On the interpretation of proton NMR spectra from brain tumours in vivo and in vitro.

Localized proton NMR spectroscopy in vivo allows focal studies of cerebral metabolites in both man and laboratory animals from image-defined regions as small as 1 mL or 64 microL, respectively. Although brain tumours lead to remarkable spectral alterations relative to normal brain, a number of problems may compromise the interpretation of the results. Potential complications arise from the chosen experimental conditions (method, TE, size and location of volume of interest), from regional metabolic heterogeneity in and around tumours, from differences between human tumours and animal models, and from discrepancies between in vivo and in vitro findings. Strategies and pitfalls are illustrated with use of selected examples from primary brain tumours, a rat tumour model and perchloric acid extracts of resected specimens.     

Volume-selective water-suppressed proton spectra of human brain and muscle in vivo

Volume-selective water-suppressed proton spectra were recorded from live human brain and muscle at 1.5T by combining a stimulated echo acquisition mode pulse sequence for localization and two saturation pulses for water suppression (Frahm et al., SMRM Abstracts, 1987). Metabolite signals were observed in voxels of size 4-64 cm3. Signals from -CH3 and beta-CH2 of N-acetylaspartate, =N-CH3 and =N-CH2 of phosphocreatine/creatine, -N(CH3)3 of choline and inositol protons were visible in the brain spectra from normal subjects. Differences in metabolite levels were observed between gray and white matters of brain from their water-suppressed spectra. Peaks from =N-CH3 of phosphocreatine/creatine and -N(CH3)3 of choline and carnitine were present in normal muscle spectra along with several resonances from fatty acyl chains.     

Neutron spectra from deuteron and proton bombardment of thick lithium targets: potential for neutron therapy.

Neutron energy spectra and yields produced by the bombardment of thick lithium targets by deuterons and protons have been measured using the time-of-flight method. Measurements were made at angles up to 45 degrees for deuteron energies of 8, 12 and 15 MeV and a proton energy of 15 MeV. The average neutron energy of the (d, n) reactions is shown to vary approximately as 0.44Ed. The (p, n) reaction has En = 4.7 MeV. The tissue penetration of neutron therapy beams is dependent on their average neutron energy and thus the low average neutron energy for these reactions appears to preclude their use for practical neutron therapy at these incident particle energies.     

Drug resistance. An updated, user-friendly guide to genotype interpretation

Genotypic antiretroviral resistance testing (GART) has been shown to be of value in selecting antiretroviral therapy. Unfortunately, GART reports often are difficult to interpret and, at times, can be misleading. Published lists of "primary" resistance mutations often do not include the combinations of "secondary" mutations, which also limit the efficacy of antiretroviral agents. This article tries to rectify this situation by introducing a general approach to genotype interpretation and by providing more "user-friendly" tables of key single mutations and key mutation combinations.     

Editors and editing of anti-DNA receptors.

Receptor editing is a means by which immature bone marrow B cells can become self-tolerant. Rearrangements of heavy (H) and/or light (L) chain genes are induced by encounter with autoantigens to change the specificity from self to nonself. We have developed site-directed transgenic mice (sd-tg) whose transgenes code for the H chain of antibodies that bind DNA. B cells that express the transgenic H chain associate mainly with four of the 93 functional Vkappa genes of the mouse. Numerous aspartate residues that might inhibit DNA binding by the V(H) domain distinguish these L chain Vkappa sequences, but engaging these Vkappa editors often requires multiple rearrangements. Among the edited B cells is a subset of multispecific cells that express multiple receptors. One consequence of multispecificity is partial autoreactivity; these multispecific B cells may contribute to autoimmunity.     

Proton editing and imaging of lactate.

Highly specific NMR assays for the detection, quantitation and imaging of lactate in vivo are described. Applications in animals include tumor monitoring, the determination of hypoxic cell distribution and the demonstration of the efficacy of tumor-sensitizers. The methods (GE-DQCOSY and GE-HMQC) may be particularly useful in heteronuclear NMR in vivo.     

Design, development, and interpretation of HIV neutralization assays.

In developing therapeutic reagents for the control of HIV infection, it is necessary to screen candidate products in vitro for their ability to reduce or neutralize viral infection. Although the current literature describes numerous neutralization assays, no universally accepted standards have been adopted. In this article, we briefly review the available neutralization assays and describe in detail the methods we have selected in our laboratory for the screening and characterization of reagents with potential anti-HIV properties. After evaluating many different technical protocols and experimental procedures, we have found the syncytium inhibition and syncytial focus assays to be particularly useful and have found p24 gag antigen production to be an excellent objective measure of HIV infection under a variety of conditions. These assays proved reproducible and sensitive and are suitable for use in the majority of laboratories.     

Some observations on the interpretation of ESCA spectra of fluorine containing polymers and their relation to the degree of crystallinity,to the surface tension,and to the content of adsorbed gas

An analysis is presented of recently published data concerning the ESCA spectra of some fluorine containing polymers. The claim that the ESCA data may be directly related to degree of crystallinity and to surface tension and content of adsorbed gas is examined and shown to be incorrect.     

The use and interpretation of RAST to stinging insect venoms.

Quality controlled, standardized RAST systems for five stinging insect venoms are described. These systems were evaluated using 375 sera from insect reactive patients from six diverse geographic regions. Ninety-four percent of patients with recent histories of systemic allergic reactions to stings were positive to at least one venom while 4 percent of normal local reactors were positive. The cross reactions between honey bee and vespid venoms were studied by RAST inhibition. A quantitative method for interpretation of venom RAST is presented to account for cross-reactivities and the approach to diagnosis is discussed.     

Approaches to patient and family education with affective disorders.

This paper provides an overview of prevalence, types, effects and treatment for affective disorders, with particular emphasis on educational and psychoeducational interventions. It reviews several models of psychoeducation including the approaches used in various programs at the Psychiatric hospital in which the authors work. These approaches are based on the Psychoeducational Model of Family Treatment developed by Dr. Carol Anderson and colleagues. Outcome data from several studies are also presented evidencing the positive impact of these interventions on patients and families.     

Acid tolerance, proton permeabilities, and membrane ATPases of oral streptococci.

Differences in acid tolerance among representative oral streptococci were found to be related more closely to the dynamic permeabilities of the bacteria to protons than to differences in the sensitivities of cell membranes to gross damage caused by environmental acidification. For Streptococcus mutans GS-5, Streptococcus sanguis NCTC 10904, and Streptococcus salivarius ATCC 13419, gross membrane damage, indicated by the release of magnesium from whole cells, occurred at pH values below about 4 and was rapid and extensive at pH values of about 3 or less. A more aciduric, lactic acid bacterium, Lactobacillus casei ATCC 4646, was more resistant to environmental acidification, and gross membrane damage was evident only at pH values below 3. Assessments of the movements of protons into S. mutans cells after an acid pulse at various pH values indicated that permeability to protons was minimal at a pH value of about 5, at which the average half time for pH equilibration across the cell membrane was about 12 min. The corresponding values for the less aciduric organism S. sanguis were pH 7 and 8.2 min, and the values for the intermediate organism S. salivarius were pH 6 and 6.6 min. The ATPase inhibitor dicyclohexylcarbodiimide acted to increase markedly the permeability of each organism to protons, and this action indicated that permeability involved not only the passive inflow of protons but also active outflow through the proton-translocating membrane ATPase. Membranes were isolated from each of the bacteria, and pH profiles for ATPase activities indicated pH optima of about 7.5, 7.0, 6.0, and 5.0 for S. sanguis, S. salivarius, S. mutans, and L. casei, respectively. Thus, the pH profiles for the enzymes reflected the acid tolerances of the bacteria and the permeabilities of whole cells to protons.     

Approaches to the demonstration of congenital heart disease.

Advances in antenatal screening techniques have increased the interest in obtaining a detailed pathological correlation with the ultrasonographic findings obtained before death. As a consequence, inadequacies in traditional methods used by pathologists to display congenital malformations have been brought to light. We describe a simple technique of inflation and wax impregnation for the permanent proof of congenital heart defects that can be used in routine perinatal necropsies.