Narrow spectrum of cross-sensitization with pyridine derivatives.
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Biomedical subjects
Publications and source records attributed to K Yu.
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In-vitro/in-vivo correlations (IVIVC) are useful for predicting in-vivo results from in-vitro data. An IVIVC has been used to optimize a hydrocolloidal-based matrix tablet designed to be bioequivalent to an existing once-daily diltiazem HC1 product (Dilacor XR 240mg; Rhone-Poulenc Rorer). Data from a preliminary formulation dosed to fasted and fed subjects were used to establish the IVIVC. The correlation was then used during reformulation of the dosage forms to predict changes in the maximum plasma concentration (Cmax) and the area under the plasma-concentration-time curve (AUC) for fasted and fed subjects using in-vitro dissolution data. The IVIVC adequately predicted plasma profiles of two optimized formulations in studies with fasted and fed subjects.
In a series of experiments psychophysical techniques were used to study the relation between binocular rivalry and motion perception. An initial series of experiments confirmed that motion enhances the predominance of an eye during rivalry, although the direction of motion does not matter. The presence of an annulus of motion immediately surrounding one eye's rival target greatly enhances dominance of that target, but the influence of the annulus progressively decreases as the separation between disk and annulus increased. Opponent directions of motion in disk and annulus yield greater dominance than when dots in the disk and annulus moved in identical directions. In a second experiment that two eyes were adapted to orthogonal directions of motion, generating strong, distinctively different monocular motion aftereffects (MAEs). Even though the two eyes view physically identical random-motion displays following differential adaptation, binocular rivalry of the discrepant MAEs can occur. Finally, using a stimulus replacement technique to measure detectability of translational and rotational motion, it was found that both types of motion were readily detected during periods of dominance but went undetected during periods of suppression. Taken together, these results bear on the process responsible for rivalry and its neural locus relative to the analysis of different types of motion.
OBJECTIVE: To study the correlation between cholelithiasis and the infection of HBV. METHOD: 32 formalin-fixed and paraffin-embedded gallbladder samples of cholelithiasis patients and 20 gallbladder samples of non-cholelithiasis patients were investigated using the polymerase chain reaction-Ethidium bromide (PCR-EB) assay. The 52 patients were positive to HBV serologic markers. RESULT: The results showed that HBV-DNA was found in 13 gallbladder samples of 32 cholelithiasis patients (40.63%), significantly higher than that in 3 gallbladder samples of 20 non-cholelithiasis patients (15%). CONCLUSION: The infection of HBV and the formation of cholelithiasis are correlated.
OBJECTIVE: To study the effects of graded spinal cord injury (SCI) on the motor evoked potentials (MEP) characteristics and the prognostic value of MEP for the motor function. METHOD: Modified Allen's method was used by weight drop force of 30 gcf, 50 gcf, 80 gcf and 100 gcf on the T(8 - 9) spinal cord of 40 SD rats in order to make SCI models. MEP was recorded continuously at L(1 - 2) epidurally and bilateral gastrocnemius muscles before and after the spinal cord lesion was produced (followed up for 1 month). The inclined plane and Tarlov technique were used to assess clinical neurological function. RESULT: The amplitude of rat's MEP changed significantly with graded SCI, the more sever the lesion, the lower the potentials. mMEP was more sensitive than scMEP, though the abolishment of mMEP soon after SCI didn't indicate that the animals could not regain ambulation. Changes in amplitude of scMEP recorded early after SCI were collaborate significantly with inclined plane (gamma = 0.9665, P < 0.01) and Tarlov scale (gamma = 0.8893, P < 0.01) assessed 1 month later, and can be used as a chronic measure parameter of motor function prognosis. scMEP still existed 1 month after SCI in 3 of 11 rats (27.3%) without any voluntary movement in bilateral hindlimbs, suggesting that some parts of conductive function still existed in the spinal cord. So it should be called "discomplete SCI". CONCLUSIONS: scMEP can be used as a reliable parameter for motor function prognosis, because it reflects objectively and sensitively the severity of central motor neurol fiber injury.
OBJECTIVE: To probe into the possibility of early diagnosis of cervical spondylotic myelopathy (CSM) prospectively and to screen the premorbid signs of CSM clinically, radiologically and electro-physiologically. METHOD: Twenty-nine items related to the occurring of CSM were chosen as common characteristics of CSM and considered as the criteria of prospective study. 81 patients who met the criteria were studied. All patients were followed up and observed for 2 - 6.5 years (mean 3.7 years). RESULT: Twenty-nine patients showed CSM during investigation. Thirteen items of the criteria were related to the occurring of CSM. The significant items include upper limb pain and abnormal sensation limb numbness, positive dynamic Hoffmann's sign, cervical canal stenosis, lower cervical instability, cervical intervertebral disc herniation, and delay of central motor conduct time. CONCLUSION: CSM can be early diagnosed. The patients who meet the established criteria should be followed up and observed closely. Early operation results in good effect.
OBJECTIVE: To study the antiproliferative effects of homoharringtonine (Hh) on glaucoma filtering surgery. METHODS: In a randomized control clinical trial, 78 patients (88 eyes) with refractory glaucoma underwent trabeculectomy with and without Hh. In the Hh-treated eyes (n = 46), the therapeutic dose of Hh was: intraoperative application of Hh 0.4 mg and postoperative subconjunctival injections of Hh 0.62 +/- 0.20 mg (ranged 0.53 - 0.75 mg). In the control eyes (n = 42), Hh was not used. The follow-up period was 18 to 48 months, and the data were analyzed by using the life-table method of Kaplan-Meier. RESULTS: The cumulative success probability in Hh group was 84.5% and that in control group was 50.9%, the difference being significant (P < 0.05). The cumulative percentage of functioning bleb in Hh group was 84.2% and that in control group was 52.9% (P < 0.05). The rates of corneal erosion were 23.9% and 7.1%, and the rates of conjunctival wound leak were 6.5% and 2.4% in Hh and control group respectively. There was no significant change in corneal endothelial density following the use of Hh (P > 0.05). CONCLUSION: The study indicates that Hh is a safe and effective antiproliferative agent for the use in glaucoma filtering surgery, it not only can increase the success probability considerably, but also maintain at least the postoperative IOP at relatively low normal level for 3 years.
A novel method of EEG signals compression representation and epileptiform spikes recognition based on wavelet neural network and its algorithm is presented in this paper. Wavelet network not only can compress data effectively but also can recover original signal. In addition the characteristics of the spikes and the spike-slow rhythm are detected automatically from the time-frequency isoline of EEG signal. This method can be generalized in the field of the electrophysiological signal processing and time-frequency analyzing.
The aim of this study was to cover up the surface of human hard tissue substitute biomaterials with albumin. The cidex cross-link method was adopted to adsorb albumin so as to form a membrane for wrapping hydroxyapatite(HA), bio-glass ceramics(BGC), and hydroxyl poly-calcium sodium phosphate (HP). The results showed that this membrane of protein could enwrap the biomaterials so firmly that urea solution could not wash it off.
This study explored the conditions on combining albumin of surfaces of hydroxyapatite (HA), bioglass ceramics(BGC) and hydroxyl poly-calcium sodium phosphate (HP) by using the method of BrCN activation. The result demonstrates that albumin can be combined with HP, but it can not be combined with HA and BGC.
Approximately 40,300 patients are diagnosed with cutaneous melanoma annually in the United States with a disease-related mortality rate of approximately 7,300 per year. Although treatment strategies have been defined for cutaneous melanoma, therapeutic approaches for this hormonally sensitive tumor are difficult in the gravid patient. Epidemiologic studies suggest that there continues to be an increasing incidence of melanoma with an associated decrease in age at presentation for patients in the United States. These trends suggest that approximately 35% of women will be diagnosed with melanoma during their childbearing years. Hence, the perplexing challenge of melanoma management during pregnancy will perhaps increase over the next decade. This case report documents the occurrence of cutaneous melanoma in women during pregnancy and highlights key issues in the natural history of this disease. Detailed review of the current literature related to melanoma during pregnancy will provide insight into optimal therapeutic approaches.
Low ratio hybridization subtraction technique was previously used in this laboratory to enrich and isolate a number of low abundance UV-inducible hamster transcripts (Fornace, A. J., Jr., Alamo, I. J., and Hollander, M. C. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 8800-8804) that led to the identification and cloning of five important hamster and human GADD genes (Fornace, A. J., Jr., Nebert, D. W., Hollander, M. C., Luethy, J. D., Papathanasiou, M., Fargnoli, J., and Holbrook, N. J. (1989) Mol. Cell. Biol. 9, 4196-4203). In this study we have characterized the remaining DNA damage-inducible (DDI) transcripts. Of the 24 DDI clones, 3 clones (A13, A20, and A113) representing different regions of the same hamster cDNA exhibited near perfect homology to human p21(WAF1/CIP1) cDNA. The DDI clones A26, A88, and A99 displayed very high sequence homologies with the human proliferating nuclear antigen, rat translation initiation factor-5 (eIF-5), and human thrombomodulin, respectively, whereas clones A29 and A121 matched with express sequence tagged sequences of unknown identity. The DDI clones A18, 106, and A107 were different isolates of the same hamster cDNA (hereafter referred to as A18) and displayed high sequence homology with the members in the heterogeneous ribonucleoprotein (hnRNP) family. Using the hamster A18 partial-length cDNA as a probe, we screened human fibroblast cDNA library and isolated the corresponding full-length human cDNA. The deduced amino acid sequence revealed that the putative protein contains all the canonical features of a novel glycine-rich hnRNP. The A18 mRNA levels were specifically increased in response to DNA damage induced by UV irradiation or UV mimetic agents. Thus the putative A18 hnRNP is the first hnRNP whose mRNA is specifically regulated in response to UV-induced DNA damage; accordingly, it may play some role in repair of UV-type DNA damage.
Regulators of G protein signaling (RGS) proteins accelerate GTP hydrolysis by Gi but not by Gs class alpha-subunits. All RGS proteins share a conserved 120-amino acid sequence termed the RGS domain. We have demonstrated that the RGS domains of RGS4, RGS10, and GAIP retain GTPase accelerating activity with the Gi class substrates Gialpha1, Goalpha, and Gzalpha in vitro. No regulatory activity of the RGS domains was detected for Gsalpha. Short deletions within the RGS domain of RGS4 destroyed GTPase activating protein activity and Gialpha1 substrate binding. Comparable protein-protein interactions between Gialpha1-GDP-AlF4- and the RGS domain or full-length RGS4 were detected using surface plasmon resonance.
The presence of receptors for ATP has not been established in any native preparation of retinal neurons or glia. In the present study, we used conventional electrophysiological and [Ca2+]in fluorescence imaging techniques to investigate the effects of ATP added to Ringer's solution perfusing the retinal-facing (apical) membrane of freshly isolated monolayers of bovine retinal pigment epithelium (RPE). ATP (or UTP) produced large, biphasic voltage and resistance changes with a Kd of approximately 5 microM for ATP and approximately 1 microM for UTP. Electrical and pharmacological evidence indicates that the first and second phases of the response are attributable to an increase in basolateral membrane Cl conductance and a decrease in apical membrane K conductance, respectively. The ATP-induced responses were not affected by adenosine, but were reduced by the P2-purinoceptor blocker suramin. ATP also produced a large, transient increase in [Ca2+]in that was blocked by cyclopiazonic acid, an inhibitor of endoplasmic reticulum Ca2+-ATPases. The calcium buffer BAPTA attenuated the voltage effects of ATP. We also found that apical DIDS significantly inhibited the ATP-evoked [Ca2+]in and electrical responses, suggesting that DIDS blocked the purinoceptor. Measurements of fluid movement across the RPE using the capacitance probe technique demonstrated a significant increase in fluid absorption by apical UTP. These data indicate the presence of metabotropic P2Y/P2U-purinoceptors at the RPE apical membrane and implicate extracellular ATP in vivo as a retinal signaling molecule that could help regulate the hydration and chemical composition of the subretinal space.
BACKGROUND: Several serotonin selective reuptake inhibitors have been reported to be inhibitors of the cytochrome P450 2D6 (CYP2D6). Thus, they may increase the plasma level of secondary amine tricyclic antidepressants, which are predominantly metabolized through this enzyme. Except for a few case reports, no clinical data document the degree of this drug-drug interaction in elderly depressed patients. METHOD: We systematically examined this interaction by determining the change in plasma nortriptyline levels in 14 elderly depressed patients in whom sertraline was added to nortriptyline. RESULTS: After addition of 50 mg/day of sertraline, the median increase in plasma nortriptyline level over baseline was 2% (range, -26% to 117%; p = .30). In 2 patients (14%), there was an increase of 50% or more. For patients taking higher sertraline doses (N = 7; 100 or 150 mg/day), the median increase in plasma nortriptyline level over baseline was 40% (range, -12% to 239%; p = .08). CONCLUSION: Overall, a modest effect of sertraline was observed on nortriptyline metabolism in these elderly depressed patients. This is consistent with prior reports of a weak inhibition of CYP2D6 by sertraline in vitro and in young healthy volunteers. However, some patients showed a change in plasma nortriptyline level that would be considered clinically significant. Thus, careful monitoring of plasma nortriptyline levels is recommended in all patients treated with a combination of nortriptyline and sertraline.
OBJECTIVE: To evaluate the therapeutic effects of a combined laser technique for plateau iris glaucoma. METHODS: 20 cases (37 eyes) of early plateau iris glaucoma were treated by a laser technique that included argon laser peripheral iridoplasty and argon + Nd:YAG laser iridectomy. RESULTS: The postoperative follow-up ranged from 8 months to 4 years and 7 months (30 eyes for more than 2 years, mean 2.7 years). 17 cases (32 eyes) obtained satisfactory effects, no acute-attacks were seen in the follow-up, intraocular pressure decreased from 5.8 +/- 1.04 kPa to below 2.74 kPa, peripheral anterior chamber depth increased, angle widened, the iris retracted away from the trabecular meshwork, thus further synechiae of chamber angle were prevented effectively, and the dark room provocative test results turned to negative in 86.7% of cases. CONCLUSION: Argon laser peripheral iridoplasty combined argon + Nd:YAG laser iridectomy may be a safe and effective method for treatment of plateau iris glaucoma.
Regional limb perfusion with antineoplastic agents stresses the local vasculature in a variety of ways. However, by monitoring the perfusates from limbs treated with melphalan alone or with melphalan plus tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma), we were able to distinguish the effect of the cytokines on the observed coagulant and fibrinolytic responses. We collected samples of effluent from a series of lower extremities that were perfused with the cytokines and/or melphalan as treatment for localized melanoma. Both regimens produced statistically significant evidence of coagulant and fibrinolytic activation. However, limbs receiving cytokines in addition to the melphalan responded with a sharper rise in tissue plasminogen activator (tPA) and plasmin (plasmin-antiplasmin complexes [PAP]) than limbs treated with melphalan alone. Evidence of thrombin formation (prothrombin fragment 1 + 2 [F1 + 2], thrombin-antithrombin complexes [TAT]) was also greater when the cytokines were included, although the response was delayed and less consistent than the fibrinolytic activation.
Deregulated overexpression of c-Myc (Myc) confers susceptibility to apoptosis in several cell types, but the molecular regulation of these processes has not been well established. Here we have characterized several molecular changes that may modulate Myc-dependent apoptosis. Ectopic overexpression of Myc in both Rat1 fibroblasts and human osteosarcoma cells causes a dramatic increase of cellular p53 mRNA and protein, and this induction of p53 correlates with apoptosis triggered by withdrawal of serum. Stable transfection of a wild-type human p53 gene into Myc-transformed cells further potentiates apoptosis. Anticancer agents vinblastine and nocodazole also induce apoptosis in Myc-transformed Rat1 fibroblasts but are cytostatic to the same cells without Myc overexpression. We demonstrate that induction of Myc-dependent apoptosis in these cells is specifically associated with an activation of p46 c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) activity, whereas this JNK/SAPK activation is absent in stress-treated cells without Myc overexpression. Moreover, overexpression of the Mdm-2 gene in Rat1-myc cells significantly inhibits apoptosis induced by low serum but has little effect on apoptosis triggered by chemotherapeutic drugs. Interestingly, differential inhibition by Mdm-2 paralleled differential activation of p46 JNK/SAPK. Thus, our data support a functional involvement of p53 in Myc-dependent apoptosis and implicate potential regulatory roles for JNK/SAPK and Mdm-2 pathways in the regulation of apoptosis in Myc-transformed tumor cells.