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PubMed1999

Evolution of antigen binding receptors.

This review addresses issues related to the evolution of the complex multigene families of antigen binding receptors that function in adaptive immunity. Advances in molecular genetic technology now permit the study of immunoglobulin (Ig) and T cell receptor (TCR) genes in many species that are not commonly studied yet represent critical branch points in vertebrate phylogeny. Both Ig and TCR genes have been defined in most of the major lineages of jawed vertebrates, including the cartilaginous fishes, which represent the most phylogenetically divergent jawed vertebrate group relative to the mammals. Ig genes in cartilaginous fish are encoded by multiple individual loci that each contain rearranging segmental elements and constant regions. In some loci, segmental elements are joined in the germline, i.e. they do not undergo genetic rearrangement. Other major differences in Ig gene organization and the mechanisms of somatic diversification have occurred throughout vertebrate evolution. However, relating these changes to adaptive immune function in lower vertebrates is challenging. TCR genes exhibit greater sequence diversity in individual segmental elements than is found in Ig genes but have undergone fewer changes in gene organization, isotype diversity, and mechanisms of diversification. As of yet, homologous forms of antigen binding receptors have not been identified in jawless vertebrates; however, acquisition of large amounts of structural data for the antigen binding receptors that are found in a variety of jawed vertebrates has defined shared characteristics that provide unique insight into the distant origins of the rearranging gene systems and their relationships to both adaptive and innate recognition processes.

Amphibians↗
PubMed2000

Endogenous carriers and ligands in non-immunogenic site-specific drug delivery.

Targeted drug delivery has gained recognition in modern therapeutics and attempts are being made to explore the potentials and possibilities of cell biology related bioevents in the development of specific, programmed and target oriented systems. The components which have been recognized to be tools include receptors and ligands, where the receptors act as molecular targets or portals, and ligands, with receptor specificity and selectivity, are trafficked en route to the target site. Although ligands of exogenous or synthetic origin contribute to the selectivity component of carrier constructs, they may impose immunological manifestations of different magnitudes. The latter may entail a continual quest for bio-compatible, non-immunogenic and target orientated delivery. Endogenous serum, cellular and extracellular bio-ligands interact with the colloidal carrier constructs and influence their bio-fate. However, these endogenous bio-ligands can themselves serve as targeting modules either in their native form or engineered as carrier cargo. Bio-regulatory, nutrient and immune ligands are sensitive, specific and effective site directing handles which add to targeted drug delivery. The present review provides an exhaustive account of the identified bio-ligands, which are not only non-immunogenic in nature but also site-specific. The cell-related bioevents which are instrumental in negotiating the uptake of bio-ligands are discussed. Further, a brief account of ligand-receptor interactions and the set of biological events which ensures ligand-driven trafficking of the ligand-receptor complex to the cellular interior is also presented. Since ligand-receptor interaction is a critical pre-requisite for negotiating cellular uptake of endogenous ligands and anchored carrier cargo, an attempt has been made to identify differential expression of receptors and bio-ligands under normal and etiological conditions. Studies which judiciously utilized bio-ligands or their analogs in negotiating site-specific drug delivery have been reviewed and presented. Targeted delivery of bioactives using endogenous bio-ligands offers enormous options and opportunities through carrier construct engineering and could become a future reality in clinical practice.

Animals↗
PubMed1981

Cell surface appearance of unexpected host MHC determinants on thymocytes from radiation bone marrow chimeras.

The phenotypic appearance of cell surface antigens on murine thymocytes from long-term radiation bone marrow chimeras was analyzed using indirect immunofluorescence and flow microfluorometry. Cells maturing in the thymi of these mice were typed for MHC (Kk, I-Ak, H-2b, Kb, and Ib) and non-MHC (Lyt 1, Ly 9, and TL) determinants. All cells were of donor origin as determined by non-MHC (Ly) phenotype in P1 leads to P2, P1 X P2 leads to P1, and P1 leads to P2 radiation chimeras. In contrast, the MHC phenotypes of these thymocytes were markedly affected by the host environment. Specifically, H-2 and I-A determinants of both parental phenotypes were detected on thymocytes from P1 leads to P1 X P2 chimeras; I-A determinants of host phenotype were present, whereas I-A determinants of donor phenotype were reduced on thymocytes from P1 X P2 leads to P1 chimeras; and thymocytes from P1 leads to P2 chimeras possessed H-2 and I-A determinants of host phenotype but showed reduction of donor I-A phenotype determinants. The appearance of host cell surface H-2 and I-A determinants on thymocytes from chimeras closely parallels the functional recognition of MHC determinants by T cells from chimeric mice and thus may be significantly related to the development of the self-recognition repertoire by maturing T cells.

Animals↗
PubMed1988

Mental rotation: effects of dimensionality of objects and type of task.

The original studies of mental rotation estimated rates of imagining rotations that were much slower when two simultaneously portrayed three-dimensional shapes were to be compared (R. Shepard & J. Metzler) than when one two-dimensional shape was to be compared with a previously learned two-dimensional shape (Cooper and her associates). In a 2 X 2 design, we orthogonally varied dimensionality of objects and type of task. Both factors affected reaction times. Type of task was the primary determiner of estimated rate of mental rotation, which was about three times higher for the single-stimulus task. Dimensionality primarily affected an additive component of all reaction times, suggesting that more initial encoding is required for three-dimensional shapes. In the absence of a satisfactory way of controlling stimulus complexity, the results are at least consistent with the proposal that once three-dimensional objects have been encoded, their rotation can be imagined as rapidly as the rotation of two-dimensional shapes.

Attention↗
PubMed1988

T suppressor efferent circuit which affects contact sensitivity to picryl chloride: the late-acting, second nonspecific T suppressor factor bears I-A determinants which are responsible for the I-A genetic restriction in its interaction with its target cell.

The T suppressor efferent circuit in the picryl (TNP) system, which inhibits the passive transfer of contact sensitivity, involves at least two antigen-nonspecific factors. The second nonspecific T suppressor factor (ns-2) bears I-A determinants of both the alpha and the beta chain as shown by affinity chromatography on immobilized anti-I-A monoclonal antibodies. Sequential absorption shows that the determinants of the alpha and beta chain occur on the same molecular complex. No absorption was obtained with anti-I-E antibody. There are two genetic restrictions associated with ns-2--the first is in its release from the second T suppressor efferent cell (on exposure to antigen) and the second is in its inhibitory interaction with its target cell. Both are MHC restricted and matching in I-A (but not I-E, or I-J) is sufficient. The question was asked whether the I-A of the ns-2 was directly responsible for the I-A genetic restriction in its action. F1 TsF was made in (H-2k X H-2b)F1 mice by injecting picrylated parental cells intravenously and triggering the release of ns-2 with the corresponding picrylated parental cells. Both I-Ak- and I-Ab-positive ns-2 were produced and were separated by affinity chromatography on immobilized anti-I-A monoclonal antibody. The I-A phenotype of these separated ns-2 of F1 origin determines the genetic restriction in their action; i.e., I-Ak+ ns-2 only inhibits passive transfer by H-2k cells and I-Ab+ ns-2 only acts on H-2b cells. In contrast, the I-A haplotype of the picrylated cell used to induce the Ts cell which makes ns-2 is unimportant. It was concluded that the I-A on the ns-2, and not a possible recognition site for I-A, serves as a restriction element. This finding suggests that ns-2 may act directly on the I-A-restricted T cell which mediates contact sensitivity.

Animals↗
PubMed1993

Purification of the large mobilization protein of plasmid RSF1010 and characterization of its site-specific DNA-cleaving/DNA-joining activity.

A site-specific and strand-specific nick, introduced into the RSF1010 plasmid origin of transfer (oriT), initiates unidirectional DNA transfer during bacterial conjugation. We have previously reproduced this nicking at the duplex oriT in vitro using purified preparations of the three known RSF1010-mobilization proteins: MobA (78-kDa form of RSF1010 primase), MobB and MobC [Scherzinger, E., Lurz, R., Otto, S. & Dobrinski, B. (1992) Nucleic Acids Res. 20, 41-48]. In this study we report the purification of MobA to apparent homogeneity and demonstrate that this 78-kDa protein by itself is capable of creating the oriT-specific nick if the DNA is present in the single-stranded form. By studying the cleavage of sets of oligodeoxyribonucleotides varying successively by single nucleotides at the 5' or 3' end, the minimal substrate for cleavage has been defined. The results identify the MobA recognition sequence within the 11-residue oligonucleotide AAGTGCGC-CCT which is cleaved at the 3' side of the G at position 7. During the cleavage reaction, MobA becomes covalently linked to the 5'-phosphate end of each broken DNA molecule and retains its activity for the rejoining reaction. It can transfer the attached DNA to an incoming acceptor strand provided that the DNA molecule contains at its 3' end at least the seven nucleotides upstream of the nick site. The covalent MobA-DNA linkage has been determined by two-dimensional thin-layer electrophoresis to be a tyrosyl phosphate. Extensive digestion of the 32P-labeled MobA-oligonucleotide complex with lysine carboxypeptidase yielded a single DNA-bound peptide which was purified and sequenced. The resulting peptide sequence consists of amino acid residues at positions 22-30 in the MobA sequence and identifies Tyr24 as the residue linked to DNA in the covalent complex.

Amino Acid Sequence↗
PubMed1994

Hemispheric asymmetry in the maturation of the extrastriate checkerboard onset evoked potential.

Recently we have shown that the single positive deflection in the checkerboard onset evoked potential (EP) of young children of striate origin develops into a negative-positive complex. However, also an early positive peak becomes apparent in the checkerboard onset EP. To determine the origin and development of the activity underlying this early positive deflection we studied the checkerboard onset EPs in children of 9-16 years of age. It was found that for the children in this age group two different dipole sources are responsible for the activity underlying the pattern onset EP. One of the dipoles corresponds to the activity generated in the striate cortex, whereas a second dipole of extrastriate origin is responsible for the appearance of the early positive deflection. This extrastriate activity shows hemispheric asymmetry, i.e. the strength of the right hemispheric extrastriate source exceeds the strength of the left hemispheric source. These results are in accordance with histological studies of Conel (1939-1963) [The postnatal development of the human cerebral cortex (Vols 1-8). Cambridge, Mass.: Harvard Univ. Press] which show that the maturation of the extrastriate areas of the left hemisphere is delayed with respect to the right hemisphere.

Adolescent↗
PubMed1993

Evolutionary conservation of major histocompatibility complex-DR/peptide/T cell interactions in primates.

Many major histocompatibility complex (MHC) polymorphisms originate from ancient structures that predate speciation. As a consequence, members of the Mhc-DRB1*03 allelic lineage are not only present in humans but in chimpanzees and rhesus macaques as well. This emphasizes that Mhc-DRB1*03 members must have been present in a common ancestor of these primate species that lived about 30 million years ago. Due to the accumulation of genetic variation, however, alleles of the Mhc-DRB1*03 lineage exhibit species-unique sequences. To investigate the biological importance of such conservation and variation, we have studied both the binding and antigen presentation capacity of various trans-species Mhc-DRB1*03 lineage members. Here we show that p3-13 of the 65-kD heat-shock protein (hsp65) of Mycobacterium leprae and M. tuberculosis binds not only to HLA-DR17(3) but also to some chimpanzee and rhesus macaque class II-positive cells. Comparison of the corresponding human, chimpanzee, and rhesus macaque Mhc-DRB1*03 lineage members revealed the presence of uniquely shared amino acid residues, at positions 9-13 and 26-31, of the antigen-binding site that are critical for p3-13 binding. In addition it is shown that several nonhuman primate antigen-presenting cells that bind p3-13 can activate HLA-DR17-restricted T cells. Certain amino acid replacements, however, in Mhc-DRB1*03 lineage members did not influence peptide binding or T cell recognition. Therefore, these studies demonstrate that some polymorphic amino acid residues (motifs) within the antigen-binding site of MHC class II molecules that are crucial for peptide binding and recognition by the T cell receptor have been conserved for over 30 million years.

Amino Acid Sequence↗
PubMed1999

The dnaA gene region of Mycobacterium avium and the autonomous replication activities of its 5' and 3' flanking regions.

A 3.9 kb DNA fragment containing the dnaA gene region of Mycobacterium avium was cloned and its nucleotide sequence was determined. Nucleotide sequence analyses indicated that this region encodes three genes in the order rpmH (ribosomal protein L34), dnaA (the putative initiator protein) and dnaN (the beta subunit of DNA polymerase III). The intergenic regions between the rpmH-dnaA and dnaA-dnaN genes were found to contain several putative DnaA boxes, 9 nt long DnaA protein recognition sequences. A DNA fragment containing the 3' but not the 5' flanking region of the M. avium dnaA gene when cloned in Escherichia coli plasmids, which are otherwise non-replicative in mycobacteria, exhibited autonomous replication activity in M. avium but not in Mycobacterium bovis BCG and Mycobacterium smegmatis. The 5' flanking region of dnaA, on the other hand, exhibited autonomous replication activity in M. bovis BCG but not in M. avium and M. smegmatis. The implications of these results for the understanding of the M. avium oriC replication initiation process are discussed.

3' Untranslated Regions↗
PubMed1991

Self-nonself discrimination and repertoire selection of human T cells differentiated in an HLA-semiallogeneic environment following bone marrow transplantation for severe combined immunodeficiency.

We have analyzed allorecognition, HLA restriction and T cell receptor (TcR) diversity in an HLA-heterozygous (HLA-DRw6,7) severe combined immunodeficiency (SCID) patient whose T cell system had been repopulated by HLA-homozygous (HLA-DRw6) paternal T cells following T cell-depleted bone marrow transplantation (BMT). Donor origin of T cells and host origin of antigen-presenting cells (APC) in peripheral blood and BM is shown by HLA typing of separated cell populations and two-color immunofluorescence using an anti-HLA monoclonal antibody (mAb). Peripheral blood lymphocytes (PBL) from the chimeric patient proliferate normally against PHA, anti-TcR/CD3 mAb, pooled allogeneic PBL, and also against the recall antigen (Ag) tetanus toxoid and purified protein derivative of tuberculin (PPD) following immunization, suggesting recognition by donor (DRw6) T cells of Ag presented by host (DRw6,7) APC. PPD-specific cytotoxic T lymphocytes generated in vitro from patient PBL post-BMT display specific cytotoxicity against targets expressing DRw6 and DR7, but not against DR-mismatched targets, suggesting that HLA restriction of Ag recognition may occur through determinants expressed by the host and not by the donor. Donor T cells differentiated in the HLA-semiallogeneic host show specific proliferative and cytotoxic responses against HLA-mismatched stimulators, but not against stimulators taken from the host, expressing the host-specific HLA-haplotype, or expressing the host-specific HLA-DR7 antigens. Compared to T cells directly taken from the donor, differentiation of donor T cells in the host is associated with a significant decrease of T cells expressing TcR V beta 5 and V alpha 2 determinants, while no differences in the abundance of of TcR V beta 6, V beta 8 and V beta 12 subsets were noticed. We conclude that allorecognition, major histocompatibility complex (MHC) restriction and TcR diversity generation of human T cells can be modulated through differentiation in an MHC-different environment, as had been previously shown to be the case in murine model systems.

Antigen-Presenting Cells↗
PubMed1987

The cytochrome oxidase subunit I gene of Tetrahymena: a 57 amino acid NH2-terminal extension and a 108 amino acid insert.

The gene sequence for cytochrome oxidase subunit I (COI) in the ciliate Tetrahymena mitochondrial DNA has been determined and shown to be coded by the same strand as codes the genes (in order) for 14S rRNA, tRNA(trp), tRNA(glu), 21S rRNA, tRNA(leu) and tRNA(met). The predicted protein has 698 amino acids, including an NH2-terminal 57 amino acid extension and a 108 amino acid insert originally found in Paramecium COI. These extension and insert segments are not highly hydrophobic but are relatively rich in lysine, arginine and serine. In analogy with the presequence of nuclear-encoded mitochondrial proteins, they might function as a transmembrane signal. The remaining polypeptide segments show a hydrophobicity characteristic of membrane spanning proteins. TCOI shows a 64% amino acid identity with Paramecium COI but less than a 38% amino acid conservation with human COI. The Tetrahymena mitochondrial code is analogous with the mammalian mitochondrial code; but differs from the Tetrahymena nuclear genetic code; TGA is exclusively translated as tryptophan; ATA is used as an initiation codon probably for methionine, and TAA as a stop codon; the arginine codons (CGN) are not used. The use of the leucine codon TTA in TCOI is contradictory to the codon recognition pattern previously obtained from the isolated tRNA(leu) isoacceptors recognizing only the CUN codons, but consistent with the tRNA(leu) (anticodon UAA) gene encoded in the genome. The reason for this inconsistency has not been resolved.

Amino Acid Sequence↗
PubMed1978

Effect of neonatal deafferentation on synaptogenesis in the rat interpeduncular nucleus.

Changes in the normal synaptogenetic pattern of the interpeduncular nucleus (IPN) were induced by destruction of one or both habenular nuclei in neonatal rats. The S synapses, the principal habenulointerpeduncular (H-IPN) afferents, were reduced in number and delayed in time of appearance by unilateral lesions. They were eliminated by bilateral lesions. The crest synapses, also of habenular origin, appeared at ten days of age and were apparently normal in structure after unilateral lesions. However, this actually represented a change in connectivity, since normal crest synapses are of bilateral origin. Following bilateral habenular lesions abnormal crest synapses appeared at 28 days of age. These had normal postsynaptic structure, but presynaptically were formed by non-habenular axons, usually of two different types of each crest synapse. Lesions induced an early appearance of F synapses, at three days, instead of the normal time after six days of age. Apparently similar processes containing flattened vesicles formed somatic contacts only in lesioned animals beginning at 21 days of age. The axosomatic synapses which were only occassional in the adult appeared at the normal time in lesioned animals. At 28 days of age in both unilaterally and bilaterally lesioned animals there was an increase in the number of somatic synapses. This increase was due to an increase of the normal somatic endings plus the appearance of somatic synapses containing flattened vesicles. Both types of somatic contacts were found in similar numbers at subsequent ages up to three months. The changes in S synapses represent Wallerian degeneration. The formation of unilaterally derived crest synapses in unilaterally lesioned animals is interpreted as evidence for a specific recognition mechanism. A postsynaptic control mechanism is proposed to explain the formation of heterologous crest synapses, with the usual distinctive geometry but involving abnormal, non-habenular presynaptic elements four weeks following neonatal bilateral lesions. The increase in axosomatic synapses is unusual since the dendrites of IPN neurons were deafferented, not their somata. The factors leading to the changes in somatic synapses are discussed. The findings reveal new examples of the complexity of neuronal adaptation to CNS lesions in early life.

Afferent Pathways↗
PubMed2006

Subsampling models and anti-alias filters for 3-D automultiscopic displays.

A new type of three-dimensional (3-D) display recently introduced on the market holds great promise for the future of 3-D visualization, communication, and entertainment. This so-called automultiscopic display can deliver multiple views without glasses, thus allowing a limited "look-around" (correct motion-parallax). Central to this technology is the process of multiplexing several views into a single viewable image. This multiplexing is a complex process involving irregular subsampling of the original views. If not preceded by low-pass filtering, it results in aliasing that leads to texture as well as depth distortions. In order to eliminate this aliasing, we propose to model the multiplexing process with lattices, find their parameters and then design optimal anti-alias filters. To this effect, we use multidimensional sampling theory and basic optimization tools. We derive optimal anti-alias filters for a specific automultiscopic monitor using three models: the orthogonal lattice, the nonorthogonal lattice, and the union of shifted lattices. In the first case, the resulting separable low-pass filter offers significant aliasing reduction that is further improved by hexagonal-passband low-pass filter for the nonorthogonal lattice model. A more accurate model is obtained using union of shifted lattices, but due to the complex nature of repeated spectra, practical filters designed in this case offer no additional improvement. We also describe a practical method to design finite-precision, low-complexity filters that can be implemented using modern graphics cards.

Algorithms↗
PubMed2004

Differential substrate and inhibitor profiles for human MASP-1 and MASP-2.

The mannan-binding lectin (MBL)-associated serine proteases (MASPs) circulate in serum complexed with mannan-binding lectin, a recognition molecule of the complement system. MASP-2 cleaves the complement components C4 and C2 to form the C3 convertase C4b2a. A definitive natural substrate for MASP-1 has not yet been described. We investigated the substrate specifities of MASP-1 and MASP-2 using cleavage of fluorescent amide substrates by recombinant and serum-derived MASPs. Recombinant MASP-1 cleaved Phe-Gly-Arg-aminomethylcoumarin (AMC) most rapidly at a rate of 16.8 nmol min(-1) microg(-1) rMASP-1. Recombinant MASP-2 barely cleaved any of 14 substrates used. This provides means of measuring MASP-1 activity in the absence of a known natural substrate. An assay for MBL-bound MASP-1 was established using the substrate Val-Pro-Arg-AMC. Assay of MBL-bound MASP-2 was done by cleavage of a natural protein substrate, C4. The condition of the serum used for the assays is important; simulated aging showed decreased detectable MASP-1 and MASP-2 activity. The inhibitors Z-D-Phe-Pro-methoxy-propylboroglycinepinanediol ester (boroMpg), anti-thrombin III in the presence and absence of heparin, hirudin and C1 inhibitor were tested against the MASPs. C1 inhibitor inhibits both enzymes, but the protease-serpin complex is unusually unstable at alkaline pH. The thrombin inhibitor boroMpg inhibited MASP-1 but not MASP-2 while hirudin did not inhibit either protease. Anti-thrombin III alone was not inhibitory, but in the presence of heparin inhibited both MASP-1 and MASP-2. The ancient origin of MASP-1 and its thrombin-like activity suggests its involvement in a coagulation-based defense mechanism in the early evolution of innate immunity.

Enzyme Inhibitors↗
PubMed2003

Vascular evaluation and arterial reconstruction of the diabetic foot.

Findings of diminished or absent pulses, pallor on elevation, redness of the foot on lowering of the leg, sluggish refilling of the toe capillaries, and thickened nails or absence of toe hair are consistent with impaired arterial perfusion to the foot. When ischemia is recognized as contributing to pedal ulceration and infection in the diabetic foot, quantitation of its severity may be difficult. Standard clinical evaluation of trophic changes is limited in an infected foot with its accompanying swelling, edema, and erythema. A palpable pedal pulse does not preclude the possibility of the presence of limb-threatening ischemia. Additional non-invasive vascular studies should be undertaken for these patients. Management of the diabetic foot is often a complex clinical problem. However, the principles of care are simple, including correction of systemic factors, such as blood glucose control, cardiovascular risk factor management, and smoking, as well as local factor correction, such as debridement, pressure relief, infection control, and revascularization when indicated. When a patient presents with evidence of infection, adequate drainage and antibiotic therapy are mandatory. The next step should be performed to differentiate the more common neuropathic ulcerations from the truly ischemic ulceration. Symptoms of rest pain or claudication are not often helpful because many of these patients are asymptomatic as a result of the presence of their neuropathy and inactivity. If an infected foot requires debridement or open partial forefoot amputation, observing the wound on a daily base is also important. Once infection is eradicated, there should be prompt signs of healing, including the development of wound granulation within several days. If wounds are not showing signs of prompt healing, arteriography is necessary. Early aggressive drainage, debridement, and local foot amputations combined with liberal use of revascularization results in cumulative limb salvage of 74% at 5 years in high-risk groups. Others report that pedal bypass to the ischemic infected foot is effective and safe as long as infection adequately controlled. These studies strongly suggest that early recognition and aggressive surgical drainage of pedal sepsis followed by surgical revascularization is critical to achieving maximal limb salvage in the high-risk population. Patients who have diabetes present a unique challenge in lower extremity revascularization because of the distal origination of many bypasses, distal distribution of the occlusive disease, and the frequently calcified arterial wall. An aggressive multidisciplinary approach to foot disease associated with diabetes involving the primary care provider, medical specialists, interventional radiology, and podiatric, plastic, and vascular surgeons will provide optimal medical and surgical care. Peripheral vascular disease is highly treatable if intervention is instituted in a timely and collegial fashion.

Arteries↗
PubMed1988

Role of T-cell antigens in the cytolytic activities of large granular lymphocytes (LGLs) in patients with LGL lymphocytosis.

By analyzing surface antigens and cytolytic functions of proliferating large granular lymphocytes (LGLs), three types of T cell LGL lymphocytosis were delineated. The first, most commonly encountered type exhibited CD3+4-8+16+, WT31+ phenotype, low or undetectable non-major histocompatibility complex (MHC)-restricted cytotoxicity, and moderate to strong antibody-dependent cellular cytotoxicity (ADCC) and lectin-dependent cellular cytotoxicity (LDCC). Because these LGLs carried T cell antigen receptor (Ti) recognized by WT31 monoclonal antibody (MoAb), and treatment with anti-Ti, anti-CD3 MoAbs and phytohemagglutinin elicited non-MHC-restricted cytotoxicity, they may have developed from populations of in vivo primed cytotoxic T lymphocytes with unknown antigen specificity. The second, rare type of LGL lymphocytosis exhibited CD3+4-8-16+, WT31 phenotype, and strong non-MHC-restricted, ADCC and LDCC cytotoxicities. These cells were probably derived from the lymphocytes of the same phenotype found in small numbers in normal peripheral blood. Because anti-CD3 MoAb inhibited non-MHC-restricted cytotoxicity of the LGLs, a Ti not detected by WT31 MoAb, but putatively present seemed to serve as a specific receptor for target tumor cell recognition. The third type of LGL lymphocytosis showed CD3+4+8-16+, WT31+ phenotype, and lacked cytolytic activities and parallel tubular arrays. These LGLs probably evolved from cells with the same characteristics selectively located in the germinal centers of lymphoid tissues. Taken together, in patients with LGL lymphocytosis, T cell-associated antigens expressed on LGLs were shown to be involved in the regulation of LGL-mediated cytolytic activities. In addition, studies of surface antigens and the effects of MoAbs and lectins on cytolytic activities may be useful in clarifying the normal counterpart of LGLs from which leukemic or reactively proliferating LGLs originate.

Adult↗
PubMed1987

Histiocytosis X. Langerhans' cell histiocytosis.

Histiocytosis X is a complex and poorly understood entity. Nevertheless, it would appear as if certain themes are found recurrently throughout the literature dealing with this disease and a review of them serves as a useful summary. 1. Problems with Nomenclature. To name or categorize a disease based on end-organ pathology is generally not clinically useful, but this is what we have done with histiocytosis X. It has caused substantial confusion among physicians and patients alike concerning diagnosis, prognosis, and treatment. Further attempts at improving the nosology of this disease will not be useful unless those new names also reflect scientific advances in our understanding of etiology, pathogenesis, and therapy. 2. Identification of the Langerhans' Cell as the Consistent Pathognomonic Cell in the Lesions of Histiocytosis X. Although the Langerhans' cell was identified more than a century ago, it has only recently been recognized as the cell that proliferates in this disease. Nevertheless, several important questions remain regarding the relationship of the Langerhans' cell to histiocytosis. Foremost among these questions is whether the Langerhans' cell is a truly normal Langerhans' cell, responding appropriately to immune system signals, or if it is an abnormal variant, possibly even neoplastic. 3. Recognition that Immune System Dysfunction Is a Critical Part of Histiocytosis X. The immune system is the focus of most recent clinical research. Results of these studies are obviously important with regard to both the biology and management of this disease. 4. Histiocytosis X Is an Extremely Heterogeneous Clinical Disorder. As mentioned before, the term histiocytosis X was originally intended by Lichtenstein to describe a pathologic, and not clinical, entity. It is rare to find two patients with this disease who are exactly alike. To make matters even more confusing, the disease includes both infants with disseminated fatal disease as well as middle-aged adults with solitary bony lesions. 5. The Disease Requires Improved Therapy, but it Is a Difficult Setting in which to Perform Clinical Studies. Improved therapy is required in patients with this disease, especially those with the disseminated form. But it will be difficult to develop improved therapy until definitive answers are provided to some of the basic questions of etiology and pathogenesis. Unfortunately, these clinical studies are not readily available because of the rare occurrence of this disease and its extreme clinical heterogeneity.(ABSTRACT TRUNCATED AT 400 WORDS)

Bone Neoplasms↗
PubMed1996

Effects of temporal lobe epilepsy on spatial and figural aspects of memory for a complex geometric figure.

The preoperative delayed memory performance on the Rey-Osterrieth Complex Figure (Lezak, 1983) of 54 patients with complex partial seizures of temporal lobe origin was analyzed using 3 different indices. One index (composite) was derived using a common scoring method that included both spatial and figural aspects of memory in its score. The other two indices were derived emphasizing either spatial or figural aspects of memory for the elements of the figure separately. All 3 indices distinguished between individuals with right-sided (RTLE) and left-sided (LTLE) seizure onset. However, spatial memory was significantly lower than figural memory in individuals with RTLE as compared to those with LTLE. Both the spatial and figural memory indices were significantly lower in the presence of magnetic resonance imaging (MRI) evidence for hippocampal sclerosis in individuals with RTLE. Results suggest that while both the spatial and figural aspects of nonverbal memory are sensitive to right hippocampal dysfunction, figural memory may be less vulnerable to the effects of RTLE.

Adult↗