Biomedical subjects

K Yu

Publications and source records attributed to K Yu.

At least 73 records · Page 4Linked to original sources

PubMed1999

Alcohol and drug use in victims of life-threatening trauma.

OBJECTIVE: Alcohol and drug use has been implicated as a contributing factor to all types of trauma. This investigation seeks to determine the prevalence of alcohol and drug use in patients who are victims of life-threatening injuries and the association of alcohol and drug use with intentional trauma. METHODS: The Medical Center of Louisiana at New Orleans (Charity Campus) trauma registry was used to identify patients sustaining life-threatening injuries that presented to our American College of Surgeons Level 1 trauma center over a 6-month period. Serum ethanol levels and urine toxicology were assessed at initial presentation for all patients. RESULTS: A total of 557 patients were evaluated. Seventy percent (n = 319) of tested patients (n = 450) had positive serum ethanol and/or urine toxicology results. Male gender (75% vs. 55%; p < 0.001) was associated with positive screens; ethnicity was not. No difference in hospital days or mortality was seen between positive and negative screens. Victims of intentional trauma showed a higher percent of positive screens (80% vs. 63%; p < 0.005). CONCLUSION: These data suggest that alcohol and drug use is associated with life-threatening injury, especially intentional injury. Prevention of substance abuse is essential for the prevention of trauma.

Adolescent↗

PubMed1999

Reactivation of latent tuberculosis: variations on the Cornell murine model.

Mycobacterium tuberculosis causes active tuberculosis in only a small percentage of infected persons. In most cases, the infection is clinically latent, although immunosuppression can cause reactivation of a latent M. tuberculosis infection. Surprisingly little is known about the biology of the bacterium or the host during latency, and experimental studies on latent tuberculosis suffer from a lack of appropriate animal models. The Cornell model is a historical murine model of latent tuberculosis, in which mice infected with M. tuberculosis are treated with antibiotics (isoniazid and pyrazinamide), resulting in no detectable bacilli by organ culture. Reactivation of infection during this culture-negative state occurred spontaneously and following immunosuppression. In the present study, three variants of the Cornell model were evaluated for their utility in studies of latent and reactivated tuberculosis. The antibiotic regimen, inoculating dose, and antibiotic-free rest period prior to immunosuppression were varied. A variety of immunosuppressive agents, based on immunologic factors known to be important to control of acute infection, were used in attempts to reactivate the infection. Although reactivation of latent infection was observed in all three variants, these models were associated with characteristics that limit their experimental utility, including spontaneous reactivation, difficulties in inducing reactivation, and the generation of altered bacilli. The results from these studies demonstrate that the outcome of Cornell model-based studies depends critically upon the parameters used to establish the model.

Animals↗

PubMed1999

Mechanistic basis for coding end sequence effects in the initiation of V(D)J recombination.

V(D)J recombination is directed by recombination signal sequences. However, the flanking coding end sequence can markedly affect the frequency of the initiation of V(D)J recombination in vivo. Here we demonstrate that the coding end sequence effect can be qualitatively and quantitatively recapitulated in vitro with purified RAG proteins. We find that coding end sequence specifically affects the nicking step, which is the first biochemical step in RAG-mediated cleavage. The subsequent hairpin formation step is not affected by the coding end sequence. Furthermore, the coding end sequence effect can be ablated by prenicking the substrate, indicating that the coding end effect is specific to the nicking step. In reactions in which both 12- and 23-substrates are present, a suboptimal coding end sequence on one signal can slow down hairpin formation at the partner signal, a result consistent with models in which coordination between the signals occurs at the hairpin formation step. The coding end sequence effect on nicking and the coupling of the 12- and 23-substrates explains how hairpin formation can be rate limiting for some 12/23 pairs, whereas nicking can be rate limiting when low-efficiency coding end sequences are involved.

Allergens↗

PubMed1999

Leukemia inhibitory factor and oncostatin M stimulate collagenase-3 expression in osteoblasts.

Leukemia inhibitory factor (LIF) and oncostatin M (OSM) have multiple effects on skeletal remodeling. Although these cytokines modestly regulate collagen synthesis in osteoblasts, their effects on collagenase expression and collagen degradation are not known. We tested whether LIF and OSM regulate the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in osteoblast-enriched cells isolated from fetal rat calvariae. LIF and OSM increased collagenase-3 (MMP-13) mRNA and immunoreactive protein levels in a time- and dose-dependent manner. LIF and OSM enhanced the rate of transcription of the collagenase gene and stabilized collagenase mRNA in transcriptionally arrested cells. LIF and OSM failed to regulate the expression of gelatinase A (MMP-2) and B (MMP-9). LIF and OSM modestly stimulated the expression of TIMP-1 but did not alter the expression of TIMP-2 and -3. In conclusion, LIF and OSM stimulate collagenase-3 and TIMP-1 expression in osteoblasts, and these effects may be involved in mediating the bone remodeling actions of these cytokines.

Animals↗

PubMed1999

Malignant mixed mesodermal tumors of the ovary: preoperative diagnosis.

Early diagnosis of malignant mixed mesodermal tumors of the ovary is very difficult because of the rarity and the insidious onset. The purpose of this report is to review the magnetic resonance imaging features of an ovarian malignant mixed mesodermal tumor, which occurred in a 52-year-old woman, aiding in the differential diagnosis.

Chemotherapy, Adjuvant↗

PubMed1999

Dexamethasone reduces oxygen induced retinopathy in a mouse model.

Dexamethasone is widely used in the postnatal period. Its impact on retinopathy of prematurity (ROP) is extremely controversial; published studies have found a detrimental, protective, or no effect on ROP. The goal of this study was to test the hypothesis that use of dexamethasone during the injury phase (oxygen exposure) reduces the severity of oxygen-induced retinopathy (OIR) in a mouse model. C57BL6 mice pups were exposed to either room air or hyperoxia (75% FiO2) from postnatal d 7 through 12 (PN7-12) with or without dexamethasone (0.5 mg/kg/d s.c.) and killed on PN17-21. Retinopathy was assessed by a scoring system of retinal flat mount preparations and periodic acid-Schiff (PAS) staining of retinal sections. Pups exposed to dexamethasone and oxygen had a lower median retinopathy score of 5 (4, 6) [median (25th, 75th quartile)] compared with animals exposed to oxygen alone with median score of 9 (6, 10) with p < 0.001. PAS staining for extra retinal neovascularization in the dexamethasone and oxygen treated animals showed a significant reduction in number of nuclei extending beyond the inner limiting membrane when compared with oxygen exposed alone (p = 0.04). Animals treated with dexamethasone had decreased weight gain compared with control animals. Dexamethasone did not appear to affect the normal development of retinal vasculature as assessed by the scoring system when compared with control animals. Thus, dexamethasone decreases severity of OIR without having an adverse effect on normal retinal vascular development in the mouse model. We speculate that dexamethasone decreases the injury response that occurs during the hyperoxic phase, thus protecting the developing vasculature and improving the subsequent retinopathy.

Animals↗

PubMed1999

Indomethacin improves oxygen-induced retinopathy in the mouse.

Retinopathy of prematurity is a disease commonly affecting extremely premature babies. Indomethacin is widely used in the perinatal period. The goal of the present study was to test the hypothesis that indomethacin will improve retinopathy in a mouse model when administered during the period of injury (hyperoxia exposure) to the developing retinal vasculature. C57BL6 mice pups were exposed to 75% oxygen from postnatal d 7 through 12. Indomethacin was administered along with the oxygen exposure as a single subcutaneous dose of 0.5 mg/kg/d for 5 d. Animals were killed on postnatal d 17 through 20. The severity of retinopathy was assessed by a retinopathy scoring system of fluorescein-conjugated dextran-perfused retinal flat mounts and by quantitation of extraretinal nuclei by use of periodic acid-Schiff-stained retinal sections. Animals that received indomethacin during hyperoxia exposure had a significantly lower median (25th, 75th quartile) retinopathy score 5 (4.5, 6) compared with animals that received oxygen [8 (7.5, 10)]. Animals given indomethacin during hyperoxia exposure had a significantly lower extraretinal nuclei count per section (13.3 +/- 4.6) (mean +/- SD) compared with animals that were oxygen exposed (41.9 +/- 14.7). Indomethacin did not affect the normal development of the retinal vasculature or the growth of the animals. The data show that indomethacin improves oxygen-induced retinopathy when administered concurrently with the injury phase without affecting the normal retinal development or growth of the animals.

Animals↗

PubMed1999

Overexpression of G11alpha and isoforms of phospholipase C in islet beta-cells reveals a lack of correlation between inositol phosphate accumulation and insulin secretion.

It has been suggested that insulin secretion from pancreatic islets may be mediated in part by activation of phospholipases C (PLCs) and phosphoinositide hydrolysis. The purpose of this study was to determine whether the relatively modest fuel-stimulated insulin secretion responses of rodent beta-cell lines might be explained by inadequate expression or activation of PLC isoforms. We have found that two insulinoma cell lines, INS-1 and betaG 40/110, completely lack PLC-delta1 expression but have levels of expression of PLC-beta1, -beta2, -beta3, -delta2, and -gamma1 that are similar to or slightly reduced from those found in fresh rat islets. Adenovirus-mediated overexpression of PLC-delta1, -beta1, or -beta3 in INS-1 or betaG 40/110 cells results in little or no enhancement in inositol phosphate (IP) accumulation and no improvement in insulin secretion when the cells are stimulated with glucose or carbachol, despite the fact that the overexpressed proteins are fully active in cell extracts. Overexpression of PLC-beta1 or -beta3 in normal rat islets elicits a larger increase in IP accumulation but, again, has no effect on insulin secretion. Because the effect of carbachol on insulin secretion is thought to be mediated through muscarinic receptors that link to the Gq/11 class of heterotrimeric G proteins, we also overexpressed G11alpha in INS-1 cells, either alone or in concert with overexpression of PLC-beta1 or -beta3. Overexpression of G11alpha enhances IP accumulation, an effect slightly potentiated by co-overexpression of PLC-beta1 or -beta3, but these maneuvers do not affect glucose or carbachol-stimulated insulin secretion. In sum, our studies show a lack of correlation between IP accumulation and insulin secretion in INS-1 cells, betaG 40/110 cells, or cultured rat islets. We conclude that overexpression of PLC isoforms and/or G11alpha is not an effective means of enhancing fuel responsiveness in the insulinoma cell lines studied.

Adenoviridae↗

PubMed1999

[Studies of the mechanism of lowering intraocular pressure on Erycibele alkaloid].

OBJECTIVE: To investigate the molecular pharmacological mechanism of lowering intraocular pressure of Erycibele alkaloid. METHODS: Rabbit pupil diameter was measured by a pupillary ruler in constant illumination and the intraocular pressure (IOP) was measured by pneumatonometer. Iris contracting force was measured in an experiment of isolated rabbit iris. Radioimmune method was used to determine the content of cyclonucleotide. RESULTS: The pD(2) value (the affinity to M-receptors of agonist) of Erycibele alkaloid's miosis is 3.60 +/- 0.15 and its IOP lowering action is 3.49 +/- 0.07. In the isolated iris contracting experiment, its pD(2) value is 6.38 +/- 0.12. M(3) receptor antagonist is the strongest antagonist in inhibiting the miosis, IOP lowering action and isolated iris pupillary contracting action of Erycibele alkaloid. 0.01% Erycibele alkaloid can cause the decrease of cAMP and the increase of cGMP in the aqueous humor. CONCLUSIONS: The effects of miosis and IOP lowering of Erycibele alkaloid are all mediated by M(3) receptor subtype and its signal transductive mechanism is connected with cyclic nucleotide system.

Animals↗

PubMed1999

[A wavelet neural network algorithm of EEG signals data compression and spikes recognition].

A novel method of EEG signals compression representation and epileptiform spikes recognition based on wavelet neural network and its algorithm is presented. The wavelet network not only can compress data effectively but also can recover original signal. In addition, the characters of the spikes and the spike-slow rhythm are auto-detected from the time-frequency isoline of EEG signal. This method is well worth using in the field of the electrophysiological signal processing and time-frequency analyzing.

Adult↗

PubMed1999

[Inverse problem identification of parameters in heat transfer processes of human body].

In order that the distortion of the relative skin temperatures which is accompanied with the physiological destruction of an organ in the abdominal cavity and its physical-physiological mechanism may be investigated, we adopt in this paper the mathematical model for heat transfer problems in human layered tissues and a perfect parametric identification approach-inverse problem method. By utilizing the extremum method and integrating with the experimental data of an artificial thermo-focus, this difficult biophysical problem is solved.

Algorithms↗

PubMed1999

An experimental study on homoharringtonine liposome and glaucoma filtration surgery.

PURPOSE: To observe the inhibitory action of homoharringtonine liposome during the healing process of wounds in the filtering sites. METHODS: Posterior sclerectomies were performed in 14 rabbits. Postoperatively one eye of each rabbit received subconjunctival injections of HH liposome and fellow eye received saline injection in a randomized masked fashion. RESULTS: Fourteen days after operation the IOP of experimental eyes reduced significantly (P < 0.01) as compared with the controlled eyes, and the number of remaining filtering blebs increased noticeably (P < 0.05). Pathohistological examination revealed that the number of fibroblasts per square micron in the filtering sites and the thickness of the scars in the center of the filtering sites of the experimental eyes were less than those of the controlled eyes. No serious ocular toxic and side effects were found. CONCLUSION: This experiment suggest that homoharringtonine liposome can markedly inhibit the scar formation of filtering sites after glaucoma filtering surgery, promote the formation of filtering blebs, and provide an experimental evidence for its clinical use in future.

Animals↗

PubMed1998

Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum.

Chromosome 2 of Plasmodium falciparum was sequenced; this sequence contains 947,103 base pairs and encodes 210 predicted genes. In comparison with the Saccharomyces cerevisiae genome, chromosome 2 has a lower gene density, introns are more frequent, and proteins are markedly enriched in nonglobular domains. A family of surface proteins, rifins, that may play a role in antigenic variation was identified. The complete sequencing of chromosome 2 has shown that sequencing of the A+T-rich P. falciparum genome is technically feasible.

Amino Acid Sequence↗

PubMed1998

Promiscuous coupling of receptors to Gq class alpha subunits and effector proteins in pancreatic and submandibular gland cells.

Mice with deficiencies in one or more Gq class alpha subunit genes were used to examine the role of the alpha subunit in regulating Ca2+ signaling in pancreatic and submandibular gland cells. Western blot analysis showed that these cells express three of the four Gq class subunits, Galphaq, Galpha11, and Galpha14 but not Galpha15. Surprisingly, all parameters of Ca2+ signaling were identical in cells from wild type and four lines of mutant mice: 1) Galpha11-/-, 2) Galpha11-/-/Galpha14-/-, 3) Galpha14-/-/Galpha15-/-, and 4) Galphaq-/-/Galpha15-/-. These parameters included the Kapp for several Gq class coupled receptors, induction of [Ca2+]i oscillations by weak stimulation, and a biphasic [Ca2+]i response by strong stimulation. Furthermore, Ca2+ release from internal stores and Ca2+ entry were not affected in cells from any of the mutant mice. We conclude that Galphaq, Galpha11, and Galpha14 promiscuously couple several receptors (m3 muscarinic, bombesin, cholecystokinin, and alpha1 adrenergic) to effector proteins that activate both Ca2+ release from internal stores and Ca2+ entry.

Animals↗

PubMed1998

Genetic selection of intragenic suppressor mutations that reverse the effect of common p53 cancer mutations.

Several lines of evidence suggest that the presence of the wild-type tumor suppressor gene p53 in human cancers correlates well with successful anti-cancer therapy. Restoration of wild-type p53 function to cancer cells that have lost it might therefore improve treatment outcomes. Using a systematic yeast genetic approach, we selected second-site suppressor mutations that can overcome the deleterious effects of common p53 cancer mutations in human cells. We identified several suppressor mutations for the V143A, G245S and R249S cancer mutations. The beneficial effects of these suppressor mutations were demonstrated using mammalian reporter gene and apoptosis assays. Further experiments showed that these suppressor mutations could override additional p53 cancer mutations. The mechanisms of such suppressor mutations can be elucidated by structural studies, ultimately leading to a framework for the discovery of small molecules able to stabilize p53 mutants.

Animals↗

PubMed1998

A simple and sensitive ribonucleotide reductase assay.

Ribonucleotide reductase (RR) is a key regulatory enzyme in the DNA synthesis pathway and is the target of the cancer chemotherapeutic agent hydroxyurea. The study of RR is significantly hindered by the tedious and labor-intensive nature of enzymatic assay. In this report, we present a novel RR assay in which detection of the deoxyribonucleotides produced by RR occurs via coupling to the DNA polymerase reaction, and is enhanced by using RNase to degrade endogenous RNA. Cell extracts from various cell lines were treated with RNase and then reacted with ATP and radioactive ribonucleotide diphosphate as the substrate. Incorporation of the radioactive substrate [14C]CDP into DNA was linear over 30 min and was linear with the amount of extract, which provided RR activity. The reaction was inhibited by hydroxyurea and required Mg2+ and ATP, suggesting that the assay is specific to RR activity. While RR activities determined by our method and by a conventional method were comparable, this novel method proved to be simpler, faster, more sensitive and less expensive. In addition, assay of the RR activity for multiple samples can easily be performed simultaneously. It is superior to other RR assays in all aspects.

Calibration↗

PubMed1998

Quantification of 5-(hydroxymethyl)uracil in DNA by gas chromatography/mass spectrometry: problems and solutions.

Oxidation of the thymine methyl group results in the formation of 5-(hydroxymethyl)uracil (HmU). HmU is a recognized endogenous DNA damage product, and HmU levels in DNA are increased by oxidant stress. Previous studies have reported substantially conflicting values for HmU levels in DNA. In studies utilizing postlabeling methods, HmU levels have been reported to be as high as or higher than the levels of some of the more commonly described DNA oxidation damage products such as 8-oxoguanine. In some studies utilizing GC/MS methods, however, HmU has been undetectable. In acid solution, the hydroxymethyl group of HmU can undergo condensation reactions with carboxylic acids, alcohols, and amines. While HmU can be accurately measured by GC/MS, the first step in the preparation of samples for GC/MS analysis is acid hydrolysis of the DNA. Such hydrolysis would be expected to result in substantial derivatization of HmU. We have utilized chemically synthesized oligonucleotides containing a known amount of HmU as well as an isotopically enriched standard to investigate the chemical modification of HmU during the acid hydrolysis of DNA. We conclude that HmU levels reported by GC/MS following acid hydrolysis may be up to an order of magnitude lower than the actual levels. Further, we propose modifications to the standard hydrolysis protocols which maximize recovery of HmU prior to silylation and analysis by GC/MS.

DNA↗

PubMed1998

Guar gum-based sustained release diltiazem.

PURPOSE: This study was performed to examine the use of guar gum to sustain the release of diltiazem under in vitro and in vivo conditions. METHODS: Guar gum tablet formulations were prepared and evaluated under a variety of in vitro dissolution conditions. The formulations, along with Dilacor XR, were administered to a group eight fasted, healthy volunteers in a four period crossover study. RESULTS: Varying the lot of guar gum as well as using guar from different suppliers had little effect on diltiazem dissolution. Also, dissolution of diltiazem from guar gum tablets was essentially independent of stir speed under normal conditions (USP Apparatus II) The stability of guar-based formulations under stressed conditions (40 degrees C/75% relative humidity for 3 months) was also established. All four formulations gave similar plasma concentrations over time in the healthy volunteers pharmacokinetic study. CONCLUSIONS: Guar gum-based matrix tablets represent a simple and economical alternative to existing diltiazem sustained release dosage forms.

Antihypertensive Agents↗