Distant ancestor of mankind unearthed: 520 million year-old fish-like fossils reveal early history of vertebrates.
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Animals↗
Biomedical subjects
C W Li
Publications and source records attributed to C W Li.
Does Ser364Pro mutation of connexin 43 exist in Taiwanese patients with Ivemark syndrome?
BACKGROUND: A previous study by Britz-Cunningham et al (N Engl J Med, 1995) indicated that a mutation of the connexin 43 (CX43) gap junction gene might be responsible for Ivemark syndrome. Ser364Pro substitution (TCA-->CCA) is the most common mutation located in the cytoplasmic tail domain of CX43. This domain may be an important part of the conductance channel of the gap junction. It may, therefore, result in heart anomalies and situs inversus during embryonic development, resulting in Ivemark syndrome. METHODS: We investigated 10 patients with Ivemark syndrome, 10 healthy individuals, one patient with Kartagener syndrome and one with polysplenia and situs inversus but without heart anomaly for this mutation. Seminested polymerase chain reaction (PCR) was performed using a DNA template from DNA extracted from peripheral blood cells. Direct sequencing was done after purification of the second round of PCR products. Then, the sequence was compared with the last 402 bp of the cDNA-coding region of CX43. RESULTS: No base changes were found in the patients with Ivemark syndrome or other patient groups at the previously reported CX43 residues of Thr326, Gln352, Ser364, Ser365 and Ser373. CONCLUSIONS: The results indicate that Ser364Pro mutation of CX43 did not exist in the 10 Taiwanese patients with Ivemark syndrome. Other genes responsible for the Ivemark syndrome should be further investigated.
Abnormalities, Multiple↗
[The relationship between retinoid acid receptor and head and neck squamous cell carcinoma]
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Journal Article↗
Mutational and crystallographic analyses of interfacial residues in annexin V suggest direct interactions with phospholipid membrane components.
Annexin V belongs to a family of eukaryotic calcium-dependent membrane-binding proteins. The calcium-binding sites at the annexin-membrane interface have been investigated in some detail; however, little is known about the functional roles of highly conserved interfacial residues that do not coordinate calcium themselves. In the present study, the importance of tryptophan 185, and threonine or serine at positions 72, 144, 228, and 303, in rat annexin V is investigated by site-directed mutagenesis, X-ray crystallography, and functional assays. The high-resolution crystal structures of the mutants show that the mutations do not cause structural perturbations of the annexin molecule itself or disappearance of bound calcium ions from calcium-binding sites. The assays indicate that relative to wild-type annexin V, loss of the methyl substituent at position 72 (Thr72-->Ser) has no effect while loss of the hydroxyl group (Thr72-->Ala or Thr72-->Lys) causes reduction of membrane binding. Multiple lysine substitutions (e.g., Thr72,Ser144,Ser228,Ser303-->Lys) have a greater adverse effect than the single lysine mutation, suggesting that in annexin V the introduction of potentially favorable electrostatic interactions between the lysine side chains and the net negatively charged membrane surface is not sufficient to overcome the loss of the hydroxyl side chains. Replacement of the unique tryptophan, Trp185, by alanine similarly decreases membrane binding affinity. Taken together, the data suggest that the side chains mutated in this study contribute to phospholipid binding and participate directly in intermolecular contacts with phospholipid membrane components.
Alanine↗
Simultaneous 3D NMR spectroscopy of proton-decoupled fluorine and phosphorus in human liver during 5-fluorouracil chemotherapy.
Simultaneous acquisition of 1H-decoupled 31P and 19F 3D CSI is demonstrated in the liver of a patient undergoing 5-fluorouracil chemotherapy. Both 31P and 19F shared the same voxel size (64 or 27 ml), bi-level 1H-decoupling and 0.35 s TR. The measurements were done in a 1.5 Tesla clinical imager with three radio-frequency (RF) channels and a triple-tuned surface-coil. The overall MRI and MRS examination time was under 90 min. Simultaneous acquisition of 31P and 19F permits localized study of the influence of hepatic metabolism on the uptake and catabolism of fluoropyrimidine drugs without extra measurement time or higher SAR.
Absorption↗
Proton-decoupled 19F spectroscopy of 5-FU catabolites in human liver.
An RF network and a dual-tuned surface coil are described for obtaining proton-decoupled, NOE enhanced 19F spectra from a whole body clinical imager operating at 1.5 Tesia. The network removes 19F frequency noise from the decoupler transmitter, and prevents preamplifier saturation from high-level decoupling signals. Proton decoupling of 19F spectra was optimized using a sample of urine containing 5-fluorouracil (5-FU) and its catabolite fluoro-beta-alanine (FBAL). Proton-decoupled 19F spectroscopy in vivo is demonstrated by obtaining both nonlocalized spectra and spectra localized with three-dimensional chemical shift imaging from the liver of patients undergoing 5-FU chemotherapy.
Fluorouracil↗
Metabolic characterization of human soft tissue sarcomas in vivo and in vitro using proton-decoupled phosphorus magnetic resonance spectroscopy.
We applied 1H-decoupling and nuclear Overhauser enhancement to obtain well-resolved 31P magnetic resonance spectra accurately localized to 20 soft tissue sarcomas in vivo, using three-dimensional chemical shift imaging. Fifteen spectra had large phosphomonoester signals (21% of total phosphorus) that contained high amounts of phosphoethanolamine (compared to those of phosphocholine) but no signals from glycerophosphoethanolamine, and glycerophosphocholine was detected in only four cases. Prominent nucleoside triphosphates (52% of phosphorus) and low inorganic phosphate (10% of phosphorus) indicated that a large fraction of these 15 sarcomas contained viable cells, and this impression was confirmed histologically in 13 of the sarcomas. High-resolution in vitro 31P spectra of extracts of surgical specimens of four of the sarcomas studied in vivo and six additional sarcomas confirmed the in vivo assignments of metabolites and revealed considerable inter- and intratumoral variations of metabolite concentrations associated with histological variations in the relative amounts of cells and of matrix materials or spontaneous necrosis. Seven sarcomas, all high grade with pleomorphic or round cells rather than spindle cells, contained an unidentified phosphodiester signal in vivo; its absence in the extract spectra indicates that it may be from an abnormally mobile membrane component. We have documented a means to obtain new information about in vivo metabolism in human sarcomas and to provide a basis on which to examine the uses of 31P magnetic resonance spectroscopy in the clinical management of sarcomas.
Adult↗
Quantitation of resonances in biological 31P NMR spectra via principal component analysis: potential and limitations.
This paper examines the potential and limitations of peak area quantitation of biological NMR spectra using principal component analysis (PCA), including its requirement for prior knowledge. The principles of the method are presented without in-depth mathematical treatment. PCA is illustrated for simulated data, 31P NMR spectra obtained consecutively over 1-2.5 days from perfused Rat-2 cells metabolizing the choline analogue phosphoniumcholine (Chop) and in vivo proton-decoupled, NOE-enhanced, three-dimensional CSI localized 31P NMR spectra of the liver of healthy volunteers. The results show that PCA can be used to quantitate strongly overlapping peaks without prior knowledge of the peak shapes or positions and to reconstruct spectra with significantly reduced noise variance. Two major limitations of PCA are presented: (1) PCA cannot separate peaks whose intensities are well correlated; (2) PCA is sensitive to differences in chemical shift and line-width of peaks between spectra. The discussion focuses on what knowledge of the biological and spectroscopic features of the samples and the principles of PCA is necessary for peak area quantitation via PCA.
Humans↗
Molar quantitation of hepatic metabolites in vivo in proton-decoupled, nuclear Overhauser effect enhanced 31P NMR spectra localized by three-dimensional chemical shift imaging.
Proton decoupling and nuclear Overhauser effect (NOE) enhancement significantly improve the signal-to-noise ratio and enhance resolution of metabolites in in vivo 31P MRS. We obtained proton-decoupled, NOE-enhanced, phospholipid-saturated 31P spectra localized to defined regions within the normal liver using three-dimensional chemical shift imaging. Proton-decoupling resulted in the resolution of two major peaks in the phosphomonoester (PME) region, three peaks in the phosphodiester (PDE) region and a diphosphodiester peak. In order to obtain molar quantitation, we measured the NOE of all hepatic phosphorus resonances, and we corrected for saturation effects by measuring hepatic metabolite T1 using the variable nutation angle method with phase-cycled, B1-independent rotation, adiabatic pulses. After corrections for saturation effects, NOE enhancement, B1 variations and point spread effects, the following mean concentrations (mmol/l of liver) (+/-SD) were obtained: [PME1] = 1.2 +/- 0.4, [PME2 + 2,3-DPG] = 1.1 +/- 0.1, [Pi + 2,3-DPG] = 2.8 +/- 0.5, [GPEth] = 2.8 +/- 0.7, [GPChol] = 3.5 +/- 0.6 and [beta-NTP] = 3.8 +/- 0.3. T1 and NOE enhancement were strongly correlated (r = 90), and indicated that the fractional contribution of 1H-31P dipolar relaxation to total 31P relaxation is minimal for NTPs, moderate for PMEs and high for PDEs in liver. Proton-decoupling and NOE enhancement permit one to obtain more information about in vivo metabolism of liver than previously available and should enhance the utility of 31P MRS for the study of hepatic disorders.
Adult↗
Simultaneous 3D NMR spectroscopy of fluorine and phosphorus in human liver during 5-fluorouracil chemotherapy.
Simultaneous multivoxel 31P and 19F 3D localized NMR spectroscopy is demonstrated on a phantom and in the liver of patients undergoing bolus-infusion 5-fluorouracil chemotherapy. The 19F and 31P spectra were localized with 8 x 8 x 8 3D chemical-shift imaging, with both nuclei sharing the same field of view and voxel size (27 and 64 ml in phantom and liver, respectively) using a 1.5-Tesla clinical imager with two RF channels and a dual-tuned surface coil. The repetition time (TR = 0.26 s) and Ernst nutation angles (theta E = 32 degrees for 19F, 28 degrees for 31P) were chosen to optimize the signal-to-noise ratio (SNR) per-unit time for the 0.5- to 2-s T1 range of the 19F and 31P metabolites of interest. The overall examination time, including tuning, imaging, shimming and dual-nuclear spectroscopy, was under 90 min. Simultaneous acquisition of 31P and 19F spectra will permit the study of the influence of hepatic and/or tumor metabolism on the uptake and catabolism of fluoropyrimidine drugs with no extra measurement time.
Adult↗
Quantitation of 5-fluorouracil catabolism in human liver in vivo by three-dimensional localized 19F magnetic resonance spectroscopy.
The development of clinical applications of 19F magnetic resonance (MR) spectroscopy of 5-fluorouracil (5-FU) has been limited by the inability to localize 19F spectra to specific regions of interest, making it difficult to quantitate drug and metabolite concentrations accurately. To develop methodology for quantitation, we studied the liver of patients receiving rapid bolus i.v. injections of 5-FU. In serial studies, 5-FU disappeared from the liver within 17-26 min, and its catabolite, alpha-fluoro-beta-alanine (FBAL), rose to reach a plateau after 40 min. A high peak level of fluoro-ureido-propionic acid preceded that of FBAL in only one patient, and dihydrofluorouracil was never observed. During the plateau, we obtained MR imaging-directed 19F MR spectra localized using three-dimensional chemical shift imaging. The spin-lattice relaxation time of FBAL in liver, measured using a variable nutation angle method, was 1.6 +/- 0.2 s (mean +/- SD; n = 5). The concentration of FBAL at 60 +/- 10 min after injection was 1.0 +/- 0.2 mm in liver (mean +/- SD; n = 7). This amount represents approximately 20% of the injected dose and 1.4 times the initial hepatic 5-FU concentration. Our approach may permit one to obtain molar concentrations of fluoropyrimidine metabolites simultaneously in hepatic cancers and surrounding liver, and it helps expand pharmacokinetic modeling of fluoropyrimidine catabolism.
Antimetabolites, Antineoplastic↗
Metabolic characterization of human non-Hodgkin's lymphomas in vivo with the use of proton-decoupled phosphorus magnetic resonance spectroscopy.
Development of biological and clinical uses of in vivo 31P magnetic resonance spectroscopy has been hampered by poor anatomic localization of spectra and poor resolution of overlapping signals within phosphomonoester and phosphodiester regions of the spectrum. We applied 1H-decoupling and nuclear Overhauser enhancement to improve resolution of 31P magnetic resonance spectra accurately localized to 21 non-Hodgkin's lymphomas (NHL) by using three-dimensional chemical shift imaging. All 21 spectra had large phosphomonoester signals (26% of total phosphorus) that contained high amounts of phosphoethanolamine relative to phosphocholine. There were no signals from glycerophosphoethanolamine or glycerophosphocholine but only a broad signal from membrane phospholipids in the phosphodiester region (20% of phosphorus). Prominent nucleoside triphosphates (47% of phosphorus) and low inorganic phosphate (7% of phosphorus) indicate well-perfused tissue with viable cells. Mean intracellular pH was 7.23. These characteristics were similar in all grades and stages of NHL. By analogy with recently reported studies in cell lines in vitro, we hypothesize that the pattern of phospholipid metabolites observed in NHL in vivo is partly a manifestation of sustained activation of phospholipase C or D. The techniques we implemented permitted us to obtain more information about in vivo metabolism of NHL than has heretofore been available. This information is important for the establishment of appropriate experimental models and provides a basis from which to examine potential clinical uses of 31P magnetic resonance spectroscopy.
2,3-Diphosphoglycerate↗
Translocation of ferritin and biomineralization of goethite in the radula of the limpet Cellana toreuma reeve.
The radula of the limpet, Cellana toreuma, consists of a continuous series of teeth in various stages of iron biomineralization. The major iron-binding protein of the limpet's iron-containing granule (siderosome) has been purified and identified as ferritin. Limpet ferritin has a M(r) of 575 kDa and can be resolved into two bands by SDS-PAGE analysis, with respective M(r)s of 26 and 21 kDa. The partial N-terminal amino acid sequences of these two subunits were confirmed, and antisera against them were respectively generated. The specifity of these two antisera shows no difference between them. By using transmission electron microscopy and immunogold staining techniques the following two events were revealed: (1) in the superior epithelial cell of the radula, ferritin was disassembled through autophagy or heterophagy before exocytosis; (2) of the limpet ferritin, at least the 26-kDa subunit was found to pass through the microvilli, resulting in the accumulation of iron in the extracellular tooth chamber and the formation of goethite needles. Intracellular ferritin being translocated to the extracellular environment is discussed in the text.
Amino Acid Sequence↗
[Oral survey in children of three different nationalities in Menghai county of Yunnan province]
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Journal Article↗
A nonlinear fluid model for pulmonary blood circulation.
In this paper, we apply a quasi-one-dimensional unsteady nonlinear fluid model to study human pulmonary circulation. Eighteen generations of blood vessels composed of the branching arterial, capillary and venous distensible vessel segments make up the complete pulmonary circulation. The numerical result gives satisfactory agreement with the physiological experimental data: a dramatic pressure drop occurs in the arterioles and postcapillaries, a negative transmural pressure is shown in the postcapillary and small venous segments, a large reverse flow occurs in the main pulmonary artery during the diastolic period, and the reverse flow decreases gradually along the pulmonary tree. In the microgravity case where g = 180 cm s-2, the computation illustrated the effect of gravity force on the blood distribution in the different parts of the pulmonary circulation. The effect of gravity on the total output is not obvious. The effect of local factors which initiate the variations of the geometrical or pulmonary circulation can be stimulated quantitatively by this model. The proposal model can be very useful for clinical practice and for studying the extreme cases which are very difficult to investigate by experiments.
Arteries↗
Vestibulo-ocular compensation following unilateral vestibular deafferentation.
Vestibulo-ocular compensation following vestibular deafferentation was investigated in 26 acoustic neuroma patients following tumor removal and in 5 Menière's disease patients following vestibular nerve section by using sinusoidal harmonic acceleration testing. All three test parameters (phase lead, gain, and asymmetry), when averaged, shifted significantly on the first postoperative test (average 0.4 months after operation). A marked progression in central compensation with gain returning to the range of normal control values was seen in the tests performed 1 to 6 months (average 2.6 months) postoperatively. However, phase lead and asymmetry (especially at 0.01, 0.02, 0.04, and 0.08 Hz) remained outside the range of normal control values, and all three parameters failed to return to their preoperative level even when tested at more than 12 months (average 20.2 months) after operation. This finding indicates that the deficits of the vestibulo-ocular reflex to head acceleration are of long duration if not permanent.
Adaptation, Physiological↗
Sinusoidal harmonic acceleration testing in normal humans.
Forty-one normal humans were tested with sinusoidal harmonic acceleration. Phase lag at 0.01, 0.02, and 0.04 Hz was the most stable parameter, with less test-retest variability than gain and asymmetry. There was no significant difference between men and women for phase lag, gain, or asymmetry at any of the five testing frequencies. Gain decreased as age increased. Age had no effect on phase lag at most test frequencies or on asymmetry at any frequency.
Acceleration↗
[Traditional Chinese and Western medicine in the treatment of 27 patients with malignant lymphoma].
Twenty-seven patients with malignant lymphoma (14 Hodgkin's disease, 9 histiocytosarcoma, 2 plasmacytoma, 2 lympholeucosarcoma) were treated by Ailin-injection plus Chinese herbal medicine. The latter's composition and dose varied depending on the clinical manifestations. All the patients had stage III and IV lesions. The total remission rate was 70.37% (complete remission 13 patients, partial remission 6 patients, no remission 8 patients). In addition, we also studied the suppressive effect of Ailin on transplanted tumor in vivo (S-180). The suppression rates were 36.09%, 48.80%, 32.67% by three repetitions with an average of 39.18% (P less than 0.002). They were 37.25%, 35.29% on S37 with an average of 36.27% (P less than 0.005). They were 46.53%, 44.56%, 51.35%, 45.95% on Ehrlich ascites tumor cells with an average of 47.09% (P less than 0.001). The clinical and experimental studies suggest that Ailin-1 has no serious side effects and is well tolerated by patients with malignant lymphoma at moderate or advanced stages. No toxic reactions were observed at the clinical dose. In the above combination therapy, the Chinese herbal medicine has obvious supplementary effect in the treatment of the patients' cachexia and immuno-suppression.
Adolescent↗