Biomedical subjects

M Mescher

Publications and source records attributed to M Mescher.

10 recordsLinked to original sources

PubMed2000

Intermolecular zero-quantum coherence imaging of the human brain.

The first intermolecular zero-quantum coherence (iZQC) MR images of the human brain at 4T are presented. To generate iZQC images, a modified echo-planar imaging pulse sequence was used which included an additional 45 degrees RF pulse and a correlation gradient. The observability and nonconventional contrast of human brain iZQC images at 4T is demonstrated. Axial images are presented for various pulse sequence parameters, and a zero-quantum relaxation map is obtained.

Brain↗

PubMed1998

Lactate turnover in rat glioma measured by in vivo nuclear magnetic resonance spectroscopy.

Elevated tissue lactate concentrations typically found in tumors can be measured by in vivo nuclear magnetic resonance (NMR) spectroscopy. In this study, lactate turnover in rat C6 glioma was determined from in vivo 1H NMR measurements of [3-13C]lactate buildup during steady-state hyperglycemia with [1-13C]glucose. With this tumor model, a narrow range of values was observed for the first-order rate constant that describes lactate efflux, k2 = 0.043 +/- 0.007 (n = 12) SD min-1. For individual animals, the standard error in k2 was small (< 18%), which indicated that the NMR data fit the kinetic model well. Lactate measurements before and after infusing [1-13C]glucose showed that the majority of the tumor lactate pool was metabolically active. Signals from 13C-labeled glutamate in tumors were at least 10-fold smaller than the [3-13C]lactate signal, whereas spectra of the contralateral hemispheres revealed the expected labeling of [4-13C]glutamate, as well as [2-13C] and [3-13C]glutamate, which indicates that label cycled through the tricarboxylic acid cycle in the brain tissue. Lack of significant 13C labeling of glutamate was consistent with low respiratory metabolism in this glioma. It is concluded that lactate in rat C6 glioma is actively turning over and that the kinetics of lactate efflux can be quantified noninvasively by 1H NMR detection of 13C label. This noninvasive NMR approach may offer a valuable tool to help evaluate tumor growth and metabolic responsiveness to therapies.

Animals↗

PubMed1998

MR imaging contrast enhancement based on intermolecular zero quantum coherences.

A new method for magnetic resonance imaging (MRI) based on the detection of relatively strong signal from intermolecular zero-quantum coherences (iZQCs) is reported. Such a signal would not be observable in the conventional framework of magnetic resonance; it originates in long-range dipolar couplings (10 micrometers to 1 millimeter) that are traditionally ignored. Unlike conventional MRI, where image contrast is based on variations in spin density and relaxation times (often with injected contrast agents), contrast with iZQC images comes from variations in the susceptibility over a distance dictated by gradient strength. Phantom and in vivo (rat brain) data confirm that iZQC images give contrast enhancement. This contrast might be useful in the detection of small tumors, in that susceptibility correlates with oxygen concentration and in functional MRI.

Animals↗

PubMed1998

Simultaneous in vivo spectral editing and water suppression.

Water suppression is typically performed in vivo by exciting the longitudinal magnetization in combination with dephasing, or by using frequency-selective coherence generation. MEGA, a frequency-selective refocusing technique, can be placed into any pulse sequence element designed to generate a Hahn spin-echo or stimulated echo, to dephase transverse water coherences with minimal spectral distortions. Water suppression performance was verified in vivo using stimulated echo acquisition mode (STEAM) localization, which provided water suppression comparable with that achieved with four selective pulses in 3,1-DRYSTEAM. The advantage of the proposed method was exploited for editing J-coupled resonances. Using a double-banded pulse that selectively inverts a J-coupling partner and simultaneously suppresses water, efficient metabolite editing was achieved in the point resolved spectroscopy (PRESS) and STEAM sequences in which MEGA was incorporated. To illustrate the efficiency of the method, the detection of gamma-aminobutyric acid (GABA) was demonstrated, with minimal contributions from macromolecules and overlying singlet peaks at 4 T. The estimated occipital GABA concentration was consistent with previous reports, suggesting that editing for GABA is efficient when based on MEGA at high field strengths.

Brain Chemistry↗

PubMed1998

Micromechanical devices for intravascular drug delivery.

Microfabrication technology, more commonly applied to the manufacture of integrated circuits, can be used to build devices useful for mechanical delivery of drugs and genes. Microprobes fabricated using silicon micromachining have been used to deliver DNA into cells as an alternative to bombardment and microinjection. This idea can be extended to intravascular stents with integrated microprobes capable of piercing compressed plaque and delivering anti-restenosis therapies into coronary arteries. Preliminary experiments using filleted rabbit arteries have demonstrated transection of the internal elastic lamina. New nonplanar microfabrication technologies are necessary for creating practical devices with cylindrical symmetry; a promising possibility is to use microfabricated structures of anodic metal oxides.

Animals↗

PubMed1983

Extensive polymorphism surrounding the murine Ia A beta chain gene.

A segment of the murine immune response-associated (Ia) antigen A beta chain mRNA has been cloned, and this cDNA clone has been used to examine the organization of the genes encoding these highly polymorphic cell surface proteins. To isolate this clone, pIA beta-1, we screened 5000 cDNA clones by a filter hybridization-selection assay using a rabbit heteroantiserum to identify the A beta chain produced in in vitro translation reactions. This clone corresponds to a segment of the mRNA encoding the beta chain of the murine I-A antigen. The 464 bp nucleotide sequence of the insert is consistent with a cDNA clone encoding the carboxyl end of the murine A beta chain. Comparison of this nucleotide sequence to a human Ia beta chain-derived cDNA clone suggests that the two clones could encode proteins that are about 90% homologous in this region. Southern blot analysis using pIA beta-1 as a probe to investigate the structure of the A beta chain gene in inbred strains of mice allows two conclusions. First, there is only one A beta chain gene homologous to this cDNA clone in each haploid mouse genome. Second, the restriction fragments encoding this gene are highly polymorphic. We postulate that the mechanism which generates polymorphic variation of the A beta chain may be involved in generating the restriction site polymorphism within or near the A beta chain gene.

Animals↗

PubMed1978

The induction of virus-specific cytotoxic T lymphocytes with solubilized viral and membrane proteins.

Reconstituted membranes were prepared from detergent solubilized P815 (H-2d) tumor cell membranes and solubilized Sendai virus protein. These reconstituted membranes stimulated a virus-specific H-2-restricted secondary CTL response. Stimulating activity was dependent upon the presence of both viral and P815 protein in the same membrane and was restricted to the H-2 specificity present in the reconstituted membrane. Liposomes prepared from solubilized Sendai virus proteins and partially purified H-2 alloantigen also had activity for CTL induction. The results demonstrate the feasibility of using detergent solubilized membrane proteins to study antigen recognition by virus-specific, H-2 restricted cytolytic T lymphocytes.

Animals↗

PubMed1978

The induction of secondary cytolytic T lymphocytes by solubilized membrane proteins.

Membrane-bound antigens responsible for induction of a secondary allogeneic murine cytolytic T-cell (CTL) response have been obtained in a soluble, biologically active form by deoxycholate solubilization of tumor cell plasma membranes. The active proteins are soluble by the criteria of both ultracentrifugation and gel filtration. The immunological specificity of the induced CTL and removal of the activity from solution by treatment with B6 anti-P815 (anti-H-2d) antiserum and Protein A-Sepharose demonstrate that the CTL-inducing activity is dependent upon solubilized major histocompatibility complex antigens.

Animals↗

PubMed1978

Induction of secondary cytotoxic T lymphocytes by purified HLA-A and HLA-B antigens reconstituted into phospholipid vesicles.

Mouse cytotoxic T lymphocytes were induced by culturing primed spleen cells with cells, membranes, or detergent-solubilized and dialyzed membranes from the human lymphoblastoid cell line JY. Cytotoxic T cells could also be induced by coculturing primed spleen cells with phospholipid vesicles containing purified HLA-A and -B antigens derived from JY cells. The induction of killer cells by all subcellular fractions demonstrated an optimal response as a function of the amount of material added and, in the case of HLA-containing liposomes, this optimum was dependent upon the density of the HLA molecules in the liposomes. In addition, the maximal level of cytotoxicity elicited was also dependent upon this density. Finally, the cytotoxic cells demonstrated specificity as judged by a lower level of lysis on an HLA-unrelated lymphoblastoid cell line than on the appropriate target, JY. These results suggest that major histocompatibility antigens alone are sufficient for the induction of a secondary cytotoxic T lymphocyte response. It is proposed that this system may be useful in defining possible sites on the HLA molecule recognized by cytolytic T lymphocytes.

Animals↗

PubMed1978

Inhibition of the induction of cytolytic T lymphocytes with alloantisera directed against H-2K and H-2D gene products.

Alloantisera directed at gene products of the H-2Kd or H-2Dd loci on the stimulator cell were shown to inhibit specifically the generation of cytolytic T lymphocytes to those antigens. Thus, masking the antigens of one H-2 locus on the stimulator cell inhibits the induction of CTL to products of that locus but does not inhibit the induction of CTL to antigens of another H-2 locus. Alloantisera inhibition of the induction of cytolytic T lymphocytes occurred with both normal and primed responder cells and also occurred when the stimulating antigens were on whole cells or purified plasma membrane. Absorption on the appropriate spleen cells removed the inhibitory capacity of these alloantisera.

Absorption↗