Missense mutations of the PS-1/S182 gene in German early-onset Alzheimer's disease patients.
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Age of Onset↗
Biomedical subjects
D Zhang
Publications and source records attributed to D Zhang.
Severe recurrent cholestatic hepatitis C following orthotopic liver transplantation.
Recurrent infection with hepatitis C virus (HCV) is almost universal following orthotopic liver transplantation although clinical severity varies. Data on 135 patients who underwent transplantation for hepatitis C cirrhosis were reviewed. We describe a progressive, severe cholestatic form of hepatitis occurring in a subgroup of patients with recurrent hepatitis C. Ten patients with severe recurrent hepatitis C were identified; 1 has died, 1 awaits retransplantation, and 8 have undergone retransplantation. All 10 developed severe progressive cholestatic hepatitis, with a mean rise in bilirubin to 24.7 mg/dL at the time of retransplantation. Histology at initial recurrence was of mild hepatitis without evidence of rejection. The failed grafts showed either cirrhosis or confluent hepatic necrosis. The onset of cholestasis preceded retransplantation by less than 5 months. Our study suggests that a minority of patients with recurrent hepatitis C after undergoing liver transplantation develop a severe progressive cholestatic hepatitis and liver failure.
Adult↗
Destabilizing effect of proline substitutions in two helical regions of T4 lysozyme: leucine 66 to proline and leucine 91 to proline.
A class of temperature-sensitive (ts) mutants of T4 lysozyme with reduced activity at 30 degrees C and no activity at 43 degrees C has been selected. These mutants, designated "tight" ts mutants, differ from most other T4 lysozyme mutants that are active at 43 degrees C, but only manifest their ts lesion by a reduced halo size around phage plaques after exposure of the growth plates to chloroform vapors. For example, in the series of T4 lysozyme mutants at position 157, the original randomly selected mutant, T1571, is the least stable of the series, yet, apart from the halo assay and subsequent in vitro protein stability measurements, this mutant is indistinguishable from wild type (WT) even at 43 degrees C. Two mutants were identified: L91P and L66P. Both insert proline residues into alpha-helical regions of the WT protein structure. The stabilities (delta delta G) as determined by urea denaturation are 8.2 kcal/mol for L91P and 7.1 kcal/mol for L66P. CD spectra indicate that no major conformational changes have occurred in the mutant structures. The structures of the mutants were modeled with a 40-ps molecular dynamics simulation using explicit solvent. For L91P, the reduction of stability appears to be due to an unsatisfied hydrogen bond in the alpha-helix and to a new buried cavity. For L66P, the reduction of stability appears to be due to a disruption of the interdomain alpha-helix, at least two unsatisfied hydrogen bonds, and a newly formed solvent-filled pocket that protrudes into the hydrophobic core, possibly reducing the stabilizing contribution of a partially buried intrachain salt bridge.
Circular Dichroism↗
A primary care application of an integrated computer-based pharmacy system.
Primary care demands a continuous flow of current pharmaceutical information to the front lines of patient services. With a wide spectrum of drugs to prescribe and a continuous production of new drug-related information, the practicing physician is faced with a social and professional mandate to deliver the most acceptable drug in a safe and efficacious manner. The legal implications of this product and knowledge explosion have exposed the human brain's inability to store, update, and recall what is currently available. Physicians can no longer trust their memory or their paper-based medical record to protect them from potential liability. The tools to correct this mental imbalance are now available and it should be standard practice to implement a sophisticated computer-based pharmacy system (CBPS) for every outpatient in the United States.
Clinical Pharmacy Information Systems↗
MDX--a medical diagnostic decision support system.
The MDX diagnostic decision support system contains a multitude of clinical facts as reported in a variety of medical textbooks and national medical journals. The database was custom designed for the medical diagnostic process and offers users the widest range of diagnostic knowledge available from a single source in the industry. The database consists of diseases, conditions, chemicals, drugs, and toxins that are known to cause medical illness. Each causal element has an associated file for signs, symptoms and findings. This fully referenced source of encoded clinical knowledge used in MDX comes from the world's experts as they transmit their experience in the written word of books and journals.
Databases, Factual↗
Ginseng extract scavenges hydroxyl radical and protects unsaturated fatty acids from decomposition caused by iron-mediated lipid peroxidation.
This study was conducted to investigate whether or not the antioxidation effect of ginseng extract directly inhibits decomposition of unsaturated fatty acid caused by iron and hydrogen peroxide-induced lipid peroxidation, and whether this effect involves a hydroxyl radical-scavenging mechanism. Thiobarbituric acid-reactive substances (TBARS), gas chromatography, and electron spin resonance (ESR) spectrometer were used to measure lipid peroxidation, unsaturated fatty acid, and hydroxyl radical. The results showed TBARS formed and the loss of arachidonic acid during lipid peroxidation, and that hydroxyl radical formed by the Fenton reaction were completely inhibited by ginseng extract. This antioxidant effect of ginseng may be responsible for its wide pharmacological actions in clinical practice by a free radical reaction-inhibition mechanism.
Arachidonic Acid↗
Volume and enthalpy changes in the early steps of bacteriorhodopsin photocycle studied by time-resolved photoacoustics.
We have studied the photoinduced volume changes, energetics, and kinetics in the early steps of the bacteriorhodopsin (BR) photocycle with pulsed, time-resolved photoacoustics. Our data show that there are two volume changes. The fast volume change ( < or = 200 ns) is an expansion (2.5 +/- 0.3 A3/molecule) and is observed exclusively in the purple membrane (PM), vanishing in the 3-[(3-cholamidopropyl)-dimethylammonio] -1-propane-sulfonate-sulfonate-solubilized BR sample; the slow change (approximately 1 micros) is a volume contraction (-3.7 +/- 0.3 A3/molecule). The fast expansion is assigned to the restructuring of the aggregated BR in the PM, and the 1-micros contraction to the change in hydrogen bonding of water at Asp 212 (Kandori et al. 1995. J. Am. Chem. Soc. 117:2118-2119). The formation of the K intermediate releases most of the absorbed energy as heat, with delta Hk = -36 +/- 8 kJ/mol. The activation energy of the K --> L step is 49 +/- 6 kJ/mol, but the enthalpy change is small, -4 +/- 10 kJ/mol. On the time scale we studied, the primary photochemical kinetics, enthalpy, and volume changes are not affected by substituting the solvent D2O for H2O. Comparing data on monomeric and aggregated BR, we conclude that the functional unit for the photocycle is the BR monomer, because both the kinetics (rate constant and activation energy) and the enthalpy changes are independent of its aggregation state.
Acoustics↗
TGF-beta 1 perturbation of the fibroblast cell cycle during exponential growth: switching between negative and positive regulation.
We have demonstrated previously that SV40 T antigen and serum regulate the length of G1 in exponentially growing NIH-3T3 cells in part by inhibiting density dependent negative cell cycle regulation. In these studies it was suggested that T antigen positively regulated G1 in a density independent manner as well. In this report we show that, 24 h after treatment, TGF-beta 1 perturbs the cell cycle of exponentially growing fibroblasts in a manner similar to T antigen. However, prior to 24 h, TGF-beta 1 produced a negative response, elongating the G1 phase of the cell cycle that was followed by a positive response, both of which were density independent. This biphasic response was measured between 0 and 12 h post-treatment and was relative to responses from serum. This switch from an early inhibitory effect to a late stimulatory effect was associated with changes in Rb phosphorylation, the timing and magnitude of which indicated that Rb may be directly regulating TG1 rather than reporting changes in the population. This is further substantiated by abrogation of the inhibitory effect by expression of wild-type SV40 T antigen and retention of the effect in cells that express an Rb-binding mutant of T antigen (K1). The biphasic regulatory effects of TGF-beta 1 were also displayed in WI-38 and IMR-90 human fibroblasts. This suggests that this biphasic effect is a property of fibroblasts.
3T3 Cells↗
Acoustic nonlinearity parameter tomography for biological specimens via measurements of the second harmonics.
The acoustic nonlinearity parameter B/A is a new parameter in ultrasound tissue characterization. In this paper, on the basis of a theoretical analysis of finite amplitude ultrasonic wave propagation in fluidlike media, an experimental system for nonlinearity parameter tomography is developed. Using this system, the amplitude of the second harmonic wave cumulated in the propagation path of the primary wave is measured and the finite amplitude insert-substitution method is used in the conventional computer tomography (CT) technique. The filtered convolution algorithm is implemented using the amplitude of the second harmonic as the projection data, then the B/A tomography can be reconstructed. The B/A images for several biological samples are obtained. Besides, the image of porcine pathological liver tissue is studied and is compared with that of porcine normal liver tissue. These results show the potential applications of the nonlinearity parameter B/A in medical diagnosis.
Animals↗
Biotransformation of chlorpromazine and methdilazine by Cunninghamella elegans.
When tested as a microbial model for mammalian drug metabolism, the filamentous fungus Cunninghamella elegans metabolized chlorpromazine and methdilazine within 72 h. The metabolites were extracted by chloroform, separated by high-performance liquid chromatography, and characterized by proton nuclear magnetic resonance, mass, and UV spectroscopic analyses. The major metabolites of chlorpromazine were chlorpromazine sulfoxide (36%), N-desmethylchlorpromazine (11%), N-desmethyl-7-hydroxychlorpromazine (6%), 7-hydroxychlorpromazine sulfoxide (36%), N-hydroxychlorpromazine (11%), 7-hydroxychlorpromazine sulfoxide (5%), and chlorpromazine N-oxide (2%), all of which have been found in animal studies. The major metabolites of methdilazine were 3-hydroxymethdilazine (3%). (18)O(2) labeling experiments indicated that the oxygen atoms in methdilazine sulfoxide, methdilazine N-oxide, and 3-hydroxymethdilazine were all derived from molecular oxygen. The production of methdilazine sulfoxide and 3-hydroxymethdilazine was inhibited by the cytochrome P-450 inhibitors metyrapone and proadifen. An enzyme activity for the sulfoxidation of methdilazine was found in microsomal preparations of C. elegans. These experiments suggest that the sulfoxidation and hydroxylation of methdilazine and chlorpromazine by C. elegans are catalyzed by cytochrome P-450.
Antipsychotic Agents↗
Fungal biotransformation of the antihistamine azatadine by Cunninghamella elegans.
The metabolism of the antihistamine azatadine by the zygomycete fungus Cunninghamella elegans ATCC 9245 was investigated. Within 72 h from the addition of the drug to 48-h-old cultures grown in Sabouraud dextrose broth, 95% of azatadine was biotransformed. Two major metabolites, 7-hydroxyazatadine (25%) and 8-hydroxyazatadine (50%), and two minor metabolites, N-desmethylazatadine and 9-hydroxyazatadine, were isolated by high-performance liquid chromatography and characterized by mass spectrometric and proton nuclear magnetic resonance spectroscopic analyses.
Biotransformation↗
VLSI neural system architecture for finite ring recursive reduction.
The use of neural-like networks to implement finite ring computations has been presented in a previous paper. This paper develops efficient VLSI neural system architecture for the finite ring recursive reduction (FRRR), including module reduction, MSB carry iteration and feedforward processing. These techniques deal with the basic principles involved in constructing a FRRR, and their implementations are efficiently matched to the VLSI medium. Compared with the other structure models for finite ring computation (e.g. modification of binary arithmetic logic and bit-steered ROM's), the FRRR structure has the lowest area complexity in silicon while maintaining a high throughput rate. Examples of several implementations are used to illustrate the effectiveness of the FRRR architecture.
Algorithms↗
Use of the sensitive anterograde tracer cholera toxin fragment B reveals new details of the central retinal projections in turtles.
Previous anterograde degeneration and autoradiographic studies have yielded inconsistent results on the extent and target areas of the central retinal projections in turtles. We used the highly sensitive anterograde and retrograde tracer, cholera toxin B fragment (CTB), to re-examine the central retinal projections in Pseudemys scripta elegans. In contrast to the results of the previous anterograde degeneration studies and autoradiographic studies, immunohistochemical detection of CTB-labeled central retinal axons and terminals revealed these projections with great morphological detail and clarity. In addition, the CTB labeling revealed much more extensive projections than previously realized to all known major retinorecipient areas, particularly in the dorsal and ventral lateral geniculate nuclei, the pretectal region, the nucleus of the basal optic root and the optic tectum. Although the contralateral projections were always much more extensive, ipsilateral projections were clearly present (and in some cases abundant) in all previously known retinorecipient areas. In addition, prominent contralateral (and lesser ipsilateral) retinal projections to several novel target, including the basal hypothalamus, the perirotundal nuclei, the suprapeduncular nucleus and the region between the pretectal nuclei and the tegmentum, were observed. Our results suggest that the use of CTB as a tracer to examine central retinal projections in diverse other species will show that central retinal projections are much more widespread and extensive than previously realized.
Animals↗
Nine new triterpene saponins, polygalasaponins XXXIII--XLI from the roots of Polygala fallax Hemsl.
Nine new oleanane-type saponins, polygalasaponins XXXIII--XLI, along with seven known saponins were isolated from the roots of Polygala fallax HEMSL. Polygalasaponins XXXIII-XLI were elucidated as 3-O-beta-D-glucopyranosyl presenegenin 28-O-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl- (1-->2)-(4-O-acetyl)-beta-D-fuco-pyranosyl ester, 3-O-beta-D-glucopyranosyl presenegenin 28-O-beta-D-galactopyranosyl-(1-->4)-beta-D-xylopyranosyl- (1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-(4-O-acetyl)-beta-D- fucopyranosyl ester, 3-O-beta-D-glucopyranosyl presenegenin 28-O-beta-D-galactopyranosyl-(1-->4)-beta-D-xylopyranosyl-(1-->4)- alpha-L-rhamnopyranosyl-(1-->2)-(3,4-di-O-acetyl)-beta-D-fucopyranosyl ester, 3-O-beta-D-glucopyranosyl presenegenin 28-O-beta-D-galactopyranosyl-(1-->4)-beta-D-xylopyranosyl-(1-->4)- [(5-O-acetyl)-beta-D-apiofuranosyl-(1-->3)]-alpha-L-rhamnopyranosy l- (1-->2)-(3,4-di-O-acetyl)-beta-D-fucopyranosyl ester, 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl presenegenin 28-O-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)- (3-O-acetyl)-beta-D-fucopyranosyl ester, 3-O-beta-D-glucopyranosyl- (1-->2)-beta-D-glucopyranosyl presenegenin 28-O-beta-D-galactopyranosyl-(1-->4)-beta-D-xylopyranosyl- (1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-(4-O-acetyl)-beta-D- fucopyranosyl ester, 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl presenegenin 28-O-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)- [alpha-L-rhamnopyranosyl-(1-->3)]-(4-O-acetyl)-beta-D-fucopyranosyl ester, 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl presenegenin 28-O-beta-D-galactopyranosyl-(1-->4)-beta-D-xylopyranosyl-(1-->4)- [beta-D-apiofuranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)- (3,4-di-O-acetyl)-beta-D-fucopyranosyl ester and 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl presenegenin 28-O-beta-D-galactopyranosyl-(1-->4)-beta-D-xylopyranosyl-(1-->4)- [(5-O-acetyl)-beta-D-apiofuranosyl-(-->3)]-alpha-L-rhamnopyranosyl - (1-->2)-(3,4-di-O-acetyl)-beta-D-fucopyranosyl ester, respectively, on the basis of spectroscopic and chemical evidence.
Carbohydrate Sequence↗
Five new triterpene saponins, polygalasaponins XXVIII-XXXII from the root of Polygala japonica Houtt.
Five new oleanane-type saponins, polygalasaponins XXVIII-XXXII, along with one known saponin, polygalasaponin XXIV, and one known acylated sucrose, tenuifoliside C, were isolated from the root of Polygala japonica. The structures of these new compounds were elucidated as 3-O-beta-D-glucopyranosyl pesenegenin 28-O-beta-D-xylopyranosyl (1-->4)-alpha-L-rhamnopyranosyl (1-->2)-beta-D-fucopyranosyl ester, 3-O-beta-D-glucopyranosyl presenegenin 28-O-beta-D-galactopyranosyl (1-->5)-beta-D-apiofuranosyl (1-->4)-beta-D-xylopyranosyl (1-->4)-alpha-L-rhamno-pyranosyl (1-->2)-beta-D-fucopyranosyl ester, 3-O-beta-D-glucopyranosyl presenegenin 28-O-beta-D-galactopyranosyl (1-->4)-beta-D-xylopyranosyl (1-->4)-alpha-L-rhamnopyranosyl (1-->2)-[4-O-p-methoxycinnamoyl]-[beta-D-glucopyranosyl (1-->3)]-beta-D-fucopyranosyl ester, 3-O-beta-D-glucopyranosyl presenegenin 28-O-alpha-L-arabinopyranosyl (1-->3)-beta-D-xylopyranosyl (1-->4)-[beta-D-apiofuranosyl (1-->3)]-alpha-L-rhamnopyranosyl (1-->2)-[4-O-3,4,5-trimethoxycinnamoyl]-beta-D-fucopyranosyl ester, 3-O-beta-D-glucopyranosyl persenegenin 28-O-alpha-L-arabinopyranosyl (1-->3)-beta-D-xylopyranosyl (1-->4)-[beta-D-apiofuranosyl (1-->3)-alpha-L-rhamnopyranosyl (1-->2)-[4-O-p-methoxycinnamoyl]-[alpha-L-rhamnopyranosyl (1-->3)-beta-D-fucopyranosyl ester, respectively, on the basis of spectroscopic and chemical evidence.
Carbohydrate Sequence↗
[Study on history of cosmopolitan medicine in China].
Roughly, three stages may be differentiated in the studies on the history of cosmopolitan medicine in China. The first stage (1907-1949) is mainly focussed on the translation of articles on medical history from abroad, mostly for popularization of the knowledge on medical history. The second stage (1950-1979), like the first stage, is a stage of translation of papers on medical history from foreign countries, mainly the USSR and Eastern European countries. The third stage (1980-1995) deals with, in addition to translation, studies on special topics with increasing coverage for investigation.
China↗
[ACNU and methyl-CCNU in combination chemotherapy for advanced gastric cancer: a randomized comparative study. Shanghai ACNU Collaborative Study Group].
The study was conducted to compare the efficacy between a combined chemotherapy of ACNU (Nimustine hydrochloride, brand name Nidran), a new nitrosourea agent, and a combined chemotherapy of methyl-CCNU for advanced gastric cancer. One hundred and three cases of advanced gastric cancer were randomly allocated into Group A (Me-CCNU, 5-Fu and ADM) and Group B (ACNU, 5-Fu and ADM). The results showed that in Group A there was no CR or PR, while in Group B, although no CR, there were 8 PR (8/64 cases), denoting the response rate of 0% in Group A and 17.4% in Group B. The median survival period in Group A was 108 days and in Group B 112 days. Both groups well tolerated the treatment and there were no serious adverse effects. Quality of life (QOL) was better in Group B than in Group A. It is concluded that ACNU combination is superior to Me-CCNU combination for advanced gastric cancer.
Adenocarcinoma↗
[Diagnosis and treatment of pleural mesothelioma: a report of 40 cases].
Forty patients with pleural mesothelioma confirmed pathologically including 2 benign and 38 malignant lesions are reported. In the 38 malignant mesotheliomas, 12 were histopathologically defined while the rest were unclassified. In this series, 33 surgical resections and 3 thoracotomy biopsies were carried out, whereas 4 patients were not operated. In 36 thoracotomies, there was one death with an operative mortality of 2.8% (1/36). Of 33 surgical resections, 10 (31%) received combined therapy. Of the 3 thoracotomy biopsy cases, postoperative irradiation was given to one, irradiation plus chemotherapy to the second and no treatment to the third. In 4 who were not operated, one died without treatment, two accepted chemotherapy and the fourth was treated with irradiation plus chemotherapy. Only two (5%) of these 40 patients had history of exposure to asbestos. The pre- and intra-operative diagnostic conformity rate was 50%. Ten patients were lost from follow-up. The longest survival was twelve years and one month. The authors sum-up their 31-year (1963-1994) experience of this disease and discuss the occupational factors in etiology, clinical diagnosis, treatment options and the significance of pathological types on prognosis of pleural mesothelioma.
Adolescent↗