Biomedical subjects

B Kalman

Publications and source records attributed to B Kalman.

30 records · Page 2Linked to original sources

PubMed1995

Characteristics of the T lymphocytes involved in experimental allergic encephalomyelitis.

Both heterogeneity and restricted heterogeneity of the encephalitogenic myelin basic protein (MBP) peptide-specific T cell receptors (TCRs) were demonstrated in inbred animals depending on the strain-specific genetic characteristics, the stage of the disease, the compartment of the lymphocytes obtained and the methodology used. Nevertheless, the similar features of some MBP-specific TCRs demonstrated across species suggest that conservation of these autoantigen-specific molecules undoubtedly exists, even though the degree of this conservation is controversial. However, the unequivocal heterogeneity of the immune response directed at one of the most important myelin constituents, proteolipid lipoprotein (PLP), which occurs either as a primary or a secondary event during experimental allergic encephalomyelitis (EAE), indicates the complexity of the in vivo situation. Intramolecular and intermolecular spreading of antigen specificity during the course of the disease indicates that a TCR directed therapy may not be the choice of intervention in established disease even in individual strains of laboratory animals with restricted heterogeneity of the primary MBP-specific response. Studying the sequence of events, the recruited regulatory cells and cytokines, and the stromal factors controlling persistence or death of activated, memory cells in the tissue lesion, may reveal new therapeutic modalities with more universal applicabilities.

Animals↗

PubMed1995

Artificial neural networks for screening patients needing emergency cranial computed tomography scans in emergency departments.

RATIONALE AND OBJECTIVES: We evaluated the potential for a neural network to screen candidates for emergency cranial computed tomography (CT) scans in an emergency department setting. METHODS: Data were collected from 1625 patients undergoing emergency cranial CT scanning in two different emergency departments (EDs). Singular value decomposition (SVD) was used to remap input data for network training. Data were randomly divided into six subsets, and one was reserved as a test set to analyze network performance. Five networks were then trained on data from the five remaining sets using fivefold cross-validation. Each trained network was allowed an independent vote on need for CT scanning in each case from the test set. The majority vote was used as the final prediction. A similar analysis was done on data from each individual ED. Results are compared with prior statistical studies of the same data. RESULTS: The network performed well when predicting clinical variable patterns that consistently produced negative CT scans and on patterns that were ambiguous in terms of the CT scan results. It performed poorly, however, on patterns that consistently predicted positive scans. This last finding appears to have resulted from inadequate training material. The two populations from which data were taken were shown to be distinct, but a network trained on the combined data performed as well as the networks from the individual EDs in predicting patients requiring CT scanning. Variables with the greatest contribution to the networks' prediction were consistent with those in prior statistical studies. CONCLUSION: Although preliminary in nature, neural networks show promise as a screening device for selecting patients for emergent cranial CT scanning.

Analysis of Variance↗

PubMed1995

Mitochondrial DNA mutations in multiple sclerosis.

The presence of mitochondrial DNA mutations, including eight of those frequently associated with Leber's hereditary optic neuropathy (LHON), was investigated by sequencing and restriction endonuclease analysis in randomly selected patients with MS. Class I LHON mutations with primary pathogenic significance for blindness were not detected in any of the MS patients studied. A trend was observed for higher frequency of class II LHON mutations with unknown pathogenic significance in the MS patients than in the controls. Specifically, the mutation at position 4216 and its associated simultaneous mutations occurred with a higher frequency. Eleven of the 53 patients (20.8%) were positive for at least two (4216 and 4917 or 13,708) or three (4216, 13,708, 15,257) simultaneous class II LHON mutations, while 7 of the 74 controls (9.5%) carried simultaneous mutations (P = 0.036). Earlier studies reported the occurrence of either the 11,778 or 3460 LHON type mutations in MS patients with a positive LHON pedigree and/or with a disease course predominantly involving the optic nerves. The mutations we detected did not correlate with the severity of visual loss in either LHON or MS, rather they seemed to be present in randomly selected MS patients. We conclude that the mutations with primary pathogenic significance for blindness are not shared between LHON and randomly selected MS. However, the presence of further mitochondrial mutations cannot be excluded in MS. The increased incidence of the simultaneous class II LHON mutations in MS patients (and LHON) vs controls may indicate that certain sets of mitochrondrial DNA mutations/variants are associated with and predispose to MS, a possibility which needs to be investigated further. Alternatively, a biological disadvantage may be associated with the coexistence of the mutations detected.

DNA, Mitochondrial↗

PubMed1994

Preferential but not exclusive T cell receptor V beta chain utilization of myelin basic protein and peptide-specific T cell clones in mice.

The repertoire of T cell receptor (TCR) V beta chain utilization was investigated in PL/J, CXJ-1, SJL/J and B10.S-->SJL/J chimeric mice in response to either myelin basic protein (MBP) or the strain-specific encephalitogenic peptide. Our analysis showed that there was an overlapping predominance in the TCR V beta gene utilization in the MBP-specific responses, which were independent of the major histocompatibility complex (MHC) class II haplotype present, and the immunodominant peptide region recognized in these different strains. In those mice having the TCR V beta b haplotype (PL/J, CXJ-1, and the B10.S-->SJL chimera) either the TCR V beta 4, 8, and 13 or the TCR V beta 4, 6, and 13 predominated. In contrast, in mice with TCR V beta a haplotype (SJL/J) V beta 4, 6, and 17a were found. However, the quantitative distribution of these preferentially utilized TCR V beta chains in each strain was defined by the MHC class II haplotype and the immunodominant peptide recognized. The expression of the V beta 8 gene product in the peripheral TCR repertoire did not always correlate with predominant V beta 8 utilization in the MBP-specific response.

Amino Acid Sequence↗

PubMed1994

Diagnosis of focal bone lesions using neural networks.

RATIONALE AND OBJECTIVES: Use of a neural network to diagnose focal lesions of bone was evaluated. METHODS: Imaging features of 709 lesions were encoded into a predetermined database. Data were divided into four groups and were analyzed using cross-validation by a two-layer feed-forward neural network. RESULTS: The lesions comprised 43 different pathologic diagnoses. Overall, the network was 85% accurate in distinguishing benign from malignant lesions. With a differential list of five diagnoses, the list was internally consistent regarding benign and malignant lesions 81.9% of the time. The network correctly diagnosed 56% of the lesions by pathologic diagnosis as its first choice. It included the correct diagnosis 71.8% of the time in a differential list of three diagnoses and 87.3% of the time in a differential list of nine diagnoses. CONCLUSION: Although not yet adequate for clinical use, neural network diagnosis of bone lesions is in its infancy and has important implications for the future analysis of focal bone lesions.

Bone Neoplasms↗

PubMed1993

Phase equilibria and formation of vesicles of dioleoylphosphatidylcholine in glycerol/water mixtures.

The lipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) forms a lamellar liquid crystalline phase (L alpha) in arbitrary mixtures of glycerol and water. The phase has been characterized by means of X-ray diffraction, 31P-NMR spectroscopy and differential scanning calorimetry (DSC). In the L alpha state, and for DOPC concentrations greater than 50% (w/w), the thickness of the lipid bilayer decreases, while the area of the polar head group increases with increasing glycerol concentration. The phase transition from gel to L alpha state occurs in the range of 240 to 260 K. Contrary to a previous (McDaniel, R.V., McIntosh, T.J. and Simon, S.A. (1983) Biochim. Biophys. Acta 731, 97) study of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) we find that in the gel state, the thickness of the DOPC lipid bilayer is greater than that in the L alpha state. This suggests that in the gel state, the lipid acyl chains of DOPC are in extended configuration. The lamellar phase reaches its maximum swelling at about 50% (w/w) of DOPC. At lower DOPC concentrations a two-phase system is formed where the lamellar phase exists in equilibrium with excess of solvent. Unilamellar vesicles can be prepared from a diluted suspension of the lamellar phase either by using the sonicator or extruder technique. We show this by means of 31P-NMR, EPR and fluorescence spectroscopy. The mean radius of the vesicles, prepared by a sonicator, has been determined at different glycerol/water mixtures. It is found to decrease continuously from 100 A at 100% water to a minimum of 75 A at about 50% water in the solvent mixture. By further decreasing the water content in the solution, the radius rapidly increases, and a mean radius of 450 A is estimated at a water content of 10%. The rotational relaxation times of a fluorescent probe and two EPR spin probes, solubilized in DOPC vesicles, have been measured at different glycerol/water mixtures. It is found that the rotational rates are always much slower in the systems containing glycerol.

Calorimetry, Differential Scanning↗

PubMed1993

Two sisters with multiple sclerosis, lamellar ichthyosis, beta thalassaemia minor and a deficiency of factor VIII.

Two of four sisters have multiple sclerosis (MS), lamellar ichthyosis, beta thalassaemia minor and a quantitative deficit of factor VIII-von Willebrand complex. The mother and the other sisters have only beta thalassaemia minor. The association of MS and a cluster of genetically determined diseases is rare. Such families could offer a new approach to the investigation of the polygenetic background of MS.

Adult↗

PubMed1993

T cell receptor V beta gene utilization in myelin basic protein specific clones from CXJ1 recombinant inbred mice.

CXJ1 mice are a recombinant inbred strain generated from experimental allergic encephalomyelitis (EAE) resistant BALB/c and EAE susceptible SJL/J progenitors. CXJ1 derive their major histocompatibility complex (MHC) class II and TCR genes from the BALB/c progenitor. However, their susceptibility to EAE is similar to SJL/J. Utilizing myelin basic protein (MBP)-specific CD4+ hybridoma clones and a MBP-specific T cell line (TCL) from CXJ1, we found the predominant T cell receptor (TCR) V beta chain expression to be V beta 8 and V beta 13. Our data support the concept of preferential, but not exclusive, TCR V beta usage in the MBP-specific response which is independent of MHC class II haplotype or immunodominant peptide.

Amino Acid Sequence↗

PubMed1993

Effects of staphylococcal enterotoxin B on T cell receptor V beta utilization and clinical manifestations of experimental allergic encephalomyelitis.

Staphylococcal enterotoxin B (SEB) is a superantigen (SA) that up-regulates and then subsequently down-regulates and deletes T cells expressing V beta 8 T cell receptor (TcR) chains (Marrack and Kappler, 1990; Johnson et al., 1991). We have investigated the effect of SEB on experimental allergic encephalomyelitis (EAE) in PL/J mice, where the predominant encephalitogenic T cells are V beta 8+ (Acha Orbea et al., 1988; Zamvil et al., 1988). SEB did not enhance induction of EAE when administered prior to or after immunization for EAE. PL/J mice pretreated with SEB developed anergy and deletion of V beta 8 bearing cells and concomitant reduction in the incidence of EAE. Following SEB pretreatment, a redistribution in the TcR utilization of MBP-specific lymphocytes occurred. As a result, there was a low frequency of V beta 8 and expansion of other, normally less frequent, myelin basic protein (MBP)-specific clones. These observations indicate that systemic exposure to superantigen can influence organ-specific autoimmune diseases. We observed V beta-specific elimination, rather than activation, of autoimmune clones, a finding of potential therapeutic value. Modification of the TcR repertoire by systemic exposure to this SA indicates plasticity of immune reactivity and demonstrates a mechanism by which an environmental exposure (SEB) can influence a genetically determined, T cell mediated autoimmune disease.

Animals↗

PubMed1993

Monoclonal anti-gamma interferon antibodies enhance experimental allergic encephalomyelitis.

Interferon-gamma (IFN-gamma) is a cytokine with multiple activities on a variety of cells. Under various circumstances, IFN-gamma can exhibit either pro-inflammatory or inhibitory actions. Treatment of SJL/J mice with a monoclonal antibody (Mab) to IFN-gamma during the afferent limb of the immune response to myelin protein produced an enhancement of acute experimental allergic encephalomyelitis (EAE), with increased morbidity, mortality and earlier onset of disease. Systemic administration of IFN-gamma did not improve or worsen clinical outcome, but delayed disease onset. Passive transfer of immune lymph node cells co-activated with MBP and anti-IFN-gamma Mab resulted in more sever disease than that induced by MBP stimulated cells or MBP and IFN-gamma co-stimulated cells. However, in vitro proliferation of an MBP specific T cell line was not influenced by IFN-gamma nor anti-IFN-gamma treatment. Mab to IFN-gamma inhibited suppressor function, in a non-specific assay. These in vivo and in vitro results suggest that systemic IFN-gamma serves as a physiological regulator of a suppressor mechanism in EAE. The abrogation of this regulatory mechanism by anti-IFN-gamma administration contributes to a more severe form of experimental allergic encephalomyelitis.

Animals↗

PubMed1991

Electronic energy transfer and fluorescence quenching in the active sites of mercuric reductase.

The FAD-containing enzyme mercuric reductase has been studied by means of steady-state and time-resolved fluorescence spectroscopy. The fluorescence relaxation of the excited state of the isoalloxazine ring of FAD can be described by a sum of two exponential functions. The two lifetimes are not due to a different lifetime of each of the two FAD molecules of mercuric reductase. The FAD molecules are quenched dynamically by a quencher that is not sensitive to the solvent viscosity. In vitro activation induces a dynamic quenching of fluorescence, while upon binding of NADP+ the FAD molecules are both statically and dynamically quenched. Time-resolved fluorescence anisotropy experiments of mercuric reductase in water show that the isoalloxazine ring probably undergoes a rapid and restricted vibrational motion of small amplitude. Electronic energy transfer occurs between the two FAD molecules at a rate of about 3.4 x 10(7) s-1. The angle between the emission transition dipole of the donor and the absorption transition dipole of the acceptor is 137 +/- 2 degrees (or 43 +/- 2 degrees). From previous X-ray data of glutathione reductase we find that the corresponding angle is 160 degrees. This suggests that the isoalloxazine rings of mercuric reductase and glutathione reductase are mutually tilted in slightly different ways.

Binding Sites↗

PubMed1989

Estradiol potentiates poke-weed mitogen-induced B cell stimulation in multiple sclerosis and healthy subjects.

Female preponderance in many diseases suggested with autoimmune pathogenesis, multiple sclerosis (MS) being classified as one of them, indicates a role for hormonal factors such as estrogen in disease development. To bypass monthly hormonal fluctuations in females, we evaluated in male patients with MS and male blood donors the effect of 17-beta-estradiol on numbers of IgG, IgA and IgM producing cells in cultures of peripheral blood lymphocytes. While estradiol alone had no effect, estradiol in combination with poke-weed mitogen (PWM) yielded in both groups higher numbers of IgG and IgA producing cells when compared with numbers obtained by PWM stimulation alone, indicating an additory effect of estradiol to that of PWM on B cell maturation. This effect was less pronounced in MS than in blood donors, especially for IgG producing cells, probably reflecting higher B cell activation in vivo taking place in MS. On the contrary, cells producing IgG, IgA and IgM antibodies against myelin, myelin basic protein and measles virus were not detectable after stimulation with PWM, nor with PWM and estradiol. Estradiol can in many patients with MS and in blood donors be considered a potent co-activator of B cells in presence of B cell stimulating factor in the form of PWM.

Adult↗