Proton spin-lattice relaxation studies and elemental analysis of human lymph nodes afflicted with lymphoma.
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Biomedical subjects
Publications and source records attributed to S S Ranade.
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Pulsed nuclear magnetic resonance studies have been carried out on bone marrow of normal human subjects and patients with leukemia: chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). It was observed that the proton spin-lattice relaxation time (T1) value was discriminatory in the normal and leukemic cases with a statistical significance of (p less than 0.01). Ouabain treatment of cells did not show any perceptible change of T1 value when compared with the nontreated cells, indicating that the concomitant cation effluxes do not affect spin-lattice relaxation time. The water contents of normal, leukemic, and ouabain treated cells were in the range 60%-80%. Higher Fe levels were encountered in the normal than the leukemic samples, while levels of Zn, Cu, Mn, Co, and Ni were elevated in the leukemic samples compared with the normals. Despite the T1 differences observed, the multiparameter studies do not uniquely pinpoint factors responsible for the elevation of T1 in the malignant state.
Water proton spin-lattice relaxation times (T1) were measured in nuclear fractions from liver, kidney, and spleen tissues from normal and tumor-bearing animals (TBA) at two frequencies. At 9 MHz, the T1 values for TBA nuclear fractions are less than those for normal nuclear fractions, contrary to observations at the cellular level. Trace metal ion concentration and nucleic acid content estimated for these nuclear fractions suggest that the DNA-metal ion interaction might be responsible for the observed differences in the T1 of nuclear fractions at low frequencies.
The pulsed nuclear magnetic resonance technique was explored for its potential diagnostic value in human cancer. Measurements of proton spin-lattice relaxation times (T1) of cellular water protons of normal and malignant esophageal tissues showed elevated T1 values in the latter. In some cases, tissues which appeared normal on gross examination assumed as uninvolved tissues had T1 values higher than the other grossly uninvolved tissues and often closer to the T1 of the corresponding tumor tissue. A histopathological study of the assumed uninvolved areas also studied for the T1 values was therefore undertaken. A preliminary study demonstrated the presence of malignant cell groups or clusters in some of the uninvolved samples with higher T1 compared to the true uninvolved tissues, which had a normal histological picture and low T1 values. This observation has brought out the importance of histopathological studies in addition to relaxation studies to comprehend contributory factors to relaxation. Secondly, it lends support to the thesis of elevated T1 values being characteristics of the malignant state.
In this report we present an analysis by atomic absorption spectrometry of some of the transition metals Fe, Zn, Cu, Mn, Co, and Ni in tissues and nuclear fractions in an experimental tumour system.
Nuclear fractions isolated from normal liver tissues and an experimental tumor--mouse fibrosarcoma (MFS)--were studied by pulsed NMR. Findings were: (1) T1 values of nuclear fractions are higher than those of the tissues or origin. (2) T1 values of nuclear fractions isolated from liver of tumor-bearers are higher than T1 values of nuclear fractions of normal liver. (3) T1 values of nuclear fractions of MFS tumor are higher than nuclear fractions of liver of tumor-bearing mice. Comparison of T1 values of the nuclear fractions shows a hierarchy of T1 from liver to MFS.
The effect of U.V.-irradiation of template DNA has been studied in vitro in the E. coli RNA polymerase system with native and U.V.-treated lambda DNA. Lambda DNA is more susceptible to U.V. than is calf-thymus DNA, yet a residual activity is observed at a U.V. dose of 0-5+10(4) erg/mm2. From the kinetic analysis of the reaction and the incorporation of lambda 32P-labelled nucleoside triphosphates, it seems reasonable to conclude that U.V.-irradiation probably does not affect the DNA initiation sites, recognizable by RNA polymerase. The transcription products made with U.V.-irradiated lambda DNA are assymmetrical, and hybridized to the right half (R) and the left half (L) of lambda DNA with the ratio of R/L = 4/1, and they show a lower hybridizability than the transcripts with native lambda DNA. The initiation sites recognizable by RNA polymerase seem to be the same on both native and U.V.-irradiated lambda DNA though the transcription of U.V.-treated lambda DNA appears to terminate with rather short RNA chains.
Pulsed nuclear magnetic resonance (NMR) studies of human bone marrow reveal that the proton spin-lattice relaxation times (T1) of acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) are much greater than the T1 of normal bone marrow.
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With a view to ascertaining the possible role of water content of the cells in the reported elevated values for proton spin-lattice relaxation time (T1) in malignant tissues, measurements of percent water content as well as T1 were undertaken in 68 cases of normal and concerous tissues from diverse sites in human patients. T1 values for the uninvolved samples were found to lie in the range of 400-1000 msec while the corresponding range for the involved samples was from 450-1520 msec. Water content of both normal and uninvolved tissues mostly lay in the narrow range of 70-90%. Occasionally samples with large T1 values showed lower water content as well. Data obtained weakens the case for characterization of tumor cells on the basis of their water content alone.
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