Biomedical subjects

M Lai

Publications and source records attributed to M Lai.

At least 73 records · Page 4Linked to original sources

PubMed1999

The application of two different blood cell separators to harvest CD34+ cells in patients suffering from non Hodgkin's lymphoma.

From January 1996 until now, thirty-eight PBSC procedures were carried out on 20 patients suffering from NHL, mobilized by polichemotherapy regimens plus recombinant human Granulocyte-Growth Factor (rhG-CSF). Patients were enrolled in PBSC procedures using Dideco Excel (group A) and Cobe Spectra v.4.7 (group B) blood cell separators. Twelve patients were enrolled in group A (6 males and 6 females, median age 33) and 9 patients in group B (5 males and 4 females, median age 55). The mean White Blood Cell (WBC) and Mononuclear Cells Fraction (MNC) peripheral blood counts were not statistically different in either group and neither were blood CD34+ cell peripheral counts. CD34+ cell peripheral value was predictive of the CD34+ yield while mean values of harvested CD34+ cells were not significantly different. CD34+ cell efficiencies were statistically the same. The CD34+ cell purity of the apheresis harvest was statistically different between the two groups (group A = 3.0+/-2.2%; group B = 1+/-0.9%) p = 0.001. High CD34+ cell yields were observed in both groups which confirms that both blood cell separators are able to harvest hematopoietic progenitor cells from peripheral blood.

Adolescent↗

PubMed1999

[Comparison of results of chamber angle examination by ultrasound biomicroscopy and gonioscopy].

OBJECTIVE: To compare the consistency of the chamber angles examined by ultrasound biomicroscope (UBM) and gonioscope and provide gonioscopic examination with new methods and technology. METHODS: 10 patients (20 eyes) were selected for the research. The same eyes were examined by UBM and gonioscope in turns. The results from the two methods were compared and the data were analyzed with Spearman correlation test. RESULTS: The results of two methods of chamber angle examination were well consistent when the angle was wide, but the consistency was not good when it was narrow. The angle examined by a gonioscope was wider than that by UBM. When the iris root insertion was evaluated in a narrow angle, the consistency was also not good, and when the peripheral iris morphology was evaluated, there were almost inconsistent results in one-fourth of the patients. CONCLUSIONS: The results of chamber angle examined by a gonioscope show a little wider than its natural status. Especially, it is difficult to distinguish the functional closure from the adhesive closure. Under the influence of light, the determination of iris root insertion by a gonioscope has a sense of conjecture. When peripheral iris morphology is evaluated, the influence of irregular iris might result in a wrong conclusion. Therefore, the technique of gonioscopic examination should be improved.

Adult↗

PubMed1999

[Microsatellite alterations on chromosome 9p21-22 in sporadic colorectal cancer].

OBJECTIVE: To study whether alteration of p16 plays an important role in the development of colorectal carcinomas and the relationship between the molecular changes of 9p21-22 chromosome subregion in sporadic colorectal cancers. METHODS: To detect microsatellite instability (MSI) and loss of heterozygosity (LOH) by PCR, denatured-polyacrylamide gel-electrophoresis and silver staining (microsatellite DNA-PCR-silver staining method) and to compare the results with the clinopathological parameters. RESULTS: Between MSI positive and negative cases and the clinopathological findings, some evidences found in the MSI positive group were as follows: (1) tendency towards younger patients (usually < 50 years in age, P < 0.05); (2) more frequently seen in mucoid carcinomas (P < 0.01). CONCLUSIONS: Microsatellite DNA-PCR-silver staining method is very sensitive in detecting even a tiny change of a single base. MSI occured in the selected microsatellite loci of different subregions and different chromosomes might be different in significance, therefore, a right choice of the suitable loci for studying the microsatellite changes is important. Since the frequency of loss of heterozygosity at 9p21-22 is low (merely 8.42%), it is considered that p16 is not closely associated with the development of sporadic colorectal cancer.

Adult↗

PubMed1998

Phase II study of Temodal in the treatment of patients with advanced nasopharyngeal carcinoma.

PURPOSE: A single-institution phase II trial of Temodal (temozolomide, SCH52365) in Chinese patients with advance nasopharyngeal carcinoma was undertaken to determine the efficacy and safety of the drug in this population. METHODS: A total of 14 patients with metastatic or locoregionally recurrent nasopharyngeal carcinoma were entered into the study. One patient was unevaluable. Temodal was given at doses of 150 or 200 mg/m2 daily on days 1-5 every 28 days. RESULTS: In all, 30 cycles of Temodal were given with no significant toxicity. All 13 (100%) evaluable patients had progressive disease after 2 (84.6%) or 4 (15.4%) courses. CONCLUSION: Temodal given on this schedule has no activity in advanced nasopharyngeal carcinoma.

Adult↗

PubMed1998

Capillary electrophoresis separation of an asparagine containing hexapeptide and its deamidation products.

A capillary electrophoresis (CE) method was developed for the separation of a model hexapeptide (L-Val-L-Tyr-L-Pro-L-Asn-Gly-L-Ala) and its degradation products. Separations using CE had much shorter analysis times than the RP-HPLC assay used previously. CE was also evaluated for possible use in analyzing peptide samples containing polymers. With a thorough rinsing procedure between runs, the presence of a model polymer did not affect the separation of the peptides. The CE assay can be applied to the study of peptide stability in polymers.

Asparagine↗

PubMed1998

Splenic sympathetic response to endotoxin is blunted in the fetal alcohol-exposed rat: role of nitric oxide.

This study was designed to test the hypothesis that nitric oxide (NO) mediates the blunted splenic sympathetic response to lipopolysaccharide (endotoxin) that occurs in young rats exposed to alcohol in utero (FAE). The subjects, 26-29-day-old rats, were progeny of pregnant dams fed an alcohol diet (35% of the calories were derived from ethanol) or their control and pair-fed (PFC) cohorts. We examined the effects of lipopolysaccharide (LPS) (0.5 mg/kg, i.p.) on splenic norepinephrine (NE) turnover, an index of sympathetic neural activity, splenic inducible NO synthase (iNOS) protein immunoreactivity, and NO metabolites nitrite/nitrate concentrations in plasma. In response to LPS, splenic NE turnover was increased by more than twofold in the PFC groups, but the increase did not occur in their FAE cohorts. The blockade of NOS with L-NAME (30 mg/kg, i.p.) reversed this difference. In both the PFC and FAE rats, basal levels of splenic iNOS protein immunoreactivity were equally barely detected and plasma NO metabolite levels were relatively low (25 microM in both groups). In response to LPS, however, iNOS protein displayed a marked increase in the PFC group and an even greater increase (by close to threefold) in the FAE rats. LPS also substantially increased plasma NO metabolite levels by close to eightfold in the control groups, but by 15-fold in their FAE cohorts compared to the basal levels. These findings support the hypothesis that in the FAE rat, an augmented NO formation accounts for the blunted sympathetic response to endotoxin.

Animals↗

PubMed1998

An evaluation of two-phase treatment with the Herbst appliance and preadjusted edgewise therapy.

The purpose of this study was to evaluate the skeletal and dentoalveolar changes occurring during two-phase orthodontic treatment. A cephalometric study of Class II correction was carried out in 40 subjects (20 females, 20 males) who had been treated with the acrylic-splint Herbst appliance immediately followed by a second phase of preadjusted edgewise therapy. The average age at the start of Herbst therapy was 12.5 +/- 0.8 years for females and 13.6 +/- 1.2 years for males. Descriptive cephalometric data were compared with the normative values derived from the University of Michigan Elementary and Secondary School Growth Study. Control values were generated for each of the 40 Herbst patients based on gender, initial age, and duration of treatment. The results of this study indicate that the Class II correction achieved during Phase I treatment with Herbst appliance was due mainly to an increase in mandibular length, as well as distal movement of the maxillary molars and mesial movement of the mandibular molars and incisors. The accelerated mandibular growth rate observed during Herbst therapy was followed by a diminished growth rate during the edgewise phase that was less than control values. The overall increase in mandibular length was slight (approximately 1 mm), but significantly greater than control data for the whole group and the male subgroup; however, it was not significantly different between the treatment group and control data in the female subgroup. There were no significant treatment effects on lower anterior facial height and the mandibular plane angle at the end of either phase of treatment. The skeletal changes contributed to 55% of the molar correction during the Herbst therapy, whereas at the end of the second phase of treatment, skeletal change accounted for 80%. Significant anteroposterior dentoalveolar rebound was seen during the edgewise phase.

Adolescent↗

PubMed1998

Heterogeneity in the occurrence of a subset of autoantibodies to glutamic acid decarboxylase in autoimmune polyendocrine patients with islet cell antibodies.

Glutamic acid decarboxylase-65 (GAD-65) is a major target for autoantibodies and autoreactive T cells in patients with insulin-dependent diabetes mellitus (IDDM). Autoantibodies to GAD are also found in patients with stiff man syndrome (SMS) or polyendocrine autoimmunity (PE). The epitope specificities of autoantibodies to GAD in IDDM and SMS have been well documented, but the locations of autoantibody epitopes of GAD in PE patients have not been mapped. Thus, the properties of anti-GAD antibodies in PE patients (with or without diabetes) were investigated. The ability of PE serum antibodies to inhibit the binding of the mouse monoclonal antibody, GAD-6, to native GAD in ELISA was determined. For PE patients without diabetes, levels of inhibition of GAD-6 binding ranged from 0% to almost 70% and were unrelated to the level of binding of serum antibodies to GAD (P = 0.351) or to the functional affinities of these antibodies. This suggests differences in the epitope specificities of anti-GAD antibodies in different patients. Levels of inhibition were also unrelated to clinical condition. SMS antibodies showed similar levels of inhibition of GAD-6 binding. Similar analysis was applied to PE patients with diabetes and levels of inhibition of GAD-6 binding to GAD were determined. These ranged from 0% to 80%, and levels of inhibition were similar in samples taken before or after diabetes onset. There was no significant difference between anti-GAD antibodies from PE patients with or without diabetes in the range of abilities to inhibit GAD-6 binding to GAD, although the highest levels of inhibition were given by sera from non-diabetic patients. This raises the possibility of differential expression of subsets of anti-GAD antibodies in progressive versus slow or non-progressive anti-islet autoimmune responses. Serum antibodies of PE and SMS patients did not inhibit the binding of antibodies specific for the extreme C-terminus of GAD, indicating that this is not the site of the epitopes for the patients' antibodies or for GAD-6.

Adolescent↗

PubMed1998

Conserved T-cell receptor class II major histocompatibility complex contact detected in a T-lymphocyte population.

T-cell receptor (TCR) interacts with an antigenic peptide deeply buried in the major histocompatibility complex (MHC) molecule. How class II MHC is contacted by TCR during antigen recognition remains largely elusive. Here we used a panel of I-Ek mutants to identify two I-Ek residues that were frequently contacted by TCR among a large pool of T cells specific for the same antigen. The restricted TCR interaction with I-Ek was independent of the antigen peptides. We also identified a dominant heteroclitic residue on I-Ek, beta81H, in which mutation led to increased recognition of antigens in individual T-cell clones. Moreover, both the conserved TCR-I-Ek interaction and the heteroclitic TCR-I-Ek recognition were detected in T lymphocytes freshly isolated from mice primed with the specific antigens. The identical TCR-I-Ek interaction in a heterogeneous T-cell population suggested the dominance of invariant TCR-class II MHC interaction.

Animals↗

PubMed1998

Quantitative techniques for lesion load measurement in multiple sclerosis: an assessment of the global threshold technique after non uniformity and histogram matching corrections.

The quantitative assessment of abnormalities on brain MRI (magnetic resonance imaging) in multiple sclerosis (MS) provides a widely used endpoint in monitoring treatment efficacy. Semi-automated intensity thresholding (global thresholding) is an established method of lesion segmentation, but it is limited by the heavy dependence of derived volumes on the chosen intensity threshold. Inconsistency in threshold choice substantially contributes to its suboptimal reproducibility. A potential improvement to global thresholding is to utilize the histogram matching algorithm to correct for variations in scanner sensitivity. This study evaluated whether or not a single intensity threshold could then be applied across multiple histogram matched images. Eight MS patients were scanned at baseline and after nine months. After non-uniformity correction, the histogram matching correction was applied, reducing the mean absolute percentage variation in normal appearing white matter signal intensity from 15.2 to 3.8% for baseline scans and from 11.9 to 2.1% across serial studies. Lesion volumes were measured with the global threshold technique using a single threshold selected from one scan. A local thresholding technique (contouring) was also performed as a gold standard measure. Agreement between techniques for baseline lesion volumes was only moderate with an intra-class correlation coefficient (ICC) of 0.46 and there was little agreement for change in lesion volume (ICC = 0.17), reflecting inconsistencies in the volume of non-lesion regions included by the threshold. Agreement was improved by deleting non-lesion regions, but this was time consuming and less reproducible than contouring method. At present, the contour technique remains a more appropriate method for lesion load quantification.

Journal Article↗

PubMed1998

Serial magnetization transfer imaging to characterize the early evolution of new MS lesions.

OBJECTIVE: To explore the temporal relation of demyelination and blood-brain barrier breakdown during new lesion formation. BACKGROUND: Conventional MRI appears sensitive for detecting changes due to MS, but may be limited by poor pathologic specificity. By indirectly assessing protons bound to rigid macromolecules, magnetization transfer (MT) imaging may provide information relating to tissue structure and, by inference, myelin integrity. METHODS: Gadolinium contrast-enhanced MRI and MT imaging were performed at weekly intervals for 3 months in three patients with MS. For each enhancing lesion, the largest corresponding area of proton density hyperintensity seen during the study was outlined and magnetization transfer ratio (MTR) calculated at each time point from coregistered calculated MTR images. Lesions greater than 20 mm2, not affected by partial volume effects, and first enhancing after the baseline study were analyzed. Two-dimensional registration software allowed accurate evaluation of MTR in regions both before and after the initial appearance of MS lesions. RESULTS: Mean lesion MTR decreased significantly during the first week of enhancement (29.6 percent units [pu] immediately pre-enhancement versus 28.2 pu at first documented stage of enhancement). No significant MTR reduction was noted before this. CONCLUSION: The lack of observable change in MTR before the first detectable gadolinium enhancement within MS lesions suggests that blood-brain barrier disruption is closely related to, but not preceded by, demyelination.

Adult↗

PubMed1998

Cell wall active antifungal compounds produced by the marine fungus Hypoxylon oceanicum LL-15G256. III. Biological properties of 15G256 gamma.

15G256 gamma is a cyclic lipopeptide antifungal agent discovered in a mechanism of action screen for cell wall acting antifungal agents. The compound shows moderate activity in both greenhouse tests against plant disease caused by pathogenic fungi and in in vitro tests against human fungal pathogens. Microscopic examination of treated fungi suggests that the compound acts by the inhibition of cell wall biosynthesis. However, in vitro inhibition of Neurospora crassa glucan and chitin synthase were only observed at high drug concentrations suggesting that 15G256 gamma may act on a novel cell wall target.

Antifungal Agents↗

PubMed1998

[Ultrasound biomicroscopic dark room provocative test].

OBJECTIVE: To compare the clinical application of ultrasound biomicroscopic (UBM) dark room provocative test and traditional one in screening primary angle-closure glaucoma (PACG). METHOD: 22 eyes (22 cases) with PACG in prodromal stage and 30 eyes (15 cases) with deep anterior chamber and wide angle of 15 normal persons were observed in this trial. Traditional dark room provocative test and UBM dark room provocative test were performed on all the 52 eyes at the same day time on separate days. With different positive diagnostic criteria, the sensitivity of the two methods was compared by using chi-square analysis. RESULTS: After staying in dark room for 2 hours, in PACG group, the intraocular pressure (IOP) in 10 of 22 eyes raised more than 1.07 kPa (1 kPa = 7.5 mmHg), and in 12 eyes less than 1.07 kPa or had no changes; appositional angle closure was found by Goldmann gonioscopy in 8 eyes; 3 eyes in two quadrants, 5 eyes in more than two quadrants; the appositional angle closure was found by ultrasound biomicroscopy in 15 eyes; 3 eyes in one quadrant, 5 eyes in two quadrants, 7 eyes in more than two quadrants. In the control group, IOP raised more than 1.07 kPa in 3 eyes. There was no appositional angle closure found in the control group. With the appositional angle closure as a positive diagnostic criterion, the sensitivity of the traditional test and UBM dark room test was 31.8% and 68.2%, respectively. With statistic chi-square test, there is a statistically significant difference between the two methods (P < 0.05). CONCLUSIONS: The sensitivity of UBM dark room provocative test is higher than that of the traditional one. The specificity of both methods is 100%. UBM dark room provocative test elevates the sensitivity and specificity of traditional dark room test, and reduces the false negative or positive rate in screening PACG, that is helpful to its accurate diagnosis.

Glaucoma, Angle-Closure↗

PubMed1998

[Quantitative real time measurement of iris configuration in living human eyes].

OBJECTIVE: To evaluate the intraobserver and interobserver reproducibility of real time measurement of iris morphology in living human eyes. METHODS: Based on the platform of software (Autocad, version 12), we developed an ultrasound biomicroscopy (UBM) image assistant measuring system. Using the system, we can perform the iris configuration quantitative measurement in living eyes. The measuring parameters include: iris rest length, radius of iris curvature and the thickness of different part of iris. Ten anterior segment images of one normal individual were obtained by a single operator to evaluate the intraobserver reproducibility of image capture, and ten times of measurement of one image were performed by a single operator to assess the reproducibility of image measurement. The measurements of three independent observers were compared to investigate interobserver reproducibility in quantitative measurement. Intraobserver and interobserver reproducibility of measurement were assessed by calculating the coefficient of variation for each individual observer and by using F test to detect a difference among the observers. The iris configurations of 96 subjects (192 eyes) were measured. RESULTS: Intraobserver reproducibility ranged from 0.9 - 4.9% in all measured parameters. Interobserver reproducibility for some of the measured parameters varied considerably and was affect by subjective interpretation of visualized anatomic landmarks. The preliminary measured parameters in Chinese show that iris rest length is 3.699 +/- 0.397 mm, radius of iris curvature is 9.101 plus minus 1.408 mm, the average thickness of iris is 0.406 +/- 0.042 mm. CONCLUSIONS: The intraobserver reproducibility and the measured accuracy can fit the requisition of the ocular biometry, physiology and pharmacology studies. The method supplies a new assistance for UBM image measurement.

Female↗

PubMed1997

Focal brain injury increases activin betaA mRNA expression in hippocampal neurons.

The role of activin in the mammalian brain is of increasing interest as evidence accumulates to suggest a number of different neural functions. Here, we report that activin betaA mRNA is transiently induced in dentate gyrus neurons after unilateral mechanical brain injury by saline injection. Expression is dependent on NMDA receptor activation since pretreatment with MK801 (5 mg/kg, i.p.) largely attenuates the signal. Induction also requires de novo protein synthesis, as cycloheximide (10 mg/kg, i.p.) pretreatment abolishes the expression of activin betaA mRNA 1 h after injury. These results show that activin betaA mRNA expression is regulated by excitatory activity induced by focal brain injury and suggests a possible neuroplastic role in the recovery from such injury.

Animals↗

PubMed1997

Effect of dimerization on signal transduction and biological function of oncogenic Ros, insulin, and insulin-like growth factor I receptors.

The avian sarcoma virus UR2 codes for an oncogenic Gag-Ros fusion protein-tyrosine kinase (PTK). We have previously derived two retroviruses, T6 and NM1, coding for oncogenic Gag-insulin receptor and Gag-insulin-like growth factor I receptor (IGFR) fusion proteins, respectively. The Gag-IGFR fusion protein dimerizes, whereas Gag-Ros does not. To identify sequences affecting dimerization and the effect of dimerization on signaling and biological functions, we generated recombinants exchanging the extracellular and transmembrane sequences among the three fusion receptors. The presence of multiple cysteines in the Gag sequence appears to preclude dimerization, since deletion of the 3' cysteine residue allows for dimerization. Most of the chimeric receptors retain high PTK activity and induce transformation regardless of their configuration on the cell surface. UT, a UR2/T6 chimera, retained mitogenic activity but has a markedly reduced transforming ability, while UN7, a UR2/NM1 recombinant, which also harbors Y950F and F951S mutations in IGFR, exhibits dramatic reductions in both activities. All of the fusion receptors can phosphorylate insulin receptor substrate 1 and activate PI 3-kinase. UT protein induces Shc phosphorylation, whereas UN7 protein does not, but both are unable to activate mitogen-activated protein kinase. Our results show that overexpressed oncogenic Gag-fusion receptors do not require dimerization for their signaling and transforming functions and that the extracellular and transmembrane sequences of a receptor PTK can affect its specific substrate interactions.

Adaptor Proteins, Signal Transducing↗

PubMed1997

Evaluation of a new protocol for peripheral blood stem cell collection with the Fresenius AS 104 cell separator.

In this report we analyzed sixty leukapheresis procedures on 35 patients with a new protocol for the Fresenius AS 104. Yields and efficiencies for MNC, CD 34+ cells, and CFU-GM indicate that the new protocol is able to collect large quantities of hemopoietic progenitors. Procedures were performed processing 8.69 +/- 2.8 liters of whole blood per apheresis and modifying 3 parameters: spillover-volume 7 ml, buffy-coat volume 11.5 ml, centrifuge speed 1,500 rpm; blood flow rate was 50 ml/min and the anticoagulant ratio was 1:12. No side effects were observed during apheresis procedures except for transient paresthesia episodes promptly resolved with the administration of calcium gluconate. Yields show a high capacity of the new program to collect on average MNC 17.28 +/- 10.85 x 10(9), CD 34+ 471 +/- 553.5 x 10(6) and CFU-GM 1278.7 +/- 1346.3 x 10(4) per procedure. Separator collection efficiency on average was 49.91 +/- 23.28% for MNC, 55.1 +/- 35.66% for CFU-GM, and 62.97 +/- 23.09% for CD 34+ cells. Particularly interesting are results for MNC yields and CD 34+ efficiency; these results make the new program advantageous or similar to the most progressive blood cell separators and capable to collect a sufficient number of progenitor cells for a graft with a mean of 1.80 +/- 0.98 procedures per patient.

Adolescent↗

PubMed1997

An oblique cylinder contrast-adjusted (OCCA) phantom to measure the accuracy of MRI brain lesion volume estimation schemes in multiple sclerosis.

A new OCCA phantom using Oblique Cylinders and Contrast Adjustment for measuring the accuracy of brain lesion volume estimation schemes is described. It uses obliquely oriented cylinders made from acrylic rod, mounted in a water bath, to give realistic partial volume errors. Image intensities are inverted, scaled, and shifted, and noise is added, to form images that have realistic values of lesion-white matter contrast (5-30%) and contrast-to-noise ratio (3-20%). Artificial gray matter, CSF (cerebrospinal fluid), and scalp lipid are added because these bright areas may determine how the gray level display window is set. The performance of manual and contouring methods for estimating lesion volume was measured for three observers and nine lesions with individual volumes from 0.3 to 6.2 ml. There was a large variation, depending on the choice of method, the observer, and the lesion contrast. Volumes were usually overestimated, with the error increasing at high contrasts. The average error in estimating total lesion volume was 17% (range -16% to +30%). The OCCA phantom may have a role in training observers to improve their accuracy (and hence inter- and intraobserver reproducibility).

Brain↗