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Biomedical subjects

C Liu

Publications and source records attributed to C Liu.

At least 523 records · Page 29Linked to original sources

Effects of size of macrocyclic polyamides on their rate of diffusion in model membranes.

A series of homologous amphiphilic molecules with surface areas in the range of 0.3 nm2 to 3.0 nm2 were prepared and used to investigate the diffusion in model dimyristoylphosphatidylcholine membranes as a function of temperature. The diffusion behavior of smaller molecules can be described by the interfacial viscosity limited free area theory promoted by Vaz and his co-workers, and that of the larger molecules can best be modeled by a recent interpretation of the theoretical description proposed by Evans and Sackmann. The experimental data show that the rate of diffusion is controlled by the size of the molecules at the interface of the lipid membrane, and provide evidence for a view of the membrane as a hydrodynamic triple layer with a low-viscosity central layer encased by two more viscous, yet fluid, layers.

Benzoxazoles↗

Evaluation of the biocompatibility of a nonceramic hydroxyapatite.

In this study, the biocompatibility of calcium phosphate cement (CPC) was systematically investigated, which included systemic injection acute toxicity assay, cell culture cytotoxicity assay, gene mutation assay (Ames test), chromosome aberration assay (micronucleus test), DNA damage assay (unscheduled DNA synthesis test) and implant histological evaluation. The results showed that the CPC had no toxicity and all tests for mutagenicity and potential carcinogenicity of CPC extracts are negative. CPC was implanted into the femurs of rabbits under no-load condition and the histology of specimens revealed that the implant tightly joined with the surrounding bone, only a very slight histological inflammatory reaction occurred. Thus, CPC is a highly biocompatible material and seems to be safe for application in humans.

Animals↗

Apoptosis and hair cell degeneration in the vestibular sensory epithelia of the guinea pig following a gentamicin insult.

Apoptosis plays a key role in the steady state of continuously renewing tissues. The goal of this study was to determine whether apoptosis was a mode of hair cell loss in mammalian inner ear sensory epithelia. Hair cell loss was induced by systemic treatment with the ototoxic aminoglycoside antibiotic gentamicin in guinea pig. The vestibular sensory epithelia were examined at different times after administration via semi-thin and thin sections in situ labeling by the terminal deoxynucleotidyl transferase catalysis of digoxigenin tagged nucleotides to the free 3'-OH ends of fragmented DNA. Apoptotic labeling was detected 3-7 days after treatment. The majority of the apoptotic nuclei was found adjacent to the luminal surface. Analysis of semi-thin and thin sections revealed two modes of hair cell degeneration: (1) Apoptosis within the epithelium, showing typical morphological changes of condensation and fragmentation of the nucleus and modifications of cytoplasmic organelles. (2) Swelling of the cell, vacuolation and distortion of cell shape, and extrusion into the lumen. The results indicated that vestibular hair cells undergo apoptosis after ototoxic traumas.

Animals↗

Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock.

The pineal hormone melatonin elicits two effects on the suprachiasmatic nuclei (SCN): acute neuronal inhibition and phase-shifting. Melatonin evokes its biological effects through G protein-coupled receptors. Since the Mel1a melatonin receptor may transduce the major neurobiological actions of melatonin in mammals, we examined whether it mediates both melatonin effects on SCN function by using mice with targeted disruption of the Mel1a receptor. The Mel1a receptor accounts for all detectable, high affinity melatonin binding in mouse brain. Functionally, this receptor is necessary for the acute inhibitory action of melatonin on the SCN. Melatonin-induced phase shifts, however, are only modestly altered in the receptor-deficient mice; pertussis toxin still blocks melatonin-induced phase shifts in Mel1a receptor-deficient mice. The other melatonin receptor subtype, the Mel1b receptor, is expressed in mouse SCN, implicating it in the phase-shifting response. The results provide a molecular basis for two distinct, mechanistically separable effects of melatonin on SCN physiology.

Animals↗

Commissioning of enhanced dynamic wedge on a ROCS RTP system.

The enhanced dynamic wedge (EDW) is clinically commissioned on a ROCS RTPS (Version 5.03) in a manner similar to that used for any standard physical wedge. The required data set for implementation includes central axis depth dose, and open and wedge beam profiles at several depths and output factors. The features distinguishing the EDW from the physical wedge are a sharp change in output with field size in the wedge plane and a primary intensity difference at the end of the wedge field because the moving jaw stops 0.5 cm short of the fixed jaw position for all field sizes, for safety reasons. The monitor unit (MU) calculation for an EDW field in ROCS is based on scaling factors that are derived from a normalized golden STT (NGSTT). This approach requires no change in the data file structure of ROCS. It was found that the output for EDW is very sensitive to the value of final moving jaw position. Every 0.5 cm difference between planned and set value can cause 3.5% error.

Radiotherapy Planning, Computer-Assisted↗

Targeted damage effects of high intensity focused ultrasound (HIFU) on liver tissues of Guizhou Province miniswine.

HIFU can pass through tissues and accurately damage target tissues inside organisms. This article reports on the oriented damage effects of HIFU upon miniswine internal and external liver tissues, and suggests a new conception of the 'biological focal field'. The results revealed that: (1) HIFU can be used to damage accurately liver tissues under the guide of a B-modal ultrasound device; (2) the scope of the injury is connected with sound intensity and irradiation time; and (3) the different layers of tissue through which the ultrasound has passed remain undamaged.

Animals↗

Differential expression of TPS11, a phosphate starvation-induced gene in tomato.

Plants respond to phosphate (Pi) deficiency through adaptive mechanisms involving several morphological, biochemical and molecular changes. In this study, we have characterized the structure and expression of a tomato (Lycopersicon esculentum L.) phosphate starvation-induced gene (TPSI1). A 3.5 kb genomic fragment containing the 474 bp TPSI1 transcript was isolated. The TPSI1 transcript contains an open reading frame of 174 nucleotides encoding a 58 amino acid polypeptide. TPSI1 is an intron-less gene and only one copy could be detected in the tomato genome. The promoter region of TPSI1 contains several conserved sequences found in phosphate starvation induced genes of yeast. The TPSI1 transcripts are rapidly induced in roots and leaves during Pi starvation. A significant increase in the TPSI1 mRNA was observed in cell cultures and roots after 3 and 12 h of Pi starvation, respectively. Induction of the TPSI1 gene appears to be a response specific to Pi starvation since it is not affected by starvation of other nutrients (nitrogen, potassium and iron). The amount of TPSI1 transcript decreased rapidly when Pi-starved tomato plants were resupplied with Pi. These results suggest that TPSI1 gene expression may be a part of the early Pi starvation response mechanism in plants.

Adaptation, Physiological↗

Pharmacokinetics and acute toxicology of intraventricular 131 I-monoclonal antibody targeting disialoganglioside in non-human primates.

Tumors metastatic to the leptomeninges are often incurable despite current aggressive treatment modalities. Regional therapy by intrathecal administration of monoclonal antibodies (MoAbs) can maximize their concentration to tumor sites while reducing systemic toxicities. Anti-GD2 antibody 3F8 has successfully targeted human neuroectoderm derived tumors. Disialoganglioside GD2 expression in the central nervous system is identical between humans and cynomolgus monkeys. We studied the pharmacokinetics and the acute and subacute toxicities of intraventricular 131I-3F8 in 8 cynomolgus monkeys. Four animals were purposely immunized with intravenous 3F8 administered 2-4 weeks prior to injections. All animals remained clinically stable. Toxicities included weight loss, fever and CSF leukocytosis. One animal developed a left-sided hemiparesis following his seventh injection, presumably due to a local drug accumulation in the setting of an intermittently patent catheter. The estimated radiation dose to the CSF was 19-48 Gy in the immunized monkeys and 19-82 Gy in the nonimmunized monkeys, and to blood was 0.11-0.98 Gy and 0.29-2.03 Gy, respectively. Histopathology revealed chronic reactive changes adjacent to the region of catheter placement and a focal vasculitis in 2 animals. Peripheral blood counts and bone marrow examinations remained normal. Because of the blood-brain barrier, CSF monkey-anti-mouse antibody titers were less than 10 per cent of those in the serum. In contrast to the CSF radioactivity clearance which was similar in all animals, blood clearance was substantially accelerated in 3F8-immunized animals versus controls. Correspondingly, the CSF to blood dose ratio was improved 1.3 to 6.6 fold (mean 3.5). We conclude that intraventricular administration of 131I-3F8 in primates is tolerable. It can deliver very high doses of radiation to the CSF space with minimal toxicity to blood and bone marrow. Serum anti-mouse antibody accelerates the clearance of 131I-3F8 in blood and may improve the therapeutic index.

Animals↗

Effect of crystal seeding on the hydration of calcium phosphate cement.

In this paper, the effect of crystal seeding on the hydration of calcium phosphate cement (CPC) has been carefully investigated. The setting time of the CPC slurry not containing any crystal seeds was 150 min, while the setting time for the specimen containing 5 wt% low crystallinity hydroxyapatite used as a crystal seed was 7 min. This improvement in the setting time was due to HAP serving as a substrate for heterogeneous nucleation which accelerated nucleation. In addition, the compressive strength of the specimen containing the crystal seeding was deduced and we report values different from those previously reported in the literature. The calorimetric curve indicated that crystal seeding could reduce the induction period. A.c. impedance spectroscopy revealed that at the beginning of hydration, the rate of reaction increased and also that the mean diameter and porosity decreased as the seed content increased. At the end of the hydration reaction the situation was changed with the mean diameter and porosity in the sample without any seeds being a minimum, which indicated that the compressive strength was a maximum. This result could be explained by the dissolution and reprecipitation of small hydration products produced by the high rate of reaction produced by the introduction of the crystal seeds.

Journal Article↗

The prevalence of cataract in two villages of northern Pakistan with different levels of ultraviolet radiation.

To study the effect of ultraviolet (UV) light on the development of age-related cataract, a community-based cross-sectional study was undertaken in two villages in the mountainous Northern Areas of Pakistan. The relative UV light exposure was calculated by the UK Universities Global Atmospheric Modelling Program using the variables direct sunlight hours per day, latitude and ground reflectivity. A total of 797 subjects (410 men, 387 women) over the age of 40 years from both villages were examined for the presence of cataract. The prevalence of cataract increased with age (p < 0.001) and was significantly higher in women at all ages (p < 0.01). There was no significant difference in the overall prevalence of cataract between the two villages. The male population in each village was subdivided into those who worked predominantly indoors and those who worked predominantly outdoors. All women worked outdoors. There was no significant difference in the prevalence of cataract between the male outdoor workers in the two villages. The indoor workers in the village with higher UV light exposure (Hunza) had a significantly higher cataract prevalence (p < 0.001) than the indoor workers in the village with lower UV light exposure (Nomol). In the village with lower UV light exposure (Nomol), the male outdoor workers had a significantly higher prevalence of cataract than the male indoor workers (p < 0.001). There was no significant difference in the prevalence of cataract between the male indoor and outdoor workers in the village with higher UV light exposure (Hunza). Overall, these results are not strongly supportive of UV light being of major importance in cataractogenesis, but they are consistent with a saturation model of UV light as a risk factor for cataract formation.

Adult↗

Early reconstitution of immunity and decreased severity of herpes zoster in bone marrow transplant recipients immunized with inactivated varicella vaccine.

Varicella-zoster virus (VZV) causes herpes zoster after bone marrow transplantation (BMT). The immunogenicity of heat-inactivated varicella vaccine and effects on VZV pathogenesis were evaluated in 75 BMT patients randomized to receive vaccine or no intervention. Among 14 patients given a single dose at 1 month after transplantation, the mean (+/-SE) stimulation index (SI) was 12.20 +/- 3.13 compared with 4.83 +/- 2.74 (P = .036) in 14 unvaccinated patients, but clinical disease was not altered. Among 24 patients vaccinated at 1, 2, and 3 months, mean SI was 8.43 +/- 3.89 versus 2.00 +/- 0.33 (P = .014) in 23 unvaccinated patients at 4 months and 8.56 +/- 2.81 versus 5.30 +/- 2.47 (P = .043) at 5 months. Disease severity associated with VZV reactivation was decreased dramatically in vaccinees given three doses; severity scores were 6.4 +/- 1.0 versus 11.8 +/- 1.1 (P = .007). This experience with varicella vaccine in BMT patients is the first evidence that active immunization can reduce morbidity due to herpesvirus reactivation in high-risk populations.

Adolescent↗

"Growing pains": clinical and behavioral correlates in a community sample.

Parents of 183 children identified them as having "pain in arms, legs, or joints during the previous 12 months." This group was compared with a group of children without pains selected randomly from the rest of a 1605-member community-based cohort in a study of chronic illness. The pains were most likely to be deep seated, to involve predominantly the lower limbs, and to be described in vague, nonspecific terms. These children were significantly more likely to have recurrent abdominal pain, a negative mood, and behavior problems, and to be aggressive, anxious, and hyperactive. There were no differences between the groups on any teacher ratings of behavior, temperament, social skills, or academic achievement. We conclude that children with "growing pains" are rated by their parents, but not their teachers, as having different temperamental and behavioral profiles than controls. These data suggest a psychosocial contribution to growing pains akin to that seen with other pain syndromes.

Adolescent↗

A targeting-and-extracting technique to enhance hearing in the presence of competing speech.

A targeting-and-extracting procedure of speech enhancement for hearing aids in the presence of background noise, especially competing speech, is proposed. The procedure is composed of two steps: targeting by a fixed (or deterministic) beamforming array, followed by a post-targeting extracting step. Emphasis is placed on the extracting step, which performs noise cancellation based on the acoustic difference between the desired speech and interfering speech. Either comb filtering or attenuation is applied to the signal in accordance with the current voiced/unvoiced/silence state of the desired signal. The comb filter design is based on the fundamental pitch frequency of the desired speech. Algorithms for deciding the voiced/unvoiced/silence state and determining the fundamental frequency are developed. The performance of the system is evaluated through computer simulation. The simulation results indicate significant noise cancellation and intelligibility improvement.

Amplifiers, Electronic↗

FLAG epitope positioned in an external loop preserves normal biophysical properties of CFTR.

We asked whether inclusion of the FLAG epitope in the fourth extracellular loop of the cystic fibrosis transmembrane conductance regulator (M2-901/CFTR), which permits detection of cell surface expression, affected CFTR's biophysical properties or channel regulation by kinases, phosphatases, and nucleotides. Channel activity of M2-901/CFTR was evaluated in numerous cell types and expression systems to characterize its gating and regulation. Our results show that M2-901/CFTR required adenosine 3',5'-cyclic monophosphate-dependent protein kinase phosphorylation to initiate channel activity. Subsequently, ATP alone was sufficient to support channel gating, and ADP inhibited channel opening. Current fluctuation analysis indicated that the nucleotide-dependent gating rates were indistinguishable from those of wild-type (wt) cystic fibrosis transmembrane conductance regulator (CFTR). Channel conductance in symmetric Cl- (11.2 pS), anion permeability ratio (1.66), and block by gluconate indicate that the anion conduction pathway is indistinguishable from wtCFTR. Sulfonylureas (glibenclamide and LY-295501) inhibited M2-901/ CFTR channel activity by an identical mechanism to that described for wtCFTR. Finally, CFTR-dependent insertion and retrieval of cell membrane was unaffected by the presence of the FLAG epitope. These results indicate that this structural alteration does not affect the control mechanisms for channel gating and suggest that the fourth extracellular loop of CFTR does not contribute to the ion pore. Detection of M2-901/CFTR by a commercially available monoclonal antibody (M2), together with presentation of normal functional properties, makes M2-901/CFTR a valuable tool to evaluate CFTR protein expression and cellular location.

Animals↗

Detection of metastatic neuroblastoma in bone marrow: when is routine marrow histology insensitive?

PURPOSE: To measure the sensitivity of histologic examination in detecting metastatic solid tumor in bone marrow. PATIENTS AND METHODS: A total of 145 patients with stage 4 neuroblastoma underwent 840 marrow examinations, each consisting of six sites (four aspirates and two biopsies), from October 1990 to June 1996 at Memorial Sloan-Kettering Cancer Center. Metastasis was detected by either histology (aspirate by Wright-Giemse and biopsy by Hematoxylin-Eosin stains) or immunostaining of aspirates using anti-G(D2) monoclonal antibodies. RESULTS: The absence of tumor by histology at a single marrow site was a poor guarantee of the absence of disease. The number of false-negative sites increased as the percent of G(D2)-positive tumor cells in the marrow decreased: zero of six if tumor cell count was > or = 1%, and approximately six of six sites if < or = 0.003%. Sensitivity was comparable between marrow aspirate and biopsy. A lower bound (LB) for the probability of false-negative histology was calculated from the (1) discordance among the six marrow samplings and (2) comparison with immunofluorescence. When disease was extensive (eg, at diagnosis), the LB was 0.13 and 0.3, respectively. After treatment, it increased to 0.37 and 0.8. Examining multiple marrow sites can decrease the LB to 0.15. However, at least three sites have to be negative at relapse, six at diagnosis, and more than 50 during treatment or off-therapy follow-up. The marginal decrease in the LB by additional samplings rapidly diminished to less than 0.05 after two sites. CONCLUSION: Except at diagnosis and relapse when gross disease is present, marrow sampling by histology has limited sensitivity. Current practice grossly underestimates the true prevalence of marrow disease.

Biomarkers, Tumor↗

Expression and characterization of a putative high affinity human soluble leptin receptor.

Leptin, a circulating 16-kDa protein secreted by adipocytes, decreases body weight by reducing food intake and enhancing energy utilization. Leptin receptors that share homology to the glycoprotein gp130 have been recently cloned. In addition, differentially spliced leptin receptor messenger RNAs have been identified. Functional mutations in either the leptin or leptin receptor gene cause obesity. In the present study, expression of the full length human leptin receptor complementary DNA encoding the long cytoplasmic domain of leptin receptor in COS7 cells resulted in high affinity membrane binding of 125I-leptin (Ki approximately 200 pM); no detectable binding was present in the medium. In addition, we expressed the extracellular domain of human leptin receptor in COS7 cells and identified a soluble leptin receptor in the conditioned medium that binds human and mouse leptin with high affinity comparable with the full length membrane receptor. Transfected COS7 cells expressing the soluble leptin receptor also demonstrated modest specific 125I-leptin binding in whole cells, presumably due to association of the soluble leptin receptor to cell membrane proteins. Data from cross-linking studies identified two specific bands in the 125I-leptin/soluble leptin receptor complex with molecular masses of approximately 130-150 kDa and 300 kDa. The 130-150 kDa molecular mass was confirmed in Western blot analysis and Coomassie staining of the purified soluble receptor and probably represents the glycosylated form of the receptor. The 300-kDa band most likely represents a homodimer of the soluble leptin receptor complex because HPLC gel filtration analysis of the 125I-leptin/soluble leptin receptor complex identified a single peak corresponding to a molecular mass of approximately 340 kDa. The soluble leptin receptor antagonized 125I-leptin binding to the membrane receptor, suggesting its potential utility as a functional tool for determining the role of endogenous leptin.

Animals↗

Zona pellucida glycoprotein mZP3 bioactivity is not dependent on the extent of glycosylation of its polypeptide or on sulfation and sialylation of its oligosaccharides.

During fertilization in mice, free-swimming sperm bind to mZP3, one of three egg zona pellucida glycoproteins. Sperm recognize and bind to specific serine/threonine-linked (O-linked) oligosaccharides located at the mZP3 combining site for sperm. Shortly after binding to mZP3, sperm undergo the acrosome reaction, a form of cellular exocytosis. Here, we examined the influence of extent of glycosylation, sulfation, and sialylation of mZP3 (M(r) approximately 65,000-100,000) on its bioactivity; i.e. its ability to inhibit binding of sperm to eggs and to induce the acrosome reaction in vitro. Low (av. M(r) approximately 70,000), medium (av. M(r) approximately 82,000), and high (av. M(r) approximately 94,000) M(r) fractions of mZP3 were purified and shown to vary in extent of asparagine-linked (N-linked) glycosylation. All three size-fractions exhibited bioactivity, suggesting that the ability of mZP3 to inhibit binding of sperm to eggs is not related to the extent of glycosylation of its polypeptide (M(r) approximately 44,000). Digestion of mZP3 by neuraminidase decreased its average M(r) from approximately 83,000 to approximately 77,000 and increased its average pI from approximately 4.7 to approximately 6.0, but did not significantly affect mZP3 bioactivity. Terminal sialic acid largely accounts for the glycoprotein's acidic nature, but is not an essential element of the mZP3 combining site for sperm. Experiments with stably transfected embryonal carcinoma (EC) cells that secrete bioactive EC-mZP3 revealed that, of the sulfate present, approximately 70-75% was located on N-linked and approximately 25-30% on O-linked oligosaccharides. EC-mZP3 devoid of sulfate inhibited binding of sperm to eggs and induced the acrosome reaction to the same extent as sulfated EC-mZP3. These results suggest that sulfation of EC-mZP3 oligosaccharides is not essential for bioactivity. Overall, these findings contrast with those reported for certain other glycoproteins involved in cellular adhesion that require sulfate and/or sialic acid for bioactivity.

Animals↗