Randomized clinical trial of Helicobacter pylori from dental plaque(Br J Surg 2001; 88: 200-5).
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Dental Plaque↗
Biomedical subjects
A Chaudhuri
Publications and source records attributed to A Chaudhuri.
Acute cervical hyperextension-hyperflexion injury may precipitate and/or exacerbate symptomatic multiple sclerosis.
We report here 39 cases in which definite multiple sclerosis (MS) was precipitated or exacerbated by specific hyperextension-hyperflexion cervical cord trauma. The worsening or onset of the symptomatic disease bore a striking temporal relationship to the focal injury. Our data suggests that central nervous system (CNS)-specific acute physical trauma such as cervical cord hyperextension-hyperflexion injury may aggravate latent clinical symptoms in MS. The deterioration of MS bore no direct relationship with the severity of neck injury. Possible pathogenic mechanisms of focal CNS-specific trauma aggravating the course of asymptomatic or benign MS are discussed. This may have implications in improving our understanding of the factors that may modify the clinical course of MS.
Adult↗
Immunization of transgenic mice for production of MoAbs directed at polymorphic blood group antigens.
BACKGROUND: Antibodies of human origin for blood typing are increasingly difficult to obtain, and, despite aggressive efforts, MoAbs with specificities to several blood group polymorphisms have eluded production. As an approach for the generation of MoAbs with defined specificities, the feasibility of immunizing mice that are transgenic for the target polymorphism, Fy(a)/Fy(b) of the Duffy blood group system, was tested with a source of the antithetical antigen. STUDY DESIGN AND METHODS: Nontransgenic mice were immunized with recombinant Fy(b), and transgenic mice expressing human Fy(b) were immunized with recombinant Fy(a). RESULTS: Immunization of the nontransgenic mice resulted in the production of MoAbs to the Duffy protein, but not to the Fy(a)/Fy(b) blood group polymorphism. However, immunization of the transgenic mice resulted in production of the first example of murine Fy(a) MoAb (MIMA-19). This antibody is being used to screen for Fy(a-) blood donors and has been evaluated by many laboratories in an international workshop. CONCLUSION: This approach provides an effective method for producing MoAbs with specificities to polymorphic epitopes. These MoAbs are needed in transfusion medicine to identify antigen-negative donors and to alleviate the critical shortage of blood bank typing reagents, which currently are available only from human-derived sources.
Animals↗
Multistability of overlapped face stimuli is dependent upon orientation.
Stimuli composed of two overlapped faces, one rotated 45 degrees clockwise and the other 45 degrees counterclockwise, produce perceptual rivalry whereby both faces cannot be simultaneously perceived. We obtained subjective and quantitative measures of this rivalry effect and examined if it persists with inverted stimuli. Our results show that upright stimuli are multistable, with alternations occurring from one face to the other within 2 s. Inverted stimuli were instead perceived as ambiguous in half of the trials, indicating weaker perceptual rivalry in that condition. We suggest that overlapped faces produce perceptual rivalry because each face is readily interpreted into a Gestalt, an effect that in turn is dependent upon orientation.
Adolescent↗
Neural activity profiles of the neocortex and superior colliculus after bimodal sensory stimulation.
Current efforts at functional mapping of multisensory neurons are hampered by the need for both cellular-level resolution and the separate visualization of activity by different sensory cues. We have used a recently developed technique that exploits the differential time course of zif268 mRNA versus protein induction in neurons after sensory stimulation. Adult male rats were visually and acoustically deprived and then exposed to one of the following stimulation sequences: (i) no sensory stimulation; (ii) 2 h visual stimulation followed by 30 min auditory stimulation; (iii) 2 h auditory stimulation followed 30 min of visual stimulation; and (iv) 2 h compound visual and auditory stimulation. The neocortex and superior colliculus (SC) were then processed for fluorescent immunocytochemistry and in situ hybridization for staining of Zif268 protein and mRNA products. We have found that activity patterns in primary visual and auditory cortices were in accord with the sequence of the compound stimulus. We also show that SC superficial layers contained a pool of exclusively unimodal neurons, similar to that of visual cortex. Activity patterns of deep SC layers contained multimodal neurons with varying degrees of visual and auditory convergence. The deep SC layers also showed that auditory processing was largely carried out by a small, bimodal group of neurons whereas visual processing was coordinated by both a large unimodal and a small bimodal pool of neurons.
Acoustic Stimulation↗
Multigenerational cortical inheritance of the Rax2 protein in orienting polarity and division in yeast.
Diploid yeast cells repeatedly polarize and bud from their poles, probably because of highly stable marks of unknown composition. Here, Rax2, a membrane protein, was shown to behave as such a mark. The Rax2 protein itself was inherited immutably at the cell cortex for multiple generations, and Rax2 was shown to have a half-life exceeding several generations. The persistent inheritance of cortical protein markers would provide a means to couple a cell's history to the future development of a precise morphogenetic form.
Cell Division↗
Identification of differentially expressed genes in the visual structures of brain using high-density cDNA grids.
The hybridization patterns of 18,371 high-density-grid-arrayed non-redundant complementary DNA (cDNA) clones were examined using three different sources of cDNA probes. The first set of probes was synthesized from mRNA isolated from visual brain areas MT and V4 of Vervet monkey. The second set of probes was derived from cDNA libraries constructed from two micro dissected sets of layers of the monkey Lateral Geniculate Nucleus layers within the visual pathway, namely the magnocellular and parvocellular layers. The third set of cDNA probes was synthesized from the subtracted fractions of the cDNAs enriched for either the magnocellular or the parvocellular layers of the Lateral Geniculate Nucleus. Software, linked directly to the Genbank database, was developed to aid in the rapid identification of both expressed and differentially expressed genes. Our results indicate that both the cDNA probes synthesized from mRNA and cDNA libraries can identify similar fractions of expressed genes. However, the subtracted cDNA probes improve the efficiency of detection for those genes that are expressed at much lower abundance. Analyses of these results for the differential expression patterns of these genes were validated by semi-quantitative PCR on the DNA derived from the whole tissue cDNA libraries. A list of some known genes that are statistically differentially expressed within the magnocellular layers of the LGN and area MT in the primate visual areas is derived.
Animals↗
Protease inhibitors stimulate hematopoiesis and decrease apoptosis and ICE expression in CD34(+) cells.
Highly active retroviral therapy has been associated with a decline in the frequency of cytopenia in patients with human immunodeficiency virus (HIV) infection. This may result from lower hematologic toxicity of newer antiviral drugs and their increased efficacy against HIV-1. Protease inhibitors, in addition to their effects on HIV replication, appear to affect various cellular functions. Recently, it was reported that ritonavir inhibited caspase-1 expression in normal CD4(+) cells. It was hypothesized that protease inhibitors may improve hematopoietic function owing to their direct effects on the bone marrow progenitor cells. When ritonavir was added to methylcellulose cultures of bone marrow cells from HIV-infected patients and normal controls, colony formation increased 2.4-fold (n = 5) in control cultures and 4-fold (n = 5) in cultures of cells from HIV-infected patients. In the presence of ritonavir, cultures of CD34(+) cells showed markedly decreased apoptosis in comparison with untreated cultures (45% decrease in apoptotic cell number; n = 6). A synthetic inhibitor of caspase 1 (Ac-Tyr-Val-Ala-Asp-aldehyde [single-letter amino acid codes]), which inhibits activation of several caspases including CPP32 and interleukin 1beta-converting enzyme (ICE or caspase 1), also decreased the rate of apoptosis and enhanced colony formation by progenitor cells derived from HIV-infected patients (3-fold; n = 5). In ritonavir-treated samples derived from HIV-infected individuals, the number of cells expressing ICE also decreased. In conclusion, HIV protease inhibitors may, by blocking the caspase-dependent apoptotic pathway, overcome inhibition of hematopoiesis seen in patients with HIV infection, an effect unrelated to their antiviral activity. (Blood. 2000;96:2735-2739)
Antiretroviral Therapy, Highly Active↗
Fatigue and basal ganglia.
Fatigue is a common symptom in neurology and occurs in the diseases of the central and peripheral nervous system. In order to understand the mechanism of fatigue, it is important to distinguish symptoms of peripheral neuromuscular fatigue from the symptoms of physical and mental fatigue characteristic of disorders like Parkinson's disease or multiple sclerosis. We have introduced and defined the concept of central fatigue for the latter disorders. We have further proposed, with supportive neuropathological data, that central fatigue may occur due to a failure in the integration of the limbic input and the motor functions within the basal ganglia affecting the striatal-thalamic-frontal cortical system.
Animals↗
Light-induced down-regulation of the rat class 1 dynein-associated protein robl/LC7-like gene in visual cortex.
Dynein and kinesin are the main microtubule-dependent motors that mediate intracellular movement in eukaryotic organisms. We have cloned a full-length cDNA encoding rat dynein light chain protein, robl/LC7-like (class 1), from visual cortex. We found that rat robl/LC7-like gene is highly expressed in neocortex and displays the unusual feature of being rapidly down-regulated by sensory stimulation. This effect was seen at both mRNA and protein levels in visual cortex, being detectable in as little as 45 min after the onset of visual stimulation. Down-regulation by sensory stimulation was also found within ocular dominance columns of area V1 in monocularly deprived monkeys. Our results suggest a high turnover rate of the robl/LC7-like protein and the presence of a repressor mechanism in neurons that is tightly coupled to synaptic stimulation.
Amino Acid Sequence↗
Lactose intolerance and neuromuscular symptoms.
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Causality↗
"Snap-shooting" the interface of AOT reverse micelles: use of chemical trapping
The first use of the phenyl cation trapping technique in "snap-shooting" the local molar concentrations of water and sulfosuccinate head-groups in the interfacial region of AOT-2,2,4-trimethylpentane-water reverse micelles has been accomplished. Our results demonstrate that the interfacial concentrations of the sulfosuccinate head-groups in AOT (0.1 M)-2,2,4-trimethylpentane-water reverse micelles are remarkably high (2.75-2.34 M) across the W0 (the molar ratio of water to surfactant) range 12 to 44. However, the interfacial concentrations of water in AOT- 2,2,4-trimethylpentane-water reverse micelles across the same range of solution compositions are significantly lower (27.9-32.0 M) than the molar concentration of bulk water (55.5 M). The present results provide new insight on the microenvironments of interfacially located enzymes such as lipases entrapped in AOT-2,2,4-trimethylpentane-water reverse micelles, the most extensively exploited reverse-micellar system in micellar biotechnology.
Journal Article↗
Pharmacologic doses of granulocyte colony-stimulating factor affect cytokine production by lymphocytes in vitro and in vivo.
Peripheral blood stem cell (PBSC) transplantation is successful in improving engraftment without increasing acute graft-versus-host disease (GVHD), despite much larger numbers of T cells in unmanipulated PBSCs than in bone marrow grafts. In mouse models and retrospective human studies, granulocyte colony-stimulating factor (G-CSF) therapy has been associated with less acute GVHD. We studied the effect of G-CSF on interferon (IFN)-gamma and IL-4 expression in CD4(+) lymphocytes. CD4(+) cells co-cultivated with G-CSF and stimulated with PHA or CD3 monoclonal antibodies showed significant decreases in IFN-gamma and increases in IL-4 expression (n = 13; P <. 01). G-CSF appeared to have a direct effect on CD4(+) cells independent of monocytes present in the culture because purified CD4(+) cells exposed to G-CSF, washed, and cocultivated with untreated monocytes demonstrated similar changes in IFN-gamma and IL-4 expression, whereas untreated CD4(+) cells cocultured with G-CSF-stimulated monocytes behaved as controls. We then studied peripheral blood mononuclear cells (PBMCs) from G-CSF-mobilized PBSC donors. When their PBMCs were cultured with PHA or CD3 monoclonal antibody, the percent of IFN-gamma-expressing cells decreased by a mean of 55% and 42%, respectively, whereas the percent of IL-4-containing cells increased by a mean of 39% and 58%, respectively, following G-CSF stimulation. Increased apoptosis of IFN-gamma-producing CD4(+) cells was not responsible for the shift in TH1/TH2 subsets. G-CSF-R mRNA was present in both CD4(+) and CD8(+) cells. These results suggest that G-CSF decreases IFN-gamma and increases IL-4 production in vitro and in vivo and likely modulates a balance between TH1 and TH2 cells, an effect that may be important in PBSC transplantation.
Antibodies, Monoclonal↗
The relationship of MS to physical trauma and psychological stress: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.
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Humans↗
Molecular linkage underlying microtubule orientation toward cortical sites in yeast.
Selective microtubule orientation toward spatially defined cortical sites is critical to polarized cellular processes as diverse as axon outgrowth and T cell cytotoxicity. In yeast, oriented cytoplasmic microtubules align the mitotic spindle between mother and bud. The cortical marker protein Kar9 localizes to the bud tip and is required for the orientation of microtubules toward this region. Here, we show that Kar9 directs microtubule orientation by acting through Bim1, a conserved microtubule-binding protein. Bim1 homolog EB1 was originally identified through its interaction with adenomatous polyposis coli (APC) tumor suppressor, raising the possibility that an APC-EB1 linkage orients microtubules in higher cells.
Adenomatous Polyposis Coli Protein↗
In vitro infection of megakaryocytes and their precursors by human cytomegalovirus.
Apart from congenital human cytomegalovirus (HCMV) infection, manifest HCMV disease occurs primarily in immunocompromised patients. In allogeneic bone marrow transplantation, HCMV is frequently associated with graft failure and cytopenias involving all hematopoietic lineages, but thrombocytopenia is the most commonly reported hematologic complication. The authors hypothesized that megakaryocytes (MK) may be a specific target for HCMV. Although the susceptibility of immature hematopoietic progenitors cells to HCMV has been established, a productive viral life cycle has only been linked to myelomonocytic maturation. The authors investigated whether HCMV can also infect MK and impair their function. They demonstrated that HCMV did not affect the thrombopoietin (TPO)-driven proliferation of CD34(+) cells until MK maturation occurred. MK challenged with HCMV showed a 50% more rapid loss of viability than mock-infected cells. MK and their early precursors were clearly shown to be susceptible to HCMV in vitro, as evidenced by the presence of HCMV in magnetic column-purified CD42(+) MK and 2-color fluorescent staining with antibodies directed against CD42a and HCMV pp65 antigen. These findings were confirmed by the infection of MK with a laboratory strain of HCMV containing the beta-galactosidase (beta-gal) gene. Using chromogenic beta-gal substrates, HCMV was detected during MK differentiation of infected CD34(+) cells and after infection of fully differentiated MK. Production of infectious virus was observed in cultures infected MK, suggesting that HCMV can complete its life cycle. These results demonstrate that MK are susceptible to HCMV infection and that direct infection of these cells in vivo may contribute to the thrombocytopenia observed in patients infected with HCMV. (Blood. 2000;95:487-493)
Antigens, CD↗
Developmental profiles of SMI-32 immunoreactivity in monkey striate cortex.
A monoclonal antibody that recognizes a nonphosphorylated epitope on the medium and high molecular weight subunits of neurofilament (NF) proteins was used to investigate laminar and cell morphology changes in monkey striate cortex during post-natal development. Six cortices were obtained from monkeys of a variety of ages: five from developing animals with ages spanning the critical period and one adult. At post-natal day (PD) 0, immunohistochemistry with the SMI-32 antibody revealed immunoreactive (IR) cells in layer IVB and in infragranular layer VI. Early in the critical period (PD 7), these layers become more defined with an increase in the density of immunopositive cells. At the height of the critical period (PD 30 and 42), a drastic increase in the density of SMI-32 labelled pyramidal neurons in layers V and VI was observed. Similarly, layer IVC showed an abundance of dendritic fragments and dendrites that appeared to originate from the infragranular layers. At the end of the critical period (PD 103), a trend toward morphological maturation for individual neurons found within each layer was observed. During any developmental time point, neurons at first appearance tended to show an immature morphology with staining largely restricted to the cell bodies. As such, the characteristic arborizations common to mature pyramidal and multipolar cells was not evident. We propose that the staining pattern seen in this study is consistent with the idea that layers anatomically associated with the magnocellular (M) pathway develop earlier than their parvocellular (P) counterparts.
Aging↗
High-level, stable expression of blood group antigens in a heterologous system.
The detection and identification of blood group antibodies in patients is crucial for successful allogeneic blood transfusions. Current methods are highly subjective and rely on red blood cells (RBCs), which simultaneously express many blood group antigens, have a short shelf-life, and carry potential biohazard risks. To overcome these problems, we have used the approach of expressing individual blood group antigen-bearing proteins in a heterologous system. We report here the high-level surface expression of type I (Knops), type II (Kell), and type III/multi-pass (Duffy) membrane proteins that carry blood group antigens in mouse erythroleukaemic (MEL) cells using a vector containing the beta-globin locus control region. Importantly, the antigens expressed were detected specifically by a panel of patients' sera containing alloantibodies at sensitivities that are comparable to antigen-positive RBCs. Furthermore, in contrast to other mammalian expression systems, antigen expression was stable following freezing and thawing of the cell lines. Thus, this system has the potential both to replace the current use of RBCs by providing a one step method to detect and identify blood group antibodies and to allow the automation of antibody identification for the clinical laboratory.
Animals↗