate and the unchanged carboxylate group of residue D32. Such an antideterminant effect is not well compensated by putative attractive interactions which had been expected to arise from the newly-introduced side-chains. In this mutant, recognition of NAD+ is slightly affected with respect to that known on the wild-type, because mutations only weakly destabilize hydrogen bonds and van der Waals contacts originally present in the natural enzyme. Thus, the B-S mutant does not mimic efficiently the chloroplastic GAPDHs, and long-range and/or second-layer effects, not easily predictable from visual inspection of three-dimensional structures, need to be taken into account for designing a true "chloroplastic-like" mutant of cytosolic GAPDH. In the case of the D32G-S mutant, the dissociation constants for NAD+ and NADP+ are practically reversed with respect to those of the wild-type. The strong alteration of the affinity for NAD+ obviously proceeds from the suppression of the two wild-type hydrogen bonds between the adenosine 2'- and 3'-hydroxyl positions and the D32 carboxylate group. As expected, the efficient recognition of NADP+ is partly promoted by the removal of intra-subunit electrostatic repulsion (D32G) and inter-subunit steric hindrance (L187A, P188S). Another interesting feature of the reshaped NADP+-binding site is provided by the local stabilization of the extra 2'-phosphate which forms a hydrogen bond with the side-chain hydroxyl group of the newly-introduced S188. When compared to the presently known natural NADP-binding clefts, this result clearly demonstrates that an absolute need for a salt-bridge involving the 2'-phosphate is not required to switch the cofactor selectivity from NAD to NADP. In fact, as it is the case in this mutant, only a moderately polar hydrogen bond can be sufficient to make the extra 2'-phosphate of NADP+ well recognized by a protein environment.

Binding Sites↗
PubMed1988

Characterization of a T-cell clone recognizing idiotypes as tumor-associated antigens.

Although heterogeneous T cells recognizing idiotypic determinants have been demonstrated to occur spontaneously in vitro or to be expanded by immunization with antigen or idiotype, their in vitro propagation and cloning was not successful. These previous studies have relied extensively on soluble immunoglobulin to induce proliferation of idiotype-specific T cells. This report describes a unique approach to obtain a stable T-cell clone specific for a monoclonal beta 2-6 fructosan binding myeloma ABPC48 (BALB/c origin), bearing well-defined A48 regulatory idiotopes. Following repeated immunizations with ABPC48 myeloma protein of C.B/R3 mice (H-2d, VHb, CHa), which differ only in the VH locus from BALB/c mice (H-2d, VHa CHa), several stable T-cell clones were obtained after stimulation in vitro with ABPC48 myeloma cells. The proliferation of a T-cell clone A48.B2 was observed with irradiated myeloma cells or hybridomas producing antibodies bearing A48 idiotype encoded by genes deriving from the VH 441-4 family. Proliferation of the clone did not occur with soluble ABPC48 myeloma protein or with Sepharose 4B-bound ABPC48 myeloma protein. Both anti-A48Id and anti-Iad monoclonal antibodies can specifically inhibit the proliferation of this clone when stimulated with ABPC48 myeloma cells. These results demonstrate recognition of idiotypes on B-cell tumours by T cells and implicate the role of class II major histocompatibility complex determinants in this cellular interaction.

Animals↗
PubMed1984

Description and distribution of the subtypes of chronic schizophrenia based on Leonhard's classification.

Prior to the introduction of neuroleptics a lack of interest in complex classifications of the chronic schizophrenias was due to the lack of effective treatment. With the recognition of neuroleptic response heterogeneity, and of the hazards of long-term neuroleptic administration, interest in subtype classification such as that of Leonhard has grown. A simplification of the Leonhard scheme is presented. The first distinction drawn is between systematic or process schizophrenia and nonsystematic or episodic schizophrenia. Both groups are further subdivided according to whether the symptomatology is dominated by cognitive, affective or motor features. In the case of the systemic schizophrenias, further subdivision of the 3 major types is made on the basis of both severity and specific symptom characteristics. If such a scheme were a natural or biologically-based classification, rather than merely an artificial subdivision of schizophrenia, one might expect that similar proportions of the different subtypes would be found in independently selected samples. Preliminary data composing subtype proportions in Leonhard's original group, a population reported by Astrup, and a recently obtained international sample are presented. Some significant correlations between the samples are observed, and despite methodological short comings, the similarities in the distribution of subtypes across time and across countries give some support to Leonhard's taxonomy.

Chronic Disease↗