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Biomedical subjects

K Yang

Publications and source records attributed to K Yang.

At least 73 records · Page 4Linked to original sources

[Investigation of the tongue squamous cell carcinoma prognostic factors].

OBJECTIVE: The aim of this study was to investigate the factors which influence the prognosis of the tongue squamous cell carcinoma (TSCC). METHODS: The Cox's proportional hazard model was used to analyze 121 cases of TSCC treated by the affiliated dental hospital of West China University of Medical Sciences in the period from 1990 to 1994. Thirteen parameters (age, sex, occupation, primary tumor site, clinical stage, tumor differentiation, clinical therapy, cervical lymph node metastasis, surgical margin status of the primary tumor, amount of blood transfusion, smoking, drinking, reconstruction during operation) were evaluated. RESULTS: The monofactor analysis showed that factors influencing the postoperative survival of TSCC included primary tumor site, the surgical margin status of the primary tumor and the cervical lymph node metastasis (P < 0.05). Multifactor analysis demonstrated that two of these thirteen relevant factors influenced the postoperative survival of TSCC independently. They are successively the surgical margin status of the primary tumor and the cervical lymph node metastasis (P < 0.05). CONCLUSION: This study suggests that it is critical for surgeons to resect the primary tumor and the metastatic cervical lymph nodes thoroughly to improve the survival rate of TSCC patients.

Adult↗

[Preparation of cucurbitacinBE polylactic acid nano-particles for targeting cervical lymph nodes].

OBJECTIVE: Anti-cancer nano-particles for targeting cervical lymph nodes were designed and prepared on the basis of the physiologic and anatomic properties of the peri-oral cancer lymphatic capillaries. METHODS: The biodegradable polylactic acid (PLA) was selected as the carrier material, and cucurbitacinBE (CuBE) with very high anticancer activity against oral squamous cell carcinoma was used as the model drug. According to the criteria of the diameter of the nano-particles, drug loading (DL) and embedding ratio (ER), the preparing technology was optimized by uniformly designing experiment on the basis of single-factor experiment. CucurbitacinBE poly-lactic acid nano-particles (CuBE-PLA-NP) was prepared with the method of emulsion solvent evaporation, and then CuBE-PLA-NP lyophilization injection was prepared by using 10% manninositose as the supporting agent. RESULTS: The diameter distribution for optimized CuBE-PLA-NP lyophilization injection ranged from 47 nm to 120 nm, and the average diameter was 85 nm. DL and ER were 23.03% +/- 0.47% and 93.00% +/- 0.10% respectively. The release study of the thermostatics also demonstrated that Higuchi equation was adequate to fit the release curve of CuBE-PLA-NP. CONCLUSION: CuBE-PLA-NP can be used as the release agent, as CuBE-PLA-NP can enter peri-oral cancer lymphatic capillaries for targeting cervical lymph nodes by the peri-cancer submucosal injection. Therefore, it can also used for animal and clinical experiments.

Antineoplastic Agents↗

[Acute toxicity and local stimulate test of cucurbitacinBE polylactic acid nano-particles of targeting cervical lymph nodes].

OBJECTIVE: The aim of this experiment was to study acute toxicity and local stimulation of cucurbitacinBE poly-lactic acid nano-particles (CuBE-PLA-NP) for targeting cervical lymph node. METHODS: Various doses of CuBE-PLA-NP lyophilization injection and cucurbitacinBE (CuBE) were hypodermically or veno-injected into the mice, and then the drug toxicity and side effects were observed; 50% lethal dose (LD50) was counted. CuBE-PLA-NP lyophilization injection and CuBE were also injected into the quadriceps femoralis muscle of rabbits to observe the local stimulate responses of drugs. RESULTS: The fifty percent lethal doses of subcutaneous and venous CuBE-PLA-NP in mice were 16.74 mg/kg +/- 1.83 mg/kg and 5.60 mg/kg +/- 0.83 mg/kg respectively, that were higher than those of CuBE which were 8.63 mg/kg +/- 1.00 mg/kg and 2.50 mg/kg +/- 0.30 mg/kg respectively. Local stimulate response in rabbit quadriceps femoralis muscle after CuBE-PLA-NP and CuBE injected are 0 grade and 0.1 grade respectively. CONCLUSION: The acute toxicity of CuBE-PLA-NP is lower than that of CuBE. Both CuBE-PLA-NP and CuBE are adequate for local injection, but the local stimulation of CuBE-PLA-NP is smaller than that of CuBE.

Animals↗

[Analgesic mechanisms of noradrenaline in the spinal dorsal horn].

The superficial laminae of the spinal dorsal horn play important roles in nociceptive transmission and modulation. Noradrenergic fibers originated from brainstem pain-control system terminate and release noradrenaline (NA) in the superficial dorsal horn. The released NA might take part in the modulation of nociceptive transmission through the following pathways: (1) inhibits the glutamate and substance P release from primary afferent terminals; (2) increases the release of inhibitory neurotransmitters from lamina II (substantia gelatinosa) neurons. Morphological findings also raise the possibility that NA directly inhibits projection neurons in laminae I/III which convey the nociceptive information to the thalamus, thus inhibit nociceptive transmission at spinal level.

Analgesics↗

[Studies on the hydroxyl free radical-scavenging effect of combined selenium and germanium].

The effect of selenium, carboxyethyl-germanium sesquioxide (Ge-132) and the combination of selenium and Ge-132 on the production of hydroxyl free radical in liver microsomes of rats treated with Fe2SO4-NADPH system was studied with electron spin resonance technique (ESR). The results showed that the production of hydroxyl free radical was decreased significantly by adding selenium, Ge-132 and combined selenium and Ge-132, indicating a direct scavenging effect on hydroxyl free radical. It was also observed a enhanced scavenging effect at the low concentration of combined selenium and Ge-132.

Animals↗

Intracellular labeling study of neurons in the superficial part of the magnocellular layer of the medullary dorsal horn of the rat.

Morphology and electrical membrane properties of neurons in the superficial part of the magnocellular layer of the rat medullary dorsal horn (MDH: caudal subnucleus of the spinal trigeminal nucleus) were examined by using horizontal slice preparations. Intracellular recording and biocytin-injection combined with histochemical and immunohistochemical staining were done. Twenty-four neurons were examined successfully and classified into projection neurons (PNs) and intrinsic neurons (INs). The PNs were further divided into type I PNs (I-PNs) and type II PNs (II-PNs). The I-PNs sent axons to the medullary reticular formation; the II-PNs sent axons to the interpolar subnucleus of the spinal trigeminal nucleus but had no axons extending to the medullary reticular formation. The INs that sent no axons to the brain regions outside the MDH were also divided into small INs with spiny dendrites (INSSs) and large INs with aspiny dendrites (INLAs). The dendritic fields of the PNs extended to laminae I and II of the MDH and occasionally further to the spinal tract of the trigeminal nerve, whereas those of the INs were confined within the magnocellular layer of the MDH. The axonal branches of each IN formed a dense axonal mesh around the cell body of the parent neuron. Although the main bodies of the axonal fields of the INs were located in the magnocellular layer, some axonal branches extended to laminae I and II of the MDH. Immunoreactivity for NK1 receptor (substance P receptor) was found in approximately half of the PNs but not in the INs. Although no strong correlation was found between morphology and electrical membrane properties, there were some differences in electrical properties among the morphologically classified neuron groups, e.g., hyperpolarizing sag was observed in some PNs but not in the Ins; inward rectification was observed in some of the INSSs and INLAs but not in the PNs; the slow ramp depolarization and the slow afterdepolarization were observed in all INSSs examined but not in the PNs or INLAs.

Animals↗

Selective diphosphine ligand chelation and pi bond coordination in CoRu(CO)7(mu-PPh2): kinetics and X-ray structure of CoRu(CO)4(mu-bma)(mu-PPh2).

Thermolysis of CoRu(CO)7(mu-PPh2) (1) in refluxing 1,2-dichloroethane in the presence of the diphosphine ligands 2,3-bis(diphenylphosphino)maleic anhydride (bma) and 4,5-bis(diphenylphosphino)-4-cyclopenten-1,3-dione (bpcd) furnishes the new mixed-metal complexes CoRu(CO)4(mu-P-P)(mu-PPh2) [where P-P = bma (3a), bpcd (3b)] along with trace amounts of the known complex CoRu(CO)6(PPh3)(mu-PPh2) (4). The requisite pentacarbonyl intermediates CoRu(CO)5(mu-P-P)(mu-PPh2) [where P-P = bma (2a), bpcd (2b)] have been prepared by separate routes (mild thermolysis and Me3NO activation) and studied for their conversion to CoRu(CO)4(mu-P-P)(mu-PPh2). The penta- and tetracarbonyl complexes have been isolated and fully characterized in solution by IR and NMR spectroscopy. The kinetics for the conversion of 2a-->3a and of 2b-->3b were measured by IR spectroscopy in chlorobenzene solvent. On the basis of the first-order rate constants, CO inhibition, and the activation parameters (2a-->3a, delta H++ = 29.2 +/- 1.4 kcal mol-1 and delta S++ = 8.2 +/- 3.8 eu; 2b-->3b, delta H++ = 27.7 +/- 0.6 kcal mol-1 and delta S++ = 1.4 +/- 1.6 eu), a mechanism involving dissociative CO loss as the rate-limiting step is proposed. The solid-state structure of CoRu(CO)4(mu-bma)(mu-PPh2) (3a), as determined by X-ray crystallography, reveals that the two PPh2 groups are bound to the ruthenium center while the maleic anhydride pi bond is coordinated to the cobalt atom.

Journal Article↗

Spontaneous breakdown of translational symmetry in quantum hall systems: crystalline order in high landau levels.

We report on results of systematic numerical studies of two-dimensional electron gas systems subject to a perpendicular magnetic field, with a high Landau level partially filled by electrons. Our results are strongly suggestive of a breakdown of translational symmetry and the presence of crystalline order in the ground state. This is in sharp contrast with the physics of the lowest and first excited Landau levels, and in good qualitative agreement with earlier Hartree-Fock studies. Experimental implications of our results are discussed.

Journal Article↗

Tumor-associated Apc mutations in Mlh1-/- Apc1638N mice reveal a mutational signature of Mlh1 deficiency.

Apc1638N mice, which are heterozygous for a germline mutation in Apc, typically develop three to five spontaneous intestinal tumors per animal. In most cases this is associated with allelic loss of wildtype Apc. We have previously reported that the multiplicity of intestinal tumors is increased dramatically by crossing Apc1638N with an Mlh1-deficient mouse strain that represents an animal model of hereditary non-polyposis colorectal cancer (HNPCC). The increased tumor multiplicity in these mice was associated with somatic mutations in the Apc tumor suppressor gene. Here, we have examined the nature and distribution of 91 Apc mutations implicated in the development of intestinal tumors in Mlh1-/- Apc1638N animals. Protein truncation mutations were detected in a majority of tumor samples, indicating that the prevailing mechanism of Apc mutation in tumors is altered from allelic loss to intragenic mutation as a result of Mlh1 deficiency. The observed mutations were a mixture of base substitutions (27%) and frameshifts (73%). Most frameshifts were detected within dinucleotide repeats and there were prominent mutational hotspots within sequences of this sort at codons 927-929, 1209-1211 and 1461-1464. The observed Apc mutations caused protein truncation upstream of the third 20 amino acid beta-catenin binding domain and the first Axin-binding SAMP repeat, yielding Apc proteins that are predicted to be deficient in destabilizing beta-catenin. Our results reveal a characteristic mutational signature in Apc that is attributable to Mlh1 deficiency. This demonstrates a direct effect of Mlh1 deficiency in the mutation of Apc in these tumors, and provides data that clarify the role of Mlh1 in mammalian DNA mismatch repair.

Adaptor Proteins, Signal Transducing↗

Functional implications of disulfide bond, Cys206-Cys210, in recombinant prochymosin (chymosin).

Prochymosin (chymosin) contains three disulfide bonds: Cys45-Cys50, Cys206-Cys210, and Cys250-Cys283. We have demonstrated that Cys250-Cys283 is indispensable for correct refolding of prochymosin, whereas Cys45-Cys50 is dispensable but has some contribution to the stability and substrate specificity of the enzyme. Here, we report the results about the functions of Cys206-Cys210 by site-directed mutagenesis studies. In a glutathione redox system C206A/C210A mutant exhibited oxidative refolding kinetics and efficiency ( approximately 40% reactivation) similar to those of the wild-type prochymosin, indicating that Cys206-Cys210 is also dispensable for refolding. However, C206S/C210S and single-site mutants (C210A, C210S, and C206A) showed only about 3 and 0-0.4% reactivation, respectively. This is quite different from the Cys45-Cys50 deficient mutants (C45A, C50A, C45A/C50A, C45D, C50S, C45D/C50S, C45A/C50S), which have comparable refolding efficiencies, implying that the substituents at position 206 and 210 play more important role in determining correct refolding than those at position 45 and 50. Urea-induced denaturation and fluorescence quenching studies indicated that the prochymosin mutants C206A/C210A and C206S/C210S were 2.1 and 4.8 kJ/mol less stable than prochymosin and some tryptophan residue in the mutated molecules was less exposed. However, the wild-type and mutant prochymosins shared similar far-UV CD and fluorescence emission spectra and similar specific potential activity, suggesting that the overall conformation was maintained after mutation. Activity assay and kinetic analysis revealed that mutation did not change the specific milk-clotting activity significantly but resulted in an increase in K(m) and k(cat) toward a hexapeptide substrate. On the basis of the above-mentioned perturbance of tryptophanyl microenvironment and the three-dimensional structure of chymosin, we proposed that deletion of Cys206-Cys210 may induce a propagated conformational change, resulting in a perturbance of the local conformation around active-site cleft and in turn, an alteration of the substrate specificity.

Air↗

Postsynaptic origin of N-methyl-D-aspartate-induced slow currents in substantia gelatinosa neurons: an in vitro voltage-clamp study in adult rat.

We investigated whether N-methyl-D-aspartate (NMDA)-induced slow current in substantia gelatinosa (SG) neurons might be of presynaptic or postsynaptic origin. Whole-cell voltage-clamp recordings were made from adult rat spinal cord slices to examine the effect of NMDA receptor upon miniature excitatory postsynaptic currents (mEPSCs) in SG neurons. At a holding potential of -70 mV, bath application of NMDA (10 microM, 30s), an NMDA receptor agonist, affected neither the frequency nor the mean amplitude of mEPSCs, while NMDA induced a slow excitatory membrane current which persisted in the presence of tetrodotoxin. On the other hand, AP-5 (an NMDA receptor antagonist) had no noticeable effects on mEPSCs in the SG neurons tested, while it markedly depressed the NMDA-induced slow currents. The NMDA-induced slow currents varied with the changing of holding potentials (from -70 to 0 mV). The results suggested that the NMDA-induced slow currents in SG neurons were of postsynaptic origin.

2-Amino-5-phosphonovalerate↗

Capsaicin induces a slow inward current which is not mediated by substance P in substantia gelatinosa neurons of the rat spinal cord.

Whole-cell voltage-clamp techniques were employed to investigate a capsaicin-induced current in substantia gelatinosa (SG) neurons in the dorsal horn of adult rat spinal cord slices. Bath-applied capsaicin (2 microM) for 30 s activated a slow excitatory current having an amplitude of 21.3+/-6.3 pA and a duration of 93+/-13 s (n=10; V(H)=-70 mV). This capsaicin current was compared in amplitude under various conditions among different SG neurons. After either neonatal capsaicin treatment or sciatic-nerve transection, by which C-afferent fibers are known to degenerate, this capsaicin current was reduced in amplitude to 5.0+/-3.5 pA (n=8) or 4.5+/-2.3 pA (n=6), respectively. A non-N-methyl-D-aspartate (NMDA)-receptor antagonist, CNQX (10 microM), depressed greatly the capsaicin current to 4.0+/-1.3 pA (n=9). On the other hand, this current had an amplitude of 14.4+/-2.7 pA (n=10) in the presence of an NMDA-receptor antagonist, AP-5 (50 microM); this value was not significantly different from that in the control (P>0.05). Substance P (SP; 1-2 microM) superfused for 2 min had no detectable effect on all SG neurons examined (n=7). After SP washout, however, these cells exhibited a capsaicin current (22.8+/-12.1 pA); this current persisted in the presence of a neurokinin-1 receptor antagonist, L-732,138 (1 microM; 19.8+/-3.5pA, n=9). The capsaicin current was not abolished by an intracellular dialysis with GDP-beta-S (1 mM; 20. 2+/-2.4 pA, n=9) which inhibited a baclofen (10 microM) response mediated by the G-protein-coupled GABA(B) receptor. These results indicate that the capsaicin-induced current is mediated through the activation of C-fibers by non-NMDA receptors. This mechanism in SG neurons is different from that known in neurons in other laminae of the dorsal horn that is thought to be a direct action of SP released from C-fibers. This current in SG neurons would contribute to the pain sensation caused by capsaicin.

Animals↗

Morphologic features and electrical membrane properties of projection neurons in the marginal layer of the medullary dorsal horn of the rat.

Possible correspondence between morphologic features and electrical membrane properties of projection neurons in lamina I [the marginal zone (MZ)] of the caudal subnucleus of the spinal trigeminal nucleus [the medullary dorsal horn (MDH)] was examined by using intracellular recordings and biocytin-injections combined with histochemical and immunohistochemical staining techniques. The experiments were done in horizontal slice preparations of the rat brain. Thirteen MZ neurons were recorded stably and stained successfully. These neurons were confirmed to send their axons to the brain regions outside the MDH by camera lucida reconstruction. They were divided into two types on the basis of branching patterns of their axons within the MDH: Type I projection (P-I) neurons (n = 7 neurons) had main axons that rarely emitted axon collaterals within the MDH, whereas type II projection (P-II) neurons (n = 6 neurons) had main axons that emitted many axon collaterals within laminae I, II (substantia gelatinosa), and III (magnocellular part) of the MDH and also to the spinal tract of the trigeminal nerve; these axon collaterals usually constituted a dense mesh of axonal processes within laminae I and II of the MDH, especially in lamina II. About half of the neurons of each type showed immunoreactivity for the neurokinin-1 receptor. Resting membrane potentials were significantly more positive in P-I neurons than in P-II neurons. The P-II neurons had higher input resistance, a longer membrane time constant, and a higher threshold for spike than P-I neurons. In response to weak, long depolarizing current pulses, P-II neurons often showed slow ramp depolarization; the same neurons exhibited delayed repolarization to the resting potential (slow after depolarization) after the offset of the long depolarizing current pulses. Neither the slow-ramp depolarization nor the slow after depolarization was observed in P-I neurons. Slow return to resting membrane potential after offset of hyperpolarizing current pulses also was observed frequently in P-II neurons but not in P-I neurons. The results indicate that P-II neurons differ in their membrane properties compared with P-I neurons, and P-II neurons may be involved in the local circuit mechanism within the MDH more deeply than P-I neurons.

Animals↗

Harvesting the intact cadaveric cervical spine (C0-Th1).

STUDY DESIGN: Technical report on harvesting method for human cadaveric cervical spine. OBJECTIVES: Description of a new method for harvesting the intact cervical spine during routine autopsies, including the atlanto-occipital and cervico-thoracic joints, without visible disfigurement above the suprasternal notch. SUMMARY OF BACKGROUND DATA: Despite the need for cervical spine specimens, there are only few articles describing procedures for harvesting an intact cervical spine. Presently available techniques either do not preserve the atlanto-occipital joint or leave visible disfigurement. METHODS: The body was placed in a prone position with the head flexed, and a posterior midline incision was performed. The spine was separated from surrounding tissue, then the caudal end was cut off through the Th1/Th2 disc space. A circular craniotomy provided access to the cranial base. A square window surrounding the foramen magnum was cut at the cranial base (through the sella turcica, the internal occipital protuberance, and 5 cm parasagittal on either side), and the entire cervical spine extracted through the posterior incision. The defect was reconstructed using wood and plaster materials. RESULTS: Eighteen specimens were harvested to date using this method. The average time of harvesting the cervical spine was less than 30 minutes. Reconstruction using wood and plaster resulted in a nearly normal appearance of the neck. CONCLUSIONS: Using this technique, the nuchal ligament providing stability to the cervical spine can be preserved. The suggested method was found simple, efficient, and reproducible for harvesting the intact cervical spine, including the atlanto-occipital and cervico-thoracic joints, from any routine autopsy.

Atlanto-Occipital Joint↗

Josephson effect in fulde-ferrell-larkin-ovchinnikov superconductors

Because of the difference in the momenta of the superconducting order parameters, the Josephson current in a Josephson junction between a Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) superconductor and a conventional BCS superconductor is suppressed. We show that the Josephson current may be recovered by applying a magnetic field in the junction. The field strength and direction at which the supercurrent recovery occurs depend upon the momentum and structure of the order parameter in the FFLO state. Thus the Josephson effect provides an unambiguous way to detect the existence of an FFLO state, and to measure the momentum of the order parameter.

Journal Article↗