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J Krane

Publications and source records attributed to J Krane.

28 records · Page 2Linked to original sources

Proton nuclear magnetic resonance spectroscopy measurements of methylene and methyl line widths in plasma: significant variations with extent of breast cancer, duration of pregnancy and aging.

The composite methylene (chemical shift range 1.2-1.4 ppm) and methyl (0.8-0.9 ppm) resonances of the 1H NMR spectrum were analyzed in plasma samples from breast tumor patients, pregnant women, and healthy subjects. Using a 500 MHz NMR instrument operating at 25 degrees C, the peaks were analyzed for line width at half height and then averaged. A statistically significant difference (p less than 0.001) was found between the average (mean +/- SD) line width in the plasma samples from the 30 patients with metastatic breast cancer (34.1 +/- 5.0 Hz) and the controls matched for age and sex (38.7 +/- 4.4 Hz). In the 16 patients with localized breast cancer and the 16 with regional spread, the average line width was not different from that of matched controls. In 21 patients with benign tumor in the breast, the average line width was not different from that of matched controls. A difference in the average line width was found between 31 pregnant women in the third trimester (32.5 +/- 3.4 Hz) and their controls matched for age and sex (42.7 +/- 4.6 Hz) (p less than 0.001). The average line width was lower in the late (31.5 +/- 3.3) than in the early (34.5 +/- 2.5 Hz) part of the third trimester (p = 0.022). In 54 healthy male and 130 healthy female controls, line widths declined gradually with increasing age by decades, except in the fifth decade for the men and the sixth decade for the women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Proton nuclear magnetic resonance spectroscopy of plasma from healthy subjects and patients with cancer.

To evaluate the ability of proton nuclear magnetic resonance (NMR) spectroscopy to indicate the presence or absence of malignant disease, we analyzed plasma samples from 104 patients with untreated cancer of various types and from 164 healthy controls. All specimens were coded with random numbers, and the investigators were blind to patient category. A statistically significant difference (P less than 0.001) was found between the mean (+/- SD) line widths in the plasma samples from the controls (39.1 +/- 6.7 Hz) and the line widths in plasma from the patients with cancer (35.2 +/- 6.4 Hz). However, the values showed considerable overlap between the two groups. The average line widths in the 54 male (36.0 +/- 7.9 Hz) and the 110 female (40.5 +/- 5.6 Hz) controls were significantly different (P less than 0.001). Differences in the average line width were also found between 34 male controls 40 years old or older (33.9 +/- 6.5 Hz) and 20 younger men (39.6 +/- 8.8 Hz) (P = 0.008) and between 61 female controls 40 or older (38.8 +/- 5.7 Hz) and 49 younger women (42.5 +/- 4.7 Hz) (P less than 0.001). The average line widths in 36 women with cancer (35.5 +/- 6.8 Hz) and their controls matched for age and sex (39.0 +/- 6.3 Hz) were significantly different (P = 0.03) but again showed much overlap. In 29 men with cancer, the line widths were not different from those of controls matched for age and sex. We conclude that proton NMR spectroscopy is not generally reliable for the detection of cancer. Furthermore, our data demonstrate the importance of studying control groups matched for age and sex.

Adult↗

In vivo tissue pharmacokinetics by fluorine magnetic resonance spectroscopy: a study of liver and muscle disposition of fleroxacin in humans.

Magnetic resonance spectroscopy of fluorine (19F) has been used to noninvasively study the in vivo pharmacokinetics of a model drug, fleroxacin (a fluoroquinolone antibiotic agent), in healthy human subjects. After oral administration, fleroxacin was detected in 19F magnetic resonance spectra from both liver and calf muscle and four magnetic resonance examinations were undertaken during a 24-hour period. By combining plasma analysis by high performance liquid chromatography with the magnetic resonance data, the following pharmacokinetic parameters (mean values) were obtained: tmax, 1.4, 4.6, and 5.6 hours in liver, plasma, and muscle, respectively; Cmax, 53, about 250, and about 60 mumol/L in plasma, liver, and muscle, respectively; t1/2, 4.4 hours (fast phase) and 10.8 hours (slow phase) in liver and 14.2 hours in plasma. The study documents for the first time the potential use of 19F magnetic resonance spectroscopy to noninvasively observe the time-related changes of a fluorine-containing drug in human tissues after oral administration.

Administration, Oral↗

Proton n.m.r. of ferredoxin from Clostridium pasteurianum.

Proton magnetic resonance spectra at 500 MHz are reported for the oxidized and reduced forms of the 2[4Fe-4S]-ferredoxin from Clostridium pasteurianum. The reduced protein showed additional peaks in the 10-60 ppm region, which were previously unobserved, and there were significant differences between oxidized and reduced states in the whole region. The electron exchange rate in partially reduced ferredoxin is slow on the n.m.r. time scale when reduced with sodium dithionite, but fast when zinc reduced methyl viologen is used as reducing agent. We explain the difference between fast and slow exchange as being due to the different chemical properties of the two reducing agents.

Clostridium↗

The binding and hydrolysis of sphingomyelin by phospholipase C (Bacillus cereus) as shown by 31P NMR.

31P nuclear magnetic resonance studies showed that heavily inactivated phospholipase C (Bacillus cereus) initially caused line broadening in the 31P resonance from sphingomyelin thus indicating enzyme-lipid association. Using larger amounts of enzyme or longer preincubation caused a displacement of the 31P resonance to a position suggesting phosphorylcholine formation. Incubation of the heavily inactivated enzyme with a phosphonolipid caused a displacement of the 31P resonance suggesting hydrolysis.

Bacillus cereus↗

An anion binding site in the active centre of phospholipase C from Bacillus cereus.

The bi-Zn2+-enzyme phospholipase C (Bacillus cereus) is readilly inhibited by univalent anions. N.m.r. studies on the 113Cd-substituted enzyme showed the presence of an inert and a perturbable metal, neither of which seemed affected by I-. X-ray crystallographic analysis showed the binding of one I- to the enzyme 4.8 A from the nearest metal (too far for a metal-halide bond). Phospholipase C contains an arginine residue apparently necessary for substrate binding and I- partially protected against inactivation by an arginine reagent. Thus an arginine residue may represent the binding site for univalent anions in the enzyme active centre.

Anions↗

Metabolite composition in breast tumors examined by proton nuclear magnetic resonance spectroscopy.

BACKGROUND: In vivo characterisation of breast tumors using protein (1H) MR spectroscopy relies upon in vitro interpretation of tissue samples. The present study has investigated metabolite composition in extracts from breast tumors and non-involved breast tissue. Multivariate data analysis was used to determinate combinations of metabolites important for differentiation. MATERIALS AND METHODS: Tumor and non-involved breast tissue were obtained from 16 patients undergoing surgical treatment. 1H NMR spectra of perchloric acid tissue extracts were obtained at a BRUKER Avance DRX600 spectrometer. The data was analysed using principal component analysis and probabilistic neural networks. RESULTS: Low levels of glucose and high content of choline compounds were dominant findings in the tumor spectra. Principal component loadings demonstrated this strong association. The spectra were correctly classified using neural network analysis. CONCLUSIONS: Large differences in the metabolite composition of breast tumors and surrounding breast tissues have been documented.

Adult↗

Analysis and classification of proton NMR spectra of lipoprotein fractions from healthy volunteers and patients with cancer or CHD.

Human blood plasma samples from 52 subjects were collected and the very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low density lipoprotein (LDL) and high density lipoprotein were isolated by serial ultra centrifugation. 600 MHz 1H NMR spectra of the lipoprotein fractions were acquired. The methyl and methylene regions in the spectra of VLDL, LDL and HDL were utilised in further analyses via Kohonen neural networks (KNN) and generative topographic mapping (GTM), two related examples of (unsupervised learning) self-organising feature mapping techniques. Systematic variations in lipoprotein profiles can be substantially visualised through the use of KNN and GTM. The relationship between the sample positions in the Kohonen plot was visualised by surface plots of the corresponding VLDL and HDL cholesterol and VLDL triglyceride contents. The GTM maps of the VLDL and HDL fractions were used to investigate the individual properties of selected samples. A large number of the cancer patients were found clustered in the VLDL GTM map, and GTM map positions of samples in relation to CHD, diabetes and renal failure could be found. Although the study group here considered is heterogeneous in respect to age, sex, type of disease and medications within each defined class, classification of VLDL and HDL data with probabilistic neural network (PNN) was quite successful with respect to the groupings: cancer, CHD, volunteers and other (comprising patients with other diseases). Statistics based on 15 independent sets of PNN calculations gave true positive fractions usually higher than 0.83 and false positive fractions lower than 0.088. Attempts to use the corresponding LDL data and four classes were uniformly poor although some classifications (e.g., volunteer versus CHD) were easily performed.

Adult↗

Hyperthermia induced polyphosphate changes in Propionibacterium acnes as studied by 31P NMR.

The polyphosphate component in 31P NMR spectra of the Gram-positive Propionibacterium acnes increased after hyperthermia treatment. The cells were exposed to temperatures in the interval from 15 degrees C to 45 degrees C. The amount of polyphosphate increased with increasing temperature. There were no temperature induced changes in the other phosphorous components seen in the spectra with exception of a decrease in ATP for higher temperatures. The increase in polyphosphates was less than that obtained from cells irradiated by near ultra-violet light.

Hot Temperature↗

In vitro proton NMR spectroscopy of extracts from human breast tumours and non-involved breast tissue.

Proton (1H) nuclear magnetic resonance (NMR) spectra were obtained from perchloric acid (PCA) extracts of 11 breast tumours and non-involved breast tissue from 7 of the same patients. The spectra were correlated with histopathologic diagnosis. The tumour group consisted of 8 ductal carcinomas, 1 ductal carcinoma with an extensive intraductal component, 1 intraductal carcinoma and 1 fibroadenoma. Higher content of lactate, succinate and phosphocholine and low levels of glucose and inositol were characteristic findings in the tumour group as compared to non-involved breast tissue. 1H NMR spectra of PCA extracted breast specimens provide a comprehensive window into the metabolic activities of the tissue.

Adenocarcinoma, Mucinous↗