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Biomedical subjects

J Lai

Publications and source records attributed to J Lai.

At least 73 records · Page 4Linked to original sources
PubMed1999

Transvaginal ultrasound diagnosis of a live twin tubal ectopic pregnancy.

A case of live twin tubal ectopic pregnancy diagnosed by transvaginal ultrasound is presented. This is a rare occurrence and we have calculated the incidence to be approximately 1:125,000 pregnancies. There have been more than 100 case reports of twin tubal ectopic pregnancy but only four previous reports where two foetal heart motions have been visualized. The introduction of high-resolution transvaginal ultrasound has resulted in earlier diagnosis of ectopic pregnancy and contributed to the decrease in morbidity that has occurred over recent years.

Adult↗
PubMed1999

Application of laser scanning confocal microscopy in the analysis of particle-induced pulmonary fibrosis.

Laser scanning confocal microscopy (LSCM) allows us to simultaneously quantitate the degree of lung fibrosis and distinguish various pathological lesions of intact lung tissue. Lucifer Yellow has been shown an ideal fluorescent stain to examine the connective tissue matrix components of embedded lung tissue with LSCM. We evaluated the use of LSCM in quantitating lung fibrosis and compared this procedure with the more traditional method of assessing fibrosis by measuring hydroxyproline, a biochemical assay of collagen. CD/VAF rats were intratracheally dosed with silica (highly fibrogenic), Fe2O3 (non-fibrogenic), and saline (vehicle control) at a high dose of 10-mg/100 g body weight. At 60 days post-instillation, the left lung was dissolved in 6 M HCl and assayed for hydroxyproline. Silica induced increases of 58% and 94% in hydroxyproline content over the Fe2O3 and control groups, respectively. The right lung lobes were fixed, sectioned into blocks, dehydrated, stained with Lucifer Yellow (0.1 mg/ml), and embedded in Spurr plastic. Using LSCM and ImageSpace software, the tissue areas of ten random scans from ten blocks of tissue for each of the three groups were measured, and three-dimensional reconstructions of random areas of lung were generated. The silica group showed increases of 57% and 60% in the lung areas stained by Lucifer Yellow over the Fe2O3 and control groups, respectively. Regression analysis of hydroxyproline vs. lung tissue area demonstrated a significant positive correlation (p < 0.05) with a correlation coefficient of 0.91. Histological analysis of right lung tissue revealed a marked degree of granulomatous interstitial pneumonitis for the silica group, which was absent in the Fe2O3 and control groups. No significant differences (p < 0.05) in hydroxyproline content and measured tissue area were observed between the Fe2O3 and control groups. LSCM, and its associated advanced image analysis and three-dimensional capabilities, is an alternative method to both quickly quantitate and examine fibrotic lung disease without physical disruption of the tissue specimen.

Animals↗
PubMed1999

In situ microscopic analysis of asbestos and synthetic vitreous fibers retained in hamster lungs following inhalation.

Hamsters breathed, nose-only, for 13 weeks, 5 days/week, 6 hr/day, either man-made vitreous fiber (MMVF)10a, MMVF33, or long amosite asbestos at approximately 300 World Health Organization (WHO) fibers/cc or long amosite at 25 WHO fibers/cc. [World Health Organization fibers are longer than 5 microm and thicker than 3 microm, with aspect ratio >3.] After sacrifice, fiber burden was estimated (left lungs) by ashing and scanning electron microscopy (ashing/SEM) or (right middle lobes) by confocal laser scanning microscopy (CLSM) in situ. In situ CLSM also provided three-dimensional views of fibers retained, undisturbed, in lung tissue. Fibers of each type were lodged in alveoli and small airways, especially at airway bifurcations, and were seen fully or partly engulfed by alveolar macrophages. Amosite fibers penetrated into and through alveolar septa. Length densities of fibers in parenchyma (total length of fiber per unit volume of lung) were estimated stereologically from fiber transsections counted on two-dimensional optical sections and were 30.5, 25.3, 20.0, and 81.6 mm/mm3 for MMVF10a, MMVF33, and low- and high-dose amosite, respectively. Lengths of individual fibers were measured in three dimensions by tracking individual fibers through series of optical sections. Length distributions of amosite fibers aerosolized, but before inhalation versus after retention in the lung were similar, whether determined by ashing/SEM or in situ CLSM. In contrast, the fraction of short MMVF10a and MMVF33 fibers increased and the geometric mean fiber lengths of both MMVFs decreased by approximately 60% during retention. Most likely due to fiber deposition pattern and differences in sampling, fiber burdens [MMVF10a, MMVF33, and amosite (high dose; 269 WHO fibers/cc)] determined by ashing/SEM were 1.4, 1. 5, and 3.5 times greater, respectively, than those calculated from in situ CLSM data. In situ CLSM is able to provide detailed information about the anatomic sites of fiber retention and also fiber lengths and burdens in good agreement with ashing/SEM results.

Administration, Inhalation↗
PubMed1999

High-affinity interaction of (des-Tyrosyl)dynorphin A(2-17) with NMDA receptors.

The opioid peptide dynorphin A elicits non-opioid receptor-mediated, neurotoxic response in vivo, which is blocked by pretreatment with MK-801, a noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist. In the present study, we examined the possible direct interaction of dynorphin A on the NMDAR. A nonopioid dynorphin A analog, (125)I-(des-tyrosyl) dynorphin A(2-17), was used in radioligand binding analysis on rat cortical brain membranes. This radioligand exhibited a saturable, specific binding at high affinity with a K(d) value of 9.4+/-1.6 nM and maximal binding of 2.4+/-0.6 pmol/mg protein. This binding site was associated with the NMDAR complex because it was modulated by a number of NMDAR ligands. Transient expression of the rat NR1a/NR2A complex in human embryonic kidney 293 cells confirmed a coexpression of (125)I-(des-tyrosyl) dynorphin A(2-17), [(3)H]CGP39,653, and [(3)H]MK-801 binding. These data provide direct evidence of the presence of a high-affinity binding site for dynorphin A on the NMDAR. The modulatory effect of the various NMDAR-selective ligands on dynorphin A binding suggests that dynorphin A may bind preferentially to the closed/desensitized state of the NMDAR. The physiological role of dynorphin A binding to the NMDAR remains to be established.

2-Amino-5-phosphonovalerate↗
PubMed1999

Pharmacokinetics of radiolabeled polyclonal antiferritin in patients with Hodgkin's disease.

The objective was to identify pharmacokinetic parameters predictive for tumor response and normal tissue side effects after i.v. administered radiolabeled rabbit antihuman ferritin IgG. Twenty-eight patients with recurrent Hodgkin's disease received 2 mg of rabbit antihuman ferritin i.v., labeled with 4-7 mCi of In-111 followed by two doses of 0.25, one dose of 0.3, or one dose of 0.4 mCi of Y-90-labeled antiferritin per kg of body weight 1 week later. Radioactivity and HPLC measurements of blood and urine samples and liver and tumor volumes identified on sequential whole-body scans provided the data for a pharmacokinetic analysis covering the first 6 days after the administration of the radioimmunoconjugate. Side effects and tumor response were recorded. Temporary hematological toxicity was noted in all patients. Sixteen patients showed a tumor response. The Y-90 blood level at 1 h after administration correlated with the severity of subsequent hematological toxicity. The rapid blood elimination half-life of radioactivity was 4.4 h. Less than 5% of the administered radioactivity was eliminated in the first 24 h urine. The slow blood elimination half-life was 44 and 37 h for In-111 and Y-90, respectively. One of 12 retreated patients produced anti-rabbit IgG antibodies. The volume of distribution was larger for Y-90 than for In-111-labeled antiferritin (160 versus 110% of estimated blood volume). Accidentally extravasated rabbit IgG was rapidly catabolized in perivascular tissues with an effective half-life of less than 35 h. Slower catabolism was noted for rabbit IgG in blood (t(1/2) = 40 h), liver (t(1/2) = 62 h) or tumor (t(1/2) = 40-80 h). Twelve of 13 patients with an effective tumor half-life > 57 h showed a tumor response. I.v. administered polyclonal rabbit antihuman ferritin, labeled with In-111 or Y-90 is stable in vivo and targets Hodgkin's disease. Intravascular Y-90 causes a vascular leak and a larger volume of distribution for antiferritin. Elevated Y-90 blood levels at 1 h and a tumor half-life of >57 h predict for hematological toxicity and tumor response, respectively.

Adult↗
PubMed1999

Fractionated radiolabeled antiferritin therapy for patients with recurrent Hodgkin's disease.

The objective of this study was to determine the therapeutic ratio of fractionated radiolabeled immunoglobulin therapy (RIT) for patients with recurrent Hodgkin's disease. Ninety patients with recurrent Hodgkin's disease received 2 mg of yttrium-90-labeled polyclonal rabbit antihuman ferritin IgG i.v. Fifty-seven patients received a single (unfractionated) administration per treatment cycle; 11 of them were treated with 0.3 mCi/kg body weight, 39 were treated with 0.4 mCi/kg body weight, and 7 received 0.5 mCi/kg body weight per treatment cycle. Thirty-three patients had their radiolabeled immunoglobulin administration separated (fractionated) in 2 x 0.25 mCi/kg body weight (total activity, 0.5 mCi/kg). The interval between fractions was 1 week. Radioimmunoconjugates did not cause serious acute side effects. In vivo radioimmunoconjugates were stable. Human antirabbit IgG antibodies were found in 2 of 50 retreated patients (<5%). Hematological toxicity was the only side effect noted in all patients, and it was usually temporary. Response rates (RRs) were 20%, 61%, and 86% after 0.3, 0.4, or 0.5 mCi/kg unfractionated yttrium-90-labeled antiferritin. The RR for patients treated with fractionated RIT was 42%. In the fractionated RIT group, complete responses were decreased, and progressive disease increased (P < 0.05). Complete responses had a medium duration of 6 months. Median survival times were 390 days for 1 x 0.4 mCi/kg and 300 days for the 2 x 0.25 mCi/kg patient group. Fractionation did not provide the expected decrease in hematological toxicity or the expected increase in tumor RRs.

Adolescent↗
PubMed1999

Assays of ligand-human serum albumin binding using pulsed ultrafiltration and liquid chromatography-mass spectrometry.

Two approaches were utilized to increase the throughput of pulsed ultrafiltration assays of ligand binding to human serum albumin, reducing the volume of the ultrafiltration chamber and combining pulsed ultrafiltration with high performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC-MS). Affinity constants for binding of ligands to human serum albumin were determined using pulsed ultrafiltration with ultraviolet absorbance detection. The first affinity constants (Ka1) were measured for the binding of dansylsarcosine, dansylamide, 7-anilinocoumarin-4-acetic acid and warfarin, and were determined to be 1.8 x 105, 5 x 104, 8 x 104, and 2.0 x 105 M-1, respectively. The throughput of pulsed ultrafiltration analyses was tripled compared to previous pulsed ultrafiltration measurements by reducing the volume of the chamber. In addition, the use of LC-MS with pulsed ultrafiltration permitted the simultaneous comparison and rank ordering of ligand mixtures for binding to serum albumin. For example, the throughput of these pulsed ultrafiltration measurements was tripled by analyzing three ligands as a mixture.

Chromatography, Liquid↗
PubMed1998

Spinal opioid mu receptor expression in lumbar spinal cord of rats following nerve injury.

Previous studies in rats have shown that spinal morphine loses potency and efficacy to suppress an acute nociceptive stimulus applied to the tail or the paw following injury to peripheral nerves by tight ligation of the L5/L6 spinal nerves. Additionally, intrathecal (i.th.) morphine is ineffective in suppressing tactile allodynia at fully antinociceptive doses in these animals. The molecular basis for this loss of morphine potency and efficacy in nerve injury states is not known. One possible explanation for this phenomenon is a generalized, multi-segmental loss of opioid mu (mu) receptors in the dorsal horn of the spinal cord after nerve injury. This hypothesis was tested here by determining whether nerve injury produces (a) a decrease in mu receptors in the lumbar spinal cord; (b) a decrease in the affinity of ligand-receptor interaction, (c) a decrease in the fraction of high-affinity state of the mu receptors and (d) a reduced ability of morphine to activate G-proteins via mu receptors. Lumbar spinal cord tissues were examined 7 days after the nerve injury, a time when stable allodynia was observed. At this point, no differences were observed in the receptor density or affinity of [3H]DAMGO (mu selective agonist) or [3H]CTAP (mu selective antagonist) in the dorsal quadrant of lumbar spinal cord ipsilateral to nerve injury. Additionally, no change in morphine's potency and efficacy in activating G-proteins was observed. In contrast, staining for mu opioid receptors using mu-selective antibodies revealed a discrete loss of mu opioid receptors localized ipsilateral to the nerve injury and specific for sections taken at the L6 level. At these spinal segments, mu opioid receptors were decreased in laminae I and II. The data indicate that the loss of mu opioid receptors are highly localized and may contribute to the loss of morphine activity involving input at these spinal segments (e.g., foot-flick response). On the other hand, the lack of a generalized loss of opioid mu receptors across spinal segments makes it unlikely that this is the primary cause for the loss of potency and efficacy of mu opioids to suppress multi-segmental reflexes, such as the tail-flick response.

Animals↗
PubMed1998

Opioid peptide receptor studies. 7. The methylfentanyl congener RTI-4614-4 and its four enantiomers bind to different domains of the rat mu opioid receptor.

Mutational analysis of opioid receptors supports the hypothesis that dissimilar receptor domains contribute to the binding affinity of different ligands. To determine whether enantiomeric ligands can serve to distinguish between different binding pockets (which focuses the analysis on asymmetric structural factors while avoiding confounding changes in physiochemical characteristics), we analyzed the binding of the 3-methylfentanyl congeners RTI-4614-4 [(+/-)-cis-N-[1-(2-hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N- phenylpropanamide HCl)], its four stereoisomers [(2S,3R,4S)-1a, (2R,3R,4S)-1b, (2R,3S,4R)-1c, and (2S,3S,4R)-1d], and other mu agonists with cloned rat mu opioid receptors stably expressed in HEK-293 cells and mu/kappa receptor chimeras. Chimera III (kappa[aminoacids 1-141]/mu[aminoacids 151-398]), chimera IV (mu[aminoacids 1-150]/kappa[aminoacids 142-380]), and chimera XII (kappa[aminoacids 1-262]/mu[aminoacids 269-398]) bound [(125)I]IOXY (6beta-iodo-3,14-dihydoxy-17-cyclopropylmethyl-4,5alpha++ +-epoxymorphinan) with high affinities. The Ki values of 1a, 1b, 1c, and 1d at the wild-type mu receptor were 0.55 nM, 0.66 nM, 124 nM, and 59.2 nM, respectively. When the region from the N terminal to the start of the transmembrane helix 3 (TMH3) of the mu receptor was substituted by that of the kappa receptor (chimera III), the Ki value of 1b was increased (relative to the mu receptor) 590-fold compared to a 73-fold increase for 1a. When this portion of the kappa receptor was replaced by that of the mu receptor (chimera IV), the loss of affinity was not as great: 11.7-fold for 1a and 58.5-fold for 1b. Replacement of the middle of the third intracellular loop and third extracellular loop (e3) of the kappa receptor with that of the mu receptor (chimera XII) lowered (relative to their Ki values at the kappa receptor) the Ki values of [D-Ala2,D-Leu5]enkephalin and [D-Ala2-MePhe4,Gly-ol5]enkephalin to a much greater extent than the Ki values of the isomers. The kappa/chimera XII shift was greater for isomers 1c and 1d than for 1b and 1a. Viewed collectively, these data suggest that the region from the N terminal to the start of the TMH3 of the mu opioid receptor determines the binding affinity of RTI-4614-4 and its isomers and that the e3 loop also plays a major role in determining the binding affinity of mu agonist peptides. These data also show that the stereoisomers of RTI-4614-4 probably bind to different domains of the mu receptor and suggest that manipulation of stereochemistry may be a useful tool for designing domain-specific ligands.

Affinity Labels↗
PubMed1998

Opioid peptide receptor studies. 8. One of the mouse brain deltaNCX binding sites is similar to the cloned mouse opioid delta receptor: further evidence for heterogeneity of delta opioid receptors.

Quantitative ligand binding studies resolved two subtypes of the delta opioid receptor, termed delta(ncx1) and delta(ncx2), in mouse brain membranes depleted of mu receptors by pretreatment with the irreversible ligand, BIT. The purpose of the present study was to compare the binding parameters, ligand-selectivity profile and pharmacological properties of the cloned mouse delta receptor (MDOR) stably expressed in a cell line to the delta(ncx) binding sites of mouse brain. [3H][D-Ala2,D-Leu5]enkephalin labeled a single binding site in membranes prepared from MDOR cells under several different assay conditions including BIT-pretreatment. The MDOR had high affinity for delta agonists and antagonists. [3H][D-Ala2,D-Leu5]enkephalin labeled two binding sites in mouse brain membranes depleted of mu receptors by pretreatment with BIT: the delta(ncx1) site (high affinity for DPDPE and deltorphin) and the delta(ncx2) site (low affinity for DPDPE and deltorphin). Some agents were moderately selective for the delta(ncx2) site: [pCl]DPDPE (10.9-fold), JP41 (5.9-fold) and JP45 (3.8-fold). The Ki values of 12 opioids at the mouse MDOR were determined. These values were highly correlated with their values at the delta(ncx1) site but not the delta(ncx2) site. These data suggest that the delta(ncx2) site may be distinct from the cloned delta opioid receptor.

Animals↗
PubMed1998

Opioid peptide receptor studies. 9. Identification of a novel non-mu- non-delta-like opioid peptide binding site in rat brain.

Quantitative binding studies resolved two high-affinity [3H][D-Ala2,D-Leu5]enkephalin binding sites in rat brain membranes depleted of mu binding sites by pretreatment with the irreversible agent BIT. The two binding sites had lower (delta ncx-2, Ki = 96.6 nM) and higher (delta ncx-1, Ki = 1.55 nM) affinity for DPDPE. The ligand-selectivity profile of the delta ncx-1 site was that of a classic delta binding site. The ligand-selectivity profile of the delta ncx-2 site was neither mu- or delta-like. The Ki values of selected agents for the delta ncx-2 site were: [pCl]DPDPE (3.9 nM), DPLPE (140 nM), and DAMGO (2.6 nM). Under these assay conditions, [3H][D-Ala2,D-Leu5]enkephalin binding to the cells expressing the cloned mu receptor is very low and pretreatment of cell membranes with BIT almost completely inhibits [3H]DAMGO and [3H][D-Ala2,D-Leu5]enkephalin binding. Intracerebroventricular administration of antisense DNA to the cloned delta receptor selectively decreased [3H][D-Ala2,D-Leu5]enkephalin binding to the delta ncx-1 site. Administration of buprenorphine to rats 24 h prior to preparation of membranes differentially affected mu, delta ncx-1, and delta ncx-2 binding sites. Viewed collectively, these studies have identified a novel non-mu- non-delta-like binding site in rat brain.

Analgesics, Opioid↗
PubMed1998

[Relationship between the risk factors of coronary artery disease and the severity of coronary artery lesions].

OBJECTIVE: To investigate the relationship between the risk factors of coronary artery disease and the severity of the coronary artery lesions. METHODS: A total of 446 consecutivey admitted patients were studied retrospectively. All patients suspected to have coronary artery disease and underwent a selective coronary angiography and a survey of risk factors during the hospitalization. RESULTS: Through Logistic regression analysis, advanced age, smoking, hyperlipidemia and course of diabetes mellitus were confirmed to be independent risk factors for coronary artery disease (OR = 1.02-1.23, P = 0.0406-0.0001). A significant correlation (F = 2.3130-19.2165, P = 0.1291-0.0001) between the severity of the coronary artery lesions and the age, the number of cigarettes in a day, the level of plasma lipids and the course of diabetes mellitus of the patients was found from the multiple regression analysis. CONCLUSIONS: Not only the development but also the severity of the coronary artery lesions is affected by the risk factors of advanced age, smoking, hyperlipidemia, and diabetes mellitus.

Adult↗
PubMed1998

[Determination of aluminium in healthy person's hair by FAAS and FAES].

In this paper, two methods of N2O/C2H2 FAAS and FAES are applied to determine aluminium in healthman hair. The requirement of determination, interferences of inorganic ions and organic substances and the results of determination are contrasted respectively. It is shown experimently that the interference ratio of substances, accuracy, sensitivity and recovery ratio of FAES are superior to FAAS at 396.1 nm wavelength in acidity medium. The RSD (n = 9) of FAES and FAAS are 2.2 and 2.7% respectively and detect limit is 0.07 microg/mL for FAES and 0.25 microg/mL for FAAS. The recovery ratio of adding 20.0 microg aluminium to 1.0 g hair samples are 96.5-105.0% and 93.5-106.5% respectively.

Aluminum↗
PubMed1997

Cadmium inhibits DNA strand break rejoining in methyl methanesulfonate-treated CHO-K1 cells.

The cogenotoxicity of Cd has been recognized. This effect may stem from Cd inhibition of DNA repair. We studied the effects of Cd on DNA repair of methyl methanesulfonate (MMS)-damaged Chinese hamster ovary cells (CHO-K1) by single-cell alkaline electrophoresis. The results indicate that in the presence of Cd, DNA strand breaks accumulated in MMS-treated cells. Using hydroxyurea (Hu) plus cytosine-beta-D-arabinofuranoside (AraC) to block DNA polymerization, DNA strand breaks accumulated and Cd had little inhibitory effects on these accumulations. However, Cd inhibited the rejoining of these DNA strand breaks, which could be rejoined 6 hr after release from Hu plus AraC blockage. These results indicate that the potency of Cd inhibition of DNA repair replication and/or ligation may be greater than the inhibition of DNA adduct excision. To further elucidate this mechanism, we used an in vitro cell-free assay system to analyze the Cd effects on DNA repair synthesis, DNA polymerization, and DNA ligation. We have shown a dose-dependent inhibition of these three activities by Cd in CHO-K1 cell extract. The IC50s of Cd were 55, 26, and 10 microM, respectively. Moreover, Cd inhibition of DNA ligation in cell extract could be recovered partially by thiol compounds such as glutathione, beta-mercaptoethanol, dithiothreitol, and metallothionein. Since both in vivo and in vitro studies demonstrated that Cd was more effectively involved in interfering with the DNA ligation step and that thiol agents could partially remove Cd inhibition of DNA ligation, we speculate that part of the Cd inhibition of DNA repair may be through binding of Cd to the proteins participating in DNA ligation.

Animals↗
PubMed1997

Ventilatory stability to transient CO2 disturbances in hyperoxia and normoxia in awake humans.

Modarreszadeh and Bruce (J. Appl. Physiol. 76: 2765-2775, 1994) proposed that continuous random disturbances in arterial PCO2 are more likely to elicit ventilatory oscillation patterns that mimic periodic breathing in normoxia than in hyperoxia. To test this hypothesis experimentally, in nine awake humans we applied pseudorandom binary inspired CO2 fraction stimulation in normoxia and hyperoxia to derive the closed-loop and open-loop ventilatory responses to a brief CO2 disturbance in terms of impulse responses and transfer functions. The closed-loop impulse response has a significantly higher peak value [0.143 +/- 0.071 vs. 0.079 +/- 0.034 (SD) l . min-1 . 0.01 l CO2-1, P = 0.014] and a significantly shorter 50% response duration (42.7 +/- 13.3 vs. 72.3 +/- 27.6 s, P = 0.020) in normoxia than in hyperoxia. Therefore, the ventilatory responses to transient CO2 disturbances are less damped (but generally not oscillatory) in normoxia than in hyperoxia. For the closed-loop transfer function, the gain in normoxia increased significantly (P < 0.0005), while phase delay decreased significantly (P < 0.0005). The gain increased by 108.5, 186.0, and 240.6%, while phase delay decreased by 26.0, 18.1, and 17.3%, at 0. 01, 0.03, and 0.05 Hz, respectively. Changes in the same direction were found for the open-loop system. Generally, an oscillatory ventilatory response to a small transient CO2 disturbance is unlikely during wakefulness. However, changes in parameters that lead to additional increases in chemoreflex loop gain are more likely to initiate oscillations in normoxia than in hyperoxia.

Adult↗