Progression of cerebroventricular enlargement and the subtyping of schizophrenia.

Several anatomic abnormalities in the brains of schizophrenics have frequently been reported. However, it remains unresolved whether such neuropathology is fully expressed and static at the onset of psychosis or whether further deterioration evolves during the course of illness. To address this important question, we obtained serial volumetric magnetic resonance images (MRI) of the cerebral ventricles of 18 patients with schizophrenic symptoms. Repeated blind measurements of total ventricular volume (TVV) revealed < 2% error of the segmentation method. Over a 2-3 year period, the rate of ventricular expansion (RVE) was 2.2 +/- 1.6 cm3/year in the patients and 0.7 +/- 0.6 cm3/year in controls. The RVE in the patients was not normally distributed, but clustered into two groups: a group similar to controls (n = 10; RVE, 0.9 +/- 0.5 cm3/year) and a group with a significantly greater rate of expansion (n = 8; RVE, 3.9 +/- 0.7 cm3/year) (P < 0.001). These results suggest that there are at least two subpopulations within the schizophrenias: one with relatively static ventricles and another with progressively enlarging ventricles. At least two distinct etiologic processes may thus underlie the clinical presentation of schizophrenic symptoms. Factors which might influence ventricular expansion (neuroleptic compliance, alcohol and recreational drug abuse, and some clinical correlates) could not account for differences between groups.

Dermatomyositis: correlative MR imaging and P-31 MR spectroscopy for quantitative characterization of inflammatory disease.

Magnetic resonance (MR) imaging and phosphorus-31 MR spectroscopy were used to examine four patients with dermatomyositis and five control subjects. T2-weighted images of the thigh muscles of patients showed increased signal intensity, with focal and inhomogeneous involvement predominantly in the vastus lateralis and secondarily in the vastus intermedius and vastus medialis. T1 and T2 values of the vastus lateralis in patients were significantly higher than those of the control subjects. T1 values of the rectus femoris and biceps femoris with more generalized inflammation were moderately elevated but still significantly higher than those of the control subjects. P-31 MR spectra of the quadriceps muscles were obtained during rest, during exercise at two graded levels, and in recovery. Concentrations of adenosine triphosphate and phosphocreatine (PCr) in the diseased muscles were 30% below normal values, and the inorganic phosphate/PCr ratios were increased in the patients' muscles at rest and throughout exercise. The T1 and T2 values as well as the P-31 metabolite data correlated with symptoms and clinical assessment.

Mössbauer, EPR and NMR studies of the acid-induced reduction and changes in spin state of ferric bleomycin.

Iron-57 Mössbauer, electron paramagnetic resonance (EPR) and H-1 nuclear magnetic resonance (NMR) studies of iron-bleomycin complexes in the pH range from 1.0 to 6.0 are reported. Sequential protonation of the ligands produces a variety of high-spin and low-spin complexes of the metal. Of particular interest is the reversible equilibrium between Fe(III)- and oxygen-stable Fe(II)-bleomycin. Below pH 3.5 Fe(II) complexes form, with maximal reduction occurring at approximately pH 2. At still lower pH, Fe(III) complexes unassociated with bleomycin become dominant. The observed reduction in the absence of exogenous reducing agents suggests the possible involvement of intramolecular autoreduction in bleomycin-mediated DNA degradation.

Tissue contrast enhancement: image reconstruction algorithm and selection of TI in inversion recovery MRI.

It is clearly demonstrated that the proper application of the inversion recovery imaging pulse sequence is dependent on the method of image reconstruction and the selection of TI for optimum tissue contrast. There are two methods of 2DFT image reconstruction of IR sequence time-domain raw data. The first is a modulus-image reconstruction algorithm (contrast-obliterating option), and the second is a phase-correction routine for reconstructing "phase-sensitive" true IR-images. The second option generates proper "in-phase" images, retains proper scale of contrast, but can invert the algebraic sign of image-values under certain conditions. A series of "phase-sensitive" and "modulus" reconstructed brain images, obtained with conventional and optimized new IR pulse sequences, are shown to demonstrate these effects. They illustrate the considerable advantages gained, in practical clinical situations, if one generates "phase-sensitive" true IR-images from IR-sequence raw data at optimum TI for tissue contrast enhancement.

Loss of high-energy phosphate following hyperthermia demonstrated by in vivo 31P-nuclear magnetic resonance spectroscopy.

We have used in vivo 31P-nuclear magnetic resonance spectroscopy to study the changes in high-energy phosphates following hyperthermia. Immediately after heating, there is a fall in adenosine triphosphate and apparent intracellular pH and an increase in inorganic phosphate. Following sublethal heating (40 degrees for 15 min), these changes were partial, and they resolved over the subsequent 45 hr. With tumors given severe hyperthermia (47 degrees for 15 min), there was complete disappearance of adenosine triphosphate, with no recovery by 24 hr posttreatment. Qualitatively similar effects were seen after heating of normal leg muscle. The degree of fall of the adenosine triphosphate/inorganic phosphate concentration ratio was directly proportional to the heat dose and to thermal cell kill. 31P-Nuclear magnetic resonance spectroscopy may be useful in thermal dosimetry and treatment evaluation following hyperthermia.

Combined use of COSY and double quantum two-dimensional NMR spectroscopy for elucidation of spin systems in polymyxin B.

Two-dimensional single quantum correlation NMR spectroscopy (COSY) and two-dimensional double quantum NMR spectroscopy (2QT) are used to study spin systems in the 1H NMR spectrum of polymyxin B. Because of different frequency relationships, the two types of two-dimensional NMR experiments are found to be highly complementary. This is demonstrated by combined use of COSY and 2QT spectroscopy to obtain a complete analysis of the complicated spectral overlap which occurs in the 1H NMR spectrum of polymyxin B.

Studies on bleomycin-DNA and bleomycin-iron interactions.

The bleomycins, a group of antitumor antibiotics (Figure 1), cause the degradation of DNA by a process requiring iron(II) and dioxygen (1,2). DNA degradation appears to involve two steps: association of the drug with the nucleic acid and degradation of the DNA. As part of studies directed toward achieving an understanding of how the bleomycins degrade DNA, we have examined various properties of the drug using a variety of chemical and physico-chemical techniques, including NMR and Mössbauer spectroscopy. We have studied both the interaction of the antibiotic with its target (DNA) as well as its association with its metal ion cofactor. This work has been performed on the intact drug and its derivatives as well as on synthetic models of the parent drug. This paper reviews and updates the recent work from this laboratory on the bleomycins.

Conformational and spectral analysis of the polypeptide antibiotic N-methylleucine gramicidin S dihydrochloride by nuclear magnetic resonance.

The 220-MHz proton magnetic resonance spectrum of the cyclic decapeptide antibiotic, mono-N-methylleucine gramicidin S, is reported and all the resonances have been assigned to specific protons of the constituent amino acids. Three methods--temperature dependence and solvent mixture (methanol-trifluoroethanol and dimethyl sulfoxide-trifluoroethanol) dependence of peptide NH proton chemical shifts and proton deuteron exchange--habe been utilized to delineate peptide NH protons. The results of the above methods, coupled with the observed vicinal alpha-CH-NH coupling constants and chemical shifts, indicate that in trifluoroethanol the peptide NH PROTONS OF D-Phe4, D-Phe9, L-Orn2, and L-Val6 are exposed to the sovent, and those of L-Val1, L-Orn7, and L-Leu8 are solvent shielded and intramolecularly hydrogen bonded. In trifluoroethanol, dimethyl sulfoxide, and methanol, the decapeptide has no C2 symmetry, and there are only minor conformational differences in the different solvents. In the proposed conformation in trifluoroethanol, one-half of the decapeptide retained the hydrogen bonding pattern of gramicidin S, i.e. cyclo-(L-Val1 NH--O-C L-Leu8) (a beta turn) and cyclo-(L-Leu8 NH--O-C L-Val1). The second half of the molecule exhibits a different type of stable beta turn involving the ten-atom hydrogen-bonded ring, cyclo-(L-Orn7-NH--O-C D-PHE4).