Optimizing the efficiency of high-field multivoxel spectroscopic imaging by multiplexing in space and time.

A new strategy to yield information from the maximum number of voxels, each at the optimum signal-to-noise ratio (SNR) per unit time, in MR spectroscopic imaging (MRSI) is introduced. In the past, maximum acquisition duty-cycle was obtained by multiplexing in time several single slices each repetition time (TR), while optimal SNR was achieved by encoding the entire volume of interest (VOI) each TR. We show that optimal SNR and acquisition efficiency can both be achieved simultaneously by multiplexing in space and time several slabs of several slices, each. Since coverage of common VOIs in 3D proton MRSI in the human brain typically requires eight or more slices, at 3 T or higher magnetic fields, two or more slabs can fit into the optimum TR (approximately 1.6 s). Since typically four or less slices would then fit into each slab, Hadamard encoding is favored in that direction for slice profile reasons. It is demonstrated that per fixed examination length, the new method gives, at 3 T, twice as many voxels, each of the same SNR and size, compared with current 3D chemical shift imaging techniques. It is shown that this gain will increase for more extensive spatial coverage or higher fields.     

Diagnostic value of computer analysis of multipeaked EMG spikes.

Computer analysis of absolute number of peaks per second and the number of peaks in the multipeaked spikes/sec was carried out in the EMG interference recordings of 5 healthy, 6 myopathic and 8 neuropathic subjects. The purpose of the study was to detect diagnostically different patterns. A spike was considered multipeaked if it had 6 or more peaks. The amplitude of elimination (baseline) was examined at 1: 5, 1: 10 and 1: 15 of the average amplitude per second. Both the number of peaks and the number of peaks in multipeaked spikes in the neuropathic and myopathic muscles showed statistically significant differences when compared to healthy muscles. This technique could give an indication for the differential diagnosis of myopathic, neuropathic or healthy state of the muscle.     

In vivo phosphorus polarization transfer and decoupling from protons in three-dimensional localized nuclear magnetic resonance spectroscopy of human brain

Refocused insensitive nucleus enhancement by polarization transfer (RINEPT) from protons (¹H) to a J-coupled phosphorus (³¹P) has been incorporated into three-dimensional (3D) chemical-shift-imaging (CSI) sequence on a clinical imager. The technique is demonstrated on a phantom and in in vivo human brain. The polarization-transfer efficiency (～1.2) is lower than the theoretical maximum of γ¹H/γ³¹P≈ 2.4 resulting from ¹H-¹H homonuclear J couplings of similar magnitude competing with the ¹H →³¹P transfer. Nevertheless, compared with direct ³¹P Ernst-angle excitation, signal gains of up to × 1.8 were obtained mainly as a result of T¹ differences between ³¹P and the ¹H. Spectral interpretation is simplified by editing out all non-proton-coupled ³¹P signals. The duration, ～50 min, and power deposition, ～1 W · kg^?1, make the application suitable for human studies.     

Is there any relationship between human leucocyte antigen class II and chronic urticaria? (chronic urticaria and HLA class II)

The Human Leukocyte Antigen (HLA) typing of large groups of patients with various autoimmune diseases has demonstrated that some HLA alleles occur at higher frequencies in specific diseases than in the general population. Chronic urticaria has been shown to have an autoimmune basis by a previous study which found an association between chronic urticaria and specific HLA groups. We investigated the HLA subtypes of Turkish chronic urticaria patients. For this purpose 42 Turkish patients with chronic urticaria and 115 healthy controls were typed for HLA-DR and DQ by PCR-SSP (Polymerase Chain Reaction Sequence Specific Primers) low resolution DNA technique. We found an increased frequency of DR4 (42.9%, p=0.01) in chronic urticaria patients in comparison with that in healthy controls. This study supports the hypothesis that HLA alleles may be involved in the pathogenesis of chronic urticaria and that they appear to be directly involved in the initiation of the immune response.     

Switching yeast from meiosis to mitosis: double-strand break repair, recombination and synaptonemal complex

Background:

When Saccharomyces cerevisiae cells that have begun meiosis are transferred to mitotic growth conditions (‘return-to-growth’, RTG), they can complete recombination at high meiotic frequencies, but undergo mitotic cell division and remain diploid. It was not known how meiotic recombination intermediates are repaired following RTG. Using molecular and cytological methods, we investigated whether the usual meiotic apparatus could repair meiotically induced DSBs during RTG, or whether other mechanisms are invoked when the developmental context changes.

Results:

Upon RTG, the rapid disappearance of meiotic features—double-strand breaks in DNA (DSBs), synaptonemal complex (SC), and SC related structures—was striking. In wild-type diploids, the repair of meiotic DSBs during RTG was quick and efficient, resulting in homologous recombination. Kinetic analysis of double-strand breakage and recombination indicated that meiotic DSB formation precedes the commitment to meiotic levels of recombination. DSBs were repaired in RTG in dmc1, but not rad51 mutants, hence repair did not occur by the usual meiotic mechanism which requires the Dmc1 gene product. In haploids, DSBs were also repaired quickly and efficiently upon RTG, showing that DSB repair did not require the presence of a homologous chromosome. In all strains examined, SC and related structures were not required for DSB repair or recombination following RTG.

Conclusions:

At least two pathways of DSB repair, which differ from the primary meiotic pathway(s), can occur during RTG: One involving interhomologue recombination, and another involving sister-chromatid exchange. DSB formation precedes commitment to recombination. SC elements appear to prevent sister chromatid exchange in meiosis.

     

The antiatherogenic effect of allicin: possible mode of action.

OBJECTIVE: Garlic (Allium sativum) has been suggested to affect several cardiovascular risk factors. Its antiatherosclerotic properties are mainly attributed to allicin that is produced upon crushing of the garlic clove. Most previous studies used various garlic preparations in which allicin levels were not well defined. In the present study, we evaluated the effects of pure allicin on atherogenesis in experimental mouse models. METHODS AND RESULTS: Daily dietary supplement of allicin, 9 mg/kg body weight, reduced the atherosclerotic plaque area by 68.9 and 56.8% in apolipoprotein E-deficient and low-density lipoprotein (LDL) receptor knockout mice, respectively, as compared with control mice. LDL isolated from allicin-treated groups was more resistant to CuSO(4)-induced oxidation ex vivo than LDL isolated from control mice. Incubation of mouse plasma with (3)H-labeled allicin showed binding of allicin to lipoproteins. By using electron spin resonance, we demonstrated reduced Cu(2+) binding to LDL following allicin treatment. LDL treatment with allicin significantly inhibited both native LDL and oxidized LDL degradation by isolated mouse macrophages. CONCLUSIONS: By using a pure allicin preparation, we were able to show that allicin may affect atherosclerosis not only by acting as an antioxidant, but also by other mechanisms, such as lipoprotein modification and inhibition of LDL uptake and degradation by macrophages.     

Growth hormone co-treatment for ovulation induction may enhance conception in the co-treatment and succeeding cycles, in clonidine negative but not clonidine positive patients

To investigate the effect of co-treatment with growth hormone(GH) for ovulation induction with human menopausal gonadotrophins(HMG) on conception, we compared the pregnancy rate and responseto co-treatment with GH versus HMG/human chorionic gonadotrophin(HCG) alone in a prospective, randomized, cross-over protocolof volation induction for either in-vivo or in-vitro fertilization(IVF). The main outcome measures were the amount of gonadotrophinused and conception. Co-treatment with GH was associated witha reduction of 30% in gonadotrophin requirement. In 24 clonidinenegative patients 14 pregnancies were achieved (58.3%) eitherin the GH/HMG/HCG cycle or in the succeeding one. GH co-treatmentdid not generate any pregnancy in eight clonidine positive patients.We conclude that growth hormone may increase the pregnancy ratewhen combined with HMG/HCG for ovulation induction, not onlyin the co-treatment cycle but also in the succeeding one. Thebeneficial, synergistic effect of GH co-treatment was detectedin clonidine negative but not in clonidine positive infertilepatients.     

Possibilities of interference with the immune system of tumor bearers by non-lymphoid Fc gamma RII expressing tumor cells.

The ectopic expression of Fc gamma RII by PyV transformed 3T3 cells derived from tumors of long latency has been established. It was suggested that this expression is one of several changes conferring upon the cells an increased capacity for survival. We found that in one case cells expressing a very high level of Fc gamma RII had also a very high metastatic phenotype as compared to FcR negative cells. Direct evidence that Fc gamma RIIbl functions as a progression factor was provided by transfection experiments. The transfected gene conferred an increased malignancy and invasive phenotype upon PyV or c-Ha-ras transformed cells. In the present study we tested the possibility that Fc gamma RII expressing tumor cells could interfere with the immune system. The following subjects were investigated: 1) The ability of Fc gamma R on the tumor cells to bind the ligand and/or release IBF. 2) The effect of a local accumulation of ligand and/or IBF (assumed to take place in situ in the tumor) on Fc gamma RII expressing T cells. It was found that both tumor-derived receptor positive and beta l transfected PyV transformed cells were capable of binding aggregated mouse IgG. The binding of bivalent ligand was followed by an increase in membrane Fc gamma RII expression. Also both types of cells were capable of releasing IBF. We then tested the possibility that a local accumulation of IgG within the tumor could effect Fc gamma R expressing T cells. It was found that aggregated mouse IgG (as well as IgGl) could stimulate the proliferation of the T cell hybridoma (T2D4) and other Fc gamma RII expressing T cells. We also found that the expression of beta Fc gamma RII specific mRNA peaked at the logarithmic phase of T2D4 cultures, in parallel with their maximal potential to release IBF. Several pathways for interference with the immune system are suggested.