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Biomedical subjects

M Lai

Publications and source records attributed to M Lai.

At least 19 recordsLinked to original sources
PubMed2006

Role of acetylcholine transmission in nucleus accumbens and ventral tegmental area in heroin-seeking induced by conditioned cues.

The involvement of cholinergic transmission in heroin self-administration and the reinstatement of heroin-seeking was examined in rats trained to nose-poke for i.v. heroin. Systemic treatment with physostigmine, an inhibitor of acetylcholinesterase, modestly reduced the acquisition and rate of heroin self-administration, and this suppression of heroin intake was reversed by pretreatment with scopolamine but not by mecamylamine. Following 10-14 days of self-administration, rats were left in the home environment for 14 days. Subsequently, rats were evaluated for extinction of nose-pokes during the first hour after being returned to the self-administration apparatus. One hour later a conditioned stimulus (house light, light in the nose-poke hole, sound of the infusion pump) was presented to initiate cue-induced reinstatement. Physostigmine produced a dose-dependent inhibition of cue-induced reinstatement, but only the dose of 0.5 mg/kg significantly decreased nose-poke responding in the extinction test. Chronic treatment with physostigmine (0.1 mg/kg) did not impair performance during acquisition of heroin self-administration. However, during a subsequent reinstatement test conducted in the absence of physostigmine pretreatment, heroin seeking was significantly below that of rats chronically pretreated with saline. To evaluate brain regions mediating the effects of systemic drug treatment on reinstatement, physostigmine was microinjected into the nucleus accumbens (NAc) or ventral tegmental area (VTA). Microinjection of physostigmine into the NAc prior to presenting conditioned cues inhibited the reinstatement of heroin-seeking, without affecting extinction responding. In contrast, microinjection of physostigmine into the VTA augmented the reinstatement induced by conditioned cues and extinction responding. Inactivation of either NAc or VTA by microinjecting tetrodotoxin blocked both extinction responding and cue-induced reinstatement. These data demonstrate that cholinergic transmission influences heroin self-administration and reinstatement. Moreover, cue-induced reinstatement was inhibited by physostigmine in the NAc and potentiated by cholinergic stimulation in the VTA.

Acetylcholine↗
PubMed2006

Effect of hydroxypropyl cellulose (HPC) on dissolution rate of hydrochlorothiazide tablets.

Hydrochlorothiazide (HCTZ) 60 mg strength tablets containing commonly used excipients and hydroxypropyl cellulose, marketed as either Klucel-EF (HPC, NF from Hercules, USA) or HPC-L (HPC, NF from Nippon Soda, Japan), as a binder were manufactured using identical aqueous wet granulation process. The tablets containing Klucel-EF as a binder exhibited higher dissolution rates than those manufactured using HPC-L. The granulations containing Klucel-EF or HPC-L showed no significant differences in compressibility and compactibility based on analysis performed using the Instron-Stress-Strain Analyzer. Both HPC grades met NF specifications and there were no differences for the NF test results in the certificates of analysis by their respective vendors. Further evaluation of both HPC grades indicated that the cloud point values for Klucel-EF and HPC-L in water were 39(+/- 1) and 48 degrees C, respectively. The differences in cloud points of Klucel-EF and HPC-L were correlated to the differences in the percent hydroxypropoxy content and the degree of molecular substitution, which were higher for Klucel-EF than for HPC-L. These structural features make Klucel-EF less hydrophilic. Since the cloud point of Klucel-EF was similar to the dissolution medium temperature of 37(+/- 2) degrees C, it may present a less viscous layer surrounding the HCTZ granules enabling faster dissolution of the drug.

Cellulose↗
PubMed2006

Aetiological factors related to a positive direct antiglobulin test result in human immunodeficiency virus-infected patients.

BACKGROUND AND OBJECTIVES: The aim of this study was to examine the clinical importance and causes of a positive result in the direct antiglobulin test (DAT) in human immunodeficiency virus-infected (HIV(+)) patients. We therefore studied haematological parameters in outpatient samples, and also analysed the impact of highly active anti-retroviral therapy (HAART) on the DAT results. STUDY DESIGN AND METHODS: Haematological parameters, clinical stages, chemo-antibiotic treatments and HAART treatment were studied to determine any relationships with DAT results in 115 consecutive HIV(+) patients. RESULTS: Significantly lower haemoglobin (Hb) levels were detected in patients with HIV who had a positive DAT result. Hepatitis C virus (HCV) co-infection (odds ratio 2.529) and trimethoprim-suphamethoxazfole (TMP-SMX) prophylaxis (odds ratio 3.751) had a significant association with DAT positivity. Patients receiving HAART were less likely to have a positive DAT [odds ratio (OR) 0.383; P = 0.035]. Among the patients treated with TMP-SMX, those with a positive DAT had lower Hb levels (11.9 g/dl) than those with a negative DAT (14.2 g/dl; P = 0.04). HCV antibody positivity and TMP-SMX prophylaxis showed a cumulative effect on positive DATs (OR 4.533). The surface exploratory analysis indicated the distribution of the positive DATs in relationship with the CD4(+) count and Hb levels. CONCLUSIONS: Significantly lower Hb levels were detected in DAT-positive HIV(+) patients. HCV co-infection and TMP-SMX prophylaxis appear to confer an increased risk of DAT positivity. The presence of red blood cell autoantibodies may be associated with anaemia in HIV disease in the absence of overt haemolysis.

Anemia↗
PubMed2005

Interaction of loci within the HLA region influences multiple sclerosis course in the Sardinian population.

We examined the influence of alleles at the HLA loci, previously found to be associated with multiple sclerosis (MS) in Sardinia, on the clinical course of the disease in 835 relapsing (R) and 100 primary progressive (PP) patients. Multivariate analysis was carried out on predisposing 0301 or non-associated DPB1 alleles, susceptible or non-associated DRB1-DQB1 haplotypes, both predisposing and non-predisposing, and negatively and non-negatively associated D6S1683 alleles, taking interaction between them into account. Intra-patient analysis showed that the presence of the susceptible or protective D6S1683 allele interacting with predisposing DP 0301 modulated risk of PP disease. These findings suggest that a locus telomeric to HLA class I exerts an effect on alleles at the DPB1 locus in modulating disease course.

Adolescent↗
PubMed2005

Impurity analysis of 1,4-dioxane in nonionic surfactants and cosmetics using headspace solid-phase microextraction coupled with gas chromatography and gas chromatography-mass spectrometry.

1,4-Dioxane impurity in nonionic surfactants and cosmetics were analyzed using solid-phase microextraction (SPME) coupled with gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). Experimental results show that there is no significant difference using SPME-GC and SPME-GC-MS for analysis of 1,4-dioxane in three types of nonionic surfactants at the 95% confidence level. The relative standard deviation (R.S.D.) values of each analytical method were smaller than 3%. The amount of 1,4-dioxane was found to vary from 11.6 +/- 0.3 ppm to 73.5 +/- 0.5 ppm in 30% of nonionic surfactants from manufacturers in Taiwan. These methods were linear over the studied range of 3-150 ppm with correlation coefficients higher than 0.995. The recoveries of 1,4-dioxane for these nonionic surfactants following SPME were all higher than 96 +/- 1% (n = 3). The detection limits of 1,4-dioxane for these nonionic surfactants following SPME were from 0.06 ppm to 0.51 ppm. The experimentally determined level of 1,4-dioxane in cosmetics from manufacturers in Taiwan varied from 4.2 +/- 0.1 ppm to 41.1 +/- 0.6 ppm in 22% of daily used cosmetics following SPME coupled with GC and GC-MS. Conventional solvent extraction takes around 1 h for extraction and reconcentration but SPME takes only around 10 min. SPME provides better analyses of 1,4-dioxane in nonionic surfactants and cosmetics than conventional solvent extraction and head space pretreatments in term of simplicity, speed, precision, detection limit, and solvent consumption.

Calibration↗
PubMed2005

HLA-DR,DQ and APOE genotypes and gender influence in Sardinian primary progressive MS.

The authors examined the influence of APOE and human leukocyte antigen-DRB1-DQB1 polymorphisms on the course of multiple sclerosis in 871 patients, 773 with relapsing and 98 with primary progressive disease, and 348 control subjects. The risk of the primary progressive course was increased (odds ratio = 6.81, p = 0.002) in women carrying the APOE4 but not the DRB1-DQB1 predisposing genotype, suggesting in this subgroup of patients a reciprocal influence between these genes and gender in modulating clinical variability of the disease.

Apolipoprotein E4↗
PubMed2004

Bias in parental transmission of the HLA-DR3 allele in Sardinian multiple sclerosis.

The authors analyzed the female: male (F:M) ratio according to the HLA-DRB1-DQB1 genotype in a cohort of multiple sclerosis (MS) patients from Sardinia, where the disease is associated with DR3 and DR4. In the whole cohort of 1,097 patients, F:M ratio was 2.24; however, it was 2.88 in DR3/DR3 and 2.52 in DR3/DRX (X#DR3 and DR4) individuals. Parental transmission of DR3 and DR4, assessed in a set of 565 case-parent triads, showed evidence of paternal inheritance of DR3 in affected women, thus explaining the excess of females in the DR3 category.

Alleles↗
PubMed2004

Anticipation of age at onset in multiple sclerosis: a Sardinian cohort study.

BACKGROUND: To assess the temporal trend in multiple sclerosis (MS) onset during the last 50 years in Sardinia, Italy. METHODS: The authors used a cohort study to assess age at onset in 1,513 MS patients at the MS clinic in Cagliari, all born and living in Sardinia. They also assessed age at onset in 41 pairs of familial patients from two generations and 78 pairs of affected sibs. Each familial couple was paired with three couples of sporadic patients born in the same year as the familial ones. The time interval between the first symptoms and diagnosis was analyzed in first and second-diagnosed patients from both familial and control couples. RESULTS: Mean age at onset progressively decreased from the most remote to the most recent decade of birth (log-rank test 778.27, p < 0.0001), being 41 years in the former decade and 22 years in the latter. A genetic influence was ruled out, because the younger member of familial patients coming from two generations had onset 14.0 years earlier than the older one (p < 0.0001), as in the paired control couples (11.6 years, p < 0.0001). Moreover, mean onset in younger sibs was 3.4 years earlier than in older ones (p = 0.01), similar to that of control couples (4.1 years, p < 0.0001). CONCLUSION: Age at onset decreases progressively from older to younger generations in Sardinian MS patients. Nongenetic but recent widespread environmental changes might contribute to shortening of the preclinical phase-overt disease interval.

Adolescent↗
PubMed2004

Gastric medullary carcinoma, a distinct entity associated with microsatellite instability-H, prominent intraepithelial lymphocytes and improved prognosis.

AIMS: To determine the clinicopathological and molecular features of gastric medullary cancer. METHODS AND RESULTS: Clinicopathological review and microsatellite instability (MSI) analysis were carried out on 17 gastric medullary and 64 non-medullary cancers. In addition to characteristic histopathology, gastric medullary cancers had certain prominent features: (i) the average survival time was longer in medullary and low-grade non-medullary cancers than in high-grade (P = 0.004); (ii) serosal involvement was less common in medullary cancers (29.4%, 5/17) than in non-medullary cancers (9.4%, 6/64) (P < 0.05) while pushing borders were more common in medullary cancers (70.6%, 12/17 versus 17.2%, 11/64, P = 0); (iii) the presence of intraepithelial lymphocytes (IELs) in medullary and non-medullary cancers was 2380/10 high-power field (HPF) and 147/10 HPF (P = 0), respectively. Both peritumoural infiltrating lymphocytes (pTIL) and a Crohn's-like reaction were more common in medullary cancers than in non-medullary (pTIL 35.3%, 6/17 versus 3.1%, 2/64; a Crohn's-like reaction 70.6%, 12/17 versus 32.8%, 21/64; P < 0.05); (iv) medullary and high-grade non-medullary cancers were more associated with reduced ECD expression in comparison with low-grade cancers (P < 0.05); (v) higher MSI-H (Bat26+) rate was observed in medullary cancers (41.2%, 7/17) than in non-medullary (1.6%, 1/64) (P = 0). CONCLUSIONS: Gastric medullary cancer has distinct clinicopathological features and genetic alterations. Two subtypes of gastric medullary cancers, Bat26+ and Bat26-, might have prognostic implications, thus analysis of Bat26 may be of clinical value.

Carcinoma, Medullary↗
PubMed2004

Detection of the differentially expressed gene IGF-binding protein-related protein-1 and analysis of its relationship to fasting glucose in Chinese colorectal cancer patients.

IGF-binding protein-related protein-1 (IGFBP-rP1) is a member of the IGF axis. In our previous work, we separated cDNA fragments of IGFBP-rP1 from colonic adenocarcinoma and normal mucosa cDNA subtraction libraries. In this study, we compared the expression of IGFBP-rP1 by semi-quantitative RT-PCR and immunohistochemistry among colorectal cancer, adenoma, normal tissue adjacent to cancer site, and normal tissue. Associations between IGFBP-rP1 and plasma glucose were further explored. We found that the mRNA level of IGFBP-rP1 was highest in cancer, moderate in adenoma and tissue adjacent to the cancer site and lowest in normal tissue (P<0.05). A significant difference was found in the immunoreactivity of IGFBP-rP1 between paired normal and cancer tissue (P<0.05). Tumor samples with upregulated expression of IGFBP-rP1 in invading tumor cells showed an increased frequency of metastasis to the lymph node, an increased depth of infiltration and stronger staining of IGFBP-rP1 compared with other samples (P<0.05). The fasting glucose level was significantly correlated with the staining of IGFBP-rP1 in cancer tissue (Spearman's rho=0.4, P<0.000). Thus, we concluded overexpression of IGFBP-rP1 might play an important role in the initiation and promotion of colorectal cancer. IGFBP-rP1 expression may also be associated with fasting glucose level and the presence of diabetes mellitus.

Adenocarcinoma↗
PubMed2003

Differential regulation of corticosteroid receptors by monoamine neurotransmitters and antidepressant drugs in primary hippocampal culture.

Hyperactivity of the hypothalamic-pituitary-adrenal axis is a characteristic feature of depressive illness. The centrally located corticosteroid receptors, the glucocorticoid and mineralocorticoid receptors, are thought to be important modulators of this axis and changes in the levels of these receptors, particularly in the hippocampus, may underlie the hyperactivity observed. Various antidepressant drugs increase hippocampal mineralocorticoid and glucocorticoid receptor levels in vivo. These effects are thought to be mediated via alterations in monoaminergic neurotransmission. We examined whether serotonin (5HT) and noradrenaline (NA) have direct effects on glucocorticoid receptor and mineralocorticoid receptor expression in primary hippocampal neurones, and whether antidepressants also exert direct effects on target neurones. Exposure of hippocampal cells to 5HT for 4 days increased both glucocorticoid and mineralocorticoid receptor mRNA and protein expression. The induction of mineralocorticoid receptor mRNA was completely blocked by the 5HT(7) receptor antagonist SB 269970. In contrast glucocorticoid receptor induction was insensitive to the 5HT(7) receptor, whilst studies with the 5HT(1A) receptor agonist 8-hydroxy-2-(di-n-proplamino) tetralin hydrochloride and the 5HT(1A) receptor antagonist N-[2-[4-2-[O-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide trihydrochloride (WAY 100635) suggest a partial role for 5HT(1A) receptors in hippocampal glucocorticoid receptor regulation. Treatment with NA for 4 days also increased glucocorticoid receptor expression but had no effect on mineralocorticoid receptor expression. This was blocked by propanolol suggesting action via beta-adrenergic receptors. Similarly to NA, fluoxetine and amitriptyline also selectively increased glucocorticoid receptor mRNA and protein levels over this time course. However, glucocorticoid receptor induction by fluoxetine or amitriptyline was not blocked by WAY 100635 or propanolol. These results show that 5HT, NA and antidepressants act directly but via distinct mechanisms on hippocampal neurones to regulate mineralocorticoid and glucocorticoid receptor expression. Thusly, manipulation of neurotransmitter or antidepressant levels in the brain may aid in reversing hypothalamic-pituitary-adrenal axis hyperactivity by restoring hippocampal corticosteroid receptor balance.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2002

Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial.

PURPOSE: Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy (RT) and chemotherapy. This randomized phase III trial compared concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC. PATIENTS AND METHODS: Patients with Ho's N2 or N3 stage or N1 stage with nodal size > or = 4 cm were randomized to receive cisplatin 40 mg/m(2) weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The primary end point was progression-free survival (PFS). RESULTS: Three hundred fifty eligible patients were randomized. Baseline patient characteristics were comparable in both arms. There were significantly more toxicities, including mucositis, myelosuppression, and weight loss in the CRT arm. There were no treatment-related deaths in the CRT arm, and one patient died during treatment in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone arm (P =.10) with a hazards ratio of 1.367 (95% confidence interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate interaction with tumor stage, and a subgroup analysis demonstrated a highly significant difference in favor of the CRT arm in Ho's stage T3 (P =.0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was statistically significantly different in favor of the CRT arm (P =.016). CONCLUSION: Concurrent CRT is well tolerated in patients with advanced NPC in endemic areas. Although PFS was not significantly different between the concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was significantly prolonged in patients with advanced tumor and node stages.

Adult↗
PubMed2002

Genetic factors and the founder effect explain familial MS in Sardinia.

OBJECTIVE: To estimate the presence of familial aggregation and determine the contribution of genetic factors to familial clustering of MS in patients coming from Sardinia, a Mediterranean island considered a genetically homogeneous, isolated area having high disease incidence and prevalence. METHODS: Recurrence risk in siblings of 901 Sardinian patients and factors influencing risk (patient and sibling sex, patient age at onset, sibling birth cohort, and presence of affected relatives other than siblings) were examined. The presence of distant familial relationships among patients was evaluated by tracing the extended pedigrees of all patients with MS born in one Sardinian village. RESULTS: Twenty-three brothers and 36 sisters of the 2,971 siblings were affected with MS. Recurrence risk was greater in siblings of index patients with onset age less than 30 years (p < 0.01, increased risk 2.33 times) and having a relative with MS other than a sibling or parent (p < 0.01, increased risk 2.90 times). Pedigree analysis of patients from the village of L. showed that all 11 patients descended from 3 pairs of ancestors, whereas no cases occurred in the remaining 2,346 inhabitants. In descendants from the 3 couples, MS prevalence was dramatically greater than the regional average and 1.5 times greater than that observed in siblings of affected cases. CONCLUSIONS: Data from this study indicate that MS familial aggregation in Sardinians is influenced by genetic factors and that founder effect and the isolation of Sardinia can be considered causes of the enrichment of "etiologic" MS genes.

Adult↗
PubMed2002

Phosphatidylserine exposure in platelet concentrates during the storage period: differences between the platelets collected with different cell separators.

BACKGROUND AND OBJECTIVES: Platelet alterations occur during the production and storage of platelet concentrates, the so called "storage lesion". We studied the platelet alterations during the storage period in apheresis concentrates, employing flow cytometry for phosphatidylserine (PS) detection on platelets during the five days of storage. MATERIAL AND METHODS: Twenty-seven single donor platelet concentrates harvested with the Cobe Trima, Baxter Amicus, or Haemonetics MCS+ were analyzed for PS exposure by flow cytometry on the day of production (day 1) and on days 3 and 5 of storage. Furthermore PS expression was analyzed in platelet donors' blood samples withdrawn before plateletpheresis. RESULTS: PS expression on platelets gave the following median values: in blood donors before apheresis it was 1.12% (0.13-1.78) in platelets concentrates on the first day (2 h after apheresis) 2.06% (0.66-15.2), the third day 6.57% (1.98-51.13) and the fifth day 23.04% (3.86-80.23). All differences between median values of PS expression in blood samples before apheresis, and platelets concentrates on days 1, 3 and 5 of storage, are statistically significant. The expression of PS in platelet concentrates was analyzed in relation to the blood cell separator used for the collection procedure and showed the following results: on day 1 the median values of PS in platelet concentrates collected with the three different blood cell separators, Trima, Cobe and MCS, did not show statistically significant differences. On day 3, the platelets concentrates collected with the Trima and with the MCS showed differences that were statistically significant. Those were respectively 10.59% (4.56-51.13) and 3.53% (1.98-12.61), p = 0.005. The PS expression in platelet concentrates collected with the Trima and MCS showed differences that are also statistically significant on day 5 at respectively 32.4% (9.61-80.23) and 8.57% (3.86-48.42), p = 0.005. CONCLUSIONS: PS exposure in platelet concentrates on days 3 and 5 rise to levels that could compromise the quality of the platelet units. Improvements in standardized platelet quality controls, and in platelet collection systems are required to reduce the storage lesions in platelets concentrates.

Adult↗
PubMed2002

Distinct antigenic features of linear epitopes at the N-terminus and C-terminus of 65 kDa glutamic acid decarboxylase (GAD65): implications for autoantigen modification during pathogenesis.

Autoantibodies to 65 kDa glutamic acid decarboxylase (GAD65) are produced in many patients with autoimmune polyendocrine syndrome type II (APS-II) or stiff-man syndrome (SMS) and are heterogeneous in their epitope specificities, recognizing both conformational and linear determinants. Major linear epitopes of GAD, which are recognized by autoantibodies in a minority of these patients, occur in the N-terminal and C-terminal regions. We have investigated antibody recognition of the N- and C-termini of GAD65 in relation to their structural features as an approach to understanding what modifications to the native GAD structure may occur that facilitate the generation of antibodies specific to linear epitopes in these regions during the autoimmune pathogenesis. A monoclonal antibody specific to the N-terminus of GAD65 bound both native and denatured GAD in ELISA, whereas monoclonal and polyclonal antibodies specific to the C-terminus of GAD bound only denatured GAD. These antibodies were epitope mapped using random peptide phage-display libraries and the epitopes related to a previously proposed structural model of GAD65. This has led us to propose that the alpha-helical secondary structure of the C-terminus of GAD65 must be denatured to generate linear epitopes. In contrast, the N-terminus is both surface exposed and linear in the native structure, but may be masked by membrane interactions, which must be broken to facilitate recognition by B cells.

Amino Acid Sequence↗
PubMed2002

Independent contribution of elevated-rim acetabular liner and femoral head size to the stability of total hip implants.

The use of an elevated-rim acetabular liner in total hip arthroplasty is widely accepted. We sought to determine quantitatively the amount of additional stability provided by the elevated-rim liner compared with the standard nonelevated liner. The stability of the hip with a 32-mm femoral head was compared with the standard 28-mm head. Our results show that a 15 degrees elevated-rim acetabular liner placed in the posterior quadrant increased hip stability by an additional 8.9 degrees of internal rotation. Similarly the 32-mm head provided 8.1 degrees of additional internal rotation. The increases were statistically significant (P<.0001). We did not encounter increased anterior dislocation intraoperatively. The findings of this study indicate that the 32-mm head may contribute to hip stability in primary total hip arthroplasty, and in instances in which a posterior approach is used, an elevated-rim liner placed in the posterior quadrant may contribute independently to hip stability.

Acetabulum↗