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Biomedical subjects

T C Ng

Publications and source records attributed to T C Ng.

At least 37 records · Page 2Linked to original sources

Temporal lobe epilepsy: presurgical localization with proton chemical shift imaging.

PURPOSE: To assess two-dimensional phase-encoded proton chemical shift imaging for potential clinical application in presurgical localization of temporal lobe epilepsy (TLE). MATERIALS AND METHODS: Interictal chemical shift imaging studies were performed in 25 patients (17 unilateral, eight bilateral epileptogenic abnormalities) and 12 healthy volunteers. Results were compared with those of electroencephalography. For each temporal lobe, the volume of interest (VOI) included mesial, lateral, anterior, and posterior areas. RESULTS: The epileptogenic zone was characterized by an abnormal pattern of decreased signal intensity in the N-acetylaspartate (NAA) peak, either increased or unchanged choline (Cho) level relative to creatine (Cr) signal intensity, and, occasionally, elevated lactate level. NAA/Cho was the most sensitive and reliable quantitative marker for abnormality. The sensitivity and specificity of this technique compared with EEG were 90% and 85%, respectively. The difference in NAA/Cho between epileptogenic and normal temporal lobes was highly significant (P < .001). No statistically significant difference was found between normal temporal lobes and patients' uninvolved temporal lobes. CONCLUSION: NAA/Cho is an excellent marker for localizing the epileptogenic zone in TLE.

Adolescent↗

In vitro adsorption of a hydrophobic mutagen to gastrointestinal mucus glycoprotein (mucin) and dietary fibre.

The adsorption of mutagens by some dietary fibres has been suggested as one mechanism by which dietary fibres protect against colorectal cancer. It is thought that these dietary fibres carry the mutagen out of the digestive tract, decreasing the effective mutagen concentration to which epithelial cells are exposed. The ability of gastrointestinal mucin to alter the extent to which the hydrophobic mutagen 1,8-dinitropyrene (DNP) adsorbs in vitro onto the insoluble dietary fibre alpha-cellulose, was investigated. It was found that crude and purified human ileal mucins themselves adsorbed DNP and decreased the adsorption of DNP onto alpha-cellulose. Purified mucin which had been treated with trypsin also adsorbed DNP. These studies suggest that in the digestive tract there would be competition for the adsorption of DNP between mucin and insoluble dietary fibres, such as alpha-cellulose. This factor must be considered in predictions about the distribution of hydrophobic, mutagenic carcinogens in the digestive tract and their role in the etiology of colorectal cancer.

Adsorption↗

Short echo time proton spectroscopy of human brain using a gradient head coil.

Short echo time, single voxel localized proton spectroscopy was accomplished using a stimulated echo (STEAM) sequence running on a Siemens 1.5-T system with a head coil incorporating the Z and Y gradients. Spectra from the temporal lobe, the cerebellum and mid brain were acquired from a group of normal volunteers using the following parameters: voxel size = 8 ml, TE = 22 msec, 512 signal averages and TR = 1.7 sec. STEAM spectra acquired with the small diameter gradients showed significantly fewer artifacts at short TE, allowing the observation of glutamate/glutamine, GABA, taurine, and inositol in addition to the prominent resonance of choline, creatine/phosphocreatine and N-acetylaspartate (NAA). The levels of chlorine, creatine and NAA were found to be significantly different in the three regions of the brain examined.

Adult↗

Thymidine-modulated 5-fluorouracil metabolism in liver and RIF-1 tumors studied by 19F magnetic resonance spectroscopy.

19F Magnetic resonance spectroscopy was used to study the impact of the biochemical modulator thymidine (TdR) on the 5-fluorouracil (5FU) metabolism in the livers and radiation-induced fibrosarcoma (RIF-1) tumors of 5FU-treated C3H mice. The liver spectra measured after administration of 5FU (65 or 130 mg/kg IP) showed the 5 FU resonance and its catabolites alpha-fluoro-beta-ureidopropionic acid and alpha-fluoro-beta-alanine. At the latter dose, fluoronucleotide signal was also detected. The liver spectra of TdR-pretreated (500 mg/kg, IP) mice showed additional signals of fluoronucleotide and fluoronucleoside at both 5FU doses, while alpha-fluoro-beta-alanine was not detected. TdR pretreatment increased the half-life of 5FU in livers from 24 +/- 2 to 126 +/- 46 SEM min at the 5FU dose of 65 mg/kg and from 28 +/- 2 to 95 +/- 22 min at the 130 mg/kg dose (P less than .1 and P less than .01, respectively). TdR-pretreated mice had higher 5FU anabolite (fluoronucleotide + fluoronucleoside) levels in their RIF-1 tumors than nonpretreated mice that received the same 5FU doses (56 +/- 15 SEM vs. 0 arbitrary units at the 5FU dose of 65 mg/kg, and 88 +/- 21 vs. 10 +/- 3 arbitrary units at 130 mg/kg 5FU; P less than .0001). The percentage drop in tumor volume was enhanced in the mice that received TdR, from 27 +/- 4 SEM to 52 +/- 2 at the 5 FU dose of 65 mg/kg and from 24 +/- 3 to 65 +/- 4 at the 130-mg/kg dose (P less than .0001, both).

Animals↗

19F magnetic resonance spectroscopy studies of the metabolism of 5-fluorouracil in murine RIF-1 tumors and liver.

The metabolism of 5-fluorouracil (5FU) in tumors and livers of RIF-1 tumor-bearing C3H mice given i.p. injections of 5FU was serially monitored by 19F magnetic resonance spectroscopy. The levels of 5FU and fluoronucleotide detected in the tumors after a dose of 130 mg/kg (n = 13) were less than one-third of those after 260-mg/kg 5FU (n = 14). During the days after these doses, tumor size decreased by 24 +/- 3 and 52 +/- 6 SEM%, respectively. A second 130-mg/kg dose, given at day 7 after the first 130-mg/kg dose, resulted in still lower tumor fluorine levels and little change in tumor size. There was a significant correlation between the magnetic resonance spectroscopy-detected fluoronucleotide levels and the shrinkage of tumors after the 260-mg/kg dose (r = 0.44; P = 0.024). In mouse liver, the degradation of 5FU to alpha-fluoro-beta-ureidoprobionic acid and alpha-fluoro-beta-alanine after the 260-mg dose (n = 13) was slower than after a dose of 130 mg/kg (n = 14). For the respective doses, the half-life of 5FU was 59 +/- 7 versus 28 +/- 2 SEM min (P less than 0.0001). There was a negative correlation between the levels of 5FU catabolite (alpha-fluoro-beta-ureidoprobionic acid and alpha-fluoro-beta-alanine) in liver and fluoronucleotide in tumor (r = -0.80; P = 0.0020), which indicates that the degradation in liver and the activation of 5FU in tumor are competing processes.

Animals↗

Multinuclear MR investigation of the metabolic response of the murine RIF-1 tumor to 5-fluorouracil chemotherapy.

The metabolic response of the RIF-1 tumor to 5-fluorouracil (a single dose of 260 mg 5FU/kg, ip) was monitored in 10 mice using 19F and 31P MR spectroscopy. 19F MRS revealed a continuous drop in tumor 5FU level and an increase in the fluoronucleotide (Fnuc) signal to a plateau value of 50% of the initial 5FU level, during the first 2 h after chemotherapy. Although the 31P MR spectra of the tumors showed no significant initial changes, the total level of MR visible tumor phosphate decreased and tumor pH increased during the subsequent days. The changes in phosphate metabolism and tumor pH did not correlate with the detected fluorine levels or tumor response. However, the pretreatment Pi level, the plateau Fnuc level, and the 5FU induced decrease in tumor volume showed significant correlation. This indicates that both 19F and 31P MR spectroscopy have potential for predicting response to 5FU chemotherapy.

Animals↗

Magnetic resonance imaging of cutaneous neoplasms: clinicopathologic correlation.

Recently, magnetic resonance imaging (MRI) has been reported to be clinically useful, in selected cases, in patients with melanocytic skin lesions. This report describes good resolution, clinically useful MRI scans of squamous cell carcinoma, dermatofibroma, and primary cutaneous B-cell lymphoma. The tumor depth measured by MRI was in excellent correlation with Breslow's depth measurements, indicating that MRI is probably the radiologic technique of choice for preoperative evaluation of the extent and depth of primary and recurrent skin tumors. This report also provides the authors' recommendations for obtaining optimal MRI images of cutaneous lesions.

Adult↗

Effect of the delta subunit on assembly and proton permeability of the F0 proton channel of Escherichia coli F1F0 ATPase.

During the assembly of the Escherichia coli proton-translocating ATPase, the subunits of F1 interact with F0 to increase the proton permeability of the transmembrane proton channel. We tested the involvement of the delta subunit in this process by partially and completely deleting uncH (delta subunit) from a plasmid carrying the genes for the F0 subunits and delta and testing the effects of those F0 plasmids on the growth of unc+ and unc mutant E. coli strains. We found that the delta subunit was required for inhibition of growth of unc+ cells. We also tested membranes isolated from unc-deleted cells containing F0 plasmids for F1-binding ability. In unc-deleted cells, these plasmids produced F0 in amounts comparable to those found in normal unc+ E. coli cells, while having only small effects on cell growth. These studies demonstrate that the delta subunit plays an important role in opening the F0 proton channel but that it does not serve as a temporary plug of F0 during assembly, as had been previously speculated (S. Pati and W. S. A. Brusilow, J. Biol. Chem. 264:2640-2644, 1989).

Adenosine Triphosphate↗

Spectral editing of tumor 13C MRS in situ.

The editing pulse sequence DEPT (D.T. Pegg, D.M. Doddrell, and M.R. Bendall, J. Chem. Phys. 77, 2745 (1982)) was modified using a scheme of various composite pulses and a 16-step phase cycling to obtain proton-decoupled natural-abundance 13C edited subspectra of solid tumors. A solenoidal probe including a Faraday shield and an orthogonal saddle decoupling coil was built for this purpose.

Animals↗

Phosphorus metabolites and the distribution of cell cycle phase of RIF-1 tumors in response to 14 Gy irradiation.

Simultaneous measurements of DNA cell phase cycle distributions and in vivo 31P NMR spectroscopy were performed on 40 RIF-1 murine tumors irradiated with 14 Gy of X-radiation. Diploid and tetraploid tumor populations were observed. The cells blocked in G2/M phase were measured as a function of the ratios of tetraploid cell number in G2/M phase versus total cell population measured. The G2/M population reached a maximum at 32 h post irradiation, dropping to control values by 72 h, while the ratio of inorganic phosphate to beta-nucleotide triphosphate dropped significantly at 32 h and remained significantly lower than control up to 72 h post irradiation. Measurements of PME, PDE, PCr, and pH showed no significant variations at any time point. No significant change in host cell population could be observed. Since the measured G2/M population never increased to more than 3% of the total cell population, the change observed in the 31P NMR spectra were not simply the result of possible differences in NMR profiles of the different cell phase populations but were more likely due to a change in the metabolic characteristics or environment of a majority of the cells.

Animals↗

Mean inactivation dose (D). A critical analysis of a neglected parameter in radiotherapy.

By predicting treatment outcome to radiotherapy from in vitro radiobiological parameters, not only individual patient treatments can be tailored, but also new promising treatment protocols can be tried in patients in whom unfavorable outcome is predicted. In this respect, choosing the right parameter can be very important. Unlike D0 and N which provide information of the distal part of the survival curve, mean inactivation dose (D) estimates overall radiosensitivity. However, the parameters reflecting the response at the clinically relevant low-dose region are neglected in the literature. In a literature survey of 98 papers in which survival curves or D0/N were used, only in 2D was used. In 21 papers the D0/N values were important in drawing conclusions. By calculating D in 3 of these 21 papers, we show that the conclusion drawn may be altered with the use of D. The importance of 'low-dose-region-parameters' is reviewed.

Animals↗

Therapeutic response of breast carcinoma monitored by 31P MRS in situ.

In situ phosphorous MRS was employed to study the metabolites of normal and cancerous breasts, and the alterations of tumor response to therapy. In a group of 7 normal volunteers and 12 patients, the total mobile phosphate content of breast carcinomas was found to be at least two to three times higher than that of the normal breast measured off menstruation. The metabolite profiles of normal and tumorous breasts are coarsely similar. In both cases the intracellular pH (pHi) was either neutral or slightly alkaline (pH greater than 7.0). Prior to treatments, the metabolite levels of phosphoryl monoester-to-ATP ratio of breast neoplasms were higher than those of the controls and decreased after the patients received a few treatments while the pHi fluctuated at a value greater than 7.0. The phosphoryl diester-to-ATP ratio also demonstrated to a lesser extent a decreasing trend in response to therapy.

Breast↗

Monitoring therapeutic response of human superficial tumors using phase-encoded spectroscopy.

A one-dimensional phase-encoded spectroscopy sequence was implemented on a GE 1.5-T Signa imager and the feasibility of its application to monitor the 31P metabolites of superficial tumors was demonstrated. Serial 31P spectra of 1-cm slices with adequate signal-to-noise ratio and insignificant T2 weighting can be obtained in 28 min. The degree of "bleeding" effect was reduced with increased phase-encoding steps.

Adult↗

Magnetic resonance imaging of cutaneous melanocytic lesions.

This is the first literature report on magnetic resonance imaging (MRI) examination of cutaneous melanocytic or any other type of skin lesions. Good resolution, clinically useful MRI scans of a congenital nevus and a metastatic melanoma to the skin are presented. The potential usefulness of MRI technique to physicians dealing with cutaneous disease is discussed.

Adult↗

Human in vivo 31P spectroscopy of skin: potentially a powerful tool for noninvasive study of metabolism in a cutaneous tissue.

The first application of human in vivo phosphorus (31P) magnetic resonance spectroscopy to analysis of skin metabolism is presented. Our results confirm that phosphocreatine is a major energy phosphometabolite in human skin. Human in vivo 31P spectroscopy utilizing a skin coil designed in our laboratory can have clinical applications in cutaneous surgery and clinical dermatology, and will facilitate understanding of the pathophysiology of skin disease. In vitro experiments with fresh human skin indicate that complete utilization of phosphocreatine is followed by utilization of adenosine triphosphate (ATP) molecules during ischemia. These experiments also suggest that the majority of phosphocreatine in human skin is localized in epidermal and papillary dermis.

Adenosine Triphosphate↗

Human neoplasm pH and response to radiation therapy: P-31 MR spectroscopy studies in situ.

Thirty-five human neoplasms from various sites and of various histologic types and stages were examined with phosphorus-31 magnetic resonance spectroscopy in situ. The tumors included 13 squamous cell carcinomas of the head and neck (lymph nodes), eight Hodgkin lymphomas, six non-Hodgkin lymphomas, four carcinomas of the breast, one melanoma, one sarcoma, one neuroblastoma, and one mucoepidermoid sarcoma of the salivary glands. Thirty-four of the neoplasms had normal to slightly alkaline pH before irradiation. During fractionated radiation therapy, the pH stayed in a range of from near neutral to alkaline and rose to 7.6-8.0 at several time points of radiation therapy for some tumors. These results suggest that most tumor cells in human neoplasms are well oxygenated and that only a negligible fraction are chronic hypoxic cells. The fluctuating alkaline pH during radiation therapy occurred regardless of the responsiveness of the treated tumors.

Carcinoma, Squamous Cell↗

Less well known parameters of in vitro radiosensitivity.

In addition to well known parameters used for measuring in vitro cellular radiosensitivity (mean lethal dose, extrapolation number, quasithreshold dose), there are other, less well known measures that may be more important. The authors recently surveyed the literature and found that mean activation dose (D) has been neglected in the analyses. Among 70 articles published in the radiation oncology and biology literature that used cell survival curves or parameters to measure radiosensitivity, only two used the values of D in their analysis. By recalculating D from published survival curves, different conclusions may be drawn. The authors see a definite need for more prospective application of D and surviving fraction at 2 Gy.

Cell Survival↗