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Biomedical subjects

K S Chen

Publications and source records attributed to K S Chen.

At least 55 records · Page 3Linked to original sources

Thermal decomposition and reconstruction of hydroxyapatite in air atmosphere.

In this paper, the decomposition and reconstruction behavior of hydroxyapatite (HAP) during heating and cooling in air atmosphere were studied. The commercial HAP were chosen and gradually heated to 1500 degrees C and cooled to room temperature by a program controlled SiC heated furnace. X-ray diffractometer (XRD) and Fourier-transformed infrared (FTIR) analysis were used to investigate the change of crystalline phases and functional groups of HAP at different temperatures. Weight change of samples was recorded by thermogravimetric analysis (TGA) during heating and cooling. The results revealed that HAP would gradually release its OH- ions and transform into OHAP in the temperature of 1000-1360 degrees C. Above 1360 degrees C, the OHAP would decompose into TTCP and alpha TCP phase. The OH- stretching bands of HAP could be traced by FTIR even at the temperature of 1350 degrees C which was the eve of HAP decomposition. It reflected that the HAP did not dehydrate completely before decomposed. We speculated that some of OAP might be formed during dehydration and there were a great amount of OHAP still left in the system even up to the temperature of decomposition. In the temperature of 1400-1500 degrees C, there were no significant different in XRD patterns, only TTCP and alpha TCP crystalline phase were observed. When the HAP gradually cooled down from 1500 degrees C, a part of TTCP and alpha TCP would directly reconstruct into oxyapatite (OAP) around 1350 degrees C. OAP existed in the temperature of 1350 to 1300 degrees C during cooling. When the temperature down to 1290 degrees C, a part of TTCP and alpha TCP reconstructed into OHAP by rehydration reaction and OAP were rehydrated into OHAP as well. At 1100 degrees C, the rest of TTCP and alpha TCP would reconstitute into HAP. As the temperature decreased, the OHAP were gradually rehydrated and reconstituted into HAP.

Biocompatible Materials↗

pH of preparations affecting the on-off drug penetration behavior through the thermo-responsive liquid crystal-embedded membrane.

A liquid crystal (cholesteryl oleyl carbonate, COC)-embedded membrane with a controlled rate and higher reversibly thermo-responsive function was successfully fabricated by the vacuum filtration method. The aim of this study was to investigate the effect of the pH of aqueous solutions and gel preparations on the penetration of salbutamol sulfate through this thermo-responsive COC-embedded membrane. The results indicate that the on-off switching penetration behavior of salbutamol sulfate through the COC-embedded membrane in response to a repeatedly exchanging temperature cycle (10 <=> 25 degreesC) is not influenced by the pH of the medium. However, the pH-dependent ionization of salbutamol and the viscosity of the gel base, as well as the interaction between salbutamol and carbopol, might change the amount and the rate of salbutamol sulfate that penetrates across this COC-embedded membrane.

Acrylic Resins↗

Cloning, genomic structure, and expression of mouse ring finger protein gene Znf179.

ZNF179, a RING finger protein encoding gene, has been mapped within the critical deletion region for Smith-Magenis syndrome (SMS), a disorder characterized by mental retardation and multiple congenital anomalies associated with del(17)(p11.2). Here we report the cloning of Znf179, the mouse homologue of ZNF179, and characterization of its gene structure. The 3028-bp cDNA has a 1.9-kb open reading frame that contains a RING finger domain at its N-terminus and an alanine-rich and glycine-rich domain at its C-terminus. Znf179 genomic sequence includes 15 introns and spans about 10 kb on mouse chromosome 11, which maintains conserved synteny with human 17p. Northern analysis indicates that Znf179 is predominantly expressed in brain and testis. Although contained within the SMS common deletion interval, FISH experiments show that ZNF179 is not deleted in two SMS patients with smaller deletions.

Abnormalities, Multiple↗

Preparation of high-temperature stabilized beta-tricalcium phosphate by heating deficient hydroxyapatite with Na4P2O7 x 10H2O addition.

In this paper, the high-temperature stabilized beta-tricalcium phosphate (betaTCP, beta-Ca3(PO4)2) were prepared by heating the deficient HAP (d-HAP, Ca10-x(HPO4)x(PO4)6-x(OH)2-x) with tetra-sodium diphosphate decahydrate (NP, Na4P2O7 x 10H2O) addition. The betaTCP, d-HAP and d-HAP doped with 2.5, 5, 7.5 and 10 wt % NP were heated to different temperatures and were investigated by X-ray diffraction analysis (XRD) and Fourier-transformed infrared spectroscopy (FTIR). The results demonstrated that the HPO4(2-) of d-HAP condensed into P2O7(4-) occurred before 650 degrees C. The P2O7(4-) ions could be traced in the FTIR spectrum when the d-HAP was heated up to 750 degrees C. The reaction of P2O7(4-) with OH- did not occur instantly but over a wide range of temperatures. The d-HAP doped with NP would decrease the decomposition temperature of d-HAP. NP doped into d-HAP not only induced the d-HAP decomposition at lower temperature but also stabilized the betaTCP crystal structure at higher-temperature. It could also increase the conversion temperature of betaTCP to alphaTCP from 1180 degrees C up to 1300 degrees C. We could successfully prepare high-temperature (up to 1300 C) stabilized ffTCP by heating NP doped d-HAP.

Calcium Phosphates↗

Genetic mapping refines DFNB3 to 17p11.2, suggests multiple alleles of DFNB3, and supports homology to the mouse model shaker-2.

The nonsyndromic congenital recessive deafness gene, DFNB3, first identified in Bengkala, Bali, was mapped to a approximately 12-cM interval on chromosome 17. New short tandem repeats (STRs) and additional DNA samples were used to identify recombinants that constrain the DFNB3 interval to less, similar6 cM on 17p11.2. Affected individuals from Bengkala and affected members of a family with hereditary deafness who were from Bila, a village neighboring Bengkala, were homozygous for the same alleles for six adjacent STRs in the DFNB3 region and were heterozygous for other distal markers, thus limiting DFNB3 to an approximately 3-cM interval. Nonsyndromic deafness segregating in two unrelated consanguineous Indian families, M21 and I-1924, were also linked to the DFNB3 region. Haplotype analysis indicates that the DFNB3 mutations in the three pedigrees most likely arose independently and suggests that DFNB3 makes a significant contribution to hereditary deafness worldwide. On the basis of conserved synteny, mouse deafness mutations shaker-2 (sh2) and sh2J are proposed as models of DFNB3. Genetic mapping has refined sh2 to a 0.6-cM interval of chromosome 11. Three homologous genes map within the sh2 and DFNB3 intervals, suggesting that sh2 is the homologue of DFNB3.

Alleles↗

Neurodegenerative Alzheimer-like pathology in PDAPP 717V-->F transgenic mice.

In summary, PDAPP mice overexpressing a mutation associated with some cases of familial early-onset AD express several of the major pathological hallmarks associated with AD. Amyloid plaques in PDAPP mice appear quite similar to A beta deposits in AD as shown by a variety of different antibodies and stains, and are of both the diffuse and compacted varieties. Additionally, a subset of these amyloid plaques appear to be neuritic plaques. Neurodegenerative changes, including the loss of synaptic and dendritic proteins, abnormal phosphorylation of cytoskeletal elements, subcellular degenerative changes, and the deposition of lysosomal and acute phase proteins has also been seen in PDAPP mouse brains. Reactive astrocytosis and microgliosis have also been observed in association with the amyloid plaques in the PDAPP mice. No neurofibrillary tangles or paired helical filaments have been found in the mice to date. It remains unknown whether mice are capable of generating these in a manner comparable to AD in less than two years. Extensive behavioral analyses are currently being performed in these mice, and preliminary results indicate that the PDAPP mice are significantly impaired on a variety of different learning and memory tests. In conclusion, the PDAPP mouse model doesn't display all the pathological hallmarks of AD, but it does display most of them in a robust manner that increases with age and gene dosage. Therefore, this transgenic model provides evidence that alterations in APP processing and A beta production can result in AD-like neuropathology, can contribute to a mechanistic understanding of AD (since examination of AD brains yields a static view, and we are unable to view the development of various pathological changes), as well as providing an useful animal model for the testing of various therapeutic interventions directed towards specific aspects of the neurodegenerative process.

Alzheimer Disease↗

Disruption of a single allele of the nerve growth factor gene results in atrophy of basal forebrain cholinergic neurons and memory deficits.

Administration of nerve growth factor (NGF) to aged or lesioned animals has been shown to reverse the atrophy of basal forebrain cholinergic neurons and ameliorate behavioral deficits. To examine the importance of endogenous NGF in the survival of basal forebrain cholinergic cells and in spatial memory, mice bearing a disruption mutation in one allele of the NGF gene were studied. Heterozygous mutant mice (ngf+/-) have reduced levels of NGF mRNA and protein within the hippocampus and were found to display significant deficits in memory acquisition and retention in the Morris water maze. The behavioral deficits observed in NGF-deficient mice were accompanied by both shrinkage and loss of septal cells expressing cholinergic markers and by a decrease in cholinergic innervation of the hippocampus. Infusions of NGF into the lateral ventricle of adult ngf+/- mice abolished the deficits on the water maze task. Prolonged exposure to NGF may be required to induce cognitive effects, because reversal of the acquisition deficit was seen after long (5 weeks) but not short (3 d) infusion. Although NGF administration did not result in any improvement in the number of septal cells labeled for choline acetyltransferase, this treatment did effectively correct the deficits in both size of cholinergic neurons and density of cholinergic innervation of the hippocampus. These findings demonstrate the importance of endogenous NGF for survival and function of basal forebrain cholinergic neurons and reveal that partial depletion of this trophic factor is associated with measurable deficits in learning and memory.

Acetylcholinesterase↗

Genomic structure, evolution, and expression of human FLII, a gelsolin and leucine-rich-repeat family member: overlap with LLGL.

The Drosophila melanogaster flightless-I gene is involved in cellularization processes in early embryogenesis and in the structural organization of indirect flight muscle. The encoded protein contains a gelsolin-like actin binding domain and an N-terminal leucine-rich repeat protein-protein interaction domain. The homologous human FLII gene encodes a 1269-residue protein with 58% amino acid sequence identity and is deleted in Smith-Magenis syndrome. We have cloned the FLII gene and determined its nucleotide sequence (14.1 kb). FLII has 29 introns, compared with 13 in Caenorhabditis elegans and 3 in D. melanogaster. The positions of several introns are conserved in FLII-related genes and in the domains and subdomains of the gelsolin-like regions giving indications of gelsolin gene family evolution. In keeping with its function in indirect flight muscle in Drosophila, the human FLII gene was most highly expressed in muscle. The FLII gene lies adjacent to LLGL, the human homologue of the D. melanogaster tumor suppressor gene lethal(2) giant larvae. The 3' end of the FLII transcript overlaps the 3' end of the LLGL transcript, and the corresponding mouse genes Fliih and Llglh also overlap. The overlap region contains poly(A) signals for both genes and is strongly conserved between human and mouse.

Animals↗

Degradation behaviour of a new bioceramic: Ca2P2O7 with addition of Na4P2O7.10H2O.

A newly produced bioceramic, beta-Ca2P2O7 with addition of Na4P2O7.10H2O (SDCP), has been implanted into the femoral condyle of rabbits. Within 6 weeks after implantation, most of the bioceramic is replaced by new woven bone. On the contrary, block from hydroxyapatite (HA) and beta-tricalcium phosphate (beta-TCP), which are osteoconductible, do not resorb within a short period of time. We believe that the biodegradable behaviour of SDCP may occur in two steps. The first and most important step is the digestion of particles and migration of the particles by phagocytosis. The object of this study is to examine the change in morphologies, chemical compositions and crystal structure of SDCP after soaking in distilled water for a certain period of time. The SDCP ceramic was also co-cultured with leucocytes to observe how the SDCP particles were digested by the leucocytes, so that the mechanism of biodegradable behaviour of SDCP ceramic in vivo might be clarified. Four types of sintered calcium phosphate ceramics were tested in the experiment: SDCP, pure beta-Ca2P2O7 (DCP), HA and beta-TCP. They wee soaked in distilled water at 37 degrees C for up to 30 days. The microstructure and morphology of crystals deposited on the surface were observed using scanning electron microscopy. Sodium, calcium and phosphorus ion contents in the supernatant solution were detected by atomic absorption analysis and ion coupled plasma. In summary, HA and DCP showed no significant evidence of dissolution in distilled water. In static distilled water, calcium ions may be released from beta-TCP into solution during the initial 7 days and then converted into HA by reprecipitation. The results showed that the SDCP was firstly dissolved into small grains or fragments by the solution. The small fragments should be so small as to be digested by the phagocytes in a physiological environment.

Animals↗

Bioactive alkaloids from Illigera luzonensis.

Using antiplatelet aggregation as a guide to fractionation, seven aporphines, actinodaphnine (1), N-methylactinodaphnine (2), launobine (3), dicentrine (4), O-methylbulbocapnine (5), hernovine (7), and bulbocapnine (9), and two oxoaporphines, dicentrinone (6) and liriodenine (8), were isolated from the stems of Illigera luzonensis. Among them, compounds 2, 4, 5, 8, and 9 were isolated for the first time from this species. Moreover, compounds 1-5, and 8 showed significant antiplatelet aggregation and compounds 1 and 6 exhibited significant vasorelaxant activities, respectively.

Alkaloids↗

Homologous recombination of a flanking repeat gene cluster is a mechanism for a common contiguous gene deletion syndrome.

Smith-Magenis syndrome (SMS), caused by del(17)p11.2, represents one of the most frequently observed human microdeletion syndromes. We have identified three copies of a low-copy-number repeat (SMS-REPs) located within and flanking the SMS common deletion region and show that SMS-REP represents a repeated gene cluster. We have isolated a corresponding cDNA clone that identifies a novel junction fragment from 29 unrelated SMS patients and a different-sized junction fragment from a patient with dup(17)p11.2. Our results suggest that homologous recombination of a flanking repeat gene cluster is a mechanism for this common microdeletion syndrome.

Abnormalities, Multiple↗

Hemostatic and fibrinolytic response to desmopressin in uremic patients.

Desmopressin (DDAVP) 0.3 micrograms/kg was infused in 20 uremic patients with prolong bleeding time. Prior to infusion, the uremic patients had a reduced level of tissue plasminogen activator (t-PA), normal levels of von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (vWF:RCo) and elevated level of factor VIII coagulant activity (FVIII:C). Patients with lower hematocrit or t-PA levels tended to have a longer bleeding time. One hour after DDAVP infusion, the bleeding time was shortened significantly. This improvement was significant in all patient groups irrespective of the high or low initial levels of factor VIII complex components. Plasma levels of FVIII:C, vWF:Ag, vWF:RCo and t-PA all increased significantly. The magnitude of increase in these factors, however, was not significantly correlated with the extent of bleeding time shortening. The multiple regression model for predicting the extent of bleeding time shortening suggested only two variables, viz initial bleeding time and posttreatment FVIII:C activity to be of significance. The present results indicate that the hemostatic response to DDAVP is uniform in uremic patients, regardless of whether the initial activities of factor VIII complex components are high or low. Posttreatment FVIII:C activity appears to play a significant role in the hemostatic action of DDAVP. Furthermore, a depressed fibrinolytic activity was generally observed to concur with the hemostatic defect in uremic patients.

Adolescent↗

Baclofen toxicity in patients with severely impaired renal function.

OBJECTIVE: To report the toxic effects of baclofen in patients with severely impaired renal function. DATA SOURCES: From 1991 to 1995, nine patients with severely impaired renal function (2 not receiving dialysis, 1 undergoing continuous ambulatory peritoneal dialysis [CAPD], and 6 receiving maintenance hemodialysis), who exhibited clinical toxicity after baclofen therapy at our hospital were included for analysis. Another seven cases from the literature obtained by computerized (MEDLINE) and manual (Index Medicus) search methods published between 1980 and 1995 were also reviewed. INTERVENTION: Among our nine patients, the six undergoing chronic hemodialysis and one not undergoing dialysis received early (< 48 h) hemodialysis after toxic symptoms developed. The patient undergoing CAPD received late hemodialysis (> 72 h), and the other patient who had not undergone dialysis received only supportive care. RESULTS: A review of these 16 cases revealed that most patients received only small doses and very short-term baclofen therapy. Altered consciousness was the major presenting feature. Severe acute complications, such as seizures and respiratory depression, were relatively uncommon among patients with severely impaired renal function. However, abdominal pain, which has previously rarely been reported, was noted in five of our nine patients. Most patients showed clinical improvement after hemodialysis. An analysis of these nine patients revealed that those who received early hemodialysis had a shorter recovery time than the patient who received only supportive care (2.71 +/- 0.42, respectively, vs. 9 d; p < 0.01). A lag of several hours between the end of the hemodialysis session and an improvement in the level of consciousness was noted. DISCUSSION: As most patients with severely impaired renal function developed toxic symptoms soon after initiating a low-dose baclofen regimen, the accumulated dosage was small and severe complications were less common. Abdominal pain may have occurred as a result of the gamma-aminobutyric acid-mediated cholinergic effect exerted by baclofen. The delay in conscious recovery after hemodialysis may be due to a delay in the clearance of baclofen from the central nervous system. CONCLUSIONS: Patients with severely impaired renal function generally develop baclofen intoxication soon after the initiation of low-dose therapy. Thus, the administration of baclofen, regardless of the dosage, in these patients is not appropriate. Abdominal pain, in addition to altered consciousness, is a common presenting feature in patients with renal failure who have baclofen intoxication. Hemodialysis is effective in alleviating the clinical symptoms and shortening the recovery time for such patients.

Adult↗

Reactive oxygen species are involved in nickel inhibition of DNA repair.

Nickel has been shown to inhibit DNA repair in a way that may play a role in its toxicity. Since nickel treatment increases cellular reactive oxygen species (ROS), we have investigated the involvement of ROS in nickel inhibition of DNA repair. Inhibition of glutathione synthesis or catalase activity increased the enhancing effect of nickel on the cytotoxicity of ultraviolet (UV) light. Inhibition of catalase and glutathione peroxidase activities also enhanced the retardation effect of nickel on the rejoining of DNA strand breaks accumulated by hydroxyurea plus cytosine-beta-D-arabinofuranoside in UV-irradiated cells. Since DNA polymerization and ligation are involved in the DNA-break rejoining, we have investigated the effect of ROS on these two steps in an extract of Chinese hamster ovary cells. Nickel inhibition of the incorporation of (3H)dTTP into the DNase I-activated calf thymus DNA was stronger than the ligation of poly(dA) x oligo(dT), whereas H2O2 was more potent in inhibiting DNA ligation than DNA polymerization. Nickel, in the presence of H2O2, exhibited a synergistic inhibition on both DNA polymerization and ligation and caused protein fragmentation. In addition, glutathione could completely recover the inhibition by nickel or H2O2 alone but only partially recover the inhibition by nickel plus H2O2. Therefore, nickel may bind to DNA-repair enzymes and generate oxygen-free radicals to cause protein degradation in situ. This irreversible damage to the proteins involved in DNA repair, replication, recombination, and transcription could be important for the toxic effects of nickel.

Animals↗

Antiplatelet of vasorelaxing actions of some benzylisoquinoline and phenanthrene alkaloids.

Members of a series of benzylisoquinoline and phenanthrene alkaloids were tested for their antiplatelet and vasorelaxing actions. Atherosperminine HClO4 (15) and atherosperminium I (16) showed strong inhibition of adenosine 5'-diphosphate-induced platelet aggregation. dl-N-Methylcoclaurine (1), dl-coclaurine (6), 15, 16, xylopine hydroxylamine (18), and atherosperminine N-oxide (19) showed strong inhibition of arachidonic acid-induced platelet aggregation. Compounds 1, 15, 16, dicentrine methine (17), 18, and 19 showed strong inhibition of collagen-induced platelet aggregation. d-(-)-Magnocurarine I (8), 15, and 16 showed strong inhibition of platelet-activating factor-induced platelet aggregation. Compounds 15, 17, and 19 showed vasorelaxing action in rat thoracic aorta.

Alkaloids↗

Permeation behavior of salbutamol sulfate through hydrophilic and hydrophobic membranes embedded by thermo-responsive cholesteryl oleyl carbonate.

PURPOSE: To investigate the suitability of hydrophilic or hydrophobic membranes for use as potential thermo-responsive drug delivery system. METHODS: Liquid crystal was embedded in membranes using vacuum filtration method to control the penetration rate of salbutamol sulfate. Cholesteryl oleyl carbonate (COC) with smectic-cholesteric phase transition temperature near 18 degrees C was used as a model liquid crystal. RESULTS: It indicates only hydrophilic salbutamol sulfate can penetrate through the hydrophilic membranes embedded with or without COC, in which the permeation is mainly governed by the adsorption of COC. However, the hydrophilic drug do not pass through the hydrophobic membranes even if not embedded with COC. The void volume of the membrane also influences the penetration of salbutamol sulfate. The higher thermo-response efficacy of the COC-embedded membranes can be explained not only by less permeability through matrix part of the membrane but also by higher thermal motion of the COC molecules due to above the phase transition temperature. CONCLUSIONS: A COC-embedded membrane with rate-controlled and thermo-responsive function is easily prepared by vacuum filtration method. High reversibly thermo-responsive function can be achieved by choosing membrane and COC concentration properly.

Albuterol↗